UC CEIN Annual Report 2016

Transcription

University of California
Center for Environmental Implications of
Nanotechnology (UC CEIN)
DBI-1266377
Annual Report
Year 8
April 1, 2015 - March 31, 2016
UC Center for Environmental Implications of Nanotechnology
Year 8 Progress Report
TABLE OF CONTENTS
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NSF Cover Page
Table of Contents
Project Summary
List of Center Participants, Advisory Boards, Participating Institutions
Quantifiable Outputs (NSF Table 1)
Mission and Broader Impacts
Highlights
Strategic Research Plan
Research Program, Accomplishments, and Plans
Theme 1: Compositional and Combinatorial ENM Libraries for Property-Activity Analysis
Theme 2: Molecular, Cellular, and Organism HTS Screening for Hazard Assessment
Theme 3: Fate, Transport, Exposure and Life Cycle Assessment
Theme 4: Terrestrial Ecosystems Impact and Hazard Assessment
Theme 5: Marine and Freshwater Ecosystems Impact and Toxicology
Theme 6: Environmental Decision Analysis for Nanoparticles
Theme 7: Using UC CEIN Knowledge Generation to Engage and Impact Stakeholders
NSF Table 2 – NSEC Program Support
Center Diversity – Progress and Plans
Education
NSF Table 3a – Education Program Participants – All
NSF Table 3b – Education Program Participants – US Citizen/PR
Outreach and Knowledge Transfer
Shared and Experimental Facilities
Personnel
NSF Table 4A – NSEC Personnel – All
NSF Table 4B – NSEC Personnel – US Citizen/PR
Publications and Patents
Biographical Information
Honors and Awards
Fiscal Section
a. Statement of Unobligated Funds
b. Budget
Cost Sharing
Leverage
Table 5 – Other Support
Table 6 – Partnering Institutions
Current and Pending Support – PIs and Thrust Leaders
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3. Project Summary
The University of California Center for Environmental Implications of Nanotechnology (UC CEIN) was
established in September 2008 with a long-term vision of developing a multidisciplinary and quantitative
framework for assessing the potential environmental impact, hazard and exposure to ENMs, in both
their primary as well as commercial nano-enabled formulations. The Center also provides feedback and
guidance for the safer implementation of nanotechnology, including risk reduction and safer design
strategies. The multidisciplinary approach of the Center involves materials science, environmental
chemistry and engineering, toxicology, ecology, social science, computer science and modeling,
statistics, public health, law and policy formulation. Collectively, these fields of expertise are necessary
to address the complexity of the ENM physicochemical properties involved in hazard generation,
establishment of structure-activity relationships (SARs), and use of exposure assessment to evaluate
ecosystems impact. The UC CEIN’s vision is to generate predictive tools for environmental hazard and
exposure assessment as well as to develop strategies to ensure the safe implementation of
nanotechnology to the benefit of society, the environment and the economy. These tools and
knowledge are disseminated through vibrant and impactful educational and outreach programs.
The Center makes use of well-characterized compositional and combinatorial ENM libraries to study
their fate and transport in parallel with the materials' bioavailability and potential to engage
toxicological pathways in organisms and environmental life forms. Where possible, this exploration
involves high throughput screening (HTS) to develop structure-activity relationships (SARs) that can be
used to predict the impact of primary ENMs' on organisms in freshwater, seawater, and terrestrial
environments. In silico data transformation and decision-making tools are involved in data processing to
provide hazard ranking, exposure modeling, risk profiling, and construction of nano-SARs. These
research activities are combined with educational programs that inform the public, students, federal
and state agencies, as well as industrial stakeholders of the impact of CEIN’s research on the safe
implementation of nanotechnology in the environment. Collectively, these activities contribute to
evidence-based nanotechnology environmental health and safety (nano EHS) for society.
Through the pursuit of interdisciplinary, predictive and high throughput approaches, the UC CEIN has
made, and will continue to make, a transformative impact on nano EHS assessment. The cornerstone of
this impact is our ability to use an interdisciplinary approach for acquisition and synthesis of ENM
libraries, which are assessed by high throughput and facilitative test strategies that inform about
nanomaterial hazard and potential impact across a broad range of nano/bio interfaces, from cells to
ecosystems. Coupled with our computational analysis tools and fate and transport modeling, this allows
environmental impact analysis of broad material categories, including the use of this information for
safety assessment, safer design and regulatory decision-making.
A major goal of the UC CEIN is to educate the next generation of nano-scale scientists, engineers, and
policy makers to anticipate and mitigate potential future environmental hazards associated with
nanotechnology. Our educational programs are developed to broaden the knowledge base of the
environmental implications through academic coursework, research, and training courses for industrial
practitioners, public outreach, and a journalist/scientist communication program. Through the activities
of our education team (Theme 8), we have had a profound impact on the quality and quantity of
educational materials available both nationally and internationally in the area of Environmental
Nanotechnology. In partnership with Science Buddies, we developed two science fair projects aimed at
students based on research generated in the Center and we are currently finalizing an undergraduate
chemistry laboratory module based on the CEIN HTS approaches. The Center has also greatly enhanced
the professional development opportunities for graduate students and postdoctoral researchers within
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our Center, as we build a cohesive and interdisciplinary environment for science and education. We
regularly engaged the public in settings such as science museums and public libraries to inform them of
our work. We have made concerted efforts to involve minority institutions, including the recruitment of
minority faculty and students. Additionally, we are proud to have four Hispanic serving institutions
(UTEP, UNM, UCR, and UCSB) as core partners in our Center and are working to incorporate strategies
for promoting diversity and inclusion and underrepresented minorities into all of our educational
activities.
UC CEIN has become one of the most preeminent NanoEHS centers in the world. We have impacted
national and international understanding and decision-making in the areas of NanoEHS research,
protocol development, knowledge dissemination, and contributions to the regulatory agencies. In the
coming year, we will continue our predictive scientific investigation and modeling of a progressively
wider range of ENMs and their impact on the environment. We will continue to play a leading role in
national and international Nano EHS forums and continue to develop informal science education tools
for the public as well as expand our interaction with State and Federal agencies and industrial
stakeholders.
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4.
Center Participants, Advisory Boards, and Participating Institutions
Center Participants
Participants Receiving Center Support
Faculty:
Kenneth Bradley
UCLA
Jeffrey Brinker
University of New Mexico/Sandia
Bradley Cardinale
UC Santa Barbara
Gary Cherr
UC Davis
Chi-On Chui
UCLA
Yoram Cohen
UCLA
J.R. DeShazo
UCLA
Curtis Eckhert
UCLA
William Freudenberg
UC Santa Barbara
Jorge Gardea-Torresdey University of Texas, El Paso
Hilary Godwin
UCLA
Robert Haddon
UC Riverside
Barbara Herr Harthorn UC Santa Barbara
Mark Hersam
Northwestern University
Eric Hoek
UCLA
Patricia Holden
UC Santa Barbara
Milind Kandlikar
University of British Colombia
Arturo Keller
UC Santa Barbara
Hunter Lenihan
UC Santa Barbara
Alex Levine
UCLA
Shuo Lin
UCLA
Lutz Madler
University of Bremen
Timothy Malloy
UCLA
Edward McCauley
UC Santa Barbara
Jay Means
UC Santa Barbara
Huan Meng
UCLA
Nirav Merchant
University of Arizona
Andre Nel
UCLA
Roger Nisbet
UC Santa Barbara
Robert Rallo
Universitat Roriv i Virgili/UCLA
Theresa Satterfield
University of British Colombia
Joshua Schimel
UC Santa Barbara
Ponisseril Somasundaran Columbia University
Galen Stucky
UC Santa Barbara
Sangwon Suh
UC Santa Barbara
Donatello Telesca
UCLA
Sharon Walker
UC Riverside
Korin Wheeler
Santa Clara University
Tian Xia
UCLA
Jeffrey Zink
UCLA
Research Staff:
Jacob Agola
Fnu Aoergele
Dennis Bacsafra
Berenice Barajas
Raven Bier
Eric Carnes
University of New Mexico
UCLA
UCLA
UCLA
UC Santa Barbara
Sandia National Laboratory
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Associate Professor, Microbiology
Professor, Chemical/Nuclear Engineering
Assistant Professor, Ecology Evolution, Marine Biology
Professor, Environmental Toxicology/Nutrition
Associate Professor, Electrical Engineering
Professor, Chemical Engineering
Associate Professor, Public Policy
Professor, Environmental Health Sciences
Professor, Environmental Studies and Sociology
Professor, Chemistry
Professor, Environmental Health Sciences
Professor, Women’s Studies/Anthropology
Professor, Materials Science & Engineering
Professor, Civil & Environmental Engineering
Professor, Environmental Microbiology
Associate Professor, Institute for Global Issues
Professor, Environmental Biogeochemistry
Professor, Marine Biology
Professor, Chemistry and BioChemistry
Professor, Molecular, Cell, & Developmental Biology
Professor, Materials Science
Professor, Law
Professor, Ecology, Evolution, Marine Biology
Adjunct Professor, Environmental Toxicology
Assistant Adjunct Professor, Nanomedicine
Director, Biotechnology Computing, iPlant
Professor, Medicine; Chief, Division of NanoMedicine
Professor, Institute of Resources
Professor, Materials Science
Professor, Chemistry and Biochemistry
Associate Professor, Environmental Sci & Mgmt
Assistant Professor, Biostatistics
Professor, Chemical and Environmental Eng.
Assistant Professor, Chemistry
Assistant Adjunct Professor, Nanomedicine
Professor, Chemistry and Biochemistry
Robbie Castillo
Chong Hyun Chang
Irina Chernyshova
Lauren Copeland
Robert Damoiseaux
Anna Davison
Helen Dickson
Corinne Dorais
Wenchao Du
Darren Dunphy
Bryan France
Kendra Garner
Jennifer Gowan
Fred Griffin
Taimur Hassan
Sean Hecht
J.A. Hernandez-Viezcas
Susan Jackson
Aasrushi Jha
Zhaoxia Ivy Ji
Xingmao Jiang
Sambamurthy Khadrika
Frederick Klaessig
Ning Li
Yu-Pie Liao
Ya-Hsuan Liou
Yu-Shen Lin
Huiyu Liu
Rong Liu
Marianne Maggini
Huan Meng
Robert Miller
Delia Milliron
Taleb Mokari
Erik Muller
Laure Pecquerie
Jose Peralta-Videa
John Priester
Dad Roux-Michollet
David Schoenfeld
Jo Anne Shatkin
Yiming Su
Matthew Tallone
Laurie Van De Werfhorst
Carol Vines
Hongtuo Wang
Meiying Wang
Xiang Wang
William Wooten
Maria Yepez
Haiyuan Zhang
UCLA
Columbia University
UC Santa Barbara
UCLA
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
University of Texas, El Paso
UCLA
UC Santa Barbara
UC Santa Barbara
UC Davis
UCLA
UCLA
UC Davis
UC Santa Barbara
UCLA
Sandia National Labs
Columbia University
Pennsylvania NanoBio Systems
UCLA
UCLA
UC Santa Barbara
UCLA
UCLA
UC Santa Barbara
UCLA
UC Santa Barbara
Lawrence Berkeley National Laboratory
UC Sana Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UCLA
Virio Advisors
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Davis
UC Santa Barbara
UCLA
UCLA
UCLA
UC Santa Barbara
UCLA
5
Postdoctoral Researchers:
Adeyemi Adeleye
UC Santa Barbara
Carlee Ashley
Mafalda Baptista
UC Santa Barbara
Christian Beaudrie
University of British Columbia
Elizabeth Beryt
UCLA
Muhammad Bilal
UCLA
Rafaella Buonsanti
UCLA/Lawrence Berkeley National Laboratory
Bryan Cole
UC Davis
Shelly Cole-Moritz
UC Santa Barbara
Mary Collins
UC Santa Barbara
Gwen D’Arcangelis
UC Santa Barbara
Guadalupe De La Rosa
Cristina Duarte-Torres
UC Davis
Cassandra Engeman
UC Santa Barbara
Elise Fairbairn
UC Davis
Xiaohua Fang
Columbia University
Yaqin Fu
Yuan Ge
UC Santa Barbara
Saji George
UCLA
Nalinkanth Ghone
UCLA
Debraj Ghosh
UCLA
Shannon Hanna
UC Santa Barbara
Yongsuk Hong
UC Santa Barbara
Allison Horst
UC Santa Barbara
Chia-Hung Hou
UC Santa Barbara
Angela Ivask
UCLA
Wendy Jiang
UCLA
Xue Jin
UCLA
Mikael Johansson
UC Santa Barbara
Sanaz Kabehie
UCLA
Irina Kalinina
UC Riverside
Moshen Kayal
UC Santa Barbara
Myungman Kim
UCLA
Nichola Kinsinger
UC Riverside
Hiroaki Kiyoto
UC Santa Barbara
Tin Klanjscek
UC Santa Barbara
Chris Knoll
UC Santa Barbara
Konrad Kulacki
UC Santa Barbara
Jae-Hyeok Lee
Juon Lee
UC Santa Barbara
Minghua Li
UCLA
Ruibin Li
UCLA
Sijie Lin
UCLA
Yu-Shen Lin
Rong Liu
UCLA
Xiangsheng Liu
UCLA
Martha Lopez
Cecile Low-Kam
UCLA
Jianqin Lu
UCLA
Benjamin Martin
UC Santa Barbara
Nature McGinn
UC Davis
Milka Montes
UC Santa Barbara
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Monika Mortimer
UC Santa Barbara
Sumitra Nair
UCLA
Sandip Niyogi
UC Riverside
Manuel Orosco
UCLA
Olivia Osborne
UCLA
Partha Patra
Columbia
Anton Pitts
Suman Pokhrel
Philippe Saint-Cricq-Riviere UCLA
Aditi Singhal
UC Santa Barbara
Elizabeth Suarez
UCLA
Yiming Su
UC Santa Barbara
Bingbing Sun
UCLA
Won Suh
UC Santa Barbara
Paul Teehan
UC Santa Barbara
Reginald Thio
UC Santa Barbara
Jason Townson
Jessica Trujillo
Raja Vukanti
UC Santa Barbara
Xiang Wang
UCLA
Ying Wang
UC Santa Barbara
Bing Wu
UC Davis
Bing Hui Wu
UC Santa Barbara
Haiyuan Zhang
UCLA
Lijuan Zhao
Lijuan Zhao
UC Santa Barbara
Yang Zhao
UCLA
Graduate Students:
Khadeeja Abdullah
Adeyemi Adeleye
Ishaq Adisa
John Albino
Hayley Anderson
Suzanne Apodaca
Fernando Artaega
Barbora Bakajova
Susmita Bandyopadhyay
Ana Barrios
Lynn Baumgartner
Samuel Bennett
Nestor Bonilla-Bird
David Boren
Terisse Brocoto
Olivier Brun
Benjamin Carr
Savanna Carson
Chen Chen
Eunshil Choi
Kabir Chopra
Indranil Chowdhury
Tracy Chuong
Kristin Clark
UCLA
UC Santa Barbara
Columbia
UCLA
UC Davis
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UCLA
UC Santa Barbara
UC Santa Barbara
UCLA
UC Riverside
UCLA
UCLA
UC Riverside
UC Santa Barbara
UC Santa Barbara
7
Jon Conway
Alyssa de la Rosa
Laura De Vries
Caoyi Deng
Juyao Dong
Matthew Duch
Paul Durfee
Daniel Ferris
Janelle Feige
Marina Feraud
Allison Fish
Emma Freeman
Kendra Garner
Sheetal Gavankar
Thomas Glaspy
Linda Guiney
Maria Isabel Hernandez
Jose Hernandez-Viezcas
Ryan Honda
Jie Hong
Carlin Hsueh
Daniel Huang
Yuxiong Huang
Angela Hwang
Annikka Jensen
Chitrada Kaweeteerawat
Jun-Yeol Kim
Erin Lamb
Jacob Lanphere
Anastasiya Lazareva
Kathryn Leonard
Zongxi Li
Zu Lu Li
Monty Liong
Dayu Liu
Haoyang Haven Liu
Sanhamitra Majumdar
Nikhita Mansukhani
Catalina Marambio-Jones
Tyronne Martin
Yufei Mao
Suzanne McFerran
David McGrath
Ilya Medina
John Meyerhofer
Randy Mielke
Erving Morelius
Arnab Mukherjee
Loren Ochoa
Cruz Ortiz Jr.
Abigail Padilla
David Padilla
Julio Padilla
UC Santa Barbara
University of Texas El Paso
UCLA
UCLA
UCLA
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UCLA
UC Riverside
UCLA
UC Santa Barbara
UC Santa Barbara
UCLA
UCLA
UC Santa Barbara
UC Santa Barbara
UC Riverside
UC Santa Barbara
UCLA
UCLA
UCLA
UCLA
UC Santa Barbara
UCLA
UCLA
UC Santa Barbara
UCLA
UC Santa Barbara
UCLA
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
8
Sudhir Paladugu
UC Santa Barbara
Trina Patel
UCLA
Satish Ponnurangam
Columbia University
Venkata Pullagurala Reddy University of Texas, El Paso
Swati Rawat
Cyren Rico
April Ridlon
UC Santa Barbara
Michelle Romero-Franco UCLA
Esmerelda Santillan
UC Davis
April Sawvell
UC Santa Barbara
Corrinne Schmidger
UC Santa Barbara
Alia Servin
Bion Sheldon
Sharona Sokolow
UCLA
Runsheng Song
UC Santa Barbara
Louise Stevenson
UC Santa Barbara
S. Drew Story
UC Riverside
Sirikarn Surawanvijit
UCLA
Carlos Tamez
Wenjuan Tan
Mengya Tao
UC Santa Barbara
Derrick Tarn
UCLA
Alicia Taylor
UC Riverside
Nimihsa Thakur
Courtney Thomas
UCLA
Michael Tsang
UCLA
Regan Turley
Jessica Twining
UC Santa Barbara
Laura Urbisci
UC Santa Barbara
Kari Varin
UCLA
Bill Vosti
UC Santa Barbara
Pria Vytla
UC Santa Barbara
Travis Waller
UC Riverside
Zoe Welch
UC Santa Barbara
Rebecca Werlin
UC Santa Barbara
Tristan Winneker
UC Santa Barbara
Kimberly Worsley
UC Riverside
Sijing Xiong
Nanyang Technological University
Min Xue
UCLA
Kristin Yamada
UCLA
Yafeng Zhang
UCLA
Yichi Zhang
UC Santa Barbara
Dongxu Zhou
UC Santa Barbara
Akanitoro Zuverza-Mena University of Texas, El Paso
Undergraduate Students:
Richard Abraham
Carola Acuro
Aiman Ahmed
Perla Akkara
Andre Anderiasian
Nicolai Archuleta
Raul Armendariz
UC Riverside
UCLA
UCLA
UC Santa Barbara
UC Santa Barbara
9
Cindy Au
Yasmin Awad
Ana Cecilia Barrios
Arielle Beaulieu
Nicole Beaulieu
Alex Besser
Daniel Bischoff
Natalie Bouri
Alexandra Bowers
Rebecca Britt Armenta
Cameron Burgard
Lillian Burns
Cody Burr
Robert Burt
Alex Burton
Lauren Bustamante
Ryan Capps
Kelly Carpenter
Bernice Chan
Wai-Yin (Rhyn) Cheung
Manu Chopra
Jacob Chow
Tim Chow
Gwen Christiansen
Maia Colyar
Aaron Coyoca
Stephen Crawford
Brian Cruz
Jacob Dabrowski
Israel Del Toro
Hao Diu
Vivian Do
Osvaldo Dominguez
Corrinne Dorias
Yingjie Du
Daniel Dunham
Kathlynne Duong
Sahar El Abbadi
Tyler Eline
Katharine Epler
Janel Feige
Garth Fisher
Austin Fullencamp
Aaron Fulton
Ryo Furukawa
Charles Futoran
Fred Garcia
Jason Gehrke
Colton Gits
Daniel Gold
Arjan Gower
Joseph Gramespacher
Briana Gray
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UCLA
UC Santa Barbara
UC Santa Barbara
UC Davis
UC Santa Barbara
UC Riverside
UC Santa Barbara
UC Santa Barbara
UCLA
UCLA
UC Santa Barbara
UCLA
UC Riverside
UC Santa Barbara
UC Santa Barbara
UC Riverside
UC Santa Barbara
UC Riverside
UC Santa Barbara
UCLA
UCLA
UC Santa Barbara
UCLA
UC Santa Barbara
UCLA
UC Santa Barbara
UCLA
UCLA
Santa Rose Junior College
UC Santa Barbara
UC Santa Barbara
UCLA
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
10
Risa Guysi
UC Riverside
Edward Hadeler
UC Santa Barbara
Brittany Hall
UC Santa Barbara
Natalie Hambalek
Sonoma State University
Erica Harris
UCLA
Anthony Hearst
UC Santa Barbara
Trevin Heisey
Kai Henry
UC Santa Barbara
Rudolf Hergesheimer
UC Santa Barbara
Mariana Hernandez-Molina University of Texas, El Paso
Cecilia Herrera-Vega
UCLA
Elizabeth Horstman
UC Riverside
Rebecca Howard
UC Santa Barbara
Andy Hseuh
UC Santa Barbara
Edward Hu
UC Santa Barbara
Cynthia Huang
UCLA
Kevin Humphrey
Kevin Huniu
UC Santa Barbara
Avery Hunker
UC Santa Barbara
Emily Hurd
UC Santa Barbara
Sarah Hutton
UC Davis
Aaron Ibarra
Igor Irianto
UC Riverside
Kenta Ishii
UC Santa Barbara
Matthew Jackson
Otto Janek
Young Jeon
UC Santa Barbara
Natalie Johannes
Erica Johnson
UC Santa Barbara
Elaine Kang
UCLA
Grace Kao
UC Santa Barbara
Sarika Kathuria
UC Santa Barbara
Rachel Ker
UC Santa Barbara
Emily Kerchner
UC Santa Barbara
James Kim
UC Riverside
Peter Kim
Soomin Kim
UC Santa Barbara
Kathryn Kleckner
UC Santa Barbara
Katherine Krattenmaker UC Santa Barbara
Justine Ku
UCLA
Adeel Lakhani
UC Santa Barbara
Casey Leavitt
UC Santa Barbara
Andrew Lee
UCLA
Anson Lee
UCLA
Annabelle Lee
UC Santa Barbara
Claire LeMaitre
UCLA
Guan Hao Li
UC Santa Barbara
Joseph Liao
UC Santa Barbara
Leuh Yang Liao
UCLA
Joshua Lin
UCLA
Paulina Lin
UCLA
Erica Linard
UC Santa Barbara
Angela Liu
UCLA
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Malina Loeher
Amanda Lokke
Corey Luth
Wilson Mai
Michael Maidaa
Ruben Martinez
Kristin Matulich
Ariel Miller
Brianna Miner
Josh Minster
Alex Moreland
Fabiola Moreno
Ayse Muniz
Berenice Munos-Herrera
Emily Nhan
Kaysha Nelson
Diego Noeva
Ashley Noriega
Scott Obana
Michelle Oishi
Ekene Oranu
Kathleen Pacpaco
Karmina Padgett
Leanne Paragas
Robert Parker
Calvin Parshad
Scott Pease
David Pereira
Aaron Perez
Thomas Perez
Ian Perrett
Christopher Perry
Minhham Pham
Malcolm Phung
Nanetta Pon
Kellie Pribble
Scott Pritchett
Alexander Prossnitz
Ingmar Prokop
Clarisse Rangel
Sarah Rathbone
Alden Reviere
Raquel Ribeiro
Robin Riehn
Niki Rinaldi El-Adb
Brian Rodriguez
Brandon Rogers
Gabriel Rubio
Paige Rutten
Jenna Rydz
Michael Salazar
Cynthia Sanchez
Katherine Santizo
UC Davis
UC Riverside
UCLA
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UCLA
UC Santa Barbara
UC Riverside
UC Santa Barbara
UC Santa Barbara
UCLA
UC Santa Barbara
UC Santa Barbara
Columbia University
UCLA
UC Santa Barbara
UCLA
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UCLA
UC Santa Barbara
UCLA
UCLA
UCLA
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Riverside
UC Santa Barbara
UCLA
UC Riverside
UC Santa Barbara
UCLA
UC Riverside
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
12
Patricia Schultz
Jacqueline Sheng
Esther Shin
Christianna Sim
Allen Situ
Kristine Sommer
Helaine St. Amant
Amy Stuyvesant
Allen Taing
Alejandro Tafoya
Tiffany Takade
Tony Tharakan
Ryan Tjan
Stephen Tjan
Christine Troung
Nancy Tseng
William Ueng
Ryan Utz
Jesus Valdez
Jose Valle
Danielle Vallone
Colin Van Zandt
Katie Villabroza
Peter Voong
Ashley Watchell
William Wellman
Daniel White
Cody Wilgus
Brian Wilkinson
Dan Wilkinson
Christina Wong
Bobby Wu
Edward Wyckoff
Qingbai Xu
Maria Yepez
Kevin Young
Xuechen Yu
Melanie Zecca
UCLA
UC Davis
UC Santa Barbara
UCLA
UC Santa Barbara
Santa Rosa Jr. College
UC Santa Barbara
UCLA
UC Santa Barbara
Columbia University/GWU
UC Santa Barbara
UC Santa Barbara
UCLA
UC Santa Barbara
UCLA
UC Santa Barbara
UCLA
UC Riverside
UC Santa Barbara
UC Santa Barbara
UCLA
UC Santa Barbara
UC Santa Barbara
UC Riverside
UC Riverside
UC Santa Barbara
UCLA
UCLA
UCLA
UC Santa Barbara
UC Santa Barbara
UCLA
UC Riverside
High School Students (Interns):
Sherya Banerjee
UC Santa Barbara
Akanitoro Brown
Columbia University
Jose Clement
Anirudh Dayal
UC Santa Barbara
Christina Gerges
UC Riverside
Sean Hagerty
Jeremy Hutton
UC Santa Barbara
Priyanka Jian
Jessica Nelson
Courtney Kwan
UC Santa Barbara
Ashley Wachtell
UC Santa Barbara
Staff/Administration:
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Charles Alex Andres
David Avery
Colleen Callahan
John Chae
Mariae Choi
Anna Davison
Julie Dillemuth
Kristin Duckett
Meghan Horan
Vi Tuong Huynh
Catherine Nameth
Elina Nasser
Nancy Neymark
Jeri O'Mahoney
Stacy Rebich-Hespana
Maribel Robino
Leslie Sanchez
Kathleen Scheidemen
Benjamin Trieu
Christine Truong
Cristina Wilson
Virginia Zaunbrecher
UCLA
UCLA
UCLA
UCLA
UCLA
UC Santa Barbara
UC Santa Barbara
UC Santa Barbara
UCLA
UCLA
UCLA
UCLA
UCLA
UC Santa Barbara
UC Santa Barbara
UCLA
UC Santa Barbara
UC Santa Barbara
UCLA
UCLA
UC Santa Barbara
UCLA
Affiliated Participants, Not Receiving Center Support
Faculty:
Carolyn Bertozzi
UC Berkeley/Lawrence Berkeley Lab
Gretchen Bielmyer
Valdosta State University
Freddy Boey
Kenneth Dawson
University College Dublin
Francesc Giralt
Universitat Rovira I Virgili
Jordi Grifoll
Joachim Loo
Nick Pidgeon
Cardiff University
Graduate Students:
Xinxin Zhao
Professor, Chemistry, Molecular/Cell Biology
Associate Professor, Ecotoxicology
Professor, Materials Science Engineering
Professor, Physical Chemistry
Associate Professor, Chemical Engineering
Associate Professor, Materials Engineering
Professor, Applied Psychology
External Science Advisory Committee
Pedro Alvarez
Rice University
Ahmed Busnaina
Northeastern University
Sharon Dunwoody
University of Wisconsin-Madison
Menachem Elimelech
Yale University
C. Michael Garner
Garner Nanotechnology Solutions
James Hutchison
University of Oregon
Agnes Kane
Brown University
Fred Klaessig
Pennsylvania Bio Nano Systems
Marc Lafranconi
Tox Horizons
Terry Medley
DuPont
Julia Moore
Woodrow Wilson International Center
Kent Pinkerton
UC Davis
Rick Pleus
Intertox
David Rejeski
Woodrow Wilson International Center
Omowunmi Sadik
SUNY Binghamton
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Professor, Engineering
Professor, Engineering; Director, HRNM
Professor, Journalism/Mass Communication
Nanotechnology Consultant
Professor, Assoc. VP, Research
Professor, Pathology & Laboratory Medicine
Consultant and CEO
Global Director, Corporate Global Affairs
Deputy Director, PEN
Director, Center for Health/Environment
Managing Director/Toxicologist
Director, PEN
Ron Turco
Isiah Warner
Jeff Wong
Paul Zimmerman
Purdue University
Louisiana State University
Department of Toxic Substances Control
Intel
Academic Participating Institutions
University of Birmingham
University of California, Los Angeles
University of California, Santa Barbara
University of California, Davis
University of California, Riverside
Non Academic Participating Institutions
California Science Center
Environmental Protection Agency, Computational Toxicology Program
Lawrence Livermore National Laboratory
National Institute of Occupational Safety and Health (NIOSH)
National Institute of Standards and Technology (NIST)
Santa Monica Public Library
15
Professor, Agronomy
Professor, Environmental Chemistry
Retired, Deputy Director, Science
Program Manager, External Programs
Table 1: Quantifiable Outputs
Outputs
Total
2012
2013
2014
2015
2016
In Peer-Reviewed Technical Journals
45
72
71
74
68
330
In Peer-Reviewed Conference Proceedings
0
2
1
2
2
7
In Trade Journals
0
0
1
0
0
1
With Multiple Authors
45
74
73
76
69
337
Multiple Authors: Co-Authored with NSEC Faculty
45
74
73
76
69
337
0
0
0
0
0
0
Inventions Disclosed
0
0
0
0
0
0
Patents Filed
0
0
0
1
0
1
Patents Awarded
0
0
0
0
0
0
Patents Licensed
0
0
0
0
0
0
Software Licensed
0
0
0
0
0
0
Spin-off Companies Started (if applicable)
Degrees to NSEC Students
0
0
0
0
0
0
Bachelor's Degrees Granted
4
0
2
4
5
15
Master's Degrees Granted
3
4
1
2
2
12
Doctoral Degrees Granted
1
13
3
5
6
28
12
Publications that acknowledge NSF NSEC Support
Publications that do not acknowledge NSF NSEC Support
In Peer-Reviewed Technical Journals
NSEC Technology Transfer
NSEC Graduates Hired by
0
3
4
3
2
NSEC Participating Firms
0
0
0
0
0
0
Other U.S. Firms
0
3
4
3
2
12
Government
2
3
0
2
3
10
Academic Institutions
3
8
5
1
4
21
Other
0
0
0
0
0
0
Unknown
0
0
0
1
0
1
Industry
NSEC Influence on Curriculum (if applicable)
New Courses Based on NSEC Research
1
1
0
0
0
2
Courses Modified to Include NSEC Research
3
7
14
21
8
53
New Textbooks Based on NSEC Research
0
0
0
0
0
0
Free-Standing Course Modules or Instructional CDs
13
0
0
1
1
15
New Full Degree Programs
0
0
0
0
0
0
New Degree Minors or Minor Emphases
0
0
0
0
0
0
New Certificate
Information Dissemination/Educational Outreach
0
0
0
0
0
0
Workshops, Short Courses to Industry
0
3
1
1
2
7
Workshops, Short Courses to Others
1
0
1
4
1
7
198
1
212
2
222
0
138
0
113
0
883
3
Seminars, Colloquia, etc.
World Wide Web courses
16
6. Mission, Significant Advances, and Broader Impacts
The mission of the University of California Center for Environmental Implications of Nanotechnology (UC
CEIN) is to use a multidisciplinary approach to conduct research, knowledge acquisition, education and
outreach to ensure the responsible use and safe implementation of nanotechnology in the environment.
This will enable the USA and International communities to leverage the advantages of nanotechnology to
the benefit of the global economy, society and the environment. This mission is being accomplished by the
development of environmental decision making tools that consider the importance of engineered
nanomaterial (ENM) physicochemical properties in determining environmental fate, transport, exposure,
and hazard generation across a wide spectrum of nano/bio interfaces in cells, bacteria, organisms,
communities and ecosystems. The Center makes use of well-characterized compositional and combinatorial
ENM libraries to study their fate and transport in parallel with the materials' bioavailability and potential to
engage toxicological pathways in organisms and environmental life forms. Where possible, this exploration
involves high throughput screening (HTS) to explore structure-activity relationships (SARs) that can be used
for prediction making of primary ENMs' impact on organisms in freshwater, seawater, and terrestrial
environments. In silico data transformation and decision-making tools are involved in data integration to
provide hazard ranking, exposure modeling, risk profiling, and construction of nano-SARs. These research
activities are combined with educational and outreach programs that inform the public, students, federal
implementation of nanotechnology in the environment.
