Relazione ScientificaAprile2012

Transcription

Relazione ScientificaAprile2012
Scuola di dottorato di ricerca in Nanotecnologie
Resoconto dell’attività 2011
Sommario
1.
2.
3.
Relazione scientifica riassuntiva .................................................................................................. 3
Elenco dottorandi, supervisori e titolo delle tesi .......................................................................... 6
Schede attività dottorandi........................................................................................................... 10
Dottorandi del 24 ciclo:.................................................................................................................. 11
Dottorandi del 25 ciclo: • ............................................................................................................... 43
Dottorandi del 26 ciclo:.................................................................................................................. 63
Progetti Dottorandi del 27 ciclo: .................................................................................................... 93
4. Pubblicazioni dei dottorandi. ................................................................................................... 202
5. Giudizi dei referee esterni per dottorandi ammessi all’esame finale aprile 2012 .................... 210
6. Giudizi della commissione d’esame finale aprile 2012 ........................................................... 211
7. Elenco dei componenti del collegio docenti ............................................................................ 215
8. Produzione scientifica del collegio docenti 2007-2012 ........................................................... 218
Personale di ruolo nelle università italiane e INAF ..................................................................... 218
Personale non di ruolo nelle università o dipendenti di altri enti................................................. 261
9. Criteri di valuatazione delle scuole di dottorato ...................................................................... 267
10. Valutazione da parte del nucleo di valutazione dell’Ateneo .................................................... 270
11. Giudizi dei referee esterni per dottorandi ammessi all’esame finale aprile 2012 .................... 271
12. Presentazioni dei dottorandi al congesso del gennaio 2012 ..................................................... 272
Attività della scuola: situazione ad aprile 2012.
Questo documento contiene il dettaglio dell’attività didattico scientifica della scuola di dottorato in
nanotecnologie svolto durante l’anno 2011 fino ad aprile del 2012. Il documento si compone delle
seguenti parti:
1. Relazione scientifica riassuntiva (Executive summary)
2. Elenco dei dottorandi, supervisori e titolo tesi in corso.
3. Schede di attività dei dottorandi che hanno svolto attività continuativa nell’anno 2011.
Questa attività è stata presentata nel congresso di gennaio 2012 (vedi slides su CD allegato)
ed è riassunto per ogni dottorando nelle schede riportate di seguito. Le schede si riferiscono
ai dottorandi in corso dei cicli 24, 25 e 26, non esssendoci dottorandi in proroga da cicli
precedenti.
4. Progetti dei dottorandi nuovi entrati nella scuola (27 ciclo). Questa attività non è stata
presentata in gennaio 2012 poiché non ancora definiti gli accoppiamenti dottorando – tema
di ricerca.
5. Riassuntivo delle pubblicazioni dei dottorandi.
6. Giudizi della commissione d’esame finale 2012.
7. Elenco dei componenti collegio docenti.
8. Pubblicazioni rappresentative del collegio docenti.
9. Criteri di valutazione delle scuole di dottorato.
10. Valutazione della scuola da parte del nucleo di valutazione riassunta in una tabella e rimandi
ad allegati.
11. Giudizi dei reviewer esterni per i dottorandi ammessi all’esame finale (allegati).
12. Presentazioni dei dottorandi al congresso gennaio 2012 (allegati).
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
2
1. Relazione scientifica riassuntiva
La missione della scuola di dottorato è di migliorare le conoscenze ed educare studenti nel campo
delle nanotecnologie al fine di formare scienziati e tecnici per il 21° secolo. La caratteristica della
Scuola è l’interdisciplinarità: sugli argomenti di ricerca attivi lavorano in sinergia fisici, chimici,
biologi, ingegneri, medici, farmacologi, odontoiatri, biotecnologi e laureati in Agraria, mantenendo
e rafforzando la specificità della cultura di provenienza ed acquisendo la capacità di sviluppare la
propria ricerca in un quadro più ampio.
L’obiettivo principale della Scuola è di formare Ricercatori che sappiano progettare, costruire,
utilizzare e sottoporre a prove di funzionalità strumenti e dispositivi nano tecnologici, in grado di
rispondere alle crescenti e diversificate esigenze delle applicazioni. L'allievo “dottorato” di questa
Scuola sarà un professionista della ricerca e dello sviluppo tecnologico che sappia applicare le
proprie conoscenze, con capacità di valutazione critica, allo sviluppo di metodi di progettazione,
produzione e valutazione di nuovi materiali e al miglioramento di quelli esistenti. Questo anche
mirato ad una produzione industriale più efficace, economica e sostenibile dal punto di vista delle
risorse e dell'ambiente. La scuola è stata fondata nel 2006 a partire da un dottorato in
nanotecnologie.
Gli obiettivi delle ricerche sono i seguenti:
Sviluppo di nuove tecniche sperimentali per lo studio, la lavorazione, la manipolazione e la
visualizzazione su scala nanometrica di materiali nanostrutturati.
Sviluppo di tecniche spettroscopiche di rivelazione di singola molecola su substrati
nanostrutturati.
Studio delle relazioni tra la microstruttura e le proprietà dei materiali e ingegnerizzazione di
materiali nanostrutturati.
Sintesi di nanostrutture.
Applicazioni delle nanotecniche e nanostrutture a ricerche di interesse biomedico ed
energetico.
Modellizzazione molecolare multiscala di materiali e di fenomeni di interesse attraverso
tecniche di simulazione computazionale.
Salute umana con particolare attenzione allo studio ed al trattamento di tumori e malattie
degenerative.
Applicazione delle nanotecnologie nei settori medico, farmacologico, biomedico ed agroalimentare.
Questi obiettivi sono perseguiti avvalendosi delle attrezzature d'avanguardia disponibili nei
laboratori dell'Università di Trieste e degli Enti di ricerca pubblici e privati convenzionati con
l’Università di Trieste, come da seguente tabella:
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
3
n.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Tipologia del soggetto
Istituto/Ente di Ricerca non
accademici (compreso IRCCS)
Istituto/Ente di Ricerca non
accademici (compreso IRCCS)
Istituto/Ente di Ricerca non
accademici (compreso IRCCS)
Istituto/Ente di Ricerca non
accademici (compreso IRCCS)
Istituto/Ente di Ricerca non
accademici (compreso IRCCS)
Istituto/Ente di Ricerca non
accademici (compreso IRCCS)
Istituto/Ente di Ricerca non
accademici (compreso IRCCS)
Istituto/Ente di Ricerca non
accademici (compreso IRCCS)
Privato non di ricerca
Istituto/Ente di Ricerca non
accademici (compreso IRCCS)
Pubblico/Privato
PUBBLICO
Denominazione del soggetto
Sincrotrone Trieste S.C.p.A.
PUBBLICO
Laboratorio Nazionale TASC-IOM CNR
PUBBLICO
PUBBLICO
ICGEB – International Centre for Genetic
Engineering and Biotechnology
IRCSS Burlo Garofolo - Trieste
PUBBLICO
CRO Aviano
PUBBLICO
PUBBLICO
Istituto Nazionale dei tumori di Milano
Fondazione IRCSS
CNR - Institute of Chemistry of
OrganoMetallic Compounds
AIRC
PRIVATO
PUBBLICO
Indistrie Bracco
Fondazione Callerio - Trieste
PUBBLICO
Gli studenti di dottorato nel periodo in esame hanno svolto stage presso aziende ed enti di ricerca. I
più significativi sono i segnueti:
STAGE IN ITALIA
n.
Pubblico/Privato
1.
PUBBLICO
2.
3.
4.
5.
PUBBLICO
PUBBLICO
PUBBLICO
MISTO
6.
PUBBLICO
Denominazione del
soggetto
CNR-IOM TASC Laboratorio
Trieste
Elettra Sincrotrone Trieste
IRCCS Burlo Garofalo
CRO Aviano
Centro Biomedicina
Molecolare (CBM)
Università di Udine
STAGE ALL'ESTERO
n.
1.
2.
3.
4.
5.
6.
7.
8.
Denominazione del soggetto
Max Plank Institute - Halle
CNRS - Marsiglia
University Poznan - Center for
nanotechnology
Ohio University, Athens (OH)
Technische Universität di Monaco di Baviera
Soft Matter Physics Division - Leipzig
Università di San Pietroburgo
Technische Universitaet - Institut fuer
Chemie Max-Volmer-Laboratorium für
Biophysikalische Chemie
Paese
Germania
Francia
Polonia
Stati Uniti
d'America
Germania
Germania
Russai
Germania
Di seguito alcuni numeri rappresentativi dell’attività della scuola:
 n. di studenti (ad aprile 2012): 52
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
4








Numero di diplomati nel 2012: 12
Numero di diplomati nel 2011: 8
Numero di diplomati nel 2010: 7
Numero di diplomati nel 2009: 6
Numero di diplomati nel 2008: 9
Numero di diplomati nel 2007: 14
Membri del collegio docenti: 45
Enti di ricerca coinvolti nel dottorato:
oDipartimenti dell’Università di Trieste: 5 (in diminuzione per accorpamenti)
oEnti di ricerca esterni: 10
oAltre Università: 4
 Numero di pubblicazioni degli studenti:
oAnno 2007: 67
oAnno 2008: 68
oAnno 2009: 72
oAnno 2010: 105
oAnno 2011: 95
 Numero di pubblicazioni di supervisori e tutors (2006-11): 982+141 = 1123
 Risorse finanziarie (per anno): 600.000 euro
 Ultima valutazione complessiva del nucleo dell’Università di Trieste: A+ (Ottimo)
I criteri usati per la valutazione interna sono stati quelli suggeriti dal Ministero, accompagnati da
criteri interni all’Ateneo. Questi criteri sono descritti di seguito in questo documento in modo
dettagliato. I principali indicatori utilizzati dal nucleo che hanno permesso la valutazione in classe
A+ sono (vedi capitolo 10 per maggiori dettagli):
 produzione scientifica del Collegio Docenti;
 congruo numero di docenti dell’Ateneo coinvolti nel collegio;








rapporto del dottorato con il mondo del lavoro;
attrattività del dottorato nelle precedenti edizioni;
livello di soddisfazione dei dottorandi;
produzione scientifica dei dottorandi ed iniziative esistenti di pubblicizzazione e referaggio
delle tesi di dottorato;
adeguata formulazione delle tematiche scientifiche e degli obiettivi formativi,
riduzione della frammentazione dei corsi di dottorato;
accuratezza delle informazioni fornite per la valutazione;
presenza di iscritti stranieri;
 sito web del dottorato.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
5
2.Elenco dottorandi, supervisori e titolo delle tesi
La situazione riportata in tabella è quella ad aprile 2012, quindi include i dottorandi del 27 ciclo e
non quelli del 24 ciclo diplomati ad aprile.
Dottorando
Ciclo Supervisore
ABDOLLAHZADEH 27 SCOLES
Iman
Giacinto
AMBROSINI
25 RUBINI Silvia
Stefano
SSD
FIS/03
ANGELONI
Valeria
27 BRESCHI
Lorenzo
MED/28
BIDOGGIA Silvia
25 PASQUATO
Lucia
CHIM/06
BORIN Daniele
FIS/03
CAPOLLA Sara
27 LAZZARINO
Marco
27 MACOR Paolo
CASSESE
Damiano
26 LAZZARINO
Marco
FIS/03
CECCHINI Paolo
27 TOGNETTO
Daniele
MED/30
CHEN Yan Xin
25 FORNASIERO
Paolo
CHIM/03
COCEANO
Giovanna
CORVAGLIA
Stefania
COVA Andrea
27 COJOC Dan
FIS/03
26 CASALIS
Loredana
27 BRESCHI
Lorenzo
FIS/03
DAL COL
Valentina
26 PRICL Sabrina
INGIND/24
FIS/01
MED/04
MED/28
NomeDip
Department of
Physics - DF
Department of
Physics - DF
Titolo Tesi
Nanotechnology approaches for the
detection of circulating tumor cells
Sintesi di nanostrutture di
semiconduttori e loro studio
mediante luce di sincrotrone.
Clinical Department Effect of chlorexidine in the hybrid
of Medical Science, layer nano leakage in adhesive
Surgery and Healt - dentistry
DCSMCS
Department of
Gold nanoparticles as carriers for
Chemical and
drug delivery applications
Pharmaceutical
Sciences - DSCF
Department of
Micro mechanical oscillators for
Physics - DF
biochemical applications
Department of Life Use of chemotherapic-loaded
Sciences - DLS
nanoparticles in the treatment of
cancer
Department of
Design and realization of
Physics - DF
nanoelectromechanical and
plasmonic devices for Raman
spectro-microscopy
Clinical Department Bio-Materials in oculist micro
of Medical Science, surgery
Surgery and Healt DCSMCS
Department of
Nanostructured Titanium Dioxide
Chemical and
Based Materials for Photocatalysis
Pharmaceutical
and Phototelectrocatalysis
Sciences - DSCF
Department of
Characterization of the mechanical
Physics - DF
properties of cancer cells
Department of
Shaping substrates at the nanoscale
Physics - DF
for single cell characterization
Clinical Department Role of collagen cross-linkers on
of Medical Science, the stability of the bonded
Surgery and Healt - interface
DCSMCS
Department of
In silicio prediction of drug
Engineering and
resistance: from cancer targeted
Architecture - DIA therapy to cancer targeted
prevention
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
6
Dottorando
Ciclo Supervisore
DIOLOSA‘ Marina
27 CADENARO
Milena
ELISEI Elena
FORNASARO
Stefano
FRASSETTO
Andrea
GANAU Mario
GANBOLD
Tamiraa
GIORGIS
Valentina
IONESCU Andrei
Cristian
LOVAT Giacomo
LUCAFO'
Marianna
MARSICH Lucia
MARSON
Domenico
MINIUSSI Elisa
MITRI Elisa
SSD
NomeDip
MED/28 Clinical Department
of Medical Science,
Surgery and Healt DCSMCS
27 CESARO Attilio CHIM/04 Department of Life
Sciences - DLS
27 PASSAMONTI BIO/10 Department of Life
Sabina
Sciences - DLS
Titolo Tesi
Development of a new nanoengineered biopolymer-based
dental adhesive system
Nanostructured biomolecular
glasses
Targeting natural antioxidant
compounds to the brain: a
metabolomic assessment.
26 CADENARO
MED/28 Clinical Department Nanostructural analysis of the
Milena
of Medical Science, adhesive interface in dentistry
Surgery and Healt DCSMCS
25 SCOLES
FIS/03 Department of
Nanotechnology applications in
Giacinto
Physics - DF
quantitative neuroscience:
proteomics assessment of astrocyte
stressing and neuronal plasticity
27 BIASIOL Giorgio FIS/03 Department of
Development of quantum well
Physics - DF
structures for multi band photon
detection
25 ROMANATO
FIS/03 Department of
Design, fabrication and
Filippo
Physics - DF
characterization of metamaterials
inspired plasmonic structures for
sensing application
27 CADENARO
MED/28 Clinical Department The influence of resin-based dental
Milena
of Medical Science, materials upon oral biofilms
Surgery and Healt - development.
DCSMCS
27 MORGANTE
FIS/03 Department of
Study of charge transfer processes
Alberto
Physics - DF
at interfaces for photovoltaic
applications
25 SAVA Gianni
BIO/14 Department of Life Study of carbon nanostructures as
Sciences - DLS
carriers for drugs for cancer
chemotherapy.
25 SERGO Valter INGDepartment of
Design and synthesis of
IND/22 Engineering and
functionalized metal nanoparticles
Architecture - DIA for bio-analysis with SurfaceEnhanced Raman Scattering (SERS)
27 PRICL Sabrina INGDepartment of
Computer-assisted design of
IND/24 Engineering and
nanovectors for gene therapy
Architecture - DIA
26 BARALDI
FIS/03 Department of
Interaction of metal nanoclusters
Alessandro
Physics - DF
with graphene and low dimensional
systems
26 TORMEN
FIS/03 Department of
Fabrication of microfluidic devices
Massimo
Physics - DF
for studying living cells, responding
to external stimuli, by vibration
spectroscopies
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
7
Dottorando
Ciclo Supervisore
NKOUA
27 SCOLES
Ngavouka
Giacinto
Maryse Dadina
OTTAVIANI Giulia
27 ZACCHIGNA
Serena
SSD
FIS/03
MED/28 Clinical Department
of Medical Science,
Surgery and Healt DCSMCS
FIS/03 Department of
Physics - DF
FIS/03 Department of
Physics - DF
PALMA
Giuseppina
PANIGHEL Mirco
26 FRALEONI
Alessandro
27 MORGANTE
Alberto
PERONIO Angelo
25 COMELLI
FIS/03
Giovanni
27 LAZZARINO
FIS/03
Marco
27 CESARO Attilio CHIM/04
PIANTANIDA Luca
PITTIA Paola
RADIVO Andrea
26 TORMEN
Massimo
ROMEO Michele
26 FRONZONI
Giovanna
SAJID Hussain
NomeDip
Department of
Physics - DF
FIS/03
Department of
Physics - DF
Department of
Physics - DF
Department of Life
Sciences - DLS
Department of
Physics - DF
CHIM/02 Department of
Chemical and
Pharmaceutical
Sciences - DSCF
26 BIASIOL Giorgio FIS/03 Department of
Physics - DF
SALGADO
Bernardes
Pereira Simâo
Pedro
SAMMITO Davide
27 FERMEGLIA
Maurizio
INGIND/24
Department of
Engineering and
Architecture - DIA
25 ROMANATO
Filippo
FIS/03
Department of
Physics - DF
SANTESE
Francesca
26 FERMEGLIA
Maurizio
SCOTTI Nicola
27 BRESCHI
Lorenzo
STOKELJ Tina
27 FERMEGLIA
Maurizio
Titolo Tesi
Application of AFM based immune
assays to few cells proteomics
Use of nanotechnology for the
evaluation of the effect of laser
therapy on neo-angiogenesis tumor
in vivo and in vitro
Nanostructured dye-sensitized solar
cells
Organic Molecules and Carbon
Nanotubes Assembled on Metal
Surfaces:Properties and
Applications in Molecular
Electronics and Photovoltaics
Single-molecule heterogeneous
catalysis
Plasmonic ruler and the applications
to the DNA origami
Nanotecnology for food science
Experimental study of the physics of
nanostructured organic
photovoltaic devices.
Development and applications of
methodologies TDDFT for the
simulation of core spectrum for
condensed matter.
Syntesis of ordered semiconductor
nanostructures by directed selfassembly for photonic applications
Multiscale Modelling of Complex
Material Systems Morphology
Design, Fabrication and
Characterization of Plasmonic
Nanostructures for Solar Cells Light
Harvesting Enhancement.
INGDepartment of
Multiscale molecular modeling for
IND/24 Engineering and
nanostructured multifunctional
Architecture - DIA materials and coatings
MED/28 Clinical Department Laboratory evaluation of several
of Medical Science, nanofilled dental resin composites
Surgery and Healt - mechanical and chemical properties
DCSMCS
INGDepartment of
Agri-food Nanotechnology
IND/24 Engineering and
Architecture - DIA
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
8
Dottorando
STOPAR Alex
TARUSHA Lorena
TAVAGNACCO
Letizia
Ciclo Supervisore
27 TOFFOLI
Giuseppe
SSD
FIS/03
NomeDip
Department of Life
Sciences - DLS
27 PAOLETTI
BIO/10 Department of Life
Sergio
Sciences - DLS
26 CESARO Attilio CHIM/04 Department of Life
Sciences - DLS
VAIDYA Shital
26 GOTTER
Roberto
FIS/03
Department of
Physics - DF
VEGA Marienette
27 SERGO Valter
INGIND/22
VENTURELLI
Leonardo
27 SCOLES
Giacinto
FIS/03
Department of
Engineering and
Architecture - DIA
Department of
Physics - DF
VIRGILIO
Francesca
26 TORMEN
Massimo
FIS/03
WANG Lianqui
27 FORNASIERO
Paolo
ZANNIER
Valentina
ZANUSSO Chiara
27 RUBINI Silvia
CHIM/03 Department of
Chemical and
Pharmaceutical
Sciences - DSCF
FIS/03 Department of
Physics - DF
BIO/14 Department of Life
Sciences - DLS
24 TOFFOLI
Giuseppe
Department of
Physics - DF
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
Titolo Tesi
Innovative Tools for
Pharmacogenetics and
Pharmacogenomics: Protein-Nucleic
Acid Interactions Within SelfAssembled Nanosystems
Novel nanostructured biomaterials
for biomedical applications
How do water molecules probe and
control bionanostructures and food
functionalities
Low-dimensional magnetic
materials: the electronic structure
and correlation effects
Raman and fluorescence
spectroscopy of biomedical
nanomaterials
Application of Micro mechanical
oscillators to miRNA detection for
heart diseases
Development of electrochemical
sensors by nanofabrication
techniques for biological and
medical diagnostics
Design, synthesis and
characterization of nanostructured
materials for electrocatalysis
Synthesis and characterization of
semiconductor nanowires
Nanotechnologies and oncology:
pharmacokinetics and
pharmacogenomics to optimize the
antitumor therapie
9
3.Schede attività dottorandi
Questo allegato contiene le schede dei dottorandi della scuola di nanotecnologia così come sono
pervenute al 31 gennaio 2012. Sono quindi incluse le schede dei dottorandi dei cicli 24, 25 e 26.
 Dottorandi del 24 ciclo: CARGNELLO Matteo, COZZARINI Luca, D’ESTE Elisa, ERA
Daniel, FIOR Raffaella, LANZILOTTO Valeria, LUISI Immacolata, MARINI Monica,
MIGLIORINI Elisa, PAKDAST Hossein, SCIUTO Giacomo, TAVANO Federica,
ZANUSSO Chiara.
 Dottorandi del 25 ciclo: AMBROSINI Stefano, BIDOGGIA Silvia, CHEN Yan Xin,
GANAU Mario, GIORGIS Valentina, LUCAFO' Marianna, MARSICH Lucia, PERONIO
Angelo, SAMMITO Davide
 Dottorandi del 26 ciclo: CASSESE Damiano, CORVAGLIA Stefania, DAL COL Valentina.
FRASSETTO Andrea, MINIUSSI Elisa, MITRI Elisa, PALMA Giuseppina, RADIVO
Andrea, ROMEO Michele, SAJID Hussain, SANTESE Francesca, TAVAGNACCO
Letizia, VAIDYA Shital, VIRGILIO Francesca.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
10
Dottorandi del 24 ciclo:
MATTEO CARGNELLO
Laboratorio di lavoro: lab. 439-523 Dip. Sc. Chimiche e Farmaceutiche, Edificio C11
Titolo della tesi: Tailored nanoarchitectures based on transition metals for heterogeneous
catalysis
Supervisore: Prof. Paolo Fornasiero
Tutori: Prof. Raymond J. Gorte (UPenn, USA), Dr. Tiziano Montini
Attività di ricerca
L’attività di ricerca del terzo anno di dottorato è stata focalizzata su vari aspetti:
- Il completamento della caratterizzazione dei materiali preparati durante il corso del primo e del
secondo anno;
- l’estensione della procedura di incapsulamento ad altre combinazioni metallo-ossido per
ottenere strutture disperdibili;
- la sintesi di particelle metalliche di dimensioni precise e variabili per la preparazione di
catalizzatori eterogenei modello e il loro studio in condizioni di reazione reali.
Durante il corso del primo e del secondo anno di dottorato sono stati preparati materiali a base
di Cu, Pd e Au incapsulati nella ceria (CeO2) che sono stati caratterizzati utilizzando la
spettroscopia di assorbimento di raggi X, la microscopia elettronica a scansione a trasmissione e il
chemiadsorbimento (dati pubblicati). Inoltre, abbiamo dimostrato che le strutture disperdibili
Pd@CeO2 possono essere utilizzate nella preparazione di catalizzatori attivi e stabili da impiegare
nelle celle a combustibile ad ossidi solidi (Solid Oxide Fuel Cells - SOFC) (dati pubblicati).
L’approccio di incapsulamento è risultato particolarmente promettente per il palladio e questa
procedura è stata quindi estesa ad altre combinazioni di metalli e ossidi. Inizialmente, è stata
sviluppata una procedura più semplice e flessibile per preparare particelle di Pd variamente
funzionalizzate in cui i monostrati organici sono facilmente modificabili in composizione. L’attività
catalitica e la riciclabilità delle particelle sono state dimostrate in reazioni organiche di coupling
(dati pubblicati). Il metodo di embedding per l’ottenimento di strutture disperdibili è stato quindi
esteso ad un core di Pt e a shells di TiO2 e ZrO2. Questi risultati dimostrano la versatilità del metodo
e la ampia applicabilità della procedura con il risultato che diverse nanostrutture possono essere
disperse su supporti o usati in soluzione. Tutti i materiali preparati sono stati approfonditamente
caratterizzati con tecniche di microscopia a la loro attività in reazioni in fase gassosa è stata studiata
(dati inviati per la pubblicazione).
Infine, la preparazione di nanocristalli monodispersi di metalli d8 (Ni, Pd e Pt) è stata realizzata
e le particelle ottenute sono state utilizzate per la preparazione di catalizzatori modello supportati su
CeO2 o Al2O3. L’attività catalitica di tali sistemi modello è stata studiata nelle reazioni di
ossidazione del CO e conversione del gas d’acqua (WGSR) in condizioni di reazione reali. Ciò ha
permesso l’ottenimento di importanti informazioni sul meccanismo di reazione e sulla sua
dipendenza con la dimensione delle particelle e del supporto.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
11
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa)
1) M. Cargnello, A. Gasparotto, V. Gombac, T. Montini, D. Barreca and P. Fornasiero,
"Photocatalytic H2 and added-value byproducts: the role of metal oxide systems in their synthesis
from liquid oxygenates.", European Journal of Inorganic Chemistry 2011 (2011), 4309-4323,
selected as cover article.
2) M. Cargnello, N. L. Wieder, P. Canton, T. Montini, G. Giambastiani, A. Benedetti, R. J. Gorte
and P. Fornasiero, "A Versatile Approach to the Synthesis of Functionalized Thiol-protected
Palladium Nanoparticles.", Chemistry of Materials 23 (2011), 3961-3969.
3) J.-S. Kim, N. L. Wieder, A. J. Abraham, M. Cargnello, P. Fornasiero, R. J. Gorte and J. M. Vohs,
"Highly Active and Thermally Stable Core-Shell Catalysts for Solid Oxide Fuel Cells.", Journal of
the Electrochemical Society 158 (2011), B596-B600.
4) N. L. Wieder, M. Cargnello, K. Bakhmutsky, T. Montini, P. Fornasiero and R. J. Gorte, "A study
of the water-gas-shift reaction over Pd@CeO2/Al2O3 core-shell catalysts.", The Journal of
Physical Chemistry C 115 (2011), 915-919.
5) M. Cargnello, C. Gentilini, T. Montini, E. Fonda, S. Mehraeen, M. Chi, M. Herrera-Collado, N.
D. Browning, S. Polizzi, L. Pasquato and P. Fornasiero, "Active and stable embedded Au@CeO2
catalysts for preferential oxidation of CO.", Chemistry of Materials 22 (2010), 4335-4345.
6) N. L. Wieder, M. Cargnello, K. Bakhmutsky, T. Montini, P. Fornasiero and R. J. Gorte, "A
study of the water-gas-shift reaction over Pd@CeO2/Al2O3 core-shell catalysts.", The Journal of
Physical
Chemistry
C
(2010),
in
press,
doi:10.1021/jp102965e.
7) V. Gombac, L. Sordelli, T. Montini, J. J. Delgado, A. Adamski, G. Adami, M. Cargnello, S.
Bernal and P. Fornasiero, “CuOx-TiO2 Photocatalysts for H2 Production from Ethanol and Glycerol
Solutions.”, The Journal of Physical Chemistry A 114 (2010), 3916-3925.
8) M. Cargnello, N. L. Wieder, T. Montini, R. J. Gorte and P. Fornasiero, "Synthesis of dispersible
Pd@CeO2 nanostructures by self-assembly.", Journal of the American Chemical Society 132
(2010),
1402-1409.
9) M. Cargnello, T. Montini, S. Polizzi, N. L. Wieder, R. J. Gorte, M. Graziani and P. Fornasiero,
“Novel embedded Pd@CeO2 catalysts: a way to active and stable catalysts.”, Dalton Transactions
39
(2010),
2122-2127.
10) L. De Rogatis, M. Cargnello, V. Gombac, B. Lorenzut, T. Montini and P. Fornasiero,
“Embedded phases: a way to active and stable catalysts.”, ChemSusChem 3 (2010), 24-42.
Capitoli/sezioni di libri/volumi
1) L. De Rogatis, T. Montini, V. Gombac, M. Cargnello and P. Fornasiero, “Stabilized metal
nanoparticles embedded into porous oxides: a challenging approach for robust catalysts.”, in
Nanorods, Nanotubes and Nanomaterials Research Progress (2008), Wesley V. Prescott and
Arnold I. Schwartz Editors, Nova Science Publishers, 2008, New York, pp. 71-123.
Partecipazione a congressi (come relatore)
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
12
- “Metal-doped TiO2 for hydrogen production”, V. Gombac, T. Montini, M. Cargnello, M. Graziani
and P. Fornasiero, Slovenian Conference on Materials and Technologies for Sustainable Growth,
oral presentation, University of Nova Gorica, Ajdovscina, Slovenia, 12th May 2009
- Informal workshop Scuola di Dottorato di Ricerca in Nanotecnologie and Int. Max-Planck
Research School for Science and Technology of Nanostructures, oral presentation “Rare-earths
oxides-based nanostructures as heterogeneous catalysts”, Max Planck Institute of Microstructure
Physics, Halle, 15th-16th July 2009
- “I giovani e la chimica in Friuli-Venezia Giulia”, oral presentation “Self-assembled materials
based on metallic nanoparticles for heterogeneous catalysis”, Department of Chemistry, University
of Trieste, 24th September 2009
- “Active and stable Au catalysts for H2 purification”, T. Montini, M. Cargnello, C. Gentilini, L.
Pasquato, P. Fornasiero, S. Mehraeen, N. D. Browning, E. Fonda, GOLD 2009, 5th international
conference on gold technology and applications, Heidelberg (Germany), poster presentation, 25th30th July 2009
- 2nd PhD workshop, Martin-Luther Universitat Halle-Wittenberg, Wittenberg, Germany, poster
presentation “Active and stable Au catalysts for H2 purification”, 10th-11th September 2009
- XV National School of Organometallic Chemistry, oral presentation “Pd@CeO2 dispersible
structures prepared by self-assembly for heterogeneous catalysis.”, Matteo Cargnello, Noah Wieder,
Tiziano Montini, Raymond J. Gorte and Paolo Fornasiero, Bertinoro (FC), 23-27 May 2010
- “Embedded phases: a way to active and stable catalysts.”, M. Cargnello, lecture, Universidad de
Cadiz (Spain), Facultad de Ciencias, Departamento de Ciencia de Materiales e Ingeniería
Metalúrgica y Química Inorgánica, 10th June 2010
- XXXVIII National Congress of the Inorganic Chemistry Division of the Italian Chemical Society,
Trieste, Italy, “Embedded metal nanoparticles as heterogeneous catalysts: advantages and
disadvantages.”, M. Cargnello, P. Fornasiero, V. Gombac, M. Graziani, B. Lorenzut and T.
Montini, poster presentation, 14 September 2010.
- M. Cargnello, N. Wieder, R. J. Gorte and P. Fornasiero, "Synthesis of dispersible core-shell
metal@oxide materials and their application as stable fuel cell catalysts.", invited speaker at the
conference "Chemically synthesized nanoparticles and catalysis", Argonne National Lab (Argonne,
IL, USA), 28th April 2011.
- M. Cargnello, R. J. Gorte and P. Fornasiero, "Synthesis of dispersible core-shell metal@oxide
materials and their application as stable fuel cell catalysts.", ICTP-SISSA Workshop on New
Materials for Renewable Energy, ICTP, Trieste, Italy, 17th-21st October 2011.
Partecipazione a congressi (come co-autore)
- “Photocatalytic H2 production over optimized CuOx-TiO2 nanocomposites.”, V. Gombac, T.
Montini, L. Sordelli, M. Cargnello, M. Graziani, P. Fornasiero, Summer School in catalysis 2009,
Porto Carras, Greece, May 2009 (poster presentation by V. Gombac)
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
13
- “Design of active and stable catalysts for H2 purification.”, T. Montini, M. Cargnello, C. Gentilini,
L. Pasquato, P. Fornasiero, S. Mehraeen, N. D. Browning, E. Fonda, E-MRS 2009 Spring Meeting,
Strasbourg, June 2009 (oral presentation by T. Montini)
- “Photocatalytic H2 production over optimized CuOx-TiO2 nanocomposites.”, P. Fornasiero, V.
Gombac, T. Montini, L. Sordelli, M. Cargnello, M. Graziani, VII Convegno Nazionale Consorzio
Scienza e Tecnologia dei Materiali, Tirrenia, Italy, June 2009 (oral presentation by P. Fornasiero)
Attività formativa
Periodi di permanenza all’estero (data e Sede)
- Research center ICCOM-CNR Florence, Sesto Fiorentino, AFM experiments, 1-7 February 2009
- Sinchrotron Soleil, Gif-sur-Yvette, Paris, EXAFS experiments, 19-23 February 2009
- Indian Institute of Technology, Chennai, 31 March – 5 April 2009
- Universidad de Cadiz (Spain), Facultad de Ciencias, Departamento de Ciencia de Materiales e
Ingeniería Metalúrgica y Química Inorgánica, Prof. S. Bernal and Dr. J. J. Delgado, 1st June – 31st
July 2010
- Universidad de Cadiz (Spain), Facultad de Ciencias, Departamento de Ciencia de Materiales e
Ingeniería Metalúrgica y Química Inorgánica, Prof. S. Bernal and Dr. J. J. Delgado, 28th February –
9th March 2011
- University of Pennsylvania, Department of Chemistry and Materials Science and Engineering,
Prof. Christopher B. Murray, 1st April – 30th September 2011
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
- “Tecniche di caratterizzazione con luce di sincrotrone”, Prof. G. Vlaic, corso di laurea magistrale
in chimica, 40 hours
- “Proprietà fisiche dei materiali”, Prof. A. Franciosi, corso di laurea magistrale in chimica, 40
hours
- Course “Molecular self-assembling and nanostructures”, Dr. L. Casalis, Prof. A. Morgante, Prof.
L. Pasquato, 8 hours
- Course “Advanced Microscopy”, Dr. L. Felisari, Dr. C. Africh, 14 hours
- Course “Photoemission Spectroscopies”, Prof. A. Baraldi, 11 hours
Congressi, seminari, corsi avanzati e altre attività didattiche passive
- Annual meeting PhD School in Nanotechnology, 13-15 January 2009, total 20 hours
- “Information meetings for doctoral students”, 30 June 2009, 3 hours
- “Seminar on writing (and managing) a research project”, 16th October 2009, 4 hours
- Annual meeting PhD School in Chemical and Pharmaceutical Sciences and Technologies, 21-23
January 2009, total 10 hours
- 1st International Conference on Nanustructured Materials, Kottayam, Kerala (India), 6-8 April
2009
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
14
- Conference “Modeling reactions at the nanoparticle scale”, Prof. P. Westmoreland, 8 May 2009
- Conference “Chimica fisica delle interfasi in sistemi nanostrutturati”, Dr. I. Colombo, 15 May
2009
- Conference “Supramolecular Chemistry of Naphthalenediimides”, Dr. G. Dan Pantos, 8 June 2009
- Conference “New chemistry of dithiolenes: from biomimetic models to sensor”, Prof. Partha Basu,
13 July 2009
- Conference “NMR Techniques for Investigating the Supramolecular Structure in Solution”, Prof.
Alceo Macchioni, 17 September 2009
- 3rd year PhD students presentations, 26 November 2009
- Annual meeting PhD School in Chemical and Pharmaceutical Sciences and Technologies, 18-20
January 2010, total 10 hours
- Seminar on “How to present scientific results”, Dr. Hanna Mamzer, 22 January 2010, 7 hours
- Seminar “Combustili solari: nuove opportunità per la ricerca”, Prof. S. Perathoner, 1 March 2010,
1 hour
- Seminar “Energia per il XXI secolo”, Dr. N. Armaroli, 25 March 2010, 2 hours
- Sessione TEM, Dipartimento di Chimica Fisica, Università Cà Foscari di Venezia, Mestre, 14
Aprile 2010
- Sessione TEM, Dipartimento di Chimica Fisica, Università Cà Foscari di Venezia, Mestre, 14
Maggio 2010
- TEM-UCA Summer Workshop “Transmission Electron Microscopy on Catalytic Materials and
Nanoparticles”, Universidad de Cadiz (Spain), 12th-16th July 2010
- XXXVIII National Congress of the Inorganic Chemistry Division of the Italian Chemical Society,
Trieste, Italy, 13-16 September 2010
- Seminar “Can CexZr1-xO2 materials be suitable supports for polioxometallates?”, Prof. G. Ranga
Rao, 29 September 2010
- Seminar “Metal oxide nanomaterials in sensors and biomedicine”, Prof. Sangeeta Kale, 23
November 2010
- 3rd year PhD students presentations, 23 November 2010
- Durante l’anno 2011, sono state seguite numerose conferenze durante il periodo alla University of
Pennsylvania.
Attività didattica di supporto e attività didattica attiva
- Attività di tutorato per il Laboratorio di Chimica Generale per Scienze Geologiche con il Prof. P.
Fornasiero, totale 50 ore
- Esercizi di Chimica Generale e Stechiometria per il Corso Integrato di Chimica Generale per
Biotecnologie, STAN e Scienze Geologiche, 10 ore
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
15
LUCA COZZARINI
Titolo della tesi:
Supervisore:
“Nanomaterials based on II-VI semiconductor quantum dots”
Dr. Vanni Lughi
Attività di ricerca
Attività svolta nel terzo anno
Nel corso del mio terzo anno di ricerca mi sono dedicato a diverse attività:
(a) durante il mio periodo di permanenza presso il NREL1, mi sono occupato di: (i)
preparazione superficiale di cristalli di ossido di titanio (sia anatase che rutile), di
ossido di zinco e titanato di stronzio; (ii) assemblaggio di monolayers di
nanocristalli di solfuro di piombo sugli ossidi sopraelencati; (iii) misure
fotoelettriche e ottiche su ossidi sensitivizzati con nanocristalli di solfuro di
piombo; (iv) caratterizzazione di leganti organici superficiali su nanocristalli di
solfuro di piombo, con spettroscopia IR e risonanza magnetica nucleare; (v)
sostituzione di leganti organici superficiali; (vi) tentativi di misura della posizione
dei livelli energetici di nanocristalli con voltammetria ciclica.
(b) presso i laboratori del DI32, ho proseguito l’attività di ricerca volta all’ottenimento
di un materiale semiconduttore a banda elettronica intermedia, partendo da
nanocristalli di semiconduttori. Nel corso di quest’anno ho: (i) ottimizzato le
procedure di cambio tensioattivo e assemblaggio su vari substrati; (ii) studiato
tramite metodi ottici e diffrattometria X gli assemblati dopo diversi trattamenti
termici
(c) presso i laboratori del DI3, ho infine proseguito l’attività di ricerca avente come
obiettivo la sintesi di fosfori secondari per LED, tramite: (i) sviluppo di sintesi di
nanocristalli con composizione e proprietà ottiche personalizzate (controllo di
lunghezza d’onda di emissione, larghezza di banda di emissione ed efficienza di
luminescenza); (ii) inclusione di nanocristalli in una matrice polimerica trasparente
(preservando le loro proprietà ottiche)
Pubblicazioni/abstracts in conferenze
o L. Pavan, L. Cozzarini, and V. Lughi, "Interdiffusion-controlled Optical Properties
in Nanocrystalline Heterostructures and Nanostructured Materials", MRS Spring
Meeting 2011, San Francisco, CA, USA, 28.04.2011
o L. Cozzarini, F. Antoniolli and V. Lughi, "Optical properties of a novel
nanostructured CdS/CdTe material", SPIE Smart Structures/NDE, Conference 7890,
San Diego, CA, USA, 06.03.2011
Partecipazioni a congressi (come relatore)
o L. Cozzarini "Semiconductor Nanocrystals application to Optoelectronic Devices",
Finmeccanica/Fulbright meeting 2011, Washington DC, USA, 15.03.2011
Attività formativa
Periodi di permanenza all’estero
18 ottobre 2010 – 20 aprile 2011 (durata totale del periodo) presso il Solar Energy
Research Facility del NREL, Golden, CO, USA.
Ore di lezione seguite, III° anno (sostituite da lettura/studio personale):
Libri:
1
National Renewable Energy Laboratory, 1617, Cole Boulevard, Golden, CO 80401, USA
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
16
A. L. Rogach, “Semiconductor Nanocrystal Quantum Dots”, ISBN 9788-3211-75235-7
C. Harris, M. D. Bertolucci, “Symmetry and Spectroscopy”, ISBN 0-486-66144-X
Reviews:
V. Klimov, “Spectral and Dynamical properties of multiexcitons in Semiconductor
Nanocrystals”, Annu Rev Phys Chem, 58, 635 (2007)
Ore di laboratorio svolte, III° anno
o Circa 700 ore del lavoro di ricerca sono state svolte nei laboratori del DI3
o Circa 450 ore di laboratorio come ospite presso il Solar Energy Research Facility del
NREL
Congressi, seminari ed incontri organizzati dalla scuola
“Summer School of Nanotechnology”, Università degli Studi di Trieste, 20-23.09.2011
Corsi avanzati seguiti – seminari – altre attività didattiche passive
o MRS Spring Meeting 2011 conference, San Francisco, CA, USA, 25-29.04.2011
o C. G. Bailey (Rochester Institute of Technology) “Growth and Characterization of
InAs QD array GaAs p-i-n Solar Cells”, seminario, National Renewable Energy
Laboratory, 8.2.2011
o C. C. Tu (University of Washington-Seattle) “Solution-processed Optoelectronic
Devices from Colloidal Inorganic Semiconductor Materials”, seminario, National
Renewable Energy Laboratory, 15.2.2011
o M. Topic (University of Ljubljana) “PV module effective efficiency and performance
mapping across Europe”, seminario, National Renewable Energy Laboratory,
15.2.2011
Attività didattica attiva
o Circa 2 ore di supporto in laboratorio al corso “Materiali nanostrutturati”(prof.
Vanni Lughi – II semestre, AA 2010-2011)
o Co-relatore di una tesi di laurea triennale in Ingegneria Industriale (Mattia
Castellucci, “Diffusione in Nanocristalli di Semiconduttori II-VI: analisi
sperimentale”, AA 2010-2011).
2
Dipartimento di Ingegneria Industriale e dell’Informazione, Università degli Studi di Trieste, via Valerio 6A, 34127 Trieste, Italy
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
17
ELISA D’ESTE
Titolo della tesi: BIO-SAMPLE ENVIRONMENT MANIPULATION USING ADVANCED
MICROSCOPY TECHNIQUES
Supervisore: prof. Alberto Morgante; dott. Danut-Adrian Cojoc
Tutori (eventuali): prof. Enrico Tongiorgi
Attività di ricerca
Durante il terzo anno di dottorato sono state seguite tre principali attività:
1. Utilizzo della tecnologia dei liposomi, sviluppata durante il secondo anno di dottorato, al fine di
analizzare l’effetto di alcune proteine sulla morfologia dei coni di crescita (GC) di neuroni
ippocampali in coltura. In particolare, in collaborazione con il laboratorio del prof. Torre alla
S.I.S.S.A., è stato analizzato l’effetto che un diverso numero di molecole di Netrina-1 e
Semaphorin-3A hanno su filopodia e lamellipodia dei GC, nonchè sulla loro distanza dal sito di
rilascio.
2. La tecnologia dei Quantum dots (QD) consente di seguire mediante microscopia a fluorescenza il
movimento di singole molecole all’interno della cellula. Il nostro interesse è visualizzare il
trafficking del BDNF (si vedano report I e II anno) all’interno dei neuroni a seguito dell’endocitosi,
dal momento che questo processo non è stato ancora caratterizzato. Durante quest’anno è stato
ottimizzato con successo il protocollo per legare covalentemente il BDNF ai QD. Successivamente i
QD funzionalizzati sono stati incapsulati in liposomi e sono state dimostrate sia la possibilità di
manipolazione con gli Optical tweezers che il rilascio a seguito della fotolisi del doppio strato
lipidico.
3. Durante i tre mesi trascorsi presso il laboratorio del prof. Stefan Hell sono state acquisite
immagini mediante la microscopia STED (STimulated Emission Depletion) al fine di caratterizzare
meglio alcuni processi biologici di interesse per studi futuri di delivery localizzato di molecole. In
particolare sono state acquisite immagini relative all’apparato di Golgi e alla struttura di actina e
tubulina nei coni di crescita.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa),
1. D’Este E, Baj G, Beuzer P, Ferrari E, Pinato G, Tongiorgi E and Cojoc D, (2011) Integrative
Biology “Use of the optical tweezers technology for long-term, focal stimulation of specific
subcellular neuronal compartments”. May 3;3(5):568-77.
2. Pinato G, Lien LT, D’Este E, Torre V and Cojoc D, (2011) Journal of European Optical Society
“Neuronal chemotaxis by optically manipulated liposomes”. Vol 6, 11042.
3. Pinato G, Raffaelli T, D’Este E, Tavano F and Cojoc D, (2011) Journal of Biomedical Optics
“Optical delivery of liposome encapsulated chemical stimuli to neuronal cells”. Sep;16(9):095001.
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
1.“8th IBRO world congress of Neuroscience” 14-18th July 2011, Florence. D’Este E., Baj G.,
Pinato G., Tongiorgi E. & Cojoc D., “Focal delivery of BDNF to cultured neurons with optical
tweezers”.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
18
2. “EBSA 2011 – 9th European Biophysics Congress”23-27th August 2011, Budapest. D’Este E.,
Baj G., Pinato G., Tongiorgi E. & Cojoc D., “Focal delivery of BDNF to cultured neurons with
optical tweezers”.
3.“8th IBRO world congress of Neuroscience” 14-18th July 2011, Florence. Pinato G., Thuy Lien
L., D’Este E., Torre V. & Cojoc D., “Stimulation of neurite retraction and growth by local release
of guidance molecules from lipid vesicles”.
Partecipazione a congressi (come relatore)
PhD School in Nanotechnology Annual Meeting 2011, 17-20 Gennaio 2011, Trieste, “Bio-sample
environment manipulation using advanced microscopy techniques”.
Attività formativa
Periodi di permanenza all’estero (data e Sede)
24 Settembre - 24 Dicembre 2011, Max Planck Institute for Biophysical Chemistry, Department of
NanoBiophotonic, laboratorio prof. Stefan Hell, Göttingen, Germania.
Congressi, seminari, corsi avanzati e altre attività didattiche passive
“Master in Complex Actions”, S.I.S.S.A. (200 ore);
“Misure ripetute e cluster di dati con R”, 24 marzo 2011, Associazione Nazionale Biotecnologi
Italiani; Bologna (8 ore);
“PhD School in Nanotechnology Annual Meeting 2011”, 17-20 Gennaio 2011, Trieste (10 ore
circa);
“8th IBRO world congress of Neuroscience” 14-18 Luglio 2011, Firenze (30 ore);
“New Approches in Cancer Therapy”, prof. Konrad Misiura, 12 Maggio, Trieste (1 ora);
“School in Super Resolution Microscopy”, 26 settembre 2011, Göttingen (2 ore);
“1st Super Resolution Users Club Meeting”, 30 settembre 2011, Göttingen (4 ore);
“PhD CMPB Symposium”, 20 ottobre 2011, Göttingen (2 ore);
“Dissecting the neural circuits that control movement”, Prof. Dr. Martyn Goulding, 24 ottobre
2011, Göttingen (1 ora);
“Nobel Lecture 2011: Roger Tsien”, 27 ottobre 2011, Göttingen (1 ora).
Attività didattica di supporto e attività didattica attiva
Life Learning Centre Trieste, gennaio-febbraio 2011, “Guardando dentro il cervello” c/o Istituto
Deledda e liceo Galilei (8 ore).
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
19
DANIEL ERA
Titolo della tesi: Applicazioni nanotecnologiche e farmacogenetica
Supervisore: Prof. Tullio Giraldi
Tutori (eventuali):
Attività di ricerca
Questo progetto di dottorato di ricerca è finalizzato allo studio dell'applicazione nella
pratica clinica attuale della medicina di comunità, di tests farmacogenetici utili sia per la
determinazione di polimorfismi noti per influenzare la dose iniziale di warfarin nella terapia
anticoagulante orale, sia per l’analisi dei polimorfismi associati alla risposta di farmaci
antidepressivi . Gli studi si sono perciò svolti in collaborazione con la medicina territoriale, al fuori
dei centri di eccellenza e le rigorose condizioni in cui di solito vengono eseguiti i
trials. In quest’ottica, i risultati finora ottenuti, in accordo con la letteratura corrente,
supportano l'impiego dell’analisi dei polimorfismi per la determinazione della corretta dose iniziale
di warfarin. Inoltre, il polimorfismo del trasportatore della serotonina (5-HTTLPR) è stato valutato
in relazione alla risposta ai farmaci antidepressivi appartenenti alla classe degli inibitori selettivi
della ricaptazione della serotonina (SSRI), e anche nella medicina di comunità, sia in
pazienti oncologici che psichiatrici, l’analisi di 5-HTTLPR sembra essere uno strumento utile
per predire
l’esito
della
risposta
al
trattamento con
SSRI.
Infine, con lo sviluppo di nuove tecnologie, i costi per l'analisi genetica sono diminuiti,e possono
essere considerati limitati soprattutto in relazione ai vantaggi raggiunti con il loro impiego. In ogni
caso, il rapporto costo-efficacia dei test farmacogenetici potrebbe essere migliorato con lo
sviluppo di ulteriori devices che permettano un’analisi più veloce ed economica.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa
• Psychological response to cancer: role of 5-HTTLPR genetic polymorphism of serotonin
transporter. Anticancer research 30: 3823-3826 (2010);
• Pharmacogenetic of escitalopram and mental adaptation to cancer in palliative care: report
of 18 cases. Tumori 97(3):358-61 (2011).
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
•
•
•
•
Role of genetic polymorphism 5-HTTLPR of seotonin transporter in psychological response
to diagnosis of breast cancer. XI national congress Italian Society of Psycho-Oncology
(SIPO). October 1-3, 2009, Senigallia (An).
Genetics interaction between citalopram antidepressant activity and MAO-A VNTR
polymorphism in palliative care of cancer. 34° national congress Italian Society of
Pharmacology (SIF). October 14-17, 2009, Rimini.
Ruolo del polimorfismo genetico 5-HTTLPR del trasportatore della serotonina nella risposta
psicologica alla diagnosi di cancro della mammella. XVII Congresso Nazionale della
Società Italiana di neuropsicofarmacologia 22-25 settembre 2010, Cagliari;
XIV Seminario Nazionale per dottorandi in Farmacologia e Scienze affini. Siena, Certosa di
Pontignano, 20-23 Settembre 2010. Pharmacogenetic research and its applications in current
clinical practice;
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
20
•
Pharmacogenetic of warfarin and its applications in the community medicine . III
Monothematic Symposium SIF 2011 “Pharmacogenomics and cancer: from bench to
bedside”. Grado (GO), Grand Hotel Astoria, October 8, 2011;
Capitoli/sezioni di libri/volumi
Collaborazione come traduttore all’edizione italiana del libro “Farmacologia medica ed elementi di
terapia” edito da Elsevier.
Attività formative
Congressi, seminari, corsi avanzati e altre attività didattiche passive
• Nanotechnology School Annual Meeting, January 2009;
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Congress “Highlights in oncology. Recenti acquisizioni in oncologia”. February 11 2009,
Aviano (Pn);
III Meeting-Workshop “Nuove Prospettive in Chimica Farmaceutica”. February 13-14
2009, Castelvecchio Pascoli (Lu);
Prof. Maurizio Fermeglia “Uso del VPN per l’accesso remoto”. March 20 2009, Trieste;
Dr A. Bardelli “Cancer mutations and targeted therapies”. May 6 2009, Trieste;
Prof. PR Westmoreland, Dept. of Chemical Engineering, University of Massachusetts
Amherst, “Modeling reactions at the nanoparticle scale”. May 8 2009, Trieste;
Dr I. Colombo “Chimica Fisica delle interfasi in sistemi nanostrutturati”. May 15 2009,
Trieste;
Incontri informativi per i dottorandi organizzato dalla Sezione Ricerca e Dottorati in
collaborazione con il Sistema Bibliotecario di Ateneo. June 29 2009, Trieste;
34° National Congress of the Italian Society of Pharmacology “Il valore del farmaco per la
tutela della salute”. October 14-17 2009, Rimini;
Corso introduttivo alla farmacoepidemiologia, ASS1-ISS. November 19-21 2009, Trieste;
Nanotechnology School Annual Meeting, January 2010
Dr H Mamzer, Sociology Department of Adam Mickiewicz University in Poznan (Poland),
“How to present scientific results in public” January 22, 2010, Trieste.
Prof. M Nobrega, University of Minho (Portugal) “Development of On-line Monitoring
devices for the extrusion process”. June 15 2010, Trieste;
XIV Seminario Nazionale per dottorandi in Farmacologia e Scienze affini. Siena, Certosa di
Pontignano, 20-23 Settembre 2010;
Dr S Kale, Defence Institute of Advanced Technology (DIAT), India. “Metal oxide
nanomaterials in sensors and biomedicine”. November 23, 2010, Trieste;
Nanotechnology School Annual Meeting, January 2011;
Nanotechnology Summer School, September 20-23, 2011, Trieste;
III Monothematic Symposium SIF 2011 “Pharmacogenomics and cancer: from bench to
bedside”. Grado (GO), Grand Hotel Astoria, October 8, 2011;
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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RAFFAELLA FIOR
Titolo della tesi: Development of BioMEMS for the study of mechanosensitive ion channels
and mechanical cell properties
Supervisore: prof. Orfeo Sbaizero
Tutori (eventuali): -
Attività di ricerca
Descrizione delle tematiche di ricerca e dei principali risultati scientifici raggiunti
Progettazione, caratterizzazione FEA, realizzazione dispositivi:
Dispositivi per l’analisi meccanica di singole cellule
Dispositivi per l’analisi meccanica di singole cellule completamente trasparenti
Dispositivi per l’analisi meccanica di singole cellule combinata a AFM conduttivo,
completamente trasparenti
Progettazione di dispositivi per l’analisi meccanica di singole cellule combinata e planar
patch clamp
Test su singole cellule:
Protocollo di funzionalizzazione localizzata (ODS e Pluronic grafting e lithography)
Analisi morfologica e meccanica
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa),
-R. Fior, S. Maggiolino, M. Lazzarino and O. Sbaizero, “A new transparent BioMEMS for
uni-axial single cell stretching”, Microsystem Technologies 2011 doi:10.1007/s00542-0111325-8
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
-R. Fior, S. Maggiolino, M. Lazzarino and O. Sbaizero, "A completely transparent MEMS
for mechanical properties evaluation of a single living cell", Proc. SPIE 7929, 792906
(2011) San Francisco CA USA; doi:10.1117/12.874445 (proceedings- speaker)
- R. Fior, S. Maggiolino, B. Codan and O. Sbaizero, “A study on the cellular structure
during stress solicitation induced by BioMEMS”, Proc. EMBC 2011 Boston USA
(proceedings -speaker)
- R. Fior, S. Maggiolino, B. Codan, R. Lal, O. Sbaizero, “A new BioMEMS for the study of
mechanosensitive ion channels”, Nanotechitaly 2011Venice Italy (poster)
- V. Martinelli, I. Pecorari, S. Maggiolino, R. Fior, B. Codan, L. Mestroni, O. Sbaizero,
“Metabolic and proliferative cells activity on different substrates”, Nanotechitaly 2011
Venice Italy (poster)
- B. Codan, D. Dorigo, V. Martinelli, S. Maggiolino, R. Fior and O. Sbaizero, “Lithograpic
patterned substrate with nanotips for cell indentation”, Nanotechitaly 2011 Venice Italy
(poster)
- I. Pecorari, B. Codan, V. Martinelli, S. Maggiolino, R. Fior and O. Sbaizero, “Mechanical
properties of 3T3 fibroblasts due to fixation assessed using atomic force microscopy”,
Nanotechitaly 2011 Venice Italy (poster)
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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- V. Zammattio, I. Pecorari, B. Codan, V. Martinelli, S. Maggiolino, R. Fior and O.
Sbaizero, “AFM cell morphological analysis: Influence of different environmental
conditions on fixed and living cells”, Nanotechitaly 2011 Venice Italy (poster)
Partecipazione a congressi (come relatore)
-R. Fior, S. Maggiolino, M. Lazzarino and O. Sbaizero, "A completely transparent MEMS
for mechanical properties evaluation of a single living cell", Proc. SPIE 7929, 792906
(2011) San Francisco CA USA; doi:10.1117/12.874445
- R. Fior, S. Maggiolino, B. Codan and O. Sbaizero, “A study on the cellular structure
during stress solicitation induced by BioMEMS”, Proc. EMBC 2011 Boston USA
Attività formativa
Periodi di permanenza all’estero (data e Sede)
- 5 ottobre 2010 – 3 novembre 2011 University of California San Diego, Department of
Bioengineering, La Jolla CA USA
Congressi:
- SPIE Photonics West San Francisco 22-27 gennaio 2011
- EMBC 2011 Boston USA 30 agosto – 3 settembre 2011
- Nanotech Italy Venezia 23-25 novembre 2011
Corsi:
- “Electron Beam Lithography” Nano3 UCSD San Diego, CA USA
Seminari:
- 28 aprile 2011 “Amyloid ion channels and neurodegenerative diseases” R. Lal, PhD UCSD, in San
Diego
- 6 maggio 2011 “Neuro mechanics and axonal transport: implications for peripheral nerve
regenerations” S. Shah, PhD University of Maryland, in San Diego
- 13 maggio 2011 “Bio-inspired Microenvironments Regulate Cell Fate” A. Engler, PhD UCSD, in
San Diego
- 20 maggio 2011 “Probing structural features of Alzheimer’s β amyloid ion channels in membranes
using Aβ mutants” S. A. Kotler, MS UCSD, in San Diego
- 24 giugno 2011 “DNA zipper based devices” A. Mo, P. Landon, PhD in San Diego
- 5 ottobre 2011 “Integrated Atomic Force Microscopy Techniques for Analysis of Biomaterials:
Study of Membrane Proteins” L. Connelly UCSD
- 10 ottobre 2011 “Integrated cortical interfaces for analysis and control of dexterous hand
movements” M. Mollazadeth, PhD Johns Hopkins University, in San Diego
Attività didattica di supporto e attività didattica attiva
Correlatrice tesi di laurea:
Realizzazione e caratterizzazione di superfici micreostrutturate per lo studio
dell’interazione cellula-substrato. (CdL Triennale in Ingegneria dei Materiali)
Caratterizzazione del modulo elastico mediante AFM dell’espressione della desmina in un
modello cellulare. (CdL Triennale in Ingegneria dei Materiali)
Riprogettazione e realizzazione di un sistema per la stimolazione di una popolazione di
cellule su membrana siliconica. (CdL Specialistica in Ingegneria dei Materiali)
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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VALERIA LANZILOTTO
Titolo della tesi: Self-assembling and charge transfer properties of thin organic films
Supervisore: Prof. Alberto Morgante
Tutori (eventuali):
Attività di ricerca
Durante il terzo anno di dottorato ho portanto avanti due differenti linee di ricerca ma entrambe
focalizzate nel tentativo di capire le poprietà elettroniche e strutturali di interfacce organiche –
inorganiche in una prospettiva di sviluppo di dispositivi elettronici che utilizzano sistemi organici.
Il primo tipo di sistemi studiati è incentrato sull’interazione di molecole poliaromtaiche con la
superficie di TiO2(110)-1x1.
Le molecole usate sono: C60, pentacene, PTCDI e perilene.
Per quanto riguarda il C60 e il pentacene si tratta di molecole poco interagenti con la superficie di
TiO2(110)-1x1. Nonostante la poca interazione entrambe le molecole formano film perfettamente
ordinati: nel caso del C60 troviamo una C(2X5) mentre nel caso del pentacene una quasi-(1x6).
L’ordinamento è dovuto principalmente all’interazione intermolecolare e al matching esistente tra le
dimensioni delle molecole con quelle del substrato.
Il PTCDI è un derivato del perilene con due gruppi fortemente elettron attrattori ai suoi lati: il
gruppo imidico (O=CNH=O). La presenza di questi gruppi rende il core perilenico un accettore
elettronico in grado di interagire fortemente con la superficie di TiO2(110)-1x1. Quello che si
verifica è infatti un netto trasferimento di carica dagli stati Ti 3d del subastrato verso il LUMO della
molecola che essendo parzialmente riempito viene spinto al di sotto del livello di Fermi dando
origine a nuovo stato (HOMO’). Nonostante questa forte interazione anche il PTCDI è in grado di
creare uno strato molecolare perfettamente ordinato (1X5).
Il ruolo svolto dai gruppi imidici del PTCDI è confermato dalla scarsa interazione osservata invece
tra il perilene e la superficie di TiO2(110)-1x1.
La seconda attività di cui mi sono occupata è stata quella di sviluppare il set-up generalmente
impiegato per misurare la conducibilità di singole molecole. Il metodo, denominato Break-Junction,
consiste nel portare una punta STM in contatto con una superficie d’oro su cui sono state depositate
le molecole di interesse. Durante il successivo allontanamento della punta una moleocola può
rimanere intrappolata nel gap esistente dopo la rottura del contatto tra punta e superficie.
Applicando un bias tra punta e campione è quindi possibile misurare la conducibilità della molecola
temporaneamente intrappolata.
Dopo la realizzzazione del set-up ho potuto procedere con i primi esperimenti impiegando una
molecola realtivamente nuova per questo tipo di misure: la tetraaza-Cu-ftalocianina. La
caratteristica principale di questa molecola sono i sostituenti azotati presenti alle sue estremità.
Studi recenti di conducibilità di singola molecola hanno infatti mostrato come picole molecole
terminate azoto (ammine o piridine) sono in grado di fornire valori di conducibilità ben definiti.
Cercando quindi di mantenere questa caratteristica all’interno della molecola ne abbiamo aumentato
la complessità. Le break-junctions ottenute a temperatura ambiente non hanno mostrato valori di
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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conducibilità attendibili o significativi probabilmente a causa dell’elevata diffusione delle molecole
sulla superficie d’oro. Lo step successivo è stato quello di ripetere le misure a bassa temperatura
(55K) in modo da inibire la difusione delle molecole. In queste condizioni le tracce di conducibilità
mostrano salti ripetuti compresi fra 10-3-10-4G0 con lunghezza complessiva pragonabile alle
dimensioni della molecola.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa),
1. V. Lanzilotto, C. Sanchez-Sanchez, G. Bavdek, D. Cvetko, M. F. Lopez, J. A. Martin-Gago and
L. Floreano “Planar growth of Pentacene on the dielectric TiO2 surface” J. Phys. Chem. C, 2011,
115 (11), pp 4664–4672
2. C. Sanchez-Sanchez, V. Lanzilotto, C. Gonzalez, A. Verdini, P. de Andrés, L. Floreano, Maria
F. López and J. A. Martín-Gago "Floating molecular layer of spinning C60 molecules on
TiO2(110) surfaces” in preparation
3. C. Sanchez-Sanchez, V. Lanzilotto, G. Bidau, B. Gomez-Lor, R. Perez, L. Florenao, M. F.
Lopez, J. A. Martin-Gago “On-surface Dehydrogenation reactions of polycyclic aromatic
hydrocarbons on Ti02(110)” in preparation
Partecipazione a congressi (come relatore)
1.“Planar Growth of Pentacene on the Dieletric TiO2(110)-1X1” V. Lanzilotto, C. SànchezSànchez, G. Bavdek, J. A. Martin Gago and L. Floreano, Summer School of
Nanotechnology, Università di Trieste 20-23/09/2011; (poster)
Attività formativa
Congressi, seminari, corsi avanzati e altre attività didattiche passive
1. Workshop of the School of Nanotechnology, University of Trieste 17-19/01/2011;
2. “Thin film metal and complex hydrides for hydrogen storage applications” by Matteo Filippi
from Delft University of Technology, Elettra Synchrotron 11/04/2011;
3. “Time resolved photoelectron spectroscopy experiments on solids and interfaces at the TEMPO
beamline of the SOLEIL synchrotron.” by Fausto Sirotti from SOLEIL synchrotron, Elettra
Synchrotron 12/04/2011;
4. “Nanoscience at Work: Imaging and Manipulation at Atomic and Molecular Scale” by Saw-Wai
Hla from Ohio University, Elettra Synchrotron 12/07/2011;
5. Summer School of Nanotechnology. Univeristy of Trieste, 20-23/09/2011
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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IMMACOLATA LUISI
Titolo della tesi: Identificazione di scaffold proteici per il legame di piccole molecole
Supervisore: Prof. Roberto Marzari (Università degli studi di Trieste, Dip. Scienze della
Vita)
Tutori: Prof. Daniele Sblattero (Università degli studi del Piemonte Orientale “Amedeo
Avogadro”), Dott. Federico Berti (Università degli studi di Trieste, Dip. Scienze chimiche
e farmaceutiche)
Attività di ricerca
Il mio progetto di ricerca è basato sull’identificazione di nuovi scaffold proteici in grado di
riconoscere e di legare piccole molecole per il monitoraggio di farmaci e per la detection di piccole
molecole per applicazioni future in ambito biosensoristico come nuovi scaffold molecolari. A tal
fine sono state adottate diverse strategie sperimentali che prevedono un approccio duplice:
i.utilizzo di molecole non naturali basate su domini coiled-coil quali il dominio sintetico E/K.
Queste molecole vengono ottimizzate mediante una strategia di MUTAGENESI RANDOM.
ii. utilizzo di molecole naturali quali Human Serum Albumin (HSA) ottimizzate mediante strategie
di MUTAGENESI RAZIONALE.
PRIMO APPROCCIO: Mutagenesi RANDOM
La prima strategia prevede come oggetto di studio lo scaffold E/K coiled-coil. I domini coiled-coil
appartengono al gruppo di scaffold ad α-elica: si tratta di due α-eliche destrorse che dimerizzano fra
loro. Un gruppo di ricerca ha sintetizzato ex novo una nuova struttura scaffold chiamata E/K (Tripet
et al. 1996; Chao et al. 1998; Litowski and Hodges 2001) che consiste in un peptide eterodimerico
E e K formati da un’unica eptade ripetuta cinque volte. Sono state apportate mutazioni al peptide
per creare una tasca in grado di legare al suo interno diverse molecole e isolare poi nuovi interattori
molecolari con una maggiore affinità e stabilità rispetto a quelli wild type.
a) E’ stata applicata una MUTAGENESI RANDOM alle due epatadi centrali dello scaffold
andando a sostituire gli amminoacidi presenti con amminoacidi random.
b) Il primo passo per la costruzione dello scaffold è stata la creazione di una libreria di mutanti
E/K random di 2*108 cloni mutanti e la successiva verifica della diversità mediante PCR e
sequenziamento dei cloni ottenuti.
c) La libreria è stata selezionata mediante la tecnica del Phage-Display utilizzando due analiti di
nostro interesse: Aldosterone e Caffeina. Sono stati isolati alcuni cloni che mostrano una buona
affinità rispettivamente per ciascuna delle due molecole.
d) Sono state effettuate una serie di analisi di natura biochimica per validare la maggiore affinità
dei peptidi random selezionati, la stabilità e la struttura.
SECONDO APPROCCIO: Mutagenesi RAZIONALE
Durante il secondo anno di dottorato è stato preso in esame lo studio di una proteina naturale, la
Siero Albumina Umana (HSA Human Serum Albumin) come recettore naturale in grado di legare
alcuni farmaci e composti sia endogeni che esogeni. L’HSA è una proteina di 66KDa
(585amminoacidi), costituita da 3 domini omologhi ognuno con due sottodomini. La nostra
attenzione si è focalizzata sul sito I di legame dell’HSA che lega normalmente piccole molecole
eterocicliche, acidi dicarbossilici e altri composti. La strategia sperimentale è stata la seguente:
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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a) ANALISI STRUTTURALE COMPUTAZIONALE di HSAbsI (300aa) ha permesso di ridurre
questo dominio da 300aa a 100aa; la regione scelta contiene tutti gli amminoacidi a contatto con i
ligandi e tutte le cisteine che formano ponti disolfuro.
b) CLONAGGIO ED ESPRESSIONE DI HSA100: è stata clonata la sequenza nucleotidica
all’interno di un vettore procariotico per permettere l’espressione della proteina in fusione con un
tag, il GST (Glutatione S-Transferasi). Il sottodominio del sito I di legame dell’HSA è stato
prodotto mediante un sistema batterico e purificato con cromatografia di affinità con resina al
glutatione (GSH). L’HSA ricombinante è stata validata mediante esperimenti di carattere biologico
e chimico quali:
c) Test ELISA e WESTERN BLOT: hanno rivelato la corretta espressione e produzione della
proteina mediante il legame con anticorpo specifico. Diverse prove sono state condotte presso il
dipartimento di Scienze Chimiche per studiare l’interazione con il farmaco Warfarin ed Efavirenz.
d) DINAMICHE MOLECOLARI: analisi di stabilità del frammento clonato sono risultate positive,
il subdominio mantiene il folding ed ha una struttura stabile.
e) ESPERIMENTI DI CINETICHE: cinetiche di addizione dell’acetone alla 6metossinaftaldeide
hanno confermato l’attività aldolasica del sito I dell’HSA.
f) MISURE DI FLUORESCENZA: è stato misurato il quenching di fluorescenza del triptofano
presente nella proteina ricombinante in presenza di concentrazioni crescenti di entrambi i farmaci
ed è risultata una buona interazione di questo subdominio con i ligandi.
Sulla base degli studi del subdominio di 100 aa dell’HSAbsI, abbiamo pensato di mutare
determinate posizioni importanti per l’ingresso del farmaco e poi andare a studiare eventuali
miglioramenti e/o cambiamenti nell’affinità del sito per i due ligandi e comparare lo studio con le
precedenti misure del sito I wild-type dell’HSA e dell’HSA intera. Le posizioni sono state scelte a
partire da un allineamento di tutte le albumine di siero e da un’analisi bioinformatica di tutte le
sequenze riconosciute come non essenziali per il corretto folding non. In particolare il subdominio
di 100aa si può dividere in 2 subsiti che hanno il fondo idrofobico con due tasche una maggiore ed
una minore ed un ingresso polare per cui sono stati presi in considerazioni i siti di ingresso e di
contatto del ligando con le due tasche idrofobiche: Ala215-Leu238-Leu260-Ile264-Arg257-His242Ser287. È stata poi sviluppata una strategia per il clonaggio in vettori di espressione che parte con il
disegno di oligonucleotidi sullo stampo dell’HSA100 ottimizzata per inserire le mutazioni di nostro
interesse.
Durante il terzo anno di dottorato è stata innanzitutto ottimizzata la sequenza di DNA del gene
dell’HSA100 mantenendo invariata la sequenza amminoacidica per avere una maggiore espressione
in E. coli e di conseguenza una maggiore produzione della proteina ricombinante HSA100-GST. La
proteina ricombinante è stata nuovamente prodotta e dializzata con ottimi risultati: 4mg/L. Sulla
base del gene ottimizzato, sono state costruite due librerie di varianti dell’HSA100 con due
mutazioni Ala215-Leu238 nella tasca minore e Leu260-Ile264 al livello della tasca maggiore
rispettivamente. Inizialmente abbiamo lavorato con la libreria con le due mutazioni nella tasca
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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maggiore Ala215-Leu238. La libreria è stata controllata mediante PCR e sequenziamento.
Dall’analisi delle sequenze sono stati identificati sei cloni random con determinati amminoacidi
nelle posizioni selezionate. I sei cloni sono stati testati mediante Western Blot per vedere la corretta
lunghezza ed espressione dei frammenti e successivamente mediante test ELISA e analisi in
BIACORE per vedere la capacità di binding tra cloni mutanti e ligandi.
a) In ELISA tutti i cloni risultano legare l’EFV, in particolare tre cloni in modo migliore rispetto
all’HSA100 wt.
b) In BIACORE, immobilizzando l’EFV sul chip e utilizzando le proteine mutanti alla stessa
concentrazione, da un’analisi preliminare dei dati sono state ottenute delle costanti di affinità
migliori rispetto a quella dell’HSA100 wt.
c) Mediante misure di fluorescenza del quenching del Triptofano questi risultati ottenuti in
precedenza sono stati ulteriormente confermati. È risultata una maggiore sensibilità con l’Efavirenz
rispetto al Warfarin infatti, con i cloni mutanti, in presenza di Efavirenz sono state ottenute delle Kd
comparabili con la Kd tra HSA100-Warfarin (tipico ligando del sito primo di legame dell’HSA,
usato come riferimento).
Le prospettive future prevedono, dopo aver testato l’HSA100 e mutanti mediante biosensori Surface
Plasmon Resonance:
 Utilizzo su sensori elettrochimici o su microbilance
 Costruzione della seconda libreria con le mutazioni nella tasca minore Ala215 e Leu238 e di
una libreria con mutazioni nelle 7 specifiche posizioni prescelte dell’HSA100.
 Identificazione e validazione dei cloni mutanti con un’affinità migliore
 Applicazione del miglior clone HSA100 per monitoraggio terapeutico di farmaci.
Attività formativa
Congressi, seminari, corsi avanzati e altre attività didattiche passive
17-19 Gennaio 2011: Congresso annuale della scuola di dottorato in Nanotecnologie con
presentazione degli studenti
24 Marzo 2011: secondo BRAINCONTRO (Basic Research And Integrative
Neuroscience), Facoltà di medicina e chirurgia, Ospedale di Cattinara, Trieste
12 Maggio 2011: “Oxazaphosphorinane drugs in cancer therapy” Prof. Konrad Misiura
(University Copernico of Torun – Poland)
10 Giugno 2011: “Optical imaging per applicazioni biomediche” Stefania Biffi Phd and
Simeone Dal Monego, PhD, Cluster in Biomedicine (CBM Scrl) – Trieste
1 Luglio 2011: “Self assembled monolayers on gold the challenge”, Dr. HIcham
Hmamoudi from the Université-Paris Sud, Facoltà di ingegneria, edificio C1, campus of
Piazzale Europa
18 Luglio 2011: “The Effect of Confinement on Enzymes Diffusion and Reactions Inside
DNA” Matteo Castronovo Phd, Sala degli Atti, Facoltà di ingegneria, edificio C1,
Piazzale Europa
4-8 Luglio 2011: “Advances in Structural Bioinformatics”, FVG International
Summer School on Bioinformatics 2011, SISSA, via Bonomea 265, Trieste, room
128/129
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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20-23 Settembre 2011: “First Joint Summer School on Nanotechnology” Stefano De
Gironcoli SISSA, Trieste; Maurizio Fermeglia University of Treiste; Luica Selmi
University of Udine. University of Trieste, Campus of Piazzale Europa 1, 34127 Trieste
Building C2, AULA A.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa)
An albumin-derived peptide for binding and catalysis
Immacolata Luisi1, Silvia Pavan2, Giampaolo Fontanive2, Alessandro Tossi1, Fabio Benedetti2,
Roberto Marzari1, Adriano Savoini3, Elisa Maurizio1, Riccardo Sgarra1, Daniele Sblattero4*,
Federico Berti2* (in submitted)
1
Dipartimento di Scienze della Vita, Università di Trieste, via Weiss 2, 34128 Trieste, Italy. 2Dipartimento di
Scienze Chimiche e Farmaceutiche, Università di Trieste, via Giorgieri 1, 34127 Trieste, Italy. 3T&B Associati srl.,
Area Science Park, Padriciano 91, 34100, Trieste, Italy. 4Dipartimento di Scienze Mediche, Università del
Piemonte Orientale “Amedeo Avogadro”, via Solaroli 17, 28100 Novara, Italy.
Attività didattica di supporto e attività didattica attiva
Attività di tutoraggio in laboratorio di TECNOLOGIE CELLULARI E MOLECOLARI a studenti
del I anno di corso di laurea specialistica in GENOMICA FUNZIONALE.
Attività di tutoraggio in laboratorio di biologia cellulare a più studenti della laurea triennale in
biologia molecolare per un periodo complessivo di tre mesi ciascuno, che prevede l’apprendimento
delle tecniche di laboratorio principali quali la preparazione di soluzioni e terreni di colture per
crescite batteriche, preparazione di glicerolati, preparazione di cellule competenti chimiche e di
cellule elettrocompetenti, trasformazione batterica, estrazione di DNA plasmidico, PCR
(Polymerase Chain Reaction), elettroforesi su gel d’Agarosio. Produzione e purificazione di
proteine ricombinanti, preparazione di gel di Acrilammide e Western blotting, test ELISA, PhageDISPLAY.
Supporto nella stesura della tesi di laurea triennale.
Correlatore in 5 lavori di tesi triennali del corso di laurea in Scienze Biologiche (curriculum
Biomolecolare):
- STRATEGIE DI CLONAGGIO ED ESPRESSIONE DI PICCOLI PEPTIDI
LEGANTI LA MOLECOLA EFAVIRENZ
- SELEZIONE DI UNA MINILIBRERIA DI SCAFFOLD PEPTIDICI CONTRO
EFAVIRENZ
- STUDIO DI INTERAZIONE DELLA SIERO ALBUMINA UMANA
RICOMBINANTE CON PICCOLE MOLECOLE MEDIANTE SISTEMA
BIACORE
- SISTEMA DI PRODUZIONE EPURIFICAZIONE DELLA PROTEINA HSA
RICOMBINANTE
- VALUTAZIONE DI METODI DI PURIFICAZIONE DI PROTEINE
RICOMBINANTI CON AFFINITY-TAG
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MONICA MARINI
Titolo della tesi: Evolving biosensors: intelligent devices at the nanoscale
Supervisore: Giuseppe Firrao
Tutori (eventuali): Marco Lazzarino
Attività di ricerca
In questo progetto, un DNA-origami in grado di praticare dei movimenti autonomi da parte della
sua struttura è stato disegnato in silico, costruito e caratterizzato per mezzo di una combinazione di
tecniche microscopiche e di fluorescenza. Le nanostrutture a DNA sono state disegnate in silico
utilizzato il programma caDNAno(SQ) e, in una prima versione, è consistito in un disco connesso
ad un anello esterno esclusivamente in due punti diametralmente opposti. Il metodo denominato
“DNA-origami” è stato introdotto da Rothemund nel 2006, basandosi sul ripiegamento di un
polinucleotide a singolo filamento chiamato 'scaffold strand' (il genoma virale di M13mp18),
guidato da centinaia di oligonucleotidi più corti (in questo progetto circa 220), chiamati 'staple
strands', al fine di originare forme arbitrarie e precise definite solo dalla scelta degli 'staples'. La
correttezza della struttura attesa è stata verificata qualitativamente (elettroforesi standard e uso del
TEM) sia quantitativamente (AFM). Una volta ottenuto l'oggetto dalla forma e dimensioni
desiderate, un altro DNA a singolo filamento, l'attuatore, è stato connesso ai due margini del disco
perpendicolarmente all'asse di costrizione. In presenza di un acido nucleico strutturato a forma di
forcina, l'attuatore ibrida formando un doppio filamento che strattona il disco centrale fozandone le
due estremità e portandole a muoversi una verso l'altra, cambiando la conformazione delle due ali.
Verificata l'effettiva apertura del dispositivo per mezzo di microscopia a forza atomica e sistema a
fluorescenza (FRET) usando la coppia 6'-FAM/BHQ-1, il sistema è stato reso reversibile
apportando alcune modifiche alla molecola target a forcina in modo tale che quando una terza
molecola a singolo filamento, il 'competitore', viene aggiunta in soluzione essa rimuove il target
dall'attuatore, riportando il DNA-Origami allo stato di riposo iniziale. Una seconda versione del
disco a DNA è stata ottenuta usando gli stessi principi ma ottimizzando il meccanismo di apertura
per renderlo funzionale anche utilizzando target a singolo filamento. Infine la funzionalità del
sistema è stata validata con campioni reali in soluzione, utilizzando RNA virali di patogeni di
piante.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa)
Monica Marini, Luca Piantanida, Alpan Bek, Rita Musetti, Mingdong Dong, Flemming
Besenbacher, Marco Lazzarino, Giuseppe Firrao (2011) A revertible, autonomous, self-assembled
DNA-origami nanoactuator. Nano Letters
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
Abstract e Presentazione di un poster dal titolo “DNA Origami for hybrid nanosensors” presso
NanotechItaly 2010, autori: Marini M., Piantanide L, Bek A, Lazzarino M, Musetti R, Firrao G.
Abstract e Presentazione di un poster dal titolo “DNA-based autonomous devices at the nanoscale”
presso la conferenza “ Joint ICTP-KFAS Conference on Nanotechnology for Biological and
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Biomedical Applications” (10-14 Ottobre 2011), ICTP (Miramare). Autori: Marini M., Piantanide
L, Bek A, Lazzarino M, Musetti R, Firrao G.
Altre pubblicazioni
Abstract e Presentazione del poster alla Summer School presso Universitat Karlsruhe (TH), DFGCentrum fur Functionelle Nanostrukturen. Bad Herenhalb, Germania dal titolo: CFN Summer
School on Nano-Biology (7 - 11 Settembre 2009)
Abstract e Presentazione del poster allo spring college “Computational nanoscience”, ICTP Trieste
dal titolo “DNA-Origami for hybrid nanosensors” (Maggio 2010). Autori: Marini M., Firrao G.
Attività formativa
Esami sostenuti, ore di lezione e di laboratorio seguite
Corso: Ottobre 2009-Febbraio 2011, Università degli Studi di Udine. Di Giusto Sandro:
“Fondamenti di informatica”, corso tenuto nell'ambito della facoltà di ingegneria (indirizzo
meccanico).
Congressi, seminari, corsi avanzati e altre attività didattiche passive
Seminario: 4 Febbraio 2009. Museo di Scienze Naturali e Università degli Studi di Udine. Ian
Tatterstall: “Charles Darwin and human evolution”
Seminario: Aprile 2009, Università degli Studi di Trieste. AA VV. “Nanochallenge and
Polymerchallenge”.
Seminario: 15 Maggio 2009. Università degli Studi di Trieste. Dr. Italo Colombo “Chimica fisica
delle interfasi in sistemi nanostrutturati”.
Corso: Maggio 2009, ELETTRA. Maja Kiskinova: “Advanced Imaging and spectromicroscopy
methods for chemical and structural characterization of micro- and nano-materials”.
Seminario: 11 Giugno 2009. Area Science Park. KeyToNature Technology Transfer Day:
“L'identificazione rapida di organismi: dalla ricerca alle applicazioni industriali”
Seminario: 11 Giugno 2009. Università degli Studi di Udine. Robert S. Marks: “Biosensor systems
in detecting patient exposure to pathogens and monitoring water toxicity: how combining biology,
physics and chemistry helps gain in sensitivity and time.”
Seminario: 30 Giugno 2009. Università degli Studi di Trieste. “Information meeting for doctoral
students”.
Corso: Giugno 2009, Università degli Studi di Trieste. Alberto Morgante, Loredana Casalis, Lucia
Pasquato: “Molecular self-assembling and nanostructures”.
Corso: Giugno2009 - Luglio 2009, corso presso ELETTRA. Cristina Afric, Laura Felisari:
“Advanced microscopy: Scanning and Transmission Electron Microscopy, Scanning Probe
Microscopy”.
Summer School: 7 - 11 Settembre 2009. Universitat Karlsruhe (TH), DFG-Centrum fur Functionelle
Nanostrukturen. Bad Herenhalb, Germania: CFN Summer School on Nano-Biology.
Seminario: 16 Ottobre 2009. Università degli Studi di Trieste. “Writing (and managing) a research
project”
Presentazione attività dottorandi per il passaggio d'anno: Dicembre 2009
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Congresso attività dottorandi. Università degli Studi di Trieste: Gennaio 2010
Seminario: 22 Gennaio 2010. Università degli Studi di Trieste. Dr.Hanna Mamzer “How to present
scientifici results”
Congresso attività dottorandi. Università degli Studi di Udine: Aprile-Maggio 2010.
Seminario: 17 Maggio 2010. ELETTRA. Prof. Fleming Besenbacher “Dynamics of nanostructures:
diffusion, self-assembly, self-organization, DNA dolphins and nano-boxes”
Spring college: 17-28 Maggio 2010. ICTP Trieste. “Spring college on computational nanoscience”
Seminario: 15 Giugno 2010: Presentazione di “Nanochallenge and Polymerchallenge”, Veneto
Nanotech
Seminario: 15 Giugno 2010. Università degli Studi di Trieste. Prof Miguel Nobrega, University of
Minho in Portugal “Development of On-line Monitoring devices for the extrusion process”.
Seminario: 15 Giugno 2010. Università degli Studi di Trieste. Prof Maurizio Fermeglia “Use of
VPN and UGOV”.
Seminario: 23 Novembre 2010. Università degli Studi di Trieste, Dr. Sangeeta Kale “Metal oxide
nanomaterials in sensors and biomedicine”
Seminario: 23 luglio 2010. Udine, Parco del Cormor. Margherita Hack “Le quattro dimensioni di
Margherita Hack”
Presentazione attività dottorandi per il passaggio d'anno: Dicembre 2010
Congresso attività dottorandi: Gennaio 2011
Seminario: 1 luglio 2011 Università degli Studi di Trieste, Dr. Hicham Hmamoudi (Université-Paris
Sud) “Self assembled monolayers on gold the challenge”.
Seminario: 18 Luglio 2011 Università degli Studi di Trieste. Dr. Matteo Castronovo “The Effect of
Confinement on Enzymes Diffusion and Reactions Inside DNA Nanostructures”
Conferenza: 10-14 Ottobre 2011, ICTP (Miramare). Joint ICTP-KFAS Conference on
Nanotechnology for Biological and Biomedical Applications (Nano-Bio-Med)
Attività didattica di supporto e attività didattica attiva
Lezioni attive su miRNA e siRNA presso l'università degli studi di Udine per studenti della laurea
specialistica, indirizzo biotecnologie agrarie.
Attività di supporto nello svolgimento della tesi di Luca Piantanide, studente preso l'Università
degli Studi di Trieste, inerente la visualizzazione di DNA Origami per mezzo di microscopia a forza
atomica.
Correlatrice nello svolgimento della tesi (in corso) di Fredrik Francesconi, studente presso
l'Università degli Studi di Udine (Scienze e Tecnologie Agrarie), inerente lo sviluppo e la
modificazione di DNA Origami e lo studio del loro comportamento in presenza di diverse molecole
di DNA.
Correlatrice nello svolgimento della tesi (in corso) di Andrea Paiani, studente presso l'Università
degli Studi di Udine (Scienze e Tecnologie Agrarie), inerente lo sviluppo e la modificazione di
DNA Origami e studio del loro comportamento in presenza di RNA.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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ELISA MIGLIORINI
Titolo della tesi: Characterization of nanostructured substrates which control the ES Cells
differentiation into neurons
Supervisore: Marco Lazzarino
Tutori (eventuali): Elisabetta Ruaro
Attività di ricerca
Descrizione delle tematiche di ricerca e dei principali risultati scientifici raggiunti:
Il mio progetto di dottorato ha lo scopo studiare l’effetto di substrati nanopatternati sul
differenziamento neuronale di cellule staminali embrionali.
Per il guidare cellule staminali embrionali verso il differenziamento neuronale è stato utilizzato un
protocollo che prevede l’induzione del differenziamento da parte di cellule stromali (SDIA).
Risultati dei primi due anni di dottorato hanno portato evidenze che strutture quali nanopillars di
PDMS sono in grado di accelerare il differenziamento neuronale.
Nell’ultimo anno l’attenzione è stata rivolta verso il meccanismo di interazione cellula-substrato che
sta alla base del fenomeno studiato. L’indagine è servita per distinguere il contributo meccanico e
topografico dei substrati in PDMS sul differenziamento. Infatti i precursori neuronali seminati su
strutture con più alto rapporto altezza/larghezza differenziano in neuroni con una resa maggiore.
Calcolando il modulo di Young di questi substrati con spettroscopia di forze è stato possibile
correlare il differenziamento con il modulo elastico apparente dei substrati. Il differenziamento
neuronale infatti è inversamente proporzionale all’elasticità del substrato.
L’importanza dell’effetto geometrico da solo è stato testato riproducendo le stesse strutture su un
materiale simile al vetro (HSQ). Tale substrato non ha prodotto nessun incremento del
differenziamento neuronale portando ad una resa paragonabile alle strutture lisce come il vetro
standard. La prima conclusione che possiamo trarre da questa indagine è che la topografia da sola
non ha alcun effetto sul differenziamento neuronale, mentre le caratteristiche meccaniche sembrano
avere il ruolo principale su tale fenomeno.
Essendo prevalentemente un effetto meccanico sono state studiate quantitativamente le forze messe
in gioco tra cellule e substrato utilizzando la tecnica di Single Cell Force Spectroscopy.
E’ stata verificata una più intensa e rapida adesione dei precursori neruonali sui pillar in PDMS
rispetto all’adesione degli stessi su PDMS licio o sui pillar rigidi. Da questa seconda osservazione
possiamo concludere che l’effetto sul differenziamento è imputabile alla formazione anticipata di
complessi di adesione su substrati con modulo di Young apparente più simile a quello della matrice
extracellulare neuronale.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa),
 Migliorini E., Grenci G., Ban J., Pozzato A., Tormen M., Lazzarino M., Torre V., Ruaro ME.
Acceleration of neuronal precursors differentiation induced by substrate nanotopography.
Biotech and Bioeng 2011 Nov; 108,11:2736-2746
 Migliorini E., Ban J., Di Foggia V., Ruaro ME., Torre V., Lazzarino M. Nanoscale live
imaging. Imaging & Microscopy. 2011 May; 25-28
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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 Ban J*, Migliorini E*, Di Foggia V, Lazzarino M, Ruaro ME, Torre V. Fragmentation as a
mechanism for growth cone pruning and degeneration. Stem Cells Dev. 2010 Sep 13.
20(6):1031-41
 Lasalvia M, Perna G, Mezzenga E, Migliorini E , Lazzarino M, L’Abbate N and Capozzi V.
Atomic force microscopy investigation of morphological changes in living keratinocytes
treated with HgCl2 at not cytotoxic doses. J. of Microscopy. 2010 [Epub ahead of print]
 Migliorini E., Ban J., Di Foggia V., Ruaro ME., Torre V., Pozzato A., Grenci G., Tormen
M, Lazzarino M. Effect of nanopatterned substrates on growth cones activity. Eur Biophys
.J. 2009 Oct, (suppl 1) S89
 Kondra S, Laishram J., J. Ban J.,Migliorini E., Di Foggia V., Lazzarino M., Torre V., Ruaro
M.E. Integration of Confocal and Atomic Force Microscopy. Journal of Neuroscience
methods. 2009 Feb 15;177(1):94-107. Epub 2008 Oct 18.
 Laishram J., Kondra S., Avossa D., Migliorini E., Lazzarino M., Torre V. A morphological
analysis of growth cones of DRG neurons combining Atomic Force and Confocal
Microscopy. Journal of Structural Biology. 2009 Sept.
Partecipazione a congressi (come relatore)
 “Acceleration neuronal precursors differentiation induced by substrate nanotopography”.
EBSA 2011. Budapest, Hungary. Oral presentation
 “Effect of nanopatterned substrates on Embryonic Stem Cells differentiation into neuronal
lineage”. TERMIS-EU 2011. Granada, Spain. Oral presentation
 “Effect of PDMS nanopatterned substrates on Embryonic Stem Cells differentiation into
neuronal lineage”. BIOPHYSICAL SOCIETY 55TH annual meeting 2011, Baltimore
Maryland, USA. Poster presentation
 “Effect of PDMS nanopatterned substrates on Embryonic Stem Cells differentiation into
neuronal lineage”. SLONANO 2010, 20-22 October Ljubljana, Slovenia. Oral presentation
 “Effect of nanopatterned substrates on ES-differentiation into neurons”. NeuroIITscience,
14-15 june 2010, Genova. Poster presentation
 “AFM live imaging of neuronal growth cones reveals a new nanometrical morphology”.
SLONANO 2009, 19-21 October Ljubljana, Slovenia. Oral presentation
 “AFM live imaging to analyze neuronal differentiation on nanopatterns” First Interim
meeting Nanoscale project. 23 Sept. 2009, Paris France. Oral presentation.
 “AFM live imaging of ES-derived neurons and growth cones retraction at the nanoscale”.
European Biophysics Congress EBSA: 11-15 July 2009. Genoa – Italy. Poster presentation
Attività formativa
Ore di lezione seguite (data, corso, docente, tipo di corso di laurea):
 “Structural biology”, 02/2009 (24h). Docente: Silvia Onesti presso SISSA (dottorato in
biofisica)
 “Advanced imaging and spectromicroscopy”, 04/2009 (15h). Docente: Maya Kiskinova
presso Scuola di dottorato di Nanotecnologie
“Optofluidic school”, 06/2009 (40h). Coordinatore Dan Cojoc presso ICTP (summer
school)
“SEM”, 04/2009 (4h). Docente: Laura Felisari presso laboratorio TASC
Ore di laboratorio seguite:
 IOM-CNR laboratorio TASC dal 01/2009 (>60 ore). Tutor: Marco Lazzarino.
Attività: nano-microfabricazione
CBM dal 01/2009 (>60 ore). Tutor: Marco Lazzarino. Attività: AFM
SISSA dal 01/2009 (>60 ore). Tutor: Elisabetta Ruaro. Attività: colture cellulari e
saggi di immunofluorescenza.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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Congressi:
Nanotechnology meets clinical medicine 2011. 6-8/10/11. Udine, Italy (20 ore)
EBSA 23-27/08/2011. Budapest, Hungary (40 ore).
TERMIS-EU 7-10/06/2011. Granada, Spain. (36 ore)
BIOPHYSICAL SOCIETY 55TH annual meeting 5-9/03/2011, Baltimore Maryland, USA. (43
ore)
 JPK user training session (Berlin) 02-03/11/10 (18 ore).
IOM workshop (Trieste). 30/09-01/10/10 (10 ore).
 SLONANO 2010 (Lubljana). 20-22/10/10 (24 ore).
NeuroIITscience (Genova). 06-07/05/10 (16 ore).
 First interim meeting Nanoscale Project (Parigi). 23/09/2009 (8ore).
 Slonano (Lubljana). 19-21/10/09 (20 ore).
How to write (and manage) a research project. 16/10/2009 (4ore).
 EBSA Genova 2009. 11-15/07/09 (35ore).
Seminari:
High-resolution scanning X-ray diffraction microscopy. 22/01/2009. Pierre Thibault
X-ray microscopy: dealing with real-life complexities. 22/01/2009. Chris Jacobsen
Neuronal plasticity 08/04/2009 Prof. Francois Anserment & Prof. Pierre Magistretti
Modeling reactions at the nanoparticle scale 08/05/2009. Phillip R. Westmoreland
 Calcium control of gene regulation in an in-vitro model of neuronal plasticity 15/06/2009.
Giulietta Pinato
How is Enzymatic Activity Determined by Protein Dynamics? 20/07/2009. Kerstin Blank
Inhibition of scrapie prion replication by polyelectrolyte nanogold particles & Coated
Nanogold and the Brain. 22/07/2009. Fernanda Sousa
Dopaminet summer school (CBM) 5-6/10/09. Stefano Gustincich
Potential therapeutic use of neural stem cells for neurodegenerative disorders 15/3/10. Zaal
Kokaia
Mechanical properties of C-cadherin and its dependence on calcium binding 15/4/10. Aleandro
Valbuena
Combining Atomic Force Microscopy with Micro-Electrode Arrays for Studying the
Mechano-Electrical Behavior of Cardiac Myocytes. 10/5/10. Josè F. Saenz
Metal oxide nanomaterials in sensors and biomedicine. 23/11/10. Sangeeta Kale
PPE-PPV Based Materials: Tuning of Optoelectronic Properties Using Alkoxy Side Chains.
29-06-11. Dr. Daniel Ayuk Mbi Egbe
Adult stem cells and thermo-responsive polymers for cardiac muscle tissue engineering.
15/9/11. Dr. Giancarlo Forte
Nano-electro-mechanical-systems for Healthcare & Environmental Applications. 12/10/11. V.
Ramgopal Rao.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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SEID-HOSSEIN PAKDAST
Title of the thesis: Triple Coupled Cantilever (TCC) systems.
Supervisor: Marco Lazzarino
Research Activity
The final year of my PhD project has been focused on three main topics.
The first part of the project was to fabricate the new design of TCC. The previous fabrication
process resulted often with a misalignment of TCC with the membrane. The fabrication was done
on both sides of sample in two separated steps. With the new design the misalignment is avoided
and the device is fabricated on one side of the sample.
The second part of the project was to develop an alternative actuation method to measure the
frequency response of TCC. Earlier, we used frequency-modulated pulsed laser but this approach is
not suitable for further integration. With the new design of TCC we are able to actuate the
cantilevers by applying RF-signals to the electrodes. This actuation method was introduced by Eva
M. Weig et al. and published in nature in 2009.
The final goal of the project is the development of a full micro mechanical transistor using TCC. In
a transistor a high power signal is controlled by a low power signal, thus obtaining amplification. In
a Field Effect Transistor (FET), at VSD (the input voltage) constant, the output current ISD is
controlled by the Gate Voltage,VG. Since IG is negligible, the FET acts as an amplifier. In our
device an oscillating bias VRF applied to one cantilever is used to put the three cantilevers in
oscillation. A second cantilever is exposed to a DC bias that damps the cantilever motion, which is
detected on the third cantilever. So, the oscillation amplitude of the TCC is controlled by the DC
signal, which, having no RF components is a low power signal, while both excitation and
oscillation are RF signal and thus high power signal. Therefore we obtain an amplification effect.
Proof of principle investigations were performed and suggest that the device proposed is working as
expected.
Publications on scientific journals (printed or in press)
H. Pakdast and M. Lazzarino Triple Coupled Cantilever Systems for Mass Detection and
Localization. Sensors & Actuators: A. Physical, accepted for publication.
Publications/abstracts in conferences/congresses (national or international)
Nanotechnology Summer School, September 20 – 23, 2011, Trieste, Italy
Poster presentation
NANOTECHNOLOGY MEETS CLINICAL MEDICIN, 6.-8. October 2011, Italy
Joint ICTP-KFAS Conference on Nanotechnology for Biological and Biomedical Applications
(Nano-Bio-Med), 10.-14. October 2011, Trieste, Italy
Educational Activity
Support educational activity and teaching
Guiding one visiting scientist
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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GIACOMO SCIUTO
Titolo della tesi: Innovative LHTS Elements Design and Nanotechnologies
Supervisore: Prof. Roberto Muscia
Attività di ricerca
Gli obiettivi di questo progetto di dottorato sono lo studio e lo sviluppo di sistemi e dispositivi per
l’accumulo di energia termica che sfruttino materiali a cambio fase (PCM) e l’indagine
sull’eventuale compatibilità di questi con materiali nano-metrici, utilizzabili per variarne le
proprietà termo fisiche.
Nel terzo anno di attività è stata portata a termine la progettazione di un puffer domestico (attività
iniziata nel II anno di dottorato), che sfrutta la tecnologia PCM, in grado di ridurre il ciclo di
accensione/spegnimento di una caldaia a biomassa ad esso collegata.
Sono stati effettuati una serie di studi di fattibilità ed ottimizzazione per l’uso dei PCM all’interno
di cemento ed asfalto per ridurre la formazione di ghiaccio sulla superficie di strade e marciapiedi
nel periodo invernale, basandosi su studi 2D (e 1D - attività iniziata e “conclusa” nel 1 anno di
dottorato) e, simulando le condizioni climatiche con i dati meteorologici forniti dall’OSMER FVG.
Si sono individuati i margini operativi di tale tecnologia ottimizzando la scelta del materiale per
l’accumulo, forma e posizionamento degli accumulatori all’interno del manto stradale. Si è quindi
studiato l’effetto dell’aggiunta di SWCNT in diverse quantità su alcune paraffine commerciali
prodotte da Rubitherm Gmbh con temperature di fusione (27-58-65-82°C). E’ stato definita una
procedura di preparazione dei campioni e sono state misurate alcune proprietà termo fisiche (calore
latente di fusione/solidificazione, viscosità, capacità termica) dei campioni puri e dopati. Sono state
individuate alcune sostanziali differenze tra la misura del calore latente teorico e misurato nei
campioni “dopati” ed una sostanziale influenza della procedura di preparazione delle miscele sulle
caratteristiche della miscela finale. Devono essere ancora portate a termine le seguenti prove: prova
FTIR e prove al viscosimetro delle miscele e dei materiali puri.
Attività formativa
Congressi, seminari, corsi avanzati e altre attività didattiche passive
PhD Final Conference 2010 – 17-19 Gennaio 2011 – Università di Trieste
Comsol Conference 2011 – 27 Gennaio 2011
Matlab Conference – 17 Febbraio 2011
29 Luglio 2011 – M. Castronovo
Master in Complex Actions @ SISSA Gennaio-Settembre 2011
Seminari vari Imprenderò 2011
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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FEDERICA TAVANO
Titolo della tesi: Cell mobility and metastatic spreading: a study on human neoplastic cells using Optical
Tweezer
Supervisore: Dott.ssa Serena Bonin
Tutore: Dott. Dan Cojoc, Prof. Giorgio Stanta
Attività di ricerca
Negli ultimi anni un’ ampia varietà di tecniche sperimentali in biofisica sono state utilizzate per studiare le
proprietà meccaniche delle cellule. E’ ormai generalmente accettato che la biomeccanica delle cellule gioca
un ruolo essenziale nell’insorgenza e nella progressione del tumore. Caratterizzare le proprietà meccaniche
delle cellule in associazione con la membrana plasmatica e l’organizzazione del citoscheletro è importante
per una miglior comprensione dei meccanismi di migrazione cellulare e offre un enorme potenziale per
ulteriori passi avanti a livello diagnostico e terapeutico. Abbiamo utilizzato Custome made Optical Tweezer
set up, progettato e costruito durante il primo anno di dottorato per esperimenti di ”membrane tether
extraction” che rappresentano il metodo più accurato per caratterizzare quantitativamente le proprietà
viscoelastiche locali della membrana plasmatica. In questo studio abbiamo analizzato le proprietà
viscoelastiche delle membrane cellulari di tre diversi tipi di breast cell lines: MDA-MB-231, MCF-7 e HBL100, caratterizzate da diverso potenziale metastatico che rappresentano quindi un buon modello di studio
della progressione di cellule epiteliali umane attraverso il processo metastatico.
Bassi valori di membrane tether stiffnes (ovvero la compliance del membrane tether) e la membrane bending
rigidity (ovvero il contributo della tensione della membrana, legata alla deformazione locale della cellula
durante il tether pulling) caratterizzano le cellule con un più alto potenziale metastatico, suggerendo quindi
una correlazione tra la diminuzione di questi due parametri e la progressione metastatica. Al contrario la
viscosità ha mostrato una tendenza inversa: l’aumento della viscosità sembra essere associato a cellule con
un maggiore potenziale metastatico. Abbiamo analizzato le stesse tre linee cellulari mediante indentation
experiments con AFM (Atomic Force Microscope) per ricavare i valori del Modulo di Young delle cellule in
modo da avere una caratterizzazione più approfondita delle loro proprietà meccaniche. Il modulo di Young
delle cellule non neoplastiche sembra essere significativamente più basso di quello misurato nelle cellule
tumorali.
Dalle immagini ottenute con Immunofluorescenza si osserva nelle cellule con più alto potenziale metastatico
una maggior disorganizzazione del citoscheletro e la presenza di grossi accumuli di actina, avvalorando la
teoria per la quale una progressiva disregolazione della struttura del citoscheletro di actina è una delle cause
principali delle alterazioni a livello delle proprietà biomeccaniche.
Dalle prime analisi per la caratterizzazione lipidica delle membrane cellulari mediante MALDI Mass
Spectroscopy emergono differenze significative anche a livello di alcune classi di Phosphatidyl Enositols
(PE) e Phosphatidyl Inositols (PI): le cellule a più alto potenziale metastatico sembrano essere più ricche di
grassi insaturi. Questo suggerisce che le proprietà meccaniche potrebbero essere influenzate non solo da
alterazioni del citoscheletro ma anche da una diversa composizione lipidica delle membrane cellulari, e che
quindi entrambe dovranno essere studiate in modo approfondito.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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Pubblicazioni su riviste scientifiche (pubblicate o accettate per la pubblicazione)
Tavano F., Bonin S., Pinato G., Stanta G. and Cojoc D., Custom-built optical tweezers for locally
probing the viscoelastic properties of cancer cells. International Journal of Optomechatronics
September 2011
Pinato G., Raffaelli T., D’Este E., Tavano F. , Cojoc D., Optical Delivery of liposome
encapsulated chemical stimuli to neuronal cells, International Journal of Biomechanical Optics
16 (9) September 2011
Capitoli/sezioni di libri/volumi
Bonin S., Tavano F. Restoration and Reconstruction of DNA Length , Guidelines for Molecular
Analysis in Archive Tissues Springer-Verlag 2011 Giorgio Stanta Editor
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
53rd Symposium of the Society for Histochemistry -Current Role of Histochemistry in
Preclinical and Clinical Research, 12-15 October 2011, Munich, Germany (poster)
Poster Presentation:"Cell mobility and metastatic spreading: a study on human breast cancer cells
using the nano-mechanical approach"
Tavano F, StantaG., CojocC., PinatoG., MiglioriniE., D’Este E., BoninS.
2nd Physics of Cancer Symposium - Leipzig 13-15 October 2011
Poster Presentation: Local membrane mechanical probing of neoplastic and non-neoplastic
human cells
Tavano F., Bonin S., D'Este E., Pinato G., Stanta G., Cojoc D.
8th European Biophysics Congress (EBSA) - Budapest 23-27 August 2011
Poster Presentation: Cell mobility and metastatic spreading: a study on human neoplastic cells
using Optical Tweezers” F.Tavano, S.Bonin, E.D’Este, G.Pinato, G.Stanta, D.Cojoc
Pezcoller Foundation Symposium : Engineering In Cancer Research 16th -18th June 2011Trento-Italy
Poster presentation: “Cell mobility and metastatic spreading: a study on human neoplastic cells
using Optical Tweezers” ” F.Tavano, S.Bonin, E.D’Este, G.Pinato, G.Stanta, D.Cojoc
Attività formativa
Periodi di permanenza all’estero (15 settembre 2011-15 dicembre 2011, Leipzig, Germany)
Attuamente mi trovo a Lipsia per un periodo di tre mesi nel Soft Matter Physics Group del Prof.
Josef Käs al Dipartimento di Fisica dell’Università di Lipsia. Sto imparando ad utilizzare la tecnica
dell’Optica Stretcher per approfondire la caratterizzazione delle proprietà meccaniche delle cellule
precedentemente analizzate con l’Optical Tweezers al laboratorio TASC-IOM.
Congressi, seminari ed incontri organizzati dalla scuola
1. Congresso scuola di dottorato in Nanotecnologie gennaio 2011 (9 ore)
2Seminario, “Self assembled monolayers on gold the challenge” dr Hlcham Hmamoudi
(universitè –Paris Sud) giugno 2011
3Seminario Matteo Castronovo The effect of Confinement on Enzymes Diffusion and
reactions inside DNA nanostructures 29 luglio 2011
4. Seminario: New approaches in cancer therapy Prof. Konrad Misiura 12 maggio 2011
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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CHIARA ZANUSSO
Titolo della tesi: “Nanotecnologie e oncologia: farmacocinetica e farmacogenomica per
ottimizzare le terapie antitumorali”
Supervisore: prof. Tullio Giraldi
Tutori (eventuali): dr. Giuseppe Toffoli
Attività di ricerca
Lo scopo di questo studio è verificare l’incidenza di alcune varianti genetiche (polimorfismi)
coinvolte nei processi di cancerogenesi e nella progressione neoplastica. Il cancro prostatico è la
terza causa di morte negli uomini ed è un problema sanitario di rilevanza mondiale. I tassi di
incidenza e mortalità del tumore della prostata variano sostanzialmente in tutto il mondo: di
notevole importanza…i fattori di rischio ambientali, lo stile di vita e, probabilmente, la loro
combinazione con le varianti genetiche attraverso popolazioni di etnie e razze differenti. Le
caratteristiche genetiche del paziente sono uno dei fattori determinanti nella variazione interindividuale osservata nell’insorgenza del tumore e nell’outcome della terapia anti-tumorale. La
farmacogenetica si propone quindi di validare ed utilizzare nella pratica clinica alcuni marcatori
genetici al fine di personalizzare e ottimizzare la terapia. Per prima cosa è stata effettuata una
ricerca bibliografica per definire i polimorfismi genetici di possibile significato
prognostico/predittivo. Sono stati identificati polimorfismi a carico delle Glutatione S-Transferasi
(GST), trasportatori trans-cellulari (ATP-Binding Cassette) responsabili dell’estrusione del farmaco
dalla cellula, e polimorfismi a carico di geni del riparo del DNA. Sono stati arruolati 917 pts affetti
da carcinoma prostatico provenienti dal CRO di Aviano ed una popolazione di donatori di sangue
sani della regione Friuli Venezia Giulia. Le metodiche di analisi utilizzate per la valutazione dei
polimorfismi presi in esame si basano sull’amplificazione della porzione del gene di interesse
mediante tecnica PCR e successiva analisi con metodo TaqMan, che si basa su una misurazione
quali-quantitativa diretta del DNA amplificato mediante una sonda fluorescente, o con la tecnologia
del Pyrosequencing, una nanotecnologia di recente sviluppo che permette di identificare mutazioni
di tipo puntiforme (SNP) in modo molto semplice e veloce. Infine è stata effettuata un’analisi
statistica dei dati mediante il Fisher’s Exact test, sono stati calcolati odds ratios (OR) e il
corrispondente intervallo di confidenza al 95% (95% CI) per valutare il rischio relativo di
sviluppare il carcinoma prostatico.
Obbiettivi da raggiungere per l’anno successivo (se applicabile)
 Studio dei determinanti farmacoradiogenetici della tossicità e risposta al trattamento
chemioradioterapico nel carcinoma della prostata;
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
1. “FARMACOGENETICA DELLA CARDIOTOSSICITÀ DA ANTRACICLINE”
Chiara Zanusso e Giuseppe Toffoli,
(longabstract per il convegno dal titolo “Complicanze cardiovascolari in oncologia: ieri ed
oggi. La gestione delle problematiche” svoltosi a Napoli in data 25-26 marzo 2009)
2. “NANOTECHNOLOGIES AND ONCOLOGY: PHARMACOKINETICS AND
PHARMACOGENOMICS TO OPTIMIZE THE ANTITUMOR THERAPIES”
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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Chiara Zanusso, Erika Cecchin, Paola Biason, Elena De Mattia, Franca Sartor and Giuseppe
Toffoli
(Poster presentato al 2nd Phd workshop 10th/11 September 2009 presso Wittenberg)
(Abstract presentato al “Congresso Nazionale della Società Italiana di Chemioterapia”
svoltosi a Udine in data 14 ottobre 2009
Attività formativa
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
 700 ore di studio e approfondimento degli argomenti trattati mediante libri e review di tipo
cartaceo e/o elettronico dal 1 gennaio 2010.
 700 ore di laboratorio presso la “Farmacologia Sperimentale e Clinica” del CRO di Aviano
diretta dal dr. Giuseppe Toffoli dal 1 gennaio 2010.
Congressi, seminari, corsi avanzati e altre attività didattiche passive
“Nanotechnology School Annual Meeting 2010” svoltosi in data 18, 19 e 20 gennaio 2010 dalle
ore 14-17, 9-17, 9-13 presso l’Università degli Studi di Trieste.
Seminar on 'How to present scientific results' dr. Hanna Mamzer svoltosi in data 22 gennaio
2010 dalle ore 10 alle ore 17 presso l’Università degli Studi di Trieste
“Presentation of Nanochallenge and Polymerchallenge by Veneto Nanotech” svoltosi in data 15
giugno 2010 dalle 14.00 alle 14.30
“Development of On-line Monitoring devices for the extrusion process” (prof. Miguel Nobrega
of the University of Minho in Portugal) svoltosi in data 15 giugno 2010 dalle 14.30 alle 15.00
“Use of VPN and UGOV” (prof. Maurizio Fermeglia) svoltosi in data 15 giugno 2010 dalle
15.00 alle 16.30
Seminari:
“Bone marrow modelling: new insights regulation of hemopoiesis” svoltosi in data 13 gennaio
2010 dalle ore 15 alle ore 16
“Young investigators event: la due-giorni dei giovani ricercatori dell’IRCCS CRO” svoltosi in
data 10 e 11 marzo 2010 dalle ore 14.30 alle ore 18.00
“Targeting tyrosine kinase receptors in solid tumors: the lesson of GISTs” svoltosi in data 12
marzo alle ore 15.00
“Connecting the Dots between Tumor Cell Metabolism and Statins as Anti-Cancer Agents”
svoltosi in data 3 maggio 2010 dalle 14.30 alle 15.30
“Recenti progressi in nanomedicina clinica visti da una prospettiva chimico-fisica” svoltosi in
data 8 giugno dalle 15.00 alle 16.30
“Mechanisms controlling the integrity of replicating chromosomes” (dr. Foiani) svoltosi in
data 11 giugno dalle 10.00 alle 11.00
“Strutturare un protocollo di ricerca” (dr. Foiani) svoltosi in data 11 giugno dalle 11.00 alle
12.30
“Multidisciplinarità in UroOncologia” svoltosi in data 10 settembre 2010 dalle 09.30 alle 19.00
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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“The future of technologies (an overview on research technology)” svoltosi in data 6 ottobre
2010 dalle 16.00 alle 17.00
“Infertilità, gravidanza e tumori” svoltosi in data 20 ottobre 2010 dalle 14.30 alle 19.00
“Seminari in Oncologia: diagnostica, clinica e ricerca” svoltosi in data 21 ottobre dalle 15.00
alle 17.00, 4 novembre dalle 15.00 alle 17.45, 11 novembre dalle 15.00 alle 17.30, 18 novembre
dalle 15.00 alle 16.15 e 25 novembre dalle 15.00 alle 16.30.
“Incontri finalizzati all’esposizione e alla discussione dei progressi ottenuti nell’ambito dei
progetti di ricerca della SOC di FSC” svoltosi nel seguente periodo dal 01/01/2009 al 31
dicembre 2009 dalle ore 13.15 alle 14.45
Corsi:
“L'operatore sanitario e la comunicazione in sanità: Power Point come strumento informatico
per presentazioni efficaci” svoltosi in data 3 e 9 febbraio 2010 dalle 15.00 alle 18.00
“Corso di inglese scientifico livello avanzato” svoltosi in data 6-13-20-27 maggio, 3-10-17-24
giugno, 30 settembre, 7-14-21-28 ottobre, 4-11 novembre 2010. 30 ore di lezione
“L’operatore sanitario e la gestione dei dati alfa-numerici: Excel come strumento per
elaborare e visualizzare efficacemente le informazioni” Svoltosi in data 24 novembre, 1 e 7
dicembre 2010 dalle ore 15.30 alle ore 17.30.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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Dottorandi del 25 ciclo: •
STEFANO AMBROSINI
Titolo della tesi: Сrescita e caratterizzazione di nanostrutture (anche) con luce di sincrotrone
Supervisore: Silvia Rubini
Attività di ricerca
Messa a punto e perfezionamento del protocollo di crescita vapore-liquido-solido di nanofili
autocatalizzati di GaAs su substrato di GaAs/silicio ossidato. Messa a punto e perfezionamento del
protocollo vapore-solido per nanofili di GaAs su substrati di GaAs/silicio ossidato. Comprensione
delle dinamiche cristalline all’interfaccia di crescita in funzione delle condizioni locali (flusso netto
di atomi alla cima del nanofilo). Definizione di protocolli per interrompere la crescita di nanofili, da
riprendersi in un secondo momento eventualmente ex situ mediante cappaggio con As amorfo.
Studio, realizzazione e caratterizzazione (fotoluminescenza, microscopia elettronica in
trasmissione) di eterostrutture In(Ga)As/GaAs in nanofili auto e non catalizzati.
Apprendimento e studio di microscopia elettronica in trasmissione. Comprensione e studio degli
effetti del riscaldamento post crescita sulla struttura cristallina di fili Au catalizzati di GaAs
all’interno ed esterno della colonna del microscopio.
Messa a punto di un protocollo per la comprensione in situ della struttura cristallina delle nanofili in
crescita per mezzo della riflessione della diffrazione di elettroni ad alta energia RHEED.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa),
- F Martelli, M Piccin, G Bais , F Jabeen, S Ambrosini, S Rubini and A Franciosi Nanotechnology
18 (2007) 125603 (4pp)
- S. Ambrosini, M. Fanetti, V. Grillo, A. Franciosi and S. Rubini, Journal of Applied Physics 109,
094306 (2011)
- S. Ambrosini, M. Fanetti, V. Grillo, A. Franciosi and S. Rubini, AIP ADVANCES 1, 042142
(2011)
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
- Self catalyzed GaAs nanowires on GaAs (100): growth and characterization, S. Ambrosini, M.
Fanetti, V. Grillo and S. Rubini, New Trends in Nanotechnology, Braga (Portugal) 09/10
- Self catalyzed GaAs nanowires on Si-treated epiready (100) GaAs wafers by MBE,
S. Ambrosini, M. Fanetti, V. Grillo, A. Franciosi and S. Rubini, III-V Nanowire workshop, Bad
Honnef (Germany), 02/2011
Partecipazione a congressi (come relatore)
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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- In situ transmission electron microscopy analyses of thermally an- nealed self catalyzed GaAs
nanowires grown by molecular beam epitaxy, S. Ambrosini, J. B. Wagner, T. Booth, A. Savenko,G.
Fragiacomo, P. Boggild and S. Rubini, Nano2011, Yekaterinburg, 06/11
Attività formativa
Periodi di permanenza all’estero (data e Sede)
24/01/11 – 24/05/11: DTU Copenhagen, DK
19/06/11 – 01/07/11: Yekaterinburg, Russia
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
02/02/11 – 05/05/11, Transmission Electron Microscopy, Marco Beleggia, Ph.D student class, DTU
CEN, Copenhagen (DK)
Attività didattica di supporto e attività didattica attiva
Atomic Force Microscopy, a student MS in naotecnologie, DTU Nanotech, Copenhagen (DK) con
Zachary Davis, professore ordinario al DTU Nanotech, Copenhagen (DK).
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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SILVIA BIDOGGIA
Titolo della tesi: Gold nanoparticles as carriers for drug delivery applications.
Supervisore: L. Pasquato
Tutori (eventuali): /
Attività di ricerca
L’obiettivo del mio progetto di ricerca è la progettazione, sintesi e caratterizzazione di
nanoparticelle di oro ricoperte da un monostrato organico con grado di complessità, e quindi di
funzionalità, innovativi da utilizzare in ambito biomedico per il trasporto e rilascio di biomolecole
e/o composti biologicamente attivi. A tale scopo nell’arco di questo secondo anno è stata
ottimizzata la sintesi del tiolo 12-mercapto-dodecanesolfonate acid (MDDS) che, grazie al gruppo
solfonato, oltre ad impartire solubilità in acqua alle nanoparticelle favorisce complessazione di
biomolecole mediante interazioni elettrostatiche. Sono state sintetizzate e caratterizzate
nanoparticelle ricoperte da tale tiolo e da una miscela di MDDS e un tiolo perfluorurato
commerciale (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanethiol) in rapporti differenti. Questi
campioni di nanoparticelle verranno caratterizzati nel corso del terzo anno e si andrà ad investigare
quale sia l’organizzazione del monostrato mediante tecniche ESR, STM e con simulazioni
multiscala. Comprendere l’organizzazione del monostrato, infatti, è un aspetto chiave in quanto
esistono evidenze del fatto che solo nanoparticelle con pattern a strisce sono in grado di passare la
barriera cellulare senza arrecare danno. È stata messa a punto anche la sintesi di altri tioli con
funzionalità tale da rendere le nanoparticelle solubili in acqua, quali l’acido-12mercaptododecanoico e il 12-mercaptotrimetilammonio-dodecano. Ciascuno di questi tioli è stato
utilizzato per la sintesi di nanoparticelle con monostrato misto con rapporto 1 : 2 tiolo perfluorurato
: tiolo idrogenato e la caratterizzazione completa di questi campioni è ora in corso.
Nell’arco di quest’anno inoltre, in collaborazione con il gruppo del professor Fermeglia e della
professoressa Pricl, è stato messo a punto un metodo innovativo per la simulazione molecolare di
nanoparticelle ricoperte da monostrato misto composto da miscele di tioli idrogenati e fluorurati.
Questi studi hanno permesso di confermare la formazione di domini a isole all’interno del
monostrato in accordo con precedenti esperimenti ESR e in nessun caso sono presenti distribuzioni
casuali. È stato dimostrato che la forma e le dimensioni di questi domini variano dipendentemente
dal rapporto tra i due tioli presenti nel monostrato e dalla loro lunghezza. In particolare
nanoparticelle miste con rapporto 1:1 tra tiolo idrogenato e perfluorurato presentano un
organizzazione a stripes su NP con diametro > di 1.9 nm mentre per rapporti inferiori o uguali a 4 :
1 si formano domini a isola.
Più recentemente si sono sintetizzate e caratterizzate MPCs-F8-PEG e si è introdotto nel
monostrato un tiolo fluorescente allo scopo di valutare mediante esperimenti di risonanza magnetica
di 19F la possibilità di impiegare nanoparticelle perfluorurate come agenti di contrasto per imaging
in vitro e in vivo e contestualmente usare il microscopio elettronico per identificare le aree in cui si
ha accumulo di NP.
Obbiettivi da raggiungere per l’anno successivo

Individuare la sintesi più semplice ed efficace per ottenere NP con monostrato
idrogenato/fluorurato solubili in acqua.

Completare la caratterizzazione delle nanoparticelle con monostrato misto
idrogenato/perfluorurato.

Studiare l’organizzazione del monostrato misto mediante tecniche ESR ed STM e in silico.

Studio mediante microscopia elettronica del impiego di NP fluorurate per imaging in vitro
e in vivo su sistemi modello.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa): /
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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
C. Gentilini, A. Pace, S. Bidoggia, P. Posocco, P. Franchi, M. Lucarini, S. Pricl and L.
Pasquato “Self-organization of mixtures of fluorocarbon- and hydrocarbon amphiplic
thiolates on the surface of gold nanoparticles: a combined experimental and multiscale
molecular modeling study” Manuscript in preparation.
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
 S. Bidoggia; L. Pasquato; “European Winter School on Physical Organic Chemistry”;
Presentazione poster dal titolo: “Perfluorinated monolayer-protected Au nanoparticles for
membrane permeation”; Bressanone, Italia, 30 gennaio-4 febbraio 2011.
 S. Bidoggia, P. Posocco, M. Fermeglia, S. Pricl, and L. Pasquato; “Summer School on
Nanotechnology”; Presentazione poster dal titolo: “Control of the morphology of mixed
monolayers protecting gold nanoparticles using perfluoro ligands”; Trieste, 20-23 settembre
2011.
Attività formativa
Congressi, seminari, corsi avanzati e altre attività didattiche passive
 “Congresso annuale della scuola di dottorato in nanotecnologie”; Università degli Studi di
Trieste, 17-19 gennaio 2011.
 “European Winter School on Physical Organic Chemistry”; Bressanone, 30 gennaio - 4
febbraio 2011.
 Prof. Maurizio Prato dell’Università degli Studi di Trieste; seminario: ”Biomaterials and
Nanomedicine”; Savoia Excelsior Palace, Trieste, 30 marzo 2011.
 Prof. János Kristóf e Prof. Erzsébet Horváth of the University of Pannonia, Institute of
Environmental Engineering in Hungary; seminario: “Synthesis and structure elucidation of
kaolinite organo-complexes”; Università degli studi di Trieste, 3 maggio 2011.
 Prof. Maurizio Fermeglia; seminario “Use of VPN and U-GOV”; Università degli Studi di
Trieste, 3 maggio 2011.
 Dr. Hicham Hamoudi of the Université-Paris Sud; seminario: “ Self assembled monolayers
on gold the challenge”; Università degli Studi di Trieste, 1 luglio 2011.
 Dott. Matteo Castronovo; seminario: “The effect of confinement on enzymes diffusion and
reactions inside DNA nanostructures”; Università degli Studi di Trieste, 29 luglio 2011.
 “Summer School on Nanotechnology”, Università degli studi di Trieste, 20-23 settembre
2011.
 Dott.ssa Cristina Gentilini del Imperial College of London; seminario: “Biomimetic scaffold
for tissue engineering”; Università degli Studi di Trieste, 22 settembre 2011.
 Presentazione dei dottorandi del terzo anno della scuola di nanotecnologie; Università degli
studi di Trieste, 29 novembre 2011.
Attività didattica di supporto e attività didattica attiva

Attività didattica di supporto per l’insegnamento di chimica organica I con laboratorio,
corso di laurea triennale in chimica, primo anno, Università di Trieste, 40 ore.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
46
YAN-XIN CHEN
Title of the thesis: Nanostructured Titanium Dioxide Based Materials for Photocatalysis and
Photoelectrocatalysis
Supervisor: Paolo Fornasiero
Tutors (if any): Claudio Bianchini, Alessandro Lavacchi
Research Activity
At present most of the methods for the mass production of metal nanocrystals (NCs) can only
control the size, with no or little chance to select shape and surface structure. The latter being
important for tailoring the catalyitic properties for specific reactions. Pulsed Electrodeposition
(PED) provided the first examples of tetrahexadral Pd NCs, whose electroxidation activity
expressed in terms of the current density referred to the catalyst Electrochemically Active Surface
Area (EASA) has been found to range from 4 to 6 times higher than the state of the art NCs Pd
electrocatalyts. However, the catalytic activity per unit weight was still far from being competitive
with the state of the art electrocatalysts due to the relatively large size of the particles (> 50 nm).
This framework shows clearly that the design of efficient catalyst for the small organic molecule
oxidation needs for NCs with high density of poorly coordinated metal atoms at the surface. At the
same time an effective catalyst must have a large surface to volume ratio to provide high mass
specific activity also being able to be synthesized with metal loading adequate for practical
applications. To succeed in the task we propose an alkaline post-treatment aimed at i) reducing the
particle size (electrochemical milling) and ii) creating high index facets (shaping). This process
shows two main advantages as compared with the PED as i) it allows the deposition of Palladium in
the desired loading with virtually any known deposition method and ii) operates in alkaline
solutions providing particle shaping through surface oxidation/reduction without metal dissolution.
This marks a substantial difference with the PED shaping occurring via a dissolution/growth
mechanism which makes difficult to independently control particle size and shape.
Publications on scientific journals (printed or in press)
 (1) “Energy Efficiency Enhancement of Ethanol Electrooxidation on Pd-(CeO2)/C in Passive
and Active Polymer Electrolyte-Membrane Fuel Cells”, submitted to Chemsuschem, November,
2011
 Valentina Bambagioni, Claudio Bianchini, Yanxin Chen, Jonathan Filippi, Paolo Fornasiero,
Massimo Innocenti, Alessandro Lavacchi, Andrea Marchionni, Werner Oberhauser, Francesco
Vizza.
 (2) “RedOx Milling and Faceting (ROMiF) - A Post-Treatment for the Size Control and the
High Index Facets Generation of Palladium Nanoparticles.”, (manuscript in preparation)
 Y.X. Chen, M. Bevilacqua, C. Bianchini, S.G. Sun, S.P. Chen, J. Filippi, P. Fornasiero, M.
Innocenti, A. Lavacchi, F. Vizza, F. di Benedetto, A. Marchionni, W. Oberhauser, H. Miller
Publications/abstracts in conferences/congresses (national or international)
Educational Activity
Classes followed (date, course, professor, type of course)
 - Nanotechnology Summer School 2011 – September 20-23, 2011, Trieste, Italy.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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Conferences, seminars, advanced courses and other didactic activities
 - “Carbohydrate recognition: Chemistry issues and applications”, Prof. Bing-He Wang. 17/05/
2011, Firenze, Italy.
 - “Form Metal to Metal-Free Catalysts”, Dr. Cuong Phan- Huu & Dr. Francois Garin,
29/06/2011, Firenze, Italy.
 - “Stability diagram of dipolar Bose Einstein condensate in an optical lattice”, Dr. Alves
Emmauel De Lima Henn, 13/10/2011, Firenze, Italy.
 - “High resolution structure and stability of gold nanoparticles/protein complex”, Dr. Luigi
Calzolai, 18/10/2011, Firenze, Italy.
 - “Computer simulation of biomolecules”, Draio A. Estrin, 26/10/2011, Firenze, Italy.
Support educational activity and teaching
 - Read the book《Scanning Microscopy for Nanotechnology》, 2-21 May, 2011, total 30
hours
 - Read the book《Characterization of Nanophase Materials》, 10-20 Auguest, 2011, total 40
hours
 - Read the book《Renewable Resources and Renewable Energy: A Global Challenge,
Second Edition》, 5-20 October, 2011, total 60 hours
 - Read the book《Handbook of Electrochemistry by Cynthia G. Zoski》, 1-20 November,
2011, total 80 hours
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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MARIO GANAU
Titolo della tesi: Applicazioni nanotecnologiche nell’ambito delle neuroscienze quantitative:
analisi proteomica dei gliomi cerebrali di alto grado
Supervisore: Prof. GIACINTO SCOLES e Dr.ssa LOREDANA CASALIS (SENIL
Nanoinnovation Lab. - Sincrotrone Elettra, Trieste)
Tutori (eventuali):/
Attività di ricerca
Il principale obbiettivo della presente Tesi di Dottorato è l’analisi proteomica di cellule astrocitarie
sotto influenza di stimoli esterni al fine di chiarire il ruolo delle cellule gliali nei processi di
oncogenesi. Una review sistematica della letteratura relativa all’analisi proteomica dei gliomi ha
evidenziato l’alterazione di circa 100 proteine. L’attuale limite tecnico degli studi di proteomica dei
gliomi cerebrali è legato all’elevata sensibilità necessaria per monitorare le pathways cellulari, e le
loro relative interazioni proteiche, sotto stimoli fisiologici e patologici. Per superare questo limite
abbiamo deciso di sviluppare un approccio nanoquantitativo che consenta un’analisi proteomica
precisa, ad alta sensibilità e basso costo, con potenzialità di screening in tempo reale e
sottotipizzazione di tumori cerebrali.
Al termine del primo anno avevamo tracciato due approcci paralleli e sinergici da perseguire: 1)
uno basato sulla fabbricazione di microwells per l’immobilizzazione di cellule viventi, e 2) l’altro
volto all’ottimizzazione di nanopatches per l’analisi di proteine o anticorpi in soluzione. In tal senso
al fine di valutare la capacità delle cellule selezionate (E.Coli gentilmente forniti dallo Structural
Biology Lab @ Elettra) di aderire e sopravvivere all’interno dei microwells di PDMS, erano stati
condotti una serie di trials, con e senza mezzo di coltura, che avevano dimostrato con successo la
possibilità di immobilizzare cellule viventi e di consentire la loro attiva replicazione all’interno dei
microcostrutti.
Nel corso del secondo anno ci si è quindi dedicati all’ottimizzazione di nanopatches per la specifica
analisi proteomica di cellule astrocitarie. I biomarkers su cui si è focalizzata la nostra attenzione
sono la Glial Fibrillary Acidic Protein (GFAP), che appartine alla famiglia dei filamenti intermedi
che svolge un riolo cruciale per il funzionamento del citoscheletro celluare; e la p53 che appartiene
alla classe degli oncosoppressori. Entrambe queste proteine sono alterate nelle cellule gliomatose
mentre la prima può anche essere repertate nel secretoma di astrociti tumorali, la seconda richiede
una loro analisi proteo mica.
Per la fabbricazione di nanoarrays, concepiti per l’immobilizzazione di qualsiasi anticorpo
biotinilato specifico per le suddette proteine è stato scelto un approccio basato sul nanografting con
Microscopio a Forza Atomica (AFM).
Le due seguenti strategie sono state adottate:
1)
DNA-directed-immobilization (DDI) di anticorpi biotinilati. Nanopatches di DNA a
singola elica (ssDNA) sono stati graftati in una matrice di monostrati autoassemblati
(SAM) di superfici d’oro alchiltiolo modificato. Al fine di sfruttare la capacità della
streptavidina (STV) di legarsi ad un anticorpo biotinilato è stata successivamente
indotta l’ibridazione di un filamento di DNA complementare (cDNA) a quello
precedentemente immobilizzato sulla superficie nanoassemblata che presentasse
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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2)
anche un tag di STV. Sfortunatamente, nonostante i ripetuti esperimenti e l’impiego
di diversi filamenti di DNA [i.e. cf5 and cf9], questo approccio è risultato
insoddisfacente nell’ottenere un costrutto DNA-STV funzionale, ciò è probabilmente
dovuto ad un problema di stabilità a lungo termine del coniugato STV-DNA. E’ stato
pertanto sfruttato un approccio leggermente più sofisticato, necessitante due fasi per
la realizzazione del suddetto coniugato DNA-STV. Un differente filamento di ssDNA
[i.e. cf4] è stato ibridizzato al suo cDNA che presentava un ligando specifico per la
tirosine piuttosto che un tag di STV. La formazione di un coniugato DNA-STV è stata
quindi ottenuta in una seconda fase dell’esperimento grazie all’interazione tra il
ligando per la tirosina e i residui tirosinici della STV stessa. In tal modo si è riusciti
ad ottenere la formazione di coniugati DNA-STV, purtroppo però ad ora questi non
sono risultati sufficientemente stabili da immobilizzare anticorpi biotinilati antiGFAP
(GFAP Ab).
Fabbricazione di biotina alchiltiolo modificata. Nanopatches di biotina sono stati
graftati in una matrice di monostrati autoassemblati (SAM) di superfici d’oro
alchiltiolo modificato. I siti di legame per la biotina propri della STV [4 siti per
ciascun tetramero di STV] sono stati sfruttati per immobilizzare ai patches di biotina
anticorpi monoclonali antiGFAP. Al momento questa strategia ha dimostrato di essere
la più efficace.
Obbiettivi da raggiungere per l’anno successivo (se applicabile)
Il passo successivo nel percorso di ricerca è costituito dall’ottimizzazione dei nanopatches di
biotina alchiltiolo-modificata coniugata alla STV, che al momento pare il substrato più conveniente
per l’immobilizzazione di anticorpi biotinilati (i.e. per la GFAP). Nonostante ciò la nostra
attenzione sarà comunque focalizzata anche al conseguimento della strategia con DDI (nella
speranza che costrutti più stabili possano rappresentare la risposta ai problemi incontrati durante
l’anno appena trascorso), che risulta mandatoria per poter realizzare un’analisi multiplexing. Inoltre
ci riserviamo di testare i nostri nanopatches di anticorpi antiGFAP con 1) GFAP di controllo
ricombinante, e 2) GFAP umana contenuta nel lisato di astrociti maligni.
Attività formativa
Posters/Abstracts a congressi nazionali e internazionali
 M.Ganau, P.Parisse, S.Corvaglia, L.Ianeselli, D.Scaini, C.Sanavio, L.Casalis, G.Scoles.
Proteomic analyses of malignant gliomas. Regional Summer School of Nanotechnology
2011
 S.Corvaglia, M.Ganau, Fruk L, Sanavio B, Ianeselli L, Cesselli D, Beltrami AP, Scoles G,
Scaini D, Casalis L. Combination of novel protein nanoarrays and microwells devices for
single cell protein profiling. Gordon Research Conference Proceedings 2011
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
11-14 Gennaio, 2011: Corso di Statistica per Specializzandi in Medicina c/o UniTs
11 Aprile, 2011: Prof Livesey, Seminario “Stem cell models of human cerebral cortex
development and disease” c/o UniTs
24 Giugno, 2011: Prof Legname (SISSA), Prof Zanusso (UniVr), Prof Geschwind (UCSF)
Seminario: Molecular Biology and clinical aspects of prion diseases c/o UniTs
29 Luglio, 2011: Dr Castronovo (Temple University): The Effect of Confinement on
Enzymes Diffusion and Reactions Inside DNA Nanostructures c/o UniTs
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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31 Ottobre – 1 Novembre, 2011: Lectures on Quantitative approaches to Biological
Problems c/o ICTP
Congressi, seminari, corsi avanzati e altre attività didattiche passive
17-19 Gennaio 2011: Congresso annuale della Scuola di Dottorato in Nanotecnologie c/o
UniTs
2 Febbraio, 2011: Seminario “BioMol” c/o Elettra
24 Marzo, 2011: Seminario “Brain Awareness Week” c/o Centro Interdipartimentale per le
Neuroscienze Brain
19-23 Settembre, 2011: Summer School Regionale di Nanotechnologia c/o UniTs
10-14 Ottobre, 2011: Joint ICTP-KFAS conference on Nanotechnology for Biological and
Biomedical Applications (Nano-Bio-Med) c/o ICTP
31 Ottobre – 1 Novembre, 2011: Conference on System Biology and New Sequencing
Techniques c/o ICTP
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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VALENTINA GIORGIS
Titolo della tesi: Development, design and characterization of Metamaterials
Supervisore: Filippo Romanato
Tutori (eventuali):
Attività di ricerca
Il progetto di ricerca è focalizzato sulla progettazione, fabbricazione e caratterizzazione di
metamateriali, in particolare sulla geometria Split Ring Resonator (SRR). Il primo passo, la
progettazione, viene eseguito con il supporto del software COMSOL, con l'aiuto dei teorici del
gruppo (LaNN, PAdova). I campioni sono fabbricati con la tecnica della litografia a raggi X e
vengono poi cresciuti utilizzando la crescita elettrolitica in soluzione d'oro. Altre tecniche utilizzate
come supporto alla fabbricazione degli SRR sono wet e dry etching (produzione membrane per
maschere X), l'evaporazione di metalli (produzione di un substrato conduttivo), lo sputtering
(produzione substrato). Nello step litografico sono stati utilizzati resist di tono positivo e negativo e
diversi substrati: silicio, membrane di nitruro di silicio, vetro e ITO. Lo scopo finale è la
fabbricazione di strutture alte (600-700nm) su substrato trasparente. Al momento sono stati prodotti
campioni di area estesa su supporto trasparente (vetro e ITO) ed è stata caratterizzata una maschera
per litografia utilizzando l'ellissometro presso LaNN. Sviluppo futuro della ricerca: analisi di
differenti geometrie (diverse simmetrie, strutture inclinate), eventuale utilizzo dei campioni come
sensori biochimici.
Oltre al progetto di tesi ho collaborato a diversi progetti di ricerca all'interno del mio gruppo, nella
fabbricazione di campioni (crescita elettroliticha, evaporazione), e all'interno di progetti con aziende
a altre università.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa),
F. Romanato, M. Massari, T. Ongarello, M. Carli, G. Pirruccio, D. Sammito, V. Giorgis, D. Garoli,
R. Bozio, R. Pilot, R. Signorini, P. Schiavuta, F. Marinello, “Design, Fabrication and
characterization of Plasmonic Gratings for SERS”, Microelectronic Engineering 88 (8), pp. 27172720
D. Garoli, M. Natali, G. Parisi, T. Ongarello, E. Sovernigo, M. Massari, V. Giorgis, G. Ruffato, S.
De Zuani, F. Romanato “Fabrication of metamaterials in the optical spectral range”,
Microelectronic Engineering 88 (8), pp. 1951-1954
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
V. Giorgis, F. Romanato, M. Massari, G. Parisi, M. Carli, D. Sammito, E. Sovernigo, “Design,
Fabrication and Characterization of Split Ring Resonators using X-Ray Lithography”, MNE 2011
G. Bovo, D. Sammito, D. De Salvador, G. Biasiol, M. Gaio, T. Ongarello, V. Giorgis, “Design of a
plasmonic structure integrated on a GaAs HEMT photodetector for biosensing applications”, MNE
2011
D. Sammito, G. Zacco, P. Zilio, V. Giorgis, A. Martucci, J. Janusonis, “Design and fabrication of
plasmonic gratings for bulk Silicon solar cell light harvesting enhancement”, MNE 2011
S. De Zuani, M. Natali, D. Garoli, V. Giorgis, M. Massari, G. Parisi, “Ferroelectric metamaterials:
towards a refractive index control”, Metamaterials 2011
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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Altre pubblicazioni
D. Sammito, P. Zilio, G. Zacco, V. Giorgis, F. Romanato, “Nanotrutture plasmoniche per la raccolta
della luce, PV Technology, 4/4/2010, p,46
Attività formativa
Congressi, seminari, corsi avanzati e altre attività didattiche passive
Nanotechnology Summer School 2011, Trieste, 20/09/2011-23/09/2011
Metamaterials 2011, Barcellona, 10/10/2011-13/10/2011
Metamaterials Doctoral School, 14/10/2011-15/10/2011
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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MARIANNA LUCAFO’
Titolo della tesi: NANOSTRUTTURE DI CARBONIO COME VETTORI PER FARMACI
ANTITUMORALI
Supervisore: PROF. GIANNI SAVA
Tutori (eventuali): DOTT. SABRINA PACOR, PROF. SONIA ZORZET E DOTT. TATIANA DA
ROS
Attività di ricerca
Il progetto prevede lo studio di nuove nanostrutture di carbonio, quali ad esempio fullereni, il cui
impiego in campo biomedico è di forte interesse grazie alla possibilità di essere funzionalizzati
agendo come sistemi di drug delivery per il trasporto di farmaci. Sono stati condotti studi in vitro su
fullereni funzionalizzati impiegando diverse linee cellulari con l’obiettivo di valutare se gli effetti
tossici o meno di questi composti possano variare a seconda dalla linea cellulare utilizzata. I modelli
di studio utilizzati sono linee cellulari neoplastiche di carcinoma mammario umano, di
adenocarcinoma umano di colon e di adenocarcinoma polmonare umano non a piccole cellule. Gli
studi di citotossicità hanno permesso di individuare un fullerene che presenta una limitata tossicità
(F2)
con il quale sono state eseguite prove citofluorimetriche sulla linea MCF7 che hanno
dimostrato come sia in grado di attraversare le membrane plasmatiche e di accumularsi nelle cellule
già dopo un’ora, aumentando in quantità fino a 12 ore. L’analisi è stata condotta fino alle 72 ore,
tempo in cui il valore di fluorescenza del fullerene sembra rimanere stabile. Mediante microscopia a
fluorescenza, sono stati condotti studi di distribuzione sub-cellulare, dai quali è emerso che F2 non
colocalizza né a livello mitocondriale nè lisosomiale; quest’ultima evidenza lo renderebbe un
vettore stabile per farmaci acido-labili. Inoltre, la mancata internalizzazione del fullerene a livello
nucleare escluderebbe la possibilità di un danno diretto a carico del materiale genetico. In parallelo
sono stati condotti i primi esperimenti sul coniugato F2-DOXORUBICINA ma le prove di
citotossicità hanno indicato che il coniugato, nella linea MCF7 ed MCF7/ADR, ha attività
irrilevante rispetto alla doxorubicina libera. Tuttavia risulta che la doxorubicina trasportata da F2
viene internalizzata maggiormente nella linea MCF7/ADR rispetto alla linea MCF7, contrariamente
a quanto avviene con la doxorubicina libera. È possibile quindi affermare che F2 si potrebbe
dimostrare un valido vettore per eludere il problema della multidrug resistence nei confronti di
farmaci antitumorali causata dall’attività estrusiva della pompa P-gp. L’ostacolo da superare rimane
quindi la scelta del farmaco da coniugare visto che questo ipotetico vettore non entra nel nucleo (e
che quindi la doxorubicina e altri antitumorali ad azione nucleare non potrebbero svolgere le proprie
funzioni) nelle linee studiate. In alternativa si potrebbe pensare di legare il farmaco al fullerene
attraverso un legame più debole in modo da facilitarne il rilascio citosolico.
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
28-30 Marzo 2011 –Trieste- 5° Meeting Nuove Prospettive in Chimica Farmaceutica SIF;
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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14-17 Settembre 2011 -Bologna- 35° Congresso Nazionale Della Società Italiana di Farmacologia;
Attività formativa
Congressi, seminari, corsi avanzati e altre attività didattiche passive
20-23 Settembre 2011 -Trieste- Nanotechnology Summer School 2011
Attività didattica di supporto e attività didattica attiva
Correlatrice nella tesi di laurea della facoltà di Farmacia, dal titolo: Nanovettori per farmaci
antitumorali: studio di un fullerene funzionalizzato ed analisi preliminare del coniugato con la
doxorubicina. Relatore Pacor S. (Orlando R., C.d.L. CTF, A.A. 2010-2011)
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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LUCIA MARSICH
Titolo della tesi: “Design and synthesis of functionalized metal nanoparticles for bio-analysis
with Surface-Enhanced Raman Scattering (SERS)”
Supervisore: Valter Sergo
Tutori: Alois Bonifacio
Attività di ricerca
Durante il primo anno di dottorato ho sviluppato un substrato SERS attivo, costituito da
nanoparticelle di argento ridotte con il citrato ricoperte dalla poli-L-lisina (PLL-AgNPs). Il
substrato così ottenuto è stato utilizzato per misurare la bilirubina libera.
All'inizio del secondo anno una curva di calibrazione è stata costruita, le bande di confidenza, il
limite di rilevabilità (LOD) e il limite di rilevabilità quantitativo (LOQ) è stati calcolati, con lo
scopo di poter quantificare la bilirubina in campioni con concentrazione incognita. E` stata
analizzata l'interazione dell'albumina con le nanoparticelle, dal momento che in presenza di questa
proteina il segnale SERS della bilirubina diminuisce. Le immagini TEM raccolte d dopo aver
aggiunto l'albumina alle PLL-AgNPs mostrano la proteina legata allo strato di PLL attorno alle
NPs. La bilirubina è stata isolata dalle proteine del siero con un filtro ibrido di
poliacrilamide/agarosio utilizzando un sistema per gel-elettroforesi. Ma lo spettro non ha mostrato
alcuna banda vibrazionale. Attualmente sono oggetto di studio altri metodi per isolare la bilirubina
dalle proteine del siero. Si sta pianificando di utilizzare le PLL-AgNPs per quantificare l'uptake di
culture cellulari esposte a concentrazioni nanomolari di bilirubina. A riguardo sono stati effettuati
degli esperimenti preliminari, in particolare per trovare una soluzione tampone che possa essere
applicata per la crescita delle cellule e per le misure SERS. L’HEPES è risultato avere queste
caratteristiche. La bilirubina è stata quantificata nelle soluzioni di HEPES e l’intensità dello spettro
risulta proporzionale alla concentrazione.
Durante il periodo presso la Technische Universitaet a Berlino (gruppo del prof Hildebrandt)
saranno sviluppate delle NPs per rilevare il Citocromo-C attaccato ad un elettrodo d’oro.
Attualmente sono oggetto di studio diversi tipi di substrati SERS attivi costituiti da AgNPs.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa):
Marsich, L., Moimas, L., Sergo, V., Schmid, C.; “Raman spectroscopic study of bioactive silicabased glasses: The role of the alkali/alkali earth ratio on the Non-Bridging Oxygen/Bridging
Oxygen (NBO/BO) ratio”; Spectroscopy 23, 2009; pp 227-232
In preparation: Marsich L., Bonifacio A., Sergo V.; “Polylysine coated silver nanoparticles as
sensors for bilirubin quantification using Surface Enhanced Raman Spectroscopy”.
Poster:
Polylysine coated silver nanoparticles as sensors for bilirubin quantification using Surface
Enhanced Raman Spectroscopy (SERS)”, L. Marsich, A. Bonifacio, V. Sergo; Yellow Retreat –
Trieste, 06 – 07 giugno 2011 (Congresso sulla biliribina organizzato dal Centro Studi Fegato)
Attività formativa
Periodi di permanenza all’estero (data e Sede)
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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Dal 24 ottobre 2011 fino al Aprile 2012 - Berlino (Germania) presso la “Technische Universitaet”
nel “Institut fuer Chemie Max-Volmer-Laboratorium für Biophysikalische Chemie”.
Esami sostenuti, ore di lezione e di laboratorio seguite (sostituiti da studio personale)
Libri:
o R. Aroca, “Surface-Enhanced Vibrational Spectroscopy” 2006 John Wiley & Sons, Ltd
o “Bile pigments and Jaudice , Edited by J. Donald Ostrow. New York: Marcel Dekker, Inc., 1986.
o D. Harvey, “Modern Analytical Chemistry”, 2000 McGraw-Hill Higher Education
o F. Siebert and P. Hildebrant, “Vibrational spectroscopy in Life Science”, 2008, WILEY-VCH
Reviews:
 Hyunhyub Ko at al., ”Nanostructured Surfaces and Assemblies as SERS Media”, Small 2008, 4,
No. 10, 1576–1599
 Richard J. C. Brown, Martin J. T. Milton, “Nanostructures and nanostructured substrates for
surface-enhanced Raman scattering (SERS)”, J. Raman Spectrosc. 2008; 39: 1313–1326
 Xiu-Mei Lin, Yan Cui, Yan-Hui Xu, Bin Ren, Zhong-Qun Tian, “Surface-enhanced Raman
spectroscopy: substrate-related issues”, Anal Bioanal Chem, DOI 10.1007/s00216-009-2761-5
 J. Millstone et al. “Colloidal gold and silver triangular nanoprisms.”, Small, 2009, Vol 5, Issue 6,
Pages 646-664
 A. Guerrero Martinez “Nanostars shine bright for you: Colloidal synthesis, properties and
applications of branched metallic nanoparticles” Current Opinion in Colloid & Interface Science,
Volume 16, Issue 2, April 2011, Pages 118-127.
Congressi, seminari, corsi avanzati e altre attività didattiche passive
Final Conference 2009 – Trieste,18 - 20 gennaio 2010 (PhD School in Nanotechnology)
How to present scientific results, Trieste 22 gennaio 2010
Yellow Retreat – Trieste, 08 – 09 marzo 2010 (Congresso sulla bilirubina organizzato da
Centro Studi Fegato)
Intensive course about "Molecular self-assembling and nanostructures” , Trieste 23 giugno - 13
luglio 2010
Tour of SENIL laboratories (Elettra) - Trieste, 20 luglio 2010
XVI Scuola Nazionale di Scienza dei Materiali – Bressanone (BZ), 27 settembre - 02 ottobre
2010
“High-Resolution Integrated Micro Electrode Arrays (MEAs) for Imaging Neurophysiological
Signaling” – Trieste, 25 ottobre 2010
“Introduzione alla tecnologia MEMS”, Dr Ing Cristina Bertoni – Trieste, 12 aprile 2011
“Synthesis and structure elucidation of kaolinite organo-complexes”, János Kristóf and
Erzsébet Horváth – Trieste, 3 maggio 2011
Yellow Retreat – Trieste, 06 – 07 giugno 2011 (Congress about bilirubin studies organized by
Centro Studi Fegato)
“Self assembled monolayers on gold the challenge”, Dr. HIcham Hmamoudi - 1 luglio 2011
“The Effect of Confinement on Enzymes Diffusion and Reactions Inside DNA
Nanostructures”, Matteo Castronovo – 18 luglio 2011
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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Regional Summer School of Nanotechnology – Trieste, 19 – 23 settembre 2011
Attività didattica di supporto e attività didattica attiva
20 h di tutoraggio a tre studenti nel laboratorio di spettroscopia Raman.
Addestramento tesisti alla sicurezza nel laboratorio chimico.
Correlatore di una tesi specialistica in ingegneria dei materiali dal titolo: “Sintesi e
caratterizzazione di nanoparticelle ibride semiconduttore-metallo come marcatori ottici per
applicazioni biomediche”.
Correlatore di una tesi triennale in ingegneria industriale dal titolo: “Nanostrutture metalliche
per applicazioni SERS (Surface Enhanced Raman Spectroscopy) ottenute per deposizione di
oro”.
Correlatore di una tesi triennale in ingegneria industriale dal titolo: “Valutazione dei rischi e
pianificazione del sistema di prevenzione e protezione: applicazione ad un laboratorio
chimico universitario a scopo didattico e di ricerca”.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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ANGELO PERONIO
Titolo della tesi: Catalisi eterogenea a livello delle singole molecole
Supervisore: prof. Giovanni Comelli
Tutori (eventuali): dr. Carlo Dri
Attività di ricerca
Il mio tema di ricerca è lo studio di sistemi modello per la catalisi eterogenea a livello delle singole
molecole che li compongono, utilizzando le tecniche di microscopia e spettroscopia con risoluzione
sub-molecolare messe a disposizione da un microscopio a scansione ad effetto tunnel a bassa
temperatura (LT-STM).
Quest’anno in particolare ho proseguito lo studio del coadsorbimento di NO e NH3 sulla superficie
(111) del platino mediante simulazioni di struttura elettronica basate sulla teoria del funzionale della
densità (DFT). Innanzitutto la geometria di adsorbimento di questo sistema – ipotizzata in
precedenza a partire dai risultati STM – è stata confermata riproducendo le immagini STM e vari
risultati di spettroscopia elettronica e vibrazionale presenti in letteratura; successivamente lo spettro
vibrazionale calcolato su questa geometria ha permesso di interpretare correttamente le misure
effettuate lo scorso anno di spettroscopia vibrazionale su singole molecole (IETS); in questo
momento è in corso la caratterizzazione del legame NO – NH3 con l’ipotesi che si tratti di un
legame a idrogeno.
Ho caratterizzato inoltre il rumore nella corrente di tunnelling del microscopio, che al presente
rende estremamente difficoltose le misure IETS per energie maggiori di 100 meV. La misura della
densità spettrale della corrente ha permesso di individuare e distinguere i contributi principali al
rumore, inoltre ho messo a punto un metodo quantitativo per determinare la miglior frequenza di
misura e per paragonare le prestazioni di diversi convertitori tensione-corrente, tenendo conto anche
della funzione di trasferimento tensione/corrente misurata dell’STM.
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
27 ottobre 2011: poster “A NH3‒NO coadsorption complex on Pt(111)” presso la conferenza
Slonano 2011, Institut Jožef Stefan, Ljubljana (SLO).
Attività formativa
Periodi di permanenza all’estero (data e Sede)
7 novembre 2011 – 22 dicembre 2011: presso il gruppo del prof. Saw-Wai Hla, Ohio University,
Athens, Ohio, USA
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
21 giugno 2011 – 15 luglio 2011: corso “Molecular self-assembling and nanostructures”, docenti
d.ssa Loredana Casalis, prof. Alberto Morgante, prof.ssa Lucia Pasquato, ore seguite 10.
Congressi, seminari, corsi avanzati e altre attività didattiche passive
17-19 gennaio 2011: “Congresso annuale della Scuola di Dottorato in Nanotecnologie”,
Università degli Studi di Trieste;
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3 maggio 2011: seminario “Synthesis and structure elucidation of kaolinite organo-complexes”
dei proff. János Kristóf ed Erzsébet Horváth dell’Università della Pannonia, Università degli
Studi di Trieste;
1 luglio 2011: seminario “Self assembled monolayers on gold the challenge” del dr. Hicham
Hamoudi dell’Université-Paris Sud, Università degli Studi di Trieste;
20-23 settembre 2011: First Joint Summer School on Nanotechnology, Università degli Studi
di Trieste;
27 ottobre 2011: conferenza Slonano 2011, Institut Jožef Stefan, Ljubljana (SLO).
Attività didattica di supporto e attività didattica attiva
4 aprile 2011: seminario con laboratorio per studenti delle scuole superiori “La fisica delle celle a
combustibile ad idrogeno” presso il dipartimento di Fisica dell’Università degli Studi di Trieste,
all’interno del Progetto Lauree Scientifiche dell’Università degli Studi di Trieste. Vincitore del
primo premio del concorso nazionale Progetto Lauree Scientifiche.
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DAVIDE SAMMITO
Titolo della tesi: Design, Fabrication and Characterization of Plasmonic Nanostructures for Solar
Cells Light Harvesting Enhancement
Supervisore: prof. Filippo Romanato
Attività di ricerca
La mia attività di ricerca è dedicata allo studio dell’integrazione di reticoli metallici nanostrutturati
su dispositivi opto-elettronici al fine di sfruttarne gli effetti plasmonici e controllare le
caratteristiche di assorbimento della radiazione luminosa. In particolare, nel corso dell’ultimo anno,
ho lavorato su tre differenti applicazioni dei cristalli plasmonici.
La prima, nell’ambito del progetto europeo ORION, riguarda l’integrazione di nanowire di argento
con sezione rettangolare periodicamente disposti sulla superficie superiore di celle solari
convenzionali in Silicio. Tramite simulazioni numeriche sono state individuate configurazioni
geometriche del reticolo capaci di aumentare l’assorbimento della cella per una polarizzazione della
luce (TM) fino a 3.6% mentre non esistono configurazioni che determinano un miglioramento per
radiazione non polarizzata. E’ stato sviluppato un processo di fabbricazione basato su litografia
laser interferenziale capace di realizzare le nanostrutture progettate sulle ampie superfici delle celle
solari. Dopo aver implementato un upgrade sul setup di misura dell’efficienza quantica, sono stati
caratterizzati diversi dispositivi integranti i reticoli plasmonici e sono stati estratti spettri in accordo
con l’andamento simulato.
La seconda attività riguarda la modellizzazione ottica di cristalli plasmonici all’interno di celle
solari organiche aventi come strato attivo un bilayer costituito da C60 e CuPc. Un aumento del 11%
dell’assorbimento per luce non polarizzata può essere ottenuto ottimizzando un reticolo inserito
nello strato di trasporto per le buche.
L’ultima attività invece riguarda la realizzazione di un fotorivelatore per applicazioni in biosensoristica costituito da eterostrutture epitassiali in AlGaAs/GaAs. Reticoli a forma di solchi a V
coperti da un sottile strato di oro sono stati realizzati sulla superficie superiore per rivelare la
presenza di analiti tramite effetti plasmonici.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa),
 Garoli D., Romanato F., Zilio P., Natali M., Marinello F., Ongarello T., Sammito D., De
Salvador D., “Fabrication of "nano-rocket-tips" for plasmonic nanofocusing” (2011)
Microelectronic Engineering, 88 (8), pp. 2530-2532.
 Romanato F., Pilot R., Massari M., Ongarello T., Pirruccio G., Zilio P., Ruffato G., Carli M.,
Sammito D., Giorgis V., Garoli D., Signorini R., Schiavuta P., Bozio R., “Design,
fabrication and characterization of plasmonic gratings for SERS” (2011) Microelectronic
Engineering, 88 (8), pp. 2717-2720.
 Zacco G., Romanato F., Sonato A., Sammito D., Ruffato G., Morpurgo M., Silvestri D., Carli
M., Schiavuta P., Brusatin G., “Sinusoidal plasmonic crystals for bio-detection sensors”
(2011) Microelectronic Engineering, 88 (8), pp. 1898-1901.
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 Zilio P., Sammito D., Zacco G., Romanato F., “Absorption profile modulation by means of 1D
digital plasmonic gratings” (2010) Optics Express, 18 (19), pp. 19558-19565.
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
 Poster: D. Sammito, P. Zilio, G. Zacco, A. Martucci, M. Dai Prè, J. Janusonis, J. Ulbikas, S.
Padovani, F. Rasello, S. Sinesi and F. Romanato, “The ORION project: nanotechnology
applied to bulk Silicon solar cells”, NanotechItaly 2011, Venezia 23-25 Novembre 2011
 Poster and Conference Proceedings: G. Zacco, D. Sammito, P. Zilio, G. Melcarne,
G. Gigli, M. Mazzeo, F. Romanato, “Light harvesting enhancement in organic solar cells
through the integration of plasmonic crystals”, 26th European Photovoltaic Solar Energy
Conference and Exhibition, Hamburg 5-9 Settembre 2011
 Poster: G. Bovo, D. Sammito, D. De Salvador, G. Biasiol, M. Gaio, V. Giorgis, P. Zilio, T.
Ongarello and F. Romanato, “Design of a plasmonic structure integrated on a GaAs HEMT
photodetector for biosensing applications”, 37th International Conference on Micro and
Nano Engineering, Berlino 19-23 Settembre 2011
 Poster: V. Giorgis, F. Romanato, M. Massari, G. Parisi, M. Carli, D. Sammito, E. Sovernigo,
“Design, Fabrication and Characterization of Split Ring Resonators using X-Ray
Lithography”, 37th International Conference on Micro and Nano Engineering, Berlino 19-23
Settembre 2011
Partecipazione a congressi (come relatore)
 “Design and fabrication of plasmonic gratings for bulk Silicon solar cell light harvesting
enhancement”, 37th International Conference on Micro and Nano Engineering, Berlino 1923 Settembre 2011
Attività formativa
Congressi, seminari, corsi avanzati e altre attività didattiche passive
 Congresso: “Nanotechnology school congress”, Università di Trieste 17-19 Gennaio 2011
 Corso su linguaggio di programmazione Labview presso Sincrotrone Trieste Aprile 2011
 Corso: “Molecular self-assembling and nanostructures”, Università di Trieste Giugno-Luglio
2011
 Seminario: “Self assembled monolayers on gold the challenge”, Hicham Hmamoudi presso
Università di Trieste 1 Luglio 2011
 Seminario: “The Effect of Confinement on Enzymes Diffusion and Reactions Inside DNA
Nanostructures”, Matteo Castronovo presso Università di Trieste 29 Luglio 2011
 Summer school: “International Summer School on Photovoltaics and New Concepts of
Quantum Solar Energy Conversion”, organizzato da Helmholtz Zentrum Berlin presso
Hirschegg (Austria) 11-18 Settembre 2011
Attività didattica di supporto e attività didattica attiva
 Tutor di Gianluca Bovo nell’attività sperimentale finalizzata con la tesi di laurea magistrale in
Scienza dei Materiali presso l’Università di Padova dal titolo “Multilayer electro-plasmonic
nanostructures for biosensing architechtures”
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Dottorandi del 26 ciclo:
DAMIANO CASSESE
Title of the thesis:Design and realization of nanoelectromechanical and plasmonic devices for
Raman spectro-microscopy
Supervisor: Marco Lazzarino
Tutors (if any):
Research Activity
During the first year, the following research activities were carried:
 Design: FEM simulation were performed with COMSOL software to study the development
of a cantilever chip capable of high temperature heating (>400oC) in a small area (<2
micrometers), to localize the nanowires growth. Following the result obtained, an optical
mask for the chip fabrication was designed with Ledit software.
 Fabrication: the chip fabrication was begun, even though further analysis of structure
compensation in wet etching is needed. Nanowires growth has been achieved on silicon
oxide in PECVD; some tests of growth with MBE are underway.
 Raman spectroscopy: the Raman spectroscopy setup was optimized and the optical
components aligned. Some spectra of various samples of interest (graphene, AlGaAS
nanowires, carbon nanotubes) were taken along with Raman maps aat the micro-scale using
an Andor Technologies spectrograph coupled with JPK AFM movement stage and a ZEISS
inverted microscope.
Objectives for the following year (if applicable)
In the following year we aim to produce the chips with the cantilevers integrated; following the
optimization of the nanowires growth process, the complete devices will be produced.
The chips will be tested, to confirm their TERS potentiality and their behaviour as AFM cantilevers.
We will also focus on raman spectroscopy and maps of samples, both using micro-Raman and
TERS,
Educational Activity
Classes followed (date, course, professor, type of course)
 Intense course on “Molecular self-assembling and nanostructures”, held by A. Morgante, L.
Casalis, L. Pasquato, 21/06/2011 – 18/07/2011
 Winter collage in Optics: advances in nano-optics and plasmonics (and preparatory school)
at ICTP, to be held from 30th of January till 17th of February
Conferences, seminars, advanced courses and other didactic activities
 Massimiliano Di Ventra (Department of Physics University of California, San Diego), “Fast
DNA sequencing: a physicist’s perspective”, seminar at SISSA – Condensed Matter
department
 Workshop on "Circulating Tumor Cells", 7th November 2011, Udine
 Conference Monalisa’s Quidproquo “Nanotechnology Meets Clinical Medicine", October 68, 2011, Aviano/Udine
 Summer school of Nanotechnology, Trieste, September 20-23
 Konrad Misiura, ‘New Approches in Cancer Therapy’, Trieste
 János Kristóf and Erzsébet Horváth, “Synthesis and structure elucidation of kaolinite
organo-complexes”, May 12 2011
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STEFANIA CORVAGLIA
Titolo della tesi: Modellare substrati su scala nanometrica per la caratterizzazione di singole cellule
Supervisore: dr. Loredana Casalis, dr. Denis Scaini
Tutori (eventuali):
Attività di ricerca
La ricerca in ambito biomedico dei meccanismi molecolari di patologie come il cancro ha rivelato
come i tessuti malati provenienti da biopsie presentino una distribuzione spaziale molto eterogenea
di popolazioni di cellule tumorali all’interno dello stesso campione che lasciano supporre differenze
sostanziali anche tra singole cellule. Le tecniche attuali riescono al meglio ad estrapolare dati
mediando su campioni di qualche centinaio di cellule e sono perciò insensibili alle variazioni a
livello di singola cellula. Per questo, abbiamo come obiettivo lo sviluppo di una nuovo metodologia
che ci permetta di isolare e caratterizzare decine di singole cellule dal punto di vista del contenuto
proteico (secretoma/proteoma) e di farne un’analisi statistica. Abbiamo sviluppato un array di
micropozzetti delle dimensioni di una singola cellula, con lo scopo di immobilizzare le cellule in un
volume piccolo che aumenti la concentrazione di proteine rare. Per la detection della proteine
stiamo lavorando allo sviluppo di un nano/microarray di anticorpi specifici, prodotto utilizzando
una litografia AFM-mediata (Nanografting), a chiusura del pozzetto per l’analisi di specifiche
proteine, biomarkers significativi dello stato della cellula. In questo primo anno di dottorato ho
lavorato alla realizzazione degli array di micropozzetti, con particolare attenzione alla scelta del
materiale più adatto alla crescita di cellule, allo studio dell’influenza delle proprietà meccaniche del
materiale sull’adesione e la crescita, all’intrappolamento all’interno del pozzetto di singole/poche
cellule e alla chiusura del pozzetto per l’analisi. Sto testando il sistema utilizzando un modello
cellulare semplice e facilmente reperibile (linea tumorale HeLa) che faciliti l’applicazione futura a
sistemi d’interesse medico.
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
- SIBBM Frontiers in molecular Biology, Trieste, Italy- poster abstract_26-28 maggio 2011;
- EBSA 8th European Biophysics congress, Budapest, Ungheria- poster abstract, 23-27 agosto
2011;
- CFN Summer School on Nano-Biology, Karlsruhe, Germany- poster abstract, 7-10 settembre
2011;
- Summer school of Nanotechnology, Trieste, Italy- poster abstract, 20-23 settembre 2011;
- ICTP Conference on Nanotechnology for Biological and Biomedical Applications (Nano-BioMed), Trieste, Italy- poster abstract, 10-14 ottobre 2011
Attività formativa
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
- 21 giugno 2011- 15 luglio 2011, corso "Molecular self-assembling and nanostructures" Lucia
Pasquato, Alberto Morgante and Loredana Casalis
Congressi, seminari, corsi avanzati e altre attività didattiche passive
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-17-19 gennaio 2011, congressino nanotecnologie, Scuola di dottorato in Nanotecnolgie,
università di Trieste, Trieste, Italy ;
-2 febbraio 2011 workshop biomol @ ELETTRA
Seminari:
-10 febbraio Zehra Sayers, “Structural and functional studies on plant metallothioneins and
heteromeric G-proteins”;
-1 aprile Filippo Lutisani, “Single molecule fluorescence microscopy: new insights”;
-7 aprile Ario de Marco “Application opportunities for single domain antibodies”;
- 3 maggio
-11 maggio Alessandro Laio “Colloquium on condensed matter physics: Exploring the universe
of protein structures beyond the protein data bank”.
-12 maggio Konrad Misiura, “New approaches in cancer therapy”
-13 maggio Giacinto Scoles, “The importance of numbers (with units) and common sense: the
inevitability of solar energy for the resolution of energy need”.
-21 giugno Massimiliano di Ventra, “Fast DNA sequencing: a physicist’s perspective”;
-1 luglio Hlcham Hmamoudi “Self assembled on gold the challenge”
-6 luglio Flavio Maran “Superefficient electron transfer trought 310 –helical peptides”
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VALENTINA DAL COL
Titolo della tesi: In silico prediction of drug resistance: from cancer targeted therapy to cancer
targeted prevention
Supervisore: Prof.ssa Sabrina Pricl
Tutori (eventuali): Prof. Maurizio Fermeglia
Attività di ricerca
Le recenti scoperte sulla natura dei processi genetici, implicati nelle trasformazioni neoplastiche,
hanno permesso di identificare le lesioni cellulari che promuovono il cancro, individuando target
selettivi per la progettazione di nuovi agenti terapeutici efficaci. Durante questo primo anno il mio
studio si è focalizzato su due diversi sistemi recettoriali: il recettore tirosin chinasico c-Kit e il
recettore 1. Per il primo sistema si è andati a studiare, attraverso tecniche di simulazione
molecolare, i cambiamenti strutturali che coinvolgono il dominio JXM (juxtamembrane) del c-Kit
in seguito a due differenti mutazioni geniche: 559-560 e V560G. Queste modificazioni portano ad
una diversa interazione tra il farmaco d’elezione (Imatinib) e la tasca di binding recettoriale. Si è
visto che la mutazione di delezione (559-560) conduce ad uno shifting dell’equilibrio verso la
forma attiva della chinasi mentre la missense (V560G), andando ad alterare la conformazione del
dominio JXM, permette una migliore interazione dell’Imatinib con il recettore nella sua
conformazione chiusa.
Si è inoltre sviluppato un modello predittivo 3D, per omologia, del recettore 1, per il quale è
mancante una struttura cristallizzata. E’ stata utilizzata una procedura multistep: sviluppo e
ottimizzazione della struttura 3D, identificazione del possibile sito di binding, docking di una serie
di ligandi, conseguente calcolo dell’energia libera di binding così da confrontare i risultati con i
valori sperimentali e, alla fine, verifica della capacità predittiva utilizzandolo per il design di una
nuova classe di composti. L’obiettivo finale è renderlo, dopo ulteriori validazioni, uno strumento
per il design di ligandi altamente selettivi e per comprendere meglio le interazioni che il recettore
instaura con altri sistemi biologici.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa),
“2-Difluoromethylene-4-methylenepentanoic acid, a paradoxical probe able to mimic the
signaling role of 2-oxoglutaric acid in Cyanobacteria” Liu X, Laurini E, Dal Col V, Posocco
P, Ziarelli F, Fermeglia M, Zhang CC, Pricl S, Peng L Organic Letters, Jun 3; 13(11):29247
“Homology model and docking-based virtual screening for ligands of the σ1 receptor” Laurini
E, Dal Col V, Mamolo MG, Zampieri D, Posocco P, Fermeglia M, Vio L, Pricl S ACS Med
Chem Lett 2011, 2: 834-839
“Activate and respond. A molecular rationale for c-kit activation and drug response by
juxtamembrane mutations in GISTs” Dal Col V et al. Mol Cancer Ther 2011 submitted
“Activity vs. toxicity of acridine compounds as anti-BVDV agents: a molecular modeling
study” Dal Col V et al. Antiviral Res 2011 submitted
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
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Comunicazione a VNPCF Trieste 2011 28-30 marzo “The long and winding road of the c-Kit
JXM domain” Dal Col V et al.
Comunicazione a VNPCF Trieste 2011 28-30 marzo “Overview on σ1 receptors: a 3D
homology model to solve a part of the enigma” Dal Col V et al.
Comunicazione a CDDD L’Aquila 2011 21-23 novembre “Nanozapped! DNA, siRNA, and
their dendritic nanovectors: a combined in silico/in vivo/in vitro approach” Dal Col V et al.
Comunicazione a CDDD L’Aquila 2011 23-25 novembre “The Sigma-Enigma. A multistep
homology modeling of 1 receptors” Dal Col V et al.
Comunicazione a Nanotechitaly 23-25 novembre 2011 “Trekking across GISTs: the clinical journey
of KIT, PDGFRA, and the in silico prediction of drug resistance in cancer targeted therapy” Dal Col
V et al.
Attività formativa
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
60 ore laboratorio MOSE
Scuole
AMBER school 3-6 maggio 2011 Barcellona
Summer school on Nanotechnology 20-23 settembre Trieste
COST Training school 2011 (Dendrimers as composites of advanced drug delivery nano systems)
Atene 3-7 ottobre 2011
Congressi, seminari, corsi avanzati e altre attività didattiche passive
Congressi
VNPCF (Vcongresso nuove prospettive in chimica farmaceutica) Trieste 28-30 marzo 2011
CDDD (Computationally driven drug discovery) L’Aquila 21-23 novembre 2011
Seminari
“Brached Peptides as Therapeutics” Prof. Bracci 21 marzo 2011
“Challenging the mistery of marine toxins” Prof. Yasumoto 15 aprile 2011
“New approaches in cancer therapy” Prof. Misiura 12 maggio 2011
“Nanosistemi per il drug e il gene delivery a base di derivati dell’acido aspartico” Prof. Cavallaro 1
giugno 2011
“Self assembled monolayers the Challenge” Dr. Hicham Hamoudi 1 luglio 2011
“The effect of confinement on enzyme diffusion and reaction inside DNA nanostructures” Dr.
Castronovo 29 luglio 2011
Corsi
“Molecular self- assembling and nanostructures”, Prof. Morgante, Casalis, Pasquato
Periodo 21/06-29/07/2011
Altre attività didattiche passive
Congresso dottorandi Scuola di Nanotecnologie 17-19 gennaio 2011
Presentazione delle attività scientifiche dei gruppi di ricerca del dipartimento DI3 25 febbraio 2011
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ANDREA FRASSETTO
Title of the thesis: Nanostructural analysis of the adhesive interface in dentistry
Supervisor: Prof. Milena Cadenaro
Tutor: Prof. Lorenzo Breschi
Research Activity
The first part of the program was focused on the literature review of the adhesive layer degradation
and nanoleakage development and on laboratory training, including an accurate analysis at SEM of
the interaction of different adhesive systems with the dentin substrate, by the application of
adhesive agents on human dentin surfaces, then stored in appropriate in vitro conditions to simulate
the oral environment for different time intervals in order to assess nanoleakage expression. Despite
acceptable immediate bonding effectiveness of dental adhesives, the durability of resin bonded
interface on dentin created by several bonding systems remains questionable. All the commercial
adhesives tested presented nanoleakage phenomena after 6 months of aging in artificial saliva. Thus
the intrinsic degradation mechanisms originated from beneath dentine hybrid layer by the slow
action of matrix metalloproteinases (MMPs) was investigated. The release and activation of these
endogenous enzymes during bonding to dentin are thought to be responsible for the in vitro and in
vivo manifestation of thinning and disappearance of collagen fibrils from incompletely infiltrated
hybrid layers in aged, bonded dentine. Collagen degradation generates several collagen fragments;
one of them (ICTP) was quantified by means of commercialized immunoassays. Moreover the loss
of mechanical properties of dentinal collagen was correlated, in particular the biaxial flexural
modulus of elasticity (EBF). Evaluation of both collagen denaturation and E-modulus could lead to a
more clear understanding of the durability of adhesive systems and nanoleakage development.
Objectives for the following year (if applicable)
• Analysis of new inhibitors of the enzymatic activity of dentin endogenous matrix
metalloproteinases (MMPs)
•
Influence of collagen cross-linkers in the inhibition of MMPs’ activity and subsequent
increase of mechanical properties of the adhesive layer
Publications on scientific journals (printed or in press)