The research of the UC CEIN is carried out by 29 distinct but interactive research projects (supported by 4
service cores) across seven interdisciplinary research themes and our education/outreach program:
• Theme 1: Compositional and Combinatorial ENM Libraries for Property-Activity Analysis
• Theme 2: Molecular, Cellular, and Organism High-Throughput Screening for Hazard Assessment
• Theme 3: Fate, Transport, Exposure, and Life Cycle Assessment
• Theme 4: Terrestrial Ecosystems Impact and Hazard Assessment
• Theme 5: Marine and Freshwater Ecosystems Impact and Toxicology
• Theme 6: Environmental Decision Analysis for ENMs
• Theme 7: Using UC CEIN Knowledge Generation to Engage and Impact Multiple Stakeholders
• Theme 8: Education, Career Development, Knowledge Dissemination, and Interactive Efforts
Through the pursuit of interdisciplinary, predictive and high throughput approaches, the UC CEIN has made,
and will continue to make, a transformative impact on nano EHS assessment. The cornerstone of this
impact is our ability to acquire and synthesize ENM libraries, which are assessed in an interdisciplinary
approach by high throughput and facilitative test strategies that inform about nanomaterial exposure and
hazard across a broad range of nano/bio interfaces, from cells to ecosystems. Coupled with our
computational analysis tools and fate and transport modeling, this allows environmental impact analysis of
broad material categories, including the use of this information for safety assessment, safer design and
regulatory decision-making. Over the past year, key Center highlights include:
The synthesis, design, acquisition, purification, and characterization of compositional and combinatorial
ENM libraries by Theme 1, selected based on the materials relevance in the development of commercial
applications (such as electronics, optical displays, and imaging), are chosen and studied in order to
understand the role of physicochemical properties of ENMS in hazard generation and exposure, with a view
to develop SARs to guide safer design principles. Major progress over the past 12 months includes:
• Building on our discoveries surrounding the effects of the electronic structure of metal oxide
particles on biological response to exposure, we modified the crystal structures and band gaps of
17
•
•
•
CuO by doping with Fe ions, which lead to a decrease in interference in the zebrafish hatching
enzyme (Theme 2 and 5). These data are being used by the Cu-working group to study the role of
dissolution and bioavailability in various environmental settings.
A new library of manganese-doped iron oxides was synthesized and will be used to extend studies
of the effects of semiconductor materials and determine if there is a correlation between magnetic
properties (caused by unpaired electrons on toxicity in Theme 2).
A library of fumed SiO 2 particles, doped with aluminum and/or titanium, was synthesized to study
the effectives of doping on adverse cellular effects and pro-inflammatory potentials both in vitro
and in vivo, with Theme 2 reporting doping led to progressive reduction in both.
New libraries of materials were introduced that display unique 2D properties such as graphene,
graphene oxides, and molybdenum disulfide (MoS 2 ), rare earth oxides that are used in applications
ranging from catalysis to optical displays and imaging, and a new emerging class of hybrid/inorganic
nanoparticles. Early characterization of the hazard potential of these new materials, including
early indicators of potential environmental impact, is of considerable importance due to their rapid
pace of commercialization.
Theme 2 is continuing the development of predictive toxicological paradigms premised on adverse
outcome pathways to forecast the likelihood of in vivo toxicological injury, which also plays a role in the
pathogenesis of a disease, thereby allowing hazard ranking and tiered risk assessment analysis. In the
current period, this was demonstrated by accomplishing predictive toxicological paradigms for nano-Ag, IIIV semiconductor materials, metal oxides (MOxs) and rare-earth (RE)-doped ENMs. Major progress includes:
• Prior results for 24 MOxs ly tested in mammalian cells also apply to growth of E. coli in minimal
trophic media. 7 key MOxs were found to exert significant inhibitory effects, which was correlated
with assays assessing bacterial membrane damage and oxidative stress responses. Overall, there is
good correlation of MOx hydration energy and conduction band energy levels with the biological
outcome in bacteria.
• The generation of lysosomal injury and inflammasome activation, resulting from the surface
interactions of RE-doped UCNPs with cellular phosphate residues, has allowed us to develop a
predictive toxicological paradigm that links inflammasome activation to the generation of chronic
inflammation and pulmonary fibrosis. The SAR linked to phosphate complexation and precipitation
of RE-PO 4 complexes on the particle surfaces allowed us to develop a safer-by-design strategy using
phosphonates to passivate particle surfaces.
• The transition to luminescence-based HTS screening methods has allowed for the introduction of
more sensitive screening assays which as less receptive to signal quenching than fluorescencebased methods.
• Our studies using zebrafish embryos and larvae for high content screening have allows us to engage
in creative environmental research, allowing for novel investigation of broad categories of
materials. One example is the ability to perform environmental risk assessment of Cu-based
fungicides by using zebrafish embryo screening of the effluent obtained from a model wastewater
treatment system (with Theme 3). This research demonstrated the importance of changing the
bioavailability of Cu as a result of its organic speciation, allowing us to track the transformation of
materials in a complex exposure environment without the need for direct particle imaging.
Theme 3 provides quantitative information on the fate and transport of nanoparticles, the life cycle
implications of ENMs, and experimental methods to measure and estimate likely NP exposure
concentrations in difference environmental media (e.g., freshwater, estuaries, coastal, terrestrial). These
data inform the experimental design of studies in Themes 2, 4, and 5.
18
•
•
•
Our Life Cycle Assessments to predict annual mass release of ENMs to various environmental
compartments (air, water, soils) was expanded to include the use of ENMs in food. The most
commonly used ENMs in food are titanium dioxide, silicon dioxide, calcium carbonate, and silver
with concentrations ranging from 0.5mg/kg to over 3,000 mg/kg (SiO 2 ). A large fraction (>99%) of
these ENMs pass through the wastewater treatment plant and end up in treated effluent (5-10%)
or in biosolids (90-95%). The material flow analysis model has been incorporated into the webbased, open access modeling framework developed by Theme 6.
A study of the leaching of copper biocides from commercial antifouling paints was conducted.
Release of copper from the paint matrix and its transformation in natural water was monitored for
180 days. The amount of copper released was strongly dependent on the ionic strength of water,
surface material, and paint curing time. The quantification of nanoparticulate Cu release from
antifouling paints is useful in properly assessing the exposure levels of aquatic organisms to these
particles and informs the exposure studies conducted by Themes 2 and 5. We also used the data
for alternatives analysis in a workshop held on this topic on the UCLA campus in Theme 7.
In studies to quantitatively determine the uptake, bioaccumulation, biotransformation and
transport of ENMs in terrestrial systems, we found that TiO 2 and CeO 2 at 100mg/kg were shown to
significantly increase the bioavailability of phosphorous in potting soil and farm soil, while TiO 2 was
also seen to increase the water extractable fraction of phosphorous in potting soil. Additionally
photo-induced ROS production by photoactive ENMs (TiO 2 and CeO 2 ) interfere with the
photosynthetic mechanisms of plants, except in unfertilized soil, perhaps due to the production of
more antioxidant compounds as a stress response to low nutrient conditions. This data will be used
to enhance the multimedia environmental fate and transport model in Theme 6.
Theme 4 is delivering a new understanding of ENM hazards in the terrestrial environment, including how to
assess and predict impacts to microbes, how food production and food quality are susceptible to ENMs,
and how to mitigate agricultural impacts. The major impacts of Theme 4 research over the last twelve
months are:
• MWCNT trophic transfer from bacteria to protozoans was quantified for low amounts of 14C-labeled
MWCNTs from NIST that were traced sensitively into prey and predators by use of accelerator mass
spectrometry at LLNL. This study newly quantifies low, environmentally relevant, amounts of
MWCNTs moving through trophic levels at the base of food chains, showing that bioaccumulation
occurs but not biomagnification, and that similar proportions of NM are bioaccumulated whether
protozoans are consuming MWCNT-encrusted prey or are directly uptaking MWCNTs from media.
• Across a broad spectrum of NMs including metal oxide, metal, coated and uncoated, there are
effects to most food plants studied as measured by plant growth and yield, plant health and
nutrient content, and internalized NM or constituent metals.
• Nano-CeO 2 in particular commonly induces plant stress biochemical markers, and causes DNA
damage, reproductive delays, compromised seed quality or production, impaired light harvesting
apparatuses, and sap flow impairment. Further, there is greater trophic transfer of Ce from plants
into herbivorous insects when Ce is administered as NMs versus in bulk form.
• Copper compounds including salts, micron-sized Cu NMs, and commercially used Cu hydroxide NPs,
interfered with seed germination, and soil-grown plant chemical stoichiometry. Similar types of
changes were observed in Ag NM-treated plants.
• Carbonaceous engineered NMs (graphene and three types of MWCNTs) similarly impacted soil
microbial communities as compared to negative control benchmark materials of industrial CB and
biochar.
• One type of MWCNT impaired soybean growth in B. japonicum- inoculated soil. When comparing
effects of MWCNTs to those of CB and graphene, soybean plant growth was differentially impacted
19
•
across these NMs and doses; effects were not apparent across these NMs when soybeans were
heat-stressed or pest-infected.
DEB modeling of plant growth, and microbial-plant interactions, advanced, and a generalizable
model of ROS effects, and organismal positive and negative feedbacks was developed. The model
showed that interpretation of correlations between internal ROS levels and metrics characterizing
cellular damage requires data at multiple time points. It was used to guide the sampling regime in
all experiments on soybean exposed to carbonaceous engineered NMs.
Theme 5 examines the impacts of ENMs on marine and freshwater aquatic ecosystems by utilizing sentinel
organisms in studies of biological injury mechanisms and studies that aim to characterize ecological
interactions that translate to impacts on ecosystem services. Over the past year, research highlights
include:
• Analysis and modeling of results from phytoplankton HCS assessment of numerous cytological
effects caused by metal oxide ENMs (e.g., ZnO, CuO, CeO 2 , nano-Ag) to quantify the extent to
which they are linked to reduced photosynthetic efficiency and reduced population growth. The
only cellular level data that allowed prediction of population growth rate involved photosynthesis;
the other metrics were shown to have limited predictive value.
• Further development of the HCS platform for mussel hemocytes as a tool for a wide range of ENMs.
• Experiments on effects of CuO (as well as ZnO) ENMs on sea urchin embryos, which showed no
effect on hatching success, including Pacific herring (in contrast with findings for zebrafish).
Internalization of ENMs caused inhibition of the major defense system for early life stages. These
findings highlight the need for testing platforms to include more marine organisms.
• A mesocosm experiment demonstrated impact of exposure to CuO on osmoregulation capacity of
killifish. This is an injury mechanism of particular importance in estuarine environments, as many
estuarine environments experience large fluctuations in salinity.
• Completion of the first study of the long-term (entire lifetime) effects on a zooplankter (Daphnia) of
exposure to a ENM (citrate coated silver) with food availability similar to typical field levels that are
up to 100X lower than those normally used in toxicity tests. At these realistic food levels, there is a
much stronger reduction in fecundity in response to exposure than under standardized chronic test
conditions. This finding implies that standardized tests on a widely used model organism may
underestimate risk.
• Completion of the first multi-generation population level study of the effects of sustained exposure
of a zooplankter (Daphnia) to an ENM (citrate coated nAg). The results demonstrated the
importance of ecological feedbacks for predicting population viability from data on individual
organisms. DEB modeling tested two hypotheses on feedback mechanisms that could reduce
toxicity: (i) impacts via the algal food environment; (ii) toxicity mitigation via zooplanktongenerated DOC. Feedbacks via food alone are sufficient to explain the data.
Theme 6 is engaged in the development of an advanced modeling platform for environmental impact
assessment (EIA) of nanomaterials and case studies to elucidate these potential impacts. Theme 6 utilizes
machine learning and statistical methods to analyze large quantities of ENM toxicity data to develop hazard
ranking. Key accomplishments over the last year include:
• Supporting the CEIN mission of developing predictive toxicology via the construction of advanced
nano-QSARs. In collaboration with Theme 2 and the University of Toronto, we studied the role of
protein corona in the cellular association of Au NPs. QSAR development was also expanded to
include a new model for cellular uptake of surface-modified iron oxide core NPs. Additional
collaboration with Theme 2 resulted in a highly predictive QSAR for bacterial toxicity of metal oxide
NPs confirming the relevance of hydration enthalpy and conduction band energy for toxicity
20
•
•
•
•
•
prediction. Another collaboration provided correlation analyses and data visualization in support of
the study on the bacterial toxicity of Cu NPs.
In order to establish the significance of delivered versus administered dose on NP toxicity ranking
an improved NP sedimentation model was developed that accounts for the complete size
distribution, fractal structure, and permeability of NP agglomerates. The developed in-vitro
dosimetry model allows CEIN researchers to estimate the amount of settled NPs in HTS toxicity
tests and thus assess the implications for toxicity ranking.
Given the growing interest in evaluating the body of evidence regarding the ENMs toxicity a novel
approach was developed for deriving predictive relationships for QDs toxicity via meta-analysis.
Here we collaborated with the US Naval Research Laboratory and Theme 2 on knowledge
extraction from compiled literature data.
Given the need to better understand the impact of ENMs on microbial communities, we
collaborated with Theme 4 to assess soil bacterial community susceptibility via advanced data
visualization techniques.
The computational simulation platform for assessing the release of ENMs to the environment and
their multimedia distribution has enabled rapid assessment of the potential multimedia exposure
concentrations for different ENMs.
Integration of analysis of potential ENM releases and exposure scenarios with CEIN toxicity
information enabled the construction of a powerful Bayesian Network tool for assessing the
environmental impact of nanomaterials which accounts for the body of evidence with
considerations of data uncertainty.
Over the past year, the UC CEIN continued to expand its science translation and outreach efforts to multistakeholder communities (Theme 7). The knowledge and approaches generated in the UC CEIN are being
used to engage national and international thought leaders in the areas of nano EHS policy, governance, and
anticipatory decision making. In March 2015, we convened a multi-stakeholder workshop at UCLA entitled:
Implementing Environmentally-Relevant Exposures for Improved Interpretation of Laboratory Toxicology
Studies of Manufactured and Engineered Nanomaterials (M&ENMs) leading to a Critical Review piece
(submitted to ES&T Feb. 2016). In summer 2015, we established an Industrial Discussion Forum Series
where CEIN is engaging a broad range of industry partners in discussions about CEIN research advances and
how these can be utilized by industry to foster worker safety, safer design, rapid implementation, and
responsible commercialization of nanomaterials. Public outreach materials developed in the past year
include the submission of two videos to ACS Nano per their request highlighting major findings of recently
published articles (videos posted to the ACS Nano YouTube page). From the policy perspective, work
continues to apply formal decision analysis tools to regulatory alternatives analysis in the completion of a
case study of alternatives to copper-based anti-fouling paints for recreational boats: preliminary results
were presented at the annual Society for Environmental Toxicology and Chemistry meeting (November
2015). Additionally, collaboration with the UCLA Institute for Society and Genetics continues in the
development and conduct of an international survey of toxicologists regarding the viability and application
of alternative testing strategies in business and regulatory contexts.
A major goal of the UC CEIN Education Program (Theme 8) is to train the next generation of nano-scale
scientists, engineers, and policy makers and to develop a comprehensive workforce to assist in the safe
implementation of nanotechnology for the benefits of society, the environment and our economy. Our
programs are developed to ensure the science performed and the discoveries made within the Center are
levered to serve broader societal needs. The activities of our education and outreach team has had a
considerable impact on knowledge development and dissemination in the area of Environmental
Nanotechnology, designing programs that foster collaborative interdisciplinary science, advance discovery
and understanding while promoting teaching training and learning, mentor students and postdocs. This
21
includes the participation of underrepresented groups in the sciences. In partnership with Science Buddies,
we develop science fair projects for middle school students based on research generated in the Center. Our
second validated science fair project Looking Downstream: Could Nanosilver in Consumer Products Affect
Pond Life? was made publicly available this past fall. Additionally, the Center has designed and pilot tested
a research-based laboratory module for undergraduate chemistry classes based upon the high throughput
screening assays used within the CEIN. The module, piloted at Santa Clara University, will be submitted for
publication in the Journal of Chemical Education and is currently being considered for incorporation into the
existing curriculum of two community colleges in California. The Center has greatly enhanced the
professional development opportunities for graduate students and postdoctoral researchers within our
Center, as we build a cohesive and interdisciplinary environment for science and education. We regularly
engaged the public in settings such as science museums and public libraries to inform them of our work.
We make concerted efforts to involve minority institutions, including the recruitment of minority faculty
and students. We have four Hispanic serving institutions as core partners in our Center, and are working to
incorporate strategies for promoting diversity and inclusion and underrepresented minorities into all of our
educational activities.
22
NSF: DBI‐1266377
Toxicological paradigm built on metal oxide bandgap & biological oxidative stress in mammalian cells & bacteria
23
NSF: DBI‐1266377
Predictive paradigms based
on NP dissolution chemistry
24
NSF: DBI‐1266377
Mapping of global ENM
materials flows highlights
applications with most
environmental implications
25
NSF: DBI‐1266377
Use of a modeled septic tank
system for a comparative study
of a commercial Cu-based
fungicide in zebrafish embryos
26
NSF: DBI‐1266377
Tiered ecotoxicity workflow
and capabilities
27
28
ZnO
500 mg/kg Zn
Cu
Mn
Peralta‐Videa et al. 2014 PPB
CeO2
1000 mg/kg P
Cu
Na
Ca
CeO2 and ZnO: Changes in Soybean Nutrients
Rico et al. 2014 ES&T
Number of Spikes
CeO2: Decrease in Barley Spikes
Hong et al. 2014 Environ Sci: Processes & Impacts
Cu‐based products: Changes in Alfalfa and Lettuce Nutrients
FRUIT
Rico et al. 2014 ES&T
CeO2: Decrease Spikes in Wheat
NSF: DBI‐1266377
Expanded Investigations of MNMs’ Effects on Plant Populations
NSF: DBI‐1266377
NSF: DBI‐1266377
Nanoinformatics models and
tools for ENMs
Environmental Impact
Assessment
29
NSF: DBI‐1266377
Copper NP Working Group
30
NSF: DBI‐1266377
Carbonaceous Working Group
also focusing on Graphene
31
NSF: DBI‐1266377
NSF: DBI‐1266377
Multi-stakeholder workshop
ATS utility for ENM
categorization and tiered risk
assessment
32
8. Strategic Plan
The emergence and rapid expansion of nanotechnology, now reaching a large number of consumers in
products such as personal care products, food additives, pharmaceuticals, electronics, energy
harvesting, coatings, and paints, has generated considerable concern about the environmental health
and safety (EHS) of engineered nanomaterials (ENMs). In response to this concern, the University of
California Center for Environmental Implications of Nanotechnology (UC CEIN) was established in
October 2008 with a long-term vision of developing a multidisciplinary and quantitative framework for
assessing the potential environmental impact, hazard and exposure to nanomaterials, in both their
primary as well as consumer product formulations. The Center also provides feedback and guidance for
the safer implementation of nanotechnology, including risk reduction and safer design strategies. The
multidisciplinary approach involves materials science, environmental chemistry and engineering,
toxicology, ecology, social science, computer science and modeling, statistics, public health and policy
formulation. Collectively, these fields of expertise are necessary to address the complexity of the ENM
physicochemical properties involved in hazard generation, establishment of structure-activity
relationships (SARs), and use of exposure assessment to evaluate ecosystems impact. The CEIN’s vision
is to generate predictive tools for environmental hazard and exposure assessment as well as to develop
strategies to ensure the safe implementation of nanotechnology to the benefit of society, the
environment and the economy. These tools and knowledge are being disseminated through vibrant and
impactful educational and outreach programs. This vision is clearly aligned with the National
Nanotechnology Initiative’s (NNI) and national research needs, as echoed by the 2012 PCAST report.
Towards continuing the implementation of this vision over the second five years, our strategic plan
includes the use of a multidisciplinary approach to achieve four overarching goals, namely:
i.
ii.
iii.
iv.
To develop hazard ranking and structure-activity relationships (SARs) that relate the
physicochemical properties of compositional and combinatorial ENM libraries to
toxicological responses in cells, bacteria and multi-cellular organisms, with a goal to develop
predictive toxicological paradigms to understand the environmental impact of
nanotechnology;
To estimate environmentally relevant exposure concentrations of high-volume and
potentially high-impact ENMs (primary nanoparticles as well as commercial nano-enabled
products) using life cycle assessment (LCA) and fate and transport modeling to obtain
quantitative information about the uptake, bioaccumulation, and hazard of nanoparticles in
terrestrial and estuarine ecosystems;
To determine the potential of ENMs, selected through high throughput screening (HTS), SAR
analysis, LCA and multimedia modeling, to impact ecosystem services in model ecosystems.
These include terrestrial mesocosms with food crop plans and bacterial populations that
control nutrient cycles, and estuarine mesocosms comprised of a representative natural
food web;
To use UC CEIN knowledge acquisition and environmental impact assessment tools to
educate the next generation of nano EHS scientists as well as to inform and engage
academic, government, industrial and societal stakeholders involved in risk perception,
regulatory decision-making, policy development, risk management and safe implementation
of nanotechnology.
The multidisciplinary UC CEIN team addresses these overarching goals through four major thrusts, which
include eight research themes. The first thrust (Structure-Activity Relationships) involves nanomaterial
acquisition and characterization with a view to perform high-content screening (HTS) of ENM libraries to
33
understand
structure-activity
relationships at the nano/bio interface.
This task is carried out by material
Environmental
Structure/Activity
Ecosystems
scientists and chemists who acquire
Modeling
Relationships
Impacts
and synthesize compositional and
Theme 3:
Theme 1:
Theme 4:
Environmental Fate
ENM
combinatorial ENM libraries that are
Terrestrial Impacts
& Transport; Life
Physical/Chemical
(Food supply)
Cycle Modeling
Characteristics
used to assess the physicochemical
properties that could contribute to
Theme 5:
Theme 6:
Theme 2:
Estuarine Impacts
hazard generation in cells, bacteria,
Exposure Modeling;
HTS and Predictive
(Benthic and
and QSARs
Toxicology
Pelagic Organisms)
yeast, zebrafish embryos, terrestrial
and aquatic life forms.
Where
possible,
the
hazard
assessment
is
Societal
Outputs
carried
out
by
automated
high
Theme 7:
Theme 8:
Stakeholder Engagement and
Educational Programs and Workforce
throughput screening (HTS) in the
Development
Translational Activities
Molecular Shared Screening Resource
Integrated UC CEIN research thrusts and themes: Thrust 1 includes Theme 1,
(MSSR) in the California NanoSystems
which is responsible for the synthesis, acquisition and characterization of ENM
Institute (CNSI). The rich data sets
libraries and commercial ENMs. These materials are used for high content and
HTS in cells, bacteria, yeasts, and zebrafish embryos by Theme 2. The rich data
emerging from the HTS are deposited
content is used for hazard ranking and development of QSARs by the
into the UC CEIN data repository,
computational modeling efforts in Theme 6. Theme 6, in collaboration with the
enabling computer scientists and
fate and transport in LCA studies in Theme 3, is responsible for environmental
modeling in the second thrust, thereby assisting the planning and execution of
engineers to develop a computational
terrestrial and estuarine ecosystems impact studies being conducted in the
framework
for
assessing
the
Ecosystems Impacts thrust in Themes 4 and 5, respectively. The Thrust for
Societal Outputs is responsible for stakeholder outreach, engagement and
environmental impact of ENMs
translational activities (Theme 7) while Theme 8 is responsible for educational
through the use of knowledge
programs and the development of a future nano EHS workforce.
extraction and machine learning
methods for data visualization (e.g., heat maps and Self-Organizing Maps), hazard ranking and
establishment of quantitative structure-activity relationships (SARs). The second major thrust
(Ecosystems Impacts) looks at the impacts of selected materials, identified through hazard ranking and
exposure modeling, on terrestrial and aquatic ecosystems. The terrestrial theme emphasizes the ENM
impact on microbes and plants, while the aquatic theme looks at estuarine species that are chosen
based on the likelihood of suspension (pelagic organisms) or sedimentation (benthic organisms)
exposures. Both environmental themes are focused on ENM impacts on ecosystem services (e.g.,
nutrient cycling, food webs, and biodiversity) and ecological processes (e.g., growth, primary
production, and trophic transfer). The ecosystems studies also include development of dynamic energy
budget (DEB) models that quantify and integrate the ecosystem impacts across scales and life stages.
The third major thrust examines Environmental modeling through the lens of environmental fate and
transport lifecycle analyses. In combination with multimedia modeling tools developed by Theme 6, this
research is used for ENM environmental decision analysis and modeling of the environmental exposure
scenarios. The fourth thrust (Societal Outputs) is engaged in societal implications, education and
outreach activities that generate new knowledge about societal contexts for ENM risk and also
translates our research, knowledge acquisition and decision-making to students, experts, the public and
industry stakeholders.
UC CEIN Research Integration
34
9. Research Program, Accomplishments, and Plans
The Center makes use of well-characterized compositional and combinatorial ENM libraries to study
their fate and transport in parallel with the materials' bioavailability and potential to engage
toxicological pathways in organisms and environmental life forms. Where possible, this exploration
involves high throughput screening (HTS) to develop structure-activity relationships (SARs) that can be
used to predict the impact of primary ENMs' on organisms in freshwater, seawater, and terrestrial
environments. In silico data transformation and decision-making tools are involved in data processing to
provide hazard ranking, exposure modeling, risk profiling, and construction of nano-SARs. These
research activities are combined with educational programs that inform the public, students, federal
implementation of nanotechnology in the environment. Collectively, these activities contribute to
evidence-based nanotechnology environmental health and safety (nano EHS) for society.
The research of the UC CEIN is carried out by 35 distinct but interactive research projects (supported by
4 service cores) across seven interdisciplinary research themes and our education/outreach program:
• Theme 1: Compositional and Combinatorial ENM Libraries for Property-Activity Analysis
• Theme 2: Molecular, Cellular, and Organism High-Throughput Screening for Hazard Assessment
• Theme 3: Fate, Transport, Exposure, and Life Cycle Assessment
• Theme 4: Terrestrial Ecosystems Impact and Hazard Assessment
• Theme 5: Marine and Freshwater Ecosystems Impact and Toxicology
• Theme 6: Environmental Decision Analysis for ENMs
• Theme 7: Using UC CEIN Knowledge Generation to Engage and Impact Multiple Stakeholders
• Theme 8: Education, Career Development, Knowledge Dissemination, and Interactive Efforts
Details of the key accomplishments and research plans for each of the Center’s research themes are
summarized on the following pages. For more information about the Center’s support cores, please
refer to Section 14: Personnel.
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Theme 1: Synthesis of ENM Libraries For Property-Activity Analysis
Faculty Investigator List:
Jeffrey I. Zink, UCLA, Professor of Chemistry and Biochemistry – Theme leader
C. Jeffrey Brinker, University of New Mexico and Sandia National Laboratory, Professor of Chemical
Engineering and Sandia Fellow
Mark Hersam, Northwestern University, Professor of Chemistry
Lutz Mädler, University of Bremen (Germany), Professor of Production Engineering
Galen Stucky, UC Santa Barbara, Professor of Chemistry
Graduate Students: 8; Undergraduate Students: 10; Postdoctoral Researchers: 5
Short Summary of Theme 1
The primary goals of Theme 1 are to synthesize, purify, characterize and disperse in relevant media
libraries of nanomaterials that are chosen in order to develop property-activity relationships between
fundamental physical/chemical properties of nanoparticles and responses in cells, bacteria and
organisms. An important subsidiary goal is to identify and test new materials that are being developed
for commercial applications before they are in widespread production in order to pre-empt
environmental danger. Fundamental understanding will lead to practical applications such as the ability
to predict whether a nanomaterial will have deleterious environmental impacts and the ability to design
nanomaterials with a desired function but greater safety than existing materials.
Theme 1 Projects:
There are four continuing projects and two seed projects (ENM5 and ENM6) in Theme 1 as listed below.
Multiple faculty investigators contributed to the projects; the names of the investigators who made
significant contributions are given in the summaries of the major accomplishments discussed in the next
section. Results from ENM5 are combined with those of ENM4 and those from ENM6 with ENM1.
• ENM-1: Relationships between ENM Electronic Structure and Biological Outcomes (Zink, Stucky, Madler, Brinker)
• ENM-2: Relationships between ENM Shape/Size and Biological Outcomes –
(Hersam, Brinker, Zink)
• ENM-3: Relationships between ENM Surface Structure/Chemistry and Biological Outcomes –
(Zink, Hersam, Brinker, Madler)
• ENM-4: Relationships between Novel ENM Properties and Environmental Outcomes –
(Zink, Hersam)
• ENM-5: Evaluation of the Toxicological Effects of Rare Earth Oxide and Rare Earth Oxide/Silica
Core/Shell Nanoparticles on Bacterial Organisms – (Seed: Brinker)
• ENM-6: Electroanalytical Evaluation of Cytotoxicity of Metal Oxides – (Seed: Stucky)
Major Accomplishments since March 2015:
ENM-1: Relationships between ENM Electronic Structure and Biological Outcomes.
To continue to refine CEIN’s understanding of the importance of semiconductor properties and
dissolution of nanoparticles on biological and environmental impact, the members of Theme 1
synthesized two libraries of new nanoparticles for detailed study. In addition, a new electroanalytical
technique to evaluate the conduction band energy was developed.
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The Mädler laboratory synthesized a homologous library of (1-10%) Fe doped CuO. Doping the particles
with iron was expected to reduce dissolution. The particles were characterized using BET, XRD, Raman
spectroscopy, HRTEM and EELS. The respective primary particle sizes were in the range of 10-12 nm.
The crystallite sizes extracted using Rietveld analysis of the XRD patterns were in the range of 9-12 nm.
The Fe content in CuO after flame spray was determined using energy-dispersive X-ray spectroscopy
(EDX) and the results showed efficient composition control during FSP preparation. Raman spectroscopy
measurements indicated a strong Fe incorporation in the lattice. These particles were first exposed to
zebrafish embryos for hatching response. The results showed hatching interference via CuO NPs
exposure but 6 and 10 % Fe doped CuO showed reduced interference. The dissolution experiments
(particles suspended in Holtfreter's medium for 48 h) indicated 5.8 and 0.4% (from 0.5 ppm) ionization
of pure and 10%F e doped CuO, respectively. Higher Fe loading significantly lowered zebrafish hatching
interference which might have emerged through the variation in the crystal arrangement. These
particles together with commercially available CuO NPs were exposed to a white sea urchin marine
model. At 96 h post exposure, no significant oxidative damage was detected but a reduction in the total
antioxidant capacity was observed. All of the NPs were significantly internalized by embryos and their
differential dissolution played a critical role in toxicity profiles. FSP CuO NPs had greater toxicity
compared to the commercial CuO resulting in specific developmental abnormalities due to changes in
the redox environment caused by dissolution. The dissolution of Fe doped CuO NPs was evaluated
theoretically via ionic equilibration approach using PHREEQCi and Matlab software. The chemical
composition and pH of the Holfreter’s medium were key factors for the dissolution model. The
equilibration of CuO at concentration of 0.5 ppm (6.286 µmol/L) in the Holfreter’s medium was
conducted. The results showed 6 % copper was dissolved in the Holfreter’s medium at pH 7.6 suggesting
a strong dependence of pH in the Cu2+ release. To determine the release equilibration of the doped CuO,
spherical particles with homogeneous Fe distribution on the surface along with pH of the test media
were considered. Results showed with increasing Fe content, the dissolution also decreased with
increasing thickness of Cu-Fe-O layer on the surface
To study the effects of tuning the conduction band energies and of changing the numbers of unpaired
electron spins of metal oxides by changing the crystal structures, the Zink group synthesized specific
crystalline forms of manganese-doped iron oxide. Prior work has shown that overlap of the conduction
band energy with the energies of intracellular reducing agents is correlated with toxicity.
Iron−manganese oxide (MnxFe1−xO) nanoplates were prepared by a thermal decomposition method.
Irregular development of crystalline phases was observed with the increase of annealing temperature.
Magnetic properties (caused by unpaired electrons) are in accordance with their respective crystalline
phases, and the selective magnetic evolution from their rich magnetism of MnxFe1−xO and MnFe2O4 is
achieved by controlling the annealing conditions. The rock-salt structure of MnxFe1−xO (space group
Fm3̅m) is observed in as-synthesized nanoplates, while MnFe2O4 and MnxFe1−xO with significant
magnetic interactions between them are observed at 380 °C. In nanoplates annealed at 450 °C, soft
ferrites of Mn0.48Fe2.52O4 with MnxFe1−xO are observed. The differential and early development of
the crystalline phase of MnxFe1−xO and the inhomogeneous cation mixing between Mn and Fe cause
this rather extraordinary magnetic development. The tendencies of divalent metal oxides to have cation
vacancies and the prolonged annealing time of 15 h enables ordering and contributes to these
properties. Metal oxides composed of Fe and Mn are among the most common oxides, and this work
explains the development of diverse structures and magnetism as a function of the annealing
temperature.
In a second study of mixed metal oxides by the Zink group, a new approach to the synthesis of Fe3O4
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and MnFe2O4 NPs, starting from Mn oxide seeds was devised. In this study, mixed ferrite NPs between
Fe and Mn were synthesized and examined for their magnetic behaviors. Seeds of Mn oxide NPs were
used for the preparation of crystalline Fe3O4 and MnFe2O4 NPs. In addition, MnFe2O4@MnxFe1 xO
core–shell NPs were synthesized in a seed-mediated method from MnFe2O4 NPs. MnxFe1 xO adopts a
rock salt structure as do MnO, FeO, and other similar divalent metal oxides. Diverse magnetic and
electrical properties can be achieved by occupying vacant cation sites with other dopants, for example,
as seen in the electrical band gap engineering of metal oxides. This new approach opens the door to a
synthetic method for making magnetically active and magnetically diverse soft ferrite nanomaterials.