Frassetto A, Navarra CO, Marchesi G, Turco G, Di Lenarda R, Breschi L, Ferracane JL,
Cadenaro M. Contraction stress and degree of conversion of self-adhesive resin cements.
Dental Materials, submitted.
Publications/abstracts in conferences/congresses (national or international)
Stress of polymerization of a new self-adhesive vs a conventional dual-cured cement. XVII
National Meeting of the College of Dentistry Teachers, Siena.

Stress of polymerization and degree of conversion of two self-adhesive vs a
conventional dual-cured cement. 21st European Dental Materials Conference; Turku
(FI).

Microtensile bond strength test of four self-etch commercial adhesives. 21st European
Dental Materials Conference; Turku (FI).
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
Influence of chewing simulation on bond strength of cemented composite-disks. Dent
Mater 2011; 27s: e8.

Effects of 6-month water storage on micro-tensile bond strength of self-etch
adhesives. Dent Mater 2011; 27s: e10.

Influence of chewing simulation on bond strength of cemented ceramic-disks. Dent
Mater 2011; 27s: e24.
Participation to conferences (as speaker)

Firenze-Siena 14-16 April 2011; XVII National Meeting of the College of Dentistry
Teachers. Poster Presentation, Stress of polymerization of a new self-adhesive vs a
conventional dual-cured cement.
Educational Activity
Periods abroad (date and place)

San Diego (USA) 16-19 March 2011

Augusta (USA) 20-22 March 2011

Seili-Turku (FI) 22-26 August 2011

Salvador (BR) 13-15 October 2011
Classes followed (date, course, professor, type of course)

Course of Material Sciences, CLSOPD II Semester, Prof. L. Breschi

Course of Adhesive Dentistry, CLSOPD II Semester, Prof. L. Breschi
Conferences, seminars, advanced courses and other didactic activities

Trieste 17-20 January 2011; Annual Meeting of the PhD School in Nanotechnology

San Diego (USA) 16-19 March 2011; Annual Meeting of the International Association
of Dental Research

Augusta (USA) 21-22 March 2011; Research Stage at Medical College of Georgia (Prof.
D. Pashley)

Trieste 8 April 2011; PhD Final Dissertations of School in Nanotechnology

Firenze-Siena 14-16 April 2011; XVII National Meeting of the College of Dentistry
Teachers

Trieste 12 May 2011; Seminar of Prof. K. Misiura: New Approaches in Cancer Therapy

Trieste 1 July 2011; Seminar of Dr. H. Hamoudi: Self assembled monolayers on gold the
challenge

Trieste 4-8 July 2011; FVG Summer School/Workshop on Structural Bioinformatics

Trieste 12 July 2011; Seminar of Prof. S.-W. Hla: Nanoscience at Work: Imaging and
Manipulation at Atomic and Molecular Scale
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
Seili (FI) 22-24 August 2011; Dental Materials Summer School

Turku (FI) 24-26 August 2011; European Dental Materials Conference

Trieste 15 September 2011; Seminar of Dr. G. Forte: Adult Stem Cell and Thermoresponsive Polymers for Cardiac Muscle Tissue Engineering

Trieste 20-23 September 2011; Summer School of the PhD School in Nanotechnology

Salvador (BR) 13-15 October 2011; Annual Meeting of Academy of Dental Materials

Bologna 18-19 November 2011; Annual Meeting of Italian Academy of Prosthetic
Dentistry

Milano 25-26 November 2011; Annual Meeting Expo Dental
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ELISA MINIUSSI
Titolo della tesi: Interaction of metal nanoclusters with graphene and low dimensional systems
Supervisore: Dr. Alessandro Baraldi
Tutori (eventuali):
Attività di ricerca
Il mio progetto di Dottorato verte sulla produzione e caratterizzazione di nanocluster metallici
depositati su opportune superfici solide, in modo particolare sul grafene cresciuto epitassialmente su
diversi substrati. La mia attività si articola dunque essenzialmente su due versanti: la crescita
epitassiale del grafene e lo sviluppo di una macchina per la produzione e deposizione di nanocluster
selezionati in massa.
Sul primo fronte, un risultato di rilievo è stato recentemente ottenuto con la pubblicazione su
Physical Review Letters di uno studio, iniziato durante la mia tesi specialistica, sul grafene cresciuto
epitassialmente su un nuovo substrato, un cristallo singolo di Re(0001). È noto che la forza di
interazione tra il grafene e il substrato determina la corrugazione del layer di carbonio, che a sua
volta è responsabile delle proprietà di trasporto sia elettronico che termico di quest’ultimo. Le
nostre ricerche hanno evidenziato una diretta correlazione tra la forte corrugazione del grafene su
questo substrato e la sua instabilità ad alte temperature.
È stato inoltre intrapreso lo studio di un nuovo sistema, il grafene cresciuto epitassialmente su una
lega di superficie PtRu, finalizzato a comprendere come variando la concentrazione di Pt nel primo
layer sia possibile modificare selettivamente l’accoppiamento grafene-substrato, e di riflesso le
proprietà morfologiche ed elettroniche del sistema.
In parallelo, sono iniziati i lavori di assemblaggio della sorgente di nanocluster presso il laboratorio
di Fisica delle Superfici (Dipartimento di Fisica dell’Università di Trieste e Laboratorio TASC
(IOM-CNR)). Nell’ambito di questo progetto ho trascorso quattro mesi con una borsa Erasmus
Placement presso il Dipartimento di Chimica Fisica della Technische Universität di Monaco di
Baviera (TUM), dove questa tecnologia è stata sviluppata allo stato dell’arte nel corso degli ultimi
anni. In questo modo ho potuto apprendere i principi di funzionamento e le modalità operative delle
sorgenti e della strumentazione scientifica utilizzata in combinazione con esse. Ho successivamente
sfruttato le conoscenze così acquisite per portare a termine la fase preliminare di assemblaggio della
macchina.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa)
E. Miniussi, M. Pozzo, A. Baraldi, E. Vesselli, R. R. Zhan, G. Comelli, T. O. Menteş¸ M. A. Niño,
A. Locatelli, S. Lizzit, and D. Alfè, “Thermal Stability of Corrugated Epitaxial Graphene Grown
on Re(0001)”, Phys. Rev. Lett. 106, 216101 (2011).
Altre pubblicazioni
E. Miniussi, M. Pozzo, A. Baraldi, E. Vesselli, R. R. Zhan, G. Comelli, T. O. Menteş¸ M. A. Niño,
A. Locatelli, S. Lizzit, and D. Alfè, “A link between corrugation and thermal stability of epitaxial
graphene”, Elettra Highlights 2010-2011, pagg. 66-67.
Partecipazione a congressi (come relatore)
Presentazione orale del seminario intitolato: “A link between corrugation and thermal stability of
epitaxial graphene”, in occasione dell’assegnazione del premio Fonda-Fasella 2011 conferitomi
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durante il workshop “Nanoenergetics: theoretical and experimental approaches” (Trieste, 15-16
Novembre 2011).
Attività formativa
Periodi di permanenza all’estero (data e Sede)
Borsista Erasmus Placement dal 1 aprile 2011 al 31 luglio 2011 presso il Dipartimento di Chimica
Fisica della Technische Universität di Monaco di Baviera (TUM) (tutori presso l’istituzione
ospitante: Prof. U. Heiz e Dr. F. Esch).
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
“Physikalische Chemie von Nanoteilchen und Oberflächen” (Chimica Fisica delle Nanoparticelle e
Superfici) http://www.pc.ch.tum.de/index.php?id=193 - Docenti: Dr. F.Esch, Prof. U. Heiz Numero di ore: 40
Contenuti: Introduzione alla Chimica Fisica dei cluster: transizione dagli oggetti di dimensioni
atomiche ai solidi di bulk; fabbricazione dei cluster, loro proprietà fondamentali e caratterizzazione
sperimentale (diffrazione, spettroscopia, microscopia); cluster elementari ed eterogenei, cluster
supportati e loro proprietà catalitiche.
Congressi, seminari, corsi avanzati e altre attività didattiche passive
Seminar at Elettra: Optical and Dynamical Properties of Hydrogen Bonded Systems
Nadja Doslic, Department of Physical Chemistry, University of Zagreb
10 Febbraio 2011, Seminar Room (Elettra)
Seminar at Elettra: X-Ray absorption spectroscopy and science at extreme conditions: previous
results and new opportunities for the XAFS beamline at Elettra
Giuliana Aquilanti, Sincrotrone Trieste
14 Marzo 2011, Seminar Room (Elettra)
Seminar at Elettra: Images of excited states
Giovanni Piani, Laboratoire Francis Perrin, CEA Saclay, France.
14 Marzo 2011, Seminar Room (Elettra)
Seminar at Elettra: Electronic Properties of Functionalized Quasi-Free-Standing Graphene and
Monolayer Boron Nitride
Danny Haberer, IFW Dresden, Dresden, Germany
21 Marzo 2011, Seminar Room (Elettra)
Joint Workshop on Energy and Sustainability: Materials and Processes
Chemistry Department, Northwestern University, and Catalysis Research Center, Technische
Universität München
Institute for Advanced Study (IAS) Technische Universität München, Lichtenbergstr. 2a, 85748
Garching, Germany
13-14 Maggio 2011
4. Joint Nanoworkshop of TU/e, DTU and TUM
TUM Institute for Advanced Study (IAS)
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TUM Campus Garching
1 Giugno 2011
DFH/UFA Photokat Workshop 2011: Photokatalytische Eigenschaften von Nanostrukturen
/ Propriétés photocatalytiques des structures nanométriques
IAS Building, TUM Campus
14-15 Luglio 2011
XI School on Synchrotron Radiation: Fundamentals, Methods and Applications
Duino Castle, Trieste, Italy
5-16 Settembre 2011
First Joint Summer School on Nanotechnology
Università di Trieste, Campus di Piazzale Europa
20-23 Settembre 2011
Seminar at Elettra: Adventures in Catalytic Nanospace: resolving catalytic phenomena at the
atomic scale
Michael Bowker, Wolfson Nanoscience Laboratory and Cardiff Catalysis Institute, School of
Chemistry, Cardiff University, Wales, UK.
2 Novembre 2011, Seminar Room (Elettra)
Workshop on Nanoenergetics: theoretical and experimental approaches
ICTP, Adriatico Guesthouse, Trieste, Italy
15-16 Novembre 2011
Seminar at Elettra: Probing ultrafast symmetry changes with light
Simon Wall, Department of Physical Chemistry, FHI (Berlin)
25 Novembre 2011, Seminar Room (Elettra)
Seminar at Elettra: XAFS at Elettra: recent achievements and future projects
Giuliana Aquilanti, Sincrotrone Trieste
1 Dicembre 2011, Seminar Room (Elettra)
Attività didattica di supporto e attività didattica attiva
Lettura di articoli e review su argomenti attinenti alla mia attività di ricerca, in particolare: studio
sperimentale e teorico delle proprietà del grafene (in generale), crescita del grafene su diversi
substrati solidi e sua caratterizzazione, nano cluster metallici e investigazione della loro morfologia,
proprietà elettroniche e reattività.
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ELISA MITRI
Titolo della tesi: Fabbricazione di dispositivi microfluidici per lo studio della risposta biologica di
cellule vive sottoposte a stimoli chimico-fisici mediante tecniche di microspettroscopie vibrazionali
Supervisore: Massimo Tormen
Tutori: Gianluca Grenci, Lisa Vaccari
Attività di ricerca
La microspettroscopia infrarossa (MIRS) è considerata tra i più promettenti metodi per lo screening
medico e diagnostico, grazie alle informazioni strutturali e conformazionali, contenute in uno
spettro infrarosso. Lo studio di cellule vive tramite MIRS richiede l'utilizzo di un set-up
microfluidico trasparente all'IR, capace di mantenere le condizioni necessarie alla vita delle cellule.
Negli anni scorsi presso il mio gruppo è stata messa a punto una piattaforma microfluidica su
finestre di CaF2 (materiale trasparente all'IR). Il dispositivo è stato testato con successo presso la
beamline SISSI (Elettra, Trieste). Nel mio primo anno di dottorato ho lavorato all'ottimizzazione del
set-up con l'intento di risolvere i problemi emersi nei precedenti esperimenti, tra cui:
 Scarsa aderenza del resist durante il processo fabbricativo dovuto alla bassa energia
superficiale del CaF2 (30-50 mJ/m2).
 Effetti sconosciuti del CaF2 sulle linee cellulari (es neuroni)
 Protocollo di chiusura del dispositivo
In riferimento ai punti 1 e 2, abbiamo modificato le proprietà superficiali del CaF2 tramite
sputtering di un sottile strato di Silicio. Questo approccio porta i seguenti vantaggi:
 Possibilità si operare il processo litografico su un substrato Si-like
Assenza di contatto tra cellule e CaF2

Per migliorare il protocollo di incollaggio si propone un nuovo metodo che sfrutta la quantità di
solvente residuo nel resist per promuovere l'adesione e la protezione dell'ambiente in cui si
confineranno le cellule. Per dimostrare la validità del nostro approccio abbiamo condotto una serie
di studi, monitorando diverse linee cellulari (MCF-7, HCT116) all'interno del dispositivo per
intervalli di tempo fino a 48 ore.
Pubblicazioni/abstracts in conferenze/congressi
“Optimization of Microfluidic Systems for IRMS real Time Monitoring of Living Cells”
Gianluca Grenci1, Giovanni Birarda1, Elisa Mitri1, Luca Businaro2, Sabrina Pacor3, Lisa Vaccari4,
Massimo Tormen1
1CNR-IOM, Laboratorio TASC – Lilit beam line, Basovizza/Italy, 2 CNR ISTITUTO DI FOTONICA E, ROMA/Italy, 3 Life Science Dept., Trieste
University, Trieste/Italy, 4 Elettra Synchrotron Light Laboratory, SISSI beam line, Basovizza/Italy
“Microfluidic devices for real-time infrared imaging of living cells”
G. Birarda1, G. Grenci2, L. Businaro3, E. Mitri2, M. Tormen2, S. Pacor4 and L. Vaccari1
1 Elettra Synchrotron Light Laboratory, ITALY, 2 IOM - CNR, ITALY, 3 Istituto di Fotonica e Nanotecnologie, ITALY, and 4 Trieste University,
ITALY
Attività formativa
Esami sostenuti, ore di lezione e di laboratorio seguite
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“Nanotecnologie e nanomicroscopie” (60 h 7,5 CFU laurea specialistica in biotecnologie mediche)
Carlo Dri - Gianluca Grenci
“Biologia Cellulare Animale” (48 h, 5 CFU laurea magistrale in chimica e tecnologie
farmaceutiche) Sabrina Pacor
Congressi, seminari, corsi avanzati e altre attività didattiche passive
Seminari
"Synthesis and structure evaluation on kaolinite Organo-Complexes" Prof. Janos Kristof – Dr.
Elisabeth Horvath 03/05/11
“Self assembled monolayers on gold the challenge” Dr. Hicham Hamoudi
“” Dr. Matteo Castronovo
Congressi
Congresso annuale della scuola 17-19 gennaio 2011, Trieste
Conferenze
Wirms 2011 - 6th International Workshop on Infrared Spectroscopy and Microscopy with
Accelerator-Based Sources – 4-9 settembre 2011, Trieste
MNE 2011- 37th International Conference on Micro and Nano Engineerin – 19-23 Settembre 2011
Berlino
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GIUSEPPINA PALMA
Titolo della tesi: Celle solari dye-sensitized nanostrutturate
Supervisore: Alessandro Fraleoni Morgera
Tutori (eventuali):
Attività di ricerca
Le attività di ricerca del primo anno di dottorato possono essere riassunte in tre punti fondamentali:
1) Comprensione generale dello stato dell’arte relativo alla fabbricazione ed ottimizzazione di celle
solari a colorante organico; 2) Messa a punto del set up di caratterizzazione che consiste in un
sistema di misura di curve I/V e uno di efficienza quantica; 3) fabbricazione di dispositivi come da
letteratura e studio preliminare di metodi per lo sviluppo di uno strato semiconduttore altamente
poroso da impiegare nelle celle suddette per aumentarne l’efficienza.
Il punto 1) è stato perseguito mediante uno screening approfondito della letteratura del settore e la
frequenza di una scuola internazionale dedicata al settore fotovoltaico. Il punto 2) è stato sviluppato
dapprima attraverso la frequenza di un corso base di programmazione in Labview, strumento
utilizzato per realizzare i software di guida di un set up di caratterizzazione I/V, costituito da un
simulatore solare accoppiato ad un multimetro, e di un sistema di determinazione di efficienza
quantica. Il punto 3) è stato perseguito cercando di riprodurre le prestazioni delle DSSC riportate in
letteratura, che raggiungono l’11% di efficienza. Attualmente la realizzazione di dispositivi
altrettanto validi non è stata ancora raggiunta, dato che il lavoro effettivo sui dispositivi è iniziato a
partire da Settembre 2011. In particolare, ad oggi i parametri di fill factor e V oc delle celle
realizzate sono in linea con i valori dei dispositivi stato dell’arte, mentre la corrente estraibile dal
circuito è ancora scarsa. Questo problema verrà affrontato introducendo uno strato compatto di
TiO2 tra l’anodo e lo strato semiconduttore mesoporoso, così da reprimere il forte processo di
ricombinazione locale; inoltre verrà caricata una maggiore quantità di colorante sullo strato
mesoporoso attraverso un processo di multidipping. Inoltre ottimizzazioni dello spessore dello
strato nano cristallino e della struttura generale dei dispositivi (contro-elettrodo, elettrolita,
isolamento dall’ambiente esterno, ecc) dovrebbero portare ad aumentare l’efficienza globale dei
dispositivi, attualmente ferma allo 0.7%.
Studi preliminari sull’utilizzo della metodologia ASB-SANS (Auxiliary Solvent-Based
Sublimation-Aided NanoStructuring) per incrementare l’efficienza delle celle, attraverso l’aumento
di porosità dello strato nanocristallino di TiO2, sono in corso.
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
• 19-23 Settembre 2011: Nanotech Summer School; Trieste, poster session
• 17-21 Ottobre, 2011: Workshop on New Materials for Renewable Energies, ICTP, Trieste,
poster session
Attività formativa
Periodi di permanenza all’estero (data e Sede)
 11-18 Settebre 2011: Quantsol Summer School; Hirschegg (Austria)
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Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
 7 Aprile- 5 Maggio 2011: Corso base di Labview, G. Cautero, corso di formazione presso
Elettra (16h)
 21 Giugno- 15 Luglio 2011: Summer course on Molecular self-assembling and nanostructures
(docenti: L. Casalis (8h), A. Morgante (6h), L. Pasquato (6h))
Congressi, seminari, corsi avanzati e altre attività didattiche passive
 17-19 Gennaio 2011: Workshop sulle nanotecnologie (Università di Trieste)
 03 Maggio 2011 ore 10: Seminario Nanotech: Synthesis and structure elucidation of kaolinite
organo-complexes (János Kristóf and Erzsébet Horváth, University of Pannonia, Institute of
Environmental Engineering, Hungary)
 03 Maggio 2011 ore 14: Seminario Elettra: The unusual physics of Dirac fermions in graphene
(Alessandra Lanzara, University California, Berkeley)
 13 Maggio 2011 ore 15: Seminario Elettra: The importance of numbers (with units) and
common sense: the inevitability of solar energy for the resolution of energy needs (Giacinto
Scoles, University of Udine, Faculty of Medicine, Department of Medical and Biological
Sciences, Ospedale di S. Maria della Misericordia in Udine, Italy.
 27 Maggio 2011: Celle solari polimeriche e dye-sensitized (Alessandro Fraleoni Morgera,
Sincrotrone Trieste)
 29 Luglio 2011: ‘The Effect of Confinement on Enzymes Diffusion and Reactions Inside
DNA Nanostructures’ (Matteo Castronovo)
 1 Luglio 2011 ‘Self assembled monolayers on gold the challenge’ Dr. HIcham Hmamoudi
(Université-Paris Sud)
 19-23 Settembre 2011: Nanotech Summer School; Trieste (Italia)
 17-21 Ottobre 2011: Workshop on New Materials for Renewable Energies, ICTP, Trieste,
Italy
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ANDREA RADIVO
Titolo della tesi: Studio sperimentale della fisica di dispositivi fotovoltaici organici
nano strutturati.
Supervisore: Massimo Tormen
Tutori : Simone Dal Zilio, Enrico Sovernigo
Attività di ricerca
In questo primo anno ho concentrato la prima parte del mio lavoro sull’acquisizione delle
conoscenze necessarie al progetto e sulla messa a punto di procedure di preparazione e
caratterizzazione di celle fotovoltaiche organiche. A tal fine, ho quindi prodotto e caratterizzato
celle fotovoltaiche aventi un'interfaccia planare tra strati donore ed accettore, utilizzando diverse
combinazioni di materiali. In una seconda parte del mio lavoro, ho elaborato un processo per
produrre celle fotovoltaiche organiche aventi un'interfaccia nano strutturata con una struttura
interdigitata di materiali donore ed accettore, conformazione che viene considerata in letteratura
come ottimale al fine di incrementarne il rendimento. Ho scelto, come materiali attivi diverse
coppie di piccole molecole organiche e fullereni ampiamente trattate in letteratura, e come tecnica
di nano strutturazione a costo contenuto, il nanoimprinting. La categoria di materiali in esame offre
un’ampia gamma di possibili coppie di materiali dalle diverse proprietà optoelettroniche, tuttavia
pochi di questi sono risultati adatti al nanoimprinting diretto. Ho quindi scelto un approccio
indiretto: nanoimprinting del substrato PEDOTT-PPS, utilizzato come conduttore/collettore di
lacune e facilmente stampabile, ottenendo una struttura a righe con diversi periodi e larghezze;
deposizione di uno strato conformale di materiale donore per evaporazione; riempimento delle
strutture rimanenti mediate deposizione da soluzione o evaporazione del materiale accettore;
evaporazione del contatto in alluminio per terminare la cella. Ho applicato questa procedura a
diversi materiali, ed i migliori risultati sono stati ottenuti con la coppia Pentacene-PCBM. E’ stato
infatti possibile depositare il pentacene in modo quasi conformale sul substrato nanostrutturato in
PEDOT:PPS e riempire in modo apparentemente completo e con poche porosità le strutture, con
PCBM depositato da soluzione, ottenendo così una struttura interdigitata dei due materiali.
Obbiettivi da raggiungere per l’anno successivo:
Gli obbiettivi per il prossimo anno di lavoro si possono articolare in:
 Affinare i processi di produzione per avvicinarsi allo stato dell’arte nella qualità e rendimento
delle celle planari;
 Proseguire con lo sviluppo delle celle nano strutturate in pentacene PCBM e trovare altri
materiali per cui il medesimo approccio sia possibile;
 Sviluppare nuovi sistemi di nano strutturazione delle celle fotovoltaiche organiche;
 Caratterizzare approfonditamente le celle prodotte per determinare l’effetto della variazione di
processi, strutture e materiali, sul rendimento e le proprietà optoelettroniche della cella;
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
Poster alla Summer school di nanotecnologie. Titolo del poster: Experimental Study of the
physics of nanostructured organic photovoltaic devices.
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Attività formativa
Esami sostenuti, ore di lezione e di laboratorio seguite:
Formazione in laboratorio all’utilizzo di strumenti di caratterizzazione e fabbricazione celle
fotovoltaiche presso laboratorio TASC e Elettra. In particolare:
Caratterizzazione: formazione per l’utilizzo autonomo di AFM, SEM, Simulatore solare,
diffrattometria RX profilometria e fotoluminescenza.
Fabbricazione: formazione su macchinari e nozioni necessarie a deposizione film per spin
coating, evaporazione termica a vuoto, sputtering, deposizione elettrochimica; formazione
utilizzo pressa per il nanoimpriting, tecniche per il patterning di substrati e celle (attacco
chimico e fotolitografia).
 Trattamenti substrati e celle: formazione per l’utilizzo di forno ossidativo, RIEE, tecniche di
pulizia e funzionalizzazione substrati.
Congressi, seminari, corsi avanzati e altre attività didattiche passive
Attività organizzate dalla scuola di dottorato:
Summer school of nanotechnology dal 20 al 23 settembre.
Seminario: Matteo Castronovo. The Effect of Confinement on Enzymes Diffusion and
Reactions Inside DNA Nanostructures. July 18 2011
Seminario: János Kristóf and Erzsébet Horváth; synthesis and STRUCTURE elucidation of
kaolinite organo-complexes
Seminar: Dr. Hicham Hmamoudi ‘Self assembled monolayers on gold the challenge’ July 1,
2011
Attività al di fuori della scuola di dottorato:
Workshop on New Materials for Renewable Energy 17 - 21 ottobre 2011 (ICTP, Miramare,
Trieste, Italy). (36h di seminari, poster session, con certificato di partecipazione).
Presentazione: Michael Felsmann, da Gatan, presentazione sulle tecniche EELS, TEM e SAM
ed I recenti avanzamenti in queste tecnologie. (1h)
Seminario: Serdar Sariciftci on organic photovoltaic at ICTP 13 Aprile (1h)
Attività didattica di supporto e attività didattica attiva
Studio di articoli scientifici e rewiews riguardanti le celle fotovoltaiche organiche o l’elettronica
organica in generale.
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MICHELE ROMEO
Titolo della tesi: “Sviluppo e applicazione di metodologie DFT e TDDFT per la
descrizione di osservabili spettroscopici in sistemi condensati”
Supervisore: Prof. GIOVANNA FRONZONI (DSCF)
Tutori (eventuali):
Attività di ricerca
L'adsorbimento di molecole organiche su superfici semiconduttrici ha attratto un'attenzione
crescente per la sua importanza nelle tecnologie emergenti.
La spettroscopia NEXAFS viene largamente utilizzata per caratterizzare strutture adsorbite su
superfici dal momento che permette di investigare i vari modi di adsorbimento così come
l'estensione dell'interazione adsorbato-substrato. Computazioni quantistico-chimiche sono
importanti per acquisire la maggior parte di informazione dagli esperimenti che sono spesso di
difficile interpretazione e razionalizzazione. L'obiettivo principale del progetto è lo sviluppo di uno
schema computazionale utile per la simulazione di spettri NEXAFS di molecole adsorbite su
superfici nel contesto del design di modelli molecola/superficie ed in quello del calcolo ed
interpretazione dei risultati spettroscopici. Durante il primo anno di dottorato è stata condotta una
simulazione di spettri NEXAFS di etilene adsorbita su una superficie regolare di Silicio, nella
fattispecie Si(100), considerando diverse geometrie di adsorbimento. Un primo step ha riguardato
l'implementazione di un codice di interfaccia con ADF (Amsterdam Density Functional code) per il
calcolo si spettri NEXAFS risolti angolarmente per date direzioni di polarizzazione della luce
incidente secondo l'espressione canonica di calcolo. In un secondo step sono stati ottimizzati
modelli di superfici adsorbenti con e senza le molecole di etilene per mezzo di computazioni DFT
periodiche su opportuni geometrizzazioni di slab. Sono state considerate entrambe le geometrie di
adsorbimento on-top e bridge. Dalle strutture risultanti dal calcolo periodico sono stati estratti
razionalmente cluster finiti utili alla successiva computazione degli spettri NEXAFS dell'etilene a
livello C1s. Il confronto fra gli spettri risolti angolarmente calcolati e quelli sperimentali è risultato
soddisfacente e mette in luce l'evidente potenziale della tecnica computazionale nello studio delle
configurazioni di adsorbimento di molecole su superfici.
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
“C K-edge NEXAFS Spectra of Model Systems for C2H4 on Si(100): a DFT Simulation”,
contenuti riportati negli “Atti del XXIV Congresso Nazionale della Società Chimica Italiana”
per la Divisione Computazionale
Attività formativa
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
 Marzo - Giugno 2011, Chimica Quantistica, Prof. Mauro Stener, corso specialistico
 Marzo - Giugno, 2011, Applicazioni Chimiche della Simmetria Molecolare, Prof. Piero
Decleva, corso specialistico
Congressi, seminari, corsi avanzati e altre attività didattiche passive
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
Serie di seminari su Molecular Self-assembling and Nanostructures, 21 Giugno – 15 Luglio,
2011, Trieste
 Scuola Estiva del FVG su Bioinformatica Strutturale, 4-6 Luglio 2011, SISSA, Trieste
 Scuola Estiva su Tecniche di Simulazione Atomistiche, 11- 29 Luglio 2011, SISSA, Trieste,
(affiliazione CECAM-SISSA)
 Scuola Estiva di Nanotecnologia 2011, 20-23 Settembre 2011, Scuola di Dottorato in
Nanotecnologie, Trieste
 Workshop su Nanoenergetica, 15-16 Novembre, 2011, ICTP, Trieste
Attività didattica di supporto e attività didattica attiva