The Stucky group conducted a detailed investigation of the experimental conditions affecting MottSchottky measurements in order to obtain experimental details about the conduction band energy. To
increase the repeatability of this technique (electrochemical impedance spectroscopy, EIS), a new kind
of conductive substrate, FTO, for nanoparticle deposition was chosen for extensive EIS tests. A new
method for deposition of nanoparticles onto FTO was also developed, namely, hot drying using aqueous
suspension at ~80 oC. Several electrochemical parameters for EIS were optimized, including the voltage
range (based on the redox potentials of water media at different temperatures and pH with different
electrolyte properties), oxygen-free condition (argon bubbling), electrolyte properties (phosphate buffer
with high pH buffering capacity as opposed to a common single-salt electrolyte). Based on the optimum
EIS method that was established, it was observed that the flat-band potential of TiO 2 is dependent on
the pH value of phosphate buffer electrolyte, which is consistent with previous reports about the
Nernstian dependence -- H+ and OH- are potential determining ions adsorbed on the solid surface within
the Helmholtz layer. Several other semiconductor nanomaterials were tested, including both n-type
(undoped and doped TiO 2 , CeO 2 ) and p-type (NiO, Co 3 O 4 ) semiconductors. The relative values of
measured flat-band potentials show the same trends as reported using theoretical calculation. However,
the EIS method gives a quantitative experimental measurement of the flat-band potential for n type
nano materials, which is directly related to the conduction band energy. The latter can be used to
predict the potential toxicity of tested nanomaterials.
ENM-2: Relationships between ENM Shape/Size and Biological Outcomes.
During this reporting period, no nanomaterials were made with the explicit purpose of studying shape
and size effects on biological outcomes. However, during the course of the nanomaterial syntheses in
projects 1 and 4, particles with plate-like shapes (Mn x Fe 1-x O 4 ), sheet shapes (graphene and graphene
oxides) and rod/wire shapes (carbon nanotubes) were synthesized. These studies provide valuable
input to furthering understanding of the effects of morphology.
ENM-3: Relationships between ENM Surface Structure/Chemistry and Biological Outcomes.
It is known from the previous year’s investigations that the specific surface properties such as
reconstruction of strained three-membered rings and surface silanol framework on the surface of fumed
silica could trigger biological responses. The deprotonation of the silanol rings at physiological
conditions is a key for strong electrostatic interaction between silica particles and the biological
components. Hence to disrupt such framework structure on the surface, the Mädler group reengineered fumed silica by doping titanium and/or aluminum (0-7%) using versatile flame spray
pyrolysis (FSP). Extensive material characterization revealed that both Ti and Al were proportionally
doped in the silica matrix. The physicochemical characterization (BET, XRD, small angle XRD, Raman
spectroscopy, TEM and EPR measurements) showed amorphous nature of the particles with
homogenous distribution of the dopant except aluminum which segregated as larger particles (∼20-50
nm) in the matrix at higher doping level such as 10%. The cellular toxicity assessment carried out in
Theme 2 showed that fumed silica induced toxic effects in THP-1 cells. However, with Al and/or Ti
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doping, the toxicity was significantly decreased. Results showed induction of toxic effects in THP-1 cells
similar to the MTS assay while Al- and/or Ti-doping reduced the cytotoxicity. To further confirm this
effect, the induction of NLRP3 inflammasome and IL-1β production was determined. Dose dependent IL1β production data showed fumed silica induced significant IL-1β production in THP-1 cells while the
effect was progressively reduced through Al and/or Ti doping concentration. The probable hydrogenbonding and surface electrostatic interactions of the Si-O-Si or O-Si-O network of fumed silica and/or
surface defects on the amorphous silica with the extracellular fluid might have caused cellular response
observed through Nalp3 inflammasome. The significant decrease in the cytokine IL- 1β secretion with
doping evidently gave rise to a safer material. In summary, doping reduces fumed silica surface total
silanol display and the surface reactivity. This safer design strategy reduced fumed silica-induced proinflammatory potentials both in vitro and in vivo.
With the above studies, it was observed that pristine fumed silica induces a dose-dependent increase in
IL-1β production while increasing Ti and/or Al doping was associated with a progressive decrease in
cytokine production. To demonstrate that this effect was solely via doping, physically mixed non-doped
fumed silica with either TiO 2 or Al 2 O 3 nanoparticles at the same weight ratios as doped materials were
investigated. In fact the mixing did not affect IL-1β production, suggesting that doping is necessary and
effective for reducing the pro-inflammatory effects of fumed silica.
Previously, the Brinker group had observed the presence of three types of strained three membered
rings (3MRs) in fumed silica through Raman spectroscopy of hydrated fumed silicas: surface, bulk, and
3MRs with trapped radical defects. Hypothesizing that a simple UV/O 3 exposure could be used to
remove the radical centers from the last category of 3MRs, potentially leading to the development of a
scalable processing method to reduce the toxicological potential of pyrogenic silica, they continued their
Raman studies of hydrated fumed silicas by examining a commercial material, Aerosil A200, after
different UV/O 3 (or straight O 3 ) processing times. After the UV/O 3 treatment, the dry 3MR
concentration increases as vibrational symmetry-removing radical defects are removed from 3MRs
(allowing previously ‘invisible’ 3MRs to appear in the Raman spectrum). During water treatment, UV/O 3
preferentially removes near-surface defects, as would be expected for a transport-limited reaction
mechanism. Toxicological studies of fumed silicas processed as described were characterized by cell
viability, IL-1β, and abiotic radical generation assays. Exposure to colloidal silica without UV/O 3
treatment resulted in poor cell viability and enhanced IL-1β production, effects that were nullified after
even 5 minutes of ozone exposure. This behavior was attributed to an unknown toxic residue present on
the dried material that is removed by this treatment.
ENM-4: Relationships between Novel ENM Properties and Environmental Outcomes.
The new materials introduced during the last year were selected because of their rising importance in
applications such as electronics, photonics and imaging. These include materials that display unique 2D
properties such as graphene, graphene oxides, and molybdenum disulfide (MoS 2 ), rare earth metal
oxides that are important in applications ranging from catalysis to optical displays and imaging, and a
newly emerging class of hybrid organic/inorganic nanoparticles. Early characterization of the hazard
potential of these new nanomaterials, including their environmental impact, are of considerable
importance due to the pace of commercialization.
To test the hypothesis of phosphate extraction from bacterial membranes, the Brinker group
synthesized a 0%-10% Eu doped La 2 O 3 nanoparticle library. These particles are currently under further
investigation. The composition and properties of optically-active europium-doped lanthanum oxide (510% Eu) nanoparticles produced by the team of L. Mädler were also characterized and used in
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investigations of rare earth oxide nanoparticle interactions with bacteria, including the formation of
phosphate ‘urchin’ nanoparticle structures in phagosomal simulated fluid (PSF).
The Brinker group in collaboration with Theme 2 had shown previously that Ln 2 O 3 dissolution in
macrophage lysosomes gave rise to toxic effects due to phosphate extraction from lipid bilayers. To test
the hypothesis of phosphate extraction from bacterial membranes, they continued studies of rare earth
oxide (REO) nanoparticle (NP) interactions with both gram-negative (Escherichia coli and Salmonella
enterica) and gram-positive (Staphylococcus aureus) bacteria with a library of REO NPs obtained from
commercial sources as well as hybrid RE/SiO 2 NPs (produced in-house) and binary REO NPs (synthesized
by the Mädler group), in media simulating both phosphate rich and limited environments. TEM, SEM,
and elemental mapping by EDS all show the rapid (~ 15 minute) deposition of insoluble RE phosphate
crystals on the surface of Salmonella membranes from solubilized RE ions; these crystals fall off after
approximately 120 minutes, leaving only membrane-bound RE (RE/P ratio of ~0.1 by EDS) that
significantly alter the interaction of the bacteria with other organisms. REO-induced toxicity to bacteria
was observed only in limited phosphate media and attributed to phosphate starvation, and not direct
toxicity of RE ions.
The Hersam Group continued to investigate the environmental transport and fate of graphene and its
analogues in collaboration with the EPA. Because graphene oxide has the potential to be reduced
naturally in the environment, it is important to understand the environmental behavior of both
graphene oxide and reduced graphene oxide. Towards this end, a library of graphene oxide
nanomaterials was prepared with a wide range of oxidation levels in order to investigate the role that
oxidation state plays in the aggregation and stability of graphene oxide in the environment. Most
recently, the role of pH, natural organic matter, and environmentally relevant cations have been
considered. It has been shown previously that the addition of natural organic matter increases the
stability of graphene oxide, but this effect is even more pronounced for reduced graphene oxide,
indicating that reduced graphene oxide may persist in aqueous environments over the long-term. In the
case of cations, it was determined that both ionic strength and ion valence play a key role in the stability
of graphene oxide and reduced graphene oxide. While monovalent cations show minimal effects,
divalent cations, such as Ca2+, immediately destabilize the nanomaterials in aqueous solution, even at
relatively low concentrations (0.1 mM).
The Hersam Group in collaboration with Theme 2 created hydrated graphene oxide samples which have
been chemically modified to increase the number of radicals on the surface of the material. The in vitro
toxicity of these nanomaterials was investigated on both mammalian cells and bacteria. It was
determined that the number of radicals present on the surface of the material, as measured by electron
paramagnetic resonance spectroscopy, directly correlated to the toxic effect in both the mammalian and
bacterial populations. These results indicate that the toxicity mechanism for these nanomaterials is due
to the surface radical density and not necessarily due to oxidative stress caused by the oxidation state of
the nanomaterials, as was previously believed.
The Hersam group investigated the role of electronic type of single-walled carbon on mammalian cells.
Using density gradient ultracentrifugation, single-walled carbon nanotubes were sorted according to
electronic type (i.e., metallic or semiconducting) at purities greater than 97%. Both populations of
nanotubes showed negligible cytotoxicity in mammalian systems in vitro but did induce the production
of cytokines involved in inflammatory pathways, indicating a potential for inflammation and lung
fibrosis. This result was further confirmed in an in vivo study in the lungs of mice. In both the in vitro and
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in vivo system, no significant differences were observed between the metallic and semiconducting
carbon nanotube populations.
Despite the worldwide interests generated by periodic mesoporous organosilica (PMO) bulk materials,
the toxicity of PMO nanomaterials with controlled morphology remains unexplored. The Zink group
synthesized PMO nanoparticles (NPs) based on meta-phenylene bridges, and conducted a systematic
structure-properties relationship investigation with para-phenylene-bridged PMO NPs. The change of
the molecular structure drastically affected the structure, morphology, size, porosity and thermal
stability of PMO materials. The para-based PMO had high porosity which was likely due to a higher
molecular periodicity. Additionally, the para isomer could generate multipodal NPs. This research
developed the first synthesis of m-P PMO NPs; showed that careful tuning of organoalkoxysilane
concentrations leads to micro- and nano-objects with spherical and miltipodal structures and high pore
volumes. The Zink group also designed new porous organic-inorganic nanomaterials with chemical
functions designed to enable biodegradation. Mesoporous bridged silsesquioxanes (MBS) NPs were
synthesized via the co-condensation of 1,4-bis(triethoxysilyl)benzene and (N,N’-bis(3-(triethoxysilyl)propyl)oxamide). MBS NPs had a remarkably high organic content (~50 wt%), and a monodisperse 100
nm size with a high surface area (850 m2 g-1). Oxamide functions provided biodegradability in simulated
biological medium. This study paves the way for versatile porous hybrid NPs possessing decreased
bioaccumulation via functional pore walls.
Impacts on the Overall Goals of the Center
The results of the synthetic research programs in Theme 1 continue to expand the nanoparticle library
of the CEIN with new compounds designed to enlarge our knowledge of the factors that contribute to
toxicity and the designs that can be used to increase safety. A major component of our current
understanding of biological responses to metal oxide materials is the electronic structure of the
particles, specifically the energies of the conduction bands and the Fermi levels. In this reporting period
we modified the crystal structures and band gaps of CuO by doping with Fe ions. Zebrafish studies in
Theme 2 and 5 showed that increased iron doping decreased hatching interference. These data are
being used by the Cu-working group to study the role of dissolution and bioavailability in various
environmental settings. A new library of manganese-doped iron oxides was synthesized and will be used
to extend the studies of the effects of semiconductor materials and determine if there is a correlation
between magnetic properties (caused by unpaired electrons) on toxicity in Theme 2. In addition to the
electronic and crystal structural effects, dissolution of ions plays a key role in materials such as ZnO and
CuO. Dissolution of copper ions decreased with increasing iron concentration on the particles. Surface
properties of nanomaterials have an enormous effect on biological outcomes. A library of SiO 2 with
aluminum and/or titanium was synthesized, and dose-dependent studies showed that adverse cellular
effects and pro-inflammatory potentials were progressively reduced through doping both in vitro and in
vivo. In a further study of silica, strained rings and trapped electrons were measured using Raman
spectroscopy and correlated with cellular responses. New materials selected for addition to the library
were chosen because of their increasing importance in applications such as electronics, optical displays
and imaging. A library of hybrid organic/inorganic nanoparticles with catalytic and therapeutic
properties was introduced for study. New two-dimensional layered materials such as graphene oxide
and reduced graphene oxide with a wide range of oxidation levels were prepared and then studied by
Theme 2. The numbers of radicals on the surfaces directly correlated to the toxic effect in both bacterial
and mammalian populations. Reduced graphene oxide persists in the environment for a long time, but
divalent cations such as calcium destabilize the material in aqueous solution. Rare earth oxide
nanoparticles rapidly cause deposition of insoluble RE phosphate crystals on the surface of Salmonella
membranes from solubilized rare earth ions that fall off after approximately 120 minutes, leaving only
membrane-bound ions that significantly alter the interaction of the bacteria with other organisms.
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The synthetic efforts by the members of Theme 1 continued to contribute not only libraries of new
chemical compositions, but also libraries of particles with specifically designed structural, electronic and
morphological properties that in collaboration with Theme 2 are leading to a more detailed
understanding of dangerous characteristics and of strategies to make them safer.
Major Planned Activities for the Period.
We will continue to synthesize new libraries of nanoparticles to assist in the development of predictive
models of toxicity. The libraries related to electronic structure will include not only doping of materials
to fine tune their conduction band energies and Fermi levels, but also synthesis of polymorphs for fine
tuning the energies and for exploring crystal structural effects on toxicity. Detailed studies by tuning
band energies using libraries of mixed metal oxides, p and n doping of metal oxides, p-n junctions
between different metal oxides and metal nanoparticles and metal oxides, and by comparing catalytic
activities of metal oxide nanoparticles with biological outcomes will be carried out. The prior history of
nanoparticles, including the temperature at which they were synthesized, calcined or annealed, changes
their effects on cells and organisms. Libraries of metal oxide nanoparticles made by flame-spray
pyrolysis, hydrothermal methods and sol-gel or aerosol methods will be synthesized. The synthesis
methods affect the surface structure, and safe by design nanomaterials will be synthesizable by
changing the synthesis temperature. We will continue to work closely with Theme 2 and the zebrafish
studies in Theme 5 to design and synthesize specialized nanoparticles to test and develop new
hypotheses about toxicity. All of the above new data will be used for modeling in Theme 6. A continuing
focus will be to develop safer materials that can be used commercially.
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Theme 2: Molecular, Cellular and Organism High Throughput Screening for Hazard Assessment
Faculty Investigators:
André Nel, UCLA – Professor, Medicine; Chief, Division of NanoMedicine- Theme leader
Hilary Godwin, UCLA – Professor, Environmental Health Sciences
Patricia Holden, UC Santa Barbara – Professor, Environmental Microbiology
Shuo Lin, UCLA – Professor, Molecular, Cellular, and Developmental Biology
Tian Xia, UCLA- Assistant Adjunct Professor, Medicine, Division of NanoMedicine
Huan Meng, UCLA- Assistant Adjunct Professor, Medicine, Division of NanoMedicine
Short summary of Theme 2:
The main goal of Theme 2 is to use high content screening (HCS) and high throughput screening (HTS)
for Engineered Nanomaterials (ENMs) at cellular and organismal (zebrafish) levels to develop predictive
toxicological paradigms, hazard ranking and SARs to guide nano EHS decision-making and ecological
research (Themes 4 and 5). HTS of industrially important Ag, Cu, metal oxide (MOx), rare earth oxides
(REO) and III-V semiconductor as well as in-house synthesized doped ENMs (Theme 1) were used since
February 2015 for cellular, bacterial, and zebrafish screening. HTS was also used to assist center-wide
copper and carbonaceous material case studies. In addition to continue developing mechanistic
toxicological assays that are predictive of in vivo toxicological outcomes, we have also introduced new
approaches, including: (i) more sensitive luminescence-based assays to replace fluorescence-based
methods for assessing oxidative stress, organelle dysfunction, and cytotoxicity; (ii) a predictive paradigm
for assessing the effect of III-V particulates and ionic forms generated during planarization of
semiconductor wafers; (iii) HTS of semiconductor metal oxide ENMs based on bacterial oxidative stress
pathways; and (iv) sub-chronic toxicity assessment in adult zebrafish.
Theme 2 Projects:
• HTS-1: Zebrafish HTS and Sub-chronic Toxicity Studies on developing larvae and adults –
(Lin/Nel)
• HTS-2: Use of multi-parametric oxidative stress screening to compare the toxicological effects
of metal oxide, semiconductor, and Ag nanoparticles in mammalian cells – (Xia)
• HTS-3: High Throughput Screening to Determine the Mechanistic Toxicology of Engineered
Nanomaterials in Bacteria – (Godwin/Holden)
• HTS-4: Assessment of the toxicological potential of rare earth oxide nanoparticles with a view
to develop safer design strategies– (Xia)
• HTS-5: Developing of Lab-on-a-Chip Technology for rapid and cost-effective assessment of
ENM-induced cytokine responses in cells – (Meng/Chui)
• HTS-6: Effects of MWCNT nanocomposite degradation particles on zebrafish larvae - (Seed:
Lin/Xia)
Major Accomplishments and progress in Theme 2 projects since February 2015:
Theme 2 conducted 6 productive projects, resulting in 8 UC CEIN funded publications, 6 leveraged
publications and 2 papers that have been submitted or are being drafted. The progress reported in
these projects is as follows:
HTS-1: Zebrafish HTS and Sub-chronic Toxicity Studies on developing larvae and adults
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The goal of this project was to delineate size dependent differences of AgNPs (20nm and 110nm) vs
ionic control in two known target organs for Ag in fish, namely the gills and intestines, with the aims to
explore the toxicity of the particles and the mechanism behind the toxicity observed in the target
organs. We knew from past literature that silver toxicity affects gills and intestines and, therefore, we
wanted to corroborate this for silver nanoparticles. In Aim 1 we developed a subchronic exposure
platform for adult zebrafish with the intention to use this approach to study toxicokinetics and perform
histopathological analysis of critical target organs. The study demonstrated different toxicokinetic
profiles for different particle sizes. The gills showed a significantly higher Ag content for particles of 20
nm, compared with particles of 110 nm33. While both particulate materials were retained after a
depuration period, there were striking size-dependent differences upon histopathological analysis. The
20 nm particles showed the loss of distinguishable primary and secondary filaments, as a result of fusion
of the secondary filaments. Silver staining of the gills and intestines confirmed prominent silver
deposition in the basolateral membranes for the 20 nm, but not for the 110nm particles33. To further
analyze the mechanism of toxicity observed in the target organs, we also explored a well-known target
for Ag in fish: the Na+/K+ ATPAse pump in the gill. Therefore, Aim 2 set out to link the deleterious
consequences on the target organs to a possible impact on this pump. We performed
immunohistochemical analysis on the α subunit of the Na+/K+ ion channel which is localized in the
basolateral membrane, the same site for observed silver deposition. The use of an ATPase assay
demonstrated that 20nm particles caused more inhibition and reduction in ATPase activity than the
110nm particles or an ionic control33. In summary, we achieved the goal of our project by demonstrating
size dependent differences across different Ag treatment groups that included different size AgNPs and
an ionic control. In the next year of study, we propose to use the adult platform as well as new assays to
assess the hazard potential of III-V materials present in CMP slurries.
HTS-2: Use of multi-parametric oxidative stress screening to compare the toxicological effects of
metal, metal oxide and semiconductor nanoparticles in mammalian cells
The goals of this project were to use multi-parametric HTS assays to: (i) delineate and explain the Ag
responsiveness or resistance in mammalian cell lines; (ii) assess the hazardous effects of semiconductor
nanoparticles and their toxicity contribution to the chemical-mechanical planarization (CMP) slurries,
generated as waste products by the semiconductor industry; (iii) investigate the toxicity of metal oxide,
semiconductor, and Ag nanoparticles using luminescence instead of fluorescence assays for higher
efficiency and interference-free biological response detection. Aim 1 was based on the interspecies
differences in Ag sensitivity and previous observed differences in the cytotoxic responses of mammalian
cells to silver nanoparticles (Ag NPs). In order to explore these response outcomes, six cell lines,
including epithelial cells (Caco-2, NHBE, RLE-6TN, and BEAS-2B) and macrophages (RAW 264.7 and THP1), of human and rodent origin, were exposed to 20 nm citrate- and PVP-coated Ag NPs with Au cores,
as well as 20 nm citrate coated particles without cores (2). A MTS assay shows that while Caco-2 and
NHBE cells are resistant to particles over a 0.1–50 µg mL−1 dose range, RAW 264.7, THP-1, RLE-6TN, and
BEAS-2B cells were more susceptible. We also observed differences in anti-oxidant defense and
metallothionein expression among different cell types, which can partially explain the differential
sensitivity to Ag NPs. This study shows the importance of cell-specific differences in exploring the
hazardous effects of ENMs, including nano Ag in nanosafety screening46. In order to address Aim 2, we
compared the toxicity of sub-micron III-V particulates and ionic components in screening for the hazard
potential of III-V semiconductor materials present in the spent CMP slurries16. Large volumes of
hazardous waste are generated during polishing of wafers CMP process. We obtained GaP, InP, GaAs
and InAs as micron (0.2-3 μm) and nanoscale (< 100 nm) particles for comparative analysis of their
cytotoxic potential in macrophage (THP-1) and lung epithelial (BEAS-2B) cell lines. We found nano-sized
III-V arsenides, including GaAs and InAs, could induce significantly more cytotoxicity over a 24-72 h
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observation period16. In contrast, GaP and InP particles of all sizes, as well as ionic GaCl3 and InCl3, were
substantially less hazardous. The principal mechanism of III-V arsenide nanoparticle toxicity is
dissolution and shedding of toxic As(III) [and to a lesser extent As(V)] ions]. GaAs dissolved in the cell
culture medium, as well as in acidifying intracellular compartments, while InAs dissolved (more slowly)
inside cells. Chelation of released As by 2,3-dimercapto-1-propanesulfonic acid (DMPS) interfered in
GaAs toxicity. Collectively, our study demonstrates that III-V arsenides, GaAs and InAs nanoparticles,
contribute in a major way to the toxicity of III-V materials that could appear in slurries16. By gaining an
understanding of the contribution of abraded III-V particulates and ionic species released from the
wafer surface, we can use cellular studies to predict toxicity outcomes in animal studies, as well as use
the system to study actual CMP slurries. Aim 3 was to develop luminescence-based HTS to replace
fluorescence methods through the introduction of new luminescence reagents. One example includes
the use of assays from Promega (e.g., CellTiter-FluorTM, ROS-GloTM, CytoTox-FluorTM and GSH-GloTM)
to assess cell viability, cellular ROS generation, cell death, and GSH levels, respectively, as well as to
compare the results with our fluorescence-based single and multi-parameter HTS assays decsribed in
Aims 1 and 2446,16. Moreover, we envisage combining these assays with luminescence-based reporter
cell lines that contain stable transfected gene response elements (ARE-luc or AP1-luc) to assess the
transcriptional activation of Tier 1 and Tier 2 oxidative stress pathways. Overall, luminescence-based
assays appear to be more sensitive than fluorescence based screening, since they lead to less
background interference because of the interaction of fluorescent dyes with nanoparticle surfaces.
HTS-3: High Throughput Screening to Determine the Mechanistic Toxicology of Engineered
Nanomaterials in Bacteria
The goal of this project is to demonstrate that HTS of ENMs in bacteria can be used to assess and predict
the hazard that different ENMs pose in environmental systems. Because bacteria form one of the
biological foundations for ecosystems and because specific bacterial may be critical sentinel species,
demonstration of effective use of HTS for nanotoxicology in bacterial systems is a high priority for the
UC CEIN. Aim 1 was to determine how the formulation of Cu antimicrobials impacts the magnitude and
mechanism of their toxicity in bacteria found in wastewater treatment systems and whether the toxicity
varies depending on the taxa of the bacteria. Since February 2015, we have completed studies on how
Cu NPs impact two species of enteric bacteria (Escherichia coli and Lactobacillus brevis) using a growth
inhibition assay and a series of sublethal assays17. These studies demonstrated that the mechanisms of
toxicity exhibited by nano-sized Cu particles are different than those exhibited by micron-sized particles
or ionic Cu2+. These studies also demonstrated that different bacterial species can respond differently to
Cu ENMs, both qualitatively and quantitatively, and suggest that studying effects across diverse taxa is
important and that Cu ENMs may alter bacterial population structures in waste treatment systems17. We
have also performed 3D TEM studies on nano-Cu in E. coli, which confirmed that particles of such size
enter the cells. Combined with the results from the in vitro DNA damage assay, these data demonstrate
an important difference in the impact of nano-Cu on bacteria compared to other copper species that
were studied. Aim 2 was to determine which physicochemical properties of metal oxide (MOx) ENMs
correlate with their toxicity in bacteria and use this analysis to develop a predictive paradigm for the
toxicity of MOx ENMs in bacteria. We completed a study in which we used a suite of sublethal assays to
investigate 24 MOx ENMs, previously used for toxicological profiling of mammalian cells, and
demonstrated that the toxicity of MOx ENMs correlates with their hydration energy and conduction
band energy. These data suggest that, although MOx ENMs as a class are not highly toxic to E. coli, the
growth inhibitions observed in E. coli parallel those found in mammalian cells. The student who was
taking the lead on this project (Chitrada Kaweeteerawat) successfully defended her thesis in 2015 and
was awarded her PhD in June 2015. The project is now completed.
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HTS-4:
Assessment of the toxicological potential of rare earth oxide nanoparticles with a view to
develop safer design strategies
The goal of this project is to develop safe implementation and safer design of rare earth (RE) based
ENMs, which are increasingly being used for applications such as magnets, catalysis, electronics, and
biomedicine, among others. These materials have become of great strategic and economic significance
since China has implemented a moratorium on the export of RE minerals. Because of increased mining
activity for RE materials in the US and a history of occupational lung disease, we have previously
demonstrated that RE nanoparticles pose a particular hazard due to the ability to disrupt cellular
phosphate homeostasis and lysosome function in pulmonary macrophages. Upconversion nanoparticles
(UCNPs), which are generated by doping with RE metals, are increasingly used for bio-imaging because
of the advantages over conventional fluorophores. Over the past year, we observed that RE-based
UCNPs, including NaYF4 : Er, Yb and La(OH)3 : Er, Yb, transform to mesh-like or urchin-shaped structures
after treatment with phagolysosomal simulated fluid (PSF). This transformation is due to the deposition
of REPO 4 on the particle surface. Similar transformation could also be observed in THP-1 cells exposed
to UCNPs, leading to lysosomal damage, cathepsin B release and IL-1β production. Besides the effect on
cellular toxicity, the particle transformation also leads to fluorescence quenching, as demonstrated by
the decreased intensity of the emission peaks during PSF treatment or lysosome processing. Because of
the strong binding affinity between RE particles and phosphate, we studied the hypothesis that
phosphonate coating could serve as a safer design procedure that prevents biological transformation of
UCNPs. To test this hypothesis, Aim 1 was to prepare two UCNPs, including in-house synthesized
La(OH)3 doped with Er, Yb, NaYF4 : Er, Yb that is commercially available. These NPs were thoroughly
characterized in Theme 1 to determine size, zeta potential and hydrodynamic size in water and cell
culture media. We delineated the pro-inflammatory potential of UCNPs in macrophages, and found that
the complexation of cellular phosphates is responsible for this outcome. Aim 2 was to develop coatings
to passivate the surface of UCNPs. In collaboration with Zhaoxia Ji and Chong Hyun Chang in Theme 1,
we found that phosphonates can provide this protection, among which EDTMP provides the most stable
coating to prevent the UCNP transformation. The high affinity binding of EDTMP to the particle surface
can be attributed to the unique complexation of lanthanide atoms on the surface This coating also
reduced the proinflammatory effects of these particles in vitro and in vivo. Aim 3 was to evaluate the
imaging capability of coated UCNPs. Comparison of the various coatings demonstrate that while PMIDA,
BPPA, PVP, and citrate had minimal protective effects and AMPA only provides marginal improvement,
EDTMP was able to prevent the decay of fluorescence intensity as demonstrated by fluorescence
spectrometry. A comparison of the fluorescence imaging intensity of uncoated and EDTMP-coated
particles during confocal microscopy showed that while only 18% of the cells treated with uncoated
particles exhibited fluorescence intensity after 24 h, 92% of cells treated with coated particles remained
fluorescent. A similar finding was made when examining pulmonary alveolar macrophages obtained
from the bronchoalveolar lavage fluid (BALF) of animals receiving oropharyngeal aspiration of coated
and uncoated particles 40 h prior to animal sacrifice. These results indicate that EDTMP coating
effectively preserves the fluorescence imaging properties of UCNPs in vitro and in vivo. In future, we will
collaborate with Drs. Lin and Godwin to test the hazard effects of RE nanomaterials in zebra fish or
bacteria. We will also develop other safer design approaches such as core-shell structure with Dr. Zink in
Theme 1 for different application purposes.
HTS-5:
Developing of Lab-on-a-Chip Technology for rapid and cost-effective assessment of ENMinduced cytokine responses in cells
Significant efforts have been devoted to develop in vitro toxicological analysis of engineered
nanomaterials (ENMs). This includes the development of multi-parameter HTS assays, which frequently
require the use of an automated HTS facility. HTS facilities are costly and not widely available. The
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assessment of pro-inflammatory and pro-fibrogenic cellular responses was used in the development of
predictive toxicological paradigms for redox-active metal oxides and long aspect ratio (LAR) materials.
Their toxicities are being studied by using protein biomarkers (e.g. cytokine, chemokine, growth factor)
that are routinely analyzed by relatively expensive, time-consuming, and labor-intensive ELISA assays in
96-well plates. Compared to ELISA, a semiconductor electronic label-free assay (SELFA), which is based
on electrical current and carried out by nanowire field-effect transistors (nwFET), offers superior
detection sensitivity. This measurement is further facilitated by the use of a novel T-shape signal
amplification design. There are additional advantages such as the rapid turnaround time, multiplexing,
and low-cost integration to perform rapid throughput analysis. The goal of this project is to design a labon-a-chip system capable of rapid and quantitative determination of pro-inflammatory and profibrogenic cellular responses by LAR and metal oxide ENMs. Aim 1 was to fabricate and test the
performance characteristics (sensitivity and selectivity) of the nwFET biosensors in the detection of the
representative biomarker IL-1β, diluted in PBS. We have fabricated approximately 20 nwFET devices
includeing the T-shaped p-type Si nanowires in our clean room facilities at UCLA. The nanowires were
decorated by immobilized human IL-1β antibody. To avoid readout interference by fabrication defects,
we have calibrated each device before use and developed a portable chip-with-wire connection that
could be used in the lab where we perform biological experiments. Our data demonstrated that we
could achieve a ~30-fold higher sensitivity and comparable selectivity with the nwFET measurement
compared to ELISA. Aim 2 was to use the nwFET platform to quantify ENM-induced IL-1β production in
THP-1 cells exposed to a range of LAR materials such as CeO2 nanorods and MWCNTs. The parallel
analysis for IL-1β measurement using nwFET and ELISA has led to highly consistent results, which were
further confirmed by the magic red staining in THP-1 cells, a confocal visualization to discern lysosome
damage, NLRP3 inflammasome activation, and IL-1β production. In a small scale animal experiment, we
selected 3 ENMs with SELFA determined IL-1β release profile, with a view to predict their acute lung
inflammation. This allowed us to deploy SELFA to predict the inflammatory potential of a range of ENMs
in vitro, and validate the results with magic red assay and confirmatory animal experiment in vivo. Based
on the abovementioned progress, we are preparing a manuscript to publish our IL-1β analysis data. We
envisage that a key challenge to meet beyond this stage of testing is to advance to commercial
production of the biosensors to meet the objective of reduced cost. We are planning to expand our
measurements in using nwFET for more cytokine(s) in other CEIN interested toxicological scenarios.
HTS-6: Effects of MWCNT Nanocomposite Degradation Particles on Zebrafish Larvae
This seed project was initiated in response to one of the renewal goals of CEIN, namely to incorporate
commercial nanomaterials, including nanocomposites from which hybrid materials can be released
through sanding, grinding, weathering, and UV light, among others. In collaboration with the leading
chemical company, BASF, we studied two MWCNT composites, i.e. MWCNT-POM (polyoxymethylene)
and MWCNT-cement. These materials were subjected to two fractionation methods, namely probe
sonication and shaking, to derive sub-micron degradation particles for zebrafish toxicity testing. The goal
of this project was to investigate the environmental hazard potential of the MWCNT degradation
fragments on zebrafish larvae. The rationale is that the degradation of MWCNT composites by
mechanical abrasion and environmental weathering can result in environmental exposure. In order to
achieve the goal, Aim 1 was to study the release from MWCNT composites under two degradation
conditions: (i) sonication of the nanocomposite to mimic an intense mechanical abrasion process; (ii)
immersing the MWCNT composites in zebrafish growth medium, followed by agitation in an orbital
shaker for a week. Subsequently, Aim 2 was to utilize our previously developed (Theme 2, HTS-1) pulseexposure method to study the hazard potential of composite fragments (obtained from Aim 1) in the
gastrointestinal tract (GIT) of developing zebrafish larvae. To date, we have fully characterized the submicron degradation particles (MWCNT DPs) resulting from the aforementioned two degradation
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processes using TEM and confocal Raman microscopy. Based on TEM analysis, we ranked the degree as:
MWCNT-cement (probe) > MWCNT-POM (probe) > MWCNT-cement (shaker) > MWCNT-POM (shaker).
The acquired sub-micron fragments allowed us to perform hazard assessment using zebrafish larvae.
After repetitive (3x) pulse exposures, no significant growth retardation was found (larval length and
weight) in the larvae exposed to either the MWCNT-POM or the MWNCT-cement degradation particles.
Although the confocal Raman microscopy confirmed the presence of MWCNT in the GIT, we did not
observe any significant GIT damage as evidenced by studying digestive function. In contrast, we have
previously shown that CeO nanorods cause severe digestive malfunction. This pilot project shows our
adoptive approach to studying industrial nanomaterials, including the use of a developmental lifeform
to study the impact of released particles, fragments and ions. We have also published the study on the
impact of Cu nanoparticles on zebrafish embryos, after addition of the particles to a simulated septic
tank treatment system and written up in unpublished form in February 2015.
Impacts on the Overall Goals of the Center:
The work in Theme 2 continues our approach of using predictive toxicological paradigms premised on
adverse outcome pathways (AOP) to forecast the likelihood of in vivo toxicological injury, premised on
AOP’s, which also play a role in the pathogenesis of a disease. In the current period, this was
demonstrated by accomplishing predictive toxicological paradigms for nano-Ag, III-V semiconductor
materials, MOx’s and RE-based ENMs. In the case of MOx ENMs, we have previously shown that overlap
of the conduction band energy with the biological redox potential of select materials predict the MOx’s
that can generate cellular oxidative stress, leading to triggering of pro-inflammatory pathways in cells
and in the lung. The research in HTS-3 demonstrated that similar results for the 24 MOx’s previously
tested in in mammalian cells also applied to the growth of E. coli in minimal trophic media. Thus, of the
24 materials studied, ZnO, CuO, CoO, Mn 2 O 3 , Co 3 O 4 , Ni 2 O 3 , and Cr 2 O 3 were found to exert significant
growth inhibitory effects. This growth inhibition correlated with assays assessing bacterial membrane
damage and oxidative stress responses. Overall, there is good correlation of MOx hydration energy and
conduction band energy levels with the biological outcome. The similarity of the response in
mammalian cells, demonstrates that the mechanisms of MOx toxicity are consistent across different
taxonomic domains. Similarly, the generation of lysosomal injury and inflammasome activation,
resulting from the surface interactions of RE-doped UCNPs with cellular phosphate residues, has allowed
us to develop a predictive toxicological paradigm that links inflammasome activation to the generation
of chronic inflammation and pulmonary fibrosis. The SAR linked to phosphate complexation and
precipitation of REPO 4 on the particle surfaces, also allowed us to develop a safer-by-design strategy
using phosphonates to passivate particle surfaces. In addition to using our existing in vitro screening
methods, including the use of fluorescence-based methodology for HTS, the transition to luminescencebased methods allows the introduction of even more sensitive screening assays, which are less
susceptible to signal quenching than fluorescence-based methods. Moreover, the introduction of
nanowire field-effect transistors for lab-on-a-chip detection of cytokines and cellular biomolecules holds
the promise of further refining our screening assays. Altogether, the development of alternative test
strategies (ATS) that reduces or replaces animal testing, has allowed CEIN to participate in discussions
with a multi-stakeholder community between academia, government and industry to discuss its possible
use for nano EHS decision analysis and categorization. These accomplishments are discussed in Theme
7.
Our studies using the zebrafish embryo and larvae for HCS have allowed CEIN to engage in creative
environmental research, which allows broad categories of materials to be investigated in a novel way.
One example is the ability to perform environmental risk assessment of Cu-based fungicides by using
zebrafish embryo screening of the effluent obtained from a model wastewater treatment system. This
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research has demonstrated the importance of changing the bioavailability of Cu as a result of its organic
speciation, thereby allowing us to track the transformation of these materials in a complex exposure
environment without the need for direct particle imaging. The novel use of zebrafish screening
procedures has also been extended to Theme 5, in which zebrafish embryos and larvae have been used
for studying the effect of semiconductor III-V slurries, particulates, and ionic components on the
hatching, growth and lifestage development.
Major Planned Activities for the next period:
We will continue the development of predictive toxicological paradigms to perform safety testing,
ranking and development of tiered decision analysis for commercial and synthesized ENM libraries. We
will expand the use of commercial ENMs in order to be in alignment with the 2014 PCAST
recommendations for nano EHS, which advocates the “development of a multidisciplinary
nanotechnology environmental, health, and safety ecosystem that promotes non‐animal based
(alternative) test strategies for safety assessment and multi‐stakeholder participation in regulatory
decision making and safe implementation to facilitate market access of nanomaterials and
nanotechnology‐enabled products.” The specific exploration in each project is highlighted in each
section discussed above. In addition to addressing commercial ENMs, CEIN will also continue the use of
zebrafish studies in Theme 5 to leverage the success of this organism for high content screening, with
the ability to prioritize studies on aquatic and estuarine species in theme 5. We will work closely with
the investigators in Themes 4, 5 and 7 to develop predictive ecotoxicological approaches that will have
the same impact as achieved in mammalian systems. We are assisting Dr. Holden in the write up of a
workshop report, Considerations of Environmentally Relevant Test Conditions for Improved Evaluation
of Ecological Hazards of Engineered Nanomaterials, which will endeavor to outline predictive
toxicological approaches for in the field of nano-ecotoxicity. This necessitates continuous performance
mechanistic studies on new ENMs libraries, as well as implementation of safer design approaches, to
develop the SARs that can be used for Theme 6 modeling. In collaboration with theme 6, we have also
demonstrated the development of computational tools for deriving predictive relationships for quantum
dots cellular toxicity, based on meta-analysis.
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Theme 3: Fate, Transport, Exposure and Life Cycle Assessment
Arturo Keller (UCSB) - Theme leader & Professor, Bren School of Environ. Science & Mgmt.
Sharon Walker (UC Riverside) – Associate Dean and Professor, Chemical Engineering
Sangwon Suh (UCSB) – Associate Professor, Bren School of Environ. Science & Mgmt.
Theme 3 provides the UC CEIN with quantitative information on the fate and transport of the
nanoparticles (NPs), the life cycle implications of engineered nanomaterials (ENMs), and experimental
methods to measure and estimate likely NP exposure concentrations in different environmental media
(e.g. freshwater, estuaries, coastal, terrestrial).
Theme 3 Projects:
• FT-1: Life Cycle Impacts Assessment of Engineered Nanomaterials (Suh, Keller)
• FT-2: Exposure Assessment in Aquatic Environments (Keller)
• FT-3: Exposure Assessment in Terrestrial Environments (Keller)
• FT-4: Transformation of nanoparticles in wastewater treatment (Walker)
Major Accomplishments since February 2015:
FT-1: Life Cycle Assessment
The goal of this project is to perform screening Life Cycle Assessments (LCA) of different engineered
nanomaterials (ENMs), including metals, metal oxides, and carbon nanotubes, to predict the annual
mass of ENMs released to various environmental compartments (air, water, soils). This information
provides predicted environmental concentrations (PECs) of ENMs, for use in the dosimetry of
toxicological studies in CEIN themes. Building on our methodology that allocates the worldwide release
estimates for the top ENMs, we extended it to the use of ENMs in food. We found that the most
commonly used ENMs in food are titanium dioxide, silicon dioxide, calcium carbonate and silver. ENM
concentrations in food range from 0.5 mg/kg to over 3,000 mg/kg (for SiO 2 ). The estimate total use in
the U.S. for ENMs in this application is 35,000 to 60,000 metric tons per year. A large fraction (99+ %) of
these ENMs eventually pass through the wastewater treatment plant and end up in the treated effluent
(5-10%) or in biosolids (90-95%).
In addition we developed a stochastic “vintage” LCA model to estimate the release of ENMs to the
environment throughout time. A “vintage” model tracks the emissions from different years to estimate
the potential accumulation of ENMs in different compartments. This project focused on the cumulative
ENMs releases from the coatings and pigments markets, and the prediction of future releases based on
the ENMs production rate. We estimated the in-use and end-of-life releases for each ENM and market
individually, and the total release is the summation of these two. In-use releases are determined by the
rate of attrition of ENM during its use phase. This rate is based on experiments in previous studies. Endof-life releases are the portion of ENMs that is disposed with the product when it reaches the maximum
lifetime. We estimate that as of 2010, total SiO 2 releases from coatings and pigments were about 34,000
metric tons. We also predict that by 2020, total SiO 2 releases will reach 45,000 metric tons, due to the
increasing production of new ENMs and retirement of old products. These results will provide a better
understanding about historical ENMs releases and help manage ENM use in the future.
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The material flow analysis model developed by Theme 3 has now been incorporated into the webbased, open access framework developed by Theme 6. The release estimates also provide predicted
environmental concentrations that are used to design exposure studies in Themes 2, 4 and 5. The
release and exposure estimates are also being used by Themes 6 and 7 in the development of case
studies on Risk Assessment and Alternatives Analysis.
FT-2: Exposure Assessment in Aquatic Environments
This project seeks to determine the behavior of ENMs in complex aquatic environments such as
estuaries, with dynamic salinity, sediment and biota. Our previous studies showed that soluble EPS
isolated from a marine phytoplankton interacts with copper-based particles thereby affecting the
surface and colloidal properties of the particles. In a follow-up study, soluble EPS were extracted from a
freshwater (Chlamydomonas reinhardtii) and a marine organism (Dunaliella tertiolecta) and their effects
on the surface properties and fate of three nTiO 2 (uncoated P25, anionic and cationic coated TiO 2 ) were
studied. Interactions between EPS and nTiO 2 were investigated via electrophoretic light scattering and
infrared spectroscopy. EPS adsorbed to the surface of the nTiO 2 via electrostatic interactions as well
chemical bonding, which involves the carboxylic groups of EPS proteins. Phosphate groups in nucleic
acid or phospholipids of EPS also mediated interactions with the ENMs. The adsorption of EPS was
dependent on particle size, intrinsic surface charge, and hydrophobicity. Charge reversal of positively
charged nano-TiO 2 was observed at pH 7 in the presence of 0.5 mg-C/L EPS. The critical coagulation
concentration of nano-TiO2, a measure of their stability in aqueous media, increased in the presence of
EPS. These results indicate the presence of natural EPS can have a significant stabilizing effect on ENMs
released into natural waters, resulting in more bioavailability.
In another study we investigated the leaching of biocides (copper) from commercial antifouling paints,
and confirmed the presence of nanosized Cu in paint via scanning electron microscopy and dynamic light
scattering analyses. X-ray diffraction analysis showed that the main phase of copper in the paint is cupric
oxide (Cu 2 O). Release of copper from paint matrix and transformation of the Cu 2 O particles in natural
waters was monitored for 180 days. X-ray diffraction, X-ray photoelectron spectroscopy, and
transmissions electron microscopy were used to characterize the physicochemical phase of particles in
the paint leachate. The amount of copper released was strongly dependent on ionic strength of water,
surface material, and paint curing time. The range of nano-sized copper concentrations detected in lab
release experiments was between 0-180 days was 0-0.54 mg/L, 0-2.19 mg/L, and 0-7.46 mg/L in
freshwater, estuary, and seawater, respectively. The presence of nanosized Cu 2 O particles in paint
leachate was confirmed via TEM analyses. Toxicity of paint leachate to a variety of aquatic organisms
was also tested in collaboration with Themes 2 and 5. Quantification of nanoparticulate Cu released
from antifouling paints is useful for properly assessing the exposure levels of aquatic organisms to these
particles.
FT-3: Exposure Assessment in Terrestrial Environments
The goal of this project is to identify and quantify the physicochemical interactions between ENMs and
biological systems that lead to bioaccumulation, trophic transfer, and physiological. In particular, we aim
to quantitatively determine the uptake, bioaccumulation, biotransformation and transport of different
ENMs in CEIN Terrestrial Theme 4 studies. In collaboration with Dr. Mazer at UCSB we investigated the
interactions between terrestrial plants, ENMs (TiO 2 , CeO 2 and Cu(OH) 2 ), nutrients, and soil. This threepart project looked at how ENM fate and transport in the terrestrial environment through soil affects
plant uptake of the ENMs, how ENMs interact with important nutrients in soil and water, and how
plants are affected by the presence of nanomaterials during their life cycle. TiO 2 and CeO 2 at 100 mg
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ENM kg-1 soil were shown to significantly increase the bioavailability of phosphorous in potting soil and
farm soil, respectively, and TiO 2 was also seen to increase the water extractable fraction of P in potting
soil. No effects on P were seen in grassland soil, possibly due to its low natural concentration of P. In
transport studies all three ENMs were seen to be retained in the upper 3 cm of a soil column and
showed increased transport when coated with Suwannee River humic acid. We have found that the
photoactive ENMs TiO 2 and CeO 2 reduce the photosynthesis rates of Clarkia unguiculata plants grown in
fertilized potting soil, while non-photoactive Cu(OH) 2 does not. Additionally, no effects from ENMs were
seen in plants grown under low illumination simulating shade conditions. Together, these results suggest
that photo-induced ROS production by the two photoactive ENMs interfere with the photosynthetic
mechanisms of the plants. No effects were seen in plants grown in unfertilized soil, which may be due to
the production of more antioxidant compounds as a stress response to low nutrient conditions. We
began a number of experiments in which cucumber plants are exposed to nano-Cu in hydroponic or soil
systems. In addition to determining the bioavailability of the ENMs, we measured their uptake,
translocation and effect on plant physiology and metabolites.
The projects mentioned above address questions regarding actual environmental exposure levels in
Theme 4 studies, as well as the bioavailability of ENMs and nutrients needed for plant growth. The
information will also be useful for enhancing the Multimedia Environmental Fate & Transport model
developed by Theme 6.
FT-4: Transformation and Effects of Nanomaterials in Model Wastewater Systems
As the production and application of engineered nanomaterials (ENMs) continues to grow, the
environmental implications are of the utmost importance. As approximately 25% of American homes
still rely on decentralized wastewater treatment this project focuses specifically on septic systems and
the impact of ENMs on the septic performance. ENM studies in wastewater treatment plants have
determined that a majority of particles entering the treatment facilities are subsequently removed
through biosolids association; however a fraction of the particles is still released back into the
environment. The effects of ENM bioaccumulation within the septic tank are of particular interest as the
septic performance is governed by the effluent quality and the health of the microbial community.
Studies have reported toxicity is often experienced through bacterial membrane surface interactions
often amplified by an increasing ENM concentration in the experimental system. Therefore the objective
of this project is to monitor the impact of a model ENM (TiO 2 ) on the overall septic system performance.
A bench scale model human colon and model septic tank are being utilized to monitor the variations
within these complex systems due to ENM introduction. Traditional water quality tests, including pH and
chemical oxygen demand, are being employed to monitor effluent quality while genotypic tests,
including pyrosequencing, will assist in monitoring the health of the microbial community. Notably,
septic performance is being evaluated comparing exposure to food- or industrial grade TiO 2 . Since
March 2015, exposure experiments have been conducted in the model septic system using the industrial
grade ENM and analyses of samples collected are ongoing. Food grade experiments will begin in 2016.
Other CEIN-related projects:
Aggregation Behavior of 2D Engineered Nanomaterials (Walker, Brinker, Hersam)
Currently, we are examining the structural morphology of aggregates comprised of unique 2dimensional ENMs as well as the more traditional 3-dimensional ENMs. Some examples of 2-D (or
planar) ENMs include both carbonaceous materials such as graphene oxide, and inorganic materials such
as molybdenum disulfide. Prevalent 3-D ENMs include spherical and amorphous metal oxides, such as
titanium dioxide and zinc oxide. Morphology of aggregates, often quantified by fractal dimension, can
provide predictive insight regarding the transport behavior, namely, the deposition tendencies. When
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examining planar ENMs, the use of multiple microscopic methods will also be needed. Cryogenic
transmission electron microscopy (cryo-TEM) (Brinker) will be used in conjunction with atomic force
microscopy (AFM) (Hersam) to visually verify the fractal dimension measurements and calculations
(Walker) of the light scattering methods, as well as provide information on the parallel stacking of
individual plates. Since March of 2015, the fractal dimension measurement, conducted with static angle
light scattering has been ongoing for the graphene oxide and molybdenum disulfide particles across a
range of relevant simple, salt solutions. Further characterization (TEM and AFM) will commence in
2016.
A major goal of the center is to determine the likelihood of exposure to ENMs, and the concentrations
and doses at which humans and other organisms may be exposed. By providing estimates of ENM
releases to air, soil and water, and the concentrations of the releases (e.g. wastewater effluent,
biosolids), Theme 3 provides estimates of realistic exposure concentrations for Themes 2, 4 and 5. Since
many ENMs will be processed in wastewater treatment, understanding their transformation and effects
on these systems also serves to determine their fate, which is important for Themes 4 and 5, which deal
with the effluent and biosolids. We are advancing models to predict the behavior of ENMs in the
environment, which are modeled with Theme 6 tools. These findings are translated into information
used for risk and alternatives assessments in Theme 7.
Major Planned Activities for the Period:
Project FT-1 is completing the first application of the vintage LCA model and plans to extend it to other
ENM applications. Project FT-2 is working closely with Theme 5 on the fate and transport of Cu and
other ENMs in an estuarine mesocosm. Project FT-3 will be studying the transfer of ENMs from biosolids
to soils, in support of Theme 4 terrestrial mesocosms. Project FT-4 will begin evaluating other ENMs in
their septic system, including additional metal oxides and carbonaceous ENMs.
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Theme 4: Terrestrial Ecosystems Impact and Hazard Assessment
Patricia Holden, UC Santa Barbara – Professor, Environmental Microbiology – Theme Leader
Jorge Gardea-Torresdey, University of Texas, El Paso – Professor, Environmental Chemistry
Roger Nisbet, UC Santa Barbara – Professor, Theoretical Ecology
Joshua Schimel, UC Santa Barbara – Professor, Ecosystem Ecology
Short Summary of Theme 4:
The main goals of Theme 4 are to develop approaches to study, and to determine the impacts of,
selected manufactured nanomaterials (NMs) as related to terrestrial processes involving soils, microbes,
and plants, and then to model the processes to predict hazards at population, community and
ecosystem scales. Nano-TiO 2 , ZnO, CeO 2 , Ag-based, Cu-based, multiwalled carbon nanotubes
(MWCNTs), graphene, and carbon black (CB) are focal NMs on the basis of either their high production
volumes as per Theme 1, their hazards as per high throughput screening (HTS) in Theme 2, or their
propensity to migrate into terrestrial environments as per material flow analyses (Theme 3) and
transport simulations (Theme 6). Progress over the last year has been in modeling and measuring
multiple NM variants (e.g. MOx, MWCNTs, Ag- and Cu-based) for their impacts on microbial and plant
populations, microbial communities and trophic transfer, and plant-microbe interactions. We have
assessed MNM impacts on environmental microorganisms including bacteria and protists, and
broadened the understanding of how NMs are translocated into plants, and how they affect plant
health, food quality, and soil microbial communities that support plant growth. Our work has expanded
dynamic energy budget (DEB) models to better represent formation and depletion of reactive oxygen
species (ROS), and to simulate NM effects on environmentally-relevant bacterial populations and plantmicrobe interactions for soil-grown soybean. Theme 4 leads the Carbonaceous NM Working Group (C
WG, including participants from CEIN, US EPA, NIST and Lawrence Livermore National Laboratory or
LLNL). In association, several soil-grown soybean mesocosm studies were collaboratively conducted to
compare effects of MWCNTs, graphene, and CB on this major food crop’s yield, food quality, N 2 -fixing
symbioses, plant health, and soil microbial communities. Theme 4’s overall impact derives from
emphasizing hazard assessment of food crops, using a transferable ecological nanotoxicology system
that begins with screening NM hazards using environmentally-relevant bacteria and hydroponic plants,
mechanistically predicting hazards across terrestrial exposures, quantifying the potential for trophic
transfer via base microbial food chains, and judiciously examining bioavailability and trophic interactions
using terrestrial mesocosms.
Theme 4 Projects:
• TER-1 Interactions of metal, metal oxide, and carbonaceous NMs with environmentallyrelevant microorganisms (Schimel, Holden)
• TER-2 Toxicity and uptake of nanoparticles by terrestrial plant species (Gardea-Torresdey)
• TER-3 Metal oxide and carbonaceous MNM effects and fates in terrestrial soil systems
(Holden)
• TER-4 DEB bacterial population and plant growth modeling (Nisbet)
Major Accomplishments and progress in Theme 4 projects since March, 2015:
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TER-1: Interactions of metal, metal oxide, and carbonaceous NMs with environmentally-relevant
microorganisms
The goals of this project are to develop approaches for determining the impacts of metal, metal oxide,
and carbonaceous NMs on environmentally-relevant microorganisms, and to apply the approaches to
understand hazards to microbial populations, communities, and ecosystem-level microbial processes.
Theme 4 benefited from two studies led by Theme 2 (Godwin), one discovering that Cu ions impact
enteric bacteria differently from Cu NMs, and another demonstrating the use of rapid E. coli screening
to reveal that hydration and conduction band energies determine MOx NP toxicity, as was previously
determined by Theme 2 (Nel) for mammalian cells. Similar screening approaches are planned by Theme
4, using the environmentally-relevant N 2 -fixing symbiotic bacterium Bradyrhizobium japonicum USDA
110. Progress this year included refining a B. japonicum growth medium around a sole carbon source
which allows for validating dynamic energy budget model (DEB;TER-4) simulations of bacterial
population growth; the new medium also prevents ion complexation and precipitation including of Cu
ions shed from NPs, and supports testing effects of carbonaceous NMs (carbon nanotubes, graphene
and carbon black) on B. japonicum, which is also underway. A former seed project, collaborative with
LLNL and NIST, was completed to assess effects of multiwalled carbon nanotubes (MWCNTs) on
Pseudomonas aeruginosa bacteria and Tetrahymena thermophila protozoa as model prey and
predators, respectively. At low environmentally relevant MWCNT concentrations (4 µg/L to 1 mg/L),
there was no toxicity as evidenced by normal population growth, viability (protozoans), membrane
integrity, or reductase activity (bacteria). Bioaccumulation of 14C-labeled MWCNTs (provided by NIST)
was sensitively quantified by either liquid scintillation counting (LSC) or accelerator mass spectrometry
(AMS, at LLNL) to determine bacterial and protozoan MWCNT bioconcentration directly from media, and
MWCNT trophic transfer from prey to predator. Several novel methods were developed to support this
research, including new density gradient centrifugation approaches to separate protozoans from prey
and fecal pellets prior to 14C label quantification (by LSC or AMS). New methods in optical micrograph
image analysis were also developed to quantify MWCNT aggregates bioaccumulated in protozoans,
showing parity with 14C label quantification. This will allow future quantitative visualization of other
carbonaceous NMs (graphene or CB) for which 14C-labeled material is unavailable. Using 14C-labeled
MWCNTs, including the first use of AMS in nanoecotoxicology, MWCNT loading onto bacteria was
precisely quantified, as was uptake into protozoans by trophic transfer and direct feeding from media.
There was no MWCNT biomagnification from bacterial prey to protozoan predators. A major finding was
that protozoan bioaccumulation depended strictly on initial dose, rather than feeding regime. The
consequence to future experimentation is that direct feeding, an efficient exposure route for research,
can be used in conjunction with optical image analysis to quantify other C-based NM bioaccumulation in
protists. Lastly, with co-leadership from Theme 7 and the UC CEIN Executive staff, and with participants
from Themes 1, 2, 3, 5, and 6, Theme 4 led a 1-1/2 day workshop at UCLA in March that attracted 39
participants nationally and internationally to deliberate “environmental relevance” in ecotoxicology of
nanomaterials. A workshop report, written as a critical review synthesized from the participants’
contributions, is undergoing peer-review for publication as per the outcome of a prior successful UC
CEIN workshop in NM categorization.
TER-2: Toxicity and uptake of nanoparticles by terrestrial plant species
The objective of this project is to determine the biological impacts [6, 7] and uptake [8] of several NP
types in terrestrial plants. During this reporting period, new experiments were completed on mesquite
(Prosopis spp), alfalfa (Medicago sativa), lettuce (Lactuca sativa), wheat (Triticum aestivum), barley
(Hordeum vulgare), common bean (Phaseolus vulgaris), tomato (Solanym lycopersicum), corn (Zea
mays), radish (Raphanus sativus), and cilantro (Coriandrum sativum). Studies demonstrated that in
mesquite, a desert plant, CeO 2 NPs were mostly adsorbed onto the root surface as NPs. In common
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bean exposed to 0-500 mg/kg, seed Ce accumulation was driven by the soil organic matter (OM)
content, and seed nutrient quality was affected the most with high OM. In addition, OM induced a dosedependent seed Ce accumulation. At 62.5 and 125 mg nano-CeO 2 /kg, stress-related proteins were
upregulated. Seed proteins for nutrient storage (phaseolin) and carbohydrate metabolism (lectins) were
down-regulated in a dose-dependent manner. In addition, trophic transfer studies demonstrated that
adult Mexican bean beetles feeding on nano-CeO 2 -exposed plants accumulated 76% more Ce than
beetles feeding on plants grown with bulk-CeO 2 , suggesting particle size-dependent trophic transfer. In
wheat, nano-CeO 2 at 100 and 400 mg/kg agglomerated chromatin in nuclei, delayed flowering by 1
week, and reduced the size of starch grains in the endosperm, but increased grain protein. In barley,
plants exposed to 250 mg nano-CeO 2 /kg had higher (294 %) Ce accumulation, and higher P, K, Ca, Mg, S,
Fe, Zn, Cu, and Al, compared with control plants. Grains also had more methionine, aspartic acid,
threonine, tyrosine, arginine, and linolenic acid contents. However, at 500 mg/kg there was no grain
formation. In corn, at 800 mg nano-CeO 2 /kg, there was a 38% yield reduction and redistribution of Cu,
K, Mn, and Zn in kernels. In addition, FTIR studies showed that nano-CeO 2 at 0-500 induced changes in
root xylem of barley, rice, and wheat. In alfalfa, exposure to 250, 500, and 750 mg nano-CeO 2 /kg
reduced chlorophyll b by 64%, 48%, and 60%, respectively. In tomato, citric acid-coated nano-CeO 2 had
inconsequential effects on agronomic and physiological parameters, and did not affect the homeostasis
of nutrient elements in tissues or catalase and ascorbate peroxidase in leaves. Studies with nano-ZnO in
alfalfa and green pea showed different effects on plant physiology and seed quality. In alfalfa, exposure
to nano-ZnO, bulk-ZnO, and ZnCl 2 (0-750 mg/kg) showed that bulk-ZnO at 500 and 750 mg/kg and all
ZnCl 2 concentrations reduced germination (50%). In addition, nano-ZnO and ZnCl 2 reduced root and
shoot biomass by 80% and 25%, respectively. In another study, green pea plants were exposed to nanoZnO, 2 wt% alumina doped (Al 2 O 3 @ZnO NPs, or 1 wt% aminopropyltriethoxysilane coated NPs
(KH550@ZnO NP) at 250 and 1000 mg/kg. At 250 mg/kg nano-ZnO seed Zn increased, while Al 2 O 3 @ZnO
NPs at 1000 mg/kg significantly increased sucrose in grains [19]. Studies performed with Cu(OH) 2
(Kocide and CuPRO), nano-Cu, micro-copper (µCu), nano-copper oxide (nano-CuO), micro-copper oxide
(µCuO) and CuCl 2 in soil-grown cilantro (20 and 80 mg/kg soil) showed that nano-CuO, µCuO and CuCl 2
significantly reduced seed germination. In general, all Cu compounds altered one or more of the plant
nutrient elements including B, Zn, Mn, Ca, Mg, and S, and all of them reduced P in shoots. However, all
Cu NPs and Cu compounds increased Cu, P, and S in alfalfa shoots and decreased P and Fe in lettuce
shoot, excluding Fe in the CuCl 2 treatments. In radish sprouts, nano-Ag at 500 mg/kg reduced Ca, Mg, B,
Cu, Mn, and Zn accumulation and FTIR studies showed changes in the bands corresponding to lipids,
proteins, lignin, pectin, and cellulose.
TER-3: Metal oxide and carbonaceous NM effects and fates in terrestrial soil systems
The goals of this project are to assess the impacts of metal oxide and carbonaceous NMs on terrestrial
ecosystems through hazard assessment of microbial communities and plant-microbe interactions, and
to develop the capacity to predict NM effects on terrestrial ecosystems. A new visualization method for
phylogenetic soil microbial community composition data was developed to rapidly explore effects of
ZnO and TiO 2 NMs, led by Theme 6. A long-term (ca. 1 year) exposure of unplanted grassland soils to
natural, industrial, or engineered condensed carbonaceous nanostructured materials (biochar, and the
NMs industrial CB, and engineered MWCNT or graphene) was completed to examine effects on
microbial community biomass, respiration, and phylogenetic composition. While all materials affected
soil microbial communities relative to the no-NM controls, the engineered NM treatments were
indistinguishable from each other and from benchmark materials (unregulated industrial CB , and
natural biochar) treatments that served as negative controls for engineered NM effects. This study
tested the C WG proposal to use CB as a negative control NM for relative hazard assessment, and newly
uses biochar—a nanostructured material produced as an intentional soil amendment—as a natural
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negative control material. In another study, four soil-grown soybean mesocosm (greenhouse) studies
were conducted over 9 months: 1) an undergraduate thesis project to determine effects of B. japonicum
inoculation, versus no inoculation, on MWCNT effects to soybean growth; 2) a large scale study of two
different soils amended with three concentrations of either MWCNTs, graphene, or CB, all inoculated,
and with intermediate and final harvests; 3) a repeat of the first study, to determine N 2 -fixation
potentials of root symbioses; 4) a repeat of the second study, focusing on one of the two soils and with
added control plants to add temporal resolution for DEB modeling. In the first study, inoculation
apparently exacerbated effects of MWCNTs since plant growth was stunted compared to non-inoculated
plants. In the third (repeat) study, N 2 -fixation potentials were unaffected by MWCNT treatments. The
2nd and 4th studies were planned and conducted in collaborative dialog with the U.S. EPA. In the 2nd
study, plants experienced transient heat stress and became infested with insect pests (thrips).
Nonetheless, intermediate harvests for both soils and a final harvest for one of the soils were
conducted, and the measures (plant growth rate, plant biomass, leaf area, and leaf ROS and lipid
peroxidation) are interpretable for these realistically stressful growth conditions. Interestingly, NMs did
not affect the growth of heat- and pest-stressed plants. However, in the 4th study, healthy plants grew
differently according to carbonaceous NM type and dose. The resulting mesocosm datasets are large,
and all measures for the 4th study (plant growth rate, plant biomass, leaf area, N 2 -fixation potential, leaf
ROS and lipid peroxidation, bean protein and protein carbonyl, 15N plant tissue content, and plant
macro- and micronutrient contents) are under analysis. Soil microbial community analyses are planned
for the 4th study, to determine interactive effects to soil microbes from NM effects on plants.
TER-4: DEB bacterial population and plant growth modeling
The overarching goal of this project is to extend dynamic energy budget (DEB) bacterial population
modeling and plant hazard assessment into a model of the effects of NMs in the soil on planted
agricultural crop growth. This involves formulating and analyzing new bacterial and plant models that
predict hazard effects on selected food crops with their bacterial symbionts, using results of mesocosm
studies. This project responds to the need for transferable models of NM effects on ecological processes
through the use of DEB modeling. DEB models characterize the flow and transformations of energy and
key elements within organisms, making it possible to build models that can connect individual function,
population growth, and ultimately community composition and function. Previously, we developed a
general modeling framework appropriate for modeling bacterial responses to chemical and nanoparticle
stressors, the resulting DEB models being the first to invoke reactive oxygen species (ROS) as a
mathematically-represented damage-inducing “generalized compound” that impacts cell physiology and
population dynamics. In this period, we developed a more general, DEB-based, representation of ROS
dynamics in cells that allows tracking of ROS generation, transformation, and accumulation of the
associated cellular damage [25]. Once created, ROS causes “damage”. ROS dynamics are determined by
a control system with both positive and negative feedbacks. The positive feedback occurs when ROS
produces damage compounds that in turn accelerate ROS production. On-going DEB research focuses on
the development, analysis and testing of DEB-based models of N 2 -fixing terrestrial bacterial responses
to nano-CeO 2 and nano-copper (Cu and CuO) particles, which will be iterative with testing N 2 -fixing
bacterial responses to NPs mechanistically (TER-1) for populations, and at the ecosystem (plantmicrobe-soil, TER-3) scale. The latter project involves development of DEB models that are maximally
simple and parameter-sparse, yet include enough detail to make predictions on the large number of
variables measured in the CEIN soybean mesocosms. The models are being used to help interpret
completed studies on the responses of soybean exposed to metal oxide NMs and have contributed to
the design of mesocosm experiments involving carbonaceous NMs. Taken together, these studies are
defining a platform upon which many other bacterial-NM and plant-bacterial-NM interactions can be
predicted, and such modeling is a cornerstone of the UC CEIN’s vision of “ecological nanotoxicology”.