Analisi Matematica, Fisica ed attività di esercitazione per studenti del 1o anno dei corsi
fondamentali di Fisica
 Attività di esercitazione intensiva per studenti del 1o anno dei corsi di STAN e Scienze
Geologiche
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SAJID HUSSAIN
Title of the thesis: Synthesis of Ordered Semiconductor Nanostructures by Directed Self-Assembly
for Photonic Applications
Supervisor: GIORGIO BIASIOL
Research Activity
Silicon mold with 45 - 50nm diameter pillars, with a height of 90nm & period of 300nm have been
fabricated using nanoimprint lithography. These molds are used in a second nanoimprint
lithography step to pattern the GaAs substrates used for QDs growth. Different nanoimprint &
optical resist have been tried, but good surface quality (i.e. RMS surface roughness ≥ 0.2nm) of
GaAs substrate after the removal of the resist have been achieved using mr-I 7010E. After hot plate
pressing of the mold and resist coated GaAs wafer, there is a very thin residual layer of resist inside
the holes underneath of the pillars. This residual layer is etched using oxygen plasma in Inductively
Coupled Plasma (ICP) system. These GaAs patterned substrates are chemically etched to get 5060nm dia holes with a 5 – 10nm depth. Different solutions (i.e. HCl:H2O2:H2O &
NH4OH:H2O2:H2O) with different dilution have been tried to fabricate these nanopores. Best results
have been achieved with HCl:H2O2:H2O solution with a ratio of 1:1:9. Substrate is cleaned using
wet chemistry & oxygen plasma in Reactive Ion Etching (RIE) system. Then oxide layer from the
patterned GaAs substrate is thinned chemically before its introduction into the Molecular Beam
Epitaxy (MBE) System. Silicon molds and patterned GaAs substrates have been analysed using
Scanning Electron Microscopy & Atomic Force Microscopy at different stages of the process. Then
patterned GaAs substrate is loaded in MBE system for QDs growth. Since thermal removal of the
oxide before growth would lead to a disappearance of the holes and to a roughening of the surface.
We are testing a method to desorb chemically the oxide through exposure to atomic Ga beams,
followed by annealing in As4 and deposition of a thin (<10nm) GaAs buffer before deposition of
InAs QDs. Understanding & optimization of the growth kinetics and parameters of QDs growth
using MBE System is in process.
Objectives for the following year (if applicable)
Kinetics and parameters of QDs growth using Molecular Beam Epitaxy System will be studied. All
parameters of QDs growth (i.e. Oxide layer removal using Ga flux, annealing, buffer layer
thickness, InAs QDs growth) will be optimized using Molecular Beam Epitaxy System.
Currently, nanopores on GaAs substrate are being fabricated using wet etching. As an alternative to
reduce hole size, dry etching will be used to fabricate these nanopores using RIE/ICP system.
Optical characterization of the QDs samples will be done using photoluminescence & microphotoluminescence spectroscopy.
Educational Activity
Conferences, seminars, advanced courses and other didactic activities
Seminar of Dr. HIcham Hmamoudi from Université-Paris Sud on ‘Self assembled monolayers on
gold the challenge’ at University of Trieste on July 1, 2011.
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Seminar of Matteo Castronovo on ‘The Effect of Confinement on Enzymes Diffusion and Reactions
Inside DNA on July 18 2011.
The regional Summer school on Nanotechnology 2011 at University of Trieste on 20 -23 September
2011
Support educational activity and teaching
Literature study/survey for material selection for QDs fabrication.
Research papers/thesis/articles have been studied to carry out the research work.
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FRANCESCA SANTESE
Titolo della tesi: Modellistica molecolare per materiali e rivestimenti multifunzionali nanostrutturati
Supervisore: Prof. Maurizio Fermeglia
Tutori (eventuali): Prof.ssa Sabrina Pricl
Attività di ricerca
Durante il mio primo anno di dottorato ho concentrato la mia attività di ricerca su due progetti
principali. Il primo è un progetto europeo, Multhybrids, il cui obiettivo primario era lo sviluppo di
una tecnologia innovativa per la preparazione di componenti con nanomateriali multifunzionali; il
secondo è un progetto nazionale, Nanostrata, che ha come scopo lo sviluppo di nuovi rivestimenti
nanostruttuati per diverse applicazioni industriali. In Multhybrids abbiamo caratterizzato 13 sistemi
con nanofillers di diversa natura e forma, puri o modificati con diversi compatibilizzanti, in diverse
matrici polimeriche, utilizzando una procedura di modellistica molecolare multiscala sviluppata dal
nostro gruppo di ricerca. I risultati ottenuti sono incoraggianti vista l’ottima concordanza dei valori
delle proprietà termofisiche calcolate con i corrispetivi dati sperimentali. Inoltre, si è visto che nei
sistemi esfoliati le caratteristiche chimico/fisiche dei modificatori non influiscono sulle proprietà
macroscopiche, mentre le dimensioni e la forma dei nanofillers hanno un grande impatto sulle
proprietà del materiale finale. In Nanostrata abbiamo svolto uno studio sulla bagnabilità di superfici
polimeriche con liquidi di diversa natura (acqua, olio, miscela di acqua e sapone) per sviluppare una
metodologia che consenta di predire alcune importanti proprietà dell’interfaccia, quali l’angolo di
contatto, la tensione superficiale e il lavoro di adesione. La concordanza dei risultati ottenuti con i
valori sperimentali disponibili in letteratura ha permesso di convalidare la procedura sviluppata. Si
potrà quindi procedere con la progettazione di nuovi rivestimenti andando a modificare le matrici
polimeriche con l’aggiunta di nanoparticelle di diversa natura.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa),
“Size and shape matter! A multiscale molecular simulation approach to polymer nanocomposites”
R. Toth, F. Santese, S. P. Pereira, D. R. Nieto, S. Pricl, M. Fermeglia and P. Posocco, Journal of
Material Chemistry, 2011 sottomesso
“Contact angles of water and oil on polymer surfaces by MD simulations” F. Santese, D. R. Nieto,
P. Posocco, R. Toth, S. Pricl, M. Fermeglia, Chemical Communications, 2011, sottomesso
“Water, oil, and surfactant solution on polymer surfaces: converging simulation methods for contact
angle determination” F. Santese, D. R. Nieto, P. Posocco, R. Toth, S. Pricl, M. Fermeglia, Journal
of Physical Chemistry C, 2011 sottomesso
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
AIChE Annual Meeting 2011, comunicazione: “The Factory of the Future: Integrating Multiscale
Modeling and Experiments to Produce New, Better Nanocomposite Materials” M. Fermeglia, P.
Posocco, R. Toth, D. R. Nieto, F. Santese and S. Pricl, 24 ottobre 2011 Minneapolis
Eurofillers 2011 comunicazione: “Chemistry and shape effects in polymer based nanocomposites: a
multiscale modeling study.” M.Fermeglia, P. Posocco, R. Toth, D. Romero, F. Santese, S. Pricl 2122 agosto 2011 Dresden, Germany
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NanotechItaly, comunicazione: “Nanoparticles at large. A multiscale molecular modeling protocol
to predict/explain structure-property relationships in nanocomposite systems” P. Posocco, F.
Santese, D. R. Nieto, E. Laurini, M. Fermeglia, J. W. Handgraaf, H. G.E.M. Fraaije, M. Lisal, S.
Pricl, 23-25 novembre 2011, Venezia
NanotechItaly 2011, comunicazione: “Interfacial wettability of polymeric surfaces by oil, water and
surfactant/water nanodroplets. A molecular dynamic study” F. Santese, D. R. Nieto P. Posocco, R.
Toth, M. Fermeglia, S. Pricl, 23-25 novembre 2011, Venezia
Attività formativa
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea)
60 ore laboratorio MOSE
Scuole
AMBER school 3-6 maggio 2011, Barcellona
Summer school on Nanotechnology 20-23 settembre, Trieste
Congressi, seminari, corsi avanzati e altre attività didattiche passive
Congressi
VNPCF (V congresso nazionale di chimica farmaceutica) Poster: “The long and winding road of
the c-Kit juxtamembrane domain”, 28-30 marzo 2011, Trieste
Seminari
“Brached Peptides as Therapeutics” Prof. Bracci 21 marzo 2011
“Seminario GPU@UniTS - Processori Grafici & Calcolo Intensivo” 18 febbraio 2011
“New approaches in cancer therapy” Prof. Misiura 12 maggio 2011
“Nanosistemi per il drug e il gene delivery a base di derivati dell’acido aspartico” Prof. Cavallaro 1
giugno 2011
“Self assembled monolayers the challenge” Dr. Hicham Hamoudi 1 luglio 2011
“The effect of confinement on enzyme diffusion and reaction inside DNA nanostructures” Dr.
Castronovo 29 luglio 2011
Corsi
“Molecular self- assembling and nanostructures”, Prof. Morgante, Casalis, Pasquato Periodo 21
giugno-29 luglio 2011
Altre attività didattiche passive
Congresso dottorandi Scuola di Nanotecnologie 17-19 gennaio 2011
Presentazione delle attività scientifiche dei gruppi di ricerca del dipartimento DI3, 25 febbraio 2011
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LETIZIA TAVAGNACCO
Titolo della tesi: Ruolo dell'acqua nel riconoscimento molecolare di bionanostrutture in
sistemi alimentari.
Supervisore: Prof. Attilio Cesàro
Tutori (eventuali): Prof. John W. Brady
Attività di ricerca
Il tema di questo progetto di dottorato è rivolto alla identificazione di possibili parametri molecolari
che controllano la sicurezza e la qualità degli alimenti. Particolare attenzione è rivolta verso l'acqua
negli alimenti ed il suo ruolo fondamentale all'interfaccia di superfici biomolecolari. L'obbiettivo
generale è ottenere informazioni sulla strutturazione dell'acqua in alimenti tradizionali attraverso
l'utilizzo di una varietà di tecniche sperimentali a diversa risoluzione.
In questo primo anno di dottorato, si è considerato il sistema caffè, e in particolare la caffeina è stata
identificata come molecola modello di studio in quanto costituita da una superficie idrofobica ma
solubile in acqua grazie alla presenza di gruppi funzionali capaci di formare legami a idrogeno.
Attraverso simulazioni di dinamica molecolare è stato possibile caratterizzare il dettaglio
molecolare della strutturazione dell’acqua attorno alla caffeina e l’associazione del soluto in
soluzione. In particolare la caffeina si è rivelata un buon sistema perché ha reso possibile il
confronto tra risultati computazionali e misure sperimentali e recenti teorie sull’idratazione di soluti
idrofobici. Sono inoltre stati condotti esperimenti SAXS su soluzioni acquose di caffeina e
preliminari misure AFM.
Attraverso simulazioni di dinamica molecolare è stata inoltre valutata l’associazione di biomolecole
in soluzione acquosa e in particolare l’interazione della caffeina con zuccheri quali glucosio e
saccarosio.
Obbiettivi da raggiungere per l’anno successivo (se applicabile)
I principali obbiettivi per il seguente anno di dottorato riguardano innanzitutto il completamento
degli esperimenti di SAXS e AFM. Successivamente un sistema modello di estesa superficie
idrofobica sarà caratterizzato attraverso l’uso di diverse tecniche sperimentali e computazionali.
Pubblicazioni su riviste scientifiche (pubblicate oppure in stampa),
L. Tavagnacco, P. E. Mason, U. Schnupf, F. Pitici, L. Zhong, M. E. Himmel, M. Crowley, A.
Cesàro, J. W. Brady, “Sugar-binding sites on the surface of the carbohydrate-binding module of
CBH I from Trichoderma reesei” Carbohydr. Res., 2011, 345(6), 839-846.
L. Tavagnacco, U. Schnupf, P. E. Mason, M-L. Saboungi, A. Cesàro, J. W. Brady, “Molecular
dynamics simulation studies of caffeine aggregation in aqueous solution”, J. Phys. Chem. B,
2011, 115(37), 10957-10966.
J. W. Brady, L. Tavagnacco, L. Ehrlich, M. Chen, U. Schnupf, M. E. Himmel, M-L. Saboungi,
A. Ceasàro, “Weakly-hydrated surfaces and the binding interactions of small biological solutes”
Eur. BioPhys. J. DOI 10.1007/s00249-011-0776-2 (in stampa).
Pubblicazioni/abstracts in conferenze/congressi (nazionali o internazionali)
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L. Tavagnacco, A. Cesàro, J. W. Brady, “Thermodynamics of aqueous caffeine self-association:
a revisitation”, “10th Mediterranean Conference on Calorimetry and Thermal Analysis MEDICTA 2011”, 24 - 27 Luglio 2011, Porto, Portogallo.
Partecipazione a congressi (come relatore)
L. Tavagnacco, A. Cesàro, U. Schnupf, P. E. Mason, J. W. Brady, “Hydration and association of
biomolecules in aqueous solution”, Studium Conference “Cosmetics and Pharmaceutics: New
Trends in Biophysical Approaches”, 14-15 Febbraio 2011, CNRS-Orleans, Francia
(presentazione orale).
L. Tavagnacco, A. Cesàro, J. W. Brady, “Thermodynamics of aqueous caffeine self-association:
a revisitation”, “10th Mediterranean Conference on Calorimetry and Thermal Analysis
MEDICTA 2011”, 24 - 27 Luglio 2011, Porto, Portogallo (presentazione orale).
L. Tavagnacco, M. Borgogna, J. W. Brady. A. Cesàro, “ How do water molecules probe and
control bionanostructures and food functionalities”, Nanotechnology Summer School 2011, 20 –
23 settembre 2011, Trieste (presentazione poster).
L. Tavagnacco, M. Borgogna, J. W. Brady. A. Cesàro, “ How do water molecules probe and
control bionanostructures: caffeine and sugars”, Studium Conference “Water in biological
systems”, 5 – 6 Dicembre 2011, CNRS-Orleans, Francia (presentazione poster).
Attività formativa
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso
di laurea)
- “Meccanica Statistica”, Prof. C. Micheletti, 8 novembre 2011 – 28 febbraio 2012, Phd course,
Sissa, Trieste.
- Laboratorio SAXS, Dr. H. Amenitsch, Elettra, Trieste, marzo – giugno 2011.
- Laboratorio AFM, Dr. D. Scaini, Nanolab, Elettra, Trieste, settembre – novembre 2011.
Congressi, seminari, corsi avanzati e altre attività didattiche passive
Nanotechnology School Congress, 17-19 gennaio 2011, Trieste.
Seminario "Synthesis and structure elucidation of kaolinite organo-complexes”, János Kristóf e
Erzsébet Horváth, Trieste.
Seminario “The Effect of Confinement on Enzymes Diffusion and Reactions Inside DNA
Nanostructures”, Matteo Castronovo, Trieste.
Corso intensivo "Molecular self-assembling and nanostructures", organizzato dalla Scuola di
Nanotecnologie, Trieste.
Giornate didattiche 2011 SISN, “Introduzione alle tecniche neutroniche per lo studio
microscopico della materia, con applicazioni alla Fisica, Chimica, Biologia e Geologia”, 25
giugno – 5 luglio 2011, Valle Aurina (Bz) – Grenoble (Francia).
XI Scuola di Radiazione di sincrotrone , “Radiazione di Sincrotrone: fondamenti, metodi e
applicazioni”, 5 – 16 settembre 2011, Castello di Duino, Trieste.
Nanotechnology Summer School 2011, 20 – 23 settembre 2011, Trieste.
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Attività didattica di supporto e attività didattica attiva
Laboratorio di Chimica delle Macromolecole II, corso di laurea magistrale in Chimica, Prof. A.
Cesàro (attività didattica di supporto).
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88
SHITAL VAIDYA
Title of the thesis: Study of magnetic properties in low dimentionality systems using synchrotron
radiation
Supervisor: Dr. Roberto Gotter
Tutors (if any):
Research Activity
Measurement of magnetic properties of NiO/Ag antiferomagnetic films by means of x-ray magnetic
linear dichroism (XMLD) at the ALOISA beam line of ELETTRA. For the estimation of the
dichroism, an accurate set of parameters have been chosen for fitting the Ni L2 edge and then
calculating areas under the peaks corresponding to Ni L2 edge. Neel (TN) transition temperature
has identified by fitting the dichroism as a function of the temperature by means of power law
exponent function for two dimensional systems.
Angle resolved Auger photoelectron coincidence spectroscopy (AR-APECS), which is able to
disentangle high spin and low spin contribution to the Auger intensity, has been performed below
and above TN in order to deepen the sensitivity of the techniques to the local magnetic order. The
data analysis for data as acquired by the new experimental set up is under development. In the mean
time a subsequent experiment on a prototypical ferromagnetic system, Ni/Cu(001), is going to be
prepared with preliminary characterizations for in-situ sample synthesis.
Theoretical study has been done by collaborating groups. On one side AR-APECS for
ferromagnetic systems has been explained by convoluting DFT ab-initio calculated DOS of
majority and minority sub-bands and on another side AR-APECS has been explained by means of
atomic-like high-spin and low-spin multiplet terms, for antiferromagnetic systems. On progress
experiments aim to join the two findings in a single modelisation, by exploiting the Cini-Sawatzky
theory, describing the trend of the Auger spectra from band-like to atomic-like behaviors depending
upon the degree of electron correlation of the system (material, dimensionality, size) and to
understand why dichroism in AR-APECS, which is related to local electronic structure, disappears
above the magnetic transition temperature (indeed it is believed that only long range magnetic order
disappear above them).
Educational Activity
Classes followed (date, course, professor, type of course)
Date
Course
24/06/2011
Molecular self-assembling Loredana
and nanostructures
Casalis
Corso per dottorato
27/06/2011
Molecular self- assembling Alberto
and nanostructures
Morgante
Corso per dottorato
28/06/2011
Molecular self-assembling Alberto
and nanostructures
Morgante
Corso per dottorato
5/07/2011
Molecular self-assembling Loredana
and nanostructures
Casalis
Corso per dottorato
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
Professor
Type of course
89
7/07/2011
Molecular self-assembling Loredana
and nanostructures
Casalis
Corso per dottorato
11/07/2011
Molecular self-assembling Lucia
and nanostructures
Pasquato
Corso per dottorato
Molecular self-assembling Lucia
and nanostructures
Pasquato
Corso per dottorato
13/07/2011
Conferences, seminars, advanced courses and other didactic activities
1) XI School on synchrotron radiation: Fundamentals, methods and applications. 5-16 September
2011.
2) Summer school of nanotechnology. 20-23 September 2011.
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VIRGILIO FRANCESCA
Titolo della tesi: “Sviluppo di sensori elettrochimici mediante processi nanotecnologici per
impieghi diagnostici biologici e medici”
Supervisore: Massimo Tormena, Paolo Ugob
Tutori (eventuali): Mauro Prasciolua
a
b
CNR-IOM, laboratorio TASC, Basovizza SS14 km 163.5, 34149 Trieste;
Dipartimento di Scienze Molecolari e Nanosistemi, Unversità Ca’ Foscari di Venezia, Santa
Marta 2137, 30123 Venezia.
Attività di ricerca
La fabbricazione degli array di nanoelettrodi è stata eseguita attraverso la deposizione di un film
sottile di polimero (strato isolante) su uno strato di materiale conduttore. Il film polimerico è stato
successivamente “patternato”, attraverso litografia elettronica, in modo tale da esporre delle aree, di
forma e geometria definita, dello strato conduttore sottostante. Nella prima parte dell’attività di
ricerca sono stati quindi valutati i materiali da utilizzare per questo processo di fabbricazione ed è
stato svolto il training per l’utilizzo dell’electron beam litography (EBL), presso il laboratorio di
microfabbricazione del TASC3. Quindi sono stati ottimizzati i parametri litografici per i materiali
selezionati e sono stati ottenuti i primi array di nanoelettrodi. Nell’ultima parte dell’anno gli array
ottenuti sono stati caratterizzati elettrochimicamente presso il Laboratorio di sensori per
elettroanalisi (LSE)4 attraverso misure di voltammetria ciclica e testati con il label luminoforo
Ru(bpy)32+ per valutare l’applicabilità di una strategia di rivelabilità di tipo
elettrochemiluminescente. Gli studi preliminari hanno dimostrato che l’ampia finestra di potenziale
di questi sistemi può consentire di utilizzare il Ru(bpy)32+ come strategia di rilevamento. La bassa
corrente di fondo del BDD (Boron Doped Diamond, materiale conduttore selezionato per la
fabbricazione)
aggiunto
alle
proprietà dei NEA e
l’elettrocatalisi del sistema Ru(bpy)32+/ammina indicano
che
questo sistema
può
essere
applicato per lo sviluppo di sensori ad alta sensibilità. Nella fase successiva si prevede di
funzionalizzare opportunamente la superficie del polimero/resist (policarbonato) con molecole
biologiche per verificare l’applicabilità nel campo di riconoscimento molecolare.
Altre pubblicazioni
 Presentazione Poster durante la Summer School on Nanotechnology
Attività formativa
Esami sostenuti, ore di lezione e di laboratorio seguite (data, corso, docente, tipo di corso di
laurea).
Lezioni:
 20h Processi elettrodici, primo semestre 05/05/2011–25/05/2011,
3
Laboratorio Nazionale CNR-IOM, S.S. 14 Km 163.5 Basovizza - 34012 Trieste.
4
Dipartimento di Scienze Molecolari e Nanosistemi, Unversità Ca’ Foscari di Venezia, Santa Marta 2137, 30123 Venezia.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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Prof. C. Tavagnacco, Corso di Laurea Specialistica in Chimica.
Trainings:
 Scanning Electron Microscopy, dott. Regina Ciancio, Researcher
CNR-IOM, TASC Laboratory;
 Electron Beam Lithography, dott. Mauro Prasciolu, Researcher
CNR-IOM, TASC Laboratory.
Libri:
 Yamazaki K. “Electron Beam Direct writing” Nanofabrication
Fundamentals and applications Ed. Ampere A. Tseng, Ch.10, 341-376.
 Moretto L.M. et al. “Templated Ensembles of Nanoelectrodes” Handbook
of Electrochemical Nanotechnology vol.1, Ed. Yuehe Lin
and Hari Singh Nalwa, Ch.4, 87-105.
Reviews:
o Chen Y., Pepìn A. “Nanofabrication: Conventional and nonconventional
methods” Electrophoresis 22, 2001, 187-207;
o Arrigan D.W.M. “Nanoelectrodes, nanoelectrode arrays and their
applications” Analyst 129, 2004, 1157-1165;
o Richter M.M. “Electrochemiluminescence (ECL)” Chem. Rev. 104, 2004,
3003-3036.
Congressi, seminari, corsi avanzati e altre attività didattiche passive
 “Syntesis and structure elucidation of kaolinite organo-complexes” J. Kistof and E.
Horvath; “Virtual private network” M. Fermeglia; 03.05.2001
 “Novel Studies in Photoelectrochemistry” H.B. Yildiz, 24.05.2011
 “Self assembled Monolayer the challenge” H. Hamoudi, 01.07.2011
 FVG Summer School on structural bioinformatics 04-06.07.2011
 “The effect of confinement on enzyme diffusion and reaction inside DNA
nanostructures” M. Castronovo, 29.07.2011
 XI School on Synchrotron Radiation: Fundamentals, Methods and Applications. 0516.09.2011
 Summer School on Nanotechnology. 20-23.09.2011
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Progetti Dottorandi del 27 ciclo:
Sono inclusi in questa parte del documento i progetti scientifici dei seguenti dottorandi del 27 cilco:
ABDOLLAHZADEH Iman, ANGELONI Valeria, BORIN Daniele, CAPOLLA Sara, CECCHINI
Paolo, COCEANO Giovanna, DIOLOSA‘ Marina, ELISEI Elena, FORNASARO Stefano,
GANBOLD Tamiraa, IONESCU Andrei Cristian, LOVAT Giacomo, MARSON Domenico,
NKOUA Ngavouka Maryse Dadina, OTTAVIANI Giulia, PANIGHEL Mirco, PIANTANIDA
Luca, PITTIA Paola, SALGADO Bernardes Pereira Simâo Pedro, SCOTTI Nicola, STOKELJ Tina,
STOPAR Alex, TARUSHA Lorena, VEGA Marienette, VENTURELLI Leonardo, WANG
Lianqui, ZANNIER Valentina.
IMAN ABDOLLAHZADEH
Email: [email protected]
Laboratory: Ospedale S. Maria della Misericordia, Building No. 13, Udine 33100
Title of the thesis: Mechanical Oscillators for the Study of Normal and Cancer Cells
Supervisor: Prof. Giacinto Scoles
Tutor: Matteo Castronovo (CRO)
Research Activity foreseen
State of the art and motivations
Cell's function can be determined by its structure. The structural organization of cells is
illustrated by certain mechanical properties [7]. It is obvious that cell structure need to be different
both in a great number of physiological processes (such as cell differentiation, growth, and
adhesion) and under pathogenesis (oxidative stress, attack of viruses, and parasites). Two
approaches for the study of cells' mechanical properties allowed that (i) the cell mechanical
properties were completely studied, where the cell is a single whole and (ii) mechanical properties
of the cell structural components were studied exactly by using isolated lipid bilayers, biomembrane
and cytosolic proteins. One of the highly superior approaches to detect the mechanical properties of
single cells is by AFM [8]. Its operation is based on the detection of repulsive and/or attractive
surface forces. In this method, by interaction between the tip of AFM and the surface of living cells
not only in the contact mode, but also in the tapping mode, one can determine cell's properties [9].
To illustrate this fact further, we can mention the estimation of Young's modulus by Mahaffy [10].
Since knowing the internal viscosity of microscopic objects like single cells is vital for
understanding the flow of chemicals and a variety of other biomolecular processes, there has been
an active search for methods to gauge microviscosity in the science community. For instance,
molecular rotors are useful as their rotational freedom and fluorescence emission depend on the
viscosity of the media. When a molecular rotor is located within a viscous media, it will occupy a
metastable conformation that is highly emissive. When, on the contrarily, it is located in a nonviscous media, the object's degrees of rotational freedom will be maximized and, in turn, its
fluorescence emission will be reduced [11]. Nowadays, in order to improve this method using the
fluorescence lifetime is more demanded by virtue of this notion that the concentration, the
homogeneity, the polarity, and the other factors can have inferior influence on the fluorescence
intensity [12, 13].
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Furthermore, the cell's density is another factor that ought to be determined in order to have
acceptable consideration of cells mechanical behavior. Recent development of the suspended
micromechanical resonator (SMR) has enabled novel label-free biological sensing applications with
unprecedented mass resolution (~1 femtogram in a 1 Hz bandwidth) [14]. By weighing each cell in
two fluids of different densities, this technique measures the single-cell mass, volume, and density
of approximately 500 cells per hour with a density precision of 0.001 g/mL [15].
The use of pillars for the weighing of cells:
One of the most innovations to weighing biomolecules is micromechanical pillars by which one
can measure the mass of sub-cellular to cells [6]. Detection of proteins at an extremely low
concentration (below fM) in a short time is the issue of the biosensors. Improvement can be
achieved only by a combination of nanotechnologies for improved sensitivity and new geometries
to depreciate the constraints of slow mass transport by diffusion. The pillars, arranged in a super
hydrophobic device could provide high sensitivity and absolute quantification and will be able to
deal with highly diluted solutions. This micromechanical sensor is based on vertically oscillating
beams in which in opposing direction from the other approaches (for example, with oscillating
cantilevers) the sensitive and active area is located at the free end of the oscillator. It was showed
[16] that a regular matrix of pillars might enforce a super hydrophobic surface and induce a Cassie
state.
Pillars can be used as mass transfer-based detectors: the adsorption of extra mass causes a
change of the resonance frequency. In addition, the extra mass exclusively adsorbs at the free end of
the beam. This avoids uncontrolled adsorption on the beam sides, which might cause several harsh
effects such as bending. Pillar oscillations can be detected optically. For instance by shining a laser
on top of the pillar and detecting the reflected beam. This approach was used to investigate the
formation of a single-strand DNA self-assembled monolayer (SAM) on the pillar's topmost surface.
The results of this study showed measuring the adsorption of mass of the order of 1.5 fg which
corresponds to 7.0x105 DNA molecules and, given the covered area, to a SAM density of 2.8x1011
molecule/cm2 [6]. The measured binding rate was 1000 times faster than the one typically measured
on macroscopic surfaces. The latter because the aforementioned, localized adsorption on the pillars
heads reduce the volume that the target molecules need to diffuse as to reach the sensing area. In
turn, the absorption rate is 3 orders of magnitude faster than on a typical 200x20 square micrometer
cantilever.
We intend to follow this approach to weigh cells faster than with the existing methods, and
more sensitively, as to detect the mass change of these cells in a - biologically speaking - timely
manner. Due to the fact that the resolution of this method is about 30 Hz/fg and its resonance
frequency is in the range of 4.5-8 MHz, determining the extra mass in the order of pg (cell's mass
order) can be available. Therefore, if we have a solution (such as blood) in which cells are
suspended, the micromechanical pillars array will evaluates every single cell mass (For instance, we
can permit each cell to enter our setup and then we can measure its mass). We aim to evaluate the
mass distribution of cells in the blood solution and explore the presence of cancer cells due to their
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higher density and mass. This application can be used to detect circulation tumor cells (CTCs)
which will present in the next section.
Alternative, optics-based methods for detecting pillars oscillations are photonic crystals.
Photonic crystals are an array of periodic holes in a slab which similar to band structure in crystals,
have a band structure for photons. The effect of dielectrics as a perturbation factor on the electrical
field on the photonic crystal shows that by applying a sharp tip at the top of pillars, photonic crystal
will be perturbed [24]. Change in the pillar's mass will ensue to change in the frequency and
therefore, in the electrical field on the photonic crystal.
Application to detect CTCs:
Circulating tumor cells (CTCs) are those that have detached from a primary tumor and circulate
in the bloodstream. CTCs may constitute seeds for subsequent growth of additional tumors
(metastasis) in different tissues. The detection of CTCs may have important prognostic and
therapeutic implications. Unfortunately, given their extremely low amount, these cells are not easy
to detect [17]. Circulating tumor cells are found in frequencies in the order of 1-10 CTC per mL of
whole blood, in patients with metastatic disease. Such a low frequency implies enrichment methods
are crucial towards detecting CTC.
Polymerase Chain Reaction (PCR) is one of the powerful approaches to detect CTCs with the
identification of tumor cell diluted with 106-l07 normal cells [18, 19]. Diminishing the sensitivity by
several tissues and fluids are among this approach's limitation [20]. The most reliable method
currently available for CTC detection is automated digital microscopy (ADM) using image analysis
for recognition of immunocytochemically labeled tumor cells. ADM, however, is disadvantaged by
its very slow scan speeds of 800 cells/sec [21]. To date the most successful of these enrichment
approaches is immunomagnetic enrichment (IME) [22]. In most implementations of IME for CTC
detection, monoclonal antibodies conjugated to small magnetic beads target the epithelial cell
adhesion molecule, EpCAM. The beads are then manipulated in magnetic fields for enrichment.
Another method is using fiber-optic array scanning technology (FAST) that can locate CTCs at a
rate that is 500-times faster than ADM with comparable sensitivity and improved specificity and,
consequently, does not require an enrichment step [23].
We aim to use micromechanical pillars approach to determine CTCs in the bloodstream.
Buildings on the hypothesis that the density and the mass of a CTC is higher than the one of a
normal cell, pillars could turn into an ideal technology for detecting CTCs relatively timely. About
70% of the cell's mass is made of water or wet mass, whereas the remaining 30% is made of dry
mass including Inorganic ions, Miscellaneous, small metabolites, RNA, DNA, Phospholipids,
Polysaccharides, and the other lipids. Probably, a tumor cell has greater mass and is denser. Due to
and different balance between the aforementioned components.
Also, the pillars can be used for studying cells motility. Cells move according to environmental
signals. Wound healing, immune response and cancer metastasis are pivotal cell motility-based
processes. One can seed cells with dielectric molecules such as plastic, and then stimulate them
with of optical tweezers to study their responsive motion. The latter depends on the inner viscosity
of cells.
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Objectives for the three years
The main objective of this project is the application of micromechanical pillars to determine
cancer cells by measurement of frequency shift due to the change of the pillar's mass. For this
reason, we will use a photonic crystal cavity apparatus to evaluate the effect of frequency change.
Given that our pillars will be applied to whole cells that are a-few-microns-large, we need to
develop and use pillars larger than those used up until now. Fortunately, the sensitivity of pillars is
high enough to determine the difference of mass between normal and cancer cells even if the elastic
beams are bigger than those used up until now.
To make a perturbation on the photonic crystal, we plan to build a dielectric tip at the top of
pillars. In turn, the frequency change in pillars can affect tips, as well, and due to the tiny size of
tips, they can apply a perturbation in the electrical field distribution of photonic crystal.
Pillars will be Si base and the gold thin layer at the top. We also make the top of pillars super
hydrophobic to prevent the cells adhesion from the sides of pillars.
The baselines of our work are:
- fabrication of micromechanical oscillating pillars for cells detection
- fabrication and optimization of photonic crystal cavity in order to have more sensitivity and
less leakage especially from the edges.
- matching light source with the photonic crystal via optical fibers or waveguides. In the latter,
we will fabricate a waveguide based on the photonic crystal structure.
- compare our method with the optical fibers as light source approach and show that ours has
better sensitivity.
- detection normal and cancer cells (CTCs).
Objectives for the first year
The main line is study of photonic crystal cavities and waveguides as well as fabrication of
pillars array and test them for cells adhesion. We hope in the first year to optimize this array for
cells. Here are the list of our activity for the first year:
- study of photonic crystal cavity and optimization of light matching with that.
- Fabrication of Micromechanical Si base with the gold deposition at the top and also fabrication
of dielectric tips in order to have perturbation on photonic crystal.
Research project
1st year
2nd year
3rd year
Study of photonic crystals, light matching, and pillars.
fabrication photonic crystal cavity and light matching with
less leakage.
fabrication of micromechanical pillars and tips
using optical fiber method instead of photonic crystal, and
comparison these two approach
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test cells, normal and cancer
preparation super hydrophobic and gold deposition on
pillars.
Educational activity foreseen
" fast detection of Biomolecules in Diffusion- Limited Regime Using Micromechanical
Pillars", By Melli et. al. 2008, Nano Lett.
" High Q photonic nanocavity in a two- dimensional photonic crystal", By Akahane. et. al.,
Nature Photonic, 2003.
" Nano- Optomechanical characterization and manipulation of photonic crystal", By
Mujumdar et. al., IEEE, 2007.
2nd summer school in nanotechnology in the university of Udine, 2012.
2nd summer school of molecular biomedicine in the University of Udine, 2012.
Nanotechnology 1 course, MSc level.
Nanocharactrization 1 course, MSc level.
Surface Physics and knowledge about superhydrophobicity.
Relevant papers and textbooks.
References:
1- Arlett, J. L.; Myers, E. B.; Roukes, M. L. Comparative Advantages of Mechanical Biosensors.
Nat. Nanotechnol. 2011, 6, 203-215.
2- Yang, Y. T.; Callegari, C.; Feng, X. L.; Ekinci, K. L.; Roukes, M. L. Zeptogram-Scale
Nanomechanical Mass Sensing. Nano Lett. 2006, 6, 583-586.
3- von Muhlen, M. G.; Brault, N. D.; Knudsen, S. M.; Jiang, S.; Manalis, S. R. Label-Free
Biomarker Sensing in Undiluted Serum with Suspended Microchannel Resonators. Anal. Chem.
2010, 82, 1905-1910.
4- Squires, T. M.; Messinger, R. J.; Manalis, S. R. Making it Stick: Convection, Reaction and
Diffusion in Surface-Based Biosensors. Nat. Biotechnol. 2008, 26, 417-426.
5- Thomas C. R.; Stenson J. D.; Zhang Z. Measuring the mechanical properties of single
microbial cells. Adv Biochem Eng Biotechnol. 2001, 124, 83-98.
6- Melli M.; Scoles G.; Lazzarino M.: Fast detection of Biomolecules in Diffusion-Limited
Regime Using Micromechanical Pillars. Acs Nano. 2011, 5, 10, 7928-7935.
7- Hansma H. G.; Surface Biology of DNA by atomic force microscopy. Annu. Rev. Phys.
Chem. 2001, 57, 71-92.
8- Kuznetsova T. G.; Starodubtseva M. N.; Yegorenkov N. I.; Chizhik S. A.; Zhdanov R. I.:
Atomic force microscopy probing of cell elasticity. Micron. 2007, 38, 824-833.
9- Mozafari M.R.; Reed C.J.; Rostron C.; Hasirci V.; A review of scanning probe microscopy
investigations of liposome-DNA complexes. J. Liposome Res. 2005, 15, 93-107.
10- Mahaffy R.E.; Park S.; Gerde E.; Ka¨s J.; Shih S.K.; Quantitative analysis of the viscoelastic
properties of thin regions of ibroblasts using atomic force microscopy. Biophys. J. 2004, 86, 17771793.
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11- Kuimova M. K.; Botchway S. W.; Parker A. W.; Balaz M.; Collins H. A.; Anderson H. L.;
Suhling K.; Ogilby P. R.: Imaging intracellular viscosity of a single cell during photoinduced cell
death. Nat. Chem. 2009, 1, 69-73.
12- Perrin F.: La fluorescence des solutions: induction mole´culaire. Polarisation et dure´e
d'emission. Photochimie. Ann. Phys. (Paris) 12, 169-275 (1929).
13- Shinitzky M.; Dianoux A. C.; Gitler C.; Weber G.: Microviscosity and order in the
hydrocarbon region of micelles and membranes determined with fluorescent probes. I. Synthetic
micelles. Biochemistry 10, 2106-2113 (1971).
14- Burg T. P.; Godin M.; Knudsen S. M.; Shen W.; Carlson G.; Foster J. S.; Babcock K.;
Manalis S. R.: Weighing of biomolecules, single cells and single nanoparticles in fluid. Nature,
2007, 446, 1066-1069.
15- Grover W. H.; Bryan A. K.; Diez-Silva M.; Suresh S.; Higgins J. M.; Manalis S. R.:
Measuring single-cell density. PNAS. 2011, 1-5.
16- Gentile, F.; Das, G.; Coluccio, M. L.; Mecarini, F.; Accardo, A.; Tirinato, L.; Tallerico, R.;
Cojoc, G.; Liberale, C.; Candeloro, P.: Ultra Low Concentrated Molecular Detection Using Super
Hydrophobic Surface Based Biophotonic Devices. Microelectron. Eng. 2010, 87, 798-801.
17- Hsieh H. B.; Marrinucci D.; Bethel K.; Curry D. N.; Humphrey M.; Krivacic R. T.; Kroener
J.; Kroener L.; Ladanyi A.; x Lazarus A.; Kuhn P.; Bruce R. H.; Nieva J.: High speed detection of
circulating tumor cells. Biosensors and Bioelectronics 2006, 21, 1893-1899.
18- Gerhard M.; Juhl H.; Kalthoff H.; Shreiber H.W.; Wagener C.; Neumaier M.: Specific
detection of carcinoembryonic antigen- expressing tumor cells in bone marrow aspirates by
polymerase chain reaction. J Clin Oncol. 1994, 12725-9.
19- Ghossein R.A.; Scher H.I. Gerald W.L.; Kelley W.K.; Curley T.; Amsterdam A.:Detection of
circulating tumor cells in patients with localized and metastatic prostatic carcinoma prostatic
carcinoma: clinical implications. Clin Oncol. 1995, 13, 1195-200.
20- Ghossein R. A.; Rosai J.: Polymerase Chain Reaction in the Detection of Micrometastases
and Circulating Tumor Cells. CANCER .1996, 78, 10-16.
21- Kraeft S.K.; Ladanyi A.; Galiger K.; Herlitz A.; Sher A.C.; Bergsrud D.E.; Even G.;
Brunelle S.; Harris L.; Salgia R.; Dahl T.; Kesterson J.; Chen L.B.: Reliable and sensitive
identification of occult tumor cells using the improved rare event imaging system. Clin. Cancer Res.
2004, 10, 3020-3028.
22- Smirnov D.A.; Zweitzig D.R.; Foulk B.W.; Miller M.C.; Doyle G.V.; Pienta K.J.; Meropol
N.J.; Weiner L.M.; Cohen S.J.; Moreno J.G.; Connelly M.C.; Terstappen L.W.; O'Hara S.M.:
Global gene expression profiling of circulating tumor cells. Cancer Res. 2005, 65, 4993-4997.
23- Rao C.G.; Chianese D.; Doyle G.V.; Miller M.C.; Russell T.; Sanders Jr. R.A.; Terstappen
L.W.; Expression of epithelial cell adhesion molecule in carcinoma cells present in blood and
primary and metastatic tumors. Int. J. Oncol. 2005, 27, 49-57.
24- C. Jian, J. J. Xiao, and J. P. Huang, Optical Force on Dielectric Nanorods Coupled to a
High-Q Photonic Crystal Nanocavity, J. Phys. Chem. C 2009, 113, 17170-17175
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VALERIA ANGELONI
Email: [email protected]
Laboratory: Department of Medical Sciences, University of Trieste-IOR, Bologna
Title of the thesis: Role of collagen cross-linkers on the stability of the bonded interface
Supervisor: Prof. Lorenzo Breschi
Tutors (if any): Prof. Milena Cadenaro
Research Activity foreseen
State of the art and motivations
The prevention and treatment of tooth decay are major challenges in dentistry. It’s estimated that
90% of adults in Western countries suffer from this dental disease (Beltran-Aguilar ED et al, 2005).
The objective of restorative dentistry is to repair and replace damage tooth structures by the
application of synthetic materials aiming at the re-establishment of tooth function and aesthetic.
Current restorative procedures generally depend on the formation of an adhesive bond between
polymeric dental materials and the tooth substrate, enamel and dentin (Pashley et al, 2011).
Dentin that represents the bulk majority of the tooth, has a complex composition that is 70% (by
weight) mineral, 20% organic component and 10% water (Breschi et al., 2008). Fibrillar type I
collagen accounts for 90% of the organic matrix, while the remaining 10% consists of
noncollagenous proteins such as phosphoproteins and proteoglycans (Breschi et al., 2008). Type-I
collagen is present in tissues as fibrils that are stabilized by lysyloxidase-mediated covalent
intermolecular cross-linking (Yamauchi and Shiiba, 2002).
In dentin, the etching procedure dissolves the peritubular dentin and dissolves the mineral phase
thereby exposing collagen/noncollagenous proteins from the intertubular dentin (Pashley et al.,
2011). Adhesive resin is used to embed collagen fibrils and provide micromechanical retention. For
effective and durable bonding, therefore, the stability and maintenance of dentin collagen fibrils is
critical (Breschi et al., 2008; Lin et al., 2011).
In the last years many studies were focused on chemical cross-linkers that have been reported to
further stabilize collagen fibrils (Cheung et al., 1990; Ritter et al., 2001; Han et al., 2003; BedranRusso et al, 2007; Cova et al., 2011). Glutaraldehyde (GD) and Proanthocyanidin (PA) are some of
the synthetic and a natural collagen crosslinking agents tested. It has been reported that both GD
and PA improve the mechanical properties of dentin and the bond strength of dentin-adhesive
interface (Bedran-Russo et al, 2007; Cova et al., 2011).
Recent findings also reported that endogenous dentin matrix metalloproteinases (MMPs), a class of
zinc and calcium dependent endopeptidases, entrapped within the mineralized dentin matrix during
tooth development, play a fundamental role in the collagen degradation and aging of the adhesive
interface (Pashely et al., 2004; Breschi et al, 2008; Liu et al, 2011). The release and the activation
of MMPs during dentin bonding are thought to be responsible for the degradation of collagen fibrils
in incompletely infiltrated hybrid layers in aged bonded dentin (Pashley et al, 2004, 2011). Recent
studies showed the efficacy of cross-linking agents, as EDC and Riboflavin, in increasing the
longevity of resin-dentin bond, supporting the hypothesis that collagen cross-linkers plays a critical
role in regulating MMPs’ activity (Al-Ammar et al, 2009; Cova et al, 2011).
The aims of this project are: 1) to investigate innovative molecules to induce collagen cross-linking
and MMPs inhibition and 2) to develop new dentin bonding systems that incorporating cross-linkers
results in improved longevity of the adhesive interface.
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References
Al-Ammar A, Drummond JL, Bedran-Russo AK. The use of collagen cross-linking agents
to enhance dentin bond strength (2009). J Biomed Mater 91:506-11.
Bedran-Russo AK, Pereira PN, Duarte WR, et al (2007). Application of crosslinkers to
dentin collagen enhances the ultimate tensile strength. J Biomed Mater Res B Appl
Biomater 80:268–272.
Beltran-Aguilar ED, Barker LK, Canto MT, Dye BA, et al. (2005) Surveillance Summaries
54: MMWR Atlanta, GA: Centers for Disease Control and Prevention; p. 1-13.
Breschi, L, Mazzoni A, Ruggeri A et al. (2008). Dental adhesion review: Aging and
stability of the bonded interface. Dent Mater 24, 90–101.
Cheung DT, Tong D, Perelman N, et al (1990). Mechanism of crosslinking of proteins by
glutaraldehyde. IV: In vitro and in vivo stability of a crosslinked collagen matrix.
Connect Tissue Res 25:27–34.
Cova A, Breschi L, Nato F, et al (2011). Effect of UVA-activated riboflavin on dentin
bonding. J Dent Res 90:1439-45.
Han B, Jaurequi J, Tang BW, et al (2003). Proanthocyanidin: a natural crosslinking reagent
for stabilizing collagen matrices. J Biomed Mater Res A 65:118–124.
 Liu, Y., Tjaderhane, L., Breschi, L., et al. (2011). Limitations in Bonding to Dentin and
Experimental Strategies to Prevent Bond Degradation. J Dent Res 90,953–968.
Pashley DH, Tay FR, Breschi L, Tjaderhane L, Carvalho RM, Carillo M et al. (2011). State
of the art etch-and-rinse adhesives. Dent Mater 27:1-16.
Pashley DH, Tay FR, Yiu C, Hashimoto M, Breschi L, Carvalho RM et al (2004). Collagen
degradation by host-derived enzymes during aging. J Dent Res 83:216-21.
Ritter AV, Swift EJ Jr, Yamauci M (2001). Effects of phosphoric acid and glutaraldehydeHEMA on dentin collagen. Eur J Oral Sci 109:348–353.
Yamauchi M, Shiiba M (2002). Lysine hydroxylation and crosslinking of collagen.
Methods Mol Biol 194:277–290.
Objectives for the three years
Objective of the research project are:
1.to investigate the nanostructure of the dentin collagen with and without the application of
collagen cross-linkers agents by means of light, transmission and scanning electron
microscopy;
2.to investigate the role of collagen cross-linkers applied to the dentin substrate to stabilize the
bond over time and inhibit the endogenous MMPs involved in the degradation collagen
fibrils within the hybrid layer created by dentin bonding systems.
Objectives for first following year
Riboflavin (Vitamin B2) and other natural collagen cross-linkers will be applied to demineralized
dentin at different time and concentrations to investigate the dentin morphology and the possible
strengthening of the ultimate tensile strength of the dentin organic matrix. Dentin proteins will be
then extracted for zymographic assays in order to assay the MMPs activity.
Research project
Testing materials:
- Microtensile bond strength test;
- Zymographic analysis;
- Light microscopy (LM);
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- Transmission electron microscopy (TEM);
- Scanning electron microscopy (SEM).
Educational activity foreseen
- Participation to national and international meetings on dental materials;
- Frequency of research laboratories at the Istituto Ortopedico Rizzoli in Bologna and at the
University of Trieste;
- Study of published papers on collagen cross-linkers agents.
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DANIELE BORIN
Email: [email protected], [email protected]
Laboratory: IOM-CNR at AREA SCIENCE PARK - Basovizza
Title of the thesis: Micro-mechanical oscillators for biochemical applications
Supervisor(s): Dr. Marco Lazzarino
Tutors (if any): Dr. Giuseppe Toffoli
Prof. Giacinto Scoles
Research Activity foreseen
State of the art and motivations
Proteomic analysis is playing a growing role in diagnostic, because protein expression and proteinprotein interactions could give important information in real time about physiological processes and
hence about patient’s health [S.M. Hanash et al., Nat.Rev.Clin.Oncol., 2011]. For this reason,
monitoring the expression level of protein, especially those that have been recognized as
diagnostically relevant, in real time and on a single patient basis, could represent a tool for early
diagnosis of diseases. In addition, high sensitivity of detection (down to the pico/femtomolar level
of most of the biomarkers of interest), high specificity (to detect biomolecules in a medium of other
species with much higher concentration), low cost and low amount of sample requirement are
certainly important features for any diagnostic tool to be developed.
Nanotechnological research is giving continuously growing effort to this field, for example through
the application of micro/nano electromechanical systems (MEMS/NEMS) to biological and
biomedical field. In the last years, micro-resonating sensors have achieved a large diffusion because
of their great sensitivity and versatility [R. Bashir, Advanced Drug Delivery Reviews, 2004].
Typically, the shift in the resonance frequency induced by the mass of adsorbed analyte is
measured, with resolution down to the zeptogram (zg) range [Y.T. Yang et al., Nano Letters, 2006].
Unfortunately, these performances degrades strongly in liquid environment, due to the damping
effect of the viscous media. To overcome this limit, mainly two different approaches have been so
far proposed in literature: the dip&dry approach, where the sensor is in contact with the liquid
sample, then dried and measured in vacuum, or the microchannel approach [T. Burg et al., Nature,
2007], where the liquid can flow within the resonator, that externally can oscillate in vacuum.
Unfortunately, both of them result to be very complex in fabrication and/or in operational
procedures.
As an alternative approach, the pillar technology has been developed by Mauro Melli during his
PhD thesis, in Marco Lazzarino and Giacinto Scoles’ group [M. Melli et al., Microel. Eng., 2010].
Pillars are vertical oscillating beams, in which the sensitive area is located at the free end of the
sensor. This geometry, compared to what is done in cantilever technology, has two main
advantages: the first is that adsorption is confined to a small spot, surrounded by a much larger area
with no adsorption of the analyte of interest. This means an increased rate of adsorption compared
to “larger” flat surfaces, as demonstrated studying the kinetics of DNA self assembled monolayer
(SAM) formation and the hybridization efficiency on top of pillars [M. Melli et al., ACS nano,
2011]. The binding rate is 1000 times higher than on a “macroscopic” surface, while the
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hybridization of a SAM of DNA with maximum density is 40%, 4 times the value reported in the
literature [Georgiadis R. et al., JACS, 2000]. This allows to reduce the time of exposure to the
analyte to get a detectable shift in resonance frequency.
In addition, due to their geometry, pillars can be organized in very dense arrays that, if properly
treated to make them hydrophobic, lead to a superhydrophobic effect: the solution droplet is in
contact only with the top surface of pillars, without wetting the lateral walls or the ground of the
array. In these conditions, the damping experienced by the pillars in a liquid environment is
dominated by the air friction on the pillars walls and thus is equivalent to the damping in air. These
results pave the way toward the design of a new class of BioMEMS operating in liquid and in real
time. This sensor can also be integrated into a microfluidic circuit to deliver the reagents for the
functionalization of pillars, the rinsing liquids and the sample to be analyzed.
Objectives for the three years
The main goal of my research activity is to make possible recognition and quantification of protein
biomarkers using the pillars technology, possibly in a liquid environment. In addition, detecting
different biomarkers in parallel can be helpful to obtain a better diagnosis about the patient health
state and to reduce the possibilities of false positives.
To obtain this, is necessary to:
 build a fluidic cell to allow measurements in liquid and improve the existing setup to
detect oscillations in liquid;
 develop a microfluidic circuit to deliver reagents, rinsing liquids and the sample to be
analyzed to the pillar matrix;
 develop a method and a protocol to functionalize the top surface of pillars with different
biomolecules (antibodies, aptamers) for recognition of different biomarkers in parallel;
 verify the effective binding of the right antigen to the right pillar and the absence of
aspecific absorption.
Objectives for the first year
In the first year of activity, measurement of resonance frequency shift of pillars due to molecular
absorption in a liquid environment should be performed. This means:
 optimize the existing protocol to make the matrix superhydrophobic maintaining a good
Quality factor of the resonator;
 develop a fluidic chamber in which the pillar matrix will be placed and actuated;
 improve the actual experimental setup to detect pillars oscillation in liquid.
We would also like to increase the actual limit of detection of pillars, that so far is around 10pM for
streptavidin: to reach this target, we plan to use biotinilated nanoparticles to amplify the resonance
frequency shift. In this way, detection of streptavidin immobilized to biotinilated pillars should be
possible also from solutions with very low concentration (sub-pM).
In the end of the first year, we would start to consider the different approaches available to
functionalize groups of pillars of the same matrix with different antibodies or aptamers.
Research project
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The first part of the project will be focused on measurement of resonance frequency of pillars in
liquid environment. The tasks are to optimize the hydrophobization procedure of pillars, develop a
fluidic chamber and improve the setup to detect oscillations in liquid. Pillars will be fabricated
using electron beam lithography, developing processes, e-beam evaporation, inductively coupled
plasma etching processes and hydrophobization processes. All the fabrication procedure will be
performed at the IOM-CNR laboratories. The liquid cell will be made of glass,
polydimethylsiloxane and polymethylmethacrylate, that can be cut in the desired shape by means of
a CO2 laser cutter also available at IOM-CNR.
Bio-recognition on top of the pillars will be tested initially exploiting the biotin-streptavidin
interaction: a biotinilated SAM will be created on a gold layer at the free end of pillars, then the
matrix will be exposed to a solution of streptavidin and, subsequently, to a solution of biotinilated
gold nanoparticles (that could be produced by Meneghetti’s group in Padua), measuring the
progressive reduction of the resonance frequency.
This step is preliminary to the use of more complex systems, like antibodies (Abs) or aptamers. In
the final goal of the project, different antibodies should be patterned into different groups of pillars,
to analyze several biomarkers involved in the same disease (for example, prostate cancer or
colorectal cancer) in parallel. To obtain this, different approaches could be used: one could use the
DNA directed immobilization (DDI) technique to bind antibodies conjugated with a DNA-oligo to a
SAM of the complementary DNA sequence on top of the pillars; alternatively, direct
immobilization of binding molecules to pillars could be used. For this target, different techniques
could be considered: photochemistry, supramolecular nanostamping, microspotting or laser
nanografting. The best approach will be evaluated in terms of feasibility and efficacy of
functionalization. For this target, a collaboration with other groups could be necessary to develop
the method and the protocol to functionalize the pillar matrix.
To test the specificity of binding, preliminary studies could be made on a small and flat surface of
silicon covered with gold, in which different patches of Abs or aptamers are patterned with one of
the previously reported methods. After exposure with a solution of a specific antigen per time, the
specific binding could be evaluated via Atomic Force Microscopy (AFM) or with fluorescence
methods, to check the antigen immobilization only on the specific area. After that, complex
solutions with other proteins could be used, to check the binding specificity of immobilized
biomolecules and the absence of aspecific adsorption.
Once this system will be developed, it should be validated at first with solutions of one or some
proteins to check the specificity of binding of the sensor, and then with complex solution of the
most abundant proteins (e.g. albumin) present in the human plasma, to evaluate the absence of
aspecific adsorption. After these preliminary tests, samples of human plasma will be used in
collaboration with the Centro di Riferimento Oncologico (CRO) in Aviano (ref. Dr. Toffoli)
directly or after preliminary purification steps.
The activities and their time scheduling are showed in the following Gantt chart:
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Year
Jan
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
Pillars fabrication and
hydrophobization
Fluidic cell development
1
Measurement in liquid with biotin-STV complex
Study of site-specific
functionalization of pillars
Site-specific immobilization of
antibodies/aptamers on pillars
Preliminary tests on flat surface for binding
2
specificity
Preliminary tests on pillars
Validation of the sensor
3
Development toward a point-of-care diagnostic tool
Educational activity foreseen
In the first year of this project I’m learning to use the Labview software, that will be useful in my
project to use and control different kind of instrumentation by computer (network analyzer,
oscilloscopes, motor-driven micro-positioning systems, micro-syringe pumps, etc. ) that can be used
for optical measurement and functionalization of pillars in an automatic way. I’ve already attended
the base course, held by Prof. Giuseppe Cautero and Dr. Dario Giuressi in March at Elettra (20
hours of frontal lectures and exercises), while the advanced course will be held in September (20
hours).
I’ve already attended the preparatory school and the “Winter College on Optics: advances in Nanooptics and plasmonics”, held at ICTP from the 30th Jan 2012 to the 3rd Feb 2012 and from the 6th
Feb 2012 to the 17th Feb 2012, to get more in contact with the laser and the optics that I’m using in
the experimental setup.
Self assembled monolayer (SAM) formation will be involved in my project, because creation of
SAM of biomolecules for detection and of inert bio-compatible polymers to avoid aspecific
adsorption is a tool for protein recognition and immobilization on top of the pillars: that’s why I’m
considering to attend the course about molecular self-assembling and nanostructures held by Prof.
Alberto Morgante, Prof. Loredana Casalis and Prof. Lucia Pasquato (about 20 hours).
I’m looking also for courses about chemical biofunctionalization and protein binding, if will be
organized at university or at Sissa. In the meantime, I’m studying the book edited by R. Förch, H.
Schönherr and A.T.A. Jenkins, “Surface Design: Application in Bioscience and Nanotechnology”,
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WILEY-VCH, 2009, with particular attention to the tutorials about biosensors and surface
treatments (pages 3-99), modification of surfaces by photosensitive silanes (pages 207-219) and the
properties of nanoparticles at the interface with planar surfaces (pages 323-338), that are topics of
great importance in my project.
I would be also interested in attending the course held by Prof. Mario Grassi about mathematical
modeling in bio-pharmaceutics, for the part about the diffusion coefficient measurements, and
because I’m interested in the connection between chemical engineering and bio-pharmaceutical
field, considering my university background.
Regarding conferences, I’m going to participate to a workshop on “Nanotechnology for health
care”, that is taking place in Trento the 25th-26th of May, and to the EMBL conference
“Microfluidics 2012” in Heidelberg (Germany) from the 25th to the 27th of July 2012.
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SARA CAPOLLA
Email: [email protected]
Laboratory: Università degli Studi di Trieste
Title of the thesis: Use of immune-nanoparticles containing chemotherapeutic agents for the
treatment of tumors.
Supervisor: Dr. Paolo Macor
Tutors (if any):
Research Activity foreseen
State of the art and motivations
Cancer treatment comprehends different types of therapies, including surgical therapy, radiotherapy
and chemotherapy. Despite their ability to attack and damage cancer cells, they also affect healthy
cells, creating high toxicity levels. Thus, the development of molecularly targeted therapies has
emerged as one approach to overcome this lack of specificity (Cho et al., 2008). In the last 40 years
the attention has been focused on the “immunotherapy” which is characterized by the development
of monoclonal antibodies which can be used in a large variety of diseases, including cancer (Chan
and Carter, 2010). This treatment is based on the antibodies capability to bind with high specificity
one particular antigen which can be selectively expressed at high levels on the surface of cancer
cells leading to lower side effects on healthy cells and lower systemic toxicity (Jaffee, 1999).
Moreover, anti-tumor antibodies can be linked to therapeutic delivery vehicles including
nanoparticles inducing a specific homing in tumor cells. The attention has been focused on the
development of these vehicles because of their small size (100-300nm) favorable for endocytic
intracellular uptake, high drug loading and tumor specific targeting.
Furthermore, they might be composed on a large variety of materials, with a particular interest on
the development of biodegradable nanopaticles (BNPs) because of their ability to maintain drug
concentrations at therapeutically relevant levels for a longer period of time (Vasir and Labhasetwar,
2007).
For this PhD project two different types of immune biodegradable nanoparticles will be used:
 Nanoparticles conjugated with selected, produced and characterized anti-CD162 antibodies and
filled with chemotherapeutic agents for the treatment of T-cell cancers. CD162 is a marker for the
recognition of anaplastic T-cells and preliminary results obtained in collaboration with Dr. Claudio
Tripodo (Università di Palermo) demonstrate also its correlation to tumor aggressiveness. The
creation and validation of these vehicles could represent an alternative to chemotherapy used to
treat this disease.
 Nanoparticles conjugated with Rituximab (anti-CD20 antibody) and filled with two different
contrast mediums, Magnevist and ProHance, for the diagnosis of B-cell cancers. Their high
expression of CD20 on the surface and the use of nanoparticles conjugated with an antibody able to
recognize this antigen permits a selective binding and homing of BNPs on cancer cells. Thus, the
creation and validation of these vehicles could represent an alternative to the commonly used
diagnostic tests.
The same approach used for the diagnosis of cancer B-cells will be performed for T-cells cancer,
after the creation of nanoparticles conjugated with anti-CD162 antibodies and filled with contrast
mediums.
REFERENCES
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Chan, A. C. and P. J. Carter (2010). "Therapeutic antibodies for autoimmunity and inflammation."
Nat Rev Immunol 10(5): 301-16.
Cho, K., X. Wang, S. Nie, Z. G. Chen and D. M. Shin (2008). "Therapeutic nanoparticles for drug
delivery in cancer." Clin Cancer Res 14(5): 1310-6.
Jaffee, E. (1999). "Immunotherapy of cancer." Annals of the New York Academy of Science
886(1): 67-72.
Vasir, J. K. and V. Labhasetwar (2007). "Biodegradable nanoparticles for cytosolic delivery of
therapeutics." Adv Drug Deliv Rev 59(8): 718-28.
Objectives for the three years
This PhD project is divided into two main parts, both focused on the use of immune biodegradable
nanoparticles.
One part of the project concerns the in vitro and in vivo characterization of previously selected and
produced anti-CD162 antibodies.
 in vitro and in vivo characterization of selected antibodies:
a) biochemical characterization through ELISA and BIACORE analysis;
b) in vitro characterization to evaluate antibodies' binding capability on different cancer Tcell lines and cells derived from patients. Evaluation of their ability to induce apoptosis,
complement-dependent cytotoxicicity (CDC), antibody-dependent cell-mediated cytotoxicity
(ADCC) and effects on the adhesion on endothelial cells;
c) in vivo imaging: intraperitoneal and intravenous injection of selected human anti-CD162
antibodies in a T-cell cancer mouse model. Evaluation of antibodies’ biodistribution;
 creation of immune biodegradable nanoparticles conjugated with anti-CD162 antibodies,
filled with chemotherapeutic agents and tested both in vitro and in vivo;
a) in vitro characterization of the nanoparticles binding capability and cytotoxic effects
(apoptosis) on cancer T-cell lines, cells derived from patients and other cell lines used as
negative control;
b) in vivo characterization of nanoparticles after intraperitoneal and intravenous injections
through in vivo imaging techniques.
The other part of the project concerns the evaluation of the diagnostic power of nanoparticles which
contain two contrast mediums (ProHance and Magnevist) through in vitro and in vivo tests. The use
of nanoparticles could be useful for the diagnosis of B-cell cancers, because of the presence of
Rituximab, a monoclonal antibody able to bind with high specificity an antigen known as CD20,
highly expressed on the surface of cancer B-cells. This part of the project will be performed through
different steps:
 Evaluation of the nanoparticles binding on lymphoma B-cell lines (MEC-a and BJAB),
CD20low cells (negative control) and cells isolated from patients by FACS analysis, electron
and confocal microscopy;
 Evaluation of the nanoparticles biodistribution through in vivo imaging assays;
 Evaluation of the magnetic resonance power both in vitro and in vivo.
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The same tests used for the characterization of CD20-BNPs will be performed for anti-CD162BNPs, filled with contrast medium.
Objectives for the first year
For what concerns the treatment of T-cell cancers, the objectives for the first PhD year comprehend:
 in vitro characterization of selected and produced anti-CD162 antibodies with ELISA and
BiaCORE analysis;
 evaluation of antibodies' binding capability on different cancer T-cell lines and cells derived
from patients and of apoptosis, complement-dependent cytotoxicicity (CDC) and antibodydependent cell-mediated cytotoxicity (ADCC) induction;
 Creation and preliminary validation of BNPs conjugated with anti-CD162 antibodies and filled
with chemotherapeutic agents through in vivo experiments;
 In vitro characterization of BNPs (filled with contrast medium) binding, apoptosis, CDC and
ADCC induction on CD20high, CD20low and cells derived from patients;
 In vivo and ex vivo characterization of CD20-BNPs toxicity in healthy mice
 Creation and preliminary validation of CD162-BNPs (filled with contrast medium) binding on
CD162high, CD162low and cells derived from patients.
Research project
The work plan will span over 3 years and is structured in 6 interrelated tasks that are individually
described below. Tasks sequentially exemplify the research strategy into developing and validating
a number of possible therapeutic antibodies.
GANTT DIAGRAM
3
6
9
12
15
18
21
24
27
30
33
36
TASK-1
TASK-2
TASK-3
TASK-4
TASK-5
TASK-6
TASK1 Biochemical characterization of selected and produced anti-CD162 human
recombinant antibodies (months 1-6)
Task 1.1 Epitope mapping
The epitope binding site will be mapped. Random fragmentation and ORF filtering recombinant
fragments covering the PSGL-1 N-terminal domain will be produced. Selected anti-CD162
antibodies will be tested for their ability to recognize these fragments by ELISA and Western Blot
identifying the minimal epitope recognized.
Task 1.2 Biochemical characterization of recombinant antibodies
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Isolated human recombinant antibodies will be tested for their specificity and affinity binding by
ELISA and BIAcore analysis respectively. Recombinant form of the PSGL-1 N-terminal portion
will be used in coating and in adsorption for the ELISA and BIAcore analysis respectively.
Moreover, the human recombinant antibodies will be tested for their ability to prevent the
interaction between adhered HUVEC cells and fluorescent-marked tumor cells.
TASK 2 Functional activity of anti-PSGL-1 antibodies on T-lymphoma cell lines (months 2-9)
Task 2.1 Apoptosis induction on lymphoma cell lines and cells isolated from patients
Apoptosis induction will be performed using T-lymphoma cell lines already provided Prof. Giorgio
Inghirami (University of Torino). Three human ALCL cell lines (SU-DHL, TS and JB6) and the
PTCL cell line (MAC1) will be incubated with human recombinant antibodies for 48 hours at 37°C.
Apoptotic cells will be than tested with the MTT assay, by Annexin V/PI staining and evaluating
the PARP/Syk expression by Western Blot analysis.
Task 2.2 Complement-dependent cytotoxicity evaluation on lymphoma cell lines and cells
isolated from patients
Complement-dependent cytotoxicity will be evaluated using lymphoma cell lines and cells isolated
from patients which will be incubated with human anti-CD162 antibodies and normal human serum
for 1 hour at 37°C. Residual viable cells will be measured using MTT assay.
Task 2.3 ADCC mediated by recombinant antibodies
ADCC will be performed using labeled lymphoma cells and cells isolated from patients which will
be incubated with human recombinant antibodies and human PBMC. Fluorescent residual viable
cells will be measured after 7 or 24 hours at 37°C.
Task 2.4 Inhibition of PSGL-1 activity
T cells are able to adhere to stimulated human endothelial cells via CD162. DID-labeled human T
cell lines will be incubated with a monolayer of LPS-activated HUVEC in the presence or in the
absence of the recombinant anti-PSGL-1 antibodies. Fluorescence analysis after cell washing will
provide evidence of T cell adhesion.
TASK 3 Creation and preliminary in vitro validation of immune anti-CD162 BNPs effects
(months 8-14)
Task 5.1 Creation and characterization of BNPs
Different types of nanoparticles will be created:
- BNP0 which will be not conjugated with anti-CD162 antibodies and do not contain
chemotherapeutic agents;
- BNP1 which are conjugated with anti-CD162 antibodies but do not contain chemotherapeutic
agents and
- BNP2 which are both conjugated with antibodies and contain chemotherapeutic agents.
Task 3.2 Evaluation of BNP0, BNP1 and BNP2 binding and effects on cancer T-cell lines, cells
isolated from patients and CD162neg cells
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Cancer T-cell lines and CD162neg cells, used as negative control, will be incubated with different
amount of Cy5.5 labeled BNPs for different time. Fixed cells will be analyzed first by flow
cytometry, fluorescence microscope and than using confocal microscope in order to evaluate BNPs
binding on and internalization in tumor cells.
Task 3.3 Apoptosis induction on lymphoma cell lines, cells isolated from patients and
CD162neg cells.
Apoptosis induction will be performed using T-lymphoma cell lines, cells isolated from patients
and CD162neg cells which will be incubated with human recombinant antibodies for 48 hours at
37°C. Apoptotic cells will be than tested with the MTT assay, by Annexin V/PI staining and
evaluating the PARP/Syk expression by Western Blot analysis.
TASK 4 Development of a human/SCID model of lymphoma (months 12-20)
Task 4.1 Injection of T-cell lymphoma cell lines in SCID mice
Five different lymphoma cell lines will be labeled with near infrared probe and injected i.p. and i.v.
in SCID mice 24 hours after an intraperitoneal treatment with cyclophosphamide. The technology
of time domain optical imaging will be used to follow tumor cell distribution and tumor
development in anesthetized animals; residual fluorescence will be also confirmed by ex-vivo
analysis of tumor mass and mouse organs. Animals will also be analyzed for their survival and the
progression of tumor model will be analyzed by histological and immunohistochemical studies in
order to monitor the expression of PSGL-1 and T-cell lymphoma markers.
TASK 5 Evaluation of anti-CD162-BNPs toxicity (months 20-26)
Task 5.1 In vivo analysis of the effects BNPs injection in healthy mice
Increasing amount of BNP0, BNP1 and BNP2 or chemotherapeutic agent (as a control) will be
injected i.p. in C57/Bl healthy mice. Animals will be followed for 2 weeks and their total body
weight and the survival will be analyzed.
Task 5.2 Ex vivo analysis of BNPs injection in healthy mice
Mouse organs will be collected 2 weeks after the end of the treatment with BNP0, BNP 1 and BNP2
or chemotherapeutic agents alone (as a control). Heart, brain, kidney, lung, spleen, liver
morphology will be evaluated.
Task 6 Evaluation of anti-CD162-BNPs effect in T-cell cancer mouse model (months 27-36)
Task 6.1 Analysis of BNPs distribution in lymphoma bearing mice
Cy5.5-labelled BNP0, BNP1 and BNP2 (maximal tolerated dose obtained from task 5) will be
injected i.p. in mice showing peritoneal tumor mass; animals will be sacrificed after 1, 2, 3, 4, 5, 6,
7 days.
Task 6.2 Ex vivo analysis of mice tissues.
Tumor mass, heart, brain, kidney, lung, spleen, liver and lymph nodes collected from BNP0 and
BNP1-treated animals will be analyzed using fluorescence microscope and confocal microscope in
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order to visualize CY5.5 fluorescence. Tissues morphology of BNP2-treated animals will be
analyzed in order to evaluated tumor infiltrates and cytotoxic effects of BNP2 (necrotic areas).
Task 6.3 Analysis of the BNPs effect in the treatment of T-cell cancer model
BNP0, BNP1 and BNP2 (maximal tolerated dose obtained from task 5) or chemotherapeutic agents
alone (as a control) will be injected i.p. in tumor-bearing mice starting 4 days after T-cell line
injection. Animals will be followed for 120 days and analyzed for their survival.
Ex vivo analysis of the effect of BNPs treatment. Tumor mass, heart, brain, kidney, lung, spleen,
liver and lymph nodes collected from treated animals will be analyzed by immunohistochemistry in
order to visualize human lymphoma cells.
For what concerns the characterization of anti-CD20-BNPs filled with contrast medium, the work
plan will span over 3 years and is structured in 5 interrelated tasks that are individually described
below. Tasks sequentially exemplify the research strategy into developing and validating a number
of possible therapeutic antibodies.
GANTT DIAGRAM
3
6
9
12
15
18
21
24
27
30
33
36
TASK-1
TASK-2
TASK-3
TASK-4
TASK-5
TASK 1 Prelilminary in vitro evaluation of anti-CD20-BNPs binding (months 1-6)
Task 1.1 Binding on CD20high, CD20low and cells derived from patients
To test BNPs binding capability, they will be labeled with Cy5.5 and incubated with different
cancer B-cells, CD20low cells and cells derived from patients. Fixed cells will be analyzed first by
flow cytometry, fluorescence microscope and than using confocal microscope in order to evaluate
BNPs binding on and internalization in tumor cells.
Task 1.2 In vitro apoptosis induction
Apoptosis induction will be performed using B-lymphoma cell lines (MEC-1 and BJAB) which will
be incubated with different amount of BNPs for 48 hours at 37°C. Apoptotic cells will be than
tested with the MTT assay, by Annexin V/PI staining and evaluating the PARP/Syk expression by
Western Blot analysis. For these tests, BNP0 (BNP without both contrast medium and anti-CD20
antibody), BNP1 (with only anti-CD20 antibody) and BNP2 (with both contrast medium and antiCD20 antibody) will be used.
TASK 2 Evaluation of anti-CD20-BNPs toxicity (months 6-12)
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Task 2.1 In vivo analysis of anti-CD20-BNPs effects after injection in healthy mice
Increasing amount of BNP0, BNP1 and BNP2 will be injected i.p. in C57/Bl healthy mice. Animals
will be followed for 2 weeks and their total body weight and the survival will be analyzed.
Task 2.2 Ex vivo analysis of BNPs injection in healthy mice
Mouse organs will be collected 2 weeks after the end of the incubation with BNP0, BNP 1 and
BNP2 or contrast medium (as a control). Heart, brain, kidney, lung, spleen, liver morphology will
be evaluated.
Task 3 Evaluation of BNPs effect in B-cell cancer mouse model (months 13-20)
Task 3.1 Analysis of BNPs distribution in lymphoma bearing mice
Cy5.5-labelled BNP0, BNP1 and BNP2 will be injected i.p. in mice showing peritoneal tumor
mass; animals will be sacrificed after 1, 2, 3, 4, 5, 6, 7 days.
Task 3.2 Ex vivo analysis of mice tissues.
Tumor mass, heart, brain, kidney, lung, spleen, liver and lymph nodes collected from BNP0 and
BNP1-treated animals will be analyzed using fluorescence microscope and confocal microscope in
order to visualize CY5.5 fluorescence. Tissues morphology of BNP2-treated animals will be
analyzed in order to evaluated tumor infiltrates and cytotoxic effects of BNP2 (necrotic areas).
Task 3.3 Analysis of the BNPs effect in the treatment of T-cell cancer model
BNP0, BNP1 and BNP2 or chemotherapeutic agents (as a control) will be injected i.p. in tumorbearing mice starting 4 days after T-cell line injection. Animals will be followed for 120 days and
analyzed for their survival.
Ex vivo analysis of the effect of BNPs treatment. Tumor mass, heart, brain, kidney, lung, spleen,
liver and lymph nodes collected from treated animals will be analysed by immunohistochemistry in
order to visualize human lymphoma cells.
Task 4 Creation and preliminary in vitro validation of anti-CD162-BNPs filled with contrast
medium (20-26)
Task 4.1 Creation of anti-CD162-BNPs filled with contrast medium
Different types of nanoparticles will be created:
- BNP0 which will be not conjugated with anti-CD162 antibodies and do not contain contrast
medium;
- BNP1 which are conjugated with anti-CD162 antibodies but do not contain contrast medium and
- BNP2 which are both conjugated with antibodies and contain contrast medium.
Task 4.2 Evaluation of BNP0, BNP1 and BNP2 binding and effects on cancer T-cell lines, cells
isolated from patients and CD162neg cells
Cancer T-cell lines and CD162neg cells, used as negative control, will be incubated with different
amount of Cy5.5 labeled BNPs for different time. Fixed cells will be analyzed first by flow
cytometry, fluorescence microscope and than using confocal microscope in order to evaluate BNPs
binding on and internalization in tumor cells.
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Task 4.3 Apoptosis induction on lymphoma cell lines, cells isolated from patients and
CD162neg cells.
Apoptosis induction will be performed using T-lymphoma cell lines. Three human ALCL cell lines
(SU-DHL, TS and JB6) and the PTCL cell line (MAC1) will be incubated with nanoparticles for 48
hours at 37°C. Apoptotic cells will be than tested with the MTT assay.
TASK 5 Evaluation of anti-CD162-BNPs toxicity (months 27-36)
Task 5.1 In vivo analysis of the effects BNPs injection in healthy mice
Increasing amount of BNP0, BNP1 and BNP2 or contrast agent (as a control) will be injected i.p. in
C57/Bl healthy mice. Animals will be followed for several weeks and magnetic resonance analysis
will be performed.
Task 5.2 Analysis of BNPs bio-distribution in lymphoma bearing mice
Labelled BNP0, BNP1 and BNP2 (maximal tolerated dose obtained from task 5.1) will be injected
i.p. in mice showing peritoneal tumor mass and they will be analyzed through an in vivo imaging
approach.
Task 5.3 Ex vivo analysis of mice tissues
Tumor mass, heart, brain, kidney, lung, spleen, liver and lymph nodes collected from BNP0 and
BNP1-treated animals will be analyzed using fluorescence microscope and confocal microscope in
order to visualize CY5.5 fluorescence. Tissues morphology of BNP2-treated animals will be
analyzed in order to evaluated tumor homing and eventual cytotoxic effects of BNP2 (necrotic
areas).
Task 5.4 Magnetic resonance analysis on mouse model
BNP0, BNP1 and BNP2 (maximal tolerated dose obtained from task 5.1) or contrast medium (as a
control) will be injected i.p. in tumor-bearing mice after T-cell line injection. Animals will be tested
through magnetic resonance.
Educational activity foreseen
During the first year, two trainings about in vitro and in vivo techniques will be performed.
The first training will be focused on FACS (Fluorescence-Activated Cell Sorting) analysis, a
technique which permits the evaluation of the expression of antigens on the surface of cells using
antibodies conjugated with fluorescent dyes. This training will be performed at C.R.O situated in
Aviano.
The second training will be focused on in vivo imaging techniques which permit the evaluation of
biodistribution of antibodies and nanoparticles in mice.
An another training about isolation, production, characterization and engineering of antibodies will
be performed in Los Alamos at the laboratory of Professor Andrew Bradbury.
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PAOLO CECCHINI
Email: [email protected]; [email protected]
Laboratory:
Title of the thesis: Analysis and implementation of glaucoma filtration devices in glaucoma
surgery
Supervisor: Prof . Daniele Tognetto
Tutors (if any):
Research Activity foreseen
State of the art and motivations
Glaucoma is a degenerative pathology of the optic nerve, leading to the loss of the optic nerve fibers
along with irreversible visual field damage. Glaucoma may eventually cause blindness if not
treated. The most frequent type of glaucoma is the primary open angle glaucoma. Briefly, in the
anterior segment of the eye the ciliary body produces the so called aqueous humor, which maintains
the intraocular pressure in a range between 10 and 20 mmHg. The aqueous humor is drained out of
the eye through a structure called trabecular meshwork. In primary open angle glaucoma, the
trabecular meshwork impedes the normal flow of the aqueous out of the eye, inducing a
pathological increase in the intraocular pressure. A high intraocular pressure causes damage to the
optic nerve fibers that undergo an apoptotic process.
The first approach to glaucoma therapy is the use of eyedrops that reduce the intraocular pressure. If
the intraocular pressure cannot be maintained at low levels, surgery is the only option.
Manual trabeculectomy is the gold standard in glaucoma filtration surgery. The goal is to surgically
remove a small part of the trabecular meshwork and let the aqueous humor flow outside the eye
under the conjunctiva. This technique, however, is quite unpredictable and depends on the surgeon
experience and technique.
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A safer approach is to implant new filtration devices, among which the most reliable seems to be
the Ex-press Glaucoma Filtration Device. The Ex-Press device is a small steel unit - similar in size
to a grain of rice, around 2.64 mm- that is implanted between the inner region and the outer region
of the eye. The EX-PRESS™ Glaucoma Filtration Device enables the drainage system of the eye,
which has been damaged by glaucoma, to be bypassed. Recent clinical studies do confirm good
results in terms of reduced intraocular pressure and less postoperative complications.
Most of the drainage systems in the past did not offer satisfactory surgical outcomes. The ideal
device should be made out of a inert material, that does not allow (or reduces) the postoperative
inflammatory response.
The aim of the research is to chemically and physically characterize the glaucoma filtration devices,
study their hydrodynamics, the superficial nano characteristics, and implement their design and
nanostructure. It would be of interest to test the flow of the devices via experimental modeling, the
superficial roughness and the possible correlation to cellular on-growth. New construction materials
or design may increase the outflow and the biocompatibility of the devices.
Objectives for the three years
The research steps will be
 State of the art data collection
 Study of the hydrodynamics with computer assisted simulations
 Study of the superficial nano-characteristics
 Study of inflammatory and fibroblastic adhesiveness on the surface
 Implementation of design and/or materials, eventually leading to a new coating of the
devices or new construction materials
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Objectives for the first year
 State of the art data collection and analysis
 Study of the hydrodynamics
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GIOVANNA COCEANO
Title of the thesis: Characterization of the mechanical properties of cancer cells
Supervisor: Dan Cojoc
Tutor (if any): Serena Bonin
Laboratory: Optical Manipulation Laboratory @ IOM-CNR, Trieste
Research Activity foreseen
State of the art and motivations
The research project is dedicated to the characterization of the mechanical properties of cancer
cells. Among these we mention: cell stiffness, local viscoelasticity, cell-matrix and cell-cell
adhesion. Cancer cells characterized by high aggressiveness specific to metastasis will make the
object of the study since metastasis represents one of the most common causes of death in cancer
patient. Metastasis means the spread of malignant cells from primary tumour to a distant organ
requiring significant modifications of the cell biomechanics.
It is accepted in general that tumour cells are softer than the corresponding non neoplastic cells
and hence are more deformable under the same mechanical stress. Metastatic cells are even softer
than primary tumour cells. In addition, they lose almost completely their cell-cell adhesion
properties. These changes are consistent with the fact that malignant cells, characterized by
increased replication and motility, have to penetrate the cellular matrix, go into the blood and
lymphatic stream, and finally leave the stream to fix on new sites. Metastatic cells are tumour cells
characterized by the ability to leave the primary tumour site and to reach a distant organ. The
conversion of malignant cells in metastatic cells is accompanied by several biological processes that
cause alterations leading to changes in cell structure and cytoskeleton. The membrane acquires new
mechanical properties that contribute to cell deformability and to the ability of the cell to attach,
move and spread. The cellular structure alteration reflects on the mechanical properties of the cell
such as stiffness, local viscoelasticity, adhesion.
The goal of the project is to characterize the mechanical properties of cancer cell with different
level of aggressiveness and different metastatic potential and to correlate this with the plasma
membrane structure and cytoskeleton organization. The study of the alterations of the membrane
mechanical properties is very important for understanding better the migration mechanisms and to
find new markers for cancer diagnosis and therapeutics. To reach this goal a novel method based on
the use of Optical Tweezers (OT) has been developed at IOM-CNR. OT is an instrument that uses a
highly focused laser beam to capture and manipulate microscopic objects by small forces (on the
order of pN). OT has been used to locally measure the viscoelastic properties of the cell membrane
for two breast cancer cell lines and a non-neoplastic one.
References
•Ashkin A. (2006). "Optical Trapping and Manipulation of Neutral Particles Using Lasers." Ed.
World Scientific Publishing Company. Physics - Optics & Light.
•Ashkin A., Dziedzic J.M., et al. (1986). "Observation of a single-beam gradient force optical
trap for dielectric particles." Opt. Lett.
•Ferrari E. PhD Thesis (2007).“ Optical manipulation and force spectroscopy at the cellular and
molecular level by means of lazer tweezers” Università degli Studi di Trieste, CNR-INFM.
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•Federica Tavano , Serena Bonin , Giulietta Pinato , Giorgio Stanta & Dan Cojoc (2011).
“Custom-Built Optical Tweezers for Locally Probing the Viscoelastic Properties of Cancer
Cells”. International Journal of Optomechatronics.
•Alia Al-Kilani, Olivier de Freitas, Sylvie Dufour, and Francois Gallet (2011). “Negative
Feedback from Integrins to Cadherins: A Micromechanical Study”. Biophysical Journal.
•Benoit Ladoux, Ester Anon, Mireille Lambert, Aleksandr Rabodzey, Pascal Hersen, Axel
Buguink Pascal Silberzan, and Rene´-Marc Mege (2010).“Strength Dependence of
Cadherin-Mediated Adhesions” Biophysical Journal.
Objectives for the three years
We plan to improve and extend the OT measurements also to other types of cancer cells, on one
hand. On the other hand we will investigate also cell-cell and cell-matrix adhesion mechanisms by
using properly functionalized beads.
This project aims also to develop new optical methods for the investigation of the mechanical
properties of cancer cells. Speckle sensing microscopy, recently applied at IOM-CNR to analyze
malaria allows to investigate the stiffness of tens of cells in one second, recording and analyzing the
dynamics of the speckle pattern produced by the cells under illumination by a tilted laser beam.
Finally we will try to find a correlation between the mechanical properties of the cell with the
presence of biomarkers as genes and proteins by molecular analysis, in an unified effort to
characterize the beginning of the metastatic progression.
Objectives for the first year
•Learn and apply the OT measurements previously developed in the lab to increase the statistics
for characterization of membrane viscosity and elasticity of two different kind of cancer cells:
MDA-MB-231, MCF-7.
•Elaboration of a new construct with two beads linked by a DNA or polymer tether to increase
the sensitivity of the local measurements of the viscoelasticity.
•Identification of the most suited cell-matrix and cell-cell adhesion proteins that can be
attached to the probe in order to measure the viscoelastic properties of cancer cells membranes
and to have local level measures
•Learn and apply the speckle sensing microscopy technique to cancer cells.
Research project
This project has been initiated several years ago, and has been developed mainly during the
doctorate of Federica Tavano, when the Optical Tweezers technique has been setup to analyze the
viscoelastic properties (force, viscosity, tether membrane) of cell membranes belonging to three
different types of breast cell lines.
My job will be to continue this research project and to apply the method prepared by Federica to
other cell lines (colon and pancreas).
During these three months of work, I got familiar with microscope techniques, I did a training
on the Optical Tweezers and I did a bibliographic research on tumour cells and their role in
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metastasis, regarded to the mechanic properties. The work will continue through the following
steps:
•Bibliographic research on membrane proteins, in particular cadherins and integrins, in order to
understand the biological mechanism of cell-cell adhesion and the role/deregulation of cellcell adhesion proteins during tumourigenesis and metastasis.
•Functionalization of probes (micro beads, or AFM tips) with cell-cell adhesion proteins and
measurements of the binding forces of their interaction with membrane proteins.
•Improve the analysis of the viscoelastic properties by means of more specific probes, which
allow us to have local measure
•Analysis of gene regulation and protein expression by molecular biology approaches at the
Cattinara Hospital in Trieste / University of Trieste
•Development of a new technique in our lab, called speckle sensing microscopy, to measure the
viscoelastic properties by monitoring the fluctuations of the cell membrane.
Educational activity foreseen
•Attend the School “Single Cell Physiology” at the “Ecole Normale Superieure”, Paris.
•Study books and reviews cell mechanics, optical methods and lithographic processes.
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ANDREA COVA
Email: [email protected]
Laboratory: R.A.M.S.E.S. Istituti Ortopedici Rizzoli, Bologna
Title of the thesis: “Role of collagen cross-linkers on the stability of the bonded interface”
Supervisor: Prof. Breschi Lorenzo
Research Activity foreseen
State of the art and motivations
The prevention and treatment of tooth decay are major challenges in dentistry. It’s estimated that
90% of adults in Western countries in the USA suffer from this dental disease (1). The primary
objective of restorative dentistry is to repair and replace damage tooth structures by the application
of synthetic materials aiming at the re-establishment of tooth aesthetics and function. Current
restorative procedures generally depend on the formation of an adhesive bond between polymeric
dental materials and the tooth substrate, enamel and dentin in particularly (2). Dentin is the tissue
underlying the dental enamel that constitutes the bulk of the tooth. I has a specifically oriented
micro-morphology composed of tubules (~1-2μm diameter) (3) surrounded by a hypermineralized
layer (~1μm), called peritubular dentin and a softer intertubular matrix, where the organic material
is concentrated (4). The intertubular matrix is mainly composed of type I collagen fibrils with
associated non-collagenous proteins and proteoglycans, forming a three-dimensional organic
network reinforced by apatite mineral crystallines (3). The repair of tooth structures with polymeric
adhesive materials generally involves three distinct processes, namely acid etching, priming and
bonding, although several self-adhesive resin also exist (2). In dentin, infiltration of the adhesive
resin in to the collagen network is a process termed hybridization. The result of this diffusion
process has been called the “hybrid layer”(5,6). It’s generally accepted that the final goal of these
adhesive procedure is the complete infiltration of the demineralized collagen fibrils by the
monomeric resin (2,5,6,7). The complexity by collagen-monomeric resin induced at the degradation
mechanism of tooth-biomaterial interface, called nanoleakage phenomenon (8). It has been shown
that nanoleakage can occur in the absence of the marginal gaps in biomaterials-dentin interface,
which led to the conclusion that host-derived proteinases make an important contribution to the
degradation of incompletely infiltrated collagen in bonded dentin (9). Breschi et al. (7) described
the presence of MMPs, a class of zinc and calcium dependent endopeptidases, trapped within the
mineralized dentin matrix during tooth development (2). The release and the activation of these
proteinases during dentin bonding (9) are thought to be responsible for the degradation of collagen
fibrils in incompletely infiltrated hybrid layers in aged bonded dentin (10). Recent studies
demonstrating the efficacy of cross-linking agents in increasing the longevity of resin-dentin bond
support the hypothesis that the collagen structure plays a critical role in regulating MMP
degradation (11,12).
The project topic of my research is to investigate the innovative nano-molecules which would
induce collagen cross-linking and if possible develop a new adhesive system to be applied to the
dentin surface to stabilize the adhesive bond in the long term.
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References:
1. Beltran-Aguilar ED, Barker LK, Canto MT, Dye BA, et al. (2005) Surveillance Summaries
54: MMWR Atlanta, GA: Centers for Disease Control and Prevention; p. 1-13.
2. Pashley DH, Tay FR, Breschi L, Tjaderhane L, Carvalho RM, Carillo M et al. (2011). State
of the art etch-and-rinse adhesives. Dent Mater 27:1-16.
3. Marshall GW, Marshall SJ, Kinney JH, Balooch M (1997). The dentin substrate: structure
and properties related to bonding. J Dent 25:441-58.
4. Bertassoni LE, Stankoska K, Swain MV (2012). Insights into the structure and composition
of the peritubular dentin organic matrix and lamina limitans. Micron 43:229-36.
5. Nakabayashi N, Kojima K, Masuhara E (1982). The promotion of adhesion by the infiltration
of monomers into tooth substrates. J Biomed Mater Res 16:265-73.
6. Sano H, Shono T, Takatsu T, Hosoda H (1994). Microporous dentin zone beneath resinimpregnated layer. Oper Dent 19:59-64.
7. Breschi L, Mazzoni A, Ruggeri A, Cadenaro M, Di Lenarda R, De Stefano Dorigo (2008).
Dental adhesion review: aging and stability of the bonded interface. Dent Mater 24:90-101.
8. Sano H (2006). Microtensile testing, nanoleakage and biodegradation of resin-dentin bonds.
J Dent Res 85:11-14.
9. Pashley DH, Tay FR, Yiu C, Hashimoto M, Breschi L, Carvalho RM et al (2004). Collagen
degradation by host-derived enzymes during aging. J Dent Res 83:216-21.
10. De Munch J, Van Meerbek B, Yoshida Y, Inoue S, Vargas M, Suzuki K et al (2003). Four
year water degradation of total-etch adhesive bonded to dentin. J Dent Res 82:136-40.
11. Al-Ammar A, Drummond JL, Bedran-Russo AK. The use of collagen cross-linking agents
to enhance dentin bond strength (2009). J Biomed Mater 91:506-11.
12. Cova A, Breschi L, Nato F, Ruggeri Jr A, Carrilho M, Tjaderhane L et al (2011). Effect of
UVA-activated riboflavin on dentin bonding. J Dent Res 90:1439-45.
Objectives for the three years
Objective of the research project is to investigate the role of collagen cross-linkers applied to the
dentin substrate, with particular reference to the role of endogenous MMPs involved in the
degradation collagen fibrils. Moreover, investigate with the light, transmission and scanning
electron microscopy the nanostructure of the dentin collagen with and without the application of
cross-linkers agents.
Objectives for first following year
Riboflavin (Vitamin B2) cross-linkers will be applied on the dentinal surface at different time
storage and will be evaluated the response of dentinal tissue in order to stabilize the bond adhesive