57
Theme 4 is delivering a new understanding of NM hazards in the terrestrial environment, including how
to assess and predict impacts to microbes, how food production and food quality are susceptible to
NMs, and how to mitigate agricultural impacts. The major impacts of Theme 4 research over the last
twelve months arise from the following:
• MWCNT trophic transfer from bacteria to protozoans was quantified for low amounts of 14Clabeled MWCNTs from NIST that were traced sensitively into prey and predators by use of
accelerator mass spectrometry at LLNL. This study newly quantifies low, environmentally
relevant, amounts of MWCNTs moving through trophic levels at the base of food chains,
showing that bioaccumulation occurs but not biomagnification, and that similar proportions of
NM are bioaccumulated whether protozoans are consuming MWCNT-encrusted prey or are
directly uptaking MWCNTs from media.
• Across a broad spectrum of NMs including metal oxide, metal, coated and uncoated, there are
effects to most food plants studied as measured by plant growth and yield, plant health and
nutrient content, and internalized NM or constituent metals.
• Nano-CeO 2 in particular commonly induces plant stress biochemical markers, and causes DNA
damage, reproductive delays, compromised seed quality or production, impaired light
harvesting apparatuses, and sap flow impairment. Further, there is greater trophic transfer of Ce
from plants into herbivorous insects when Ce is administered as NMs versus in bulk form.
• Copper compounds including salts, micron-sized Cu NMs, and commercially used Cu hydroxide
NPs, interfered with seed germination, and soil-grown plant chemical stoichiometry. Similar
types of changes were observed in Ag NM-treated plants.
• Carbonaceous engineered NMs (graphene and three types of MWCNTs) similarly impacted soil
microbial communities as compared to negative control benchmark materials of industrial CB
and biochar.
• One type of MWCNT impaired soybean growth in B. japonicum- inoculated soil. When
comparing effects of MWCNTs to those of CB and graphene, soybean plant growth was
differentially impacted across these NMs and doses; effects were not apparent across these
NMs when soybeans were heat-stressed or pest-infected.
• DEB modeling of plant growth, and microbial-plant interactions, advanced, and a generalizable
model of ROS effects, and organismal positive and negative feedbacks was developed.
• Theme 4 led the C NM WG. Theme 4 also contributed significantly to leading a workshop
regarding “environmental relevance” in ecological nanotoxicological exposures. A submitted
manuscript written as a critical review was led by Theme 4 for conveying main workshop
findings from the 39 participants.
Consistent with Center goals, Theme 4 will conduct research across its four projects over the next 12
months. Environmentally relevant N 2 -fixing bacteria will be studied for dose-dependent differential
growth effects and mechanisms of Cu-based NMs versus Cu salts, and of nano-CeO 2 . A study of low
concentration MWCNT trophic transfer from bacteria to protozoans will be published, as will a report of
methods for performing separations (NM aggregates, predator, fecal pellets, prey) in such trophic
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transfer studies. The range of food crop plants will continue to expand, as will the MNM core
chemistries and characteristics, so that the mechanistic understanding of MNM effects on plants can be
increased. Final samples and data from soybean mesocosms using graphene, MWCNTs, and CB will be
analyzed, and manuscripts prepared. Mechanistic research of C NM effects on the bacterial inoculant to
soybean studies, B. japonicum, will begin for treatments that indicate effects of C NMs on mesocosm
N 2 -fixation potential. In addition to the N 2 -fixing bacteria model, DEB modeling will work to more
effectively integrate plant and microbial effects of MNMs on soil-grown crops. DEB models will be tested
against soybean mesocosm data acquired during this period, and will be used to suggest additional
experiments to aid in model refinement.
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Theme 5: Marine and freshwater ecosystems impacts and toxicology
Roger M. Nisbet (UCSB) – Theme leader (from September 2015) & Professor, Ecology, Evolution and
Marine Biology
Gary Cherr (UC Davis) –Professor, Ecotoxicology
Hunter Lenihan (UCSB) – Theme leader (to September 2015) and Professor, Bren School of
Environmental Science and Management
Robert Miller (UCSB) – Associate Research Biologist, Marine Science Institute
Erik B. Muller (UCSB) - – Associate Research Biologist, Marine Science Institute
Andre E. Nel (UCLA) – Professor, Medicine (NanoMedicine and Nanosafety)
Toxic effects manifest themselves at all levels of biological organization (cell, organism, population,
community, ecosystem) and at multiple time scales. However, it is not possible to predict impacts on
populations or on ecosystem services using solely data on endpoints in suborganismal or organismal
studies. Thus theme 5 research encompasses studies of biological injury mechanisms in freshwater and
marine organisms in parallel with studies that aim to characterize the longer term feedbacks and
ecological interactions that influence how these injuries translate to impacts on ecosystem services. The
latter research requires long experiments testing specific hypotheses with carefully selected
nanomaterials. Quantitative predictions at population, community and ecosystem level also require
systems modeling, and theme 5 research places particular emphasis on dynamic energy budget models
that describe fundamental biological processes common to most organisms.
Testing the validity of model-based predictions across levels of biological organization (e.g. to predict
impacts on populations from data on cells, organs or individual organisms) requires long-running
experiments. This is an essential step towards predictive nanotoxicology.
Theme 5 research has two broad thrusts. Two projects focus on injury mechanisms for marine
organisms. This work has goals similar to much work in Theme 2, but specific to marine, estuarine and
freshwater organisms. The remaining work relates these findings, and other data on individual
responses, to ecologically important effects on populations and on ecosystem processes. There is also a
seed project on biodiversity. Specific theme 5 goals are: (i) to conduct high content and high throughput
screening of marine and freshwater organisms to link mechanisms of injury to specific ENM properties,
(ii) perform individual- and population-level microcosm exposures to assess the impact of specific injury
mechanisms on organisms and populations, (iii) use predictions based on HCS and microcosms to
evaluate ENMs with the highest-risk properties in mesocosm and case studies to quantify ecosystemlevel effects, and (iv) develop predictive systems models of ENM impacts through dynamic energy
budget (DEB) modeling.
Theme 5 Projects:
• MFW-1:
• MFW-2:
•
High Content Screening with Marine and Estuarine Organisms (Cherr)
Estuarine Microcosm, Mesocosm, and Field Experiments on ENM
Environmental Toxicity (Cherr, Lenihan, Miller, Nisbet)
MFW-3:
Predictive Dynamic Energy Budget models of toxic effects on an estuarine
ecosystem (Nisbet, Muller)
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•
•
MFW-4: Effects of Nanoparticle-based Antifouling Coatings on Marine Biodiversity
(Seed: Miller/Lenihan)
MWF-5: Use of Zebrafish Embryo HTS Platform to Assess the Hazard Potential of Nano-enabled
Industrial Products (semiconductor III-V materials and nanoparticles used in chemical
mechanical planarization) (Nel)
Projects MFW-1 and MWF-5 focus on injury mechanisms. Projects MFW-2 and MFW-3 relates these
findings, and other data on individual responses, to ecologically important effects on populations and on
ecosystem processes. Project MFW-4 (seed) is exploratory work to investigate effects of exposure
on biodiversity, a challenging, but vital part of ecological risk assessment.
MFW-1: High Content Screening with Marine and Estuarine Organisms
The objective of MFW-1 (in collaboration with MFW-2 and MFW-3) is to develop predictive toxicology
and screening tools that quantify ecological risks of ENMs entering estuarine, marine, and freshwater
ecosystems. This effort uses High-Content-Screening (HCS) assays with estuarine organisms designed to
test hypotheses about ENM toxicity generated by Theme 2’s High-Throughput-Screening (HTS). The HTSto-HCS approach is required because ENM bioavailability can vary dramatically as a function of changing
salinity, pH, NOM, and other features in natural estuarine, coastal marine waters. The toxicological
effects of ENMs can also vary across taxa from different ecosystems. HCS is designed to identify a
number of cytological (subcellular and cellular) injuries caused by ENMs simultaneously and results can
be used to generate predictions about ENM impacts to individuals, populations, and communities of
aquatic organisms. HCS research over the reporting period was organized around three specific goals.
Aim 1 focuses on marine phytoplankton and is a continuation of prior work designed to test the
hypotheses that (i) the toxicity of metal ENMs (ZnO, CuO, Ag, and CeO2) to marine pelagic, single-celled
phytoplankton - organisms responsible for much of world’s primary production (an essential ecosystem
service)- is highly dependent on the dissolution rate of metal ions from ENMs; and (ii) that impacts on
phytoplankton population growth, a proxy for primary production, are predictable based on
fluorescence-based HCS results that link ROS damage of mitochondrial membrane function to reduced
photosynthetic efficiency. We completed exposures and fits of DEB models to population growth rates
of marine phytoplankton for Ag, CuO, ZnO, and CeO 2 , comparing two phytoplankton species, three
periods (24, 48, and 72 hrs), and multiple cellular endpoints (mitochondria membrane potential,
membrane permeability, efflux potential, and reactive oxygen species generation). This work was done
in close concert with MFW-2 who tested responses of photosynthesis and population growth. We also
assessed cellular distribution of metals in two species. Data collection is completed, integration and
modeling is completed. The primary conclusion is that hypothesis (ii) is largely untrue: the only endpoint
or process of utility for predicting changes in population growth rate is photosynthesis. A MS is in
advanced preparation.
Aim 2 is to conduct in vitro HCS work with marine mussel hemocyctes (i.e., molluscan ”blood”)
investigating metal oxide and SWCNT impacts. 96-well plate experiments were used to determine
effects of ionic metal (silver, copper, zinc), metal oxide NMs (silver, copper, zinc), and SWCNT NMs on
hemocytes. Improvement of the HCS approach with hemocytes has included using a nuclear stain to
determine cell number for each replicate in every treatment, enabling normalization to cell number for
all cellular responses to different ENMs, across concentrations. Analyzed data has been prepared in a
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manuscript but additional data are needed for completion. A new UC MEXUS/CONACYT project entitled
Evaluating the potential toxicity of inorganic nanoparticles for potential biomedical and nutritional
applications with Universidad de las Americas Puebla, Mexico was funded to use mussel hemocytes as a
HCS tool for a wider range of ENMs from Universidad de las Americas Puebla as well as CEIN, and to
incorporate those data into the existing draft manuscript.
Aim 3 is to determine the impacts of ENMs on marine embryos and their efflux transporter defense
mechanisms. Experiments determined CuO NMs effects on development of sea urchin embryos (TorresDuarte et al. 2015, Wu et al. 2015). Two different CuO NMs were studied, one a highly purified NM from
Univ. Bremen (Madler and Pokhrel) that is marginally soluble, and a commercial NM from Sigma that
has very low solubility. Both were compared to soluble Cu2+. Oxidative stress responses (decrease in
total antioxidant capacity) were determined for all three copper compounds as was intracellular copper
levels. Key findings were that CuO NMs are internalized by embryos and impact normal development via
internalization and subsequent dissolution. Copper causes specific developmental abnormalities
including disruption of the aboral-oral axis as a result of the change in the redox environment. No
impact on hatching in either sea urchin or Pacific herring embryos was observed. In continuing work, we
initiated a collaboration with Prof. Chris Chang at UC Berkeley who has developed intracellular
fluorescent probes (CNIR4) that has a high affinity for Cu+ (rather than Cu2+) and does not bind to nanocopper. This infrared probe localizes regions of high copper in sea urchin embryos. Data generated are
being used to investigate cellular details of axis disruption by the CuO NMs.
MFW-2 : Estuarine Microcosm, Mesocosm, and Field Experiments of ENM Environmental Toxicity
The broad goal of project MFW-2 is to determine the ecological effects of ENM exposure, with the
ultimate objective of determining how injury mechanisms (from MFW-1 and MFW-5) translate to
impacts in realistic environments and at higher levels of biological and ecological organization, especially
population dynamics and ecosystem processes, that in turn impact ecosystem services. This work is very
closely integrated with Theme 3. The work over the reporting period had 5 aims. Aim 1 investigates the
effects of particle aging on toxicity. Aim 2 addresses long-term effects of nanomaterials on zooplankton,
both on individual animals and on population dynamics. Aim 3 (with Theme 3 and MFW-3) involved
studies of the effects of modified zero-valent iron nanoparticles on phytoplankton growth. This work is
reported elsewhere. Aim 4 was to complete construction of a multiparameter mesocosm and perform
an initial set of experiments.
For Aim 1, nano-Cu was aged in freshwater and seawater for up to 15 weeks and exposed to the
phytoplankton Isochrysis galbana at different time points during aging. In addition to determining
toxicity of the aged nano-Cu to the marine phytoplankton (by measuring growth rate, ROS production,
and internalized Cu), transformations of the nanoparticles during aging was monitored by (1) monitoring
different fractions of Cu: dissolved, nano, and bulk; (2) chemical species modeling using Visual MINTEQ
according to previous works done in Theme 3; and (3) transmission electron microscopy with energydispersive X-ray spectroscopy to image and chemically identify transformed Cu particles.
The theoretical background to Aim 2 was previously reported DEB modeling that showed that
information from standardized acute or chronic toxicity tests cannot alone predict population impacts of
exposure. A suite of experiments characterized the effect of silver nanoparticles (AgNPs) on individuals
and populations of Daphnia. The direct effect of AgNPs on daphnid survival, growth and reproduction
were measured using a number of food levels covering the range commonly found in natural
populations – much lower than the unrealistic levels used in standardized tests. The most important
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finding was that with realistic food levels, sublethal effects of AgNPs are substantially greater than those
observed with high food and Daphnia mortality is increased. Parallel experiments followed populations
experiencing the same AgNP concentrations for 60 days, with the important finding that the populations
were viable at nominal levels that are lethal to individuals.
Progress towards Aim 3 is reported by Theme 3 and in MWF-3. For Aim 4, the first fate and transport
experiments in collaboration with Theme 3 with CuO NMs and soluble Cu2+ were completed over
summer and are being analyzed and prepared for publication. Initial exposure experiments were
conducted with estuarine killifish (Fundulus heteroclitus). Exposure of fish to 400ppb CuO NMs in the
mesocosm had no apparent effect on fish. However, an important discovery was that when they had to
undergo adaptation to a typical salinity challenge, the reduced Na/K ATPase activity in the gill would not
permit salinity adaptation over a 3 day period. Continued experiments will determine the time frame
for gills to return to normal following exposures to CuO NMs.
MWF-3: Predictive DEB models of toxic effects on an estuarine ecosystem
DEB modeling in CEIN is split between themes 4 and 5. Project MWF-3 covers work specific to
freshwater and marine systems. During the reporting period, the scope of the research has broadened
with increasing emphasis on interpreting data from projects in themes 3 and 5 using “systems”
approaches that couple DEB models, toxico-kinetic and toxico-dynamic models to dynamic models of
nanoparticle transformations and fate. The research in the reporting period had 3 specific goals. Aim 1
(in collaboration with MWF-2) was to use a DEB model to relate data on long-running experiments on
zooplankton individuals and populations exposed to citrate coated silver MNMs. Aim 2 (in collaboration
with theme 3) was to formulate and fit a systems model that quantifies how feedback from algal
production of dissolved organic carbon compounds on toxicity of sulfide/silica-modified nZVI (FeSSi)
ENMs. Aim 3 (in collaboration with MWF-5) was to formulate and evaluate a systems model of the
hatching of zebrafish when exposed to CuO MNMs.
Aim 1: A DEB model was fitted to data (described above in MWF-2) on the response of individual
Daphnia exposed to different concentrations of AnNPs with food supply rates similar to those typically
occurring in natural populations. The resulting fitted model was used to predict population dynamics
with the aim of understanding why in the MWF-2 experiments, populations appeared to be viable at
nominal levels that are lethal to individuals. We tested two hypotheses: to explain the apparent
contradiction: (i) reduced feeding rates or increased metabolic rates of Daphnia exposed to AgNPs lead
to an increase in average food availability that compensates for a low food supply rate; (ii) DOC
produced by Daphnia mitigates AgNP toxicity. Hypothesis (i) is consistent with observations; tests of
hypothesis (ii) require additional experimentation to allow estimation of a new model parameter. These
experiments are complete and analysis is in progress. Two manuscripts are in advanced preparation.
Aim 2 modified a previously reported dynamic model to quantify how feedback from algal production of
dissolved organic carbon compounds impacts the toxicity of FeSSi MNMs to the freshwater alga
Chlamydomonas reinhardtii. The experiments (in theme 3) found evidence for steric stabilization of
FeSSi by algal organic matter, which led to a decrease in the particles’ attachment efficiency.
Transformation of FeSSi was slower in cultures entering a slow growth phase. High concentrations of
FeSSi caused a lag in algal growth, and reduction in steady state population size, especially in cultures in
exponential phase. We showed that these different outcomes are well described by a dynamic model
describing algal growth, organic carbon production and FeSSi transformations. This study showed the
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importance of feedback involving DOC produced by algae. A MS is in revision following positive reviews
(Adeleye et al. submitted).
Aim 3 developed and evaluated a mechanistic model of the hatching of zebrafish eggs that were
exposed to CuO MNMs in a high-throughput screening system and placed this model in an Adverse
Outcome Pathway (AOP) that also included CuO MNM dissolution and dissolved Cu bioaccumulation
(Muller et al. 2015). The study demonstrated that noncompetitive inhibition kinetics describe the impact
of dissolved Cu on hatching; it was estimated that indefinitely long exposure to 1.88 µM dissolved Cu in
the environment reduces hatching enzyme activity by 50%. The complexity arising from CuO ENP
dissolution and CuO ENP assisted bioaccumulation of Cu has led to apparently contradictory findings
about ionic versus ‘nano’ effects on hatching. Model-mediated data analyses indicate that this
discrepancy can be understood if, relative to copper salts, CuO ENPs increase the uptake rates of Cu into
the perivitelline space up to 8 times.
MFW 4: Effects of nanoparticle-based antifouling coatings on marine biodiversity (Seed)
Robert J. Miller, Hunter S. Lenihan, and Arturo A. Keller (Theme 3)
“Biofouling” by organisms that grow on manmade surfaces in the ocean increases drag, weakens
structures, and transports invasive species, and millions of dollars are spent addressing it and preventing
it using antifouling coatings. Most antifouling coatings at present are Cu-based paints, and some include
nano-scale Cu. CuO and ZnO nanoparticle-based paints are now available, and may reduce leaching of
metals while maintaining efficacy. However, their environmental impact has not been evaluated.
Nanomaterials can be toxic to aquatic organisms through several mechanisms. This project measures
the environmental impact of zinc and copper nanoparticle-based antifouling paint, compared to
traditional coatings, in terms of 1) biodiversity and 2) water quality. This information will be transferred
to state and federal regulators.
The project has two components. Aim 1 (in collaboration with theme 3) is to measure leaching
rates (under lab conditions) of metals from six focal paints including NP-based paints. Leaching was
measured at 2 salinity levels to evaluate the effect of estuarine conditions on release of metals. Aim 2 is
to test the biological impact and leaching rate (in field conditions) for the focal paints at three locations
across the California coast – Bodega Bay, Santa Barbara, and San Diego. This is being done by deploying
racks of fiberglass plates mimicking boat hull materials. The plates have been assigned to paint
treatments including 1) traditional Cu-based, 2) Nano-based copper, 3) Traditional zinc-based 4) Nanobased zinc. Each treatment is replicated at least 6 times at each location.
The work on Aim 1 is complete. Laboratory experiments were conducted using six antifouling
paints (four zinc oxide-based and two copper based) in two media (estuary and seawater). Release of
zinc over time was higher in estuary conditions compared to seawater for all four zinc-based paints. The
amount of nanosized and bulk zinc in leachate was negligible as dissolved zinc accounted for most of the
release. In general, release rate was higher in the nano-enabled zinc oxide-based paint compared to its
traditional (non-nano) counterpart. In the treatments coated with copper-based paints, release of
copper was faster in seawater than in estuary up to two months, after more release was observed in
estuary conditions (probably due to faster saturation in seawater). Similar to the zinc oxide paint
treatments, bulk copper was the most abundant form of copper released into media by the copperbased coatings, but dissolved copper was present at potentially toxic levels (> 1 ppm). The fraction of
nanosized copper was negligible due to the high ionic strength of the media. Preliminary analyses of the
results showed that the fate, and thus, environmental impacts of antifouling paints is based on the type
of biocide (zinc vs. copper), size of biocide used (nano vs. bulk), and water salinity.
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Aim 2 requires a long running field experiment. Racks of painted fiberglass tiles, were
constructed and deployed at the three sites in late spring 2015 to allow recruitment of fouling
organisms. Passive sampling devices were also deployed. The experiments have been checked regularly
for maintenance and will be retrieved and terminated after 8 months (March 2016). Counting and
identifying all organisms growing on the plates at the end of the experiment (total 8 months) will allow
us to detect effects on both species diversity and on abundance of single species. The project is ongoing
and we do not yet have data to report.
MWF- 5 Use of Zebrafish Embryo HTS Platform to Assess the Hazard Potential of Nano-enabled
Industrial Products (semiconductor III-V materials and nanoparticles used in chemical mechanical
planarization)
This is a recently initiated project with the aim of promoting collaboration between Themes 2 and 5. The
broad goals are: (1) to use zebrafish embryo high-content screening to assess the hazard potential of
nano-enabled industrial products as well as nanomaterials used in manufacturing processes that might
end up in the waste streams; (2) collaborate with other activities in Theme 5, including dynamic energy
budget (DEB) modeling, to quantify adverse outcome pathways (AOPs) and their implications at the
population level (Drs. Erik Muller and Roger Nisbet), and microcosm studies in marine and estuarine
organisms (Dr. Gary Cherr).
The research for goal 1 was structured under 4 “Aims”. Aim 1 was assembly and characterization of a
library of III-V nano and micron-scale materials, including GaAs, GaP, InAs, and InP as well as
representative ionic species, for study of the role of toxic waste products generated during the polishing
of semiconductor wafers. Although the ionic form of III-V materials (Ga3+, In3+, As3+, and As5+) have
been shown to exert toxicity in aquatic organisms (such as zebrafish, tilapia, and carp), the particulate
forms of these materials have not been extensively investigated. Aim 2 assessed the effect of these
materials on hatching. Different from Ag and metal oxide NPs, III-V particulates did not exert an effect
on embryo hatching or morphological development at concentrations up to 200 ppm. While we did
observe sodium arsenite, As(III) toxicity at >200 ppm, sodium arsenate, As(V), was non-toxic in the same
concentration range. Furthermore, we demonstrated that InCl3 and GaCl3 showed hatching
interference and declined survival at threshold concentrations of 120-200pm. This toxicity results from
the acidification of the Holtfreter’s medium due to a Lewis acid effect. Aim 3 is currently assessing
hazard potential in zebrafish larvae to see if this life stage is differently affected by the development of a
mouth at 5 days post fertilization, allowing nanoparticle ingestion and uptake into the gastrointestinal
tract. Among the III-V materials being tested, preliminary data suggest that sodium arsenite is the most
hazardous ionic form, while n-InAs and (to a lesser extent) n-GaAs particulates have the ability to reduce
survival. Aim 4 addresses the impact of the above materials on different larval stages to develop a
mechanistic understanding of the adverse effects of ionic and particulate III-V materials on the
gastrointestinal tract. We will also track the effect on adult zebrafish survival and assess the effect on
potential target organs, such as the gastrointestinal tract, the gill and cardiovascular system. Towards
goal 2, in collaboration with MWF-3, we developed and evaluated a mechanistic model of the hatching
of zebrafish eggs that were exposed to CuO Manufactured Nanomaterials (MNM) in a high-throughput
screening system and placed this model in an Adverse Outcome Pathway (AOP) (Muller et al. 2015). For
details see MWF-3 above.
The Theme 5 research over the past year addressed the third of the four overarching goals for years 610 of CEIN: to determine the potential of ENMs, selected through high throughput screening (HTS), SAR
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analysis, LCA and multimedia modeling, to impact ecosystem services in model ecosystems. This
research, alongside related work in themes 3 and 4, is an essential step towards CEIN’s vision of
generating predictive tools for environmental hazard assessment.
Important achievements in the reporting period include:
• Analysis and modeling of results from phytoplankton HCS assessment of numerous cytological
effects caused by metal oxide ENMs (e.g., ZnO, CuO, CeO 2 , nano-Ag) to quantify the extent to
which they are linked to reduced photosynthetic efficiency and reduced population growth. The
only cellular level data that allowed prediction of population growth rate involved
photosynthesis; the other metrics were shown to have limited predictive value.
• Further development of the HCS platform for mussel hemocytes as a tool for a wide range of
ENMs .
• Experiments on effects of CuO (as well as ZnO) ENMs on sea urchin embryos, that showed no
effect on hatching success (including Pacific herring, in contrast with findings for zebrafish) but
internalization of ENMs with inhibition of the major defense system for early life stages. These
findings highlight the need for testing platforms to include more marine organisms.
• A mesocosm experiment demonstrated impact of exposure to CuO on osmoregulation capacity
of killifish. This is an injury mechanism of particular importance in estuarine environments.
• Completion of the first study of the long-term (entire lifetime) effects on a zooplankter
(Daphnia) of exposure to a ENM (citrate coated silver) with food availability similar to typical
field levels that are up to 100X lower than those normally used in toxicity tests. At these
realistic food levels, there is a much stronger response of the animals to exposure than under
standardized test conditions.
• Completion of the first multi-generation population level study of the effects of sustained
exposure of a zooplankter (Daphnia) to a ENM (citrate coated silver). The results demonstrated
the importance of ecological feedbacks for predicting population level consequences from data
on individual organisms. DEB modeling tested two hypotheses on feedback mechanisms: (i)
impacts via the algal food environment; (ii) toxicity mitigation via zooplankton-generated DOC.
Major Planned Activities for the Next Reporting Period:
In September 2015, there were major changes in theme 5: a new theme leader (Nisbet) and a new
project (MFW-5) on the zebrafish HTS platform that strengthens theme 5 work on injury mechanisms.
Between September and December, we reviewed all theme 5 activities. With fixed funding, addition of
a new project implies reduced effort elsewhere. We decided to restrict new mesocosm studies to
simple experiments and to refocus the phytoplankton studies – already reduced in response to the 2014
budget redistribution. Current plans include:
• Further development and application of the HCS tools for phytoplankton, mussel hemocytes,
sea urchin and herring embryos and larvae. This will include ENMs from Mexican collaborators
in a new UC Mexus project.
• A substantial scaling back of the mesocosm work and restriction of its scope to narrower goals
than previously planned. Top priority will be minimally complex experiments to characterize the
impact of the biotic environment on the fate of ENMs. There are possibilities for targeted
experiments on killifish osmoregulation, but they will require non-CEIN resources.
• Priority in the marine phytoplankton work will be new field measurements of effects of ENM
exposure on primary production. To our knowledge, these will be the first such in situ studies in
the marine environment.
• The methods and the modeling approach of Stevenson et al. (2013) that were used to
characterize toxicity of Ag ENMs and FESSi will be applied to aged Cu particles.
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•
•
•
•
We will explore the possibility of developing HCS methodology for freshwater phytoplankton
involving response with and without algal produced DOC, thereby substantially potentially
reducing the time required for tests.
DEB modeling will continue to support the phytoplankton work, in particular the proposed new
in situ studies of primary production.
The tiles, deployed in spring 2015, for seed experiment on the impacts on biodiversity of
exposure of nanoparticle-based anti-fouling paints will be recovered and changes in biodiversity
determined.
A DEB model for zebrafish will be used to project population level implications of findings from
MWF-5. The primary aim will be to identify any circumstances where hazard rankings from lab
studies would be changed by ecological feedbacks.
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Theme 6: Environmental Decision Analysis for Nanomaterials
Yoram Cohen, UCLA – Professor, Chemical and Biomolecular Engineering – Theme Leader
Rong Liu, UCLA – Assistant researcher, Institute of the Environment and Sustainability
Robert Rallo, URV – Associate Professor, Departament d’Enginyeria Informatica i Matematiques
Andre Nel, UCLA – Professor, Medicine; Chief, Division of NanoMedicine
Arturo Keller, UC Santa Barbara – Professor, School of Environmental Science and Management
Hilary Godwin, UCLA – Professor, Environmental Health Sciences
Theme 6 research focuses on the development of rigorous approaches to identify and rank ENMs of
potential environmental concern. This goal is pursued through integration of knowledge derived from
high content data generated via HTS (Themes 2 and 4) and other toxicity studies (Themes 4 and 5), and
assessment of the environmental distribution of ENMs based on fate and transport (F&T) analysis based
on evaluation of potential ENM releases (Theme 3). Environmental impacts are governed by toxicity of
and exposures to ENMs. Therefore, estimates of potential ENMs exposure concentrations, dose, and
toxicity information are required for environmental impact assessment (EIA) to support decision making
regarding safe design and use of ENMs. Accordingly, Theme 6 over the past year has developed: (a)
advanced modeling tools (implemented for cloud-based computing) to assess the releases,
environmental distribution and toxicity of nanomaterials, and (b) case studies to evaluate the
significance of various factors (e.g., ENM properties, environmental conditions) that affect the
environmental exposure concentrations, toxicity and hazard. In accomplishing the above tasks, Theme 6
has deployed various advanced machine learning and statistical methods to explore voluminous ENM
toxicity data (Themes 2, 4 and 5) and to develop quantitative structure-activity relationships (QSARs).
Theme 6 is also developing Bayesian Network based models to assess ENMs potential environmental
impact by statistically integrating the body of evidence (including quantitative and qualitative
information) for ENMs toxicity and environmental exposure.
Theme 6 Projects:
• EDA-1: Computational models of Nanomaterials Toxicity (Cohen, Telesca, Rallo)
• EDA-2: Multimedia Analysis of the Environmental Distribution of Nanomaterials (Cohen, Rallo,
Keller)
• EDA-3: Environmental impact analysis for nanomaterials (Cohen, Godwin)
• EDA-4: Development of in-vitro Dosimetry Model to Improve ENM toxicity Analysis (Seed: Liu)
Major Accomplishments since April 2015:
In pursuing its objectives Theme 6 has accomplished the following:
• Developed robust and accurate QSARs for cellular uptake of surface-modified iron-oxide core NPs
• Developed QSARs for cellular association of Au NPs of different surface ligands and identified the
specific serum proteins significantly correlated with the cellular association of Au NPs.
• Derived predictive relationships for Quantum Dots (QDs) toxicity via meta-analysis
• Developed multiple data visualization tools for assessing the susceptibility of soil bacterial
communities to ENMs.
• Developed a computational simulation platform for assessing the release of ENMs to the
environment and the associated multimedia environmental concentrations.
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•
Developed an improved NP sedimentation model that accounts for the complete size distribution,
fractal structure, and permeability of NP agglomerates.
EDA-1: Quantitative Structure-Activity Relationships (QSARs) of Nanomaterials Toxicity and
Physicochemical Properties.
The improved Theme 6 workflow for nano-(Q)SAR development, capable of handling both linear and
non-linear models, was utilized to improve predictions for in addition to cellular uptake of surfacemodified iron-core oxide NPs [1] cellular association of Au NPs with different surface ligands [2]. The
resulting QSARs have been implemented as a web application. These improved QSARs, along with
previously Theme 6 developed QSARs for metal oxides NPs, provide quantitative predictions of cellular
NP uptake/association as a function of NP physicochemical properties, surface modifications, and
protein binding.
Establishing the relationship between physiochemical properties of ENMs and their toxicity based on
published literature data is often confounded by material diversity, and heterogeneity of reported data.
In order to address the above challenge, Theme 6 developed a meta-analysis (literature data
mining/knowledge-extraction) for assembly and generalization of published ENM cellular toxicity [3]. In
addition to initial models developed (based on data for cellular toxicity of QDs from more than 300
studies) for entire cell viability data, RF models were also developed based on subsets of the cell viability
data. In particular, RF models were developed for the two major cell anatomical types (epithelial and
fibroblast that account for 53% and 18% of the total QD cell viability data, respectively), MTT assay type
(which accounted for 56% of the total QD cell viability data), and cell lines (which is a subcategory under
the cell origin attribute accounting for 83% of the complete dataset). These subset RF models identified
similar set of descriptors (QD diameter, QD concentration (mg/L), surface ligand, exposure time, surface
modification, and assay type) and demonstrated comparable performance (R2≈0.67) to the RF models
developed for the entire cell viability data. It is noted that in the RF models developed for the composite
dataset (for both cell viability and IC 50 ), assay type was found to be of greater significance relative to cell
anatomical type. However, this should not be interpreted to imply that the latter attribute is not
relevant. Specific assays are typically used for specific cell types. In other words, the present body of
literature simply suggests that there is greater correlation between observed toxicity and assay type. In
further exploring the above, we note that substitution of assay type by cell anatomical type for the cell
viability RF model with the top six attributes led to model performance decrease from R2 of 0.67 to 0.64.
A χ2 test conducted between assay type and cell anatomical type resulted in a p-value ≲ 1×10-4, strongly
indicating inter-dependence of these attributes, consistent with the above marginal difference in cell
viability RF model performance. In addition, using a clustering-based approach, a number of robust
conditional attribute-IC 50 dependences were extracted from the compiled QD samples. The first
extracted conditional dependence: “If (surface ligand in {aminothiol, hydrophilicpolymer, lipid, silica},
assay type in {fluoresceinretentionassay, mtt, rtces, wst}, surface modification in {drug, toxin,
unmodified}), then IC 50 ≤ 38.6 mg/L” is supported by ∼80% of the 77 QD samples from 22 different
studies that satisfy its condition. Potential toxicity contributors to this conditional dependence include a
high percentage of samples with poorly stable surface ligands, toxic surface modifications and active
delivery. The second conditional dependence: “If (QD diameter in [3.12, 5.11] nm, surface modification
in {aminoacid, antioxidant, drug, nucleicacid, peptide}, exposure time = 48 h), then IC50 in [39.4, 175]
mg/L” is supported by 80% of the 64 QD samples that satisfy the condition. It is noted that >95% of the
above 64 QD samples were from four studies that appear to be from the same research group.
Examining the QD samples that support that above conditional dependence for IC 50 suggests that the
extended 48 h exposure period, small diameter and the specific surface modifiers may have all
contributed to either active cellular QD uptake and/or an increased toxicity response. The third
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conditional dependence: “If (assay type = crystalviolet), then IC50>1,585 mg/L” was extracted from a
single study. The extraction of such a biased conditional dependence (of limited generality) signifies that
it is important to evaluate the biological interpretation of conditional dependences identified from
machine learning approaches. Importantly, the above identified dependences directly suggest specific
QD attributes meriting further study for causative relationships with cytotoxicity.
In addition, Theme 6 expanded the analysis of Theme 4 data on the impact of ZnO and TiO 2 NPs on soil
bacterial communities via a multitude of advanced data visualization techniques [4]. Joint display of the
treatment distribution and the variance (contribution) of bacterial taxa responses were generated via
contribution biplots of subcompositional coherence property obtained from log-ratio analysis (LRA) of
the dataset. The above visualization clearly revealed that high doses of ZnO and TiO 2 NPs caused
significant compositional changes in soil bacterial communities. The above work demonstrated that
visual exploration could potentially assist in knowledge discovery and interpretation of data on soil
bacterial communities exposed to MNPs and thus evaluation of the potential environmental impacts.
EDA-2: Multimedia Analysis of the Environmental Distribution of Nanomaterials
Exposure assessment of ENMs is critical for EIA of nanomaterials. Accordingly, as part of EIA-Nano, a
model for assessing the potential release and environmental distribution of nanomaterials (RedNano)
[5] was developed integrating: (i) ENM emission estimates, based on the life cycle analysis approach in
Theme 3 (lifecycle environmental assessment for the release of nanomaterials (LearNano), (ii)
multimedia environmental distribution of nanomaterials (MendNano) model and other pertinent
approaches of estimating environmental concentrations of ENMs for various exposure scenarios, and
(iii) ENMs intake estimates for selected ecological receptors (e.g., based on uptake rate studies with
plants and aquatic organisms by Themes 4 and 5, respectively). RedNano is an online tool available as a
cloud-computing accessible simulator. Case studies for the release and exposure modeling of 6 metal
oxide NPs (Al 2 O 3 , ZnO, TiO 2 , SiO 2 , CeO 2 , Cu) in 10 different cities (i.e., Berlin (Germany), Bern
(Switzerland), Bogota (Columbia), Houston (US), London (UK), Los Angeles (US), Maricopa (US), New
York (US), Sao Paulo (Brazil), Wayne (US)) were conducted using RedNano and the simulation results
from batch scenarios were stored in NanoDatabank [6]. The results revealed, for example, that the
lowest estimated compartmental exposure concentrations for nano Cu in air and soil were in Houston
(2.4×10-3 ng/m3 and 5.3 × 10-3 µg/kg, respectively), in water in Los Angeles (3.1 × 10-4 ng/L), and in
sediment in New York (4.3 × 10-4 µg/kg). Exposure concentrations for TiO 2 and ZnO in air, water, soil and
sediment were higher among the six ENMs due in part to the higher ENM release rates. In support of the
CEIN investigation of the potential environmental impact of nano Cu, simulations of the environmental
distribution of nano Cu were carried out for the cities listed above for release rates associated with
various applications (e.g. cosmetics, aerosols, paints, pigments) as estimated from LearNano. The lowest
-3
release rate (2.5 × 10-5 Tons/yr) was for Bern, Switzerland) with highest release rate of 1.3 × 10 Tons/yr
being in London (UK) and 1.1 × 10-3 Tons/yr in Berlin (Germany). The highest exposure concentrations of
nano Cu were in the air compartment (atmosphere) in Maricopa (~0.14 ng/m3). The highest exposure
concentration in water and sediment of 0.15 ng/L and 0.15 µg/kg, respectively, were in Wayne (US)
likely due to the high precipitation rate in this region.
In addition to the above, modeling of sedimentation of nanoparticles was undertaken in support of CEIN
seed-funded project EDA-4 (now completed) which focused on assessing the implications of
administered versus delivered dose in toxicity ranking. A computational model was developed and
applied to successfully analyze experimental sedimentation data [8] as described in the summary of
EDA-4.
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EDA-3: Environmental Impact Analysis of Nanomaterials
Assessment of the potential environmental impact of ENMs is a major challenge given the rapid rate of
growth of nanotechnology and the scarcity of environmental monitoring data. Theme 6 is working on
developing in silico environmental impact analysis (EIA) platform in order to enable evaluation of risk
management and safe-by-design options for ENMs [9-11]. In this approach, an Environmental Impact
Screening (EIS) tool was developed to assess the information needed for performing an environmental
impact assessment following a weight of evidence methodology, where availability of toxicity
information and estimates of environmental exposure concentrations serve as input for impact
assessment. EIS was developed based on toxicity information regarding ENMs (e.g., from in vivo or in
vitro toxicity screening data stored in NanoDatabank and literature) for defining suitable impact metrics.
The subsequent step of EIA-Nano makes use of a Bayesian Network (BN) to enable decision making
while estimating, tracking and aggregating uncertainties throughout the analysis process. Case studies of
exposure modeling scenarios of 6 ENMs (Al 2 O 3 , ZnO, TiO 2 , SiO 2 , CeO 2 , Cu) served to validate the BN
approach, assess attribute significance, and incorporate expert judgement into the BN analysis. Using
simulation results for different regions and ENMs (EDA-3), a Bayesian Network model [7] was developed
to enable rapid assessment of the environmental mass distribution and exposure concentrations.
Making further use of the BN approach, a quantitative environmental impact index (EI) was then
calculated by combining the exposure concentrations of above ENMs and their toxicity probabilities.
Higher concentrations and toxicity probabilities of TiO 2 and ZnO resulted in higher impact indices
compared to other selected ENMs. Another BN model for nano-Cu [12] was developed, based on a
comprehensive set of exposure scenarios developed using simulation results of the releases and
environmental distributions of nanomaterials (obtained using RedNano; EDA-2), for a wide spectrum of
meteorological and geographical settings. The BN model for nano-Cu was also integrated with nano-Cu
toxicity information using the Cu data obtained from Copper Working Group (Themes 3&4). The ENM
attributes having significant impact on the toxicity of nano-Cu (using BN sensitivity analysis) were
identified as the ENM size, surface charge, reactivity, natural organic matter, and solubility.
Theme 6 EIA-Nano models (BNs) and data analysis tools (ToxNano, RedNano) were developed for
remote execution (i.e., cloud computing) as a complete impact assessment platform. These tools have
been used in various case studies demonstrating their suitability as a framework for the estimation of
ENMs releases and exposures, toxicity prediction and banding of potential ENMs impact. These case
studies incorporated the use of QSAR models, meta-analysis approaches for QD data, zebrafish toxicity
data, multimedia exposure modeling of a range of ENMs in different regions, as well as toxicity and
exposure modeling of nano-Cu. It is noted that Theme 6 is continuing its collaboration with the
nanoinformatics community to make its tools/models for environmental impact assessment available
and encourage their further development and standardization through a community-based effort.
EDA-4: Development of in-vitro Dosimetry Model to Improve ENM toxicity Analysis (Seed Funding)
It has been argued that delivered dose (i.e., NP mass settled per suspension volume) rather than
administered dose (initial NP mass concentration) should be considered for in vitro toxicity testing of
engineered nanoparticles (NPs). Accordingly, the primary goal of the project was to develop an
advanced model for estimating the delivered ENMs dose, with the following interrelated aims:
1) develop an in-vitro dosimetry model that considers the complete particle size distribution (PSD), 2)
measure ENM deposition rates needed for delivered ENMs dose calculation and validation, and
3) perform dose-response analyses based on both administered and delivered dose of ENMs. In order to
accomplish the above, a computational model (referred to as SP2N model) [8] was developed, using a
first principles “particles in a box” approach, to estimate ENM sedimentation (i.e., delivered dose)
accounting for particle Brownian diffusion and settling considering the full particle size distribution
(PSD), as well as the fractal structure and permeability of ENMs agglomerates. The SP2N model was
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evaluated using both external and internal experimental sedimentation data for metal-oxide NPs.
Detailed dose-response analysis revealed that hierarchical hazard ranking of 7 toxic metal oxide NPs
(obtained from in our previous toxicity study of a set of 24 NP), using EC 50 as the metric for calculating
delivered dose was similar to the ranking based on administered dose. This corrects the
misinterpretation in toxicity ranking through the use of simplified sedimentation calculations that
assume impermeable NP agglomerates of a single average size, which results in significant
underestimation of the settled NPs mass. Notwithstanding the above results, it is important to recognize
that in vitro dose-response outcomes could result from complex toxicodynamics, which include
triggering of dynamic cell response pathways involved in NP uptake, NP/cellular association and various
physicochemical factors that impact NP sedimentation and cellular response.
The activities of Theme 6 have impacted the CEIN main goals through the following:
• Supporting the CEIN mission of developing predictive toxicology via the construction of
advanced nano-QSARs. In this effort, Theme 6 collaborated with Theme 2 and University of
Toronto (Warren Chan’s group) on the role of protein corona in cellular association of AU
NPs. QSAR development was also expanded to include a new model for cellular uptake of
surface-modified iron-oxide core NPs. A collaboration with H. Godwin’s group (Theme 2)
resulted in a highly predictive QSAR for bacterial toxicity of metal oxide NPs confirming the
relevance of hydration enthalpy and conduction band energy for toxicity prediction. Another
collaboration (also with Godwin’s group) provided correlation analyses and data
visualization in support of the study on the bacterial toxicity of Cu NPs;
• In order to establish the significance of delivered versus administered dose on NP toxicity
ranking a improved NP sedimentation model was developed that accounts for the complete
size distribution, fractal structure, and permeability of NP agglomerates. The developed invitro dosimetry model allows CEIN researchers to estimate the amount of settled NPs in HTS
toxicity tests and thus assess the implications for toxicity ranking.
• Given the growing interest in evaluating the body of evidence regarding the ENMs toxicity a
novel approach was developed for deriving predictive relationships for QDs toxicity via
meta-analysis. Here Theme 6 collaborated with the US Naval Research Laboratory and
Theme 2 on knowledge extraction from compiled literature data;
• Given the need to better understand the impact of ENMs on microbial communities, Theme 6
collaborated with Theme 4 to assess soil bacterial community susceptibility via advanced
data visualization techniques;
• The computational simulation platform for assessing the release of ENMs to the environment
and their multimedia distribution has enabled rapid assessment of the potential multimedia
exposure concentrations for different ENMs.
• Integration of analysis of potential ENM releases and exposure scenarios with CEIN toxicity
information enabled the construction of a powerful Bayesian Network tool for assessing the
environmental impact of nanomaterials which accounts for the body of evidence with
considerations of data uncertainty.
In addition to the above, R. Liu and Y. Cohen organized and edited the first major thematic issue on
“Nanoinformatics for Environmental Health and Biomedicine“published by the Beilstein Journal of
Nanotechnology (https://www.beilstein-journals.org/bjnano/browse/singleSeries.htm?sn=36). This
thematic issue brought together the state-of-the-art in nanoinformatics with a focus on the latest
developments in nano-database management, nano-data curation, literature mining for nano-data and
meta-analysis, data mining/machine learning (e.g., QSAR development), evaluation of the body of
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evidence, simulation of nanomaterials fate & transport, simulations of nano-bio interactions, and
assessments of potential environmental and health risks associated with nanomaterials.
In continuing support of the efforts to develop suitable methods for assessing the risk potential
associated with ENMs, Theme 6 has participated in a number of workshops representing the CEIN.
These included the 2015 Nanoinformatics Workshop, 2015 Gordon Research Conference on
Environmental Nanotechnology, 2015 AIChE Annual Meeting, ASME 2015 Global Conference on NanoEngineering for Medicine and Biology, 2015 Sustainable Nanotechnology Organization Conference, 2015
CEIN exposure workshop, and 2015 QEEN Workshop: Quantifying Exposure to Engineered
Nanomaterials (QEEN) from Manufactured Products. Theme 6 researchers have given a total of 13
presentations (8 invited). In addition, Theme 6 has continued its support of the international
nanoinformatics effort through participation in the EU-US workshops (Dr. Cohen served as Co-Chair of
the Human Toxicity COR), US Government initiative on exposure modeling (I.e., QEEN workshop), and
weekly participation of the NanoWorking group.
Toxicity: Theme 6 will continue the Embryonic Zebrafish (EZ) toxicity modeling work in collaboration
with Dr. Stacey Harper’s group at Oregon State University. Data will be extracted from the provided
Nanomaterial-Biological Interactions (NBI) knowledgebase, in addition to integrating the phenotypes
into an EZ metric and developing improved BN toxicity model. In addition, our continuing collaboration
with US navy research laboratory will integrate newly compiled QD cellular toxicity data which will be
used for expanded meta-analysis. Theme 6 will also develop a robust QSAR for the rare earth oxide NPs
data generated by CEIN Theme 2.
EIA Analysis through integration of fate and transport simulations and toxicity information:
Multimedia exposure modeling will be undertaken for 13 ENMs (Al 2 O 3 , CNT, CeO 2 , Fe, Nanoclays, Ag,
SiO 2 , TiO 2 , ZnO, C60) for different selected cities (i.e., Berlin (Germany), Bern (Switzerland), Bogota
(Columbia), Houston (US), London (UK), Los Angeles (US), Maricopa (US), New York (US), Sao Paulo
(Brazil), Wayne (US)) for a range of ENM use applications. Results from the above simulations will be
used to generate a BN EIA model for establishing an environmental impact index/ranking for the above
ENMs.
Organizational system for unstructured ENMs data: Significant research progress by the UC-CEIN has
resulted in the generation of a large volume of data regarding ENMs physicochemical properties,
toxicity, and fate and transport. The generated data are of increased complexity and typically are
acquired and organized into unstructured datasets of high level of heterogeneity. The above pose a
number of challenges regarding data management, particularly with respect to the development of an
organizational meta-data system for unstructured ENM datasets, data curation/collection, QA/QC for
literature mined data, and data organization/classification. Similarity challenging is the analysis of ENM
data records, data sharing with different permission level, advanced searching and dynamic reporting,
interoperability with other nanoinformatics apps, and data visualization. The two data management
systems previously developed by Theme 6 were based on Microsoft Sharepoint and MySQL, while useful
for reasonably sized datasets, can no longer address the above challenges and keep pace with the
increased volume of ENM data generation and complexity. For example, SharePoint based data
management system (with SQL Server database embedded) and MySQL both require a pre-defined
schema and well-structured (or fixed structure) meta-data. The architecture of the above systems lacks
flexibility for accommodating the constantly changing level of ENM data complexity and heterogeneity
of unstructured datasets. Accordingly, Theme 6 will develop a new data management architecture that
is capable of handling the challenges associated with the increasing volume of unstructured and
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heterogeneous ENM data. For this purpose, a novel organizational meta-data system will be designed as
a flexible tree structure that will enable expansion (e.g., adding new ENM properties or investigation
attributes). Heuristic rules will be developed for QA/QC of ENM data. Moreover, advanced document
database platform, instead of a conventional relational database, will be utilized to better accommodate
the flexibility of the new meta-data system, improve the efficiency of data retrieval, reduce file
management tasks and enhance data security.
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Theme 7: Using UC CEIN Knowledge Generation to Engage and Impact Multiple Stakeholders
CEIN Theme Summary Report
Hilary Godwin, UCLA - Professor, Environmental Health Sciences - Theme Co-Leader
André Nel, UCLA – Professor, Medicine; Chief, Division of Nanomedicine – Theme Co-Leader
Barbara Herr Harthorn, UC Santa Barbara –Professor, Anthropology
Timothy Malloy, UCLA - Professor, Law and Environmental Health
The overarching goal of Theme 7 is to integrate and translate the research of the UC CEIN for discussion
and use by multiple stakeholder groups to assist the development of new policy approaches, safety
assessment, and safe implementation approaches for engineered nanomaterials (ENMs). This is being
accomplished by utilizing the UC CEIN’s body of knowledge to inform multiple stakeholder communities
about the potential adverse impacts of nanotechnology in the environment; working to integrate salient
scientific results into existing and developing nanotechnology decision frameworks; and elevating the
UC CEIN as a key thought leader of how predictive toxicological paradigms can assist nano
Environmental Health and Safety (EHS) policy and decision making. To achieve this goal, our focus has
been on enhancing relationships across stakeholder groups as well as recognizing the sensitivities facing
industry (e.g., confidential business information and changing established rules of engagement) with
respect to participating in open dialogue. In addition, by partnering with experts in academia, law,
policy, industry, and civil society organizations in a series of workshops, we have identified key priority
areas for engagement and science translation.
Theme 7 Projects:
• KNO-1: Stakeholder Engagement for Improved Science Utilization for Nano EHS Policy and
Decision-Making (Nel, Godwin, Malloy, Harthorn)
• KNO-2: Developing or Transforming Nano Regulatory Approaches (Malloy)
Over the past year, the UC CEIN has continued to expand its science translation and outreach efforts.
The knowledge and approaches generated in the UC CEIN are being used to engage national and
international thought leaders in the areas of nano EHS policy, governance, and anticipatory decisionmaking. Major accomplishments of KNO-1 include: completion of the multi-stakeholder workshop:
Studies of Manufactured and Engineered Nanomaterials (M&ENMs) (March 2015) leading to a Critical
Review piece (submitted to ES&T Feb. 2016); continued progress on the multi-stakeholder carbon
nanotube (CNT) validation study on pulmonary toxicity, stemming from the ENM Categorization
Workshop in May 2014; establishment of an Industrial Discussion Forum Series where CEIN is engaging a
broad range of industry partners in discussions about CEIN research advances and how these can be
utilized by industry to foster worker safety, safer design, rapid implementation, and responsible
commercialization of nanomaterials; submission of two videos to ACS Nano per their request
highlighting major findings of recently published articles (videos posted to the ACS Nano YouTube page).
Major accomplishments of KNO-2 include: preparation of two articles drawing upon outcomes from the
Advancing Alternatives Analysis (A3) Working Conference (October 2014) (referred to as the AA
Workshop); application of formal decision analysis tools to regulatory alternatives analysis in the
completion of a case study of alternatives to copper-based anti-fouling paints for recreational boats
where preliminary results were presented at the annual Society for Environmental Toxicology and
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Chemistry meeting (November 2015); collaboration with the UCLA Institute for Society and Genetics in
conducting an international survey of toxicologists regarding the viability and application of alternative
testing strategies in business and regulatory contexts.
KNO-1: Stakeholder Engagement for Improved Science Utilization for Nano EHS Policy and DecisionMaking
The goal of KNO-1 is to engage industry, NGOs, and regulatory agencies to develop opportunities for
intellectual exchanges between diverse stakeholders across sectors working within the ENM field.
Translation of the scientific work and research accomplishments in the Center to broad audiences is
crucial to transform nano EHS knowledge and enhance partnerships with multiple stakeholder groups.
As a leader in this area, the UC CEIN is well positioned to facilitate discussions about how emerging
scientific discoveries in this field can be made more useful and accessible to assist regulatory decisionmaking, with a specific focus on understanding how the Center can support efforts to optimize industry
safe handling by reducing the cost of compliance and regulatory changes and streamlining regulatory
processes to maximize timeliness of evaluation, while improving health outcomes. Engagement of multistakeholders by the UC CEIN is noted below:
The UC CEIN convened a 1.5 day multi-stakeholder workshop entitled Implementing EnvironmentallyRelevant Exposures for Improved Interpretation of Laboratory Toxicology Studies of Manufactured and
Engineered Nanomaterials (M&ENMs), referred to as the Exposure Workshop, at UCLA on March 19-20,
2015 with 40 national and international ecotoxicology researchers, exposure modelers, material
manufacturers, and government agency representatives. The need for the Exposure Workshop was to
develop a predictive toxicological approach for ecotoxicology based on expected environmental
exposures of nanomaterials. Discussions focused on the state of knowledge regarding ENM
environmental exposure conditions, what exposure conditions are used in assessing ENM ecological
hazard potential, what conditions should be simulated in ecological nanotoxicological research to best
inform risk management and mechanistic understanding, and how concepts such as environmental (or
laboratory) concentration, exposure speciation, dose and body burden can be utilized in interpreting
biological and computational findings. The basis for discussion at this workshop was premised on the
ideas presented in a review publication by Holden et al., “Evaluation of Exposure Concentrations Used in
Assessing Manufactured Nanomaterial Environmental Hazards: Are They Relevant?” (ES&T, 2014). A
Critical Review piece summarizing general recommendations from workshop participants has been
submitted for publication to ES&T.
Stemming from the multi-stakeholder workshop Categorization Strategies for Engineered Nanomaterials
in a Regulatory Context (May 2014), the UC CEIN has been conducting a voluntary multi-stakeholder
carbon nanotube (CNT) Validation Study. Participants of the workshop viewed alternative testing
strategies (ATS) worthy of consideration for categorization and regulatory decision making. Participation
from academics and researchers across the United States, Europe, and Asia contributed to the effort of
selecting a set of CNTs from various sources to be studied by commonly and individually preferred ATS
protocols. In this study, participants have been testing a series of CNT materials, both historically studied
and newly available, by mechanistic in vitro assays across a series of laboratories. Further decisions
about testing in vitro ranking of animals by a tiered approach can be made once the data are analyzed. If
confirmed that in vitro tests can predict the in vivo outcomes, then in vitro tests may gain acceptance as
a first pass screening tool to reduce the reliance on expensive animal testing. This could be done by
prioritizing and conducting in vivo tests only on those materials which show an in vitro toxicity potential.
Currently, we are in the process of data analysis, data collection, and data sharing. Future work will
include preparation of manuscripts for publication. It is important to understand that this is a voluntary
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effort that does not amount to an official validation exercise as required by the Organisation for
Economic Co-operation and Development (OECD).
In October 2015, Theme 7 participant and CNS-UCSB Director Barbara Harthorn gave invited testimony
at a Congressional Briefing on “Nanotechnology Policy: Evolving and Maturing” at the American
Chemical Society’s headquarters in Washington DC. Her discussion in Q&A included the ATS
development activities in the CEIN.
In December 2015, CEIN Director Andre Nel served as the Academic Chair and the CEIN Administrative
Staff served as the coordinators and hosts for the National Science Foundation’s annual Nanoscale
Science and Engineering Grantees Conference held in Arlington Virginia. This two day workshop, entitled
“Progress in Nanotechnology” brought together over 100 NSF funded researchers and agency
representatives to discuss the current state of the art in Nanobiotechnology, Nanomedicine, NanoEHS,
and Media and Society. The meeting program can be found at http://www.nseresearch.org/2015/.
This past year, Theme 7 has established an Industrial Discussion Forum Series where we are engaging a
broad range of industry partners in discussions about CEIN research advances and how these can be
utilized by industry to foster safer design, rapid implementation, and responsible commercialization of
nanomaterials. To ensure greater accessibility for participants, the forum is being held via online
webinars. The series was launched in November with two back-to-back presentations: “What have we
learned from carbon nanotubes?”- focusing on carbon nanotube market evolution and influence of
perceived risk and “What does this mean for graphene?”- will history repeat itself for graphene? Future
forum topics include but are not limited to discussions on silica, life cycle analysis, and nano EHS
decision support tools.
The UC CEIN was invited by ACS Nano to submit short videos highlighting the major findings of recently
published articles, “Reduction of Acute Inflammatory Effects of Fumed Silica Nanoparticles in the Lung
by Adjusting Silanol Display through Calcination and Metal Doping” and “Organ-Specific and SizeDependent Ag Nanoparticle Toxicity in Gills and Intestines of Adult Zebrafish.” These videos have been
posted on the ACS Nano YouTube page and provide increased visibility for the work of the Center with
the nanoscience and nanotechnology communities. In addition, the UC CEIN website
(www.cein.ucla.edu) continues to provide a broad and impactful overview of the scientific and
educational accomplishments of the UC CEIN. The UC CEIN continues to share researcher spotlights.
These spotlights provide key information about the societal benefits of the UC CEIN research while
educating the public on what the science means. Other social media outlets continue to disseminate
information about the UC CEIN progress and key developments in Nano EH&S. The UC CEIN Twitter (312
followers) and Facebook Page (257 likes) reach international communities of researchers as well as the
general public.
KNO-2: Developing or Transforming Nano Regulatory Approaches
The research focus of KNO-2, research on new or existing policy models, provides critical feedback to
allow regulatory agencies to respond to new and emerging data on ENMs. Malloy and Zaunbrecher are
exploring how regulatory approaches (including soft law, adaptive regulation, and prevention-based
approaches) leverage the range of predictive toxicological methods and decision-analysis tools under
development at the UC CEIN. The specific regulatory framework determines whether a specific test can
be applied for screening purposes, risk assessment purposes, or comparison purposes to assist
regulatory agencies in making decisions. Therefore, projects take a regulatory decision-centric approach
and include an analysis of the limitations and opportunities in the use of emerging science and policy
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approaches in existing regulatory frameworks. They also take into account the interest of other
stakeholders such as industry and NGOs. KNO-2 also focuses on how predictive toxicology methods
could be used in regulatory alternatives analysis (AA), to improve prevention based approaches in the
regulation of chemicals. Those within KNO-2 work closely with other themes within the UC CEIN to
provide insight on the potential translation of developments from the UC CEIN into the regulatory and
industry setting. In addition, KNO-2 is concerned about improving regulatory approaches. Analysis of
potential policy reforms involves policy adaptations (incremental changes to existing statutes and
procedures) as well as more transformational visions of regulations and treaties.
Since March of 2015, KNO-2 has focused upon the application of formal decision analysis tools to
regulatory alternatives analysis, using a case study of alternatives to copper-based anti-fouling paint for
recreational boats. Two of the alternatives incorporate ENM into the paint formulation. The first stage
of the project focused on the use of probabilistic approaches to address data gaps. Zaunbrecher
presented preliminary results at the annual Society for Environmental Toxicology and Chemistry meeting
in November. Over the next year, KNO-2, in collaboration with EDA-3, will complete an alternatives
analysis using the case study and including data generated by other CEIN Themes demonstrating the
value and limitations of such approaches in regulatory settings. In addition, KNO-2 collaborated with
the UCLA Institute for Society and Genetics in conducting an international survey of toxicologists
regarding the viability and application of alternative testing strategies in business and regulatory
contexts. A paper presenting and analyzing the results of the survey and setting out policy
recommendations is in preparation.
KNO-2 has coordinated preparation of two articles drawing upon outcomes from UC CEIN’s Advancing
Alternatives Analysis (A3)- Working Conference (October 2014) at UCLA. This meeting (referred to as the
AA Workshop) brought together over 50 leaders in the fields of AA, toxicology, engineering, and decision
making to build the knowledge and networks necessary to develop effective AA tools and methods. The
articles discuss the promise and limitation of integrating predictive toxicology and decision analysis tools
into AA, respectively, and the recommended next steps to accomplish this goal. The conference
proceedings will also encourage further collaboration and capacity building, and serve as a foundation
for future actions to blend the disciplines of predictive toxicology, decision analysis, and AA. As part of
the UC CEIN’s outreach activities, the conference proceedings publication will be useful in facilitating
future projects and networks between the UC CEIN and members of the regulatory AA community.
The mission of the UC CEIN is to use a multidisciplinary approach to conduct research, knowledge
acquisition, education, and outreach to ensure the responsible use and safe implementation of
nanotechnology in the environment. Theme 7 has continued to collaborate with other Center themes in
a multidisciplinary approach in order to inform multi-stakeholder groups such as academia, NGOs,
industry, and state and federal agencies on the impact of the Center’s research. Theme 7, in addition to
Theme 4, contributed significantly in leading the multi-stakeholder Exposure Workshop regarding
“environmental relevance” in ecological nanotoxicological exposures. This has led to a manuscript
written as a Critical Review conveying main workshop findings from the 40 international participants
which represent academia, industry, NGOs, and government agencies. Over the next year, Theme 7 will
collaborate with Theme 6 on completing an alternatives analysis using data generated by other CEIN
themes, which will demonstrate the value and limitations of these approaches in regulatory settings. In
addition to working across themes, Theme 7 collaborated with the UCLA Institute for Society and
Genetics, conducting an international survey of toxicologists on the viability and application of ATS in
business and regulatory contexts. The publication in progress presents and analyses the results of the
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survey and sets out policy recommendations for those in the industrial and regulatory fields. The UC
CEIN continues to be recognized as one of the leading think tanks for knowledge and advice regarding
the safety assessment and safe implementation of nanomaterials in the environment. Industry
representatives have actively participated in open discussions about the utility of UC CEIN ATS
approaches for hazard assessment, and several companies volunteered to actively participate in our
voluntary CNT Validation Study to confirm the use of ATS to predict in vivo outcomes. The start of our
Industrial Discussion Forum Series has led us to engage a broad range of industrial partners on CEIN
capabilities and research advances, specifically on how these can be utilized by industry to foster safer
design, rapid implementation, and responsible commercialization of nanomaterials. Forming
relationships with our industry partners will allow for further communication and collaboration. The UC
CEIN faculty continues to participate in high profile international scientific and policy forums to
disseminate the advances we have made to a broad audience. Through strengthened interactions with
the Environmental Protection Agency’s Office of Research and Development (the research branch of the
EPA) and the Office of Pollution Prevention and Toxics (the division tasked with regulatory authority
over the new chemicals program), the U.S. EPA has not only worked to adjust their internal research
mission to capture some of the research being carried out by the UC CEIN, but has also given
consideration to predictive toxicology screening during the pre-manufacturing review process.
Major Planned Activities for the Next Reporting Period:
In the coming year, Theme 7 will continue to focus on the integration and translation of UC CEIN
research for use by multiple stakeholders to assist the development of new policy approaches, safety,
assessment, and safe implementation of ENMs.
• Completion of the voluntary multi-stakeholder CNT validation study (data analysis, data
collection, and data sharing) and preparation of manuscripts for publication (KNO-1).
• Continuation of the Industry Discussion Forum Series where the UC CEIN engages industry
partners in discussions about UC CEIN research advances and how these can be utilized by
industry to foster safer design, rapid implementation, and responsible commercialization of
nanomaterials (KNO-1).
• Collaboration with EDA-3 in completing an alternatives analysis using the case study (as
described in KNO-2) and data generated by other CEIN themes demonstrating the value and
limitations of such approaches in regulatory settings.
• Submission of a publication presenting and analyzing the results of an international survey
performed by KNO-2 and the UCLA Institute for Society and Genetics of toxicologists regarding
the viability and application of ATS in business and regulatory contexts as well as setting out
policy recommendations.
• Completion of two publications from the AA Workshop (as described in KNO-2) discussing the
promise and limitation of integrating predictive toxicology and decision tools analysis in AA. In
terms of UC CEIN’s outreach activities, the conference proceedings publication may be of use in
facilitating future projects and networks between the UC CEIN and members of the regulatory
AA community.
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10. Center Diversity
The UC CEIN is committed to ensuring the cultural, gender, racial, and ethnic diversity of the UC CEIN at
all levels, particularly courting involvement of women and underrepresented minorities as UC CEIN
participants. We seek to ensure the broadest diversity possible by:
• From the inception of the Center, we have strived to place female and minority faculty in
positions of leadership within the Center, where they can serve as positive role models for
young scientists. Our Center leadership currently has 3 senior female faculty who interact with
students and postdocs across the Center on a regular basis.
• Strategically engaging minority-serving institutions as full research partners in the Center. Our
partners include 4 Hispanic-Serving Institutions (HSIs): University of Texas, El Paso (UTEP),
University of New Mexico (UNM), UC Riverside (UCR), and UC Santa Barbara (UCSB). Students
and postdocs from UTEP, UNM, UCR, and UCSB participate in our Center's workshops, annual
meetings, and working groups.
• UTEP, UNM, UCR, and UCSB participate in undergraduate mentoring programs- during Year 8,
CEIN-affiliated faculty at these four campuses mentored a total of 17 undergraduates.