interface. Proteins of dentin will be extracted for zymographic assays in order to highlight the
activities of MMPs.
Research project
Testing materials:
- Microtensile bond strength test;
- Zimographic analysis;
- Light microscopy (LM);
- Transmission electron microscopy (TEM);
- Scanning electron microscopy (SEM).
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Educational activity foreseen
- Participation to national and international meetings on dental materials;
- Frequency of research laboratories at the Istituti Ortopedici Rizzoli in Bologna and at the
University of Trieste;
- Study of published papers on collagen cross-linkers agents.
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MARINA DIOLOSÀ
Email: marina.diolosà@phd.units.it
Laboratory: Department of Medical Sciences
Title of the thesis: Development of a new nano-engineered biopolymer-based dental adhesive
system
Supervisor: Prof. Cadenaro Milena
Tutors (if any): Prof. Breschi Lorenzo
Research Activity foreseen
State of the art and motivations
Dental caries (tooth decay) has historically been considered the most important component of the
global oral disease burden. Dental caries is still a major public health problem in most high-income
countries as the disease affects 60-90% of school-aged children and the vast majority of adults.
Worldwide, dental caries prevalence is high among adults as the disease affects nearly 100% of the
population in the majority of countries (World Health Organization (WHO). Future use of materials
for dental restoration. Report of the meeting convened at WHO HQ, Geneva, Switzerland. 2011).
The principal reasons for the placement the restorations are: primary caries, secondary caries,
margin fracture/degradation and tooth fracture, other reasons comprised principally lost restorations
and endodontic access.
The placement of effective long-lasting restorations is important because this reduces the long-term
cost of dental treatment.
Longevity of dental restoration is dependent upon many different factors, including material, patient
and dentist- related factors (Manhart J, Chen H, Hamm G, Hickel R. Buonocore Memorial Lecture.
Review of the clinical survival of direct and indirect restorations in posterior teeth of the permanent
dentition. Oper Dent. 2004 Sep-Oct;29(5):481-508)
The materials used for direct and indirect restorations are the adhesive systems and resin-based
composite.
The project is focused on responding to the widespread clinical need of stable dental restoration.
The objective of this project is the development of an innovative nano-engineered biocompatible
dental adhesive system capable to form covalent chemical bonds with both the dentin collagen and
the restorative resin and with antibacterial activity.
The project is based on a new concept of adhesive system based on a biopolymer (chitosan) capable
of double covalent reticulation. The polymeric backbone will be modified in order to bear both
methacrylate groups and glutamine residues. This formulation should be able to be covalently
bonded to both the exposed dentin collagen by exploiting crosslinking reactions catalyzed by
transglutaminase enzymes and to the restorative material by means of a photopolymerization
process. The adhesive will be then enriched with nanosilver particles to improve its antibacterial
properties. If successful, this project would lead to the realization of a natural-derived adhesive
specifically designed to promote long-term stable restoration of teeth.
Objectives for the three years
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The objective of this project is the development of an innovative nano-engineered biopolymerbased dental adhesive system capable to form covalent chemical bonds with both the dentin
collagen and the restorative resin and with antibacterial properties.
Objectives for first following year (if applicable)
Chitosan will be used both as a primer or added to adhesive resins.
In the first case the chitosan diluted with ethanol will be applied on the tooth surface,
followed by the application of an experimental adhesive resin and bond strength will be
measured.
 In the second case, low pm chitosan will be added in increasing concentrations to an
experimental adhesive resin. Properties of the mixture such as degree of conversion,
elastic modulus and microhardness will be measured in order to find out if they are
compatible with the use on dental tissues. When the optimal concentration will be found,
the chitosan-based experimental adhesive will be applied on the tooth surface and bond
strength will be measured.
Research project
Testing materials:
 Degree of conversion
 Elastic modulus
 Micro-hardness
 Microtensile bond strength test
Educational activity foreseen
Participation to National and International meetings on dental materials (Congresso
Nazionale del Collegio dei Docenti di Odontoiatria, Torino April 12-14, 2012; Annual
Meeting of the Academy of Dental Materials, Orlando (USA) September 19-22, 2012)
Study of published works on dental adhesive formulation and use of chitosan for
biomedical puroposes;
 Acquisition of skills in using FTIR for the calculation of degree of conversion, in elastic
modulus and microhardness measurement and in bond strength testing.
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ELENA ELISEI
Email: [email protected]
Laboratory: Life Sciences Department – Laboratory of Physical and Macromolecular
Chemistry
Title of the thesis: Nanostructured biomolecular glasses
Supervisor: Prof. Attilio Cesàro
Tutor: Fabio Tedoldi (Bracco Imaging, Colleretto Giacosa)
Research Activity foreseen
State of the art and motivations
The aim of this research project is to investigate the perturbation and influence the glassy state has
on the magnetic properties of embedded materials. The glassy state[1] is very common in nature, is
characterized by a structural irregularity and other physical properties highly dependent on
temperature and time and on the amorphization conditions. These features give to the glassy
systems particular moldability and versatility, and as a consequence, they are used in many
technological fields[2]. The simplest procedure for glass production is the istantaneous freezing of a
liquid (said supercooled liquid), which prevents the material to crystallize. Although this technique
has been known and used for thousands of years, many questions about the way the supercooled
liquid acquires an amorphous rigidity still remains open[3]. For instance, the quantitative study of
the extraordinary viscosity increase accompanying the supercooling process and the formation of
the glass(es) (and then the glass transition) is certainly one open problem in this field[4].
Particular cases are the biomolecular glasses, which have wide applications for example in
biosciences (for the production and the processing of foods with special characteristics of
consistency, shelf life and stability)[5] or in the preservation of microorganisms life under extreme
conditions of temperature or dehydration.
Another emerging field of application, which is closely linked to this research project, is the
medical physics, because biomolecular glasses, with and without nanostructured elements, can be
used for the production of specific contrast agents for Nuclear Magnetic Resonance. More in detail,
the glassy materials are suitably doped with radical species, in order to maximize the NMR signal
with a specific procedure called DNP (Dynamic Nuclear Polarization) in order to get MRI images
with highest resolution[6-8]. The DNP principle is the following: a diamagnetic insulator contains a
small concentration of paramagnetic impurities, whose electron spins are oriented easily in an
external magnetic field, and precede around with the Larmor frequency ωe. The application of a
microwave field to the sample and the ESR resonance (Electron Spin Resonance) with frequency
ω = ωe ± δ dove |δ| << |ωe|
allow the transmission of a high degree of orientation from electron spins to the nuclear spins,
obtaining a polarization
±P
where P >> |Pneq|
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and Pneq is the nuclear polarization at equilibrium. In the latest years of the past century, the
production of intense magnetic fields using superconducting coils and very low temperatures using
dilution refrigerators (B ≈ 80 kOe, T ≈ 10 mK) has achieved a polarization of 70% for protons.
The magnetic properties of the contrast agents obtained with this technique are very sensitive to the
nanostructures and to the voids heterogeneity present within the glassy matrix. The issue of voids
and nanostructures formed during the process of amorphization because of the chemical
heterogeneity of the samples (embedding matrix, radical and other biological species) will be the
main subject of investigation.
[1] F.H. Stillinger, P.G. Debenedetti “Supercooled liquids and the glass transition” Nature 410 (2001).
[2] C.A. Angell “Formation of glasses from liquids and biopolymers” Science 267 (1995), 1924–1935.
[3] T.M. Truskett, P.G. Debenedetti, F.H.Stillinger et al “Theory of supercooled liquids and glasses: energy
landscape and statistical geometry perspectives” Adv. Chem. Eng. 28 (2001) pp. 21–79.
[4] P.W. Anderson “Through a glass lightly” Science 267 (1995), p. 1615.
[5] P. Lillford, J.M.V. Blanshard “The Glassy State in Food” Nottingham Easter School in Agricultural and
Food Sciences 1993.
[6] M. Goldman, A. Abragam “Principles of dynamic nuclear polarisation” Rep. Prog. Phys. 41(3) (1978),
pp. 395–467.
[7] F. Bloch “Nuclear Induction” Phys. Rev. 70(7-8) (1946), p. 460.
[8] W. de Boer “Dynamic Orientation of Nuclei at Low Temperatures” Journal of Low Temperature Physics
22 (1976).
Objectives for the three years
The research activities of the main part of the project are designed to study some chemical and
physical aspects underlying the DNP process:
- to study the role of the glassy state in obtaining an acceptable polarization and correlation between
the physical state (crystalline, semicrystalline or amorphous) of the sample and its hyperpolarizability;
- to identify the molecular parameters and the processes that may amplify the dynamic nuclear
polarization and its life time;
- to identify the conditions necessary to achieve a biomolecular system with characteristics of
efficiency as regards the amplification of hyperpolarization and its life time.
The research activities of a second line of the project have the purpose of investigating possibile
innovative experimental procedures (in terms of process and/or molecule) to transform a
biomolecular material (from crystalline or solution state) into a glass:
- to study, from the viewpoint of characterization and stability of the vitreous phase, both the liquid
samples at room temperature (Tm < Troom, Tg << Troom) and solid samples, the latter characterized by
greater stability and perhaps more suitable for applications in the field of DNP.
Objectives for the first year
In the first year of PhD we plan to investigate the theoretical basis of the DNP phenomenon, to
identify some model molecules and to characterize them in terms of chemical and physical
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properties. This study may provide important informations on fundamental parameters that come
into play in the hyperpolarization process, and that will be studied in the following years of PhD.
Research project
he research project will focus on the investigation of the influence of the glassy state and its
nanostructures and voids heterogeneity on the hyperpolarization efficiency (DNP) of the
biomolecular glasses used as molecular contrast agents. Furthermore, possible innovative
experimental procedures will be investigated to obtain nanostructured glasses from biomolecular
materials; the samples obtained by various procedures will be studied especially from the point of
view of structural stability. The detailed work program is shown in the following table.
Activities
2012
1
2
3
2013
4
1
2
3
2014
4
1
2
3
4
Preparation of samples (e.g. Quenching, Evaporation,
Spry drying)
Characterization and investigation on the efficiency of
magnetic transfer (e.g. Calorimetry, PALS, NMR, EPR,
Cristallography)
Data analysis and experiments correlations
Literature search
Educational activities
Paper writing and conferences
Educational activity foreseen
During the first year of PhD, it will be necessary to examine some wide themes connected with the
research project:
- Magnetism and Dynamic Nuclear Polarization, - Crystallography and X-ray Diffraction, Calorimetry and biomolecules, including biomacromolecules
For this reason it is planned to attend (I’ve already attended) schools, conferences and courses
related to these issues::
- Seminar: “Computational approaches to modeling of ESR and NMR observables”, prof. Antonino
Polimeno
- School: “Italian school on magnetism”, University of Pavia
- Course: “Spring corse of powder diffraction method”, University of Trieste
- Seminar: “Introduction to molecular magnetism and spin crossover complexes”, prof. Sylvestre
Bonnet
- Conference: “XXXIV Italian Congress on Calorimetry, Thermal Analysis and Applied
Thermodynamics”, University of Rome
- School: “IISS school on crystallography for health and biosciences”, University of Como
- Course: “Macromolecole 1”, prof. Attilio Cesàro
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STEFANO FORNASARO
Email: [email protected] (temporary)
Laboratory: Department of Life Sciences of Trieste University, via L. Giorgieri, 1 34127 Trieste Italia
Title of the thesis: Targeting natural antioxidant compounds to the brain: a metabolomic
assessment
Supervisor: Sabina Passamonti
Tutors: Fulvio Mattivi, Lovro Žiberna
Research Activity foreseen
State of the art and motivations
Population ageing has been a policy priority at both Member State and European Union (EU) levels
for more than two decades and, in recent years it has been promoted to the level of a “grand
challenge”: the number of Europeans aged 65 and over is expected to increase by 45% between
2008 and 2030, and will be over 30% of the population by 2060 [1].
Ageing is associated with many common chronic neurodegenerative diseases and the precise cause
of the neuronal degeneration underlying these diseases and, indeed, normal brain ageing remains
unclear [2]. Nevertheless it is thought that several cellular and molecular events are also involved,
including impaired mitochondria function, activation of neuronal apoptosis, the deposition of
aggregated proteins and excitotoxicity.
Representing one of the most important lifestyle factors, the diet can strongly influence the
incidence and onset of neurodegenerative disorders. Epidemiological studies have demonstrated the
positive effect of fruit and vegetable rich-diet on pathologies strictly linked with an unbalance of the
redox status, as ageing, cancer, diseases of cardiovascular system and some degenerative disease [3,
4]. Detailed investigations into the specific dietary components of these foods have consistently
suggested that a group of phytochemicals, known as flavonoids, is highly effective in reversing agerelated declines in neuro-cognitive performance. In particular, evidence suggests that foods rich in
three specific flavonoid sub-groups, the flavanols, anthocyanins and/or flavanones, possess the
greatest potential to act on cognitive processes [5]. In addition, a growing number of flavonoids
have been shown to inhibit the development of Alzheimer disease-like pathology and to reverse
deficits in cognition, suggestive of potential therapeutic utility in dementia [6-10].
Flavonoids may mediate these positive effects via a number of routes [11,12], including a potential
to protect neurons against injury induced by neurotoxins [13], an ability to suppress
neuroinflammation [14] and a potential to promote memory, learning and cognitive function [7, 8,
15]. As anti-cellular oxidative stress agents flavonoids can act either as direct chemical
antioxidants, the classic view of flavonoids as antioxidants [16, 17], or as modulators of enzymes
and metabolic and signaling pathways leading to an overshot of reactive oxygen species (ROS)
formation, a more recently emerging concept [18-28]. Despite these effects, there is a lack of
information regarding the interaction between flavonoids and the blood-brain barrier (BBB) [29].
Altogether, these data are adding more and more confusion on how to explain epidemiological data
and prevent rather than promote mechanistic explanations of flavonoid bioactivity.
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Some works have succeeded in filling gaps of knowledge concerning the fast absorption of grape
anthocyanins (wine pigments) from the stomach [30] and their fast distribution in tissues, such as
the brain [31], the liver [32], the kidney [33]. In all tissues, anthocyanins were found unmodified
with respect to their original chemical structure. The amounts recovered and measured in these
tissues were however very low, i.e. at concentrations too low to scavenge reactive oxygen species,
leaving open the possibility that their biological activities might be due to the modulation of cellular
enzymes.
Undoubtely, ”omic” approaches are the most suitable to obtain a global view on the impact of
anthocyanins on enzyme function [34-36]. However, the time window in which anthocyanins have
their peak impact on the cell is very short (less than a few min). Thus, it is unlikely that anthocyanin
effects be detected at the level of the transcriptome or of the proteome. Only changes at the level of
the metabolome might be expected. Preliminary data in support of this contention are available [37,
38]. Moreover, the same approach will also enable to better understand a crucial step of
anthocyanin bioactivity in the brain, i.e. their membrane transport, mediated by the plasma
membrane transporter bilitranslocase. In facts, specific monoclonal antibodies are available to target
the native protein and induce its functional loss in intact cells [39]. By this approach, complex
phenomena will be understood in the light of the specific nano-scale molecular recognitions taking
place at the level of this transporter.
Objectives for the three years
The aim of this project is to directly assess uptake and metabolism of the dietary anthocyanin
cyanidin 3-glucoside (C3G) into the brain, and to verify the hypothesis that the specific uptake of
flavonoids across the blood-brain barrier requires the activity of membrane transporters, among
which bilitranslocase. It may be mentioned that bilitranslocase is so far the only membrane
transporter whose role in the bioavalilability of dietary flavonoids has been established.
Obbiettivi da raggiungere per il primo anno
In the first year this project will aim at investigating the metabolic changes occurring in the brain as
a result of the intake of anthocyanins. These changes will be examined by a metabolomic analysis.
Research project
 RO1. Metabolomic analysis of rat brains after C3G administration (C3G, 5’ IV)
oAim. To identify and quantify all metabolites in a specific tissue (rat brains) in order to
obtain insights in the metabolic changes following an intravenous administration of a
pure anthocyanin (C3G).
oApproach. Rats will be treated with an i.v. dose (330 μg) of C3G. They will be
euthanized after 5'. Their blood and brains will be collected and analysed by
UPLC/QTOF-MS.
oExpected results. Previous data have shown that anthocyanins are transported into the
brain. It is expected that these compounds will undergo metabolism, consisting in
methylation of the catechol moiety, similarly to what seen in other organs. The
metabolic changes might involve multiple metabolic pathways, since no one
pathway operates in isolation. It is expected that these data will provide cues about
the molecular mechanisms whereby food rich in anthocyanins improves the mental
performance both in experimental animals and in humans.
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oCollaboration: Fondazione Edmund Mach-Istituto Agrario di San Michele all’Adige
(FEM-IASMA), Dr Fulvio Mattivi.
 RO2. Immunochemical localisation of bilitranslocase in the rat brain.
oAim. To investigate the expression and function of bilitranslocase in the whole brain,
as well as isolated neurons, and glial cells grown in culture.
oApproach. Both immunohistochemical and immunocytochemical (IHC and ICC)
analysis are planned to assess the presence of bilitranslocase in specific brain areas.
Preliminary evidence is available. Particularly interesting is its detection at the level
of the blood-brain barrier. The antibody used will be an anti-sequence antibilitranslocase, prepared as described previously [40].
oExpected results. Bilitranslocase will be identified in specific areas of the brain, which
will therefore be regarded as potential targets of dietary anthocyanins.
oCollaborations. Laboratory of Neuronatomy, Dept of Life Sciences, Prof. Enrico
Tongiorgi; Blood Transfusion Centre of Slovenia (BTCS), Dr Vladka Curin Šerbec.
 RO3. Role of bilitranslocase in anthocyanin uptake in neurons.
oAim. To investigate the mechanism of 3CG uptake into neurons and glial cells.
oApproach. Human neuroblastoma and neuroglioma cell lines will be used to asses C3G
transport into cells. C3G and its metabolites (putatively its methylation product, i.e.
peonidin 3-glucoside) will be assayed by HPLC coupled with thermal lens
spectroscopy detection. When the method will be set up and shown to be amenable
to more subtle investigations, primary hippocampus neurons explanted from murine
brains will be tested.
oExpected results. These studies will point to the occurrence of specific molecular
interactions involving dietary anthocyanins and the membrane transporter
bilitranslocase, expressed in neuronal cells.
oCollaborations. Laboratory of Neuronatomy, Dept of Life Sciences, Prof. Enrico
Tongiorgi, Blood Transfusion Centre of Slovenia (BTCS), Dr Vladka Curin Šerbec.
Analyses will be carried out at the University of Nova Gorica - Laboratory of
Environmental Research, Prof. Mladen Franko,within the scope of a research
agreement (Trans2care project).
 RO4. Role of bilitranslocase in anthocyanin uptake in the brain.
oAim. To assess the functional role of BTL in targeting natural antioxidant compounds
to the brain.
oApproach. Anaesthetized rats will receive an i.v. dose of C3G. After 1.5 min, rats will
be euthanized, and blood, liver, kidneys and brain will be collected and further
analysed by HPLC-MS/MS and UPLC/QTOF-MS. By the first approach (target
analysis), C3G and its metabolites will be assessed; by the second one (untargeted
analysis), the changes in the metabolome will be mapped. Rats will be divided in 2
groups, one serving as control, the other will be pre-treated by the i.v. injection of a
specific, monoclonal anti-bilitranslocase antibody, cleaved to yield the so-called Fab
fragment. Fab antibodies have intact hypervariable regions interacting with the
antigen, but are devoid of the Fc shaft, thus of the capacity to activate the
complement and trigger membrane permeabilisation and injury.
oExpected results. Transport of C3G into the tissues expressing bilitranslocase should be
decreased. The influence of specific membrane transporters, e.g. bilitranslocase, in
the pharmacokinetics and pharmacodynamics of drugs (e.g. anthocyanins) will be
documented in the whole organism for the first time.
oCollaborations. Fondazione Edmund Mach-Istituto Agrario di San Michele all’Adige
(FEM-IASMA), Dr Fulvio Mattivi, Central Laboratory, Agricultural Institute of
Slovenia, Dr Andreja Vanzo, Blood Transfusion Centre of Slovenia (BTCS), Dr
Vladka Curin Šerbec.
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The Gantt diagram is appended.
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Educational activity foreseen
My educational activities are ongoing since January 2012. I am preparing a review on membrane
transporters a drug development targets. I have done an thorough literature review on the topic and
deeply studied the following review papers:
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Pharmaceutics 6, 1631-1643.
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role in drug interactions, Mol. Pharmaceutics 3, 62-69.
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antimicrobial chemotherapy, J Infect Chemother 12, 241-250.
[10] Petzinger, E., and Geyer, J. (2006) Drug transporters in pharmacokinetics, Naunyn Schmied Arch Pharmacol 372,
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for membrane transporter prediction and characterization, BMC Bioinformatics 10, 418.
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Research visits in other Institutions
A research training have been set in order to provide me with strong technical and scientific skills
about new techniques and methodologies of interest for the project: during three months at the
Fondazione Edmund Mach - Istituto Agrario di San Michele all’Adige (IASMA), I will get familiar
with principles and methods of metabolomics, metabolic profiling, mass spectrometry (MS),
advanced separation techniques, both in gas chromatography (GC) and in liquid chromatography
(UPLC).
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TAMIRAA GANBOLD
Email: [email protected]
Laboratory: TASC-INFM National Laboratory CNR-IOM
Title of the thesis: Development of quantum well structures for multi band photon detection.
Supervisor: Dr. Giorgio Biasiol
Tutors (if any): Dr. rer. nat. Ralf-Hendrik Menk
Research Activity foreseen
Preliminary experiments carried out on GaAs / InGaAs quantum well (QW) structures produced
by CNR-IOM indicate that these devices are very valuable in multi band (from infrared to hard xrays) photon detection. The narrow and direct bandgap which can be adjusted as low as 0.8 eV
allows designing very fast photon detectors with respond times in the pico second range. Moreover,
internal charge amplification mechanism can be applied for very low signal levels. Within this
thesis it is foreseen to develop segmented quantum well detectors (QWDs) that will allow to
monitor simultaneously the intensity and the position of pulsed or continuous photon beams over an
extended spectral range. These devices will be arranged off axis in a circle in the plane
perpendicular to the incident radiation, and detect the scattered radiation stemming from the
interaction of the primary beam with residual gas atoms. The backprojection of the measured
signals will allow monitoring beam intensity and beam position simultaneously without altering the
primary beam. The final product will be an extremely compact stand-alone device accommodating a
multi channel QW sensor in an ultra high vacuum environment, the readout electronics, the data
acquisition and a micro controller comprising standard interfaces. The acquisition can be
synchronized with external events and will allow closing fast feedback loops. Due to its
compactness the device can be placed close to the signal source thus minimizing electromagnetic
pick-up. Although the primary application of the QWDs will be in the field of free electron lasers
(FEL) thus of ultra bright light sources and synchrotron radiation (SR) experiments, the devices
could be readily used in combination with table top lasers and exploit other fields of photonics.
The thesis will follow three phases with a duration of one year each, comprising a preparatory
phase, construction phase and an evaluation phase.
Objectives for the first year.
Preparatory phase.
The preparatory phase includes literature research, simulation of the QWD and the design of
small prototypes. The prototypes will be grown epitaxially at the high mobility molecular beam
epitaxy system at CNR-IOM, and devices will be fabricated in the CNR-IOM clean room facility.
They will be tested with existing low noise, multi channel readout electronics provided by
Sincrotrone Trieste. A small system consisting of 4 sensors will be assembled and back projection
algorithms will be tested. The objective of the first year is the proof of principle that such device
can be operated under the experimental conditions of the FERMI free electron laser.
Objectives for the second year.
Construction phase.
The construction phase includes optimization of the QWDs developed in the preparatory phase
and the realization of the multi channel QWDs. Thorough tests of this multi channel sensor will be
carried out at the FERMI FEL and at one of Elettra's bending magnet beamlines using the
polychromatic SR. Using sufficient sensors (>16) the reconstruction of the beam cross section from
the measured projection data should be feasible.
Objectives for the third year.
Evaluation phase.
Thorough tests of the multi channel sensor developed in phase two will be continued. Different
reconstruction approaches (filtered back projection, arithmetic reconstruction) will be tested and
compared to real beam cross section measures by invasive beam viewers.
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ANDREI CRISTIAN IONESCU
Email: [email protected]
Laboratory: Department of Medical Sciences, University of Trieste, Italy
Title of the thesis: The influence of resin-based dental materials upon oral biofilms development.
Supervisor:Prof. Milena Cadenaro
Tutor: Prof. Lorenzo Breschi
Research Activity foreseen
State of the art and motivations
Restorative dentistry achieved a constant technological progress in the last years, reaching one of
the highest levels of advancement in developing nanofilled composite restorative materials. These
materials show advanced mechanical and optical properties, reaching structural and aesthetic
performances comparable or very similar to those of dental tissues (1), yet a significant part of
resin-based composite (RBC) restorations undergoes failure.
The main reason for restorations failure overtime is secondary caries occurrence, that is a
reappearance of the infectious process in the hard tissues close to the restoration (2). The process is
generated by unfavorable interactions between the biofilm that colonize the surfaces of a restoration
and the surrounding tissues. In vivo studies demonstrated that oral biofilm development on RBC
restorations is higher than that occurring on natural teeth surfaces or on the surfaces of restorations
made of other materials (3). A possible explanation for this behavior may be referred to the
structure of the RBC surface. Surface finishing, indeed, significantly reduced adherent biomass on
RBC surfaces by exposing a higher amount of inorganic filler to the surface and reducing the
exposure of the resin matrix (4). The interactions between oral microflora and dental hard tissues
may therefore be influenced by the biological behavior of the RBC restorations.
The possibility of incorporating nanoparticles into RBC composition has been recently studied, with
the final aim of obtaining restorations that are able to positively interact with the oral microflora,
thus reducing the risk of secondary caries occurrence (5).
Preliminary studies highlighted promising antibacterial properties for some of the considered
nanoparticles, such as silver nanoparticles, amorphous calcium phosphate, chitosan and quaternary
ammonium salts-containing nanoparticles (6-9).
References:
1.Mitra SB, Wu D, Holmes BN. An application of nanotechnology in advanced dental materials.
JADA 2003; 134: 1382-1390.
2.Deligeorgi V, Mjor IA, Wilson NH. An overview of reasons for the placement and replacement of
restorations. Prim Dent Care 2001; 8: 5–11.
3.Hahn R, Weiger R, Netuschil L, Bruch M. Microbial accumulation and vitality on different
restorative materials. Dent Mater 1993; 9: 312–316.
4.Ionescu A, Fadini L, Brambilla E, Burgers R, Rosentritt M, Handel G, Hahnel S. Surface
properties and mutans streptococci biofilm formation on dental composites. 88th General Session
IADR 2010; Oral poster presentation.
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5.Allaker RP. The Use of Nanoparticles to Control Oral Biofilm Formation. J Dent Res 2010;
89(11): 1175-1186.
6.Morones JR, Elechiguerra JL, Camacho A, Holt K, Kouri JB, Ramirez JT. The bactericidal effect
of silver nanoparticles. Nanotechnology 2005; 16: 2346-2353.
7.Beyth N, Yudovin-Farber I, Perez-Davidi M, Domb AJ, Weiss EI. Polyethyleneimine
nanoparticles incorporated into resin composite cause cell death and trigger biofilm stress in vivo.
PNAS 2010; 107 (51): 22038–22043
8.Cheng L, Weir MD, Xu HHK,. Antonucci JM, Kraigsley AM, Lin NJ, Lin-Gibson S, Zhou X.
Antibacterial amorphous calcium phosphate nanocomposites with a quaternary ammonium
dimethacrylate and silver nanoparticles. Dent Mater 2012; 28: 561-572
9.Qi LF, Xu ZR, Jiang X, Hu CH, Zou XF. Preparation and antibacterial activity of chitosan
nanoparticles. Carbohydrate Res 2004; 339: 2693-2700
Objectives for the first year
Completing the first part of the research project, and in particular:
- Surface characterization of experimental nanofilled RBCs with different filler content;
- Evaluation of biofilm development on the surfaces of the experimental RBC and correlation of
differences in bacterial colonization with surface characteristics;
- Preliminary study on the effect of aqueous solution of chitosan nanoparticles on oral biofilms;
Objectives for the three years
-Following the first part of the research project, a series of studies will be made in order to find a
successful antibacterial nanoparticles formulation to be blended into a RBC formulation:
- study on the effect upon oral biofilms of chitosan nanoparticles incorporated into RBC or onto the
surface of RBC by addition of acrylic functional groups;
- study on the antibacterial effect of chitosan additioned with silver nanoparticles, and its possibility
to be incorporated into the formulation of a RBC;
- final part of the project: testing a novel nanoparticle-containing RBC with antibacterial properties.
Tests will be made to assess the duration of the antibacterial capacity over time.
.
Research project
To evaluate the in vitro development of oral biofilms on the surfaces of nanofilled RBC in
controlled conditions using a continuous flow bioreactor (artificial mouth system, AMS), with the
aim of discriminating the parameters influencing the biological behavior of these materials.
Surface characterization will be performed considering the following parameters: surface
roughness, surface free energy, superficial chemical composition. To this purpose tools such as
surface profilometer, optical tensiometer, atomic force microscope (AFM), surface X-ray
protoelectron spectroscopy (XPS) will be used. Biofilm development will be monitored using
quantitative evaluation of bacterial metabolism (MTT assay) and morphological observations of the
biomass by using scanning electron microscope (SEM) and confocal laser-scanning microscope
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(CLSM). The latter tool will be able to provide a semi-quantitative analysis of the distribution of
live and dead bacterial cells, their metabolism and the extra-cellular matrix synthesized by them, in
particular at the interface between biofilm and RBC surface.
Results of this first phase will provide a better comprehension of the parameters that influence
microbiological interactions with RBC nanofillers, with the aim of reducing biofilm development
on the surfaces of the studied materials.
In the following phase, different antibacterial nanoparticles in varying concentrations will be
blended into experimental RBC. These materials will be evaluated with the same procedure of
surface analysis and biological behavior already described. In addition, mechanical characteristics
(flexural strength and elastic modulus) will be determined for each tested material to verify that the
addition of nanoparticles did not affect its load-bearing capability.
Results ought to lead to the development of novel bioactive RBCs capable of reducing secondary
caries occurrence.
Educational activity foreseen
Participation to international dental meetings in which microbiological performances of dental
materials are discussed, such as the AIC meeting on May,4-5; participation to a closed meeting with
professors David Pashley and Franklin Tay from the Medical College of Georgia, U.S.A. regarding
the same topic and the development of novel adhesive systems.
- Study of published works on antibacterial properties of nanoparticles in order to select the most
appropriates to be included in the research project;
- Acquisition of knowledge about physical behavior of antibacterial nanoparticles and the best
means to synthesize each of them.
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GIACOMO LOVAT
Email: [email protected]
Laboratory: IOM-CNR Istituto Officina dei Materiali and ALOISA-HASPES beamline at Elettra
synchrotron light source.
Title of the thesis: Study of charge transfer at interfaces relevant for photovoltaic applications
Supervisor: Prof. Alberto Morgante
Tutor: Dr. Luca Floreano
Research Activity foreseen
State of the art and motivations
Organic heterojunctions made up of small molecules donor-acceptor layers are one of the most
promising systems for the development of new photoelectric devices, such as organic light-emitting
diodes (OLED) and organic photovoltaic (OPV) cells. Small molecules OPV cells rely on electronhole pairs (excitons) generation by light absorption, their dissociation at the heterojunction and the
subsequent charge carrier collection at the electrodes. The efficiency of such processes depends
strongly on the chemistry and nanoscale morphology of the donor-acceptor interface and of the
electrode-active layer interface. The former determines the exciton dissociation rate, while the latter
is important for the effective charge collection. Good interface control is a major challenge towards
boosting the overall efficiency of OPV devices, which still remains around 7-8%, thus opening the
way to their large-scale commercialization.
The stacking of small planar organic molecules on metal or dielectric surfaces can be viewed as an
archetypal model of the interface between the active part and the electrodes in an OPV device. The
active part can consists of a single organic film supported onto a dielectric (TiO 2, which can be
suitably prepared to function as transparent conducting oxide for one electrode) or a heterojunction
confined between two metallic layers. The PhD project aims at the morphological and
spectroscopical characterization of organic thin films and donor-acceptor bilayers on metals and
metal oxides (in particular on TiO2), so as to gain insight into the ordering, the molecule-substrate
and intermolecular charge transfer and transport properties exhibited by such archetypal models.
The ideal hybrid junction is obtained by molecules overlapping their π orbitals to the substrate
charge density, which is the standard configuration for the first layer of poly- and hetero-aromatic
molecules on metals. Unfortunately, in most cases a molecular reorientation takes place from the
second layer on, where van der Waal's intermolecular forces drive the molecular self-organization,
thus originating topological defects that increase the device inner resistance. On the other hand,
optimal π coupling is also required in donor-acceptor pairs to enhance the charge transfer. The
difficult task is to preserve this coupling geometry when the molecules are brought in contact with a
substrate, either a metal electrode or a supporting dielectric. Preserving i) the optimal π coupling
between the molecules, ii) its coherence with the contact layer, and iii) a good degree of
orientational order (lateral coherence) does not simply allow the realization of an ideal device
(which would be hardly engeneered into a production chain), rather it makes possible the study of
fundamental properties for a thorough development of model systems with an effective predictive
capability.
Noble metal (Cu, Ag, Au) low index crystalline surfaces, although regarded as poorly reactive
substrates, generally display the occurrence of a static charge transfer to the adsorbed molecules. On
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noble metal surfaces, the mixing of molecular species with complementary affinity leads to the selforganization of ordered structures held together by weak and reversible van der Waals interactions,
hydrogen bonds [2], and metal-ligand interactions [3]. In addition, the substrate charge density
mediates the molecule-molecule cross-talk, possibly giving rise to the rearrangement of the
molecular levels in adjacent molecules, as recently verified for the case of 2D donor-acceptor
binary layers on a metal substrate, where suitable substitution of either molecule peripheral atoms
yields the formation of a mixed mesh connected through hydrogen bonds [4]. This result could
allow the tuning of the relevant molecular interactions by the appropriate choice of molecular
species in mixed supramolecular assemblies, a new step towards controlled growth of functional
organic nanostructures. However, the hydrogen-bond based structures are inherently fragile because
of the weak intermolecular interactions. Stabilization of the supramolecular 2D network in a
controlled way directly on a surface through irreversible covalent bonding could overcome these
limitations [5]. The investigation of the electronic structure of these 2D donor-acceptor binary
networks by synchrotron radiation techniques will be part of this research project.
Among common dielectrics, the rutile TiO2 (110) surface is strongly anisotropic and can be
exploited to steer the orientation of a growing molecular film due to the presence of periodically
spaced rows of oxygen atoms protruding from the surface plane [1]. These oxygen rows are easily
reduced in vacuum by thermal desorption of oxygen atoms, which leaves the surface with an excess
of charge that is manifested in the valence band photoemission spectrum by the emergence of a
defect state in the bandgap close to the conduction band minimum [6]. The conductivity of the TiO 2
surface can thus be tuned via enhancement or quenching of the defect state by adsorption of
electron acceptor or donor molecules. Defect-free rutile (110) can also be regarded as a relatively
inert substrate suitable to probe the intermolecular interactions and the charge transfer between
donor and acceptor layers, since weak van der Waals forces bind the first adlayer on top of the
substrate. This substrate represents a suitable candidate for the growth of stacked layers of donoracceptor pairs. With respect to noble metal surfaces, the intrinsic properties of a chosen donoracceptor dyad can be studied already in a single stacked bilayer, since substrate charge transfer can
be switched off, in addition a high degree of orientational order might be preserved within the film.
References
[1] V. Lanzilotto, C. Sanchez-Sanchez, G. Bavdek, D. Cvetko, M.F. Lopez, J.A. Martin-Gago, and
L. Floreano, “Planar growth of pentacene on the dielectric TiO2(110) surface”, J. Phys. Chem. C
115 (2011) 4664.
[2] Barrena E., de Oteyza D. G., Dosch H., Wakayama Y., “2D Supramolecular Self-Assembly of
Binary Organic Monolayers ”, ChemPhysChem 8 (2007) 1915.
[3] Barth J. V., Costantini G., Kern K., “Engineering atomic and molecular nanostructures at
surfaces ” Nature 437, (2005) 671.
[4] D.G. de Oteyza, J.M. Garcia-Lastra, M. Corso, B.P. Doyle, L. Floreano, A. Morgante, Y.
Wakayama, A. Rubio, J.E. Ortega, “Modified molecule-substrate coupling in self-assembled donoracceptor nanostructures”, Adv. Func. Mat. 19 (2009) 3567.
[5] Sedona F., Di Marino M., Sambi M., Carofiglio T., Lubian E., Casarin M., Tondello E.,
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“Fullerene/Porphyrin Multicomponent Nanostructures on Ag(110): From Supramolecular SelfAssembly to Extended Copolymers”, ACS Nano 4, (2010) 5147.
[6] P. Krueger, S. Bourgeois, B. Domenichini, H. Magnan, D. Chandesris, P. Le Fevre, A.M.
Flank, J. Jupille, L. Floreano, A. Cossaro, A. Verdini, and A. Morgante, “Defect states at the
TiO2(110) surface probed by resonant photoelectron diffraction”, Phys. Rev. Lett. 100 (2008)
055501.
Objectives for the three years
The objectives of the PhD project for the three years include:
 Learning the functioning and handling of complex experimental apparatuses in order to be
able to set up and perform independently a number of experiments based on spectroscopic,
diffractive or atomic microscopic techniques.
 Characterizing the morphology and electronic properties of donor and acceptor molecules
on metal or dielectric substrates via a variety of surface probing techniques: x-ray and
ultraviolet photoemission (XPS/UPS), resonant photoemission (RPES), x-ray near edge
absorption (NEXAFS), photoelectron diffraction (PED), Helium atom scattering (HAS) and
scanning tunneling microscopy (STM).
 Reproducing the x-ray photoemission and absorption experiments by means of numerical
simulations based on Density Functional Theory (DFT) and its plane wave implementation
in the QuantumESPRESSO package.
Objectives for the first year
The objectives for the first year are:
 Theoretical modeling (DFT simulations) of the chemical bonding, core level XPS energies
and NEXAFS spectra of systems made up of two organic self-assembled monolayers (SAM)
grown on top of each other on a metal substrate (Au (111)).
 STM measurements on perylene and perylene derivatives (PTCDI, perylene tetracarboxylic
diimide) deposited on rutile TiO2 (110) surface in UHV conditions.
 HAS/UPS study of donor molecules (phthalocyanines and porphyrins) on rutile TiO2 (110)
and their interaction with the defect state.
Research project
Activity 1: study of the monolayer of acceptor (perylene and perylene derivatives) and donor
(porphyrins and phthalocyanines, both metal-free and metalated ones) molecules on a metal
substrate (Au (110)) and on rutile TiO2 (110) by means of the aforementioned spectroscopic,
diffractive and microscopic techniques.
Activity 2: study of the vertical stacking of a donor-acceptor bilayer on rutile TiO2 (110).
Combination between a carbon-pure molecule (C60 or pentacene) and a nitrogen marked one
(PTCDI or porphyrins) will be considered for spectroscopical discrimination. The Au (110)
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substrate will also be considered for the specific cases where the first adlayer binds weakly to it.
Activity 3: modeling of the electron dynamics in a monolayer and in a vertically stacked donoracceptor bilayer. The investigation will be performed by means of x-ray spectroscopic techniques,
in particular RPES at selected ionization thresholds.
Activity 4: describing the electronic properties (core level XPS shifts and NEXAFS spectra) of the
monolayers and donor-acceptor bilayers via DFT numerical simulations with the
QuantumESPRESSO software package.
Gantt chart:
Activities
Year I
Year II
Year III
1
2
3
4
Educational activity foreseen
Participation in the following schools is foreseen:
1. School on synchrotron and FEL based methods and their multi-disciplinary applications (80
h lectures + computer sessions). Organizers: N. Binggeli, M. Kiskinova, F. Mulhauser.
Period: 19 – 30 march 2012. Institution: ICTP.
2. School on numerical methods for materials science related to renewable energy
applications (40 h lectures + computer sessions). Organizers: F. De Angelis, S. Fabris, R.
Gebauer and N. Seriani. Period: 26 – 30 november 2012. Institution: ICTP.
In agreement with my supervisor, in the first year I will replace courses and lectures at university
with the study of the following textbooks and articles:
1. J. Stöhr, NEXAFS spectroscopy: Ch. 2, 3, 4, 5, 6, 7, 8
2. C. Brouder, Angular dependence of x-ray absorption spectra J. Phys. Cond. Matt. 2 (1990)
3. D. S. Scholl, J. Steckel, Density Functional Theory: a practical introduction: Ch 1, 2, 3, 4,
9, 10
4. R. Martins, Electronic structure: basic theory and practical methods: Ch 1, 2, 3, 4, 6, 7, 8,
9, 10, 11, 12, 13
5. References [1]-[6].
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DOMENICO MARSON
Email: [email protected]
Laboratory: MOSE
Title of the thesis: Coupling of experimental and computational approaches for the development of
new dendrimeric nanocarriers for gene therapy.
Supervisor: Pricl Sabrina
Tutors (if any): Laurini Erik
Research Activity foreseen
State of the art and motivations
Recent studies have focused on the application of nanotechnology in the development of
nanocarriers for RNA-interference (RNAi) based therapies. In such approach, small RNA
sequences (Short Interfering RNA, siRNA) are exploited to switch off specific genes 5. siRNA are
promising candidates for the treatment of diseases that today are very difficult to treat
pharmacologically, such as inherited genetic maladies (Huntington’s, sickle cell anemia, cystic
fibrosis…), tumors, or specific infectious diseases (AIDS, hepatitis…). A major obstacle to the
clinic exploitation of small siRNAs is their cell delivery. Indeed, siRNAs need a carrier to protect
them while traveling in the bloodstream, and to lead them into the target cells. Nowadays, various
kind of carriers have been developed: those based on viral agents are particularly effective, but at
the same they are extremely expensive and dangerous for the health of the patient. Therefore, lipids
and polymers are presently the most common non-viral vectors under investigation.
Dendrimers and dendrons are among the most promising groups of nanocarriers for the purpose of
gene delivery. These molecules are a class of polymers characterized by a branched structure and a
widely functionalized surface.
One of the critical points of these nanocarriers is to find the right balance that allows them to bind
effectively to protect the siRNA and to release it near its specific target to perform its function at the
same time. The following features are considered essential to determine a good drug delivery
sistem:
1. Recognition of the cell or target tissue;
2. Ability to deliver the drug only in the target site;
3. Ability to carry more terapeutic agents.
The optimal strategy to achieve the first two features seems today to tie to the nanovector some
structures suitable for recognition, such as antibodies. Antibodies are themselves macromolecules,
and they could be recognised by the immune system, and so be inactivated. In this perspective, the
use of dendrimers/dendrons will also protect the antibodies from their natural degradation.
Objectives for the three years
5
(a) G. J. Hannon, Nature 2002, 418, 244-251. (b) M. T. McManu, P. A. Sharp, Nature
Reviews, 2002, 3, 737-747. (c) R. Agami Current Opinion in Chemical Biology 2002, 6,
829–834.
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One of the objectives of this project is to evaluate the characteristics of the conjugate siRNAdendrimer (or dendrone), and his complexes with antibodies/proteins, in order to improve its
properties and to reduce as much as possible the side effects. To achieve this objective, it will be
appropriate to exploit molecular simulation techniques for in silico screening and subsequent
optimization of the most promising dendrimeric carrier, with the purpose of drastically reducing the
time and costs at the developing level.
The main objectives for the three years will be:
- Investigation of first generation dendrimers/dendrons coupled with a specific ligand, siRNA or
antibody. From molecular dynamic techniques is possible to get information at the molecular level
(binding free energies, interaction forces, optimal structures...) that would not be possible to achieve
with experimental techniques.
- Development end refinement of a multiscale protocol to study the interactions between the
complex nanocarrier-siRNA and DNA/proteins.
- Identification of the molecular parameters critical to optimize the design de novo of second
generations nanocarriers.
- Development of new models of structure/activity relationships for the design of new generation
dendrimers (or dendrons) more effective and selective for the targeted delivery of siRNA.
Objectives for the first year
- Investigation of first generation dendrimers/dendrons coupled with specific ligand, siRNA or
antibody.
- Development of a multiscale protocol to study the interactions between the complex nanocarriersiRNA and DNA/proteins.
Research project
This project could support, exploiting multi-scale molecular modeling techniques, the experimental
groups that synthesize dendrimers and dendron as nanocarrier. The intention is to define the
molecular characteristics necessary to obain the optimal dendrieric carrier for the transport of
siRNA. More specifically, it’s possible to examine the properties of the delivery systems and their
interactions with the siRNA, with the purpose of optimize these interactions.
The main goals aim to develop computational techniques would be:
- Investigation of first generations dendrimers/dendrons coupled with specific ligand or
antibody.
o The purpose here is, by applying a multiscale simulation strategy, to study the
properties of the carriers and their interactions with siRNA. From molecular dynamic
techniques is possible to get information at the molecular level (binding free
energies, interaction forces, optimal structures...) that would not be possible to
achieve with experimental techniques.
oThe activity will be mainly focused on the design of dendrimer-protein complexes, the
formation of the siRNA/carrier complex, the interactions with the target receptors on
the cell and the ability of the carriers to reach an effective therapeutic concentration
at their specific target site.
- Identification of the molecular parameters critical to optimize the design de novo of second
generations nanocarriers.
o Based on the results obtained, a second phase can be dedicated to the computer-aided
design of new dendrimer/dendrons able to:
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 optimize the bonds with the carried molecules;
 increase the selectivity for the target cells or tissue;
 increase the release of the siRNA on the target site.
- Structure/activity relationships analysis, for the design of new generation dendrimers (or
dendrons) more effective and selective for the targeted delivery of siRNA.
o The results of molecular simulations could then be directly correlated with the
experimental evidences. All this would be done with the ultimate goal of better
understanding the molecular mechanism of interaction siRNA/dendrimer that, to
date, is not so clear. New models of structure/activity relationship could be
developed to aid the design of new dendrimers/dendrons always more effective and
selective for the targeted delivery of siRNA.
MONTHS
YEAR 1
TASKS
1
2
3
4
5
6
7
YEAR 2
8
9
10
11
12
1
2
3
4
5
6
7
YEAR 3
8
9
10
11
12
1
2
3
4
5
6
7
8
9
10
11
12
Definitions of the
characteristics of first
generation vectors
Development and
validation of a multiscale
simulation protocol
Identification of the
critical properties of the
nanocarriers
Design of second
generation vectors
Results discussion
Research Activity
 “Catch me if you can: ligand/antibody conjugated PAMAM dendrimer.” RCOM7
Conference.
 “Nanozapped! DNA and its dendritic nanovectors: a combined in silico/in vitro
approach.”, FOMMS 2012 Conference.
 “Tell Me Something I Do Not Know. Multiscale Molecular Modeling of
Dendrimer/Dendron Organization and Self-Assembly In Gene Therapy.”, Current
Medicinal Chemistry (in press).
 “Another brick in the wall. Validation of the σ1 receptor 3D model by computer-assisted
design, synthesis, and activity of new σ1 ligands.”, Molecular Pharmaceutics
(submitted).
 “Genes within bottles. Synergism between simulation and experiment in designing
nanovectors for DNA/RNA delivery.”, Chemical and Biochemical Engineering
Quarterly (submitted).
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Educational activity foreseen
- “Annual Conference of the Ph.D. School of Nanothecnology.”, January 16-18, 2012,
Trieste (Italy)
- “Spring course on Powder Diffraction Method for Nanostructured Materials.”, March 15,
2012, University of Trieste (Italy).
- “School of Synchrotron and FEL Based Methods and their Multi-Disciplinary
Applications.”, March 19-30, 2012, Miramare, Trieste (Italy).
- “Nanotechnology Summer School 2012.”
- “Machine learning in atomistic simulation.”, September 10-12, 2012, Lugano
(Switzerland).
- “Tutorial for the AMBER set of modelling tools.”, October 8-12, 2012 Lousanne
(Switzerland).
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MARYSE DADINA NKOUA NGAVOUKA
Email: [email protected]
Laboratory: NanoInnovation Laboratory (Sincrotone Trieste)
Title of the thesis: Application of AFM based immune assays to few cells proteomics
Supervisor: Prof. Giacinto Scoles – Dr. Loredana Casalis
Tutors (if any):
State of the art and motivations
In the last two decades, many researchers in the field of nanotechnology aimed at developing
innovative, biosensors capable to investigate gene expression profiling of cells in healthy and
diseased organs, crucial in clinical research for the understanding of disease pathology at the
molecular level, for identifying new therapies and also, at a more fundamental level, to understand
protein pathways and, more generally, the biology of the cell. Most of the existing immunology
assays are based on measuring cells and their interactions on a large scale. However, the cellular
and molecular complexity of, for instance, a solid tumor microenvironment calls for the need of
studing signaling in individual cancer cells [C. Ma et al., Nature Medicine 17, 738 (2011)]. Also,
the analysis of circulating tumor cells where there can be as few as one cell in a clinical blood
sample requires single cell sensitivity. Test based on mass spectrometry, on ELISA platforms or on
standard microarrays requires a too large number of cells and cannot easily approach single cell
proteomics. New methods for the examination of single cells from small samples volumes would be
therefore of a great help [A. Salehi Rehany et al., Lab Chip, 11, 1256 (2011), J. Choi, ibc, 2, 1—
1(2010)]. The small analyte volume (pL to nL) corresponding to a few cells lysate imposes the
miniaturization of the sensor. In the case of arrays, reducing the size of each spot in the array
helps, up to a certain limit, also to increase the surface density of the probes and therefore the
signal-to-noise (S/N) ratio of the device, and then provide the best sensitivity, especially for
proteins present in a low copy number (often the most relevant to the disease).
The framework of this project is to develop a device capable of rapid and accurate detection of
proteins in rare cells. My work will be about the optimization of a nano-array format recently
introduced for the high sensitivity detection of biomolecules, based on AFM (Atomic Force
Microscopy) nanografting [Bano F. et al, Nano let. 9(7): 2614-18 (2009); Sanavio B. et al., ACS
nano. 4(11): 6607-16(2010)], to show its applicability to the very high sensitivity detection of
cancer biomarkers (and, lately, antibody-based cancer drugs). In such nano-arrays protein-capture
molecules density and protein orientation can be optimized, avoiding steric hindrance of the
bioactive sites, maximizing in this way the biological activity of the proteins and, as a consequence,
the sensitivity of the array and last but not least making the protein assay more reproducible. The
immobilization and control of the orientations of the immunoarrays will be made by the so-called
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DNA-Direct Immobilization (DDI) of protein/antibody(Ab)-DNA conjugates [Niemeyer C. et al,
Angew Chem Int Ed Engl. 40: 3685-88(2001)], on top of DNA nanoarrays. The device is then ready
to capture specific proteins present in the cell lysate. In order to optimize the number of protein
linked on the surface, I will first characterize the process of DNA adsorption and of DNA
hybridization on the nano-spot, at each stage of device development: ssDNA physisorbed on a chip
spot, cannot guarantee reproducibility, since there is no control on the number of molecules
deposited on the spot, nor on their order (or conformational state, one base of a molecule
hybridizing with the complementary base of a next molecule). Covalent or bio-affinity linking of
the DNA to the surface is therefore required to satisfy reproducibility requests, together with fine
control on the probe density. To discriminate between single-stranded and double-stranded DNA,
AFM height profile of the DNA nano-spot can be used: DNA behaves in fact as a mechanical
transducer, being the flexibility ratio of ss- and ds- DNA of about 1:40, in standard buffer solution. I
plan to study the hybridization process at different ionic strengths, to match the salt type and salt
concentration of the particular Ab buffer solution. On the other side, a polymeric microwell devices
for trapping single-few cells will be developed, taking care of opportunely functionalize the well
surface for optimal cell adhesion and growth. This part of the work will be carried out in
collaboration with Stefania Corvaglia (PhD student, Naotechnology School of the University of
Trieste, XXV cicle). The two devices, the nanoarray and the microwell, will then be used face-toface to allow for single cell protein analysis.
Objectives for the three years
We plan to build reproducible and sensitive nanosensors for detecting proteins/antibodies in small
volume biosamples (nL or less). The assay will be based on bio-affinity immobilization of
protein/antibody on oligonucleotides nanoarrays produced by AFM nanografting. The
biorecognition events will be detected via AFM topographic imaging.
We aim at:
Developing and characterizing the capture of the protein in solution via an immobilized
antibody, by the specific choice of the protein-antibody couple.
Immobilizing and characterizing of the protein-DNA conjugate from a physico-chemical point
of view.
Optimizing biosensing protocols (hybridization efficiency, choice of protein-antibody couples,
etc.) in order to achieve sensitivity required for single-cell based assays.
Exporting our knowledge on other classes of devices based, for instance, on impedance
measurements in microfluidic channels and/or micro electromechanical sensors (MEMS).
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Objectives for the first year
Study of the state of the art through review articles and papers.
DNA functionalization by covalent linking to the surface to satisfy reproducibility requests.
Detection of DNA hybridization using an Atomic Force Microscope height and compressibility
measurements and by means of fluorescence imaging
Construction of protein nanoarrays using AFM Nanografting
Developement and optimization of functionalization chemistry in order to capture the target
cells on the microwell surface .
Research project
A proposal of the research activity represented in a Gantt diagram:
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GIULIA OTTAVIANI
Email: [email protected]
Laboratory: Molecular Medicine
- International Centre for Genetic Engineering and
Biotechnology (ICGEB). Padriciano, 99
- 34149 Trieste, Italy.
Title of the thesis: use of nanotechnology for the evaluation of the effect of laser therapy on neoangiogenesis tumor in vivo and in vitro.
Supervisor: Dott.ssa Zacchigna Serena
Tutors (if any): Dott. Biasotto Matteo
Research Activity foreseen
State of the art and motivations
Oral mucositis (OM) is referred to as one of the worst side effects of radiotherapy (RT) and/or
chemotherapy (CT).6,7
The condition results in a continuum of clinical changes that range from erythema and burning of
the oral and oropharyngeal mucosa to the development of diffuse and confluent ulcerations. 8
5- 45% of people undergoing CT develop OM, but this percentage rises up to 70- 100% if
associated to high doses, bone marrow transplantation and to RT. 9 Old people and females are more
subjected to this adverse effect, even if we can also find kind of drug, its dosage and
immunosuppression among the main risk factors.10,11,12
OM is so debilitating that it affects the patients’ quality of life, making swallowing, chewing and
phonation difficult or even impossible.13,14 Sometimes it is associated to life-threatening
complications, such as hemorrhage and infection or even tracheotomy that can lead to reduction or
suspension of therapy, thus affecting the outcome of it. Disparity exists between perceived risk and
severity of OM, the burdens these cause patients, and the burden upon healthcare system. Sonis et
al. report that patients affected by OM need morphine for 5,8 days more and parenteral nutrition for
1,9 days more in respect to patients without OM.15
6
7
Lalla RV, Peterson DE. Oral mucositis. Dent Clin North Am. 2005 Jan; 49(1): 167–184
Treister N, Sonis S. Mucositis: biology and management. Curr Opin Otolaryngol Head Neck Surg. 2007 Apr; 15(2):123–129.
8 Stephen T Sonis; Efficacy of palifermin (keratinocyte growth factor-1) in the amelioration of oral mucositis; Core Evid. 2009; 4: 199–205. Published online 2010 June 15.
9
Trotti A, Bellm LA, Epstein JB, Frame D, Fuchs HJ, Gwede CK et al. Mucositis incidence, severity and associated outcomes in
patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother
Oncol 2003; 66:253-62.
10 Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy. Clinical and
economic outcomes of chemotherapy-induced mucositis. Cancer. 2003 Oct 1;98(7):1531–1539
11 Vera-Llonch M, Oster G, Ford CM, Lu J, Sonis S. Oral mucositis and outcomes of allogeneic hematopoietic stem-cell
transplantation in patients with hematologic malignancies. Support Care Cancer. 2007 May;15(5):491–496
12 Maddireddy Umameshwar Rao Naidu, Gogula Venkat Ramana, Pingali Usha Rani, Iyyapu Krishna Mohan, Avula Suman, and
Priyadarshni Roy; Chemotherapy-Induced and/or Radiation Therapy-Induced Oral Mucositis—Complicating the Treatment of
Cancer; Neoplasia. 2004 September; 6(5): 423–431.
13
Ohrn KE, Sjoden PO, Wahlin YB, Elf M. Oral health and quality of life among patients with head and neck cancer or
haematological malignancies. Support Care Cancer. 2001;9:528–538.
14
Zittoun R, Achard S, Ruszniewski M. Assessment of quality of life during intensive chemotherapy or bone marrow.
Psychooncology. 1999 Jan-Feb;8(1):64-73.
15
Sonis ST, Oster G, Fuchs H, Bellm L, Bradford WZ, Edelsberg J et al. Oral mucositis and the clinical and economic
outcomes of hematopoietic stem cell transplantation. J Clin Oncol 2001;19:2201-2205.
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It is of even greater economic import that the serious outcomes of OM led to significantly more
days of hospitalization per cycle: economically significant events. The additional estimated cost per
person in case of OM is around $42.749, in patients subjected to hematopoietic stem cells
transplantation. Elting et al. consider an increasing cost of 2.725$ per person for each CT cycle in
case of grade 1-2 of OM and of 5.565$ in case of grade 3 and 4. This calculation can even be
exacerbated in case of concomitant RT/CT. 16
Unfortunately, a standard therapy is still not available.
Recent findings confirm that laser therapy can be very useful to manage OM.
Many articles mention Laser Therapy (LT) as an innovative approach and confirm that its efficacy
is due to intracellular mechanisms involving the mitochondrial chain reactions through
chromophores activation by laser light.17,18
Since radiation emitted by level lasers (LL) has shown analgesic, anti-inflammatory and healing
properties, they have been widely used in the process of tissue repair, for their wavelength and low
densities of energy can penetrate tissues. According to Genovese’s citations,19 the biological effects
caused by LL in tissues consist of light energy, which is deposited on the tissues and which become
vital energy, thus producing primary effects (direct), secondary effects (indirect), and general
therapeutic effects, which promote analgesic, anti-inflammatory, and healing reactions. In detail,
laser light increases the releasing of ATP enhancing RNA and DNA formation, fibroblasts
proliferation, cytokines, lymphocytes, mast-cells, ROS and PG synthesis.20,21,22 One of the most
important consequences of laser light tissues’ stimulation is neoangiogenesis. In fact, the antiinflammatory and anti-edema effects exerted by laser occur through acceleration of
microcirculation, resulting in changes in capillary hydrostatic pressure. At the vascular level, LL
stimulates proliferation of endothelial cells, resulting in formation of numerous blood vessels and
increased production of granulation tissue. It also stimulates vascular smooth muscle relaxation,
thus contributing to the analgesic effects of laser therapy.23,24 Together with fibroblasts
16
Linda S. Elting Dr.P.H, Catherine Cooksley Dr.P.H.,Mark Chambers M.D., Scott B. Cantor Ph.D.,Ellen Manzullo M.D., Edward
B. Rubenstein M.D; The burdens of cancer therapy; Cancer 200; 98,7:,1531–153.
17 Karu, T.I.; Molecular mechanism of the therapeutic effect of low-intensity laser radiation; LasersLife Sci., 2, 53, 1988.
18 Karu; LOW POWER LASER THERAPY; CH 48, paragraph 48.3.2.
19
Genovese JW. Laser de baixa intensidade: aplicacoes terapeuticas em odontologia. Sao Paulo: Lovise Ltda;
2000. 175p.
20 Karu, T.I., Kalendo, G.S., and Letokhov, V.S.; Control of RNA synthesis rate in tumor cells HeLa by action of low-intensity
visible light of copper laser; Lett. Nuov. Cim., 32, 55, 1981.
21 Ronit Lavi, Asher Shainberg, Harry Friedmann, Vladimir Shneyvays, Ophra Rickover, Maor Eichler, Doron Kaplan, Rachel
Lubart; Low Energy Visible Light Induces Reactive Oxygen Species Generation and Stimulates an Increase of Intracellular Calcium
Concentration in Cardiac Cells; J Biol Chem. 2003 Oct 17;278(42):40917-22. Epub 2003 Jul 7.
22 Chen AC, Arany PR, Huang YY, Tomkinson EM, Sharma SK, Kharkwal GB, Saleem T, Mooney D, Yull FE, Blackwell TS,
HamblinM; Low Level Laser Therapy Activates NFkB via Generation of Reactive Oxygen Species inMouse Embryonic Fibroblasts;
PLoS One. 2011;6(7):e22453. Epub 2011 Jul 21.
23
Ruthineia Diogenes Alves Uchoa Lins Euler Maciel Dantas Keila Cristina Raposo Lucena Maria Helena Chaves
Vasconcelos Catao Ana Flavia Granville-Garcia Luiz Guedes Carvalho Neto Biostimulation effects of low-power laser
in the repair process; An Bras Dermatol. 2010;85(6):849-55.
24
Walsh LJ. The current status of low level laser therapy in dentistry. Part 1. Soft tissue applications. Austr Dental J.
1997;42:247-54.
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proliferation, these can be considered the most relevant elements of tissue regeneration and wound
healing. Also, it is confirmed that laser therapy has an analgesic and antimicrobical effect.25
During the last two years our research group has been dedicated to the study of laser therapy as
possible effective remedy for the care of this debilitating cancer treatment side effect. We have
already accumulated experience on both animal experimentation, in collaboration with the ICGEB
located at Area Science Park, and clinical application of the technique (on over 60 cancer patients
visited and treated with the laser therapy at the Division of Oral Medicine and Pathology, at
Ospedale Maggiore in Trieste). Both approaches support the effectiveness of laser therapy as a
valuable therapeutic aid able to confer analgesia, reduction of inflammation, biostimulation and
disinfection of the mucositis lesions. Specifically, the biostimulation has been possible thanks to the
neo-angiogenesis given to the injury, which allows a significant reduction of the healing time.
The results we obtained during the last two years of study were encouraging and prompted further
investigations on the mechanisms of actions of laser therapy, as well as on possible side effects.
Objectives for the three years
On the basis of the information obtained so far, we propose to: i) investigate the effect of laser
therapy on tumour neo-angiogenesis in a mouse model, ii) analyze which genes are involved in this
process, and iii) compare the results obtained on animals to the clinical practice, and in particular to
the NBI fiberscope, which also essentially evaluates angiogenesis.
Objectives for the first year
Since angiogenesis is expected to be one of the main achievements of laser biostimulation and may
represent an undesired side effect for a patient bearing a tumor of the oral cavity, we will use a
carcinogenesis mice-model to verify its effect on tumor-associated angiogenesis, and subsequent
tumor growth.
A total of 20 C57/B6 female mice with a mean weight of 18-20 g, 4-6 weeks old, will be housed in
appropriate sterile cages and fed and given water ad libitum.
4NQO obtained from Sigma-Aldrich will be dissolved in propylene glycol (Sigma-Aldrich) as stock
solution (4mg/ml), stored at 4°C, and diluted in the drinking water to a final concentration of
50µg/ml. Water will be changed weekly. To induce oral carcinogenesis, all mice will be given
4NQO in the drinking water for 16 weeks, after which all animal cages will be reverted to regular
water and mice will be monitored until week 22. All animals will undergo a biweekly full oral
cavity examination under general anesthesia (2-5% isoflurane (Baxter) mixed with oxygen) and
pathologic changes will be documented.
During the 17th week, the animals will be treated with laser therapy for 4 consecutive days.
25
Karu T; Mechanisms of low-power laser light action on cellular level; Institute of Laser and Informatic Technologies of Russian
Acad. Sci., 142092 Troitsk, Moscow Region, Russian Federation.
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Tumor-area will be directly irradiated. Laser pointer will be kept one centimeter far from the tongue
and continuously moved during therapy.
Animals will be euthanized on week 18 and 22 for tissue retrieval. Complete autopsies will be done
and tissues will immediately be collected and fixed in buffered zinc formalin at room temperature
for 12h. The tissues will be then transferred to 70% alcohol and processed for paraffin embedding
for further studies. Histopathological examination will be performed by three independent
reviewers.
Using this model, we aim to specifically evaluate the role of laser therapy on tumour angiogenesis
by perfusing the tumor with fluorescent spheres having a diameter in the 20-200 nm range, followed
by quantitative evaluation of the fluorescence and 3D reconstruction f the vascular network by
confocal microscopy.
Write a description of the objectives to be reached in the first year. Few lines and a bulleted list is
sufficient.
Research project
AIM1. CONSTRUCTION OF A CARCINOGENESIS MICE-MODEL AND USE OF
NANOFLUOSFERE TO QUANTIFY VASCULARIZATION.
See objectives for the first year.
AIM2. SELECTION OF GENES INVOLVED IN LASER-INDUCED NEO-ANGIOGENESIS.
Through a diode laser, set on specific wavelengths, cellular genes potentially involved in laser
therapy induced-neoangiogenesis, will be studied by high throughput screening (HTS), by
exploiting the availability of a whole genome siRNA collection and a HTS facility at ICGEB in
Trieste. Cell-based assays for high-content microscopy will be optimized for genome-wide siRNA
library screening based on laser-induced proliferation and migration functional assays. Screening
with the whole-genome siRNA library targeting the totality of the human annotated genome (18175
genes, pools of 4 siRNA per gene) will then be performed, followed by target validation by standard
siRNA pool deconvolution procedures. Genes identified to have a specific effect on endothelial cell
function upon stimulation with the three different ligands will be further analyzed by standard
bioinformatics tools (Ingenuity Pathway Analysis software), compared and contrasted among the
treatments and then followed up individually.
The in vivo relevance of the genes identified by HTS will be assessed in vivo using the same model
described above. The 5 top siRNA will be administered to tumor-bearing mice undergoing laser
therapy, using scramble siRNA oligonucleotides as controls.
When the volume of the tumor will reach 100mm3 approximately, siRNA complexes containing
2nmol siRNA will be injected intravenously through the tail vein on days 1, 4, 8, 12 after laser
therapy. Mice will then be euthanized on weeks 18 and 22 to discover if the effect of laser therapy
has been influenced by the injection of siRNA.
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AIM3. VALIDATION OF THE IN VIVO STUDY AND CORRELATION TO NBI
FIBERSCOPE.
Finally, the results obtained on animals will be compared to the images routinely obtained in the
clinics using the narrow band imaging (NBI) fiberscope. This will allow us to analyze neoangiogenesis also with this innovative technique. If it will be validated it would have important
implications on clinical oral cancer angiogenesis detection and on early dubious oral lesions, which
eventually need to be biopsied.
Activity
Year 1
Year 2
Year 3
Construction of a carcinogenesis mice-model
Use of nanofluosfere to quantify vascularization
Cellular genes involved in laser therapy inducedneoangiogenesis studied by HTS
Up and down-regulation of genes involved in tumour neoangiogenesis
Correlation to the clinical NBI fiberscope
Educational activity foreseen
The strict collaboration with the Molecular Medicine Laboratory at ICGEB will allow the
participation to the main activities organized by ICGEB for PhD students, and in particular to the
journal clubs and seminars that might be of interest for the present project (a complete and updated
list of Seminars, Meetings and Courses held at ICGEB can be found at
http://www.icgeb.org/meetings-and-courses.html and http://www.icgeb.org/seminars.html).
In addition, the Student will attend the Department of Oral Medicine and Pathology, located in
Ospedale Maggiore, to follow oncological patients during their diagnosis, surgery and prosthetic
rehabilitation. Weekly the Student will be exposed to the clinical hospital updating, regarding not
only scientific workshop on oncological topics, but also new immunohistochemical techniques to
detect and diagnose even earlier oral cancers.
The Student will participate to many international and national conferences and lectures on both on
molecular and clinical features.
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MIRCO PANIGHEL
Email: [email protected]
Laboratory: Micro and Nano Carbon Lab - Elettra
Title of the thesis: Organic Molecules and Carbon Nanotubes Assembled on Metal
Surfaces: Properties and Applications in Molecular Electronics and Photovoltaics
Supervisor: Prof. Alberto Morgante
Tutors: Dr. Andrea Goldoni, Dr. Giovanni Di Santo
Research Activity foreseen
State of the art and motivations
The control of the electronic and magnetic properties of nanostructures adsorbed on metal
surfaces is of fundamental importance from both scientific and technological point of view. For
example the study of electronic and transport properties of organic molecules, although a relatively
recent and not fully developed field, appears highly promising for the emerging spintronics and
molecular electronics, as well as for the pure basic research [1-4]. There is huge interest in these
molecules as constituents of organic-inorganic interfaces due to their flexibility and peculiar
properties. For this purpose ultra high vacuum molecular beam deposition techniques and selfassembly methods allow to engineer bulk molecular materials with long-range ordering. In
particular metal phthalocyanines (MPcs) and porphirins (TPPs) are the model candidate of
metallorganic complexes due to their ability to coordinate with many elemental ions and to selfassembly on metal surfaces: their molecular framework tunes the interactions between the
molecules and the substrate in order to constitute ordered structures on the surface, and brings
about interaction between the local magnetic moment of the molecule and the metal.
The ability of organic molecules to self-assembly on metal surfaces is particularly important
also to produce ordered substrates to be used as templates for the growth of other nanostructures:
for example the use of carbon nanotubes (CNTs) for developing high efficiency photovoltaic and
photosensitive devices is the main task in the field of organic solar cells; however, this is limited by
the difficulty in producing shaped controlled nanotubes, a fundamental requirement to have
reproducible and well defined electronic properties.
[1] Wende et al., Nat. Mat. 6, 516 (2007)
[2] Gambardella et al., Nat. Mat. 8, 189 (2009)
[3] Bernien et al., Phys. Rev. B 76, 1 (2007)
[4] Bernien et al., Phys. Rev. Lett. 102, 1 (2009)
Objectives for the three years
Preparation of the substrates for the organic molecules assembling;
Study of the electronic and magnetic properties of selected organic molecules adsorbed on
metal surfaces;
Preparation of host substrates and growth of the CNTs;
Characterization of the properties of composited nanostructures from the magnetic and
conformational point of view.
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Objectives for the first year
Upgrade of the experimental apparatus and the control software;
Individuation of the most suitable organic molecules for the project;
Developing of the preparation techniques;
Characterization of the molecules and the initial substrates.
Research project
The research project will focus on the preparation and study of different organic molecule
systems on metal surfaces, and in particular on their electronic and magnetic properties. The ability
of these molecules to self-assembly on metal surfaces allow to produce very controllable ordered
structures and the coordination with metal ions provides to the system peculiar magnetic properties
that can be studied and tuned. During the entire duration of the project will be studied and prepared
different organic based nanosystems focusing in particular on molecular electronics and spintronics
properties.. In this part will also be used organic molecules to prepare template structures for the
preparation of host adsorption sites for the consequent CNTs growth. This synthesis is based on the
use of metal or semiconducting surfaces on which the molecules can self-assembly to produce a
defined substrate: controlling the geometry of these sites the commonly used chemical vapor
deposition technique of CNTs can be simplified and optimized. Synchrotron radiation techniques
available at Elettra (XPS, UPS, XMCD) as well as experimental techniques available in the
laboratory (EELS, AFM and STM) are require for the characterization of the substrates, the
adsorbed organic molecules and the nanostructured materials based on CNTs. The structural
characterization will be also performed with scanning probe microscopy techniques (AFM and
STM) with the possibility to upgrade the experimental apparatus and the control software.
2012
2013
Experimental apparatus and software upgrade
X
X
X
X
Preparation of the substrates
X
X
X
X
Individuation of the organic molecules
X
X
X
Characterization of the substrates
X
X
X
X
Characterization of electronic and magnetic properties of the molecules
Preparation of organic molecules hosts
X
X
X
X
X
X
Carbon nanotubes evaporation
Development of composite nanostructures
X
X
2014
X
X
X
X
X
X
X
Educational activity foreseen
During the first year is desirable the attendance at schools and seminars on quantum magnetism,
molecular electronics, spintronics, carbon nanotubes growth techniques and deposition techniques
in UHV.
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LUCA PIANTANIDA
Email: [email protected]
Laboratory: CNR-IOM Laboratorio TASC
Title of the thesis: Plasmonic ruler and the applications to the DNA origami
Supervisor: Marco Lazzarino
Tutors (if any):
Research Activity foreseen
State of the art and motivations
The DNA origami method,
introduced by Rothemund in
2006 [1], allows the design
and fabrication of arbitrary
2D and 3D structures of DNA
that could be very stable and
complex. Starting from one
long single strand of DNA,
called “scaffold strand”, with
the introduction of short
oligonucleotides,
called
Fig.1 (a) Example
of a DNA origami
design;
(b)
representation
of
several
shapes
created
by
Rothemund; (c) a
DNA origami box
with movable lid
and (d) many other
3D structures with
“staple strands” which force the previous one to fold in a pre-determined way, it is possible to
complex
create a structure with the desired shape. The staple strands sequence is complementary and not
curvatures.
redundant to the scaffold sequence, in this way depending on the position and the design of the
staple strands, the scaffold assumes the desired shape. Many examples of complex structures have
been described in literature [2, 3], while few results have been reported about actuation of movable
origami [4, 5]. This technology is suitable to create a scaffold structure operating in the biological
liquid environment that provides the structural strength and flexibility necessary for a movable
actuator. Furthermore the versatile nature of the DNA allows a great possibility to functionalize the
structures, simply adding a modified staple strand sequence, allowing a big range of possible
modifications.
Recently in our group we have created a 2D DNA origami structure capable of movement after the
interaction with a DNA target molecule. It consist of a circular ring with a diameter of 100 nm and
an internal part where is allocated the actuator system. Following the hybridization between the
DNA target molecule and the actuator in the middle, the internal part moves and change its
morphological profile. The DNA origami has been characterized with atomic force microscopy
(AFM) and with fluorescence techniques. In spite of the relevant progresses in the structure analysis
we were not able to characterize this movement in detail. The speed, the direction, the movement
angle and the forces involved are still unknown parameters of the actuation. To elucidate these
characteristics we plan to use gold nanoparticles decoration and functionalization and exploit
fluorescence and plasmon resonance techniques. This last technique and in particular the localized
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surface plasmon resonance (LSPR) could help to analyze short range distance changes in
nanomaterial.
The plasmon resonance of a nano-particle depends on the NP material, shape and size. If two NP
are placed close to each other, the absorption spectrum is further modified, depending on distance
and orientation respect to the light polarization. Since the binding interactions can affect the
distances between two parts on an actuator, with this method we can obtain more information also
about the binding kinetics. These features make this technique an optimal tool to investigate
movements and interactions between two movable parts coupled with metal particles. Furthermore
when two nanoparticles are close to each other like in a dimer condition the surface plasmon
resonance increase in intensity as a field hot spot, exploiting this field enhancement we can analyze
spectroscopy features of the molecule between the two nanoparticle.
Objectives for the three years
I want to design a tool to characterize and analyze in detailed and precise way the movement and
spectroscopy features at the nano-scale in our and other system in biological conditions:
Functionalize gold nanoparticle in stable and reproducible way in order to use them in the
following parts of the project, and analyze them with different techniques;
Create a calibrated nano-plasmonic ruler with gold nanoparticles and decorate the DNA
origami structure to investigate the actuation motion;
Create a nanoparticles-dimer plasmonic hot spot tool in order to use it in spectroscopy and
also detection analysis, expecially in liquid environments;
Objectives for the first year
In the first year I have to draw up the optimized protocol for the handling of the gold nanospheres
and for their functionalization with DNA oligonucleotides . Further I should be able to create the
nanoparticle dimers and analyzing them with optical and atomic force microscopy.
Research project
The project of my research will exploit my knowledge concerning DNA origami characterization
and atomic force microscopy analysis in liquid environment to set up a plasmonic tool. The
nanoparticles interaction and DNA functionalization are the key point from which I have to start to
use them into more complex system as DNA origami. Further in the project I want to investigate the
molecular spectroscopy analysis gain that comes from surface plasmon resonance of gold
nanoparticle. For this purpose I want to use gold nanoparticle dimers to create a sort of field hot
spot in the inter-particle space, that can be used as a molecular ruler and also can enhance
spectroscopy features of molecules allocated in. Once I created the hot spot system I can exploit it
as a detection tool for target molecules that recognized by the oligonucletide situated between the
nanospheres, for instance small RNA molecules.
The project is, hence, divided into three main activities:
1.Functionalize gold nanoparticle in stable and reproducible way in order to use them in the
following parts of the project, and analyze them with different techniques;
2.Create a calibrated nano-plasmonic ruler with gold nanoparticles and decorate the DNA
origami structure to investigate the actuation motion;
3.Create a nanoparticles-dimer plasmonic hot spot tool in order to use it in spectroscopy and
also detection analysis, especially in liquid environments;
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The first activity comprise the following tasks:
Draw up a complete protocol to handling and successfully functionalize gold nanoparticles
to link principally DNA oligonucleotides to obtain dimers;
Characterize the nanospheres with electrophoresis technique and microscopy technique;
Test the stability and the efficiency of the protocol in different liquid environments;
The second activity comprise the following tasks:
Create the gold nanoparticle dimers following the protocol;
Characterize the dimer ruler with surface plasmon resonance technique and analyze it with
microscopy;
Calibrate the ruler with different inter-particle distance using different oligonucleotide
lengths;
Decorate the DNA origami with functionalized gold nanoparticle and investigate the
actuation motion with microscopy and surface plasmon resonance techniques;
The third activity comprise the following tasks:
Create the gold nanoparticle dimers following the protocol;
Use the dimers to build a plasmonic hot spot tool and characterize it with spectroscopy and
surface plasmon resonance analysis;
Create a target-binding core within the dimer to use it as detection tool in liquid
environments;
Test the dimer detection tool with endogenous molecules;
During the project I will use scanning electron microscopy and dark field microscopy to
characterize the nanoparticle systems, atomic force microscopy and fluorescence microscopy for the
actuation analysis of the DNA origami structure. Further I will use Raman spectroscopy and
plasmon resonance analysis to determine the hot spot features.
Here I report the Gantt diagram about my research project:
Tasks
2012
start
end
2013
2014
gen-mar apr-june july-sept oct-dec gen-mar apr-june july-sept oct-dec gen-mar apr-june july-s
1-Functionalize NPs
Handling NPs protocol
gen-2012
giu-2012
NPs/dimers characterization
lug-2012
dic-2014
Stability and environment test
ott-2012
giu-2013
2-Plasmonic ruler creation
Dimers creation
lug-2012 mar-2014
Ruler calibration
gen-2013
dic-2013
DNA origami decoration
lug-2013
giu-2014
Hot spot system creation
gen-2014
dic-2014
Detection tool creation
apr-2014
dic-2014
3-Dimer hot spot creation
Educational activity foreseen
During the first year I would attend the following schools and courses:
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- Preparatory School to the Winter College on Optics: Advances in Nano-Optics and
Plasmonics, from 30th january to 3rd february 2012, Miramare-Trieste.
- Winter College on Optics: Advances in Nano-Optics and Plasmonics, from 6th to 17th
february 2012, Miramare-Trieste.
- Spring course on Powder Diffraction Method, 15th march 2012, Trieste.
- DNA Nanosensors International Symposium, from 10th to 12th may 2012, Jena-Germany.
- Molecular self-assembling and nanostructures doctoral course, date to be define, Trieste.
Books that I will study:
- Principles of Nucleic Acid Structure, Stephen Neidle, Elsevier-2008.
- Surface Design: Applications in Bioscence and Nanotechnology, R.Forch, H.Schonherr, A.T.A.
Jenkins (Eds),Wiley-vch.
- DNA Nanotechnology: Methods and Protocols, G. Zuccheri and B. Samorì (Eds), Springer
Protocols-2011.
References
1.
Rothemund, P.W., Folding DNA to create nanoscale shapes and patterns. Nature, 2006.
440(7082): p. 297-302.
2.
Dietz, H., S.M. Douglas, and W.M. Shih, Folding DNA into twisted and curved nanoscale
shapes. Science, 2009. 325(5941): p. 725-30.
Douglas, S.M., et al., Self-assembly of DNA into nanoscale three-dimensional shapes.
Nature, 2009. 459(7245): p. 414-8.
Andersen, E.S., et al., Self-assembly of a nanoscale DNA box with a controllable lid. Nature,
2009. 459(7243): p. 73-6.
Kuzuya, A., et al., Nanomechanical DNA origami 'single-molecule beacons' directly imaged
by atomic force microscopy. Nat Commun, 2011. 2: p. 449.
Marini, M., Piantanida, L., et al., A Revertible, Autonomous, Self-Assembled DNA-Origami
3.
4.
5.
6.
7.
Nanoactuator. Nano Lett, 2011/10.1021/nl203217m.
Bek, A., et al., Fluorescence enhancement in hot spots of AFM-designed gold nanoparticle
sandwiches. Nano Lett, 2008. 8(2): p. 485-90.
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PAOLA PITTIA
Email: [email protected] / [email protected]
Laboratory: Physical and Macromolecular Chemistry – Life Sciences Dept. Univ. Trieste
Title of the thesis: PHYSICAL STATE OF SUGAR MATRICES AND AROMA-SUGARS
INTERACTIONS AT NANO-SCALE
Supervisor: prof. Attilio CESARO
Tutors (if any): prof. Dino Mastrocola
Research Activity foreseen
State of the art and motivations
Many natural foods contain nano-scale components (proteins, fats, carbohydrates) and their
properties are determined by their structure and how the latter are modified at the nanometer and
micrometer scales during food processing. Research into naturally occurring nanostructures in foods
is mainly designed to improve the functional behaviour of the food.
In the case of the aroma compounds is well acknowledged that, besides the intrinsic characteristics
of the aroma itself and the environmental factors, the interactions occurring at molecular level
between volatiles and non-volatile compounds (in particular those with macromolecules like
proteins, hydrocolloids and carbohydrates) are major factors that limit the release of volatiles and
thus their sensory perception as demonstrated by many studies in this field.
In the case of carbohydrates, the interactions with aroma compounds have in general a weak energy.
Complex saccharides (e.g. starch) have been widely investigated for their role in affecting the
release/retention of volatiles in food matrices, while scarce attention has been given to the presence
of mono-and di-saccharides. In diluted model systems the presence of the sugars can induce an
increase of release for some aroma compounds especially the more polar while an opposite effect
was observed for the more apolar as the they structure water molecules thus decreasing the amount
of free water in the food matrix. On the other side, in concentrated disaccharide solutions (sucrose,
trehalose) it has been evidenced a retention effect (“salting in”) for some aroma compounds
attributed to entrapment in hydrophobic regions of the highly concentrated sugars solutions.
Limited are also the citations and quite dated about the entrapment of aromas in amorphous and
crystalline sucrose systems without the explanation of the interactions at nano- and microscale.
Physical (e.g. viscosity) properties of the matrix have been recognized as factors that could affect
the liquid-vapor partition and the retention/release of aroma compounds in foods but these factors
have been studied only to a limited extent. In sugar-based matrices there is a lack of information of
the role of the physical state (amorphous, crystalline) and state and mobility of the matrix on the
release of aroma volatile compounds. Specific investigations are also needed to achieve a clear
understanding of the interactions occurring at nano-scale that could affect the retention of volatile
compounds in sugar matrices.
Objectives for the three years
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The general aim of this research project is to achieve knowledge about the role of the physical state
of disaccharides and the interactions at molecular scale on the release/retention of aroma
compounds by coupling different instrumental methodologies (NMR, FTIR) and spectroscopic
diffraction and scattering techniques using synchrotron light source.
Gas-chromatographic techniques will be used to test the retention/release of the aroma compounds
in the model systems.
Objectives to be achieved in the first year
- state of the art on the role of sugars on the retention/release of volatile compounds in liquid
and solid (amorphous/crystalline) state matrices
Identification of process conditions to obtain amorphous sugar matrices able
with high volatile retention ability
Physical characterization of the amorphous sugar matrices and study of the
volatile release as a function of water state and mobility
Research project
The research project will include the following steps
- preparation of amorphous/partly crystalline sugar matrices by using disaccharides (sucrose,
trehalose and maltose, as single component or in combination) in presence of volatile aroma
compounds at different polarity (ethyl acetate, ethyl hexanoate, linalool, limonene). The use
of spray-drying and freeze-drying as well as milling will be investigated.
- Characterization of physical properties of the sugar-volatile matrices (calorimetry, FTIR,
Raman spectroscopy)
- Evaluation of the retention/release of the aroma(s) from the sugar matrices by head space
gas-chromatography. Sugar-aroma matrices will be hydrated to achieve different water state
and mobility and the retention/release will be related to the correspondent physical properties.
Tasks and GANTT Chart
1st YEAR
A.
2nd YEAR
3rd YEAR
1
2
4
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
G
L
A
S
O
N
D
G
F
M
A
M
G
L
A
S
O
N
D
G
F
M
A
M
G
L
A
S
O
N
B.1