Additionally, there were four REU summer program participants at UNM. All of these campuses
provide laboratory research experience underrepresented minorities (URMs). These programs
encourage students to seek advanced educational opportunities in the sciences.
• Seeking partnerships with faculty at community and technical colleges, including De Anza
Community College and Pasadena City College, to integrate CEIN-authored curriculum
(Sustainable nanoMAterials Laboratory/SMAL) into current nanoscience programming.
• Encouraging our members to participate in public outreach events and to contribute to
organizations that encourage K-12 interest in STEM, such as Science Buddies, public and
independent schools, and local science museums, nature centers, and public libraries.
• Recruiting a diverse postdoctoral researcher pool. All open positions within the Center
(including postdoctoral researchers) are advertised widely, and efforts are made to recruit a
diverse applicant pool for consideration.
• The Center incorporates job skills and professional coaching into our annual Student and
Postdoctoral Fellow Leadership Workshop as well as into regular Center-wide student/postdoc
conference calls, both of which assist students/postdocs in applying for careers in academia,
government, NGOs, and industry.
Progress in the past year period:
As our Center matures, we have increased engagement from a diverse range of faculty, research staff,
postdoctoral scholars, graduate students, and undergraduates in our research and education/outreach
activities.
We have successfully engaged a high percentage of female researchers amongst our research staff
(38%), graduate students (58%), postdocs (32%), and undergraduates (52%), which is notable given the
traditionally low numbers of females in the fields of science and engineering. Additionally, 56% of our
graduate students and 90% of our undergraduate participants were US citizens in the current reporting
year.
While the Center does not have influence over the recruitment of new female and/or minority faculty at
our member institutions, we are proud of the strong female representation in our Center leadership,
with 3 area leads serving on our Executive Committee and an additional 2 female faculty active in the
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Center’s research and educational development activities. We feel this strong representation of female
faculty leadership sets a strong example to up-and-coming scientists.
Plans for the next reporting period:
Over the next year, we will continue to strengthen our education and outreach partnerships, particularly
those with the California Science Center, the Santa Monica Public Library, and Science Buddies.
Our partnership with Science Buddies is notable for many reasons, including diversity and reaching
diverse audiences: In 2013, the Science Buddies website was visited by more than 11 million unique
users (students, parents, teachers), including underrepresented minorities, and 56% of these visitors
were female. Since June 2013, the date our Tiny Titans science fair project was published on Science
Buddies’ website, over 17,000 unique users have viewed our science fair project, of which
approximately 58% of are female. Since September 2015, the date our Looking Downstream project was
published on Science Buddies’ website, it has been viewed by 2,000 unique viewers, of which
approximately 64% are female.
We will continue to participate in UCLA and UCSB outreach events, such as NISE Net’s NanoDays, geared
towards public and K-12 audiences.
The Center remains committed to our partnerships with UTEP, UNM, UCR, and UCSB and will explore
avenues through existing and new programs to strengthen the path to higher education opportunities
for minorities and women in the field of environmental nanotechnology.
We have recruited a diverse External Science Advisory Committee who will provide us valuable input on
the Center's outreach and diversity goals.
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Year 8 Annual Report
11. Education, Career Development, Knowledge Dissemination, and Integrative Efforts
Hilary Godwin, UCLA – Professor, Environmental Health Sciences – Theme Leader
Andre Nel, UCLA – Medicine; Chief, Division of NanoMedicine
Arturo Keller, UC Santa Barbara – Professor, Bren School of Env. Science & Management
Korin Wheeler, Santa Clara University – Assistant Professor, Chemistry
Short Summary of Education Program
The overarching goal of UC CEIN Education is to ensure that the science performed and the discoveries
made within the Center are leveraged to serve broader societal needs; to this end, UC CEIN Education
fosters cross-Theme and cross-campus dialogue and interaction by designing programs that foster
collaborative interdisciplinary science, advance discovery and understanding while promoting teaching,
training, and learning, mentor students and postdocs, and include the participation of underrepresented
groups in the sciences.
Following is an Education Summary Report for Year 8 (April 1, 2015-present), based on UC CEIN
member self-reporting. Education programming occurs at all UC-CEIN sites; to capture information on
this important programming and its participants, Center members report on it via an online reporting
mechanism, http://www.surveymonkey.com/s/CEINEducationOutreachReport.
Since April 2015, UC CEIN education, presentation, and dissemination highlights include:
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107 Talks
11 Posters
34 undergraduate students in 9 UC-CEIN labs
CEIN research in teaching: 8 courses on 5 campuses
Informal Science Education and Public Outreach included programming at K-12 schools &
summer camps for over 1,000 K-12 students & 50 K-12 teachers
Organization and Integration of Education Projects
CEIN Education consists of four project areas and one seed project. Project abstracts follow, while the
aggregate quantitative impacts of CEIN Education were summarized on the previous page of this report.
Project 1: Student/Postdoctoral Mentoring and Professional Development
The primary goal of the UC CEIN’s student/postdoctoral mentoring and professional development
program is to improve participants’ workforce preparation and professional skills by offering mentoring
activities and targeted professional development workshops. To help the Center’s students and
postdocs develop effective, professional communication skills for presenting their research, the Center
offers participant-centered activities and workshops throughout the year. Individual workshops focus
on spoken presentation skills or on written communication, and participants receive targeted feedback
on their skills and suggestions for areas for substantive and presentation skills improvement during each
workshop. The Center’s yearly Leadership Workshop offers students and postdocs a chance to network
with each other, engage in cross-thematic group and cross-campus interactions, and to improve on their
own mentoring and leadership skills.
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Project 2: Course Development, Workshops, and Learning Tools
The goal of this project is to develop and disseminate educational outputs related to nanoscience and
the environment. Educational outputs include lectures, workshops, and online content related to
Center research. CEIN has partnered with Science Buddies to create two validated, step-by-step science
fair project ideas, “Tiny Titans: Can Silver Nanoparticles Neutralize E. coli bacteria?”, and “Looking
Downstream: Could Nanosilver in Consumer Products Affect Pond Life?” These and other educational
outputs, such as our NISENet Linked Product, Oil Spill Clean Up Simulation, contribute to stakeholder
understanding of concepts related to nanoscale science and engineering, fill gaps in the stakeholder
knowledge base, and provide a springboard from which the Center can build future collaborations and
partnerships.
Project 3: Informal Science Education (ISE) and Public Outreach
The goal of our public outreach projects is to provide formal and informal opportunities for dialogue
between the Center and its stakeholders, and to expand the knowledge base on research, societal
implications, and risk perception related to the environmental implications of nanotechnology. The
Center engages in public outreach by hosting academic conferences, seminars, and symposia, and by
participating in public events. Yearly public events include NISENet’s NanoDays (Los Angeles and Santa
Barbara), a public lecture and discussion at the Santa Monica Public Library, and UCLA’s “Exploring Your
Universe” event. Additionally, the Center collaborates with CNSI’s ArtSci program every summer to
introduce “nanoscience and the environment” concepts to high school students, and Education partners
with the California Science Center for NanoDays with the aim of reaching underserved audiences.
Project 4: Synergistic/Integrative Center Activities
To promote collaboration, cross-fertilization, and interdisciplinary partnerships across the UC-CEIN and
with other research partners, the Education group helps to develop and deliver mechanisms to support
face-to-face and web-based meetings, such as monthly working group meetings, seminar speakers, and
the Center’s annual meeting. Monthly working group meetings include the Carbonaceous Working
Group, which is cross-Theme and cross-campus.
Project 5: Sustainable nanoMAterials Laboratory (SMAL) (Seed Project) Catherine Nameth (UCLA)
and Korin Wheeler (Santa Clara University)
This is a curriculum development project funded by the Center since June 2014. This curriculum
development project aims to translate the cutting-edge research of the UC-CEIN to an undergraduate
population by collaboratively designing and developing a research-based laboratory module for the
undergraduate chemistry classroom. In the Sustainable nanoMAterials Lab (SMAL) module, students
will evaluate the role of common biological macromolecules in nanotoxicity; this module will be based
upon the high throughput (HTP) assays already established at UC-CEIN. By bringing scientific research to
the classroom, undergraduates will engage in a learning-by-doing approach, thereby providing students
with an authentic, interdisciplinary research experience with real-world applications. Specifically,
students will be exposed to issues considered in the evaluation of chemical toxicity (in human health
and the environment) and techniques involved in sterile cell growth and safe handling of laboratory
chemicals. Many students traditionally underrepresented in the sciences do not seek out science majors
and research experiences in particular. By introducing undergraduates to research at an introductory
level, we extend the reach of the traditional research model and engage these students in the scholarly
community early in their career.
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Integration of Education Projects
CEIN Education Coordinator Catherine Nameth serves as the day-to-day point-person for the planning,
implementation, and evaluation of CEIN’s education projects. Nameth works in partnership with UCSBbased Coordinator, CEIN Assistant Alex Andres, and CEIN Outreach Coordinator Meghan Horan on the
planning and implementation of cross-Theme projects related to the translation and dissemination of
the Center’s research as well as the Center’s website and social networking sites (Facebook and Twitter).
Education Project 1 includes CEIN students and postdocs from all thematic groups and locations.
Education Project 2 includes the development of learning tools that communicate concepts from Center
research to K-12, undergraduate, and researcher audiences. Education Project 3 consists of public
education programs with partner museums and other research centers in California. Intra-Center
integrative activities comprise the thrust of Project 4 and promote interdisciplinary synergism through
working group meetings, such as the Carbonaceous Working Group. Additionally, Nameth has been
working with Bacsafra (CEIN Web and Data Specialist, Theme 6) to integrate educational reporting and
impacts into the Center’s data management system.
Major Planned Activities for the Next Reporting Period
Project 1: Student/Postdoctoral Mentoring and Professional Development: In the coming months, the
Center’s students and postdocs will be working with their faculty on professional development. Brown
bag webinars and in-person workshops are being planned. For the coming year, UC-CEIN students and
postdocs have requested workshops on career development.
Project 2: Course Development, Workshops, and Learning Tools: In the coming year, UC-CEIN’s third
project with Science Buddies will be written and published on the Science Buddies website. Nameth will
coordinate this effort with Science Buddies, Andres, and CEIN alumna (graduate student 2010-2013)
Courtney Thomas.
Project 3: Informal Science Education (ISE) and Public Outreach: The Center will continue to partner
with the California Science Center (Los Angeles, CA) and the Santa Monica Public Library, and it will
continue to provide support (education, training, funding) for Center members to participate in ISE
activities in their local areas.
Project 4: Synergistic/Integrative Center Activities: CEIN Education will continue to facilitate crossthematic and cross-disciplinary discussion and interaction by providing webinar support for meetings.
There will continue to be consistent coordination between Andres/CEIN Admin, Nameth/Education and
Horan/Theme 7/Carbon Working Group for seminars, webinars, and other integrative activities.
Project 5- Seed Project- Sustainable nanoMAterials Laboratory (SMAL): Nameth and Wheeler (Santa
Clara University) have met their benchmarks for each of the aims of this project. They have written the
lab manual as well as pre- and post-lab assignments, and they received IRB approval to conduct a
research study focused on how undergraduate student feedback informs curriculum design. About 40
undergraduates at Santa Clara University have pilot tested the module (Winter 2015 & Winter 2016),
and over half of these have participated in Nameth & Wheeler’s research study. Nameth & Wheeler will
submit the module for publication in Journal of Chemical Education, and they will also submit a
manuscript on curriculum development to Journal of Research in Science Teaching.
Although this project started as a seed project, it has evolved into a full-fledged curriculum
development project supported by CEIN. Nameth & Wheeler are working with two community
colleges- De Anza Community College and Pasadena City College- to include the SMAL module into
85
existing chemistry curriculum, and Nameth & Wheeler are partnering with NanoHUB at Purdue to create
an online community of practice for instructors interested in integrating SMAL into existing curriculum.
Planned CEIN Education Activities & Outputs for Year 9
Project Area
Activities & Outputs
1. Student/Postdoc
Monthly group conference calls; Site visit preparation (Poster
Mentoring & Professional
Preparation & Presentation skills); Spring 2016 career development
Development
workshop and retreat; Winter 2017 writing workshop
2. ISE & Public Outreach
Publication Pause-Commit-Engage: A rubric for direct observation in
informal learning environments will be submitted to Center for
Advancement of Informal Science Education (CAISE), to be made
publicly available at www.informalscience.org (Nameth)
Event #IamAscientist, Women’s History Month panel at Santa Monica
Public Library (March 2017)
New Science Buddies’ Project
3. Courses, Workshops, and Publication (Nameth, Truong, Stevenson, Science Buddies staff) for
Learning Tools
Science Buddies’ website- Tips for translating scientific research to a
science-fair project for the middle-school audience
4. Synergistic/Integrative
Evaluation Internal evaluations of programs; Annual Center-wide
survey; Collaborate with Bacsafra (Theme 6) on capturing education
impact data as part of Center’s data management system
Publications
1) Sustainable nanoMAterials Lab in Journal of Chemical Education,
2)Using undergraduate student feedback to inform curriculum design
in Journal of Research in Science Teaching
5. Seed Project (SMAL)
Nameth & Wheeler
Partnerships De Anza Community College- integrating SMAL into
curriculum; Pasadena City College- integrating SMAL into chemistry
curriculum and contributing to teacher development workshops;
nanoHUB at Purdue- creating online community of practice for
instructors interested in integrating SMAL into curriculum
86
Nameth tracks CEIN student and postdoc alumni. The number of alumni in non-profit, consulting,
industry, government, and academia are as follows:
•
•
•
•
5 in non-profit or consulting
7 in industry
10 in government
30 in academia
Impacts on the Overall Goals of the Center
CEIN Education reaches across all themes and cores of the Center and thus influences every Center
member. Graduate students and postdocs help determine the leadership activities of the Center.
Materials from all areas of CEIN research are drawn upon for the development of academic coursework
and the synthesis of information for the Center’s public education programs. We recruit participants
from all levels of the Center (undergraduate, graduate student, postdoc, research staff, and faculty) to
participate in the full range of Education activities, which are coordinated on a volunteer basis. An
annual Center-wide survey asks each member to report on their experience in an interdisciplinary
research center, which includes their participation in interdisciplinary working groups.
Postdoctoral Mentoring Plan
The UC CEIN is committed to educating and training the next generation of interdisciplinary scientists
and engineers needed to advance the field of nanotechnology and who can also anticipate and mitigate
any potential future environmental hazards associated with this important technology. To enhance the
professional development of our Center trainees, the UC CEIN Education program conducts a coherent
and effective series of annual leadership and mentoring activities within the Center designed to further
the professional development of all Center trainees (undergraduate and graduate students as well as
postdocs). UC CEIN conducts participant-centered professional development workshops and provides
one-on-one professional development/job skills support for Center students and postdocs to improve
their skills in the areas of public speaking, professional presentations, and writing. Topics for the
workshops and individual mentoring are determined by input from the Center's students and postdocs
as well as priority areas identified by Center faculty. We are committed to providing leadership
development opportunities to postdoctoral researchers at all Center partner institutions, and funds are
available in the Education budget to fund travel for out-of-state participants.
Additional development opportunities include our cross-campus trainee (students and postdocs)
seminar series. Trainees from the Center are supported to travel to a partner campus to present a
seminar and lead a discussion on their ongoing research projects. This program fertilizes crossdisciplinary discussions at the trainee level and has been extremely popular. In the first round of
funding, UCLA and UC Santa Barbara hosted "visiting researcher" graduate students and postdoctoral
scholars, and we will expand these opportunities in years 6-10. This is critical to our students and
postdocs being able to form substantive interactions with their counterparts at distant institutions
within the Center.
The UC CEIN Education Coordinator conducts both formal and informal internal evaluations of the
Student/Postdoctoral Mentoring and Professional Development Program. The Coordinator also offers
year-round in person and online sessions on presentation skills and report writing. The Coordinator is
available to all postdoctoral researchers for one-on-one consultation for writing skills, presentation
skills, and career development advice.
87
In addition to Center-wide mentoring and leadership activities, all postdoctoral researchers across the
Center develop a written training plan for their research and undergo an annual performance evaluation
with their mentor. The UC CEIN conducts evaluations of all Center mentoring activities, results of which
are summarized in our Center's annual reports and are used to inform program development.
Informal Science Education and Public Outreach
During Year 8, 38 CEIN members (faculty, staff, research staff, graduate & undergraduate students,
postdocs) reported on a range of informal science and public outreach activities. An additional three
people- CNSI graduate student McCormick, one UCLA staff (Oishi), and one CEIN alumni (Thomas)helped the public understand key concepts about nanoscience and the environment. Together, these
41 people participated in science education programming and collectively reached over 2,000 people at
museums, community organizations, K-12 schools, campus-affiliated events, lab tours, and outreach
targeted towards undergraduates.
K-12 schools and summer camps
Informal science education outreach to the K-12 community involved face-to-face as well as online
interaction by 14 CEIN members with more than 50 K-12 teachers and over 1,000 K-12 students.
Topic
Program & location
CEIN member(s)
# K-12 students or
teachers
nanoScience
Talk & Hands-on activities,
Durfee
25
New Mexico International
School, Albuquerque, NM
Exploring science
Garfield Middle School,
Durfee, Lokke, Muniz 50
Albuquerque, NM
Exploring science
Tony Hillerman Middle
School, Albququerque, NM
Exploring science
West Mesa High School,
Albuquerque, NM
Exploring careers in
South Valley Academy,
Durfee, Lokke
125
science & engineering
Albuquerque, NM
Medina, Muniz
Marine organisms
Skype show-and-tell, Elmhurst Fairbairn
30 kindergarteners
School, Elmhurst, IL
Marine organisms
MESA program, Bodega Bay
Cherr
65 middle-school
Marine Lab, Bodega Bay, CA
students
Ubiquitous electronics
Illinois Chemical Education
Hersam
100 high-school
& their sensors:
Foundation Scholarship
students
Enabling the internet of Luncheon, Des Plaines, IL
things
Bio & nano: Why should UCLA’s SciArt program, Los
S. Lin & Osborne
40 high-school
we care?
Angeles, CA
students
Preparing for college:
South Valley Academy High
Medina & Muniz
75 11th graders
STEM majors & careers School Career Day,
Albuquerque, NM
Science fair judge
Socorro Independent School
Medina Velo
100 high-school
District, El Paso, TX
students
Lab tours & discussions Biology research day for
Muniz
30 high-school
of UNM researchers’
Highland High School @
students
88
current projects
Science fair judge
Biotoxicity
Water treatment
mimics hydrologic cycle
Using confocal
fluorescent microscopy
for nanomedicine
Longfellow Elementary,
Albuquerque, NM
CNSI’s High-School Teacher
Education Program, Los
Angeles, CA
Smiley Elementary School,
Riverside, CA
UCLA’s Summer nanoLab, Los
Angeles, CA
Muniz
125
Osborne
50 teachers
Story
100 4th graders
X. Liu, B. Sun, T. Xia,
X. Wang
80 high-school
students
Outreach to undergraduates
During Year 8, over 500 undergraduates learned about CEIN research, careers in science, and scientific
writing through outreach efforts in the United States, Korea, and China. Additionally, CEIN-affiliated
faculty Jeff Brinker and his lab mentored 14 undergraduates through the NSF STEP program and hosted
two REU students during the summer of 2015- Jacob Erstling worked on a project entitled Protocell
nanocarriers for targeted delivery of cancer therapeutics, and Amanda Ramsdell did research on
Modulation of the immune response to protocells.
Event or Program
NSF STEP program
REU
Lab tour
Location
UC Davis Bodega Marine Lab
CEIN member(s)
Brinker
Brinker
Fairbairn
UTEP Research Forum
UTEP Student Research
Expo
How to get published in
scientific journals
(Workshop)
scientific journals
(Workshop)
scientific journals
(Workshop)
UCLA SPUR (Summer
Programs for
Undergraduate
Research)
Lab tours
UTEP
UTEP
Gardea Torresdey
Gardea Torresdey
# undergraduates
14
2
15 biology students
from Sacramento
City College
50
50
Kunming University of Science
& Technology, Kunming,
China
Pohang University of Science
& Technology, Pohang, Korea
Gardea Torresdey
100
Gardea Torresdey
50
University of Science &
Technology of China- Heifei
Gardea Torresdey
200
UCLA
Meng
5
University of California,
Riverside
Chen, Story, Waller,
Walker
80 undergraduates
from CalPoly
Pomona, UC
89
Career panel for
undergraduates, UCSB
EEMB 142b
UCSB
Welch
Riverside SISTERS
program, Riverside
Community College,
& University of
Redlands
10
Lab Tours
During Year 8, over 130 people toured six CEIN-affiliated laboratories. Visitors included faculty,
researchers, undergraduate and graduate students, and community members.
Laboratory location
UC Davis Bodega Marine Lab
PI
Cherr
Fairbairn
Tour guide(s)
Visitors
70 community members
UC Los Angeles
Nel
C. Chang, X. Ji, R. Li, & X. Wang
Nel
Meng
Nel
B. Sun
Holden
Mortimer, Y. Wang, & Welch
Keller
Adeleye
Nisbet
Stevenson
Gardea
Torresdey
Barrios
20 faculty & researchers,
International
Symposium for
Nanobiotechnology
10 undergraduates,
UCLA’s SRP program
25 undergraduate &
graduate students from
Dailan University of
Technology (China)
Faculty from Pasadena
City College
City College
City College
Community members
UC Santa Barbara
UTEP
Museum-based public outreach: Los Angeles, Albuquerque, London, Chicago
CEIN continues its tradition of museum-based public outreach. For the sixth year in a row, CEIN
partnered with the California Science Center in Los Angeles for NISENet’s NanoDays. Six CEIN volunteer
educators (McCormick, Nameth, Oishi, Osborne, Taylor, Truong) included CEIN staff, graduate students,
and postdocs as well as a CNSI graduate student and a UCLA staff member talked to 400 museum
visitors about nanoscale science and engineering. Later in April 2015, four CEIN volunteer educators
(Nameth, Osborne, Sokolow, Truong) participated in the museum’s “Family Night at the Museum”
event, using NISENet’s activities to help 250 visitors understand fundamental nanoscale concepts.
90
At the National Museum of Nuclear Science and History in Albuquerque, New Mexico, graduate student
Durfee helped 30 children explore science through demonstrations and discussion.
In addition to in-person informal science education at museums, Center researchers participated in
museum outreach by contributing online content Science Museum, London (Osborne), and by serving as
content expert (Hersam) for a new exhibit at Museum of Science + Industry in Chicago, Illinois.
Other public outreach
Other Informal Science Education public outreach during Year 8 included the participation of faculty
(Cherr, Gardea Torresdey, Godwin, Harthorn, Lenihan), postdoctoral fellows (Fairbairn, Osborne), and an
undergraduate (Pon) student. Such public outreach included new activities, like a National Geographic
interview (Cherr & Lenihan) and an educational session at a Rotary Club (Gardea Torresdey), as well as
annual events such as Science Uncorked (Fairbairn) in Bodega Bay as well as a panel discussion at a
public library in Santa Monica, California.
Event and/or topic
Interview with National
Geographic, Do
sunscreens’ tiny
particles harm ocean
life in big ways?
Science Uncorked
(August-December
2015)
San Mateo Faire
Environmental
implications of
nanotechnology
#IAmAScientist: Women
in nanoscale science &
engineering
Nanotechnology &
society, World
Anthropology Day
CEIN Member(s)
Cherr
Lenihan
N/A
Gourmet au Bay,
Bodega Bay, CA
Fairbairn
200
San Mateo Fairgrounds,
San Mateo, CA
Rotary Club, El Paso, TX
Fairbairn
25
Gardea Torresdey
200
Santa Monica Public
Library, Santa Monica,
CA
UCSB, Santa Barbara,
CA
Godwin, Franco,
Nameth, Osborne, Pon
10
Harthorn
100
Online
Location
# attendees
Academic Courses Incorporating CEIN-related Content
Since April 2015, 9 CEIN members- faculty, postdocs, and graduate students- reported incorporating
Center-related content into their existing courses. Through these 8 courses on 5 campuses, 250
students (90 undergraduates and 160 graduate students) have an awareness of current research related
to nanoscience and the environment.
•
•
Fairbairn- ETX 190/290- Ecological risk assessment seminar, 15 undergraduate & graduate
students, UC Davis, Spring 2015
Cherr & Fairbairn & Torres- EXT/NUT127- Environmental stress & development in marine
organisms, 9 undergraduates, UC Davis, Summer 2015
91
•
•
•
•
•
•
Holden- ESM401A- Masters group project regarding microplastics in the ocean from textile
washing, in association with Patagonia, 6 students, UCSB, Summer 2015
Lutz Mädler- Aerosol technology (I and II), Department of Production Engineering, 50 Master’s
students, University of Bremen, Winter 2016
Medina Velo- CHEM6339- Contemporary topics in biochemistry, 7 graduate students, UTEP, Fall
2015
Pokhrel- 05-MCM-3-W7M-1-Nanoparticles and Nanotechnology, 10 Master’s students,
University of Bremen, Winter 2016
Story-ENGR 118- Engineering modeling and analysis, 75 undergraduates, UC Riverside, Fall 2015
Y. Wang- ESM 202- Environmental biogeochemistry, 80 graduate students, UCSB, Winter 2016
Professional Development Activities for CEIN Students and Postdoctoral Scholars
•
•
The UC CEIN’s 2015 Student/Postdoc Leadership Workshop was held June 1 in Los Angeles,
California, preceding the Center’s NSF/EPA site visit. The 22 student/posdoc attendees chose
the topic for this year’s workshop- Data Management- and CEIN Data Manager Bacsafra led a
workshop on this topic, while Nameth planned and organized teambuilding activities.
In response to student/postdoc requests for more cross-campus interaction, since January 2015
there have been monthly- rather than biannual- student/postdoc conference calls. Nameth
organizes the calls, while students/postdocs take turns leading these conference calls. In the
past year, student/postdoc leaders have been Duarte (Bodega Bay), Mansukhani and Guiney
(Northwestern), Waller (UC Riverside), and Mortimer, Y. Wang and Welch (UCSB).
Mentoring High School and Undergraduate Students
High-school student mentoring
o Priyanka Jain (UNM- Brinker), Laboratory space, supplies, mentoring for 2016 Science &
Engineering Fair project
o Sina Mohseni (Northwestern- Hersam), Atomic force microscopy characterization of twodimensional nanomaterials
Undergraduate mentoring
1. Ayman Ahmed (UCLA- X. Wang), Cellular culture & cytotoxicity
2. Perla Akkara (UCLA- X. Wang), Cellular culture & cytotoxicity
3. Natalie Bouri (UCLA- Xia), Silica induced toxicity to cells
4. Vivon Crawford (UCSB-Vignardi), Nanotoxicology using marine phytoplankton as a model
5. Brittany Cunningham (UC Davis-Fairbairn), Morphological effects of bulk & nano zinc oxide
sunscreens on developing purple sea urchin (Strongylocentrotus purpuratus) embryos
6. Manu Chopra (UCSB-Mortimer, Y. Wang), Carbon nanotube trophic transfer in a microbial food
chain & Effects of engineered carbonaceous materials on soybeans
7. Jacob Chow (UCLA-S. Lin), Zebrafish maintenance
92
8. Osvaldo Dominguez (UTEP-Medina Velo), Exposure of kidney beans to zinc oxide nanoparticles
(Z-COTE and Z-COTE HP1)
9. Julia Ebert (UCSB- Welch), Rhizobial culture and nanopesticide effects to bacterial physiology
10. Eduardo Gonzalez (UC Davis-Fairbairn), Neurotoxic effects of silver nanoparticles on developing
zebrafish
11. Mariana Hernandez (UTEP-Gardea Torresdey), Effects of Cu NPs on sugarcane
12. Cynthia Barbara Huang (UCLA- R. Li), Nanotoxicity by graphene oxide in bacteria
13. David Huxley (UCR-Story), Aggregate morphology
14. Winnie Jiang (UCSB-Vignardi), Nanotoxicology using marine phytoplankton as a model
15. Elaine Kang (UCLA-Meng), Pancreatic Cancer nanotherapeutics
16. Sarika Kathuria (UCSB-Adeleye), Determination of CuO nanoparticles in aquatic sediment
17. Peter Kim (Northwestern- Hersam, Guiney & Mansukhani), Preparation & characterization of
aqueous dispersions of two-dimensional nanomaterials for the UC-CEIN ENM library
18. Justine Ku (UCLA-B. Sun), Fumed silica-induced toxicity
19. Anson Lee (UCLA- R. Li), Toxicity of gold clusters in mammalian cells
20. Paulina Lin (UCSB-X. Lu), Synthesis & characterization of ENMs for cancer treatment
21. Ekene Oranu (UCSB-Adeleye), Fate of Fe-doped CuO nanoparticles
22. Robert Parker (UCSB-Adeleye), Determination of CuO nanoparticles in aquatic sediment
23. Nanetta Pon (UCLA- C. Chang & Z. Ji), Nanoparticle characterization
24. Ian Perrett (UCSB-X. Lu), Synthesis & characterization of ENMs for cancer treatment
25. Felipe Sachi Patricio (UCSB-Vignardi), Aging nanomaterials
26. Robin Riehn (UCR-Story), Aggregate morphology
27. Niki Rinaldi (UCSB-Holden), MWCNT effects on nodulating versus non-nodulating soybean
28. Paige Rutten (UCSB-Adeleye), Effect of EPS/SRNOM on aggregation of TiO 2
29. Michael Salazar (UNM-Brinker), Characterization of rare earth oxide nanoparticles with bacterial
organisms
30. Allen Situ (UCLA-Meng), Pancreatic cancer nanotherapeutics
31. Katie Rose Villabroza (UCLA-Meng), Pancreatic cancer nanotherapeutics
32. Qingbai Xu (UCLA-Wang), Nanoparticle characterization
33. Xuechen Yu (UCLA-S. Lin & Osborne), Understanding toxicity of silver nanoparticles on the
zebrafish model
34. Yipin Wu (UCLA-X. Wang), Nanoparticle characterization
93
Table 3a: Education Program Participants - All, irrespective of citizenship
Gender
Student Type
Total
Male
Race Data
Female
AI/AN
NH/PI
B/AA
W
A
Mixed - incl.
AI/AN, B/AA,
NH/PI
Mixed - W/A
Not
Provided
Ethnicity:
Hispanic
Disabled
Enrolled in Full Degree Programs
Subtotal
106
49
57
1
1
4
52
40
1
1
6
26
0
Undergraduate
65
31
34
1
1
2
31
24
1
1
4
16
0
Masters
0
0
0
0
0
0
0
0
0
0
0
0
0
41
Doctoral
Enrolled in NSEC Degree Minors
Subtotal
0
18
23
0
0
2
21
16
0
0
2
10
0
0
0
0
0
0
0
0
0
0
0
0
0
Undergraduate
0
0
0
0
0
0
0
0
0
0
0
0
0
Masters
0
0
0
0
0
0
0
0
0
0
0
0
0
Doctoral
0
0
0
0
0
0
0
0
0
0
0
0
0
Enrolled in NSEC Certificate Programs
Subtotal
0
0
0
0
0
0
0
0
0
0
0
0
0
Undergraduate
0
0
0
0
0
0
0
0
0
0
0
0
0
Masters
0
0
0
0
0
0
0
0
0
0
0
0
0
Doctoral
0
0
0
0
0
0
0
0
0
0
0
0
0
Practitioners taking courses
0
0
0
0
0
0
0
0
0
0
0
0
0
Subtotal
1000
0
0
0
0
0
0
0
0
0
0
0
0
Teachers
0
0
0
0
0
0
0
0
0
0
0
0
0
Students
Total
1,000
1106
0
49
0
57
0
1
0
1
0
4
0
52
0
40
0
1
0
1
0
6
0
26
0
0
K-12 (Precollege) Education
LEGEND:
AI/AN NH/PI B/AA WAMixed - incl. AI/AN, B/AA,
NH/PI -
American Indian or Alaska Native
Native Hawaiian or Other Pacific Islander
Black/African American
White
Asian, e.g., Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other Asian
Personnel reporting a) two or more race categories and b) one or more of the reported categories includes American
Indian or Alaska Native, Black or African American, or Native Hawaiian or Other Pacific Islander
Personnel reporting a) both White and Asian and b) no other categories in addition to White and Asian
Mixed - W/A US/Perm Non-US -
U.S. citizens and legal permanent residents
Non-U.S. citizens/Non-legal permanent residents
94
Table 3b: Education Program Participants - US Citizens and Permanent Residents
Gender
Student Type
Total
Male
Female
Race Data
AI/AN
NH/PI
B/AA
W
A
Mixed - incl.