B.2

D
G
F

M
A
M




B.3
C.
D.1
D.2
E.
A. Bibliographic research
B.1 Preparation of freeze-dried and spray dried amorphous
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B.2 Instrumental characterisation of the powders
B.3 Release /retention properties of sugar powders
C. Internship
D.1 Preparation of dried sugar powders by milling
D.2 Instrumental characterisation and evaluation of aroma release
E. Writing and editing of the thesis
Educational activity foreseen – 1st YEAR
- PhD Summer School 2012 in Nanotechnology at the University of Udine (25 h)
- Attendance at the International Conference CEFFood, 24-26 May 2012, Novi Sad (Serbia)
as invited speaker with an oral presentation titled “Role of sugars in flavour
release and perception in food matrices”
- Attendance to the International Conference EURO Food’s water (Helsinki 4-6 June 2012)
- Attendance at the International Conference Frontiers in Water Biophysics, 23-26 September
2012, Perugia (Italy) as invited speaker with an oral presentation.
- Visit at the University of Lille 1 (France) for planning experiments of milling
- Training at the labs of the Department of Pharmacy of the university of Perugia to prepare
dried amorphous sugar matrices.
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SIMÃO PEDRO PEREIRA
Email: [email protected]
Laboratory: The Molecular Simulation Engineering Laboratory
Title of the thesis: Multiscale Modelling of Complex Materials Systems Morphology
Supervisor: Maurizio Fermeglia
Tutors (if any):
Research Activity foreseen
State of the art and motivations
The traditional approach of modelling materials is to employ a simple constitutive equation to
embody the material behaviour at the macroscopic level. Such approach may fail when dealing with
innovative complex systems, such as thermoplastic nanocomposites, for automotive and energy
industries, mainly due to the relevant phenomena that take place at lower length and time scales.
Thus, atomistic and mesoscopic are essential to estimate some macroscopic properties of interest, in
order to predict the correct behaviour of such materials.
The motivation is therefore to develop a robust procedure that enables to study a wide range of
complex systems from lower to larger scales, getting the relevant information at each of the
intermediate steps of the modelling approach.
Objectives for the three years
The main objectives of this project are to develop a robust multiscale modelling approach that
enables the study of complex system materials with industrial relevance. Major focus shall be given
to the morphology of such systems in order to correlate it with properties of interest. Furthermore,
experimental assessment of the properties must be compared with the output of the multiscale
procedure, for validation purposes.
Objectives for the first year
The first year must comprise a detailed literature review on multiscale approaches focused on
complex systems along with a study of the 3 systems of interest. It must include also a
familiarization with the software to be used to perform microscopic and mesoscopic simulations.
Computational based studies of the systems under investigation must be carried out.
Research project
The research project is divided into 5 tasks which are summarized below followed by a Gantt
diagram with expected time length of each task.
Task I - Code training and preparation
This task comprises preparation of the groundwork of the PhD project. The researcher will perform
an updated literature review on the subject, namely on the techniques adequate for Multiscale
Modelling of complex material systems and as well the systems to be studied. The researcher will
be also trained with the computational tools and characterization techniques that will be employed
during the PhD project.
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Task II - Computational based study of systems under study
During this task the researcher will study the behaviour of the selected materials systems using
computational modelling tools at the atomistic/mesoscale level, using codes developed for this
purpose, namely Culgi ®, Materials Studio and LAMMPS. This study will allow a comprehensive
analysis of the morphology of the systems to be investigated.
Task III - Experimental assessment of morphology evolution
The main conclusions obtained on the previous study will be experimentally assessed in this task.
For that purpose the material systems under study will be investigated using adequate techniques.
Task IV - Multiscale modelling platform
The main objective of this task is to implement the Multiscale Modelling Platform (MMP) that
should be able to model the morphology from the molecular to the macro scale for the selected
material systems.
Task V - Closure
This is the final task of the project and will consist in the writing-up and submission of the PhD
thesis. Along the project the candidate will produce internal reports and papers describing the
developments and these will be compiled into the PhD thesis.
2012
2013
2014
2015
Task I
Task II
Task III
Task IV
Task V
Educational activity foreseen
During the first year, the research must read literature information in order to get familiarized with
the topic and also attend workshops.
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NICOLA SCOTTI
Email: [email protected]
Laboratory: Chemical engineering department, Polytechnical School of Turin
Title of the thesis: Laboratory evaluation of several nanofilled dental resin composites
mechanical and chemical properties
Supervisor: Prof. Lorenzo Breschi
Tutors (if any):
Research Activity foreseen
State of the art and motivations
The use of nanofilled resin composite in restorative dentistry has markedly increased, supported by
the significant advances in resin matrix compositions, improvements in filler particles, and
optimization of the polymerization process (1-8). In fact, to improve many properties, the size of
filler particles incorporated in the resin matrix of commercial dental composites has continuously
decreased over the years, from the traditional to the nano-composite materials (9). However clinical
failures due to bulk fractures or recurrent caries are still reported (10-11), probably because of
curing problems, shrinkage stress and aging. For this reason, laboratory study focused on
conversion degree, depth of cure, hardness, volume shrinkage, wear, surface roughness and gloss,
restoration’s fracture resistance prior and after artificial aging must be assessed. The research
activity will focus on the above mentioned aspects of several nanofilled and nanohybrid resin
composites.
Part 1: conversion degree and depth of cure analysis will be performed with Micro FT-IR tests on
composites irradiated with different curing lamps (Halogen and LED) and different energy density
regimens. The tested hypothesis is that nanofilled composite show an increased depth of cure with
low energy density curing process if compared with microhybrid composites.
Part 2: mechanical tests, in terms of hardness (Vikers Test), flexural strength, flexural modulus will
be performed prior and after artificial aging. Tested composites must be cured with different energy
density regimens (same employed in Part 1) at different curing distances (2,3,4,5 mm). The tested
hypothesis is that nanofilled resin composites have similar mechanical properties which could be
strongly affected by artificial aging than microhybrid composites.
Part 3: surface roughness will be tested through mechanical profilometer and atomic force
microscopy with and without surface polishing, prior and after artificial aging. The tested
hypothesis is that nanofilled composites have lower surface roughness than microfilled composites.
However after artificial aging an important increase of surface roughness is expected because of
matrix degeneration and filler loss, which is easier in nanofilled than in microhybrid composites.
Part 4: mechanical fracture resistance will be tested. Intact teeth will be collected, similar MOD
cavities will be performed and filled with composites cured at different curing regimens. After
cyclic loading composite margins will be examined and evaluated with SEM to assess marginal
integrity. The tested hypothesis is that both nanofilled composites have better marginal integrity
than microfilled resin composites, both with ramp curing or high intensity curing.
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 Ruddell DE, Maloney MM, Thompson JY. Effect of novel filler particles on the mechanical and
wear properties of dental composites. Dent Mater 2002;18:72–80.
 Imazato S. Review: Antibacterial properties of resin composites and dentin bonding systems.
Dent Mater 2003;19:449–457.
 Watts DC, Marouf AS, Al-Hindi AM. Photo-polymerization shrinkage-stress kinetics in resincomposites: Methods development.Dent Mater 2003;19:1–11.
 Lu H, Stansbury JW, Bowman CN. Impact of curing protocol on conversion and shrinkage
stress. J Dent Res 2005;84:822–826.
 Xu X, Ling L, Wang R, Burgess JO. Formation and characterization of a novel fluoride-releasing
dental composite. Dent Mater 2006;22:1014–1023.
 Kramer N, Garcı´a-Godoy F, Reinelt C, Frankenberger R. Clinical performance of posterior
compomer restorations over 4 years. Am J Dent 2006;19:61–66.
 Wan Q, Sheffield J, McCool J, Baran GR. Light curable dental composites designed with
colloidal crystal reinforcement. Dent Mater 2008;24:1694–1701.
 Park JG, Ye Q, Topp EM, Misra A, Spencer P. Water sorption and dynamic mechanical
properties of dentin adhesives with a urethane-based multifunctional methacrylate monomer.
Dent Mater 2009;25:1569–1575.
 Ferracane JL. Current trends in dental composites. Crit Rev Oral Biol Med 1995;6:302–318.
 Sakaguchi RL. Review of the current status and challenges for dental posterior restorative
composites: Clinical, chemistry, and physical behavior considerations. Dent Mater 2005;21:3–6.
 Sarrett DC. Clinical challenges and the relevance of materials testing for posterior composite
restorations. Dent Mater 2005;21:9–20.
Objectives for the three years
During the three years it’s planned to reach a depth knowledge of laboratory test related to dental
resin composites:
infrared spectroscopy
flexural and hardness tests
atomic force microscopy
profilometer
cyclic loading
SEM
Moreover, the publication of at least two paper with the collected results are expected.
During the first year, Part 1 project (described above) will be completed.
Research project
May 2012-December 2012: Part 1 sample preparation and FT-IR analysis. Write paper related to
results.
January 2013 – June 2013: Part 2 sample preparation and mechanical test execution. Write paper
related to results.
July 2013 – December 2013: Part 3 sample preparation and surface analysis execution. Write paper
related to results.
January 2014-November 2013: Part 4 sample preparation and fracture resistance test. Write paper
related to results.
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Educational activity foreseen
Participation to National and International meetings on dental materials (American Dental
Association for Dental Research, AADR; March 21-24, 2012, Tampa, USA; Congresso
Nazionale del Collegio dei Docenti di Odontoiatria, Torino April 12-14, 2012;
Congresso Internazionale dell’Accademia Italiana di Conservativa, Riva del Garda May
4-5, 2012; IADR, June 20-23, 2012, Iguacu, Brazil; Annual Meeting of the Academy of
Dental Materials, Orlando (USA) September 19-22, 2012)
Study of previous published works on dental composite formulation and their use in
relation to their filler content;
 Acquisition of skills in using FT-IR for the calculation of degree of conversion, in elastic
modulus and microhardness measurement.
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TINA STOKELJ
Email:
Laboratory:
Title of the thesis: Development of new bran fractionation technologies
Supervisor: Maurizio Fermeglia
Tutors (if any):
Research Activity foreseen
State of the art and motivations
Processing of cereals in food industry generally requires milling to separate grain components:
endosperm, germ and bran. Endosperm fraction is used for production of grits, meals and flours,
whereas the germ and the bran today still have low value and are commonly used as feed for
animals (1). Research is therefore looking towards the potential industrial applications of these two
by-products abundant in the bakery industry. Bran is a rich source of fiber, vitamins, minerals and
antioxidant compounds, but utilization of the whole bran may have negative impact on food
properties (2, 3). Regarding safety, processing, acceptability by consumers and accessibility of the
nutrients and bioactive compounds, the food properties could be improved by preliminary
fractionation of the bran (4). However, bran is a composite material made up of several tissues and
due to the strong adhesion forces these tissues are difficult to dissociate (5). The bran fractions
could not be separated efficiently after conventional milling followed by sieving or air
classification. Mainly this is due to relatively small differences in particle size, shape and density
and because these particles are after milling still composite materials (4, 5). In order to improve
bran fractionation processes, the comprehensive Hemery et. al studies (4, 5, 6) emphasized the
importance of further investigation of bran structure, compounds responsible for tissue adhesion
and engineering methods to change mechanical properties of the bran. Combined investigation of
the chemical composition and mechanical properties of bran layers (1, 7) suggested that the major
factor controlling mechanical behavior of wheat bran is most probably the degree of arabinoxylan
crosslinking. This hypothesis was further supported by immunolabelling method in Philippe et. al
study (8). The key component establishing the covalent bridges between arabinoxylan polymer
molecules is ferulic acid. Monomer, dimer, trimer and tetramer forms of ferulate derivatives have
been isolated from the plant material. The ferulate derivatives align polysaccharide molecules
especially, but also connect polysaccharides with lignin and proteins. Through cross-linking of cell
wall polymers, ferulate derivatives control the strength, rigidity and extensibility of the plant cell
wall (9). Ferulic acid may form different isomers of mono, di and oligomers and their content in the
plant material varies between species and varieties (9, 10, 11).
1.Antoine C et. al. 2003. J. Agric. Food Chem., 51: 2026-2033
2.Rose DJ et. al. 2010. J. Sci. Food. Agric., 90: 915–924
3.Schafter MAM and Zambik ME. 1978. J. Food Sc., 43: 375-379
4.Hemery Y, 2007. Journal of Cereal Science, 46: 327–347
5.Hemery Y et. al. 2011. Journal of Cereal Science 53: 1-8
6.Hemery Y et. al. 2011. Journal of Cereal Science 53: 9-18
7.Peyron S et. al. 2002. Journal of Cereal Science, 36: 377-386
8.Philippe S et. al. 2007. Planta, 225: 1287-1299
9.Bunzel M 2010. Pytochem. Rev., 9: 47-64
10.Andreasen M et. al. 2000. J. Agric. Food Chem., 48: 2837-2842
11.Lempereur I. 1998. Journal of Cereal Science, 28: 251-258
Objectives for the three years
The main objectives of this PhD project are to obtain a better understanding of the structure and
properties of bran material by the tools of molecular modeling with a special focus on the ferulate
cross-linking, and to develop new bran fractionation technologies. The main goals of the project
are:
To evaluate the binding energy in ferulate derivatives by molecular dynamics and atomistic
simulation
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To measure the content of the ferulate derivatives in bran samples of different cereal
species or varieties
To evaluate the mechanical properties of the same bran samples
To find the correlation between the results of molecular modeling, content of ferulate
derivatives and mechanical properties of the bran
To propose how the bran properties could be modified in order to improve tissue
dissociation during milling
To approve new separation principles by milling experiments of the same bran samples
resulting in efficient bran fractionation.
Obbiettivi da raggiungere per il primo anno
The objectives to be reached in the first year are:
To do a literature overview
To learn the theory lying behind the molecular modeling
Molecular modeling
To design and perform laboratory experiments for bran structure and mechanical properties
examination
If time permits, to perform some milling experiments
Research project
Task 1: Literature overview
The PhD project should be started by doing a comprehensive literature overview resulting in a
concise report based on the scientific publications about the bran structure, mechanical properties
and ferulate cross-linking in plant material. A special focus should be given to the research dealing
with tissue adhesion and ferulate cross-linking.
Task 2: Understanding of the structure and properties of bran material by molecular modeling
Based on the literature overview, the associations of interest should be investigated by the
molecular dynamics and atomistic simulation. The estimates of the association’s binding energies
should be compared to the results of bran chemical composition and mechanical properties
previously reported in the literature. It is here hypothesized, that one or more associations will be
strongly correlated thus suggesting they importantly influence the mechanical properties of bran and
its layers.
Task 3: Characterization of the structure and properties of bran material by one or multiple
powerful techniques
Based on the results of molecular modeling, a series of experiments should be designed in order
to validate the proposed correlation between the structure and mechanical properties of the bran.
Two things that should be determined experimentally are:
- Content of the ferulate derivatives in the bran samples
- Mechanical properties of the bran samples.
Multiple methods may be used, such as biochemical analyses, nuclear magnetic resonance,
Raman spectroscopy, atomic force microscopy, Fourier transform infrared spectroscopy, traction
mechanical tests, etc. The methods used should be carefully chosen based on the literature overview
and previous research done in this field.
Task 4: Milling experiments of the engineered bran material and separation efficiency
evaluation
With better understanding of the adhesion at the molecular level and with better understanding
of mechanical properties of the bran, the new methods to break the linkages responsible for
adhesion will be proposed. The bran material will be engineered prior milling and the bran fractions
will be separated by carefully chosen techniques. The proportion of bran layers in different fractions
could be measured by several techniques, such as FTIR or biochemical analyses.
Task 5: Discussion and dissemination
The last task includes the preparation of the reports, presentations and scientific publications, to
present the research findings to the wide scientific public. This task should be given attention all the
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time in order to facilitate the research progress and to support it with the opinions and advices of the
professionals with different backgrounds.
Figure 2 bellow demonstrates the connection between the main tasks of the project, and Figure 3
is a Gannt chart showing a provisional project time schedule.
Task 1:
Literature search
Task 2:
Task 3:
Molecular modeling
Experimental
characterization
Task 4:
Experimental studies
on separation
Task 5:
Discussion and
dissemination
Figure 2: Connection between the main tasks of the project
Figure 3: Gannt chart demonstrating the time schedule of the PhD project
Educational activity foreseen
The educational activity during the first year should include:
Learning a theory lying behind the molecular modeling
Learning how to use the computer software
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ALEX STOPAR
Email:[email protected]; [email protected].
Laboratory:Nanomedicine laboratory at Experimental and Clinical Pharmacology Unit,
Centro di Riferimento Oncologico, Aviano.
Title of the thesis: Innovative Tools for Pharmacogenetics and Pharmacogenomics: ProteinNucleic Acid Interactions Within Self-Assembled Nanosystems
Supervisor:M.D. Giuseppe Toffoli
Tutors (if any): Dr. Matteo Castronovo and Dr. Flavio Rizzolio
Research Activity foreseen
State of the art and motivations
Pharmacogenomics is an helpful tool in medicine to increase the efficacy and reduce the toxicity of
pharmacological treatments1. Several common functional genetic variations (polymorphisms)
within intronic and gene regulatory regions could affect transcription factor activity by interfering
on their protein-nucleic acid interactions. The estrogen receptor transcription factor is a drug-target
for treating several and diverse diseases such as obesity, diabetes and cancer2. The molecular
mechanism of action of these drugs (e.g. tamoxifen, raloxifene) can be exclusively investigated
within in vitro, diluted solutions where the crowding conditions that are found in any biologically
relevant environment (e.g. cells or cellular lysates) are not reproduced. In turn, defining the effect of
drugs and genetic variations on protein-nucleic acid interactions within more realistic systems holds
great importance. Innovative, nanotechnology-based approaches to detect biomolecular interactions
at single molecule level such as fluorescence-3, atomic force microscopy-4 and optical tweezersbased techniques 5 have been developed. The reaction mechanism of DNA endonucleases within
surface-bound, laterally confined self-assembled monolayers of short DNA probes (DNA LCSAMs), was recently investigated by Castronovo and co-workers6. In this work, enzymatic
restriction reactions were monitored by atomic force microscopy (AFM)-based measurements of the
topographic height changes on LC-SAMs as a function of the DNA surface density6,7. This
approach can potentially allow the investigation of (at least a subset of) protein-nucleic acid
interactions in the presence of molecular crowding.
(Aim1) In my project I aim to characterize the interaction between a transcription factor and a
polymorphisms-containing DNA probe using the approach developed by Castronovo and coworkers6.
(Aim 2) Self-assembled DNA nanostructures (DNA origami)8are emerging, water-soluble nanomaterials with potential applications in the field of biomolecular detection and drug delivery9,10.
Their successful application in nanomedicine requires knowledge of their susceptibility towards
enzymatic degradation in complex biological mixtures. It was shown that DNA origami retain
higher stability in cellular lysates in comparison to linear DNA strands11,12, as they appear to be less
susceptible to non-specific enzymatic digestion. For instance, they have been shown to serve as
delivery systems in mammalian cultured cells13. In my project I aim to assess the stability of water-
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soluble DNA nano-assemblies in biological samples. Water-soluble DNA nanostructures have the
potential to extend the research program relative to Aim 1.
In conclusion, by accomplishing these aims, I plan to develop novel, very complementary, labelfree tools for the functional characterization of genetic polymorphisms that are relevant to
pharmacogenomic studies.
Objectives for the three years
AIM 1. Characterize the formation of transcription factor complexes on surface-bound
DNA nanostructures:
DNA LC-SAMs generation;
Mechanochemical analysis of DNA-transcription factor binding;
DNA-transcription factor interactions in purified solution;
DNA-transcription factor interactions in complex biological sample.
AIM2. Characterize the biochemical reactivity of water-soluble DNA nanostructures:
DNA nanostructures generation;
Biochemical reactivity of DNA nanostructures in purified solution;
Biochemical reactivity of DNA nanostructures in complex biological mixtures.
Objectives to achieve in the first year
DNA nanostructures will be designed by a CaD software. Generation of the DNA
nanostructures. Setup of folding condition. DNA nanostructures will be assessed for its
stability at room temperature by gel electrophoresis.
Generation of DNA LC-SAM by nanografting with different DNA sequences to asses
sequence binding specificity of transcription factor.
Mechanochemical characterization of DNA LC-SAM by AFM. Assessment of molecular
crowding changes by protein binding on DNA LC-SAM. Mutagenesis of DNA probe
sequence to assess its role in DNA-transcription factor binding affinity. Drug effect
assessment on DNA-transcription factor binding affinity.
Research project
Aim 1. Characterize the formation of transcription factor complexes on surface-bound DNA
probes that mimic genomic polymorphism-containing regulatory regions.
DNA LC-SAM generation. Single strand (ss)DNA LC-SAMs will be created using AFM
nanomanipulation method, the nanografting an alkylthiol-modified ssDNA within a bioresistant ethylene-glycol-terminated SAM on an ultra-flat gold surface. Conversion to
the double strand (ds)DNA form will be accomplished by adding the complementary
ssDNA. The LC-SAM height will be measured as a function of the ssDNA-to-dsDNA
transition, and also as a function of DNA length and density14. Specifically, LC-SAMs
containing ssDNA of increasing length will be measured for height before and after
addition of the complementary ssDNA. It is anticipated that (i) there will be a height
increase upon duplex formation, and (ii) there will be a direct correlation of dsDNA
height with the length of the duplex.
Mechanochemical analysis of DNA-transcription factor binding. DNA-transcription
factor interactions will be assessed by monitoring changes in height and friction over the
LC-SAMs as a function of the DNA density. It is anticipated that (i) there will be a
height increase when protein-dsDNA binding occurs, and (ii) the formation of a dsDNAprotein complex may change the mechanochemical properties of the LC-SAM contact
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interface with the AFM tip, and (iii) the latter can be detected by AFM-based lateral
force microscopy (LFM) as previously reported15. As a control, DNA-protein binding
reactions will be measured in solution with the standard analytical methods (DNA Pulldown assay and EMSA).
DNA-transcription factor interactions measured using purified components. Basic
transcription models will be assessed, using the estrogen receptor transcription factor
(ER). DNA probes containing ER-specific binding sequences will be immobilized
within LC-SAMs. The DNA-ER interaction will be studied using solutions containing
purified recombinant ER. ER binding will be assessed as a function of tamoxifen
concentration, a drug that binds ER and induces a conformational change that may
affects DNA binding (http://www.pdb.org/pdb/101/motm.do?momID=45).
Polymorphism-containing DNA probes also will be used, and ER-DNA binding will be
assessed as a function of position and length of the polymorphism within the DNA
sequence. It is anticipated that the ER recognition sequence is less than 10 bp and
therefore DNA probes of 30-50 bp can be used in this study2.
DNA-transcription factor interactions using complex biological samples. The
experiments described above also will be performed with cellular lysates of cultured
cells. ER concentrations will be determined with Western Blot analysis. Control
experiments will be performed using cellular cultures pre-treated with tamoxifen. As
control, cultured cell lines that do not express the transcription factor will be used.
Expected results. The ER transcription factor 1 (ER1) is a 66.23 KDa monomer
(http://www.uniprot.org/uniprot/P03372). ER isoforms bind to DNA as homodimer or
heterodimer16. The molecular weight of dimers is ~100 KDa, and their physical
dimensions range between 5 and 10 nm. In contrast, the average DNA-DNA distance
within LC-SAMs that are accessible to restriction enzymes dimers (MW≈50-60KDa) is
less than 10 nm (density < 1012 molecules/cm2)6. In turn, it is expected that ER-DNA
binding will cause a significant increase in biomolecular density of in the steric
hindrance within the LC-SAMs, that is expected to lead to a detectable height increase
of the LC-SAMs. It is also expected that the ER-DNA interaction will be detectably
affected by the presence of tamoxifen in solution, or polymorphism in the DNA probes.
Furthermore, it is expected that the DNA-ER recognition will depend on the DNA
surface density. The addition of tamoxifen after DNA-ER interactions are established in
the LC-SAM, followed by time-resolved AFM imaging will inform on the kinetics of
ER-DNA dissociation in complex biological samples.
Potential Problems & Alternative Strategies. DNA LC-SAMs may exhibit a reduced
stability in the presence of cellular lysates, due to the presence of DNA nucleases. In this
case, we will introduce ssDNA and/or dsDNA molecules of varying length, that do not
bind the transcription factor under investigation. These nonspecific DNAs are expected
to function as “traps” for nucleases. Their presence will slow down the nuclease activity
on the surface. Alternatively (or in addition), cellular lysates can be appropriately
diluted. For longer DNA probes within LC-SAMs, the expected height increase may be
less than expected. In this case we will add antibodies that bind the transcription factors.
In addition, fluorescence from labeled antibodies can be monitored for LC-SAMs larger
than a few tens of microns. Alternatively, dsDNA intercalating fluorescent molecules
(e.g. SYBR® Green) can be used to quantify the percent of unbound DNA within the
LC-SAM. Experiments in complex biological mixtures may be affected by non-specific
protein binding to DNA probe. In this case, we will use nuclear extracts separated from
cellular lysates with standard molecular biology methods17.
Aim 2. Characterize the biochemical reactivity of water-soluble DNA nanostructures.
DNA nanostructures origami generation. Approximately 200 staples can be located
within a 60×90 nm tile, limiting the density to 3.7×1012 molecules/cm2. According to the
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work of Castronovo and co-workers, the access of restriction enzymes within surfacebound LC-SAMs is inhibited at dsDNA densities higher than 0.5×1012 molecules/cm2 6.
The length of staples is limited by synthesis (100 bases). Approximately 30 bases are
hybridized within the 2D structure of the origami and, therefore, the maximum length
DNA forming the brush is < 70 bases. In turn, the susceptibility to enzymatic digestion
of these DNA origami can be modulated.
Analysis of the biochemical reactivity in solution of DNA origami in purified form.
DNA staples forming the brush on the DNA origami will be converted to dsDNA by
hybridization with fluorescent-labeled ssDNAs. For studying endonucleases (e.g.
BamHI or DpnII) in purified solution, dsDNAs in the brush will contain a restriction
site, half-way between the origami and the topmost brush-solution interface. After
enzymatic reaction, fluorescent labels (e.g. AlexaFluo488) will leave the origami and
will be easily separated from the latter with spin column filtration. The eluted buffer will
be measured for fluorescence. In turn, the reaction efficiency will be accurately
quantified and correlated to the aforementioned structural parameters of the DNAorigami. The size distribution of DNA fragments will be monitored by SDS-PAGE
electrophoresis, using standard molecular biology methods. The DNA origami will be
similarly collected after the reactions. The mobility in agarose gels will be compared to
that of the non-reacted DNA origami. Enzyme digested origami are expected to display
higher mobility.
Analysis of the biochemical reactivity of DNA origami in complex biological mixtures.
If the experiments described above demonstrate the nuclease reactivity of purified DNA
origami in solution, similar experiments will be conducted in the presence of the cellular
lysates. Biological samples used in the experiments described in Aim 1 can be used here.
An ER-binding DNA sequence will be included in the DNA brush flanking the origami,
in close proximity to a restriction reaction site. In this way, the ER-DNA binding could
be assessed within DNA origami by measuring changes in susceptibility to enzymatic
cleavage with respect to control origami that lack the ER binding site.
Expected Results. Our approach will introduce a novel methodology to investigate DNA
origami, and will provide structural information to study their biochemical behavior.
Although, AFM can be used to morphologically characterize the quality of the DNA
origami synthesis, most of experiments will not rely on AFM, thus avoiding its current
limitations. Furthermore, the fluorescence-based and electrophoresis-based analysis of
DNA fragments produced by enzymatic digestion both represent rigorous quantitative
approaches.
Potential Problems & Alternative Strategies. Working DNA origami concentration is
limited to about 10 nM in solution. Fluorescence detection can be problematic for
concentrations < 100 nM. The actual concentration of labeled DNA probes in solution is,
in the case of complete enzymatic cleavage, TWO orders of magnitude higher than the
one of origami (i.e. about 1 µM). In this way we expect to detect cleavage efficiency
higher than 10%. In the case that “brushy” origami are difficult to produce with long
staples, we will generate the brush by attaching preformed dsDNAs to preformed
origami. For instance thiol-modified dsDNAs could be covalently attached to short,
amine-modified ssDNA staples via commercially available protocols (sulfo-SMCC,
Pierce). Alternatively, we will assess the biochemical activity of DNA origami as a
function of compactness by generating DNA origami with a progressively decreasing
amount of staples (without staples, the origami do not form, and the linear DNA is
highly accessible to enzymes).
Timetablefor Project
DNA LC-SAMs generation
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
Year 1
Aim 1
Year 2
Year 3
181
Mechanochemical analysis of DNA-transcription factor binding
DNA-transcription factors interactions in purified solutions
DNA-transcription factors interactions in complex biological samples
DNA nanostructures generation
Biochemical reactivity of DNA nanostructures in purified solution
Biochemical reactivity of DNA nanostructures in complex biological
Aim 1
Aim 1
Aim 1
Aim 1
Aim 1
Aim 1
Aim 2
Aim 2
Aim 2
Aim 2
mixture
Educational activity foreseen
My educational activity will consist of developing the knowledge of the literature in the field of
AFM and AFM-based techniques and in the field of DNA nanostructures by review reading. I
would like to participate in meeting, seminars and courses in field of Nanomedicine and DNAbased nanotechnology. There I put seminars and meeting that I plan to participate:
Summer school on nanotechnology (~ first week of July- 4 days long)
International Symposium “DNA-NanoSensors”; May 10-12, 2012; Jena (Germany)
Educational activities carried out up until now, seminars and meetings:
Annual Meeting of PhD School in Nanotecnology; January, 16-18 (9 hours), Prof.
Maurizio Fermeglia.
“CD38 in Leucemia Linfatica Cronica: dieci anni dopo”; February, 10 (1 hour); Dr. Fabio
Malavasi.
“Molecular Modeling as a Tool for Life- and Nano-Science: the Interesting Features of
Dendritic Molecules”; February, 13 (1 hour); Dr. Giovanni Maria Pavan.
“Spontaneous And Coherent Raman Scattering for Biomedical Applications”; February, 13
(1 hour); Dr. Michele Casella.
Spring Course on Powder Diffraction Methods; March, 15 (4 hours); Prof. Norberto
Masciocchi and Prof. Antonietta Guagliardi.
“Short Peptides As Biosensor Transducers”; April, 4 (1 hour); PhD student Silvia Pavan
“Circulating Tumor Cells: Current Detection Systems, their Shortcomings, our Solutions
and Future”; April, 10 (1 hour); Prof. Giacinto Scoles and Dr. Daniela Ceselli.
YRCA Annual Meeting 2012; April, 12 (8 hours); Dr. Riccardo Spizzo.
Bibliography
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Cecchin, E. et al. Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants
and their haplotypes on the outcome of metastatic colorectal cancer patients treated with
fluorouracil, leucovorin, and irinotecan. Journal of clinical oncology 27, 2457-65 (2009).
2.
Gronemeyer, H., Gustafsson, J.-A. & Laudet, V. Principles for modulation of the nuclear
receptor superfamily. Nature reviews. Drug discovery 3, 950-64 (2004).
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Tafvizi, A., Huang, F., Fersht, A.R., Mirny, L.A. & Oijen, A.M.V. A single-molecule
characterization of p53 search on DNA. PNAS 108, (2011).
4.
Lyubchenko, Y.L. & Shlyakhtenko, L.S. AFM for analysis of structure and dynamics of
DNA and protein – DNA complexes. Methods 47, 206-213 (2009).
5.
Wagner, C. et al. DNA condensation by TmHU studied by optical tweezers, AFM and
molecular dynamics simulations. Journal of biological physics 37, 117-31 (2011).
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6.
Castronovo, M. et al. Two-dimensional enzyme diffusion in laterally confined DNA
monolayers. Nature communications 2, 297 (2011).
7.
Castronovo, M. et al. Control of steric hindrance on restriction enzyme reactions with
surface-bound DNA nanostructures. Nano letters 8, 4140-5 (2008).
8.
Rothemund, P.W.K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297302 (2006).
9.
Douglas, S.M., Bachelet, I. & Church, G.M. A logic-gated nanorobot for targeted transport of
molecular payloads. Science (New York, N.Y.) 335, 831-4 (2012).
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Chhabra, R., Sharma, J., Liu, Y., Rinker, S. & Yan, H. DNA self-assembly for
nanomedicine. Advanced drug delivery reviews 62, 617-25 (2010).
11.
Keum, J.-W. & Bermudez, H. Enhanced resistance of DNA nanostructures to enzymatic
digestion. Chemical communications (Cambridge, England) 7036-8
(2009).doi:10.1039/b917661f
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Mei, Q. et al. Stability of DNA origami nanoarrays in cell lysate. Nano letters 11, 1477-82
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Walsh, A.S. et al. ARTICLE DNA Cage Delivery to Mammalian Cells. 5427-5432 (2011).
14.
Mirmomtaz, E. et al. Quantitative study of the effect of coverage on the hybridization
efficiency of surface-bound DNA nanostructures. Nano letters 8, 4134-9 (2008).
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Staii, C., Wood, D.W. & Scoles, G. Verification of biochemical activity for proteins
nanografted on gold surfaces. Journal of the American Chemical Society 130, 640-6 (2008).
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Brzozowski, A.M. & Pike, A.C.W. Molecular basis of agonism and antagonism in the
oestrogen receptor target genes . Transcriptional regulation arises from the direct. Nature
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LORENA TARUSHA
Email: [email protected]
Laboratory: 247, building C11
Title of the thesis: “Novel nanostructured biomaterials for biomedical applications”
Supervisor: prof. Paoletti Sergio
Tutor: dott. Andrea Travan
Research Activity foreseen
State of the art and motivations
The research project that will be treated during this thesis aims to produce a biomaterial for
anastomotic leakage prevention in cases of colorectal cancer (CRC) resection.
Actually CRC is the second most common form of cancer and its management requires surgery
with resection of the affected bowel segment and suture of the extremities to restore the normal
bowel transit (anastomosis)1. The surgeon typically performs the anastomosis by handsewing or
stapling techniques.
The most frequent and feared post-operative complication is the Anastomotic Leakage (AL) which
occurs when no proper and rapid regeneration of the intestinal tissue takes place at the site of the
anastomosis5. The clinical consequences of AL vary from generalized peritonitis requiring
abdominal reoperation to a more localized leak that may be drained or to a subclinical leak detected
merely on contrast radiology2. In addition to higher costs and longer hospitalization, AL is
associated with significant increase in local recurrence of cancer and decrease in long term patient
survival8.
It has been reported in the intestine environment that butyric acid has the ability to preserve colonic
mucosa integrity and homeostasis although in the distal colon its availability is low. Till now some
studies report an alteration on butyric acid concentrations in colonic inflammation diseases4.
Recently, butyric acid was shown to reduce AL on rat models7.
At present, efficient treatments or drugs to prevent the onset of AL are still not available although
different trials have been made using biomaterials which were not been designed for this specific
application.
A reinforcement with a material that wraps the anastomosis triggering tissue healing is considered
an ideal solution by surgeon6. Such external reinforcement can be released by the stapling device or
applied exogenously to the staple line.
The material should be in form of a patch or sleeve, biocompatible, water swellable and easy to
handle also in connection to laparoscopic techniques. It has to be a material that does not cause
adhesion between viscera and abdominal wall which can lead to inflammation and infection.
The biomaterial should posses proper mechanical properties because of the peristaltic movements of
the intestine which will stress the material. An additional feature of such materials would be to
posses antibacterial activity without being cytotoxic.
Objectives for the three years
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The main research line will aim at the development of an engineered bioresorbable biomaterial
capable of promoting a safe anastomosis during the critical period of tissue healing without causing
adverse reactions. The biomaterial will be based on natural polysaccharides such as alginate and
Hyaluronic acid (HA), polymers already used in several medical applications. HA modified with
butyric acid (HAbut)3 will be inserted into the formulation in order to explore its biological activity.
The main objectives for the three years are listed below:
 production of nano-engineered materials, composed of alginate and HA and/or HAbut in
form of a patch;
 mechanical and physico-chemical characterization of patches;
 in vitro tests on fibroblasts, colonic and colonic smooth muscle primary cells with
particular attention to biocompatibility, cell proliferation and other biological effects like
phenotypic protein expression;
 introduction of antimicrobial silver nanoparticles into the patches;
 study of the effect of carbon nanotubes on the mechanical properties of polysaccharidebased materials;
 In vivo studies of the biomaterials on animal models;
Objectives for the first year
The objectives to be achieved during the first year are the following:
 production of a first generation of patches with alginate and HA using various polymers
concentrations, HA with different molecular weights and different gelation methods;
 analysis of the structure and mechanical characterization of the construct;
 development of the analytical tools to detect the release of HA from patches;
 in vitro biological tests in order to study the effects on cell vitality, proliferation and
biological activity of the single components of the patch;
Calcium ions in the presence of glycerol will be used for alginate-based hydrogel production. The
gel will then be converted in a membrane through freeze-drying techniques.
The research will proceed with characterization of gels in terms of interaction of polymers,
mechanical resistance and structure through SEM, Rheology and spectroscopy.
During the first year in vitro effects of HA, HAbut and butyrate on cells will be studied introducing
each component in the cell medium.
Research project
The research project foresees the production of different patches through steps that include: a 1 st
generation patch that consists in a freeze-dried gel made of alginate and HA and a 2nd generation
patch with the substitution of the HA with HAbut or a mixture of HA and HAbut. As a side track,
silver nanoparticles and carbon nanotubes will be used to obtain nanocomposite biomaterials.
Morphological, mechanical and physico-chemical characterizations will be performed. In addition,
the effects on eukaryotic cells will be studied in vitro and a final in vivo study will be made for both
1st and 2nd generation patches.
The activities and tasks of this project are listed below:
1. 1st generation patch production and characterization:
 production of patches with alginate and HA with various polymer concentrations,
HA with different molecular weights and different gelation methods;
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

2.
3.
4.
5.
6.
7.
structural characterization through SEM and μCT analysis;
mechanical characterization through rheological techniques and universal testing
machine;
 testing of the release of HA from patches through circular dichroism and
fluorescence spectroscopy;
In vitro biological tests:
 effects on cell vitality of the single components of the patch through biological
assays (AlamarBlue test, MTT etc.);
 effects of the single components on cell activity like matrix production through
biological assays (Elisa tests, western blotting etc.);
In vivo studies of the 1st generation patch in animal models;
2nd generation patch production and characterization:
 introduction in the 1st patch formulation of HAbut with various polymer
concentrations, molecular weights and different degree of substitution;
 structural characterization through SEM and μCT analysis;
 mechanical characterization through rheological techniques and universal testing
machine;
 testing of the release of HAbut from patches through circular dicroism and
fluorescence spectroscopy;
In vitro biological tests:
 testing of effects of HAbut on cell viability and activity;
In vivo studies of 2nd generation patch in animal models;
Development of polysaccharide-based nanocomposites that exploit the properties of silver
nanoparticles and carbon nanotubes.
1st year
2nd year
3rd year
1st generation patch production and characterization
In vitro biological tests
In vivo studies on animal models
2nd generation patch production
In vitro biological tests
In vivo studies of the 2nd generation patch
Development of polysaccharide-based nanocomposites
with silver nanoparticles and carbon nanotubes
Educational activity foreseen
 “Self assembling monolayers of DNA”, Matteo Castronovo (Centro di riferimento
oncologico di Aviano, Farmacologia Sperimentale e clinica; 3.02.2012; 1h)
 Spring course on Diffraction Methods for Nanostructured Materials. Norberto Masciocchi
and Antonietta Guagliardi, Università dell’Insubria (15.03.2012; 4h)
 Nanomicroscopies ( Modulus 1 of “Nanotechnologies and nanomicroscopies” course of the
degree in Medical Biotechnology, CV Nanotechnology, Dr. Carlo Dri; 24h)
 Biopolymers (part of “Biophysics” course of the Master Degree in Medical Biotechnology,
Curriculum Nanotechnology, prof. Sergio Paoletti; 32h)
 Other courses or schools
Reference List
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1
2
3
4
5
6
7
8
Rajput Ashwani and Bullard Dunn Kelli, "Surgical Management of Rectal Cancer,"in 34
ed.2007), pp.241-249.
C. R. Asteria, et al., "Anastomotic leaks after anterior resection for mid and low rectal cancer:
survey of the Italian Society of Colorectal Surgery," Tech Coloproctol 12(2), 103 (2008).
Ref Type: Journal
D. Coradini, et al., "Hyaluronic acid as drug delivery for sodium butyrate: improvement of the
anti-proliferative activity on a breast-cancer cell line," Int J Cancer 81(3), 411 (1999).
Ref Type: Journal
H. M. Hamer, et al., "Effect of butyrate enemas on inflammation and antioxidant status in the
colonic mucosa of patients with ulcerative colitis in remission," Clin. Nutr. (2010).
Ref Type: Journal
Y. H. Ho and M. A. Ashour, "Techniques for colorectal anastomosis," World J Gastroenterol.
16(13),
1610
(2010).
Ref Type: Journal
J. Hoeppner, et al., "Small intestinal submucosa for reinforcement of colonic anastomosis," Int J
Colorectal
Dis
24(5),
543
(2009).
Ref Type: Journal
A. J. Mathew, et al., "The Effect of Butyrate on the Healing of Colonic Anastomoses in Rats,"
23(2),
101
(2010).
Ref Type: Journal
C. S. McArdle, D. C. McMillan, and D. J. Hole, "Impact of anastomotic leakage on long-term
survival of patients undergoing curative resection for colorectal cancer," Br. J Surg 92(9), 1150
(2005).
Ref Type: Journal
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MARIENETTE MORALES VEGA
Email: [email protected]
Laboratory:
Title of the thesis: Raman and fluorescence spectroscopy of biomedical nanomaterials
Supervisor: Valter Sergo
Tutors (if any): Vanni Lughi
Research Activity foreseen
State of the art and motivations
Raman spectroscopy is an analytical technique that has been very useful in the analysis of materials.
One general limitation of conventional Raman spectroscopy, however, has been the weakness of
Raman scattering signals. When a molecule is next to certain metallic substrate, one may observe an
enhancement of the Raman scattering intensity. This observation has brought forth what is known
as surface-enhanced Raman spectroscopy (or SERS), which has a significantly extended the reach
of Raman spectroscopy as an analytical tool.
SERS is now a popular as a high-sensitivity analytic tool. Coupled with instrumental improvements
brought about by developments in nanotechnology, its versatility in various applications has
significantly increased. A wide variety of applications has been developed around the use of SERS
as a quantitative tool, including single molecule and trace detection, detection of organic pollutants,
microfluidics, separation science and DNA analysis. SERS technique is favored primarily for its
high selectivity feature. It is able to discriminate between materials of the same composition but
different structure. In addition, its high sensitivity enables detection of samples even in small
volumes. The key step to achieving the giant optical amplification lies on finding a suitable
nanoparticle system that supports the effect. Thus, preparation of SERS substrates remains a very
active research area. The quality of the signal as well as its reproducibility is dictated by the size,
shape and optical properties of the nanostructures. Platforms for SERS measurement can be in the
form of colloids of metallic nanoparticles, nanoparticle islands on planar support or periodic arrays
of nanoparticles grown on solid support. While suspensions easily generate tiny regions of localized
electromagnetic field, referred to as hotspots, very small enhancement is produced and the spectral
signal is not reproducible. Despite this drawback, there are a number of reasons for choosing to
utilize nanoparticle suspensions as substrates. They are easy and economical to synthesize through
wet chemical preparation techniques. Other than mixing the analyte with the colloid, no further
sample preparation is needed since most analytes come in solution form. Adsorption of analyte
molecules by nanoparticles is very likely since nanoparticle suspensions have very large surface
area. The presence of solvent prolongs the shelf-life of the nanoparticles. Reproducibility of the
Raman spectra is addressed by using metallic nanoparticles grown on a planar support. Thin films
or glass slides serve as support for immobilized nanoparticles. The most sophisticated type of SERS
substrates is the fabrication of periodic arrays of nanoparticles directly on solid substrates in a top
down fashion, which includes those prepared by nanolithography and template synthesis of
nanostructures. Each of these classes of substrates has proved to be suitable for specific uses; there
is no best SERS substrate available for universal use in applications. Given the versatility and
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flexibility of the surface-enhanced Raman spectroscopy, it continues to be a very active research
subject in many scientific fields. Its flexibility comes from its dependence on several factors that are
readily controllable in the laboratory (some of which I have already identified, such as nanoparticle
size and shape). The goal is then that of tuning the SERS method to suit the particular analyte of
interest.
Objectives for the three years
A key component of my PhD research will focus on contributing to the ever-growing body of
knowledge about the SERS technique and to further broaden its applicability to the characterization
of novel biomaterials.
Another key component of my PhD research will be to further explore and develop the capabilities
of Raman spectroscopy for the characterization of zirconia, which has long been used as a
biomaterial in the field of dentistry.
Obbiettivi da raggiungere per il primo anno
The first year is dedicated for learning of handling of the measurement systems, introduction into
the theory of Raman spectroscopy, particularly SERS and fluorescence, measurements on different
samples, which include zirconia other biomaterials.
Educational activity foreseen
Attendance to regular seminars/colloquia and group meetings.
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LEONARDO VENTURELLI
Email: [email protected]
Laboratory: TASC Laboratory at IOM-CNR.
Title of the thesis: Microfluidics devices for biomedical applications
Supervisor: Professor Giacinto Scoles
Tutors (if any):Danut-Adrian Cojoc
Research Activity foreseen
State of the art and motivations
The scope of my 3 years doctorate research project is to produce a biomedical device able to isolate
and study Circulating Tumor Cells (CTCs) from a blood sample.
The problem is to find a method that can anytime and anywhere identify and isolate circulating
cancer cells from a population with a great abundance of non pathological circulating cells. Indeed
right now only one diagnostic tool was been approved by the NIH committee in the USA. The same
is for European and eastern countries. This method named Veridex CellSearch™ (Johnson &
Johnson) is extremely expensive and less than 10 robot are currently used all over the Europe. This
lack of technology leave a lot of possibilities to develop newer and cheaper CTCs diagnostic
devices.
In January at the beginning of my studies I have done some computer simulation in order to decide
what kind of geometry could be the best for my research field. We (me and my tutor) have decided
to realize a microfluidic channels (like 200 um thickness and 100 um height) cutting a
polydimethylsiloxane (PDMS) membrane by a laser cutter. In order to study flux and geometry
relevance we have used a set of glass microbeads (ø: 4-30µm) trapped by laser. In the next months
we would modify channels fluidic resistance in one arm of the device and thus register pressure and
velocity deltas in the other arms (channels). Right now we are waiting for some ordered materials
for microfluidics specific approach. For example we need to use little needles for little channels and
zero dead volume valves to allow a flawless handling of micro composites.
The goal of my research would be produce a simple, useful and cheap device for medical diagnostic
application and in particular this should be a tool to investigate circulating tumor cells number in
patients’ blood.
Objectives for the following year (if applicable)
In the next future we have to develop the device by LIGA methods in a PDMS membrane for a
thorough nano-structured device. Then we will have to deposit a gold film on some arms of the
device (or evaporate, it depends by the following studies) and then functionalize it by thiol bonding.
In this way we will have a reactive layer that will be used for the next functionalization process,
useful for cells capture and studies. In the second year of doctorate I hope to begin the detect and
evaluation of the biological characteristics of CTCs using this device, like viscosity of tumor cells
and consequently their fluid-dynamic properties in order to elucidate the metastatic propensity of
these cells to detach and migrate to characteristics body sites.
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Objectives for the three years
So the three years doctorate program is:
- Develop a single functionalized device able to detect and isolate few cells (about 5-10)
from an original blood sample of around 109 cells.
- Study and evaluate viscous-dynamics properties of these cells (this goal could be better
reached by an Erasmus placement at Professor Cristofanilli Research Laboratory at Fox
Chase Cancer Center in Philadelphia, PA, USA)
- If it will work with poor channels we will need to implement it by adding like 100 parallel
connected channels and begin to think about an hypothetical commercialization of it.
Obbiettivi da raggiungere per il primo anno
-Define the device geometry.
-Make a reproducible device with LIGA method in PDMS membrane.
-Study the flux by varying the fluidic resistance of the channels.
-Doing the first analysis of the channels functionalization by charged-modified (or
magnetic, or Antibodies bonded) microbeads.
Research project
First Year Porject Description:
In the first months of my project I have identified the kind of device and the geometry to develop
and we decided to begin with microfluidic approach. After that I have begun with some computer
simulations (MathLab and MultiPhysics programs) to understand what kind of problem we will can
encounter and how I could avoid them. A geometry for the prototype is been chosen and other one
was been investigated as replacement for the first. Finally flow characteristics and materials
properties was been analyzed to identify a good compromise between materials fluidic resistance
and their capability to accept a functionalization like gold films.
Last month’s and next month’s activities take place at IOM-CNR, Sincrotrone Elettra, (ex TASC
laboratory, Trieste) where I have used a laser cutter (IR laser, λ=10600 nm) to begin to approach
with a microfluidics device with bigger dimensions than what they will be in final prototype. The
first studies with this self-made device include the use of µbeads (functionalized, magnetic, .. ,ecc)
for living cells mimicking and comprehension on what parts of the device need to be improved.
After the comprehension of the needed parameters we will proceed with soft lithography technique
that will allow us to obtain an etching of the prototype CAD design in a PDMS (height controlled)
membrane.
At the same time I am attending few university courses for example a LabView programming
course in order to learn how to communicate with laboratory’s instrumentations and a course on
microfluidics devices. Moreover I have studied, clearly, microfluidics and CTCs scientific papers
downloading them by the web or finding at the university library.
Second Year project description:
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Second year project provide using prototyped device to study living cells. The device will need a
functionalization to allow the recognition between CTCs and channels. Then we will test device’s
watertight with blood samples and how it counteract with all blood’s components. An Erasmus
placement will be hopefully profitable and necessary for a more depth knowledge of the biological
CTCs’ characteristics in the second half of the second year project.
Third Year Project Description:
At the beginning of third year prototyped device should be tested, completed and ready to use for
biomedical research laboratories tries. The next step should be implement channels’ numbers not by
using soft lithography technique or other similar methods but produced by in parallel linkage of
PEEK microtubes with functionalizable inner layer (ID: 50µm). Thus could be maybe done by
fusing microtubes in PMMA slide where an inlet tank parcel out sample in all channels. At the end
of the channels an optical fiber analyzes the samples for the recognition of positive cells. A second
control will be held by an interferometer in order to analyze pressure’s gap.
Doctorate thesis will be write in the second period of third year and consigned at the beginning of
fourth year for the final exam dissertation.
Fig. Gantt Diagram of my project.
Educational activity foreseen
I have attended in February and March a Labview programming course for beginners and in
September I think I will continue with the advanced course.
I think it will be also necessary to find a course in evaporation and deposition chemical processes
for plastics materials in order to functionalize device’s channels.
At the same time I look every week on ICTP website to find out interesting courses and seminars.
At last but not the least I am studying by myself some mathematical and physical books at home to
improve my actual knowledge and my future job perspectives.
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LIANQIN WANG
Title of the Thesis: Nanostructured Materials for Energy: Li-ion battery and Hydrogen production
from biomass by Electrolysis
Supervisor: Prof. Paolo Fornasiero
Tutors: Francesco Vizza, Alessandro Lavacchi
State of art and motivations
Anatase TiO2 is one of the candidates as high voltage anode material for Li-ion batteries. It offers
the advantage of having a low volume change upon Li+ insertion and improved rate capability as
compared to graphite. However,the practical capacity and high-rate capability are seriously limited
by the poor ion and electron conductivity of micro-sized bulk anatase TiO2. To improve the
electrochemical performance, one of the most common strategies reported is producing
nanostructured electrode materials, such mesoporous materials and nanocrystals. By reducing the
particle dimensions to nanoscale, it can serve to shorten distances of electron and lithium-ion
transport, and increase contact area between electrode and electrolyte, leading to the
electrochemical performance improvement.
In this project we plan to study anodic materials other than carbonaceous materials. Anatase TiO2
(or anatase TiO2 nanotubes) is the candidate material.
Fig. 1. (a) FE-SEM images of the as-prepared TiO2 nanowires; (b)SEM images of anatase TiO2 nanotube arrays.
Moreover, it has been known that silicon exhibits a theoretical capacity of 4200 mAh/g, much
higher than those of other anode materials. The research will be devoted to study the activity during
charge-discharge cycles of new materials such as carbon coated with SiOx or carbon mixed with
TiO2 (or TiO2 nanotubes).
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Fig. 2. SEM (a) and TEM (b) images of the TiO2 hollow spheres.
The research work will be divided into the following steps: i) Survey of the literatures; ii) Synthesis
of new materials; iii) Material characterization (XRD, TEM, SEM and ICP-OS analysis); iv)
Electrochemical measurements.
The project is also proposed to aim at designing, developing and testing a series of
"unconventional" nanostructured metal catalysts to be used for the hydrogen production from
biomass. The project draws its motivations from the expertise of the ICCOM-CNR researchers in
the synthesis of nano-structured metal catalysts featured by high thermal and chemical stability as
well as excellent activity. Some of these catalysts have been successfully employed in reforming
and steam reforming reactions of alcohols and in electrochemical process such those that occur in
direct alcohol fuel cells (methanol, ethanol, ethylene glycol, glycerol) or in electrolyzer for
hydrogen production. It has been demonstrated that the electrolysis of aqueous solutions of
compounds whose oxidated potential in alkaline environment is much lower than that of pure water.
For example, ammonia and ethanol allows for the production of hydrogen at reversible potentials,
of 0.06 and 0.10 V respectively, much more favourable compared to that of water (1.23 V).
Therefore, it decreases the production cost of electrolytic hydrogen from 5-6 Euro/Kg to 1.6-1.9
Euro/Kg in line with the UE and DOE expectations.
The study will be divided into three stages: (i) preparation of catalysts and electrodes (ii) chemicalphysical characterization (SEM, TEM, AFM, FTIR, EXAFS, ICP-AES, cyclic voltammetry,
galvanostatic and galvadynamic experiments) (iii) screening of the anode electrocatalysts for the
production of hydrogen from methanol, ethanol, ethylene glycol, glycerol in electrolyzers equipped
with anion-exchange membranes or without membrane.
Objectives for the three years
Development, fundamental and functional characterization of a variety of new materials:i) Li-ion
battery; ii) hydrogen production by electrolysis
Objective for the first year
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Literature analysis for the definition of the state of the art as a basic reference for benchmarking;
definition of the protocols for both the fundamental and functional characterization of the materials
that will be synthesized; selection trough experimental trials of the best synthetic routes for the
nanostructures.
Research project
Activity 1.1: State of the Art
The state of the art for Li-ion battery and hydrogen production by electrolysis will be critically
reviewed. The obtained data will be used to select systems and synthetic strategies.
Task 1.1: Literature Analysis
A perusal of the existing literature will be performed. The main purposes are a clear definition of
the state of the art and the extraction of the most relevant functional data on the existing systems for
the benchmarking.
Task 1.2: Selection of the Systems
The selection of the systems to be investigated will be performed according to the data provided by
the literature examination. Both the materials and the specific reaction will be selected on the basis
the potential scientific and technological impact.
Activity 2: Nanostructure synthesis
i) Synthesis of the anode material for Li-ion batteries based on mixed carbonaceous materials and
metal oxides such as anatase TiO2 or TiO2 nanotubes. Titanium dioxide will be synthesized by both
electrochemical and chemical methods for the production of both nanotube arrays and
nanostructured carbon supported powders. ii) Development of catodic and anodic electrocatalysts
for EPM (Electrolyzers with Polymeric Membrane) of AE (Alkalyne Electrolizers) type
electrolyzers to be employed in hydrogen production from renewable like ethanol, ethylene glycol
or glycerol.
Task 2.1: Electrochemical Methods
i) Materials for Li-ion batteries: Anodization of titanium metal substrates will be employed for the
synthesis of anatase TiO2 or TiO2 nanotube arrays with variable nanotube diameter and length. The
anodization will be followed by heat treatment in order to favour the formation of the active phases;
ii) Cathode and anode for hydrogen production from biomass by electrolysis: The synthesis will be
performed using controlled electrodeposition of metals such as palladium or platinum on suitable
materials such as tissues or networks of nickel and titanium.
Task 2.2: Chemical Methods
i) The chemical synthesis of titanium dioxide nanostructured powders both unsupported and carbon
supported will be performed to obtain new materials for Li-ion batteries. The possibility of doping
the Titania with Si or other metals will also be explored; ii) Synthesis of nanostructured catalysts
containing noble metals (Pd, Pt) evaluation of the catalytic activity in electrolytic cells fed by
alcohols, containing an anionic exchange membrane without membrane. The focus will be the
synthesis of spongy metal phases on conductive carbon, even with mixed binary and ternary metal
oxides. On these materials will be dispersed metal particles by spontaneous deposition and
particular attention will be given to the composition and morphology of the synthesized catalysts.
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The ultimate goal is to obtain metal-oxide catalysts in very small particles containing NP, stabilized
by interaction with metal oxides and the chemical - physical characterization of their properties,
modulated as a function of process parameters. on suitable materials such as tissues or networks of
nickel and titanium.
Activity 3: Characterization
The characterization will consist in the investigation of the catalysts basic properties (structure,
morphology, composition, basic electrochemistry) and functional performances.
This activity will conclude the project with a benchmarking of the produced materials with the state
of the art and a summary of the main findings of the three years of work.
The fundamental characterization will consist in the definition of the basic properties of the
materials. The composition, the structure and the morphology will be investigated as well as the
composition.
Educational Activity
The educational activity of the first year will mainly consists in the examination of the existing
literature. The activity will be also integrated by the seminars which will be organized by the
Istituto per la Chimica dei Composti OrganoMetallici (ICCOM).
Gantt Chart
M 1-3 M 4-6 M 7-9 M
12
10- M 13- M 16- M
15
18
M
M 25- M
M 31- M
19-
22-
27
33
21
24
2830
3436
Activity 1
State of the Art
Task 1.1
Literature analysis
Task 1.2
Selection
of
the
Systems
Activity 2
Nanostructure
Synthesis
Task 2.1
Electrochemical
Methods
Task 2.2
Chemical Methods
Activity3
Characterization
Task 3.1
Basic
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Characterization
Task 3.2
Functional
Characterization
Task 3.3
Benchmarking and
Conclusion
Figure 3: Gantt Chart
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VALENTINA ZANNIER
Email: [email protected]
[email protected]
Laboratory: Istituto Officina dei Materiali IOM – CNR
Laboratorio TASC
Area Science Park – Basovizza (TS)
Title of the thesis: Synthesis and characterization of semiconductor nanowires
Supervisor: Dr. Silvia Rubini
Tutors (if any): /
Research Activity foreseen
State of the art and motivations
Semiconductor nanowires (NWs) are quasi one-dimensional crystals with cylindrical or polyhedral
shape; they have a typical section diameter of some nanometers and length of few microns. They
represent one of the key research areas in nanotechnology due to their novel properties with respect
to the corresponding bulk materials, arising from their mono-dimensionalty, e.g. photon, phonon
and electron confinement, dislocation-free crystal growth on mismatched substrates, size-dependent
reduction in thermal conductivity and good mechanical response1. All these properties provide
significant opportunities for applications in electronics, photonics, biology and medicine. The most
recent literature, in fact, reports the use of semiconductor nanowires as building blocks for field
effect transistors, lasers, photodetectors, solar cells, optical fibers, high resolution microdisplays,
light emitting diodes and chemical sensors 1,2,3,4,5.
Furthermore, the growth of hybrid nanostructures, e.g. semiconductor nanowires grown directly on
graphene layers or on organic semiconductor substrates, has attracted much attention in the recent
years because of the interesting potentials that could result from the combination of the
semiconductor electronic and optoelectronic properties with the mechanical flexibility and the
optical trasparence of these materials 3,6,7,8.
All these features of semiconductor nanowires make them among the top applicants in scientific
research in nanotechnology. In this context, the study of the growth mechanism and the
optimization of the growth process, as well as the investigation and optimization of their structural,
chemical, electrical and optical properties, represent the first step for the realization of novel
nanodevices.
References
[1]
P. Yang, R. Yan, M. Fardy, Semiconductor nanowire: what’s next?, Nanoletters (2010), 10, 1529 – 1536
[2]
Y. Li, F. Qian, J. Xiang, C. M. Lieber, Nanowire electronic and optoelectronic devices, Materials Today
(2006) 9, 18 – 27
[3]
W. U. Huynh, J. J. Dittmer, A. P. Alivisatos, Hybrid Nanorod-Polymer Solar Cells, Science (2002) 295, 2425
– 2427
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[4]
Y. L. Cao, Z.T.Liu, L. M. Chen, Y. B. Tang, L. B. Luo, J. S.Jie, W.J. Zhang, S. T. Lee, C. S. Lee, Singlecrystalline ZnTe nanowires for application as high - performance Green/Ultraviolet photodetector, Optics
Express (2011) 19, 7
[5]
E. Gil-Santos, D. Ramos, J. Martinez, M. Fernandez-Regulez, R. Garcia, A. San Paulo, M. Calleja, J. Tamayo,
Nanomechanical mass sensing and stiffness spectrometry based on two-dimensional vibrations of resonant
nanowires, Nature Nanotechnology (2010) 5, 641 – 645
[6]
W. I. Park, C. H. Lee, J. M. Lee, N. J. Kim, G. C. Yi, Inorganic nanostructures grown on graphene layers,
Nanoscale (2011), 3, 3522 – 3533
[7]
L. Liao, Y.C. Lin, M. Bao, R. Cheng, J. Bai, Y. Liu, Y. Qu, K. L. Wang, Y. Huang, X. Duan, High-speed
graphene transistors with a self-aligned nanowire gate, Nature (2010), 467, 305 – 308
[8]
B. Kumar, K. Y. Lee, H. K. Park, S. J. Chae, Y. H. Lee, S. W. Kim, Controlled growth of semiconducting
nanowire, nanowall, and hybrid nanostructures on grapheme for piezoelectric nanogenerators, AcsNano
(2011), 5, 5, 4197 – 4204
Objectives for the three years
The potentials of semiconductor nanowires are related to their crystal quality, composition, shape
and morphology; the control of these parameters, through a precise growth method and a deep
comprehension of the growth process, is essential for the optimization of their synthesis. A detailed
characterization of the nanostructures grown is also fundamental for understanding their properties
and the possibility to use and integrate them in technological devices.
The purposes of my research project within the PhD in Nanotechnology can be summarized as
follows:
-Growth of II – VI semiconductor nanowires through the bottom-up approach, by means of
Molecular Beam Epitaxy (MBE), using different substrates and different metals as catalysts.
-Optimization of the growth process by testing different growth parameters.
-Detailed study of the growth mechanism of such nanowires, with particular interest on the
interaction between substrate and catalyst and the role it plays on the subsequent nanowire
growth.
-Morphological, structural, optical and electrical characterization of the nanostructures grown,
by means of spectroscopic and microscopic techniques, in order to understand the potential
applications of such nanostructures in novel devices.
-Integration of nanowires grown with graphene layers, organic layers, carbon nanotubes, and
characterization of the systems obtained.
Obbiettivi da raggiungere per il primo anno
For the first year I’m going to reach the following objectives:
-A good knowledge of spectroscopic and microscopic techniques useful for the study of
nanowires growth process and properties, such as X-Ray photoemission spectroscopy
(XPS), reflection of high energy electron diffraction (RHEED) scanning and transmission
electron microscopy (SEM and TEM), X-Ray diffraction, transport measurements,
photoluminescence and other optical techniques.
-Growth of ZnSe nanowires with metal nanoparticles as catalyst: investigation of the growth
mechanism under various growth conditions on different substrates.
-Growth of ZnSe and CdSe nanowires using monodispersed Au nanoparticles from colloidal
solution.
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-Optimization of the nanowires morphology, structural and optical properties.
Research project
The research project will be carried out mainly at the Molecular Beam Epitaxy Laboratory of the
Institute IOM – CNR located in Basovizza (TS). The scientific work I’m going to do there can be
divided into 3 main activities that will be carry out in a complementary way:
1)Growth of II – VI semiconductor nanowires by means of MBE.
2)In situ study of growth mechanism and characterization of nanostructures during the growth.
3)Ex situ characterization of the obtained nanowires.
The first point will include:
-ZnSe nanowires growth on different substrates, with gold and manganese as catalyst. The
growth with nanoparticles generated through the annealing of a metal layer deposited on the
substrates, as well as using monodispersed colloidal nanoparticle solutions will be studied.
-CdSe nanowires growth on different substrates with different metal nanoparticles as catalyst.
-II – VI semiconductor heterostructures growth, e.g core-shell CdSe/ZnSe nanowires, CdSe
quantum dots into ZnSe nanowires.
-Growth of ZnSe, CdSe and heterostructures on non-conventional substrates such as graphene
layers and/or conducting polymers.
The in situ characterization by means of RHEED and XPS, and the Scanning Electron Microscopy
analysis will be routinely carried out during the growth, in order to investigate the growth
mechanism under various growth conditions and optimize the growth process.
Further characterization of the nanostructures, by means of optical measurements
(photoluminescence) and electric transport measurements will be carried out to discriminate the
optimal growth protocol as soon as the major growth parameters have been selected.
Below is reported a project Gantt chart.
Duration
2012
Activities
2013
2014
Gen May Sept
–
–
–
Gen
–
May Sept
–
–
Gen
–
May Sept
–
–
Apr
Apr
Aug
Apr
Aug
Aug
Dec
Dec
Dec
Growth of II – VI semiconductor
NWs
Growth of ZnSe nanowires
Using Au film
Using
Au
nanoparticles
monodispersed
Using Mn as catalyst
Growth of CdSe nanowires
Using Au film
Using
Au
monodispersed
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
200
nanoparticles
Using other metals as catalyst
Growth of heterostructures
Core shell CdSe/ZnSe nanowires
CdSe quantum dots into ZnSe NWs
II–VI NWs grown on organic
layers
In situ characterization
RHEED
XPS
Ex situ characterization
SEM
Photoluminescence
Transport
Other techniques
Educational activity foreseen
During the first year of the PhD, my research work in the Lab will be supported by some
educational activities: I’m going to study the basic principles of all techniques and methods I’ll use
during my research activity from books and literature articles; furthermore I’m going to attend some
courses organized by the International Centre of Theoretical Physics (ICTP), for instance the School
on Sinchrotron Radiation, Free Electron Lasers and their multidisciplinary applications, in order to
learn other modern techniques that could be useful for future studies of the nanostructures and
nanodevices I’ll make.
I’m also going to participate as a speaker at the 6th Nanowires Growth Workshop, which will take
place on 4-6 June 2012 in St. Petersburg, Russia. There I will present the results obtained during the
activity carried out for my Master Degree thesis and during the firsts months of the PhD,
concerning the substrate – catalyst interaction in the epitaxial growth of ZnSe nanowires on
GaAs(111)B.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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4.Pubblicazioni dei dottorandi.
Venogono di seguito riportate le pubblicazioni dei dottorandi desunte dalla schede riportate al punto
precedente:
PUBBLICAZIONI SU RIVISTE SCIENTIFICHE
ACCETTATE PER LA PUBBLICAZIONE)
(PUBBLICATE
O
1.M. Cargnello, A. Gasparotto, V. Gombac, T. Montini, D. Barreca and P. Fornasiero,
"Photocatalytic H2 and added-value byproducts: the role of metal oxide systems in their
synthesis from liquid oxygenates.", European Journal of Inorganic Chemistry 2011 (2011),
4309-4323, selected as cover article.
2.M. Cargnello, N. L. Wieder, P. Canton, T. Montini, G. Giambastiani, A. Benedetti, R. J. Gorte
and P. Fornasiero, "A Versatile Approach to the Synthesis of Functionalized Thiol-protected
Palladium Nanoparticles.", Chemistry of Materials 23 (2011), 3961-3969.
3.J.-S. Kim, N. L. Wieder, A. J. Abraham, M. Cargnello, P. Fornasiero, R. J. Gorte and J. M.
Vohs, "Highly Active and Thermally Stable Core-Shell Catalysts for Solid Oxide Fuel
Cells.", Journal of the Electrochemical Society 158 (2011), B596-B600.
4.N. L. Wieder, M. Cargnello, K. Bakhmutsky, T. Montini, P. Fornasiero and R. J. Gorte, "A
study of the water-gas-shift reaction over Pd@CeO2/Al2O3 core-shell catalysts.", The
Journal of Physical Chemistry C 115 (2011), 915-919.
5.L. Pavan, L. Cozzarini, and V. Lughi, "Interdiffusion-controlled Optical Properties in
Nanocrystalline Heterostructures and Nanostructured Materials", MRS Spring Meeting
2011, San Francisco, CA, USA, 28.04.2011
6.L. Cozzarini, F. Antoniolli and V. Lughi, "Optical properties of a novel nanostructured
CdS/CdTe material", SPIE Smart Structures/NDE, Conference 7890, San Diego, CA, USA,
06.03.2011
7.D’Este E, Baj G, Beuzer P, Ferrari E, Pinato G, Tongiorgi E and Cojoc D, (2011) Integrative
Biology “Use of the optical tweezers technology for long-term, focal stimulation of specific
subcellular neuronal compartments”. May 3;3(5):568-77.
8.Pinato G, Lien LT, D’Este E, Torre V and Cojoc D, (2011) Journal of European Optical
Society “Neuronal chemotaxis by optically manipulated liposomes”. Vol 6, 11042.
9.Pinato G, Raffaelli T, D’Este E, Tavano F and Cojoc D, (2011) Journal of Biomedical Optics
“Optical delivery of liposome encapsulated chemical stimuli to neuronal cells”.
Sep;16(9):095001.
10.D’Este, Pharmacogenetic of escitalopram and mental adaptation to cancer in palliative care:
report of 18 cases. Tumori 97(3):358-61 (2011).
11.R. Fior, S. Maggiolino, M. Lazzarino and O. Sbaizero, “A new transparent BioMEMS for
uni-axial single cell stretching”, Microsystem Technologies 2011 doi:10.1007/s00542-0111325-8
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
202
12.V. Lanzilotto, C. Sanchez-Sanchez, G. Bavdek, D. Cvetko, M. F. Lopez, J. A. Martin-Gago
and L. Floreano “Planar growth of Pentacene on the dielectric TiO2 surface” J. Phys. Chem.
C, 2011, 115 (11), pp 4664–4672
13.C. Sanchez-Sanchez, V. Lanzilotto, C. Gonzalez, A. Verdini, P. de Andrés, L. Floreano,
Maria F. López and J. A. Martín-Gago "Floating molecular layer of spinning C60 molecules
on TiO2(110) surfaces” in preparation
14.C. Sanchez-Sanchez, V. Lanzilotto, G. Bidau, B. Gomez-Lor, R. Perez, L. Florenao, M. F.
Lopez, J. A. Martin-Gago “On-surface Dehydrogenation reactions of polycyclic aromatic
hydrocarbons on Ti02(110)” submitted
15.Immacolata Luisi, Silvia Pavan, Giampaolo Fontanive, Alessandro Tossi, Fabio Benedetti,
Roberto Marzari, Adriano Savoini, Elisa Maurizio, Riccardo Sgarra, Daniele Sblattero,
Federico Berti (submitted) An albumin-derived peptide for binding and catalysis, 2012
16.Monica Marini, Luca Piantanida, Alpan Bek, Rita Musetti, Mingdong Dong, Flemming
Besenbacher, Marco Lazzarino, Giuseppe Firrao (2011) A revertible, autonomous, selfassembled DNA-origami nanoactuator. Nano Letters
17.Migliorini E., Grenci G., Ban J., Pozzato A., Tormen M., Lazzarino M., Torre V., Ruaro ME.
Acceleration of neuronal precursors differentiation induced by substrate nanotopography.
Biotech and Bioeng 2011 Nov; 108,11:2736-2746
18.Migliorini E., Ban J., Di Foggia V., Ruaro ME., Torre V., Lazzarino M. Nanoscale live
imaging. Imaging & Microscopy. 2011 May; 25-28
19.Lasalvia M, Perna G, Mezzenga E, Migliorini E , Lazzarino M, L’Abbate N and Capozzi V.
Atomic force microscopy investigation of morphological changes in living keratinocytes
treated with HgCl2 at not cytotoxic doses. J. of Microscopy. 2011
20.H. Pakdast and M. Lazzarino Triple Coupled Cantilever Systems for Mass Detection and
Localization. Sensors & Actuators: A. Physical, accepted for publication.
21.Tavano F., Bonin S., Pinato G., Stanta G. and Cojoc D., Custom-built optical tweezers for
locally probing the viscoelastic properties of cancer cells. International Journal of
Optomechatronics September 2011
22.Pinato G., Raffaelli T., D’Este E., Tavano F. , Cojoc D., Optical Delivery of liposome
encapsulated chemical stimuli to neuronal cells, International Journal of Biomechanical
Optics 16 (9) September 2011
23.Bonin S., Tavano F. Restoration and Reconstruction of DNA Length , Guidelines for
Molecular Analysis in Archive Tissues Springer-Verlag 2011 Giorgio Stanta Editor
24.“Energy Efficiency Enhancement of Ethanol Electrooxidation on Pd-(CeO2)/C in Passive
and •Valentina Bambagioni, Claudio Bianchini, Yanxin Chen, Jonathan Filippi, Paolo
Fornasiero, Massimo Innocenti, Alessandro Lavacchi, Andrea Marchionni, Werner
Oberhauser, Francesco Vizza, Active Polymer Electrolyte-Membrane Fuel Cells”, submitted
to Chemsuschem, November, 2011
25.Y.X. Chen, M. Bevilacqua, C. Bianchini, S.G. Sun, S.P. Chen, J. Filippi, P. Fornasiero, M.
Innocenti, A. Lavacchi, F. Vizza, F. di Benedetto, A. Marchionni, W. Oberhauser, H. Miller,
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
203
“RedOx Milling and Faceting (ROMiF) - A Post-Treatment for the Size Control and the
High Index Facets Generation of Palladium Nanoparticles.”, (submitted)
26.F. Romanato, M. Massari, T. Ongarello, M. Carli, G. Pirruccio, D. Sammito, V. Giorgis, D.
Garoli, R. Bozio, R. Pilot, R. Signorini, P. Schiavuta, F. Marinello, “Design, Fabrication and
characterization of Plasmonic Gratings for SERS”, Microelectronic Engineering 88 (8), pp.
2717-2720
27.D. Garoli, M. Natali, G. Parisi, T. Ongarello, E. Sovernigo, M. Massari, V. Giorgis, G.
Ruffato, S. De Zuani, F. Romanato “Fabrication of metamaterials in the optical spectral
range”, Microelectronic Engineering 88 (8), pp. 1951-1954
28.Garoli D., Romanato F., Zilio P., Natali M., Marinello F., Ongarello T., Sammito D., De
Salvador D., “Fabrication of "nano-rocket-tips" for plasmonic nanofocusing” (2011)
Microelectronic Engineering, 88 (8), pp. 2530-2532.
29.Romanato F., Pilot R., Massari M., Ongarello T., Pirruccio G., Zilio P., Ruffato G., Carli M.,
Sammito D., Giorgis V., Garoli D., Signorini R., Schiavuta P., Bozio R., “Design,
fabrication and characterization of plasmonic gratings for SERS” (2011) Microelectronic
Engineering, 88 (8), pp. 2717-2720.
30.Zacco G., Romanato F., Sonato A., Sammito D., Ruffato G., Morpurgo M., Silvestri D.,
Carli M., Schiavuta P., Brusatin G., “Sinusoidal plasmonic crystals for bio-detection
sensors” (2011) Microelectronic Engineering, 88 (8), pp. 1898-1901.
31.Liu X, Laurini E, Dal Col V, Posocco P, Ziarelli F, Fermeglia M, Zhang CC, Pricl S, Peng L,
“2-Difluoromethylene-4-methylenepentanoic acid, a paradoxical probe able to mimic the
signaling role of 2-oxoglutaric acid in Cyanobacteria” Organic Letters, Jun 3; 13(11):2924-7
32.Laurini E, Dal Col V, Mamolo MG, Zampieri D, Posocco P, Fermeglia M, Vio L, Pricl S,
“Homology model and docking-based virtual screening for ligands of the σ1 receptor” ACS
Med Chem Lett 2011, 2: 834-839
33.Dal Col V et al. “Activate and respond. A molecular rationale for c-kit activation and drug
response by juxtamembrane mutations in GISTs” Mol Cancer Ther 2011 submitted
34.Dal Col V et al.,“Activity vs. toxicity of acridine compounds as anti-BVDV agents: a
molecular modeling study” Antiviral Res 2011 submitted
35.Frassetto A, Navarra CO, Marchesi G, Turco G, Di Lenarda R, Breschi L, Ferracane JL,
Cadenaro M. Contraction stress and degree of conversion of self-adhesive resin cements.
Dental Materials, submitted.
36.E. Miniussi, M. Pozzo, A. Baraldi, E. Vesselli, R. R. Zhan, G. Comelli, T. O. Menteş¸ M. A.
Niño, A. Locatelli, S. Lizzit, and D. Alfè, “Thermal Stability of Corrugated Epitaxial
Graphene Grown on Re(0001)”, Phys. Rev. Lett. 106, 216101 (2011).
37.E. Miniussi, M. Pozzo, A. Baraldi, E. Vesselli, R. R. Zhan, G. Comelli, T. O. Menteş¸ M. A.
Niño, A. Locatelli, S. Lizzit, and D. Alfè, “A link between corrugation and thermal stability
of epitaxial graphene”, Elettra Highlights 2010-2011, pagg. 66-67.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
204
38.R. Toth, F. Santese, S. P. Pereira, D. R. Nieto, S. Pricl, M. Fermeglia and P. Posocco, “Size
and shape matter! A multiscale molecular simulation approach to polymer nanocomposites”,
Journal of Material Chemistry, 2011 sottomesso
39.F. Santese, D. R. Nieto, P. Posocco, R. Toth, S. Pricl, M. Fermeglia, “Contact angles of
water and oil on polymer surfaces by MD simulations”, Chemical Communications, 2011,
sottomesso
40.F. Santese, D. R. Nieto, P. Posocco, R. Toth, S. Pricl, M. Fermeglia, “Water, oil, and
surfactant solution on polymer surfaces: converging simulation methods for contact angle
determination”, Journal of Physical Chemistry C, 2011 sottomesso
41.L. Tavagnacco, P. E. Mason, U. Schnupf, F. Pitici, L. Zhong, M. E. Himmel, M. Crowley,
A. Cesàro, J. W. Brady, “Sugar-binding sites on the surface of the carbohydrate-binding
module of CBH I from Trichoderma reesei” Carbohydr. Res., 2011, 345(6), 839-846.
42.L. Tavagnacco, U. Schnupf, P. E. Mason, M-L. Saboungi, A. Cesàro, J. W. Brady,
“Molecular dynamics simulation studies of caffeine aggregation in aqueous solution”, J.
Phys. Chem. B, 2011, 115(37), 10957-10966.
43.J. W. Brady, L. Tavagnacco, L. Ehrlich, M. Chen, U. Schnupf, M. E. Himmel, M-L.
Saboungi, A. Ceasàro, “Weakly-hydrated surfaces and the binding interactions of small
biological solutes”, Eur. BioPhys. J. DOI 10.1007/s00249-011-0776-2 (in stampa).
44.F Martelli, M Piccin, G Bais , F Jabeen, S Ambrosini, S Rubini and A Franciosi
Nanotechnology 18 (2007) 125603 (4pp)
45.S. Ambrosini, M. Fanetti, V. Grillo, A. Franciosi and S. Rubini, Journal of Applied Physics
109, 094306 (2011)
46.S. Ambrosini, M. Fanetti, V. Grillo, A. Franciosi and S. Rubini, AIP ADVANCES 1, 042142
(2011)
PUBBLICAZIONI/ABSTRACTS
(NAZIONALI O INTERNAZIONALI)
IN
CONFERENZE/CONGRESSI
1.M. Cargnello, N. Wieder, R. J. Gorte and P. Fornasiero, "Synthesis of dispersible core-shell
metal@oxide materials and their application as stable fuel cell catalysts.", invited speaker at
the conference "Chemically synthesized nanoparticles and catalysis", Argonne National Lab
(Argonne, IL, USA), 28th April 2011.
2.M. Cargnello, R. J. Gorte and P. Fornasiero, "Synthesis of dispersible core-shell metal@oxide
materials and their application as stable fuel cell catalysts.", ICTP-SISSA Workshop on
New Materials for Renewable Energy, ICTP, Trieste, Italy, 17th-21st October 2011.
3.L. Cozzarini "Semiconductor Nanocrystals application to Optoelectronic Devices",
Finmeccanica/Fulbright meeting 2011, Washington DC, USA, 15.03.2011
4.“8th IBRO world congress of Neuroscience” 14-18th July 2011, Florence. D’Este E., Baj G.,
Pinato G., Tongiorgi E. & Cojoc D., “Focal delivery of BDNF to cultured neurons with
optical tweezers”.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
205
5.“EBSA 2011 – 9th European Biophysics Congress”23-27th August 2011, Budapest. D’Este
E., Baj G., Pinato G., Tongiorgi E. & Cojoc D., “Focal delivery of BDNF to cultured
neurons with optical tweezers”.
6.“8th IBRO world congress of Neuroscience” 14-18th July 2011, Florence. Pinato G., Thuy
Lien L., D’Este E., Torre V. & Cojoc D., “Stimulation of neurite retraction and growth by
local release of guidance molecules from lipid vesicles”.
7.Pharmacogenetic of warfarin and its applications in the community medicine . III
Monothematic Symposium SIF 2011 “Pharmacogenomics and cancer: from bench to
bedside”. Grado (GO), Grand Hotel Astoria, October 8, 2011;
8.R. Fior, S. Maggiolino, M. Lazzarino and O. Sbaizero, "A completely transparent MEMS for
mechanical properties evaluation of a single living cell", Proc. SPIE 7929, 792906 (2011)
San Francisco CA USA; doi:10.1117/12.874445 (proceedings- speaker)
9.R. Fior, S. Maggiolino, B. Codan and O. Sbaizero, “A study on the cellular structure during
stress solicitation induced by BioMEMS”, Proc. EMBC 2011 Boston USA (proceedings speaker)
10.R. Fior, S. Maggiolino, B. Codan, R. Lal, O. Sbaizero, “A new BioMEMS for the study of
mechanosensitive ion channels”, Nanotechitaly 2011Venice Italy (poster)
11.V. Martinelli, I. Pecorari, S. Maggiolino, R. Fior, B. Codan, L. Mestroni, O. Sbaizero,
“Metabolic and proliferative cells activity on different substrates”, Nanotechitaly 2011
Venice Italy (poster)
12.B. Codan, D. Dorigo, V. Martinelli, S. Maggiolino, R. Fior and O. Sbaizero, “Lithograpic
patterned substrate with nanotips for cell indentation”, Nanotechitaly 2011 Venice Italy
(poster)
13.Pecorari, B. Codan, V. Martinelli, S. Maggiolino, R. Fior and O. Sbaizero, “Mechanical
properties of 3T3 fibroblasts due to fixation assessed using atomic force microscopy”,
Nanotechitaly 2011 Venice Italy (poster)
14.V. Zammattio, I. Pecorari, B. Codan, V. Martinelli, S. Maggiolino, R. Fior and O. Sbaizero,
“AFM cell morphological analysis: Influence of different environmental conditions on fixed
and living cells”, Nanotechitaly 2011 Venice Italy (poster)
15.R. Fior, S. Maggiolino, M. Lazzarino and O. Sbaizero, "A completely transparent MEMS for
mechanical properties evaluation of a single living cell", Proc. SPIE 7929, 792906 (2011)
San Francisco CA USA; doi:10.1117/12.874445
16.R. Fior, S. Maggiolino, B. Codan and O. Sbaizero, “A study on the cellular structure during
stress solicitation induced by BioMEMS”, Proc. EMBC 2011 Boston USA
17.“Planar Growth of Pentacene on the Dieletric TiO2(110)-1X1” V. Lanzilotto, C. SànchezSànchez, G. Bavdek, J. A. Martin Gago and L. Floreano, Summer School of
Nanotechnology, Università di Trieste 20-23/09/2011; (poster)
18.“DNA-based autonomous devices at the nanoscale” presso la conferenza “ Joint ICTP-KFAS
Conference on Nanotechnology for Biological and Biomedical Applications” (10-14 Ottobre
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
206
2011), ICTP (Miramare). Marini M., Piantanide L, Bek A, Lazzarino M, Musetti R, Firrao
G.
19.Tavano F, StantaG., CojocC., PinatoG., MiglioriniE., D’Este E., BoninS. 2nd Physics of
Cancer Symposium - Leipzig 13-15 October 2011 Poster Presentation: Local membrane
mechanical probing of neoplastic and non-neoplastic human cells
20.Tavano F., Bonin S., D'Este E., Pinato G., Stanta G., Cojoc D., 8th European Biophysics
Congress (EBSA) - Budapest 23-27 August 2011, Poster Presentation: Cell mobility and
metastatic spreading: a study on human neoplastic cells using Optical Tweezers” F.Tavano,
S.Bonin, E.D’Este, G.Pinato, G.Stanta, D.Cojoc
21.Pezcoller Foundation Symposium : Engineering In Cancer Research 16th -18th June 2011Trento-Italy Poster presentation: “Cell mobility and metastatic spreading: a study on human
neoplastic cells using Optical Tweezers” ” F.Tavano, S.Bonin, E.D’Este, G.Pinato, G.Stanta,
D.Cojoc
22.S. Bidoggia; L. Pasquato; “European Winter School on Physical Organic Chemistry”;
Presentazione poster dal titolo: “Perfluorinated monolayer-protected Au nanoparticles for
membrane permeation”; Bressanone, Italia, 30 gennaio-4 febbraio 2011.
23.S. Bidoggia, P. Posocco, M. Fermeglia, S. Pricl, and L. Pasquato; “Summer School on
Nanotechnology”; Presentazione poster dal titolo: “Control of the morphology of mixed
monolayers protecting gold nanoparticles using perfluoro ligands”; Trieste, 20-23 settembre
2011.
24.M.Ganau, P.Parisse, S.Corvaglia, L.Ianeselli, D.Scaini, C.Sanavio, L.Casalis, G.Scoles.
Proteomic analyses of malignant gliomas. Regional Summer School of Nanotechnology
2011
25.S.Corvaglia, M.Ganau, Fruk L, Sanavio B, Ianeselli L, Cesselli D, Beltrami AP, Scoles G,
Scaini D, Casalis L. Combination of novel protein nanoarrays and microwells devices for
single cell protein profiling. Gordon Research Conference Proceedings 2011
26.V. Giorgis, F. Romanato, M. Massari, G. Parisi, M. Carli, D. Sammito, E. Sovernigo,
“Design, Fabrication and Characterization of Split Ring Resonators using X-Ray
Lithography”, MNE 2011
27.G. Bovo, D. Sammito, D. De Salvador, G. Biasiol, M. Gaio, T. Ongarello, V. Giorgis, “Design
of a plasmonic structure integrated on a GaAs HEMT photodetector for biosensing
applications”, MNE 2011
28.D. Sammito, G. Zacco, P. Zilio, V. Giorgis, A. Martucci, J. Janusonis, “Design and
fabrication of plasmonic gratings for bulk Silicon solar cell light harvesting enhancement”,
MNE 2011
29.S. De Zuani, M. Natali, D. Garoli, V. Giorgis, M. Massari, G. Parisi, “Ferroelectric
metamaterials: towards a refractive index control”, Metamaterials 2011
30.Polylysine coated silver nanoparticles as sensors for bilirubin quantification using Surface
Enhanced Raman Spectroscopy (SERS)”, L. Marsich, A. Bonifacio, V. Sergo; Yellow
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
207
Retreat – Trieste, 06 – 07 giugno 2011 (Congresso sulla biliribina organizzato dal Centro
Studi Fegato)
31.D. Sammito, P. Zilio, G. Zacco, A. Martucci, M. Dai Prè, J. Janusonis, J. Ulbikas, S.
Padovani, F. Rasello, S. Sinesi and F. Romanato, “The ORION project: nanotechnology
applied to bulk Silicon solar cells”, NanotechItaly 2011, Venezia 23-25 Novembre 2011
32.G. Zacco, D. Sammito, P. Zilio, G. Melcarne, G. Gigli, M. Mazzeo, F. Romanato, “Light
harvesting enhancement in organic solar cells through the integration of plasmonic crystals”,
26th European Photovoltaic Solar Energy Conference and Exhibition, Hamburg 5-9
Settembre 2011
33.G. Bovo, D. Sammito, D. De Salvador, G. Biasiol, M. Gaio, V. Giorgis, P. Zilio, T.
Ongarello and F. Romanato, “Design of a plasmonic structure integrated on a GaAs HEMT
photodetector for biosensing applications”, 37th International Conference on Micro and
Nano Engineering, Berlino 19-23 Settembre 2011
34.V. Giorgis, F. Romanato, M. Massari, G. Parisi, M. Carli, D. Sammito, E. Sovernigo,
“Design, Fabrication and Characterization of Split Ring Resonators using X-Ray
Lithography”, 37th International Conference on Micro and Nano Engineering, Berlino 19-23
Settembre 2011
35.Dal Col V et al., Comunicazione a VNPCF Trieste 2011 28-30 marzo “The long and winding
road of the c-Kit JXM domain”.
36.” Dal Col V et al., Comunicazione a VNPCF Trieste 2011 28-30 marzo “Overview on σ1
receptors: a 3D homology model to solve a part of the enigma
37.Dal Col V et al., comunicazione a CDDD L’Aquila 2011 21-23 novembre “Nanozapped!
DNA, siRNA, and their dendritic nanovectors: a combined in silico/in vivo/in vitro
approach”
38.Dal Col V et al., Comunicazione a CDDD L’Aquila 2011 23-25 novembre “The SigmaEnigma. A multistep homology modeling of s1 receptors”
39.Dal Col V et al., Comunicazione a Nanotechitaly 23-25 novembre 2011 “Trekking across
GISTs: the clinical journey of KIT, PDGFRA, and the in silico prediction of drug resistance
in cancer targeted therapy”
40.E. Miniussi, “A link between corrugation and thermal stability of epitaxial graphene”, in
occasione dell’assegnazione del premio Fonda-Fasella 2011 workshop “Nanoenergetics:
theoretical and experimental approaches” (Trieste, 15-16 Novembre 2011).
41.Gianluca Grenci, Giovanni Birarda, Elisa Mitri, Luca Businaro, Sabrina Pacor, Lisa Vaccari,
Massimo Tormen, “Optimization of Microfluidic Systems for IRMS real Time Monitoring
of Living Cells”, “Microfluidic devices for real-time infrared imaging of living cells”, “Atti
del XXIV Congresso Nazionale della Società Chimica Italiana” per la Divisione
Computazionale, 2011
42.G. Birarda, G. Grenci, L. Businaro, E. Mitri, M. Tormen, S. Pacor and L. Vaccari, “C K-edge
NEXAFS Spectra of Model Systems for C2H4 on Si(100): a DFT Simulation”, contenuti
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
208
riportati negli “Atti del XXIV Congresso Nazionale della Società Chimica Italiana” per la
Divisione Computazionale, 2011
43.M. Fermeglia, P. Posocco, R. Toth, D. R. Nieto, F. Santese and S. Pricl, “The Factory of the
Future: Integrating Multiscale Modeling and Experiments to Produce New, Better
Nanocomposite Materials” 24 ottobre 2011 Minneapolis AIChE Annual Meeting 2011
44.M.Fermeglia, P. Posocco, R. Toth, D. Romero, F. Santese, S. Pricl, “Chemistry and shape
effects in polymer based nanocomposites: a multiscale modeling study.” Eurofillers 2011
comunicazione: 21-22 agosto 2011 Dresden, Germany
45.P. Posocco, F. Santese, D. R. Nieto, E. Laurini, M. Fermeglia, J. W. Handgraaf, H. G.E.M.
Fraaije, M. Lisal, S. Pricl, “Nanoparticles at large. A multiscale molecular modeling
protocol to predict/explain structure-property relationships in nanocomposite systems”
NanotechItaly, 23-25 novembre 2011, Venezia
46.F. Santese, D. R. Nieto P. Posocco, R. Toth, M. Fermeglia, S. Pricl, “Interfacial wettability
of polymeric surfaces by oil, water and surfactant/water nanodroplets. A molecular dynamic
study” NanotechItaly 2011 23-25 novembre 2011, Venezia
47.L. Tavagnacco, A. Cesàro, J. W. Brady, “Thermodynamics of aqueous caffeine selfassociation: a revisitation”, “10th Mediterranean Conference on Calorimetry and Thermal
Analysis - MEDICTA 2011”, 24 - 27 Luglio 2011, Porto, Portogallo.
48.Self catalyzed GaAs nanowires on GaAs (100): growth and characterization, S. Ambrosini,
M. Fanetti, V. Grillo and S. Rubini, New Trends in Nanotechnology, Braga (Portugal) 09/10
49.Self catalyzed GaAs nanowires on Si-treated epiready (100) GaAs wafers by MBE, S.
Ambrosini, M. Fanetti, V. Grillo, A. Franciosi and S. Rubini, III-V Nanowire workshop,
Bad Honnef (Germany), 02/2011
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5.Giudizi dei referee esterni per dottorandi ammessi all’esame finale
aprile 2012
Di seguito sono riportati i referee esterni scelti dal collegio per ciascuno dei dottorandi:
Dottorando
Astolfo
Alberto
Titolo
Supervisore
Development of novel ARFELLI
experimental methods for Fulvia
cell
tracking
using
nanoparticles
Bellomo
Francesca
Biopolymer based scaffold
for tissue engineering
Birarda
Giovanni
Development
of
microfluidic devices for
biomedical applications of
Synchrotron
Radiation
FTIR Microspectroscopy
Nanoscale interaction for
higher
efficiency
of
contrast media
Analysis of aging and
stability
of
bonded
interface in dentistry
Fontanive
Luca
Marchesi
Giulio
Reviewers
L. Dean Chapman, PhD
Professor, Anatomy & Cell Biology, University of
Saskatchewan
Dr. Juergen Mollenhauer
NMI Naturwissenschaftliches und Medizinisches Institut
University of Tübingen,
PAOLETTI
Dr. Niko Moritz
Sergio
University of Turku, Finland, Orthopaedic Research Unit
Dr. Judith Juhasz
University of Cambridge, United Kingdom
FRANCIOSI
Dr. Paul Dumas
Alfonso / Lisa synchrotron-soleil.fr
Vaccari
Dr. Nikolaj Gadegaard
[email protected]
CESARO
Attilio
BRESCHI
Lorenzo
Rampino
Antonio
Polysaccharide
based CESARO
nanoparticles for drug Attilio
delivery
Santarelli
Xenja
Development
of ROSEI Renzo
capabilities for ‘in situ’
analysis of nanoparticles at
the
MCX
powder
diffraction Beamline
Influence of nanostructure MORGANTE
on the electronic properties Alberto
of
heterojunctions
in
photovoltaic cells
Sovernigo
Enrico
Prof. Assuntina Morresi - Dipartimento di Chimica,
Università di Perugia Alessandro Maiocchi - Centro Ricerche Bracco Prof. Steve Armstrong, Department of Operative
Dentistry, College of Dentistry, The University of Iowa
- Iowa City, Iowa, USA
Prof. Marcela Carrilho, GEO/UNIBAN,Health
Institute, Bandeirante University of São Paulo, São
Paulo, Brazil
Carla M. Caramella - Department of Pharmaceutical
Chemistry - University of Pavia –
Paolo BLASI, Ph.D.Dip. Chimica e Tecnologia del
Farmaco - Università di Perugia Prof. Alvise Benedetti Univ. Ca Foscari:
Prof. Jennifer Mac Load, NFL Montreal:
Prof. Dr. Gvido Bratina
Università Ljubliana, SLO
Dr.ssa Francesca Brunetti, University of Rome "Tor
Vergata"
Vedi dettaglio negli allegati.
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6.Giudizi della commissione d’esame finale aprile 2012
La commissione composta dai Professori, Università di Trieste (membro interno), hanno sentito i
candidati e stilato i seguenti giudizi:
Cozzarini Luca
Il candidato ha illustrato il suo lavoro di tesi che è consistito nella progettazione e nella
realizzazione di materiali nano strutturati basati su quantum dots per moduli fotovoltaici.
La commissione ha apprezzato il livello scientifico del lavoro svolto ed ha individuato una grande
potenzialità per un approccio applicativo.
Il candidato ha dimostrato di possedere una notevole conoscenza della materia in studio,
affrontando la discussione con competenza nelle tecniche proprie del lavoro di tesi. Il candidato ha
risposto compiutamente ed in modo chiaro alle domande dei Commissari.
Approvata la relazione, la Commissione propone che al candidato VENGA conferito il titolo di
Dottore di Ricerca.
Era Daniel
Il candidato ha illustrato il suo lavoro di tesi che ha riguardato lo studio dei meccanismi di farmaco
cinetica legati a fenomeni che si estrinsecano alla nanoscala.
La commissione ha apprezzato il livello scientifico del lavoro svolto ed ha individuato una grande
potenzialità per un approccio applicativo.
Il candidato ha dimostrato di possedere una notevole conoscenza della materia in studio,
affrontando la discussione con competenza nelle tecniche proprie del lavoro di tesi. Il candidato ha
risposto compiutamente ed in modo chiaro alle domande dei Commissari.
Approvata la relazione, la Commissione propone che al candidato VENGA conferito il titolo di
Dottore di Ricerca.
D’Este Elisa
La candidata ha illustrato in lingua inglese il suo lavoro di tesi che ha riguardato la manipolazione
di sostanze biologiche tramite strumenti spettroscopici avanzati.
La commissione ha apprezzato l’eccellente lavoro innovativo e di frontiera affrontato dal candidato.
Il candidato ha dimostrato di possedere una ottima conoscenza della materia in studio, presentando
con molta competenza e con completezza il suo lavoro di tesi, rispondendo puntualmente e
compiutatamente alle domande della Commissione.
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Approvata la relazione, la Commissione propone che alla candidata VENGA conferito il titolo di
Dottore di Ricerca e, avendo verificato la sussistenza dei requisiti previsti, la certificazione
aggiuntiva Doctor Europaeus.
Lanzilotto Valeria
La candidata ha illustrato il suo lavoro di tesi che ha avuto come argomento principale i fenomeni di
auto assemblaggio a livello nanometrico in film organici sottili su superfici metalliche.
La commissione ha apprezzato il livello scientifico elevato del lavoro svolto, caratterizzato da
innovative metodologie di indagine.
La candidata ha dimostrato di possedere una ottima conoscenza della materia in studio, presentando
con competenza e con completezza il suo lavoro di tesi, rispondendo puntualmente alle domande
della Commissione.
Approvata la relazione, la Commissione propone che alla candidata VENGA conferito il titolo di
Dottore di Ricerca.
Fior Raffaella
La candidata ha presentato il suo lavoro di tesi relativo allo studio proprietà elettriche e meccaniche
di singole celle.
La commissione ha apprezzato il livello scientifico elevato del lavoro svolto, caratterizzato da un
approccio originale al problema analizzato.
La candidata ha dimostrato di possedere una ottima conoscenza della materia in studio, presentando
con competenza e con completezza il suo lavoro di tesi, rispondendo puntualmente alle domande
della Commissione.
Approvata la relazione, la Commissione propone che alla candidata VENGA conferito il titolo di
Dottore di Ricerca.
Luisi Immacolata
La candidata ha presentato il suo lavoro di tesi che ha avuto come argomento l’identificazione di
scaffold formati da proteine per legare molecole di piccole dimensioni.
La commissione ha apprezzato il livello scientifico del lavoro svolto ed ha individuato una grande
potenzialità per un approccio applicativo.
Il candidato ha dimostrato di possedere una notevole conoscenza della materia in studio,
affrontando la discussione con competenza nelle tecniche proprie del lavoro di tesi. Il candidato ha
risposto compiutamente ed in modo chiaro alle domande dei Commissari.
Approvata la relazione, la Commissione propone che alla candidata VENGA conferito il titolo di
Dottore di Ricerca.
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Pakdast Hossein
Il candidato ha presentato il suo lavoro di tesi che ha avuto come argomento principale la
progettazione e la realizzazione di risuonatori MEMS per il riconoscimento di singole molecole.
La commissione ha apprezzato il livello scientifico del lavoro svolto ed ha individuato una grande
potenzialità per un approccio applicativo.
Il candidato ha dimostrato di possedere una notevole conoscenza della materia in studio,
affrontando la discussione con competenza nelle tecniche proprie del lavoro di tesi. Il candidato ha
risposto compiutamente ed in modo chiaro alle domande dei Commissari.
Approvata la relazione, la Commissione propone che al candidato VENGA conferito il titolo di
Dottore di Ricerca.
Sciuto Giacomo
Il candidato ha presentato il suo lavoro di tesi che ha avuto come argomento principale
l’applicazione delle nano scienze al miglioramento degli scambiatori di calore industriali.
La commissione ha apprezzato il livello scientifico elevato del lavoro svolto, caratterizzato da un
approccio originale al problema analizzato.
La candidata ha dimostrato di possedere una ottima conoscenza della materia in studio, presentando
con competenza e con completezza il suo lavoro di tesi, rispondendo puntualmente alle domande
della Commissione.
Approvata la relazione, la Commissione propone che al candidato VENGA conferito il titolo di
Dottore di Ricerca.
Marini Monica
La candidata ha presentato il suo lavoro di tesi che ha avuto come argomento l’implementazione di
logiche semplificate in nano sensori ibridi bio inorganici.
La commissione ha apprezzato l’eccellente lavoro innovativo e di frontiera affrontato dal candidato.
Il candidato ha dimostrato di possedere una ottima conoscenza della materia in studio, presentando
con molta competenza e con completezza il suo lavoro di tesi, rispondendo puntualmente e
compiutatamente alle domande della Commissione.
Approvata la relazione, la Commissione propone che alla candidata VENGA conferito il titolo di
Dottore di Ricerca.
Migliorini Elisa
La candidata ha presentato il suo lavoro di tesi che ha avuto come argomento la caratterizzazione di
substrati nano strutturati per il controllo di cellule staminali embrionali.
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La commissione ha apprezzato l’eccellente lavoro innovativo e di frontiera affrontato dal candidato.
Il candidato ha dimostrato di possedere una ottima conoscenza della materia in studio, presentando
con molta competenza e con completezza il suo lavoro di tesi, rispondendo puntualmente e
compiutatamente alle domande della Commissione.
Approvata la relazione, la Commissione propone che alla candidata VENGA conferito il titolo di
Dottore di Ricerca.
Tavano Federica
La candidata ha illustrato in lingua inglese il suo lavoro di tesi che ha avuto come argomento
l’utilizzo di optical tweezer per lo studio della mobilità di cellule umane per lo studio della
propagazione metastica.
La commissione ha apprezzato il livello scientifico elevato del lavoro svolto, caratterizzato da una
notevole varietà di metodologie di indagine..
La candidata ha dimostrato di possedere una ottima conoscenza della materia in studio, presentando
con competenza e con completezza il suo lavoro di tesi, rispondendo puntualmente alle domande
della Commissione.
Approvata la relazione, la Commissione propone che alla candidata VENGA conferito il titolo di
Dottore di Ricerca e, avendo verificato la sussistenza dei requisiti previsti, la certificazione
aggiuntiva Doctor Europaeus.
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7.Elenco dei componenti del collegio docenti
Componente
Ente
Dipartimento
BARALDI
University Trieste Department of Physics - DF
Alessandro
BERTI Federico University Trieste Department of Chemical and
Pharmaceutical Sciences - DSCF
BIASIOL Giorgio IOM-CNR
Advanced Technology and
Nanosceinces - TASC INFM
BONIN Serena University Trieste Clinical Department of Medical
Science, Surgery and Healt DCSMCS
BRESCHI
University Trieste Clinical Department of Medical
Lorenzo
Science, Surgery and Healt DCSMCS
CADENARO
University Trieste Clinical Department of Medical
Milena
Science, Surgery and Healt DCSMCS
CASALIS
Elettra
Not assigned
Loredana
Synchrotron Spa
CESARO Attilio University Trieste Department of Life Sciences - DLS
COJOC Dan
Advanced Technology and
Nanosceinces - TASC INFM
University Trieste Department of Physics - DF
SSD
FIS/03
Qualifica Ruolo Collegio
RU
Exclusive
Member
CHIM/06 RU
Member
RIC
MED/34 RU
Member non
academic
Exclusive
Member
MED/28 PA
Exclusive
Member
MED/28 PA
Exclusive
Member
RIC
CHIM/04 PO
IOM-CNR
RIC
COMELLI
Giovanni
DA ROS Tatiana University Trieste Department of Chemical and
Pharmaceutical Sciences - DSCF
DANANI Andrea University School Not assigned
Italian Swiss
FIS/03
DE VITA
Alessandro
DI LENARDA
Roberto
University Trieste Department of Engineering and
Architecture - DIA
University Trieste Clinical Department of Medical
Science, Surgery and Healt DCSMCS
University Padova Not assigned
INGPA
IND/22
MED/28 PO
MED/08 PO
Member
University Trieste Department of Engineering and
Architecture - DIA
University Udine Department of Biology and Plant
Protection - DBPP (UD)
University Trieste Department of Chemical and
Pharmaceutical Sciences - DSCF
Elettra
Synchrotron Spa
INGIND/24
AGR/12
PO
Director
PA
Member
FASSINA
Ambrogio
FERMEGLIA
Maurizio
FIRRAO
Giuseppe
FORNASIERO
Paolo
FRALEONI
Alessandro
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
PO
Member non
academic
Exclusive
Member
Member non
academic
Exclusive
Member
Exclusive
Member
Member
foreing
University
Exclusive
Member
Exclusive
Member
CHIM/08 RU
RIC
CHIM/03 PA
RIC
Exclusive
Member
Member non
academic
215
Componente
Ente
Dipartimento
SSD
Qualifica Ruolo Collegio
FRONZONI
University Trieste Department of Chemical and
CHIM/02 PA
Exclusive
Giovanna
Pharmaceutical Sciences - DSCF
Member
GAMINI Amelia University Trieste Department of Life Sciences - DLS CHIM/04 RU
Exclusive
Member
GIRALDI Tullio University Trieste Department of Life Sciences - DLS BIO/14 PO
Member non
academic
KISKINOVA
Elettra
Not assigned
RIC
Member non
Maya
Synchrotron Spa
academic
LAZZARINO
IOM-CNR
Advanced Technology and
RIC
Member non
Marco
Nanosceinces - TASC INFM
academic
LUGHI Vanni
University Trieste Department of Engineering and INGRIC
Exclusive
Architecture - DIA
IND/22
Member
MACOR Paolo University Trieste Department of Life Sciences - DLS MED/04 RIC
Exclusive
Member
MARSI Stefano University Trieste Department of Engineering and INGRU
Exclusive
Architecture - DIA
INF/01
Member
MARZARI
University Trieste Department of Life Sciences - DLS BIO/06 PO
Exclusive
Roberto
Member
MORGANTE
University Trieste Department of Physics - DF
FIS/01
PA
Vice Director
Alberto
MUSCIA
University Trieste Department of Engineering and
PA
Exclusive
Roberto
Architecture - DIA
Member
ONESTI Silvia
Elettra
Not assigned
RIC
Member non
Synchrotron Spa
academic
PAOLETTI Sergio University Trieste Department of Life Sciences - DLS BIO/19 PO
Member
PASQUATO
University Trieste Department of Chemical and
CHIM/06 PA
Exclusive
Lucia
Pharmaceutical Sciences - DSCF
Member
PASSAMONTI University Trieste Department of Life Sciences - DLS BIO/10 RIC
Exclusive
Sabina
Member
PRATI Ubaldo Fund. Tommaso Not assigned
P.Osp
Member non
Campanella
academic
PRICL Sabrina University Trieste Department of Engineering and INGPA
Exclusive
Architecture - DIA
IND/24
Member
RUBINI Silvia
IOM-CNR
Advanced Technology and
RIC
Member non
Nanosceinces - TASC INFM
academic
SBAIZERO Orfeo University Trieste Department of Engineering and INGPO
Exclusive
Architecture - DIA
IND/22
Member
SCAINI Denis
Elettra
RIC
Member non
Synchrotron Spa
academic
SCHMID Chiara University Trieste Department of Engineering and INGPA
Exclusive
Architecture - DIA
IND/22
Member
SERGO Valter University Trieste Department of Engineering and INGPO
Exclusive
Architecture - DIA
IND/22
Member
STANTA Giorgio University Trieste Clinical Department of Medical
MED/08 PA
Member
Science, Surgery and Healt DCSMCS
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216
Componente
Ente
TOFFOLI
CRO Aviano
Giuseppe
TORMEN
IOM-CNR
Massimo
UGO Paolo
University Venezia
Dipartimento
Not assigned
VACCARI Lisa
Not assigned
Elettra
Synchrotron Spa
Advanced Technology and
Nanosceinces - TASC INFM
Not assigned
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
SSD
Qualifica Ruolo Collegio
P.Osp
Member non
academic
RIC
Member non
academic
CHIM/01 PA
Exclusive
Member
RIC
Member non
academic
217
8. Produzione scientifica del collegio docenti 2007-2012
Personale di ruolo nelle università italiane e INAF
1. BARALDI Alessandro
 BIANCHETTIN L, BARALDI A., VESSELLI E, DE GIRONCOLI S, LIZZIT S, PETACCIA L, COMELLI G., ROSEI R
(2007). Experimental and Theoretical Surface Core Level Shift Study of the S-Rh(100) Local Environment.
JOURNAL OF PHYSICAL CHEMISTRY. C, NANOMATERIALS AND INTERFACES, vol. 111; p. 4003-, ISSN: 1932-7447
 BARALDI A., BIANCHETTIN L, VESSELLI E, DE GIRONCOLI S, LIZZIT S, PETACCIA L, ZAMPIERI G, COMELLI G.,
ROSEI R (2007). Highly under-Coordinated Atoms at Rh Surfaces: Interplay of Strain and Coordination Effects on
Core Level Shift. NEW JOURNAL OF PHYSICS, vol. 9; p. 143-, ISSN: 1367-2630
 BUATIER DE MONGEOT F, TOMA A, MOLLE A, LIZZIT S, PETACCIA L, BARALDI A. (2007). Self-organised
synthesis of Rh nanostructures with tunable chemical reactivity. NANOSCALE RESEARCH LETTERS, vol. 2; p. 251-,
ISSN: 1931-7573
 BARALDI A., VESSELLI E., BIANCHETTIN L, COMELLI G, LIZZIT S, PETACCIA L, DE GIRCONCOLI S, LOCATELLI
A, MENTES O.T, ABALLE L, WEISSENRIEDER J, ANDERSEN J.N (2007). The (1x1)-> hexagonal phase transition on
Pt(100) studied by high resolution core level photoemission. THE JOURNAL OF CHEMICAL PHYSICS, vol. 127; p.
164702-, ISSN: 0021-9606, doi: 10.1063/1.2794344
 DING X, DE ROGATIS L, VESSELLI E, BARALDI A., COMELLI G, ROSEI R, SAVIO L, VATTUONE L, ROCCA M,
FORNASIERO P, ANCILOTTO F, BALDERESCHI A, PERESSI M. (2007). Interaction of carbon dioxide with Ni(110): a
combined experimental and theoretical study. PHYSICAL REVIEW. B, CONDENSED MATTER AND MATERIALS
PHYSICS, vol. 76; p. 195425-(1-12), ISSN: 1098-0121, doi: 10.1103/PhysRevB.76.195425
 TAIT S.L, WANG Y, LIN N, COSTANTINI G, BARALDI A., ESCH F, LIZZIT S, PETACCIA L, KERN K (2008). MetalOrganic coordination interactions in Fe-Teraphthalic acid networks on Cu(100). JOURNAL OF THE AMERICAN
CHEMICAL SOCIETY, vol. 130; p. 2108-2113, ISSN: 0002-7863, doi: 10.1021/ja0778186
 BARALDI A. (2008). Structure and chemical reactivity of transition metal surfaces as probed by synchrotron
radiation core-level photoelectron spectroscopy. JOURNAL OF PHYSICS. CONDENSED MATTER, vol. 20; p. 93001-,
ISSN: 0953-8984
 L. BIANCHETTIN, BARALDI A., S. DE GIRONCOLI, E. VESSELLI, S. LIZZIT, L. PETACCIA, G. COMELLI, R. ROSEI
(2008). Core level shifts of under-coordinated Pt atoms. THE JOURNAL OF CHEMICAL PHYSICS, vol. 128; p.
114706-, ISSN: 0021-9606
 E. VESSELLI, L. BIANCHETTIN, BARALDI A., A. SALA, G. COMELLI, L. PETACCIA, S. LIZZIT, S. DE GIRONCOLI
(2008). The Ni3Al(111) surface structure: experiment and theory. JOURNAL OF PHYSICS. CONDENSED MATTER,
vol. 20; p. 195223-195223-7, ISSN: 0953-8984
 T. STAUDT, A. DESIKUSUMASTUTI, M. HAPPEL, E. VESSELLI, BARALDI A., S. GARDONIO, S. LIZZIT, F. ROHR
AND J. LIBUDA (2008). Modelling NOx storage meterials: a high-resolution photoelectron spectroscopy study on
the interaction of NO2 with Al2O3/NiAl(110) and BaO/Al2O3/NiAl(110). JOURNAL OF PHYSICAL CHEMISTRY. C,
NANOMATERIALS AND INTERFACES, vol. 112; p. 9835-, ISSN: 1932-7447
 VESSELLI E, CAMPANIELLO M, BARALDI A., BIANCHETTIN L, AFRICH C, ESCH F, LIZZIT S, COMELLI G. (2008).
A Surface Core Level Shift Study of Hydrogen-Induced Ordered Structures on Rh(110). JOURNAL OF PHYSICAL
CHEMISTRY. C, NANOMATERIALS AND INTERFACES, vol. 112; p. 14475-, ISSN: 1932-7447
 VESSELLI E, DE ROGATIS L, DING X, BARALDI A., SAVIO L, VATTUONE L, ROCCA M, FORNASIERO P, PERESSI
M., BALDERESCHI A, ROSEI R, COMELLI G (2008). Carbon Dioxide Hydrogenation on Ni(110). JOURNAL OF THE
AMERICAN CHEMICAL SOCIETY, vol. 130(34); p. 11417-11422, ISSN: 0002-7863, doi: 10.1021/JA802554G
 S. LIZZIT, Y. ZHANG, K.L. KOSTOV, L. PETACCIA, BARALDI A., R. LARCIPRETE, D. MENZEL, K. REUTER (2009).
O- and H- induced surface core level shifts on Ru(0001): prevalence of the additivity rule. JOURNAL OF PHYSICS.
CONDENSED MATTER, vol. 21; p. 134009-, ISSN: 0953-8984
 M. BIANCHI, D. CASSESE, A. CAVALLIN, R. COMIN, F. ORLANDO, L. POSTREGNA, E. GOLFETTO, S. LIZZIT,
BARALDI A. (2009). Clean and oxygen induced surface core level shift on Ir(111). NEW JOURNAL OF PHYSICS,
vol. 11; p. 063002-, ISSN: 1367-2630
 BIANCHETTIN L, BARALDI A., DE GIRONCOLI S, VESSELLI E, LIZZIT S, COMELLI G., ROSEI R (2009). Surface
Core Level Shift: High Sensitive Probe to Oxygen-Induced Reconstruction of Rh(100). JOURNAL OF PHYSICAL
CHEMISTRY. C, NANOMATERIALS AND INTERFACES, vol. 113; p. 13192-, ISSN: 1932-7447
 S. LIZZIT, BARALDI A., CH. GRÜTTER, J.H. BILGRAM, PH. HOFMANN (2009). The surface phase transition and
low temperature phase of a-Ga(010) studied by SPA-LEED. SURFACE SCIENCE, vol. 603; p. 3222-, ISSN: 00396028
 P. LACOVIG, M. POZZO, D. ALFÈ, P. VILMERCATI, BARALDI A., S. LIZZIT (2009). Growth of dome-shaped
carbon nanoislands on Ir(111): the intermediate between carbidic clusters and quasi free-standing graphene.
PHYSICAL REVIEW LETTERS, vol. 103; p. 166101-, ISSN: 0031-9007
 DE ROGATIS L, VESSELLI E, BARALDI A., CASULA M.F, MONTINI T, COMELLI G, GRAZIANI M, FORNASIERO P.
(2009). Charge Redistribution at the Embedded Rh-Alumina Interface. JOURNAL OF PHYSICAL CHEMISTRY. C,
NANOMATERIALS AND INTERFACES, vol. 113(42); p. 18069-18074, ISSN: 1932-7447, doi: 10.1021/JP905736Q
 Golfetto E., BARALDI A., Pozzo M., Alfè D., Sala A., Lacovig P., Vesselli E., Lizzit S., Comelli G., Rosei R. (2010).
Determining the chemical reactivity trends of Pd/Ru(0001) pseudomorphic overlayers: core level shift
measurements and DFT calculations. JOURNAL OF PHYSICAL CHEMISTRY. C, NANOMATERIALS AND INTERFACES,
vol. 114 (2010); p. 436--, ISSN: 1932-7447
 BALOG R., JORGENSEN B., NILSSON L., ANDERSEN M., RIENKS E., BIANCHI M., FANETTI M., LAESGAARD E.,
BARALDI A., LIZZIT S., SLJIVANCANIN Z., BESENBACHER F., HAMMER B., PEDERSEN T.G. HOFMANN PH.,
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
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HORNEKAER L. (2010). Band Gap Opening in Graphene Induced by Patterned Hydrogen Adsorption. NATURE
MATERIALS, vol. 9 (2010); p. 315-319, ISSN: 1476-1122, doi: 10.1038/NMAT2710
 VESSELLI E, RIZZI M, DE ROGATIS L, DING X, BARALDI A., COMELLI G, SAVIO L, VATTUONE L, ROCCA M, P.
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 VISINTINI E, MAZZONI A, VITA F, PASQUANTONIO G, CADENARO M., DI LENARDA R, BRESCHI L. (2008).
Effects of thermocycling and use of ElectroBond on microtensile strength and nanoleakage using commercial onestep self-etch adhesives. EUROPEAN JOURNAL OF ORAL SCIENCES, vol. 116(6); p. 564-570, ISSN: 0909-8836,
doi: DOI: 10.1111/J.1600-0722.2008.00576.X
 ORSINI G, RUGGERI A JR, MAZZONI A, NATO A, FALCONI M, DI LENARDA R., NANCI A, BRESCHI L. (2008).
Immunohistochemical Localization of DMP1 in Human Dentin. EUROPEAN JOURNAL OF HISTOCHEMISTRY, vol. 52;
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 SABOIA VPA, NATO F, MAZZONI A, ORSINI G, PUTIGNANO A, GIANNINI M, BRESCHI L. (2008). Adhesion of a
two-step etch-and-rinse adhesive on collagen-depleted dentin. JOURNAL OF ADHESIVE DENTISTRY, vol. 10; p.
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 TETI G, MAZZOTTI G, ZAGO M, ORTOLANI M, BRESCHI L., PELOTTI S, RUGGERI A, FALCONI M (2009). HEMA
down-regulates procollagen a1 type I in human gingival fibroblasts. JOURNAL OF BIOMEDICAL MATERIALS
RESEARCH. PART A, vol. 90; p. 256-262, ISSN: 1549-3296
 CADENARO M, BRESCHI L., RUEGGEBERG FA, AGEE K, DI LENARDA R., CARRILHO M, TAY FR, PASHLEY DH
(2009). Effect of adhesive hydrophilicity and curing-time on the permeability of resins bonded to water vs.
ethanol-saturated acid-etched dentin. DENTAL MATERIALS, vol. 25; p. 39-47, ISSN: 0109-5641
 CARRILHO MR, TAY FR, DONNELLY AD, AGEE KA, TJÄDERHANE L, MAZZONI A, BRESCHI L., FOULGER S,
PASHLEY DH (2009). Host-derived loss of dentin matrix stiffness associated with solubilization of collagen.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH. PART B, APPLIED BIOMATERIALS, vol. 90; p. 373-380, ISSN:
1552-4981
 CARVALHO CA, CANTORO A, MAZZONI A, GORACCI C, BRESCHI L., FERRARI M (2009). Effect of the ethanol
application on post luting to intraradicular dentin. INTERNATIONAL ENDODONTIC JOURNAL, vol. 42; p. 129-135,
ISSN: 0143-2885
 MAZZONI A, VISINTINI E, VITA F, PASQUANTONIO G, SABOIA VP, RUGGERI A JR, DI LENARDA R, DE STEFANO
DORIGO E., BRESCHI L. (2009). ElectroBond improves immediate dentin microtensile bond strength of two etchand-rinse adhesives. JOURNAL OF ADHESIVE DENTISTRY, vol. 11(1); p. 27-33, ISSN: 1461-5185, doi:
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 BRESCHI L., CAMMELLI F, VISINTINI E, MAZZONI A, VITA F, CARRILHO M, CADENARO M., FOULGER S,
MAZZOTI G, TAY FR, DI LENARDA R, PASHLEY D (2009). Influence of chlorhexidine concentration on the durability
of etch-and-rinse dentin bonds: a 12-month in vitro study. JOURNAL OF ADHESIVE DENTISTRY, vol. 11; p. 191198, ISSN: 1461-5185
 BRESCHI L., MAZZONI A, DE STEFANO DORIGO E, FERRARI M (2009). Adhesion to intraradicular dentin: a
review. JOURNAL OF ADHESION SCIENCE AND TECHNOLOGY, vol. 23; p. 1053-1083, ISSN: 0169-4243
 ERHARDT ACG, OSORIO R, PROENÇA JP, AGUILERA FA, OSORIO E, BRESCHI L., TOLEDANO M (2009). Influence
of multiple adhesive coatings and extended etching time on the bonding effectiveness of self-etch adhesives to
dentin. OPERATIVE DENTISTRY, ISSN: 0361-7734
 SANTOS J, CARRILHO MR, TERVAHARTIALA T, SORSA T, FERRAZ C, BRESCHI L., MAZZONI A, PASHLEY DH,
TJÄDERHANE L (2009). Determination of matrix metalloproteinases in human radicular dentin. JOURNAL OF
ENDODONTICS, vol. 35; p. 686-689, ISSN: 0099-2399
 CADENARO M., BRESCHI L., RUEGGEBERG FA, SUCHKO M, GRODIN E, AGEE K, DI LENARDA R, TAY FR,
PASHLEY DH (2009). Effects of residual ethanol on the rate and degree of conversion of five experimental resins.
DENTAL MATERIALS, vol. 25(5); p. 621-628, ISSN: 0109-5641, doi: 10.1016/J.DENTAL.2008.11.005
 CADENARO M., MARCHESI G, ANTONIOLLI F, DAVIDSON C, DE STEFANO DORIGO E, BRESCHI L. (2009).
Flowability of composites is no guarantee for contraction stress reduction. DENTAL MATERIALS, vol. 25(5); p. 649654, ISSN: 0109-5641, doi: 10.1016/J.DENTAL.2008.11.010
 CARVALHO CA, MONTICELLI F, CANTORO A, BRESCHI L., FERRARI M (2009). Push-out bond strength of fiber
posts luted with unfilled resin cement. JOURNAL OF ADHESIVE DENTISTRY, vol. 11; p. 65-70, ISSN: 1461-5185
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 KOMORI PC, PASHLEY DH, TJADERHANE L, BRESCHI L., MAZZONI A, DE GOES MF, WANG L, CARRILHO MR
(2009). Effect of 2% chlorhexidine digluconate on the bond strength to normal vs caries-affected dentin.
OPERATIVE DENTISTRY, vol. 43; p. 157-165, ISSN: 0361-7734
 FALCONI M, TETI G, ZAGO M, GALANZI A, BRESCHI L., PELOTTI S, RUGGERI A, MAZZOTTI G (2009). Influence
of a commercial tattoo ink on protein production in human fibroblasts. ARCHIVES OF DERMATOLOGICAL
RESEARCH, vol. 301; p. 539-547, ISSN: 0340-3696
 MAI S, KIM YK, TOLEDANO M, BRESCHI L., LING JQ, PASHLEY DH, TAY FR (2009). Phosphoric acid esters
cannot replace polyvinylphosphonic acid as phosphoprotein analogs in biomimetic remineralization of resin-bonded
dentin. DENTAL MATERIALS, vol. 25; p. 1230-1239, ISSN: 0109-5641
 CADENARO M, PASHLEY DH, MARCHESI G, CARRILHO M, ANTONIOLLI F, MAZZONI A, TAY FR, DI LENARDA R,
BRESCHI L. (2009). Influence of chlorhexidine on the degree of conversion and E-modulus of experimental
adhesive blends. DENTAL MATERIALS, vol. 25(10); p. 1269-1274, ISSN: 0109-5641, doi:
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 NAVARRA C.O, CADENARO M, ARMSTRONG S.R, JESSOP J, ANTONIOLLI F, SERGO V., DI LENARDA R, BRESCHI
L. (2009). Degree of conversion of Filtek Silorane Adhesive System and Clearfil SE Bond within the hybrid and
adhesive layer: An in situ Raman analysis. DENTAL MATERIALS, vol. 25(9); p. 1178-1185, ISSN: 0109-5641, doi:
10.1016/J.DENTAL.2009.05.009
 MALACARNE-ZANON J, PASHLEY DH, AGEE KA, FOULGER S, ALVES MC, BRESCHI L., CADENARO M, GARCIA FP,
CARRILHO MR (2009). Effects of ethanol addition on the water sorption/solubility and percent conversion of
comonomers in model dental adhesives. DENTAL MATERIALS, vol. 25(10); p. 1275-1284, ISSN: 0109-5641, doi:
10.1016/J.DENTAL.2009.03.015
 MAZZONI A, MARCHESI G, CADENARO M, MAZZOTTI G, DI LENARDA R, FERRARI M, BRESCHI L. (2009). Pushout stress for fibre posts luted using different adhesive strategies. EUROPEAN JOURNAL OF ORAL SCIENCES, vol.
117; p. 447-453, ISSN: 0909-8836
 NAVARRA C.O, CADENARO M, CODAN B, MAZZONI A, SERGO V., DE STEFANO DORIGO E, BRESCHI L. (2009).
Degree of conversion and interfacial nanoleakage expression of three one-step self-etch adhesives. EUROPEAN
JOURNAL OF ORAL SCIENCES, vol. 117; p. 463-469, ISSN: 0909-8836, doi: 10.1111/j.1600-0722.2009.00654.x
 CADENARO M., DELISE C, ANTONIOLLI F, NAVARRA CO, DI LENARDA R, BRESCHI L. (2009). Enamel and dentin
bond strength following gaseous ozone application. JOURNAL OF ADHESIVE DENTISTRY, vol. 11; p. 287-292,
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 SABOIA VP, SILVA FC, NATO F, MAZZONI A, CADENARO M., MAZZOTTI G, GIANNINI M, BRESCHI L. (2009).
Analysis of differential artificial ageing of the adhesive interface produced by a two-step etch-and-rinse adhesive.
EUROPEAN JOURNAL OF ORAL SCIENCES, vol. 117; p. 618-624, ISSN: 0909-8836
 FERRARI M, CARVALHO CA, GORACCI C, ANTONIOLLI F, MAZZONI A, MAZZOTTI G, CADENARO M, BRESCHI L.
(2009). Influence of luting material filler content on post cementation. JOURNAL OF DENTAL RESEARCH, vol. 88;
p. 951-956, ISSN: 0022-0345
 RUGGERI A, ORSINI G, MAZZONI A, NATO F, PAPA V, PICCIRILLI M, PUTIGNANO A, MAZZOTTI G, DE STEFANO
DORIGO E, BRESCHI L. (2009). Immunohistochemical and biochemical assay of versican in human sound
predentine/dentine matrix. EUROPEAN JOURNAL OF HISTOCHEMISTRY, vol. 53(3); p. 125-133, ISSN: 1121-760X
 MAZZONI A, PASHLEY DH, RUGGERI A JR, VITA F, FALCONI M, DI LENARDA R, BRESCHI L. (2008). Adhesion to
chondroitinase ABC treated dentin. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH. PART B, APPLIED
BIOMATERIALS, vol. 86B; p. 228-236, ISSN: 1552-4981
 Marchesi G., Navarra C.O., Cadenaro M., Carrilho M.R., Codan B., Sergo V., Di Lenarda R., BRESCHI L. (2010).
The effect of ageing on the elastic modulus and degree of conversion of two multistep adhesive systems.
EUROPEAN JOURNAL OF ORAL SCIENCES, vol. 118; p. 304-310, ISSN: 0909-8836
 Cadenaro M., Navarra C.O., Antoniolli F., Mazzoni A., Di Lenarda R., Rueggeberg F.A., BRESCHI L. (2010). The
effect of curing mode on extent of polymerization and microhardness of dual-cured, self-adhesive resin cements.
AMERICAN JOURNAL OF DENTISTRY, vol. 23; p. 14-18, ISSN: 0894-8275
 Cadenaro M., Navarra C.O., Mazzoni A., Nucci C., Matis B.A., Di Lenarda R., BRESCHI L. (2010). An in vivo
study of the effect of a 38 percent hydrogen peroxide in-office whitening agent on enamel. . THE JOURNAL OF THE
AMERICAN DENTAL ASSOCIATION, vol. 141; p. 449-454, ISSN: 0002-8177
 BRESCHI L., Martin P., Mazzoni A., Nato F., Carrilho M., Tjäderhane L., Visintini E., Cadenaro M., Tay F.R.,
Dorigo E.D., Pashley D.H. (2010). Use of a specific MMP-inhibitor (galardin) for preservation of hybrid layer.
DENTAL MATERIALS, vol. 26; p. 571-578, ISSN: 0109-5641
 Paragliola R., Franco V., Fabiani C., Mazzoni A., Nato F., Tay F.R., BRESCHI L., Grandini S. (2010). Final rinse
optimization: influence of different agitation protocols. JOURNAL OF ENDODONTICS, vol. 36; p. 282-285, ISSN:
0099-2399
 Cadenaro M., Antoniolli F., Codan B., Agee K., Tay F.R., De Stefano Dorigo E., Pashley D.H., BRESCHI L.
(2010). Influence of different initiators on the degree of conversion of experimental adhesive blends in relation to
their hydrophilicity and solvent content. DENTAL MATERIALS, vol. 26; p. 288-294, ISSN: 0109-5641
 Sadek F.T., Mazzoni A., BRESCHI L., Tay F.R., Braga R.R. (2010). Six-month evaluation of adhesives interface
created by a hydrophobic adhesive to acid-etched ethanol-wet bonded dentine with simplified dehydration
protocols. JOURNAL OF DENTISTRY, vol. 38; p. 276-283, ISSN: 0300-5712
 BRESCHI L., Mazzoni A., Nato F., Carrilho M., Visintini E., Tjäderhane L., Ruggeri A. Jr, Tay F.R., De Stefano
Dorigo E., Pashley D.H. (2010). Chlorhexidine stabilizes the adhesive interface: a 2 year in vitro study. DENTAL
MATERIALS, vol. 26; p. 320-325, ISSN: 0109-5641
 Kim J., Gu L., BRESCHI L., Tjäderhane L., Choi K.K., Pashley D.H., Tay F.R. (2010). Implication of Ethanol Wetbonding in Hybrid Layer Remineralization. JOURNAL OF DENTAL RESEARCH, vol. 89; p. 575-580, ISSN: 00220345
 Taschner M, Nato F, Mazzoni A, Frankenberger R, Krämer N, Di Lenarda R, Petschelt A, BRESCHI L. (2010). Role
of preliminary etching for one-step self-etch adhesives. EUROPEAN JOURNAL OF ORAL SCIENCES, vol. 118; p.
517-524, ISSN: 0909-8836, doi: 10.1111/j.1600-0722.2010.00769.x.
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 Kim J, Uchiyama T, Carrilho M, Agee KA, Mazzoni A, BRESCHI L., Carvalho RM, Tjäderhane L, Looney S,
Wimmer C, Tezvergil-Mutluay A, Tay FR, Pashley DH. (2010). Chlorhexidine binding to mineralized versus
demineralized dentin powder. DENTAL MATERIALS, vol. 26; p. 771-778, ISSN: 0109-5641
 Carrilho MR, Carvalho RM, Sousa EN, Nicolau J, BRESCHI L., Mazzoni A, Tjäderhane L, Tay FR, Agee K, Pashley
DH. (2010). Substantivity of chlorhexidine to human dentin. DENTAL MATERIALS, vol. 26; p. 779-785, ISSN:
0109-5641
 Marchesi G, BRESCHI L., Antoniolli F, Di Lenarda R, Ferracane J, Cadenaro M. (2010). Contraction stress of lowshrinkage composite materials assessed with different testing systems. DENTAL MATERIALS, vol. 26; p. 947-953,
ISSN: 0109-5641
 Kim YK, Gu LS, Bryan TE, Kim JR, Chen L, Liu Y, Yoon JC, BRESCHI L., Pashley DH, Tay FR (2010).
Mineralisation of reconstituted collagen using polyvinylphosphonic acid/polyacrylic acid templating matrix protein
analogues in the presence of calcium, phosphate and hydroxyl ions. BIOMATERIALS, vol. 31; p. 6618-6627, ISSN:
0142-9612
 Tezvergil-Mutluay A, Agee KA, Hoshika T, Carrilho M, BRESCHI L., Tjäderhane L, Nishitani Y, Carvalho RM,
Looney S, Tay FR, Pashley DH. (2010). The requirement of zinc and calcium ions for functional MMP activity in
demineralized dentin matrices. DENTAL MATERIALS, vol. 26; p. 1059-1067, ISSN: 0109-5641
 TEZVERGIL-MUTLUAY A, MUTLUAY MM, GU LS, ZHANG K, AGEE KA, CARVALHO RM, MANSO A, CARRILHO M,
TAY FR, BRESCHI L., SUH BI, PASHLEY DH. (2011). The anti-MMP activity of benzalkonium chloride. JOURNAL OF
DENTISTRY, vol. 39; p. 57-64, ISSN: 0300-5712
 PASHLEY DH, TAY FR, BRESCHI L., TJÄDERHANE L, CARVALHO RM, CARRILHO M, TEZVERGIL-MUTLUAY A.
(2011). State of the art etch-and-rinse adhesives. DENTAL MATERIALS, vol. 27; p. 1-16, ISSN: 0109-5641
 TEZVERGIL-MUTLUAY A, AGEE KA, UCHIYAMA T, IMAZATO S, MUTLUAY MM, CADENARO M, BRESCHI L.,
NISHITANI Y, TAY FR, PASHLEY DH. (2011). The Inhibitory Effects of Quaternary Ammonium Methacrylates on
Soluble and Matrix-bound MMPs. JOURNAL OF DENTAL RESEARCH, vol. 90; p. 535-540, ISSN: 0022-0345
 TOLEDANO M, MAZZONI A, MONTICELLI F, BRESCHI L., OSORIO E, OSORIO R. (2011). ElectroBond application
may improve wetting characteristics of etched dentine. JOURNAL OF DENTISTRY, vol. 39; p. 180-186, ISSN:
0300-5712
 MAZZONI A, PAPA V, NATO F, CARRILHO M, TJÄDERHANE L, RUGGERI A JR, GOBBI P, MAZZOTTI G, TAY FR,
PASHLEY DH, BRESCHI L. (2011). Immunohistochemical and biochemical assay of MMP-3 in human dentine.
JOURNAL OF DENTISTRY, vol. 39; p. 231-237, ISSN: 0300-5712
 LIU Y, LI N, QI Y, NIU LN, ELSHAFIY S, MAO J, BRESCHI L., PASHLEY DH, TAY FR. (2011). The use of sodium
trimetaphosphate as a biomimetic analog of matrix phosphoproteins for remineralization of artificial caries-like
dentin. DENTAL MATERIALS, vol. 27; p. 465-477, ISSN: 0109-5641
 Orsini G, Stacchi C, Visintini E, Di Iorio D, Putignano A, BRESCHI L., Di Lenarda R. (2011). Clinical and histologic
evaluation of fresh frozen human bone grafts for horizontal reconstruction of maxillary alveolar ridges. THE
INTERNATIONAL JOURNAL OF PERIODONTICS & RESTORATIVE DENTISTRY, vol. 31; p. 535-544, ISSN: 01987569
 Liu Y, Tjäderhane L, BRESCHI L., Mazzoni A, Li N, Mao J, Pashley DH, Tay FR. (2011). Limitations in bonding to
dentin and experimental strategies to prevent bond degradation. JOURNAL OF DENTAL RESEARCH, vol. 90; p.
953-968, ISSN: 0022-0345
 Mazzoni A, Carrilho M, Papa V, Tjäderhane L, Gobbi P, Nucci C, Di Lenarda R, Mazzotti G, Tay FR, Pashley DH,
BRESCHI L. (2011). MMP-2 assay within the hybrid layer created by a two-step etch-and-rinse adhesive:
Biochemical and immunohistochemical analysis. JOURNAL OF DENTISTRY, vol. 39; p. 470-477, ISSN: 0300-5712
 Tezvergil-Mutluay A, Agee KA, Hoshika T, Uchiyama T, Tjäderhane L, BRESCHI L., Mazzoni A, Thompson JM,
McCracken CE, Looney SW, Tay FR, Pashley DH. (2011). Inhibition of MMPs by alcohols. DENTAL MATERIALS, vol.
27; p. 926-933, ISSN: 0109-5641
 Colonna M, Breschi M, Mazzoni A, Nato F, Ruggeri A Jr, Nucci C, Tay FR, Pashley DH, BRESCHI L. (2011). Effects
of pH, ionic strength, and applied voltage on migration of dental monomers in an organic matrix. DENTAL
MATERIALS, vol. 27; p. 1180-1186, ISSN: 0109-5641
 Cova A, BRESCHI L., Nato F, Ruggeri A Jr, Carrilho M, Tjäderhane L, Prati C, Di Lenarda R, Tay FR, Pashley DH,
Mazzoni A. (2011). Effect of UVA-activated Riboflavin on Dentin Bonding. JOURNAL OF DENTAL RESEARCH, vol.
90; p. 1439-1445, ISSN: 0022-0345
 Cadenaro M., Codan B., Navarra C.O., Marchesi G., Turco G., Di Lenarda R., BRESCHI L. (2011). Contraction
stress, elastic modulus, and degree of conversion of three flowable composites. EUROPEAN JOURNAL OF ORAL
SCIENCES, vol. 119; p. 241-245, ISSN: 0909-8836
 Tezvergil-Mutluay A, Mutluay MM, Gu LS, Zhang K, Agee KA, Carvalho RM, Manso A, Carrilho M, Tay FR,
BRESCHI L., Suh BI, Pashley DH. (2011). The anti-MMP activity of benzalkonium chloride. JOURNAL OF
DENTISTRY, vol. 39; p. 57-64, ISSN: 0300-5712
 Pashley DH, Tay FR, BRESCHI L., Tjäderhane L, Carvalho RM, Carrilho M, Tezvergil-Mutluay A. (2011). State of
the art etch-and-rinse adhesives. DENTAL MATERIALS, vol. 27; p. 1-16, ISSN: 0109-5641
 Tezvergil-Mutluay A, Agee KA, Uchiyama T, Imazato S, Mutluay MM, Cadenaro M, BRESCHI L., Nishitani Y, Tay
FR, Pashley DH. (2011). The Inhibitory Effects of Quaternary Ammonium Methacrylates on Soluble and Matrixbound MMPs. JOURNAL OF DENTAL RESEARCH, vol. 90; p. 535-540, ISSN: 0022-0345
 Mazzoni A, Papa V, Nato F, Carrilho M, Tjäderhane L, Ruggeri A Jr, Gobbi P, Mazzotti G, Tay FR, Pashley DH,
BRESCHI L. (2011). Immunohistochemical and biochemical assay of MMP-3 in human dentine. JOURNAL OF
DENTISTRY, vol. 39; p. 231-237, ISSN: 0300-5712
 Liu Y, Li N, Qi Y, Niu LN, Elshafiy S, Mao J, BRESCHI L., Pashley DH, Tay FR. (2011). The use of sodium
trimetaphosphate as a biomimetic analog of matrix phosphoproteins for remineralization of artificial caries-like
dentin. DENTAL MATERIALS, vol. 27; p. 465-477, ISSN: 0109-5641
 Toledano M, Mazzoni A, Monticelli F, BRESCHI L., Osorio E, Osorio R. (2011). ElectroBond application may
improve wetting characteristics of etched dentine. JOURNAL OF DENTISTRY, vol. 39; p. 180-186, ISSN: 03005712
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 COVA A, BRESCHI L., NATO F, RUGGERI A JR, CARRILHO M, TJÄDERHANE L, PRATI C, DI LENARDA R, TAY FR,
PASHLEY DH, MAZZONI A. (2011). Effect of UVA-activated riboflavin on dentin bonding. JOURNAL OF DENTAL
RESEARCH, vol. 90 (12); p. 1439-1445, ISSN: 0022-0345
 Tezvergil-Mutluay A., Mutluay M.M., Agee K.A., Seseogullari-Dirihan R., Hoshika T., Cadenaro M., BRESCHI L.,
Vallittu P., Tay F.R., Pashley D.H. (2012). Carbodiimide cross-linking inactivates soluble and matrix-bound MMPs,
in vitro. JOURNAL OF DENTAL RESEARCH, vol. 91; p. 192-196, ISSN: 0022-0345, doi:
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 Navarra C.O., Goracci C., BRESCHI L., Vichi A., Corciolani G., Cadenaro M., Ferrari M. (2012). Influence of post
type on degree of conversion of a resin-based luting agent. AMERICAN JOURNAL OF DENTISTRY, vol. 25; p. 1720, ISSN: 0894-8275
 Navarra C.O., BRESCHI L., Turco G., Diolosà M., Fontanive L., Manzoli L., Di Lenarda R., Cadenaro M. (2012).
Degree of conversion of two-step etch-and-rinse adhesives: In situ micro-Raman analysis. JOURNAL OF
DENTISTRY; p. ---, ISSN: 0300-5712, doi: 10.1016/j.jdent.2012.05.001
 Marchesi G., Petris L.C., Navarra C.O., Locatelli R., Di Lenarda R., BRESCHI L., Cadenaro M. (2012). Effect of
Ozone Application on the Immediate Shear Bond Strength and Microleakage of Dental Sealants. PEDIATRIC
DENTISTRY, vol. 34; p. 284-288, ISSN: 0164-1263
 Frassetto A., Navarra C.O., Marchesi G., Turco G., Di Lenarda R., BRESCHI L., Ferracane J.L., Cadenaro M.
(2012). Kinetics of polymerization and contraction stress development in self-adhesive resin cements. DENTAL
MATERIALS, vol. 28; p. 1032-1039, ISSN: 0109-5641, doi: 10.1016/j.dental.2012.06.003
 Taschner M, Krämer N, Lohbauer U, Pelka M, BRESCHI L., Petschelt A, Frankenberger R. (2012). Leucitereinforced glass ceramic inlays luted with self-adhesive resin cement: a 2-year in vivo study. DENTAL MATERIALS,
vol. 28; p. 535-540, ISSN: 0109-5641, doi: 10.1016/j.dental.2011.12.002
 G. Orsini, A. Mazzoni, M. Orciani, A. Putignano, M. Procaccini, M. Falconi, D. H. Pashley, F. R. Tay, BRESCHI L.
(2011). Matrix metalloproteinase-2 expression induced by two different adhesive systems on human pulp
fibroblasts. JOURNAL OF ENDODONTICS, vol. 37; p. 1663-1667, ISSN: 0099-2399, doi:
10.1016/j.joen.2011.07.009
 Niu LN, Jiao K, Qi YP, Yiu CK, Ryou H, Arola DD, Chen JH, BRESCHI L., Pashley DH, Tay FR. (2012). Infiltration
of silica inside fibrillar collagen. ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, vol. 50; p. 11688-11691,
ISSN: 1433-7851, doi: 10.1002/anie.201105114
 Mazzoni A, Nascimento FD, Carrilho M, Tersariol I, Papa V, Tjäderhane L, Di Lenarda R, Tay FR, Pashley DH,
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Polymerization kinetics of dental adhesives cured with LED: correlation between extent of conversion and
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of 4 dental sealants. EUROPEAN JOURNAL OF PAEDIATRIC DENTISTRY, vol. 8 (4); p. 179-182, ISSN: 1591-996X
 CADENARO M., BRESCHI L, NUCCI C, ANTONIOLLI F, VISINTINI E, PRATI C, MATIS BA, DI LENARDA R (2008).
Effect of two in-office whitening agents on enamel surface in vivo: a morphological and non contact profilometric
study. OPERATIVE DENTISTRY, vol. 33; p. 123-130, ISSN: 0361-7734
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review: Aging and stability of the bonded interface. DENTAL MATERIALS, vol. 24; p. 90-101, ISSN: 0109-5641,
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Effects of thermocycling and use of ElectroBond on microtensile strength and nanoleakage using commercial onestep self-etch adhesives. EUROPEAN JOURNAL OF ORAL SCIENCES, vol. 116(6); p. 564-570, ISSN: 0909-8836,
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Flowability of composites is no guarantee for contraction stress reduction. DENTAL MATERIALS, vol. 25(5); p. 649654, ISSN: 0109-5641, doi: 10.1016/J.DENTAL.2008.11.010
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Analysis of differential artificial ageing of the adhesive interface produced by a two-step etch-and-rinse adhesive.
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Degree of conversion and interfacial nanoleakage expression of three one-step self-etch adhesives. EUROPEAN
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 NAVARRA C.O, CADENARO M., ARMSTRONG S.R, JESSOP J, ANTONIOLLI F, SERGO V., DI LENARDA R, BRESCHI
L (2009). Degree of conversion of Filtek Silorane Adhesive System and Clearfil SE Bond within the hybrid and
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 CADENARO M., PASHLEY DH, MARCHESI G, CARRILHO M, ANTONIOLLI F, MAZZONI A, TAY FR, DI LENARDA R,
BRESCHI L. (2009). Influence of chlorhexidine on the degree of conversion and E-modulus of experimental
adhesive blends. DENTAL MATERIALS, vol. 25(10); p. 1269-1274, ISSN: 0109-5641, doi:
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 BRESCHI L, CADENARO M., MAZZONI L, NAVARRA CO, MARCHESI G, DI LENARDA R, DE STEFANO DORIGO E
(2009). La durata del legame adesivo: la nuova sfida dell’odontoiatria restaurativa. IL DENTISTA MODERNO, vol.
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 Marchesi G., Navarra C.O., CADENARO M., Carrilho M.R., Codan B., Sergo V., Di Lenarda R., Breschi L. (2010).
The effect of ageing on the elastic modulus and degree of conversion of two multistep adhesive systems.
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 CADENARO M., Navarra C.O., Antoniolli F., Mazzoni A., Di Lenarda R., Rueggeberg F.A., Breschi L. (2010). The
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 CADENARO M., Navarra C.O., Mazzoni A., Nucci C., Matis B.A., Di Lenarda R., Breschi L. (2010). An in vivo
study of the effect of a 38 percent hydrogen peroxide in-office whitening agent on enamel. . THE JOURNAL OF THE
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Dorigo E.D., Pashley D.H. (2010). Use of a specific MMP-inhibitor (galardin) for preservation of hybrid layer.
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 CADENARO M., Antoniolli F., Codan B., Agee K., Tay F.R., De Stefano Dorigo E., Pashley D.H., Breschi L.
(2010). Influence of different initiators on the degree of conversion of experimental adhesive blends in relation to
their hydrophilicity and solvent content. DENTAL MATERIALS, vol. 26; p. 288-294, ISSN: 0109-5641
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(2010). Effects of different exposure times and concentrations of NaOCl/EDTA on the structural integrity of
mineralized dentin. JOURNAL OF ENDODONTICS; p. 105-109, ISSN: 0099-2399
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 TEZVERGIL-MUTLUAY A, AGEE KA, UCHIYAMA T, IMAZATO S, MUTLUAY MM, CADENARO M., BRESCHI L,
NISHITANI Y, TAY FR, PASHLEY DH. (2011). The Inhibitory Effects of Quaternary Ammonium Methacrylates on
Soluble and Matrix-bound MMPs. JOURNAL OF DENTAL RESEARCH, vol. 90; p. 535-540, ISSN: 0022-0345
 CADENARO M., Codan B., Navarra C.O., Marchesi G., Turco G., Di Lenarda R., Breschi L. (2011). Contraction
stress, elastic modulus, and degree of conversion of three flowable composites. EUROPEAN JOURNAL OF ORAL
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 Tezvergil-Mutluay A., Mutluay M.M., Agee K.A., Seseogullari-Dirihan R., Hoshika T., CADENARO M., Breschi L.,
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L (2009). Degree of conversion of Filtek Silorane Adhesive System and Clearfil SE Bond within the hybrid and
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 Gobbo M, Ottaviani G, Mustacchi G, DI LENARDA R., Biasotto M. (2011). Acneiform rash due to epidermal
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 Perinetti G., Contardo L., Ceschi M., Antoniolli F., Franchi L., Baccetti T., DI LENARDA R. (2010). Surface
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using various Cephalometric Analyses. JOURNAL OF CLINICAL ORTHODONTICS, vol. 17/7; p. 389-392, ISSN:
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 Marchesi G., Petris L.C., Navarra C.O., Locatelli R., DI LENARDA R., Breschi L., Cadenaro M. (2012). Effect of
Ozone Application on the Immediate Shear Bond Strength and Microleakage of Dental Sealants. PEDIATRIC
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(2012). Kinetics of polymerization and contraction stress development in self-adhesive resin cements. DENTAL
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Giacca M., DI LENARDA R. (2010). A novel animal model to study non-spontaneous bisphosphonates
osteonecrosis of jaw. JOURNAL OF ORAL PATHOLOGY & MEDICINE, vol. 39; p. 390-396, ISSN: 0904-2512
 Biasotto M, Perinetti G, Serroni I, Ottaviani G, DI LENARDA R., Tirelli G (2012). Oral manifestation upon short
time cocaine abuse. A case report. MINERVA STOMATOLOGICA, vol. 61; p. 294-297, ISSN: 0026-4970
 Clozza E., Biasotto M., Cavalli F., Moimas., DI LENARDA R. (2012). Three-dimensional evaluation of bone
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11. FASSINA Ambrogio
 ALBIGER NM, OCCHI G, MARINIELLO B, IACOBONE M., FAVIA G, FASSINA A., FAGGIAN D, MANTERO F,
SCARONI C (2007). Food-dependent Cushing's syndrome: from molecular characterization to therapeutical results
. EUROPEAN JOURNAL OF ENDOCRINOLOGY, vol. 157; p. 771-778, ISSN: 0804-4643, doi: 10.1530/EJE-07-0253
 MAFFEI P, MENEGAZZO C, MICHELOTTO M, SALMASO R, MARTINI C, DE CARLO E, CARLI M, BARBAN M,
FASSINA A., VETTOR R., SICOLO N (2008). Sudden death due to aortic rupture in acromegaly
. HEART AND VESSELS, vol. 23; p. 71-74, ISSN: 0910-8327
 IACOBONE M, ALBIGER N, SCARONI C, MANTERO F, FASSINA A., VIEL G, FREGO M, FAVIA G (2008). The Role
of Unilateral Adrenalectomy in ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH).
. WORLD JOURNAL OF SURGERY, vol. 32(5); p. 882-889, ISSN: 0364-2313, doi: 10.1007/s00268-007-9408-5
 FASSINA A., FEDELI U, CORRADIN M, DA FRE' M, FABBRIS L (2008). Accuracy and reproducibility of pleural
effusion cytology. LEGAL MEDICINE, vol. 10 (1); p. 20-25, ISSN: 1344-6223
 FASSINA A., CORRADIN M, MURER B, FURLAN C, GUOLO A, VENTURA L, M. MONTISCI (2009). Detection of
Silica Particles in Lung Tissue by Environmental Scanning Electron Microscopy. INHALATION TOXICOLOGY, vol.
21; p. 133-140, ISSN: 0895-8378, doi: 10.1080/08958370802294647
 GIULIANI L, LENZINI L, ANTONELLO M., ALDIGHIERI E, BELLONI AS, FASSINA A., GOMEZ-SANCHEZ C, ROSSI
GP (2009). Expression and functional role of urotensin-II and its receptor in the adrenal cortex and medulla: novel
insights for the pathophysiology of primary aldosteronism.
. THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, vol. 94; p. 684-690, ISSN: 0021-972X, doi:
10.1210/jc.2008-1131
 GAZZIERO A, GUZZARDO V, ALDIGHIERI E, FASSINA A. (2009). Morphological quality and nucleic acid
preservation in cytopathology. JOURNAL OF CLINICAL PATHOLOGY, vol. 62; p. 429-434, ISSN: 0021-9746, doi:
10.1136/jcp.2008.059808
 FASSINA A., GAZZIERO A, ZARDO D, CORRADIN M, ALDIGHIERI E, ROSSI G.P. (2009). Detection of EGFR and
KRAS mutations on trans-thoracic needle aspiration of lung nodules by high resolution melting analysis
. JOURNAL OF CLINICAL PATHOLOGY, vol. 62; p. 1096-1102, ISSN: 0021-9746, doi: 10.1136/jcp.2009.067587
 L. Cattaruzza, D. Fregona, M. Mongiat, L. Ronconi, FASSINA A., A. Colombatti, D. Adinucci (2011). Antitumor
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activity of gold(III)-dithiocarbamato derivatives on prostate cancer cells and xenografts. INTERNATIONAL
JOURNAL OF CANCER, vol. 128; p. 206-215, ISSN: 0020-7136, doi: 10.1002/ijc.25311
 KOUSSIS H, MARUZZO M, SCOLA A, IDE EC, FASSINA A., MARIONI G, LORA O, CORTI L, KARACHONTZITI P,
JIRILLO A (2010). A case of anaplastic thyroid cancer with long-term survival.
. ANTICANCER RESEARCH, vol. 30; p. 1273-1278, ISSN: 0250-7005
 FASSINA A., FABBRO M, CAPPELLESSO R, FASSAN M (2010). Seeding of tumour cells after fine needle
aspiration cytology in liver nodules: myth or reality?. CYTOPATHOLOGY, vol. 21(6); p. 413-414, ISSN: 0956-5507
 LUMACHI F, FABBRO M, TREGNAGHI A, ANTUNOVIC L, BUI F, CECCHIN D, ZUCCHETTA P, FASSINA A. (2010).
Fine-needle aspiration cytology and (99m)Tc-pertechnetate scintigraphy together in patients with differentiated
thyroid carcinoma
. ANTICANCER RESEARCH, vol. 30; p. 3083-3086, ISSN: 0250-7005
 FASSINA A., CAPPELLESSO R, SCHIAVI F, FASSAN M (2011). Concurrent pheochromocytoma and cortical
carcinoma of the adrenal gland. JOURNAL OF SURGICAL ONCOLOGY, vol. 103(1); p. 103-104, ISSN: 0022-4790
 FASSINA A., OLIVOTTO A, CAPPELLESSO R, VENDRAMINELLI R, FASSAN M (2010). Fine-needle cytology of
cutaneous juvenile xanthogranuloma and langerhans cell histiocytosis. CANCER CYTOPATHOLOGY; p. 134-140,
ISSN: 1934-662X, doi: 10.1002/cncy.20132
 ENDRI M, CARTERI G, ZUSTOWICH F, SERINO FS, FASSINA A. (2010). Differential diagnosis of lung nodules:
breast cancer metastases and lung tuberculosis. INFECTIONS IN MEDICINE, vol. 1; p. 39-42, ISSN: 0749-6524
 GOTTARDO F, CESARI M, MORRA A, GARDIMAN M, FASSINA A., DAL BIANCO M (2010). A kidney tumor in an
adolescentwith severe hypertension and hypokalemia: an uncommon case-report and review of the literature on
reninoma. UROLOGY INTERNATIONAL, vol. 1; p. 121-124, ISSN: 1352-9544
 MARINIELLO B, FINCO I, SARTORATO P, PATALANO A, IACOBONE M, GUZZARDO V, FASSINA A., MANTERO F
(2010). SOMATOSTATIN RECEPTOR EXPRESSION IN ADRENOCORTICAL TUMORS AND EFFECT OF A NEW
SOMATOSTATIN ANALOG SOM230 ON HORMONE SECRETION IN VITRO AND IN EX VIVO ADRENAL CELLS.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, vol. 6; p. 1010-1018, ISSN: 0391-4097
 FASSINA A., CORRADIN M, EL MAZLOUM R, MURER B, FURLAN C, MONTISCI M, GUOLO A, VENTURA L. (2009).
Silica levels and lung cancer: results of an ESEM study. INHALATION TOXICOLOGY, vol. 21; p. 133-140, ISSN:
0895-8378, doi: 10.1080/08958370802294647
 LUMACHI F, BORSATO S, TREGNAGHI A, FERRETTI G, POVOLATO M, CECCHIN D, MARZOLA MC, ZUCCHETTA P,
BUI F., FASSINA A. (2009). Usefulness of Combined Sestamibi Scintimammography, Axillary Ultrasonography and
FNA Cytology in Reducing the Number of Sentinel Node Procedures in Patients with Early-stage Breast Cancer.
ANTICANCER RESEARCH, vol. 29; p. 491-494, ISSN: 0250-7005
 D. CECCHIN, SCHIAVI F, FANTI S, FAVERO M, MANARA R, FASSINA A., BRIANI C, ALLEGRI V, SANSOVINI M,
BUI F, PAGANELLI G, OPOCHER G (2011). Peptide Receptor Radionuclide Therapy in a Case of Multiple Spinal
Canal and Cranial Paragangliomas
. JOURNAL OF CLINICAL ONCOLOGY, vol. 29; p. 171-174, ISSN: 0732-183X, doi: 10.1200/JCO.2010.31.7131
 FASSINA A., R. Cappellesso, V. Guzzardo, L. Dalla Via, S. Piccolo, L. Ventura, M. Fassan (2012). Epithelialmesenchymal transition in malignant mesothelioma. MODERN PATHOLOGY, vol. 25; p. 86-99, ISSN: 0893-3952
 M. Iacobone, F. Schiavi, M. Bottussi, E. Taschin, S. Bobisse, FASSINA A., G. Opocher, G. Favia (2011). Is
genetic screening indicated in apparently sporadic pheochromocytomas and paragangliomas?. SURGERY, vol. 150;
p. 1194-1201, ISSN: 0039-6060, doi: 10.1016/j.surg.2011.09.024
 Caroccia B, FASSINA A., Seccia TM, Recarti C, Petrelli L, Belloni AS, Pelizzo MR, Rossi GP (2010). Isolation of
human adrenocortical aldosterone-producing cells by a novel immunomagnetic beads method. ENDOCRINOLOGY,
vol. 151; p. 1375-1380, ISSN: 0013-7227, doi: 10.1210/en.2009-1243
 Maniero C, FASSINA A., SECCIA TM, Toniato A, Iacobone M, Plebani M, De Caro R, Calò LA, Pessina AC, Rossi
GP. (2012). Mild hyperparathyroidism: a novel surgically correctable feature of primary aldosteronism. JOURNAL
OF HYPERTENSION, vol. 30; p. 390-395, ISSN: 0263-6352
 ROSSI GP, GIULIANI L, ANTONELLO M, LENZINI L, ALDIGHIERI E, BELLONI A.S., FASSINA A., GOMEZSANCHEZ C (2008). Expression and functional role of urotensin II and its receptor in the adrenal cortex and
medulla. HYPERTENSION, vol. 52; p. E77-E77, ISSN: 0194-911X
 OCCHI G, LOSA M, ALBIGER N, TRIVELLIN G, REGAZZO D, SCANARINI M, MONTESERIN-GARCIA J, FRÖHLICH
B, FERASIN S, TERRENI M, FASSINA A., VITIELLO L, STALLA G, MANTERO F, C. SCARONI (2011). The glucosedependent insulinotropic polypeptide receptor (GIPR) is overexpressed amongst GNAS1 mutation-negative
somatotropinomas and drives GH-promoter activity in GH3 cells. JOURNAL OF NEUROENDOCRINOLOGY, ISSN:
0953-8194
 FASSINA A., Cappellesso R, Fassan M (2011). Classification of non-small cell lung carcinoma in transthoracic
needle specimens using microRNA expression profiling. CHEST, vol. 140, ISSN: 0012-3692, doi:
10.1378/chest.11-0708
 MANIERO C, FASSINA A, GUZZARDO V, LENZINI L, FASSINA A., PELIZZO MR, GOMEZ-SANCHEZ C, ROSSI GP
(2011). Primary Hyperparathyroidism With Concurrent Primary Aldosteronism. HYPERTENSION, vol. 58; p. 341U35, ISSN: 0194-911X, doi: 10.1161/HYPERTENSIONAHA.111.173948
 Rossi GP, Ragazzo F, Seccia TM, Maniero C, Barisa M, Calò LA, Frigo AC, FASSINA A., Pessina AC. (2012).
Hyperparathyroidism can be useful in the identification of primary aldosteronism due to aldosterone-producing
adenoma. HYPERTENSION, vol. Jun 25; p. Epub ahead of print-Epub ahead, ISSN: 0194-911X
 Mariniello B, Rosato A, Zuccolotto G, Rubin B, Cicala MV, Finco I, M. Iacobone, Frigo AC, FASSINA A., Pezzani R,
Mantero F (2012). Combination of sorafenib and everolimus impacts therapeutically on adrenocortical tumor
models. ENDOCRINE-RELATED CANCER, ISSN: 1351-0088, doi: 10.1530/ERC-11-0337
 FALLO F, BERTELLO C, TIZZANI D, FASSINA A., BOULKROUN S, N. SONINO, MONTICONE S, VIOLA A, VEGLIO
F, MULATERO P (2011). Concurrent primary aldosteronism and subclinical cortisol hypersecretion: a prospective
study. JOURNAL OF HYPERTENSION, vol. 29; p. 1773-1777, ISSN: 0263-6352, doi:
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 LUMACHI F, L. NORBERTO, ZANELLA S, MARINO F, BASSO S.M.M, BASSO U, BRUNELLO A, FASSINA A. (2011).
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 FERMEGLIA M., Romero Nieto D. (2011). Molecular modeling of multifunctional nanostructured materials and
coatings . In: 9th EUROFILLERS International Conference (EUROFILLERS 2011). Dresden , april, 2011, Dresden :
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 FERMEGLIA M. (2010). Multiscale molecular modeling for nanostructured and hybrid inorganic/organic
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 FERMEGLIA M., Pricl S. (2009). Multiscale molecular modelling of dispersion of nanoparticles in polymer systems
of industrial interest. In: IUTAM Symposium on Modelling Nanomaterials and Nanosystems. Aalborg, Denmark,
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 FERMEGLIA M., Pricl S. (2010). Multiscale molecular modeling: a nano-engineering tool for the design of hybrid
organic/inorganic materials. In: 240th ACS National Meeting & Exposition. Boston, Massachusetts, US, August 2226, 2010, ACS Symp. Ser, vol. 1, p. 1-1
 Pricl S., Posocco P., FERMEGLIA M., Karatasos K., Peng L., Smith D.K. (2010). The Sound of Silence. Multiscale
Molecular Simulations and Experiments in Developing Nanocarrier/Nucleic Acid Systems. In: 2010 AIChE Fall
Annual Meeting CD. Salt Lake City, US, November 2010AICHE, p. ---, ISBN/ISSN: 9780816910656
 FERMEGLIA M., Posocco P., Pricl S., Handgraaf J.W. (2010). Multiscale Molecular Modeling of Polymer/Silica
Nanocomposites. In: 2010 AIChE Fall Annual Meeting CD. Salt Lake City, US, November 2010AICHE, p. ---,
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 FERMEGLIA M., Pricl S. (2009). COSMO-RS and process simualtion:from physical properties to environmental
impact. In: COSMO-RS Symposium 2009. Koln, March 2009COSMO-RS Symposium 2009, Koln, March 2009, p. 11
 Pricl S, Posocco P, Pavan GM, FERMEGLIA M., Scocch G, Danani A, Malek A, Napol S, Catapano CV (2008).
Designing nanovectors for siRNA delivery: coupled experimental/modeling investigations. EUROPEAN JOURNAL OF
CANCER, vol. 6; p. 173-174, ISSN: 0959-8049
 Pricl S., Posocco P., Pavan G.M., FERMEGLIA M., Scocchi G., Malek A., Maly M., Danani A., Catapano C., Peng
L., Smith D.K. (2009). The sound of silence. Experimental/computational investigations of dendrimer-based
sirna/dna delivery systems. In: FOMMS2009, Foundation of Molecular Modelling and Simulation. Semiahmoo
Resort Blane, Washington, USA, luglio 2009Cache, p. 1-5
 S. Pricl, G. M. Pavan, FERMEGLIA M., E. Tamborini, M. A. Pierotti, S. Pilotti (2008). EGFR mutations and gefitinib
affinity: molecular insights from in silico experiments. EUROPEAN JOURNAL OF CANCER, vol. 6; p. 154-155, ISSN:
0959-8049, doi: 10.1016/S1359-6349(08)72418-2
 Pricl S, Gibbons DL, Posocco P, Laurini E, FERMEGLIA M., Kantarjian HM, Talpaz M, Cortes J, Donato N, QuintasCardama A (2010). In Silico modelling of Sensitivity to Novel Tyrosine Kinase Inhibitors of Highly Resistant Single
and Polymutant BCR-ABL1. BLOOD, vol. 121; p. 1387-1388, ISSN: 0006-4971
 FERMEGLIA M., P. Posocco, S. Pricl, J-W. Handgraaf, J. Fraaije, P. Degimann, V. Kurkal-Siebert, H. Weiss
(2009). On the DPD Parameter Estimation from Atomistic / Quantum Mechanics Information. In: 2009 AIChE Fall
Annual Meeting CD. Nashville, US, November 2009AICHE, p. ---, ISBN/ISSN: 9780816910588
 P. Posocco, FERMEGLIA M., S. Pricl (2009). The long and winding road.Multiscale molecular modeling approach
to the self-assembly of di/triblock copolymers for drug delivery in aqueous solution. In: 2009 AIChE Fall Annual
Meeting CD. Nashville , US, November 2009AICHE, p. ---, ISBN/ISSN: 9780816910588
 FERMEGLIA M., P. Posocco, S. Pricl, G. Scocchi, J-W Handgraaf, J. Fraaije (2009). A Complete Multiscale
Modeling Approach for Polymer-Clay Nanocomposites. In: 2012 AIChE Spring Annual Meeting CD. Nashville, US,
November 2009AICHE, p. ---, ISBN/ISSN: 9780816910588
 Pricl S, Posocco P, Scocchi G, FERMEGLIA M. (2010). Polymer clay nanocomposites. In: Sattler K. Hanbook of
Nanophysics. p. 3-1-3-15, Boca Raton: CRC Press Taylor & Francis Group, ISBN/ISSN: 9781420075526
 FERMEGLIA M., Pricl S. (2008). Sources of thermophysical data:
data banks and predictive methods, p. 135-148
 Xiaoxuan Liu, Jiangyu Wu, Miriam Yammine, Jiehua Zhou, Paola Posocco, Stephane Viel, Cheng Liu, Fabio
Ziarelli, FERMEGLIA M., Sabrina Pricl, Genevieve Victorero, Catherine Nguyen, Patrick Erbacher, Jean-Paul Behr,
Ling Peng (2011). Structurally Flexible Triethanolamine Core PAMAM Dendrimers Are Effective Nanovectors for
DNA Transfection in Vitro and in Vivo to the Mouse Thymus. BIOCONJUGATE CHEMISTRY, vol. 22; p. 2461-2473,
ISSN: 1043-1802, doi: 10.1021/bc200275g
 Gabriele Giliberti, Cristina Ibba, Esther Marongiu, Roberta Loddo, Michele Tonelli, Vito Boido, Erik Laurini, Paola
Posocco, FERMEGLIA M., Sabrina Pricl (2010). Synergistic experimental/computational studies on arylazoenamine
derivatives that target the bovine viral diarrhea virus RNA-dependent RNA polymerase. BIOORGANIC &
MEDICINAL CHEMISTRY, vol. 18; p. 6055-6068, ISSN: 0968-0896, doi: 10.1016/j.bmc.2010.06.065
 FERMEGLIA M., Gennaro Longo, Letitia Toma (2007). A hierarchical approach for the estimation of
environmental impact of a chemical process: from molecular modeling to process simulation. COMPUTER-AIDED
CHEMICAL ENGINEERING, vol. 24; p. 1199-1204, ISSN: 1570-7946, doi: 10.1016/S1570-7946(07)80224-0
 P. Posocco, FERMEGLIA M., X. X. Liu, L. Peng, A. Malek, C. V. Catapano, D. K. Smith, S. Pricl (2010). Is variety
the spice of life? Multiscale molecular simulations support experiments in nanocarrier/nucleic acid systems design.
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 S. Pricl, D. Gibbons, E. Laurini, P. Posocco, FERMEGLIA M., V. D. Col, H. Kantarjian, M. Talpaz, J. Cortez, N.
Donato, A. Quintas-Cardama (2012). Sensitivity To Novel Tyrosine Kinase Inhibitors of Highly Resistant Single and
Polymutant Bcr-abl1: A Combined Approach. ANNALS OF ONCOLOGY, vol. 23; p. 21-22, ISSN: 0923-7534
 Pricl S., Posocco P., FERMEGLIA M., Scocchi G., Danani A., Handgraaf J.W., Fraaije H.G.E.M. (2007). The dark
side of the moon: A multiscale approach to self-assembly of dendrimers for cancer therapy. MOLECULAR CANCER
THERAPEUTICS, vol. 6; p. 3559-3559, ISSN: 1535-7163
 Posocco P., FERMEGLIA M., Pricl S. (2009). Mulholland Dr. Multiscale molecular modeling of the self-assembly of
di/triblock copolymers for drug delivery. In: FOMMS2009, Foundation of Molecular Modelling and Simulation.
Semiahmoo Resort Blane, Washington, USA, luglio 2009Cache, p. 1-5
 FERMEGLIA M., Pricl S. (2008). Multiscale molecular modeling for the design of nanostructured materials. In: -.
Chemical Engineering Greetings to prof. Eliseo Ranzi . vol. 1, p. 225-242, Milano: AIDIC Servizi S.r.l.
 FERMEGLIA M., Pricl S. (2007). Modellazione multiscala per sistemi nanocompositi di interesse industriale. In: -.
XXVIII Convegno Scuola AIM Mario Farina, Materiali polimerici nanostrutturat. vol. 1, p. 133-152, Gargnano, I :
AIM
 Pricl S., Posocco P., Laurini E., FERMEGLIA M., Karatasos K., Peng L., Smith D.K. (2010). When virtual and real
meet: computational/experimental evidences for designing efficient nanovectors for siRNA/DNA delivery. In:
NanotechItaly, Convegno Italiano di Nanotecnologie. Venezia, I, October 20-22, 2010, Venezia: Veneto Nanotech,
vol. 1, p. 1-1
 FERMEGLIA M., Posocco P., Toth R., Pereira S.P.S.B., Pricl S. (2010). Multiscale Molecular Modeling of
Polymer/Silica Nanocomposites. In: NanotechItaly, Convegno Italiano di Nanotecnologie. Venezia, I, October 2022, 2010, Venezia: Veneto Nanotech, vol. 1, p. 1-1
 FERMEGLIA M., Pricl S. (2012). Multiscale molecular modeling for the design of materials in the nano-bio-based
economy. In: EMCC7. Corfu Island Greece, April 27-May 1 2012, Corfu: EMCC-7, vol. 1, p. 1-1
 FERMEGLIA M., Pricl S. (2012). Nano tools for macro problems: multiscale molecular modeling of life and
material sciences
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 FERMEGLIA M., Pricl S., Posocco P (2012). Nano tools for macro problems: multiscale molecular modeling of
nanostrucured polymer systems. In: 11th EUROPEAN SYMPOSIUM ON POLYMER BLENDS. DONOSTIA - SAN
SEBASTIAN (SPAIN), MARCH 25 TO 28, 2012, Plaza Europa 1 20018 Donostia: Escuela Universitaria Politécnica, p.
1-1
 FERMEGLIA M., Posocco P., Pricl S. (2012). Nano tools for macro problems: multiscale molecular modeling of
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, 24-28 June 2012 ECCM15, vol. 1, p. 1-1
 FERMEGLIA M. (2012). Multiscale molecular modeling: a virtual microscope for material and life science . In:
2nd Nanosymposium on Nanomaterials. Poznan, June 20-24, 2012, Poznan: Adam Mickiewicz University, , vol. 1,
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 FERMEGLIA M. (2011). Opportunities and challenges from HPC and research. In: Towards a multi-scale, multiphenomena modelling-simulation-design-engineering environment & tools. Brussels (ERC building, Place Madou),
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 D. R. Nieto, F. Santese, R. Toth, P. Posocco, S. Pricl, FERMEGLIA M. (2012). Simple, Fast, and Accurate In silico
Estimations of Contact Angle, Surface Tension, and Work of Adhesion of Water and Oil Nanodroplets on
Amorphous Polypropylene Surfaces. ACS APPLIED MATERIALS & INTERFACES, vol. 4; p. 2855-2859, ISSN: 19448244, doi: 10.1021/am3004818
 Posocco P., Gentilini C., Bidoggia S., Pace A., Franchi P., Lucarini M., FERMEGLIA M., Pricl S., Pasquato L.
(2012). Self-organization of mixtures of fluorocarbon and hydrocarbon amphiphilic thiolates on the surface of gold
nanoparticles. ACS NANO, vol. 6; p. 7243-7253, ISSN: 1936-0851, doi: 10.1021/nn302366q
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 FIRRAO G., GARCIA-CHAPA M, MARZACHI C (2007). Phytoplasmas: genetics, diagnosis and relationships with
the plant and insect host. FRONTIERS IN BIOSCIENCE, vol. 12; p. 1353-1375, ISSN: 1093-4715, doi:
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 FIRRAO G., CONCI L, LOCCI R (2007). Molecular Identification and Diversity of Phytoplasmas. In: PUNJA Z.K.,
DE BOER S.H., SANFACON H.. Biotechnology and Plant Disease Management. p. 250-276, WALLINGFORD: CABI,
ISBN/ISSN: 9781845932886
 CETTUL E, REKAB D, LOCCI R, FIRRAO G. (2008). Evolutionary analysis of endopolygalacturonase encoding
genes of Botrytis cinerea. MOLECULAR PLANT PATHOLOGY, vol. 9; p. 675-685, ISSN: 1464-6722, doi:
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 MORETTI M, DI FABRIZIO E, CABRINI S, MUSETTI R, DE ANGELIS F, FIRRAO G. (2008). An ON/OFF biosensor
based on blockade of ionic current passing through a solid state nanopore. BIOSENSORS & BIOELECTRONICS, vol.
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 TORELLI E, GUBIANI R, FIRRAO G., CIVIDINO S, LOCCI R, GOBBI E (2010). Air analysis in the assessment of
fumonisin contamination risk in maize. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, vol. 90; p. 641649, ISSN: 0022-5142
 REKAB D, PIRAJNO G, CETTUL E, DE SALVADOR F. R, FIRRAO G. (2010). On the apple proliferation symptom
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OF PLANT PATHOLOGY, vol. 127; p. 7-12, ISSN: 0929-1873, doi: 10.1007/s10658-010-9579-z
 FIRRAO G., TORELLI E, GOBBI E, RARANCIUC S, BIANCHI G, LOCCI R (2010). Prediction of milled maize
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 BULL C.T, DE BOER S.H, DENNY T.P, FIRRAO G., M FISCHER-LE SAUX, M, SADDLER G.S, SCORTICHINI M,
STEAD D.E, TAKIKAWA Y (2010). Comprehensive List of Names of Plant Pathogenic Bacteria, 1980-2007.
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 SACCARDO F, CETTUL E, PALMANO S, NORIS E, FIRRAO G. (2011). On the alleged origin of geminiviruses from
extrachromosomal DNAs of phytoplasmas. BMC EVOLUTIONARY BIOLOGY, vol. 11; p. 185, ISSN: 1471-2148, doi:
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 FIRRAO G., BROWN D.R (2011). Minutes of the International Committee on Systematics of Prokaryotes.
Subcommittee on the taxonomy of Mollicutes. INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY
MICROBIOLOGY, vol. 61; p. 695-697, ISSN: 1466-5026, doi: 10.1099/ijs.0.030056-0
 PANE C, REKAB D, FIRRAO G., RUOCCO M, SCALA F (2008). A novel gene coding for an ABC transporter in
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 BULL C.T, DE BOER, S.H, DENNY T.P, FIRRAO G., FISCHER-LE SAUX M, SADDLER G.S, SCORTICHINI M, STEAD
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 Marcelletti S, Ferrante P, Petriccione M, FIRRAO G., Scortichini M (2011). Pseudomonas syringae pv. actinidiae
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 Cettul E, FIRRAO G. (2011). Development of phytoplasma-induced flower symptoms in Arabidopsis thaliana.
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 Torelli E, FIRRAO G., Bianchi G, Saccardo F, Locci R. (2012). The influence of local factors on the prediction of
fumonisin contamination in maize. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, ISSN: 0022-5142,
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 Scortichini M, Marcelletti S, Ferrante P, Petriccione M, FIRRAO G. (2012). Pseudomonas syringae pv. actinidiae:
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 Gaspardo B, Del Zotto S, Torelli E, Cividino S R, FIRRAO G., Della Riccia G, Stefanon B (2012). A rapid method
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 Catalano Valentina, Rekab Djaouida, FIRRAO G., Vannacci Giovanni, Vergara Mariarosaria (2012). An
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 MONTINI T, CONDO' AM, HICKEY N, LOVEY F.C, DE ROGATIS L, FORNASIERO P., GRAZIANI M (2007).
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conditions. APPLIED CATALYSIS. B, ENVIRONMENTAL, vol. 73; p. 84-97, ISSN: 0926-3373, doi:
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 MONTINI T, DE ROGATIS L, GOMBAC V, FORNASIERO P., GRAZIANI M (2007). Rh(1%)@CexZr1-xO2-Al2O3
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ENVIRONMENTAL, vol. 71; p. 125-134, ISSN: 0926-3373, doi: 10.1016/j.apcatb.2006.09.003
 ZHOU G, SHAH P.R, KIM T, FORNASIERO P., GORTE R.J (2007). Oxidation entropies and enthalpies of ceria–
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 BETTINELLI M, DALLACASA V, FALCOMER D, FORNASIERO P., GOMBAC V, MONTINI T, ROMAN L, SPEGHINI A
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 MONTINI T, SPEGHINI A, FORNASIERO P., BETTINELLI M, GRAZIANI M (2008). Effect of the thermal
pretreatments on ceria – zirconia redox properties: an Eu3+ luminescence study. JOURNAL OF ALLOYS AND
COMPOUNDS, vol. 451; p. 617-620, ISSN: 0925-8388, doi: 10.1016/j.jallcom.2007.04.074
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Ceria Surfaces. SURFACE SCIENCE, vol. 601; p. 2512-2519, ISSN: 0039-6028
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 FORNASIERO P., MONTINI T, GRAZIANI M, ZILLIO S, SUCCI M (2008). Development of Catalytic Nanoceramicloaded Fe-Al-Cr Alloy Fiber Media for Exhaust Gas Purification. CATALYSIS TODAY, vol. 137; p. 475-482, ISSN:
0920-5861, doi: 10.1016/j.cattod.2007.12.097.
 FORNASIERO P., MONTINI T, DE ROGATIS L (2007). Catalysts Design for Hydrogen Production: Embedded
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 ZINOVIEV S, FORNASIERO P., LODOLO A, MIERTUS S (2007). Non-combustion thechnologies for POPs
destruction: review and evaluation. TRIESTE: ICS-UNIDO
 FAHMY Y.M, FORNASIERO P., ZINOVIEV S, MIERTUS S (2007). Air Pollution Control Thechnologies:
Compendium. TRIESTE: ICS-UNIDO
 BEVILACQUA M, MONTINI T, TAVAGNACCO C, FONDA E, FORNASIERO P., GRAZIANI M (2007). Preparation,
characterization and electrochemical properties of pure and composite LaNi0.6Fe0.4O3 – based cathodes for ITSOFC. CHEMISTRY OF MATERIALS, vol. 19; p. 5926-5936, ISSN: 0897-4756, doi: 10.1021/cm071622n
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a combined experimental and theoretical study. PHYSICAL REVIEW. B, CONDENSED MATTER AND MATERIALS
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 NATILE M.M, POLETTO F, GALENDA A, GLISENTI A, MONTINI T, DE ROGATIS T, FORNASIERO P. (2008).
La0.6Sr0.4Co1-yFeyO3-d perovskites: influence of the Co/Fe atomic ratio on properties and catalytic activity
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 GENNARI F.C, MONTINI M, FORNASIERO P., ANDRADE GAMBOA J.J (2008). REDUCTION BEHAVIOR OF
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 FITTIPALDI M, GOMBAC V, MONTINI T, FORNASIERO P., GRAZIANI M (2008). A High-Frequency (95 GHz)
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 TONELLI M, VAZZANA I, TASSO B, BOIDO V, SPARATORE F, FERMEGLIA M, PANENI M.S, POSOCCO P, PRICL S.,
LA COLLA P, IBBA C, SECCI B, COLLU G, LODDO R (2009). Antiviral and cytotoxic activities of aminoarylazo
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and aryltriazene derivatives. BIOORGANIC & MEDICINAL CHEMISTRY, vol. 17; p. 4425-4440, ISSN: 0968-0896
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PRICL S., L. VIO (2009). Synthesis, biological evaluation, and three-dimensional in silico pharmacophore model
for sigma1 receptor ligand based on a series of benzo[d]oxazol-2(3H)-one derivatives. JOURNAL OF MEDICINAL
CHEMISTRY, vol. 52; p. 5380-5393, ISSN: 0022-2623, doi: 10.1021/jm900366z
 PAVAN G.M, DANANI A, PRICL S., SMITH, D.K (2009). Modeling the multivalent recognition between dendritic
molecules and DNA: Understanding how ligand "sacrifice" and screening can enhance binding. JOURNAL OF THE
AMERICAN CHEMICAL SOCIETY, vol. 131; p. 9686-9694, ISSN: 0002-7863
 ANGUSTI A, MANFREDINI S, DURINI E, CILIBERTI N, VERTUANI S, SOLAROLI N, PRICL S., FERRONE M,
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synthesis and anti flaviviridae activity of N6-, -O- and 5 O-substituted adenine nucleoside analogs. CHEMICAL &
PHARMACEUTICAL BULLETIN, vol. 56; p. 423-432, ISSN: 0009-2363
 SCOCCHI G, POSOCCO P, HANDGRAAF J.W, FRAAIJE J.G.E.M, FERMEGLIA M., PRICL S. (2009). A complete
multiscale modelling approach for polymer-clay nanocomposites. CHEMISTRY-A EUROPEAN JOURNAL, vol. 15; p.
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system engineering. COMPUTERS & CHEMICAL ENGINEERING, vol. 33; p. 1701-1710, ISSN: 0098-1354
 E. LAURINI, D. ZAMPIERI, M.G. MAMOLO, L. VIO, C. ZANETTE, C. FLORIO, P. POSOCCO, M. FERMEGLIA, PRICL
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 Carta A., PRICL S., Piras S., Fermeglia M., La Colla P., Loddo R. (2009). Activity and molecular modeling of a
new small molecule active against NNRTI-resistant HIV-1 mutants. EUROPEAN JOURNAL OF MEDICINAL
CHEMISTRY, vol. 44; p. 5117-5122, ISSN: 0223-5234
 Tonelli M., Boido V., La Colla P.L., Loddo R., Posocco P., Paneni M.S., Fermeglia M., PRICL S. (2010).
Pharmacophore modeling, resistant mutant isolation, docking, and MM-PBSA analysis: Combined
experimental/computer-assisted approaches to identify new inhibitors of the bovine viral diarrhea virus (BVDV).
BIOORGANIC & MEDICINAL CHEMISTRY, vol. 18; p. 2304-2316, ISSN: 1464-3391
 Jones S.P., Pavan G.M., Danani A., PRICL S., Smith D.K. (2010). Quantifying the effect of surface ligands on
dendron-DNA interactions: Insights into multivalency through a combined experimental and theoretical approach.
CHEMISTRY-A EUROPEAN JOURNAL, vol. 16; p. 4519-4532, ISSN: 0947-6539
 T. J. Stemke-Hale, K. Lazar A.J., PRICL S., Pavan G.M., Fermeglia M., Gopal Y.N.V., Yang D., Podoloff D.A., Ivan
D., Kim K.B., Papadopoulos N., Hwu P., Mills G.B., Davies M.A., Woodman, S.E. (2009). Activity of dasatinib
against L576P KIT mutant melanoma: Molecular, cellular, and clinical correlates. MOLECULAR CANCER
THERAPEUTICS, vol. 8; p. 2079-2085, ISSN: 1535-7163
 Conca, E., Negri T., Gronchi A., Fumagalli E., Tamborini E., Pavan G.M., Fermeglia M., Pierotti M.A., PRICL S.,
Pilotti S. (2009). Activate and resist: L576P-KIT in GIST. MOLECULAR CANCER THERAPEUTICS, vol. 8; p. 24912495, ISSN: 1535-7163
 Toth R., Voorn D., Handgraaf J.-W., Fraaije J.G.E.M., Fermeglia M., PRICL S., Posocco P. (2009). Multiscale
computer simulation studies of water-based montmorillonite/ poly(ethylene oxide) nanocomposites.
MACROMOLECULES, vol. 42; p. 8260-8270, ISSN: 0024-9297
 P. Posocco, Z. Posel, M. Fermeglia, M. Lisal, PRICL S. (2010). A molecular simulation approach to the prediction
of the morphology of self-assembled nanoparticles in diblock copolymers. JOURNAL OF MATERIALS CHEMISTRY,
vol. 20; p. 10511-10520, ISSN: 0959-9428, doi: 10.1039/c0jm01561j
 PIEROTTI M, TAMBORINI E., NEGRI T., PRICL S., PILOTTI S. (2011). Targeted therapy in GIST: in silico
modeling for prediction of resistance. NATURE REVIEWS. CLINICAL ONCOLOGY, vol. 8; p. 161-170, ISSN: 17594774
 DILEO P, PRICL S., TAMBORINI E, NEGRI T, STACCHIOTTI S, GRONCHI A, POSOCCO P, LAURINI E, COCO P,
FUMAGALLI E, CASALI PG, PILOTTI S. (2011). Imatinib response in two GIST patients carrying two hitherto
functionally uncharacterized PDGFRA mutations: an imaging, biochemical and molecular modeling study.
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 Tonelli M, Simone M, Tasso B, Novelli F, Boido V, Sparatore F, Paglietti G, PRICL S., Giliberti G, Blois S, Ibba C,
Sanna G, Loddo R, La Colla P. (2010). Antiviral activity of benzimidazole derivatives. II. Antiviral activity of 2phenylbenzimidazole derivatives. BIOORGANIC & MEDICINAL CHEMISTRY, vol. 18; p. 2937-2953, ISSN: 09680896
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paradigm. MOLECULAR ONCOLOGY, vol. 4; p. 19-37, ISSN: 1574-7891
 Posocco P, Fermeglia M, PRICL S. (2010). Morphology prediction of block copolymers for drug delivery by
mesoscale simulations. JOURNAL OF MATERIALS CHEMISTRY, vol. 20; p. 7742-7753, ISSN: 0959-9428
 PRICL S. (2009). Quo vadis, affinity? Clinical evidences and computer-assisted
simulations in the Imatinib saga. EUROPEAN JOURNAL OF NANOMEDICINE, vol. 2; p. 22-30, ISSN: 1662-5986
 Laurini E., Zampieri D., Mamolo M.G., Vio L., Posocco P., Fermeglia M., PRICL S., Zanette C., Florio C. (2010).
SYNTHESIS, MOLECULAR MODELING AND EXPERIMENTAL
ACTIVITY OF SOME NEW ACETAMIDE, BENZAMIDE AND
PHENYLMETHANONE DERIVATIVES AS SIGMA LIGANDS. In: Book of abstracts. Abano Terme (PD), 12-16
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 Liu X., Chen H., Laurini E., Wang Y., Dal Col V., Posocco P., Ziarelli F., Fermeglia M., Zhang C., PRICL S., Peng
L. (2011). 2-Difluoromethylene-4-methylenepentanoic Acid, A Paradoxical Probe Able To Mimic the Signaling Role
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of 2-Oxoglutaric Acid in Cyanobacteria. ORGANIC LETTERS, vol. 13; p. 2924-2927, ISSN: 1523-7060
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montmorillonite silylation: Unexpected effect of the aminosilane chain length . JOURNAL OF COLLOID AND
INTERFACE SCIENCE, vol. 2010; p. 108-115, ISSN: 0021-9797
 Pavan GM, Posocco P., Tagliabue A., Maly M., Malek A., Danani A., Ragg E., Catapano C.V., PRICL S. (2010).
PAMAM Dendrimers for siRNA Delivery: Computational and Experimental Insights. CHEMISTRY-A EUROPEAN
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M.R., Laurini E., Paneni M.S., Posocco P., Fermeglia M., PRICL S. (2011). 3-Aryl-2-[1H-benzotriazol-1yl]acrylonitriles: A novel class of potent tubulin inhibitors . EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.
46; p. 4151-4167, ISSN: 0223-5234
 M. Fermeglia, PRICL S. (2008). Multiscale molecular modeling: a tool for the design of nano structured
materials. ICP, vol. 2008; p. 225-242, ISSN: 0390-2358
 Laurini E., Dal Col V., Mamolo M.G., Zampieri D., Posocco P., Fermeglia M., Vio L., PRICL S. (2011). Homology
Model and Docking-Based Virtual Screening for Ligands of the s1 Receptor. ACS MEDICINAL CHEMISTRY LETTERS,
vol. 2; p. 834-839, ISSN: 1948-5875
 Fermeglia M., PRICL S. (2011). Nano tools for macro problems: multiscale molecular modeling of polymer
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Produce New, Better Nanocomposite Materials. In: 2011 AIChE Fall Annual Meeting CD. Minneapolis, US,
November 2011AICHE, p. 1-1, ISBN/ISSN: 9780816910700
 PRICL S., D. L. Gibbons, P. Posocco, E. Laurini, M. Fermeglia, H. M. Kantarjian, M. Talpaz, J. Cortes, M. Young,
H. Sun, L. F. Peterson, N. Donato, A. Quintas-Cardama (2010). The Novel BCR-ABL1 V304D Mutation Induces
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ISSN: 0006-4971
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Polymer/Clay Nanocomposites . JOURNAL OF MULTISCALE MODELLING, vol. Vol 3 Nos 3 & 4 ; p. 1-28, ISSN:
1756-9737
 Pierotti M, Tamborini E., Negri T., PRICL S., Pilotti S. (2011). Targeted therapy in GIST: in silico modeling for
prediction of resistance. NATURE REVIEWS. CLINICAL ONCOLOGY, vol. 8; p. 161-170, ISSN: 1759-4774
 Dileo P, PRICL S., Tamborini E, Negri T, Stacchiotti S, Gronchi A, Posocco P, Laurini E, Coco P, Fumagalli E,
Casali PG, Pilotti S. (2011). Imatinib response in two GIST patients carrying two hitherto functionally
uncharacterized PDGFRA mutations: an imaging, biochemical and molecular modeling study. INTERNATIONAL
JOURNAL OF CANCER, vol. 128; p. 983-990, ISSN: 0020-7136
 Scocchi G., G. Handgraaf J.-W., Malek A., Maly M., Fermeglia M., Fraaije J.G.E.M., Catapano C.V., Danani A.,
PRICL S., Posocco P. (2008). Base invaders. Coupling experiments and multiscale modeling of dendrimer-based
siRNA delivery agents. ADVANCES IN SCIENCE AND TECHNOLOGY, vol. 57; p. 154-159, ISSN: 1662-0356
 Posocco P., PRICL S., Fermeglia M. (2008). Multiscale molecular modeling of hybrid organic-inorganic
nanocomposites of type I and II. ADVANCES IN SCIENCE AND TECHNOLOGY, vol. 54; p. 265-269, ISSN: 16620356
 Jones S.P., Gabrielson N.P., Wong C.H., Chow H.F., Pack D.W., Posocco P., Fermeglia M., PRICL S., Smith D.K.
(2011). Hydrophobically Modified Dendrons: Developing Structure-Activity Relationships for DNA Binding and
Gene Transfection. MOLECULAR PHARMACEUTICS, vol. 8; p. 4176-429, ISSN: 1543-8384
 Barnard A., Posocco P., PRICL S., Calderon M., Haag R., Shum W.T., Pack W.D., Smith D.K. (2011). Degradable
Self-Assembling Dendrons for Gene Delivery – Experimental and Theoretical Insights into the Barriers to Cellular
Uptake. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 133; p. 20288-20300, ISSN: 0002-7863
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mutations? The BCR-ABL1 T315I paradigm. CANCER, vol. 118; p. 293-299, ISSN: 0008-543X
 Karatasos K., Posocco P., Laurini E., PRICL S. (2012). Poly(amidoamine)-based Dendrimer/siRNA
Complexation Studied by Computer
Simulations: Effects of pH and Generation on
Dendrimer Structure and siRNA Binding. MACROMOLECULAR BIOSCIENCE, vol. 12; p. 225-240, ISSN: 1616-5187
 R. Toth, F. Santese, S. P. Pereira, D. R. Nieto, PRICL S., M.Fermeglia, P. Posocco (2012). Size and shape
matter! A multiscale molecular simulation approach to polymer nanocomposites. JOURNAL OF MATERIALS
CHEMISTRY, vol. 22; p. 5398-5409, ISSN: 0959-9428
 X. Liu, C. Liu, E. Laurini, P. Posocco, PRICL S., F. Qu, P. Rocchi, L. Peng (2012). Efficient Delivery of Sticky
siRNA and Potent Gene Silencing in a Prostate Cancer Model Using a Generation 5 Triethanolamine-Core PAMAM
Dendrimer. MOLECULAR PHARMACEUTICS, vol. 9; p. 470-481, ISSN: 1543-8384
 Daniele Zampieri, Maria Grazia Mamolo, Erik Laurini, Maurizio Fermeglia, Paola Posocco, PRICL S., Elena Banfi,
Giuditta Scialino, Luciano Vio (2009). Antimycobacterial activity of new 3,5-disubstituted 1,3,4-oxadiazol-2(3H)one derivatives. Molecular modeling investigations. BIOORGANIC & MEDICINAL CHEMISTRY, vol. 17; p. 46934707, ISSN: 0968-0896, doi: 10.1016/j.bmc.2009.04.055
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nanocomposites of type I and II. In: CIMTEC 2008 - Proceedings of the 3rd International Conference on Smart
Materials, Structures and Systems - Smart Materials and Micro/Nanosystems. Acireale, 8 June 2008through13
June 2008CIMTEC, p. 265-269, ISBN/ISSN: 9783908158110
 Y. Xia, S. Viel, Y. Wang, F. Ziarelli, E. Laurini, P. Posocco, M. Fermeglia, F. Qu, PRICL S., L. Peng (2012).
Rationalizing the FS interaction discovered within a tetrafluorophenylazido-containing bola-phospholipid
. CHEMICAL COMMUNICATIONS, vol. 48; p. 4284-4286, ISSN: 1359-7345, doi: 10.1039/c2cc18147a
 Fermeglia M., PRICL S. (2009). Multiscale molecular modelling of dispersion of nanoparticles in polymer systems
of industrial interest. In: IUTAM Symposium on Modelling Nanomaterials and Nanosystems. Aalborg, Denmark,
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19-22 May, 2008Springer-Verlag, p. 261-270, ISBN/ISSN: 9781402095566
 Fermeglia M., PRICL S. (2010). Multiscale molecular modeling: a nano-engineering tool for the design of hybrid
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Molecular Simulations and Experiments in Developing Nanocarrier/Nucleic Acid Systems. In: 2010 AIChE Fall
Annual Meeting CD. Salt Lake City, US, November 2010AICHE, p. ---, ISBN/ISSN: 9780816910656
 Fermeglia M, Posocco P., PRICL S., Handgraaf J.W. (2010). Multiscale Molecular Modeling of Polymer/Silica
Nanocomposites. In: 2010 AIChE Fall Annual Meeting CD. Salt Lake City, US, November 2010AICHE, p. ---,
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 Fermeglia M., PRICL S. (2009). COSMO-RS and process simualtion:from physical properties to environmental
impact. In: COSMO-RS Symposium 2009. Koln, March 2009COSMO-RS Symposium 2009, Koln, March 2009, p. 11
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Designing nanovectors for siRNA delivery: coupled experimental/modeling investigations. EUROPEAN JOURNAL OF
CANCER, vol. 6; p. 173-174, ISSN: 0959-8049
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affinity: molecular insights from in silico experiments. EUROPEAN JOURNAL OF CANCER, vol. 6; p. 154-155, ISSN:
0959-8049, doi: 10.1016/S1359-6349(08)72418-2
 Cosoli P., Fermeglia M., Ferrone M., PRICL S., Toma L. (2008). Molecular simulation techniques for sustainable
technology and environmental applications: general overview and case studies. In: CISAP-3 : 3rd International
Conference on Safety & Environment in Process. Rome, Italy, May, 11-14, 2008, MILANO: AIDIC, vol. 1, p. 1-8,
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 PRICL S., Pavan GM, Tamborini E, DiLeo P, Gronchi A, Stacchiotti S, Pilotti S, Pierotti MA, Casali P (2008).
Activity/modeling of imatinib against gatrointestinal stromal tumors carrying PDGFRA mutations in exons 18 and
12. ANNALS OF ONCOLOGY, vol. 19; p. 43-44, ISSN: 0923-7534
 Fermeglia M., PRICL S. (2008). Message –passing multiscale molecular modeling: mapping atomistic to
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and Polymutant BCR-ABL1. BLOOD, vol. 121; p. 1387-1388, ISSN: 0006-4971
 M. Fermeglia, P. Posocco, PRICL S., J-W. Handgraaf, J. Fraaije, P. Degimann, V. Kurkal-Siebert, H. Weiss
(2009). On the DPD Parameter Estimation from Atomistic / Quantum Mechanics Information. In: 2009 AIChE Fall
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 P. Posocco, M. Fermeglia, PRICL S. (2009). The long and winding road.Multiscale molecular modeling approach
to the self-assembly of di/triblock copolymers for drug delivery in aqueous solution. In: 2009 AIChE Fall Annual
Meeting CD. Nashville , US, November 2009AICHE, p. ---, ISBN/ISSN: 9780816910588
 M. Fermeglia, P. Posocco, PRICL S., G. Scocchi, J-W Handgraaf, J. Fraaije (2009). A Complete Multiscale
Modeling Approach for Polymer-Clay Nanocomposites. In: 2012 AIChE Spring Annual Meeting CD. Nashville, US,
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 PRICL S., Posocco P, Scocchi G, Fermeglia M (2010). Polymer clay nanocomposites. In: Sattler K. Hanbook of
Nanophysics. p. 3-1-3-15, Boca Raton: CRC Press Taylor & Francis Group, ISBN/ISSN: 9781420075526
 Xiaoxuan Liu, Jiangyu Wu, Miriam Yammine, Jiehua Zhou, Paola Posocco, Stephane Viel, Cheng Liu, Fabio
Ziarelli, Maurizio Fermeglia, PRICL S., Genevieve Victorero, Catherine Nguyen, Patrick Erbacher, Jean-Paul Behr,
Ling Peng (2011). Structurally Flexible Triethanolamine Core PAMAM Dendrimers Are Effective Nanovectors for
DNA Transfection in Vitro and in Vivo to the Mouse Thymus. BIOCONJUGATE CHEMISTRY, vol. 22; p. 2461-2473,
ISSN: 1043-1802, doi: 10.1021/bc200275g
 Gabriele Giliberti, Cristina Ibba, Esther Marongiu, Roberta Loddo, Michele Tonelli, Vito Boido, Erik Laurini, Paola
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derivatives that target the bovine viral diarrhea virus RNA-dependent RNA polymerase. BIOORGANIC &
MEDICINAL CHEMISTRY, vol. 18; p. 6055-6068, ISSN: 0968-0896, doi: 10.1016/j.bmc.2010.06.065
 P. Posocco, M. Fermeglia, X. X. Liu, L. Peng, A. Malek, C. V. Catapano, D. K. Smith, PRICL S. (2010). Is variety
the spice of life? Multiscale molecular simulations support experiments in nanocarrier/nucleic acid systems design.
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side of the moon: A multiscale approach to self-assembly of dendrimers for cancer therapy. MOLECULAR CANCER
THERAPEUTICS, vol. 6; p. 3559-3559, ISSN: 1535-7163
 Posocco P., Fermeglia M., PRICL S. (2009). Mulholland Dr. Multiscale molecular modeling of the self-assembly of
di/triblock copolymers for drug delivery. In: FOMMS2009, Foundation of Molecular Modelling and Simulation.
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Personale non di ruolo nelle università o dipendenti di altri enti
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confocal and atomic force microscopy images, Journal of Neuroscience, Methods, 177. 94 (2009)
66. V Toffoli, F Esch, M Melli, A Pozzato, M Tormen and M Lazzarino, Chemical functionalization of atomically flat
cantilever surfaces, Microelectronic Eng., 86, 1200 (2009)
67. M.Polano, A. Bek, F. benetti, M. Lazzarino and G. Legname, Structural Insights into Alternate Aggregated Prion
Protein Forms, J. Mol. Biol, 393, 1033 (2009)
68. A morphological analysis of growth cones of DRG neurons combining Atomic Force and Confocal J. Laishram, S.
Kondra, D. Avossa, E. Migliorini, M. Lazzarino and V. Torre, Microscopy. Atomic Force and Confocal Microscopy. J.
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69. D. Cojoc, “Optical manipulation in support of high spatial and temporal resolution experiments in Biophysics”,
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70. E. Ferrari, L. Selvaggi, A. Moradi, S. Cantucci, P. Beuzer and D. Cojoc, “Optimized double-view imaging improves
observation of non-spherical particles in optical tweezers microscopy”, J. of Optics: Pure and Applied Optics, (2009).
71. D. Cojoc, H. Amenitsch, E. Ferrari, M. Rappolt, B. Marmirolli, B. Sartori, G. Grenci, S. Santucci, M., Burghammer
and Christian Riekel “Synchronized optical trapping and scanning micro-focused X-ray diffraction”, Nat. Methods
(2009).
72. V. Garbin, B. Dollet, M. Overvelde, D. Cojoc, E. Di Fabrizio, L. Van Wijngaarden, A. Prosperetti, N. de Jong, D.
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73. D. Cojoc, H. Amenitsch, C. Riekel, M. Rappolt, M. Burghammer, S. Santucci, G. Grenci, B. Sartori, B. Marmiroli, “Xray microdiffraction of microsamples manipulated in fluidic environment without mechanical contact”, ESRF Highlights
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74. V. Garbin, G. Volpe, E. Ferrari, M. Versluis, D. Cojoc and D. Petrov, “Mie scattering distinguishes the topological
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75. E. Connell, A. Giniatullina, J.L.K. Him, P. Scott, E. Ferrari, A. Roseman, D. Cojoc, A.R. Brisson and B. Davletov,
“Crosslinking of Phospholipid Membranes is a Conserved Property of Calcium-Sensitive, Synaptotagmins”, J. Mol. Biol.
380 42 (2008).
76. M. Mihailescu, A. Preda, D. Cojoc, E. Scarlat, L. Preda, “Diffractive patterns from a phyllotaxis type arrangement”,
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77. J. Garcia, V. Mico, D. Cojoc and Z. Zalevsky, “Full field of view superresolution imaging based on two static
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81. Visentin M, Biason P, Toffoli G. Drug interactions among the epidermal growth factor receptor inhibitors, other
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89. Electron Transfer Mediating Properties of Hydrocarbons as a Function of Chain Length: A Differential Scanning
Conductive Tip Atomic Force Microscopy Investigation, D. Scaini, M. Castronovo, L. Casalis, G. Scoles, ACS Nano, 2,
507-515, (2008)
90. MgO-Supported Rhodium Particles and Films: Size, Morphology, and Reactivity, L. Gregoratti, D. Scaini, Y. He, H.
Over, M. Kiskinova, J. Phys. Chem. C, 112, 9040-9044, (2008)
91. Primate cathelicidin orthologues display different structures and membrane interactions, F. Morgera, L. Vaccari, N.
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92. Quantitative Study of the Effect of Coverage on the Hybridization Efficiency of Surface-Bound DNA Nanostructures,
E. Mirmomtaz, M. Castronovo, C. Grunwald, F. Bano, D. Scaini, A. Ensafi, G. Scoles, L. Casalis, Nano Lett., 8, 41344139 (2008)
93. Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts, G. Cellot, E. Cilia, S.
Cipollone, V. Rancic, A. Sucapane, S. Giordani, L. Gambazzi, H. Markram, M. Grandolfo, D. Scaini, F. Gelain, L. Casalis,
M. Prato, M. Giugliano, L. Ballerini, Nature Nanotech.,4, 126-133 (2009)
94. Oriented Immobilization of Prion Protein Demonstrated via Precise Interfacial Nanostructure Measurements,
Barbara Sanavio, Denis Scaini, Christian Grunwald, Giuseppe Legname, Giacinto Scoles, Loredana Casalis, ACS Nano,
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95. Inverted tapered pillars for mass sensing. Melli M., Pozzato A., Lazzarino M. 2010 /Microelectronic Engineering/
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96. Modulation of alpha-synuclein aggregation by dopamine analogs. Latawiec, D., Herrera, F., Bek, A., Losasso, V.,
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97. Nanoscale chemical mapping using three-dimensional adiabatic compression of surface plasmon polaritons . De
Angelis F., Das G., Candeloro P., Patrini M., Galli M., Bek A., Lazzarino M. , Di Fabrizio E. /Nature Nanotechnology/ *5
* 67 (2010)
98. Berti M., Bisognin G., De Salvador D., Napolitani E., Vangelista S., Polimeni A.,Capizzi M., Boscherini F., Ciatto G.,
Rubini S., Martelli F., Franciosi A., Formation and dissolution of D-N complexes in dilute nitrides Phys. Rev. B 76,
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99. Bisognin G., De Salvador D., Napolitani E., Berti M., Polimeni A., Felici M., Capizzi M., Bais G., Jabeen F., Piccin M.,
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100. Martelli F., Piccin M.,. Bais G, Jabeen F., Ambrosini S., Rubini S., Franciosi A., Photoluminescence of Mn-catalyzed
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nanowires Physica E 37, 134 (2007).
104. Bakeine GJ, Bertolotti A, Latina M, Congiu T, Prati U, Roveda L, Trotta F, Tormen M, Fabrizio ED, Carlini G,
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105. Qazi, D. Nonis, A. Pozzato, M. Tormen, M. Lazzarino, S. Carrato and G. Scoles, Symmetric twin cantilever for
single molecole detection. Appl. Phys. Lett, *90*, 173118 (2007)
106. Maione, IA; Macucci, M; Iannaccone, G; Basso, G; Pellegrini, B; Lazzarino, M; Sorba, L; Beltram, F. , Probing
Pauli blocking with shot noise in resonant tunneling diodes: Experiment and theory. Phys. Rev. B, 75, 125327 (2007)
107. D. Cojoc, E. Ferrari, V. Garbin, E. Di Fabrizio, H. Amenitsch, M. Rappolt, B. Sartori, P. Laggner, M. Burghammer,
C. Riekel, “Scanning x-ray microdiffraction of optically manipulated liposomes”, Appl. Phys. Lett. 91 234107 (2007).
108. D. Cojoc, E. Ferrari, F. Difato, R. Shahapure, J. Laishram, M. Righi, E. Di Fabrizio, Vincent Torre, "Properties of
the force exerted by filopodia and lamellipodia and the involvement of cytoskeletal components", PLoS ONE 2(10):
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109. H. Amenitsch, E. Ferrari, M. Rappolt, B. Sartori, P. Laggner, V. Garbin, E. Di Fabrizio, M. Burghammer, C. Riekel,
D. Cojoc “Development of optical tweezers for sample fixing in microdiffraction experiments” ESRF, Newsletter 45 26
(2007)
110. M. Mihailescu, A. Preda, D. Cojoc, L. Preda E. Scarlat, I.M. Popescu, “Intensity redistribution in diffractive pattern
due to fractal phase changes”, J. Optoel. Adv. Mat. June 2007.
111. A.R. Moradi, E. Ferrari, V. Garbin, E. Di Fabrizio, D. Cojoc, “Strength control in multiple optical traps generated by
means of diffractive optical elements”,.Optoelectronics and Advanced Materials – Rapid Communications 1 158 (2007).
112. V. Garbin, D. Cojoc, E. Ferrari, E. Di Fabrizio, M. Overvelde, M. Versluis, S. van der Meer, N. de Jong, D. Lohse
“Changes in microbubble dynamics near a boundary revealed by combined optical micromanipulation and high-speed
imaging”, Appl. Phys. Lett. 90 114103 (2007).
113. M. Mihailescu, A. Preda, D. Cojoc, E. Scarlat, L. Preda, “Diffractive patterns correlation with shape and structure
of imprint objects”, J. Optoel. Adv. Mat. 9 1071 (2007).
114. Dimitrakakis C, Marmiroli B, Amenitsch H, Malfatti L, Innocenzi P, Grenci G, Vaccari L, Hill AJ, Ladewig BP, Hill
MR, Falcaro P. Top-down patterning of zeolitic imidazolate framework composite thin films by deep X-ray lithography.
Chem Commun (Camb). 2012 Aug 4;48(60):7483-5. Epub 2012 Jun 22.
115. Vaccari L, Birarda G, Businaro L, Pacor S, Grenci G. Infrared microspectroscopy of live cells in microfluidic devices
(MD-IRMS): toward a powerful label-free cell-based assay. Anal Chem. 2012 Jun 5;84(11):4768-75. Epub 2012 May
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116. Gioacchini G, Giorgini E, Merrifield DL, Hardiman G, Borini A, Vaccari L, Carnevali O., Biol Reprod. 2012 Mar
8;86(3):65. doi: 10.1095/biolreprod.111.094243. Print 2012 Mar., Probiotics can induce follicle maturational
competence: the Danio rerio case.
117. L Vaccari, G Birarda, G Grenci, S Pacor and L Businaro, Synchrotron radiation infrared microspectroscopy of
single living cells in microfluidic devices: advantages, disadvantages and future perspectives, Journal
ofPhysics:ConferenceSeries 359 (2012) 012007 doi:10.1088/1742-6596/359/1/012007
118. S. Zanotto, R. Degl'Innocenti, G. Biasiol, L. Sorba, and A. Tredicucci, “Analysis of lineshapes and strong coupling
with intersubband transitions in one-dimensional metallo-dielectric photonic crystal slabs”, Phys. Rev. B 85, 035307
(2012).
119. M. Porer, J.-M. Ménard, A. Leitenstorfer, R. Huber, R. Degl'Innocenti, S. Zanotto, G. Biasiol, L. Sorba, and A.
Tredicucci, “Nonadiabatic Switching of a Photonic Bandstructure: Ultrastrong Light-matter Coupling and Slow-down of
Light”, Phys. Rev. B 85, 081302(R) (2012).
120. N. Paradiso, S. Heun, S. Roddaro, L. Sorba, F. Beltram, G. Biasiol, L. N. Pfeiffer and K. W. West, “Imaging
Fractional Incompressible Stripes in Integer Quantum Hall Systems”, Phys. Rev. Lett. 108, 246801 (2012).
121. M. Yu. Melnikov, J. P. Kotthaus, V. Pellegrini, L. Sorba, G. Biasiol, V. S. Khrapai, Influence of e-e scattering on the
temperature dependence of the resistance of a ballistic point-contact in a two-dimensional electron system, Phys. Rev.
B 86, 075425 (2012).
122. N. Paradiso, S. Heun, S. Roddaro, G. Biasiol, L. Sorba, D. Venturelli, F. Taddei, V. Giovannetti, and F. Beltram,
“Imaging backscattering through impurity-induced antidots in quantum Hall constrictions”, Phys. Rev. B 86, 085326
(2012).
123. Kononov, G. Biasiol, L. Sorba, and E. V. Deviatov, “Energy spectrum reconstruction at the edge of a twodimensional electron system with strong spin-orbit coupling”, Phys. Rev. B 86, 125304 (2012).
124. V. Bellani, F. Rossella, F. Dionigi, M. Goiran, S. George, G. Biasiol, and L. Sorba, “Trion confinement and exciton
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125. Bozzini, M. Amati. L. Gregoratti, M. Abyaneh, M. Prasciolu, M. Tondo, A. Trygub and M. Kiskinova, In situ
electrochemical X-ray spectromicroscopy investigation of the reduction/reoxidation dynamics of Ni-Cu solid oxide fuel
cell anodic material in contact with a Cr interconnect 2 J. Phys Chem. C 116 (2012), pp. 7243-7248.
126. Bozzini, A. Gianoncelli, B. Kaulich, C. Mele M. Prasciolu and M. Kiskinova, Electrodeposition of manganese oxide
from eutectic urea/choline chloride ionic liquid: An in situ study based on soft X-ray spectromicroscopy and visible
reflectivity, Journal of Power Sources 211 2012, pp. 71-76.
127. B. Bozzini, M. Kazemian Abyaneh, M. Amati, A.Gianoncelli, L. Gregoratti, B. Kaulich, and M. Kiskinova, Soft X-ray
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9.Criteri di valuatazione delle scuole di dottorato
Nell’attesa dell’emanazione del nuovo decreto di disciplina del dottorato di ricerca (ex art. 19 L.
240/2010), il Nucleo di Valutazione ha stabilito di utilizzare nella valutazione delle proposte di
Corsi e Scuole di Dottorato per l’anno 2012 (XXVIII ciclo) il medesimo modello di valutazione
utilizzato lo scorso anno, salvo nuove indicazioni operative che dovessero pervenire dal MIUR.
RIFERIMENTI NORMATIVI
DM.224
Nota
DM.50/2010
/99 art.2
MIUR
Programmazio
ne 2010-2012
n.640/2
INDIRI
ZZI
INDICATORI E RANGE GIUDIZI
MIUR
011
punti
a)
b)
-
comma
3 lett.
a),
b), c)
(ovvero
1° - 2° 3°
Requisit
o)
punto
c)
comma
3 lett. d)
(ovvero
4°
Requisit
o)
punto B12
1
Qualità
scientifi
ca,
elevati
requisit
i di
struttur
ee
risorse
per la
ricerca
2
Impatt
o
dottora
to –
mondo
produtt
ivo
a) Composizione collegio
docenti
N docenti
esclusivi nei
SSD del corso
b) Produzione scientifica
del collegio docenti
Valutazione
c) Pubblicazioni
scientifiche dei
dottorandi
Valutazione
d) Iniziative di
pubblicizzazione delle
tesi di dottorato
Valutazione
POSITIVO / NEGATIVO
(è obbligatorio per tutti
OpenstarTS)
e) Disponibilità risorse e
strutture
Valutazione
INSUFF – SUFF – BUONO OTTIMO
f) Livello di
soddisfazione dei
dottorandi
% soddisfatti
questionario
dottorandi
2010
>= 50% INSUFF
35%< = <50% SUFF
20%<=  <35% BUONO
<20% OTTIMO
a) Inserimento
lavorativo dottori di
ricerca
(monitoraggio annuale
inviato al NV)
% dottori con
inserimento
lavorativo
connesso al
titolo ultimi 6
anni
%<=30 o non fornito => INSUFF
30< % <=50 => SUFF
50< % <=70 => BUONO
% >70 => OTTIMO
b) Cofinanziamento
delle
borse previsto per il
XXVII ciclo
% borse
finanziate con
fondi privati
italiani e
stranieri
% <= 10 BASSO
10 < % <= 30 MEDIO
% > 30 ALTO
c) Fonte di
finanziamento dei
progetti di ricerca attivi
nei dipartimenti
proponenti
% di fondi
provenienti da
privati italiani
e stranieri
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
N >= min => ADEGUATO N <
min => NON ADEGUATO
INSUFF – SUFF – BUONO OTTIMO
INSUFF – SUFF – BUONO OTTIMO
% <= 10 BASSO
10 < % <= 30 MEDIO
% > 30 ALTO
267
RIFERIMENTI NORMATIVI
DM.224
Nota
DM.50/20
/99 art.2
MIUR
10
n.640/2
Program
mazione
011
INDIRIZZI
MIUR
INDICATORI E RANGE GIUDIZI
20102012
punto
d)
punto
B12
3
a) Attrattività dottorato
Razionalizza
zione dei
corsi
b) Attrattività dottorato
sulle altre sedi
comma
3 lett. b)
(ovvero
2°
Requisit
o)
c) Apertura sede
N candidati
presenti alla
prova/ N posti
con borsa
banditi
N candidati
laureati altro
ateneo
presenti alla
prova / N
totale
candidati
presenti alla
prova
N iscritti
dottorato
provenienti da
altri atenei / N
iscritti totali
d) Dimensione prevista
del dottorato
N posti
ordinari
XXVII
e) Dimensione effettiva
del dottorato
media degli
iscritti negli
ultimi 3 cicli
(confrontata
con posti e
borse previsti)
punto
e)
comma
2
comma
3 lett.
a),
e)
(ovvero
1° - 5°
Requisit
o)
-
4
Ampiezza
delle
tematiche
scientifiche
con
riferimento a
discipline
riconoscibili
a livello
internazional
e
a) Denominazione chiara
e traducibile
Valutazione
b) Coerenza tra
tematiche scientifiche e
denominazione
Valutazione
c) Ampiezza tematiche
scientifiche
N SSD di
riferimento del
corso
d) Adeguata
formulazione delle
tematiche scientifiche e
degli obiettivi formativi
Valutazione
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
N < 2 BASSA
2 <= N <= 4 MEDIA
N > 4 ALTA
% <= 10 BASSA
10 < % <= 25 MEDIO-BASSA
25 < % <= 45 MEDIA
45 < % <= 60 MEDIO-ALTA
% > 60 ALTA
% <= 10 BASSA
10 < % <= 25 MEDIO-BASSA
25 < % <= 45 MEDIA
45 < % <= 60 MEDIO-ALTA
% > 60 ALTA
ADEGUATA – NON ADEGUATA
(con riferimento al tipo corso e agli
iscritti effettivi)
ADEGUATA – NON ADEGUATA
(con riferimento al tipo corso e al
numero delle borse)
ADEGUATA – NON ADEGUATA
SI – NO
ADEGUATA se N >= 3 NON
ADEGUATA se N < 3
ADEGUATA – NON ADEGUATA
268
RIFERIMENTI NORMATIVI
DM.224
/99 art.2
Nota
MIUR
n.640/2
011
DM.50/20
10
punto
f)
-
comma
3 lett. d)
(ovvero
4°
Requisit
o)
INDIRIZZI
MIUR
INDICATORI E RANGE GIUDIZI
Program
mazione
20102012
5
Internaziona
lizzazione
a) Convenzioni con
soggetti esteri per
attività formative
dottorandi
b) Fonte di
finanziamento dei
progetti di ricerca attivi
nei dipartimenti
proponenti
c) Presenza di iscritti
stranieri
d) Sito web del
dottorato
Valutazione
PREVISTE – NON PREVISTE
% di fondi
provenienti da
soggetti
stranieri
N iscritti
stranieri / N
iscritti totali
Valutazione
% <= 20 BASSO
20 < % <= 40 MEDIO
% > 40 ALTO
% < 10 BASSO
10 <= % < 20 MEDIO
% > =20 ALTO
INSUFFICIENTE - SCARSO –
SUFFICIENTE –
DISCRETO – BUONO – MOLTO
BUONO – OTTIMO
comma
3 lett. f)
(ovvero
6°
Requisit
o)
-
-
6
Adozione di sistemi di
valutazione
Valutazione
ADEGUATO – NON ADEGUATO
Sistemi di
Valutazione
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
269
10.Valutazione da parte del nucleo di valutazione dell’Ateneo
Dati ufficiali presenti nella relazioen del nucleo, che non sono quelli definitivi per il XXVII cilco.
Criterio
tipo_rec ord
nome_dottorato
nuova_istituzione
anno_attivazione
Dipartimento
cognome _docente
nome_docente
Borse cofinanziate
Borse richieste all'Ateneo
Iscritti con Borsa
Valutazione cofinanziamento
Posti ordinari
Cofinanziamento dichiarato
Cofinanziamento a consuntivo
N. Componenti esclusivi Collegio (vincolo >=10)
N. candidati presenti alla prova di ammissione
N. candidati presenti alla prova di ammissione
provenienti da altro ateneo
Valutazione attrattività della sede
Composizione Collegio docenti eProduzione
Scientifica
Obiettivi formativi e progetto scientifico (1° requisito
DM 224/99)
Disponibilità risorse e strutture (2° requisito DM
224/99)
Rapporto del dottorato con il mondo lavoro:
monitoraggio inserimento lavorativo
Obbiettivi formativi e progetto scientifico
Valutazione sistemi di valutazione (6° requisito DM
224/99)
Valutazione sito web
Soddisfazione dottorandi
Valutazione produzione scientifica dottorandi
Valutazione complessi va
Valutazione
Scuola di dottorato senza indirzzi
NANOTECNOLOGIE
Rinnovo
2006
Dipartimento di Fisica
Fermeglia
Maurizio
7
7
17
POSITIVO
36
54.55%
80.28%
28
28
14
MEDIO - ALTA
OTTIMO
POSITIVO
OTTIMO
OTTIMO
ADEGUATO
ADEGUATO
OTTIMO
OTTIMO
OTTIMA
A+ (OTTIMO)
Il documento completo di valutazione di tutte le scuole di dottorato dell’università di Trieste è
riportato in allegato. Questo documento è utile per posizionare la scuola anche in relativo rispetto
alle altre scuole e corsi di dottorati valutati con lo stesso metro.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
270
11. Giudizi dei referee esterni per dottorandi ammessi all’esame
finale aprile 2012
Di seguito sono riportati i referee esterni scelti dal collegio per ciascuno dei dottorandi:
Dottorando
Astolfo
Alberto
Titolo
Supervisore
Development of novel ARFELLI
experimental methods for Fulvia
cell
tracking
using
nanoparticles
Bellomo
Francesca
Biopolymer based scaffold
for tissue engineering
Birarda
Giovanni
Development
of
microfluidic devices for
biomedical applications of
Synchrotron
Radiation
FTIR Microspectroscopy
Nanoscale interaction for
higher
efficiency
of
contrast media
Analysis of aging and
stability
of
bonded
interface in dentistry
Fontanive
Luca
Marchesi
Giulio
Reviewers
L. Dean Chapman, PhD
Professor, Anatomy & Cell Biology, University of
Saskatchewan
Dr. Juergen Mollenhauer
NMI Naturwissenschaftliches und Medizinisches Institut
University of Tübingen,
PAOLETTI
Dr. Niko Moritz
Sergio
University of Turku, Finland, Orthopaedic Research Unit
Dr. Judith Juhasz
University of Cambridge, United Kingdom
FRANCIOSI
Dr. Paul Dumas
Alfonso / Lisa synchrotron-soleil.fr
Vaccari
Dr. Nikolaj Gadegaard
[email protected]
CESARO
Attilio
BRESCHI
Lorenzo
Rampino
Antonio
Polysaccharide
based CESARO
nanoparticles for drug Attilio
delivery
Santarelli
Xenja
Development
of ROSEI Renzo
capabilities for ‘in situ’
analysis of nanoparticles at
the
MCX
powder
diffraction Beamline
Influence of nanostructure MORGANTE
on the electronic properties Alberto
of
heterojunctions
in
photovoltaic cells
Sovernigo
Enrico
Prof. Assuntina Morresi - Dipartimento di Chimica,
Università di Perugia Alessandro Maiocchi - Centro Ricerche Bracco Prof. Steve Armstrong, Department of Operative
Dentistry, College of Dentistry, The University of Iowa
- Iowa City, Iowa, USA
Prof. Marcela Carrilho, GEO/UNIBAN,Health
Institute, Bandeirante University of São Paulo, São
Paulo, Brazil
Carla M. Caramella - Department of Pharmaceutical
Chemistry - University of Pavia –
Paolo BLASI, Ph.D.Dip. Chimica e Tecnologia del
Farmaco - Università di Perugia Prof. Alvise Benedetti Univ. Ca Foscari:
Prof. Jennifer Mac Load, NFL Montreal:
Prof. Dr. Gvido Bratina
Università Ljubliana, SLO
Dr.ssa Francesca Brunetti, University of Rome "Tor
Vergata"
Vedi dettaglio negli allegati.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
271
12.Presentazioni dei dottorandi al congesso del gennaio 2012
Le presentazioni PPT dei dottorandi al congresso del gennaio 2012 sono riportate negli allegati.
Scuola di dottorato di ricerca in Nanotecnologie: attività 2011
272