AI/AN, B/AA,
NH/PI
Mixed - W/A
Not
Provided
Ethnicity:
Hispanic
Disabled
Enrolled in Full Degree Programs
Subtotal
82
41
41
1
1
2
48
27
1
1
1
19
0
Undergraduate
59
30
29
1
1
1
31
22
1
1
1
15
0
Masters
0
0
0
0
0
0
0
0
0
0
0
0
0
23
Doctoral
Enrolled in NSEC Degree Minors
Subtotal
0
11
12
0
0
1
17
5
0
0
0
4
0
0
0
0
0
0
0
0
0
0
0
0
0
Undergraduate
0
0
0
0
0
0
0
0
0
0
0
0
0
Masters
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Doctoral
Enrolled in NSEC Certificate Programs
0
0
0
0
0
0
0
0
0
0
0
0
Subtotal
0
0
0
0
0
0
0
0
0
0
0
0
0
Undergraduate
0
0
0
0
0
0
0
0
0
0
0
0
0
Masters
0
0
0
0
0
0
0
0
0
0
0
0
0
Doctoral
0
0
0
0
0
0
0
0
0
0
0
0
0
0
82
0
41
0
41
0
1
0
1
0
2
0
48
0
27
0
1
0
1
0
1
0
19
0
0
Practitioners taking courses
Total
LEGEND:
AI/AN NH/PI B/AA WAMixed - incl. AI/AN,
B/AA, NH/PI Mixed - W/A US/Perm Non-US -
White
Personnel reporting a) two or more race categories and b) one or more of the reported categories includes American Indian
or Alaska Native, Black or African American, or Native Hawaiian or Other Pacific Islander
95
12. Outreach and Knowledge Transfer
One of the major goals of the Center is to train the next generation of nano-scale scientists, engineers,
and regulators to anticipate and mitigate potential environmental hazards associated with
nanotechnology, while at the same time seeking to impact the scientific, educational, and policy
communities both nationally and internationally. We seek to educate the broader community through
both Center-sponsored seminars and workshops and by participating in scientific meetings nationally
and internationally across the range of UC CEIN disciplines. The Center has become a valuable resource,
and our public profile as that of a leading Center for research on nanotechnology and Environmental
Health and Safety continues to rise at all levels- local, regional, national, and international.
Workshops hosted by UC CEIN
Studies of Manufactured and Engineered Nanomaterials (M&ENMs)- UCLA
• March 19-20, 2015- This workshop brought together an international representation of
ecotoxicology researchers, exposure modelers, material manufacturers, and government
representatives for a two-day roundtable to address the following questions: (1) What is the
state of the knowledge regarding M&ENM environmental exposure conditions, via
measurements or modeling simulations?; (2) What exposure conditions are used in assessing
M&ENM ecological hazard potential, and how do they compare to measured or modeled
exposure values?; (3) What conditions should be simulated in ecological nanotoxicological
research to best inform risk management and also mechanistic understanding?; and (4) How
should concepts such as environmental (or laboratory) concentration, exposure, speciation,
dose, and body burden be utilized in interpreting biological and computational findings? This
workshop produced and will disseminate a consensus statement that addresses the motivating
questions and provides guidance into the future.
Lectures, Seminars, and Presentations by UC CEIN members to external audiences
Adeyemi Adeleye, University of California Santa Barbara
o Release and Detection of Nanosized Copper from a Commercial Antifouling Paint, 26th Annual
International Conference on Soil, Water, Energy, and Air, San Diego, CA, March 2016
o Adsorption of algal extracellular polymeric substances to TiO2 nanoparticles: Effects on surface
properties and fate of nanoparticles, Society for Risk Analysis (SRA) 2015 Annual Meeting,
Arlington, VA, December 2015
o Experimental Release and Aquatic Toxicity of Copper (Nano)particles from Marine Paints,
Sustainable Nanotechnology Organization (SNO) Conference, Portland, OR, November 2015
o Influence of phytoplankton on fate, transformations, and effects of iron nanoparticles, 250th
American Chemical Society National Meeting, Boston, MA, August 2015
o Long-term release of nanoparticulate copper from an antifouling paint (Poster), Gordon
Research Conference on Environmental Nanotechnology, West Dover, VT, June 2015
o Influence of phytoplankton on fate and effects of iron nanoparticles, Gordon Research
Conference on Environmental Nanotechnology, West Dover, VT, June 2015
Muhammad Bilal, University of California Los Angeles
o ToxNano: An Online Toolkit for Toxicity Data Analysis of Nanomaterials (Poster), Gordon
96
C. Jeffrey Brinker, University of New Mexico
o Inorganic polymerization at cellular interfaces, Biophysical Society: Polymers & Self-Assembly,
from Biology to Nanomaterials, Rio de Janeiro, Brazil, October 2015
o Staying motivated in your STEM classes (Poster), UNM STEM Collaborative Center, Albuquerque,
NM, September 2015
o Silica @ cells: A special biotic/abiotic interface, 3rd International Conference on Advanced
Complex Inorganic Nanomaterials (ACIN), Namur, Belgium, July 2015
Gary Cherr, UC Davis Bodega Marine Laboratory
o Marine nanotoxicity within the UC-CEIN, Instituto de Ciencias Marinas y Limnológicas,
Universidad Austral de Chile, Valdivia, Chile, November 2015
Yoram Cohen, University of California Los Angeles
o Nanomaterials fate modeling, Sustainable Nanotechnology Organization (SNO) Conference,
Portland, OR, November 2015
o Environmental multimedia distribution of nanomaterials, Quantifying Exposure to Engineered
Nanomaterials (QEEN) from Manufactured Products (SPSC & NNI), Arlington, VA, July 2015
o Nanoinformatics- Development and integration of computational tools for assessing the
environmental impact of engineered nanomaterials, Gordon Research Conference on
Environmental Nanotechnology, West Dover, VT, June 2015
o Nanoinformatics Tools for Analysis and Modeling of Toxicity of Engineered Nanomaterial, ASME
2015 4th Global Conference on Nano-Engineering for Medicine and Biology, Minneapolis, MN,
April 2015
Robert Damoiseaux, University of California Los Angeles
o Assay platforms for toxicity evaluation in small molecules and nanomaterials, World Pharma
Congress, Boston, MA, June 2015
Michelle Romero Franco, University of California Los Angeles
o Environmental health and safety implications of nanotechnology, Southern California Joint
Technical Symposium, Long Beach, CA, October 2015
o Need for an integrative framework to assess the environmental impacts of engineered
nanomaterials (Poster), Gordon Research Conference on Environmental Nanotechnology, West
Dover, VT, June 2015
Jorge Gardea Torresdey, University of Texas El Paso
o Environmental implications of nanotechnology: Locating metal oxide nanoparticle
transformation in plants using synchotrol techniques, 7th International Conference on
Nanomaterials, Brno, Czech Republic, October 2015
o Physiological and biochemical effects of copper nanoparticles on sugarcane, 4th CETARS
Symposium, University of Puerto Rico, Mayaguez, Puerto Rico, August 4, 2015
o Differential Effects of ZnO and Zn ions on corn seedlings at different temperatures: Enzyme
activity, protein production, and Zn biotransformation, 2015 International Chemical Congress of
Pacific Basin Societies, Honolulu, HI, December 2015
o Effects of two commercial zinc oxide nanoparticles on red kidney bean plants, Sustainable
Nanotechnology Organization (SNO) Conference, Portland, OR, November 2015
o Impact of uncoated and citric acid coated cerium oxide nanoparticles on tomato plants,
Sustainable Nanotechnology Organization (SNO) Conference, Portland, OR, November 2015
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Bean plants exposed to cerium oxide nanoparticles modified physiological characteristics and
shows translocation to the next trophic level: Implications in plant nutrition and human health?
2015 International Symposium on Environmental Science and Technology, Chongqing, China,
November 2015
Environmental implications of nanotechnology: Locating metal oxide nanoparticle
transformation in plants using synchrotron techniques, 7th International Conference on
Nanomaterials - Research & Application, Brno, Czech Republic, October 2015
Environmental implications and applications of nanotechnology, UTEP, El Paso, TX, Oct 2015
Nanoceria modulates the kidney bean proteome and compromises its nutritional quality, 12th
International Phytotechnologies Conference, Manhattan, KS, October 2015
Combined effects of engineered carbonaceous nanomaterial exposure and environmental
stressors upon soil-grown soybeans, 2015 UC Natural Reserve System (NRS) Conference, Santa
Barbara, CA, September 2015
Monitoring the environmental effects of CeO2 and ZnO nanoparticle through the life cycle of
corn (Zea mays) and cucumber (Cucumis sativus) plants, 250th ACS Meeting, Boston, Aug 2015
Physiological and biochemical effects of copper nanoparticles on sugarcane, 4th CETARS
Symposium, Mayaguez, Puerto Rico, August 2015
Nanoparticulas de cerio y su impacto en el crecimiento de planta de frijol, Congreso del Colegio
de Quimicos de Puerto Rico, San Juan, Puerto Rico, Julio 2015
Cerium oxide nanoparticle exposure to bean plants modifies physiological characteristics and
shows translocation to the next trophic level: Are there implications in plant nutrition and
human health? The 10th Asia Pacific Conference on Sustainable Energy & Environmental
Technologies, University of Seoul, Seoul, South Korea, July 2015
Environmental Implications of nanotechnology: Tracing nanoparticle transformation in
terrestrial plants using synchrotron techniques, Kunming University of Science and Technology,
Kunming, China, June 2015
Comparison of citric acid coated and uncoated nanoceria and their impact on tomato (Solanum
lycopersicum L.) plants grown in organic soil, Gordon Research Conference on Environmental
Nanotechnology, West Dover, VT, June 2015
Nanoceria affects kidney bean proteome compromising seed nutritional quality, Gordon
Environmental implications of nanotechnology: Locating metal oxide nanoparticles
transformation in plants using synchrotron techniques, III simposio Internacional de Botanica
Aplicada, XXXV Encontro Regional de Botanicos, I Encontro de Taxonomistas de Minas Gerais,
Lavras, Brazil, Mayo 2015.
Sludge and compost amendments in tropical soils: Impact on coriander (Coriandrum sativum)
nutrient content, ICEES 2015: XIII International Conference on Environmental and Earth
Sciences, Venice, Italy, April 2015
Linda Guiney, Northwestern University
o Toxicological potential and environmental fate of molybendum disulfide (MoS2), a postgraphene 2D material, 250th American Chemical Society National Meeting, Boston, MA, August
2015
o Aqueous, High-Concentration Dispersions of Molybdenum Disulfide in Biocompatible Block
Copolymers (Poster), Gordon Research Conference on Environmental Nanotechnology, West
Dover, VT, June 2015
Barbara Herr Harthorn, University of California Santa Barbara
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Intersections of science and society: Framing, debating and governing new technologies and
risk, Society for Applied Anthropology, Vancouver, BC, March 2016
Deliberating emergent views on energy, risk and engagement, Society for Applied Anthropology,
Vancouver, BC, March 2016
Fracking, climate change, and nuclear power are like . . . hand guns: An examination of public
opinion on politically charged hazards, Society for Applied Anthropology, Vancouver, BC, March
2016
Contributions and legacy of a decade of societal work on nanotechnology, NSF Nanoscale
Science and Engineering Annual Meeting, Arlington, VA, December 2015
Nanotechnology policy: Evolving and maturing, American Chemical Society’s Science and the
Congress Project, Washington, DC, October 2015
Mark C. Hersam, Northwestern University
o Ubiquitous electronics and sensors: Enabling the internet of things, World Technology Summit,
New York, New York, November 2015
o Fundamentals and applications of low-dimensional nanomaterial heterostructures, The
University of North Carolina Materials Chemistry Seminar Series, Chapel Hill, NC, November
2015
o Solution processing and device integration of two-dimensional black phosphorous, 228th
Electrochemical Society Meeting, Phoenix, AZ, October 2015
o Fundamentals and applications of two-dimensional nanomaterial heterostructures, National
Academies Symposium on Novel Materials, Washington, DC, October 2015
o Integration challenges and opportunities for two-dimensional materials, Science and Technology
of Two-Dimensional Materials Workshop, Orlando, FL, August 2015
o Solution processing and device integration at the two-dimensional limit, 250th American
Chemical Society National Meeting, Boston, MA, August 2015
o Carbon and related nanomaterial heterostructure devices, Carbonhagen Symposium on Carbon
and Related Nanomaterials, Copenhagen, Denmark, August 2015
o Nanomaterial heterostructures for electronic and electrochemical applications, 8th International
Conference on Materials for Advanced Technologies, Singapore, July 2015
o Beyond carbon nanotube thin-film transistors: Logic circuits, memory, and heterostructures, 16th
International Conference on the Science & Application of Nanotubes, Nagoya, Japan, June 2015
o Solution processing & device integration of two-dimensional black phosphorous, 6th Graphene
and 2-D Materials Satellite Symposium, Nagoya, Japan, June 2015
o Emerging device applications for two-dimensional nanomaterial heterostructures, 73rd Device
Research Conference, Columbus, OH, June 2015
o Production & application of printable carbon nanomaterial inks, 2015 TechConnect World
Innovation Conference, Baltimore, MD, June 2015
o Anti-ambipolar gate-tunable p-n heterojunctions, 227th Electrochemical Society Meeting,
Chicago, IL, May 2015
o VLSI carbon nanotube thin-film circuits, 227th Electrochemical Society Meeting, Chicago, IL, May
2015
o Solution processing & device integration at the two-dimensional limit, European Materials
Research Society Spring Meeting, Lille, France, May 2015
Arturo Keller, University of California Santa Barbara
o Fate, transport, and implications in the terrestrial environment, Association for Environmental
Health and Sciencees (AEHS) Annual International Conference, San Diego, CA, March 2016
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Uptake, distribution, and physiological impacts of metal oxide nanoparticles in mature crop
plants: Evidence for nanophototoxicity?, 250th American Chemical Society National Meeting,
Boston, MA, August 2015
Heteroaggregation of nanoparticles with biocolloids and geocolloids, 250th American Chemical
Society National Meeting, Boston, MA, August 2015
Life cycle impacts assessment of engineered nanomaterials, Safe Implementation of Innovative
Nanoscience and Nanotechnology (SIINN), Lisbon, Portugal, July 2015
Emerging trends in environmental implications of nanomaterials, Nanotech, Arlington, VA, June
2015
Ruibin Li, University of California Los Angeles
o Using property-activity relationship for nanotoxicity assessment and safe design, The 12th
International Symposium on Persistent Toxic Substances, Riverside, CA, November 2015
o Toxicity mechanism study on rare earth oxide nanoparticles (Poster), Gordon Research
Conference on Environmental Nanotechnology, West Dover, VT, June 2015
Sijie Lin, University of California Los Angeles
o Environmental implications of nanotechnology: Use of zebrafish HTS to perform hazard
assessment of engineered nanomaterials, Southern California Joint Technical Symposium, Long
Beach, CA, October 2015
H. Liu, University of California Los Angeles
o Agglomeration of nanoparticles evaluated via a constant number Monte Carlo simulation, AIChE
Annual Meeting, Salt Lake City, UT, November 2015
Rong Liu, University of California Los Angeles
o Prediction of Nanoparticles-Cell Association on Corona Proteins and Physicochemical Properties,
AIChE Annual Meeting, Salt Lake City, UT, November 2015
o (Co-presenter with Cohen) Nanoinformatics Tools for Analysis and Modeling of Toxicity of
Engineered Nanomaterial, ASME 2015 4th Global Conference on Nano-Engineering for
Medicine and Biology, Minneapolis, MN, April 2015
Xiangsheng Lu, University of California Los Angeles
o Use of nano engeineered approach for human pancreatic cancer treatment (Poster), 2015 David
Geffen School of Medicine Research Day, Los Angeles, CA, October 2015
Lutz Madler, University of Bremen
o Process Engineering for Materials Design, CENIDE Science Talk, Duisburg, Germany January 2016
o Multidisciplinary approach for the safe implementation of nanotechnology: Perspective of
particle synthesis, Kolloqium of the HNO Clinic University of Erlangen, Erlangen, Germany,
November 2015
o Interpartikuläre Kräfte auf der Nanoskala, GDCh-Kolloquium, Paderborn, Germany, November
2015
Monika Mortimer, University of California Santa Barbara
o Separation of Bacteria, Protozoa and Carbon Nanotubes by Density Gradient Centrifugation
(Poster), Emerging Contaminants Summit, Westminster, CO, March 1-2, 2016
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Andre E. Nel, University of California Los Angeles
o An engineered approach to therapeutics and immune perturbation for pancreatic cancer, 2016
International Symposium on Nanobiotechnology, Los Angeles, CA, February 2016
o Use of alternative test strategies, predictive toxicological approaches, and categorization to
expedite decision analysis of nanomaterial safety, 2015 International Chemical Congress of
Pacific Basis Societies (PacificChem), Honolulu, HI, December 2015
o Breakthroughs in medicine and biotechnology based on nano-bio interface discoveries, 2015
NSF Nanoscale Science and Engineering Grantees Conference, Arlington, VA, December 2015
o Nanomedicine at CNSI: Development of nanocarriers for treatment of pancreatic cancer and
tumor immunology, Harbor UCLA Medical Center Grand Rounds, Los Angeles, CA, Nov 2015
o Nanomedicine grand challenges are needed to show the important contribution of nano to
healthcare, 2015 Sustainable Nanotechnology Conference, Portland, OR, November 2015
o Development of multifunctional mesoporous silica nanocarriers for treatment of pancreatic
cancer, Chinan Nano 2015, Beijing, China, September 2015
o Use of alternative test strategies, predictive toxicological approaches and categorization to
expedite decision analysis of nanomaterial safety, The Sixth International Conference on
Nanoscience & Technology/China Nano 2015, Beijing, China, September 2015
o The UCLA/CNSI EHS platform for safe implementation of emerging technologies, Directors
Forum on Nanotechnology, Beijing, China, September 2015
o What exactly is the utility of nanotoxicology in the development of nanotechnology?, UC Davis
Seminar, Davis, CA, April 2015
Catherine Nameth, University of California Los Angeles
o Two views of interdisciplinary research: A conceptual theory and a case study, Lesley University
Community of Scholars, Cambridge, MA, March 2016
o (Co-presenter with Wheeler) Sustainable nanoMAterials Laboratory (SMAL): A research-based
laboratory module for undergraduates, 251st American Chemical Society Annual Meeting, San
Diego, CA, March 2016
o (Co-presenter with Wheeler) A collaborative multidisciplinary approach to curriculum
development: The Sustainable nanoMAterials Laboratory (SMAL) (Poster), 2016 Southern
California PKAL Regional Network Annual Meeting, Irvine, CA, February 2016
o Getting the data you need: Designing student surveys for your course or program, 2016
Southern California PKAL Regional Network Annual Meeting, Irvine, CA, February 2016
o Improving the evaluation process through community networks, American Evaluation
Association, Chicago, IL, November 2015
o Pause-Commit-Engage: A rubric for direct observation in informal learning environments,
American Evaluation Association, Chicago, IL, November 2015
o Getting the information you need: Designing surveys and questionnaires for your course or
program, MATEC Networks Faculty Development Webinar, November 2015
o (Co-presenter with Wheeler) Sustainable nanoMAterials Laboratory (SMAL), High Impact
Technology Exchange Conference (HI-TEC) 2015, Portland, OR, July 2015
Roger Nisbet, University of California Santa Barbara
o Dynamical systems models based on energy budgets for ecotoxicological impact assessment,
Society of Environmental Toxicology And Chemistry (STEAC) Conference, Salt Lake City, UT,
November 2015
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Suman Pokhrel
o Physicochemical characterization for cellular toxicity evaluation of metal oxide nanoparticles:
FP7 project MODERN, Malaga, Spain, November 2015
o Synthesis and characterization of pure and Eu/CeO 2 and SiO 2 nanoparticles, Verbundtreffen im
Rahmen des BMBF-geförderten Verbundprojekts “DENANA - Designkriterien für nachhaltige
Nanomaterialien, Umweltbundesamt, Berlin, Germany, October 2015
o Nanoparticle designing criteria: Eu doped CeO 2 as an example, “DENANA - Designkriterien für
nachhaltige Nanomaterialien“ AP, A&H Workshop, Klüber Lubrication, Munich, Germany Sep
2015
Cristina Torres, UC Davis Bodega Marine Laboratory
o Propiedades de Nanomateriales y su Toxicidad: Hacia un diseño más seguro (Properties of the
Nanomaterials and their Toxicity: Towards a Safer Design), XIII Semana Cultural de la División de
Ingeniería, University of Sonora in Hermosillo, Sonora, Mexico, November 2015
Jason Townson, University of New Mexico
o Re-examining the size/charge paradigm and other misconceptions in nanocarrier-based delivery
for cancer, Materials Research Society 2015, Boston, MA, December 2015
Illya Medina Velo, University of Texas El Paso
o Effects of two commercial ZnO nanoparticles in red kidney bean plants (Poster), Sustainable
Nanotechnology Organization (SNO) Conference, Portland, OR, November 2015
Ying Wang, University of California Santa Barbara
o (Co-presenter with Welch) Combined effects of engineered carbonaceous nanomaterial
exposure and environmental stressors upon soil-grown soybeans (Poster), UCSB Conference
Celebrating the 50th Anniversary of the Natural Reserve System, October 2015
Zoe Welch, University of California Santa Barbara
o Examining the impacts of copper-based nanopesticides to free-living, planktonic populations of
the diazotrophic soybean symbiont, Bradyrhizobium japonicum USDA110, Interdepartmental
Graduate Program in Marine Science Winter Seminar Series, Santa Barbara, CA, March 2016
o (Co-presenter with Y. Wang) Combined effects of engineered carbonaceous nanomaterial
exposure and environmental stressors upon soil-grown soybeans (Poster), UCSB Conference
Celebrating the 50th Anniversary of the Natural Reserve System, October 2015
Korin Wheeler, Santa Clara University
o (Co-presenter with Nameth) Sustainable nanoMAterials Laboratory (SMAL): A research-based
laboratory module for undergraduates, 251st American Chemical Society Annual Meeting, San
Diego, CA, March 2016
o (Co-presenter with Nameth) A collaborative multidisciplinary approach to curriculum
development: The Sustainable nanoMAterials Laboratory (SMAL) (Poster), 2016 Southern
California PKAL Regional Network Annual Meeting, Irvine, CA, February 2016
o (Co-presenter with Nameth) Sustainable nanoMAterials Laboratory (SMAL), High Impact
Technology Exchange Conference (HI-TEC) 2015, Portand, OR, July 2015
o Assessment of protein coronal structure and mediation of particle reactivity (Poster), Gordon
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Tian Xia, University of California Los Angeles
o High Throughput Screening and a predictive toxicological approach for hazard ranking of
nanomaterials, Association for Environmental Health and Sciencees (AEHS) Annual International
Conference, San Diego, CA, March 2016
o The crucial role of lysosomes in autophagy regulated NLRP3 inflammasome activation, Research
Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China, Oct 2015
Jeffrey I. Zink, University of California Los Angeles
o Multifunctional inorganic nanoparticles controlled by nanomachines for in vitro and in vivo drug
delivery, Los Padres American Chemical Society Section Meeting, Buellton, CA, October 2015
o External and autonomous control of nanomachine-regulated theranostic nanoparticles, Gordon
Research Conference on Artificial Molecular Switches and Motors, Easton, MA, June 2015
o Multifunctional mesoporous silica nanoparticles controlled by nanomachines for biomedical
targeting, imaging and drug delivery, 38th Annual Meeeting of the Brazilian Chemical Society,
Aguas de Lindola, Brazil, May 2015
o Multifunctional inorganic nanoparticles controlled by nanomachines for in vitro and in vivo drug
delivery, Pennsylvania State University, State College, PA, April 2015
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13. Shared and Experimental Facilities
UCLA
(1) CEIN Laboratory(2600sq+): housed in the California NanoSystems Institute (CNSI) building, centrally
located on the UCLA campus. The CEIN has recently installed a Perkin-Elmer AAnlyast Graphite
Spectrometer and a Shimadzu ICPE-9000 to expand characterization. This equipment joins our existing
CEIN characterization and HCS equipment: Quadrasorp SI to analyze surface area and pore size of our
library NMs; Wyatt DynaPro Plate Reader Dynamic Light Scattering instrument; a Brookhaven Zeta
Potential analyzer; and an Elisa Plate. Bench space has also been outfitted to accommodate
approximately 10 working bays.
(2) Molecular Screening Shared Resource (MSSR): houses two fully integrated HTS systems: (i)
Automated liquid handling, multiple plate reading, plate filling and washing, deshielding, and delidding,
and online incubators for cell-based assays using a Beckman/Sagian system equipped with an Orca
robotic arm that delivers plates to individual work stations; Beckman Biomek FX liquid handling robot
(96-well pipetting, 96- or 384-pin transfer); Perkin–Elmer Victor3(V) plate reader (96–1536 well plates)
to assess luminescence, fluorescence, fluorescence polarization, time-resolved fluorescence, UV–Vis
absorbance modes); Molecular Devices FlexStation II plate reader equipped with an integrated pipetter
and general fluorescence and luminescence plate applications in 96- or 384-well format; Cytomat 6001
incubator: CO 2 incubator; Multidrop 384: manifold liquid dispensing into 96- or 384-well plates; ELx 405
plate washer: well washing, aspiration, dispensing. The current capacity of cell-based assay is ca. 105
wells (conditions)/day. Multiple plate readers allow fluorescence, FRET, BRET, time-resolved
fluorescence, fluorescence polarization, luminescence, and UV–Vis absorption assays. (ii) A second
Beckman/Sagian Core system for HCS using automated microscopy with an Orca arm; Molecular Devices
ImageXpress (micro) automated fluorescence microscope and a Cytomat 6001 incubator.
(3) Zebrafish Facility: under the direction of Dr. Shuo Lin, this state of the art facility in the UCLA Life
Sciences Building facilitates the use and quick access of common mutations, genetically engineered
transgenic zebrafish and routine techniques of zebrafish manipulations. The core provides four major
categories of service: i) space for housing and performing larger scale genetic or chemical genomic
screens; ii) assistance in development of zebrafish experiments; iii) generation of transgenic zebrafish;
and iv) cryostorage of zebrafish sperm and re-derivation of live fish.
(4) Molecular Instrumentation Center is a state-of-the-art campus-wide facility dedicated to molecular
characterization housed in the Department of Chemistry. With focus on Magentic Resonance, Mass
Spectrometry, Materials Characterization, and X-Ray Diffraction, equipment includes SEM, differential
scanning calorimetry, thermogravimetric analysis, magnetic resonance imaging, X-ray diffractometers,
mass spectrometry for proteomics and biochemistry instrumentation, ICP-AES for elemental analysis
and speciation.
(5) CNSI Core Facilities provide additional equipment not found in the above laboratories on a recharge
basis. Nanoelectronics Research Facility includes scanning electron microscopy (SEM) with energydispersive analysis of X-rays; transmission electron microscopy; surface profilometers and ellipsometers.
UCLA’s Environmental Nanotechnology Research Laboratory includes a programmable oven, furnace,
and microwave systems for NM synthesis, bench-top micro-centrifuge and stirred filtration cells for NM
isolation, BET analyzer for powder surface area and pore size analyses, equipment for polymer phase
inversion, interfacial polymerization, and solution casting. Nano-Bio Interfacial Forces Laboratory
includes a contact angle goniometer for powder/substrate wetting and surface energy analyses; particle
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micro-electrophoresis system for particle electrophoretic mobilities (zeta potentials); dynamic and static
light scattering for evaluating particle sizes and polymer molecular weights; upright optical and epi
fluorescence microscope; and AFM integrated with inverted optical microscopy.
UC Santa Barbara:
Four clusters of laboratories are available to CEIN:
(1) CNSI-UCSB provides recharge access to the Microscopy and Microanalysis Facility: three transmission
electron microscopes (FEI Titan FEG and two FEI Tecnai G2 Sphera), three SEMs (FEI XL40 Sirion FEG, FEI
XL30 Sirion, FEI Inspect S), five scanning probe STM/AFM microscopes (Digital Multi-mode Nanoscope,
Digital Dimension 3000, Digital Dimension 3100, Asylum MFP-3D SL, Asylum MFP-3D Bio), a secondary
ion mass spectrometer (Physical Electronics 6650 Quadrupole), X-ray Photoelectron Spectroscopy Kratos
Axis Ultra System, Focused Ion Beam System (Model DB235 Dual Beam). The Spectroscopy Facility has
seven state-of-the-art spectrometers (Nicolet Magna 850 IR/Raman, Varian Cary Eclipse Fluorimeter,
Bruker DPX200 SB NMR for solutions, DSX300 WB NMR for solids, DMX500 SB NMR for solutions, Bruker
IPSO500 WB NMR for solids, Bruker EMX Plus EPR spectrometer).
(2) Bren School of Environmental Science and Management. The School Infrastructure Lab (2350 sf)
includes a Shimadzu HPLC with fluorescence and diode array detectors, Shimadzu GC/FID, Beckman
scintillation counter, total-carbon analyzer, –80 °C Revco freezer, high-speed refrigerated Sorvall
centrifuge, two static incubators for cultivation at 37 and 41 °C, refrigerator, water baths,
spectrophotometers, hybridization oven, UV crosslinker, Nanopure water system, autoclave, icemaker,
laboratory microwave, two multi-user walk-in 4 ºC rooms for sample storage and two walk-in freezers,
and two variable-temperature rooms. Holden’s lab (930 sf) includes: HP 6890 GC/MS with autosampler;
Baker biological control cabinet; Sorvall microcentrifuge; New Brunswick shaker/incubator; analytical
balances; Nikon E-800 epifluorescent microscope equipped with a CCD camera and NIS-Elements
acquisition and analysis software; BioTek Synergy2 microplate shaker/incubator/reader with UV/Vis/TRF
detectors; PCR and qPCR thermal cyclers and other equipment related to electrophoresis, PCR product
quantification, and analyzing terminal labeled restriction fragment length polymorphisms. MicroEnvironmental Imaging and Analysis Facility (MEIAF), an environmental SEM with a cryo-stage for
imaging frozen materials and an X-ray detector for elemental analysis (300 sf). The MEIAF is available to
the public on a recharge basis. Keller’s lab (940 sf) includes: Malvern Zetasizer nano series Nano-ZS90;
and QSonica Misonix Sonicator S-4000; Shimadzu high performance liquid chromatography (HPLC)
system (SPD-M10AVP); Varian Saturn 2100T GC/MS with autosampler; Nikon Optiphot-M epifluorescent microscope with CCD camera; Thermo Cahn Radian 315 dynamic contact angle analyzer;
Brookfield viscometer; column transport pumps and controllers.
(3) Department of Ecology, Evolution, and Marine Biology. Schimel’s lab includes: two Finnegan MAT
Delta Plus MS systems equipped with elemental analyzer, gas bench, pyrolysis, and GC inlet systems
(available through MSI analytical lab); two multichannel Lachat autoanalyzers for dissolved nutrients;
C/N analyzer for solid samples; Shimadzu GC 14 for simultaneous CO 2 , CH 4 , and N 2 O analyses; microtiter
plate reader (UV/Vis) for enzyme and chemical assays. Nisbet’s lab has high-end PCs for DEB modeling,
additional access to a high-performance computing multi-node facility at UCSB is available on a recharge
basis; Leica Dissecting scope with digital color camera; Leica inverted microscope, fully motorized, with
monochrome camera; Molecular Devices Gemini EM scanning spectrofluorometer (top and bottom
reads); C/N Analyzer for solid samples; Ocean Optics Jaz portable spectrofluorometer; four peristaltic
pumps; Mettler-Toledo Ultra-microbalance; Millipore Elix water system; bath sonicator; two incubators.
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(4) MRL Facilities provide access on a recharge basis: Thermo iCAP 6300 Inductively Coupled Plasma ICP
Spectrometer; Shimadzu UV3600 UV-Nir-NIR Spectrometer; Mettler 851e TG coupled to a Pfeiffer
ThermoStar Mass Spectrometer TGA-MS for thermo gravimetric analysis; Quantum Design MPMS 5XL
SQUID Magnetometer; Bruker D8 Theta-Theta XRD; MicroMeritics TriStar Porosimeter for surface area,
pore volume, and pore size distribution measurements; Perkin Elmer LS 55 Luminescence Spectrometer.
UC Davis:
Bodega Marine Laboratory (BML) houses 16 specialized wet labs. Equipment includes state-of-the-art
fluorescence imaging facility, ultracentrifuges, ultra-cold freezers, autoclaves, a 28-ft flow-visualization
water tunnel/flume, OES mass spectrometer, and experimental climate change laboratories. Support
buildings include terrestrial and marine greenhouses, animal resources, marine operations (diving,
vessels and ocean observing), and an industrial shop (engineering, fabrication, and maintenance).
Seawater Laboratory Sensor Network: a sophisticated computer-controlled, up to 1,000,000-gallon/day
seawater system that provides seawater to the wet labs, classrooms and public displays. Specialized
laboratories on the Seawater Sensor Network include a marine pathology laboratory (the only Stateapproved facility for marine pathology studies) and salt and freshwater laboratory for studies of
threatened and endangered species. Cherr’s laboratory houses BML’s Fluorescence Imaging Facility,
which includes a Photon Technology spectrofluorometer with ratiometric and ion quantitation software;
high-speed fluorescence video imaging system on a fixed stage microscope controlled by Metamorph
software; three epifluorescence microscopes; UVP Epichem II fluorescence/chemiluminescence gel
documentation system; Tecan Genios time-resolved fluorescence/ and luminescence/absorbance plate
reader; Olympus Fluoview 500 confocal scanning laser microscope with temperature controlled stage
and water immersion objective lenses; Expert Vision System motion analysis software; and a Nikon
AZ100 fluorescence stereo zoom microscope with a computer controlled stage HCS software capabilities
UC Riverside:
Walker‘s laboratory is equipped with an inverted Olympus IX70 microscope (phase contrast or
fluorescent mode), used to image bacterial cells or particle attachment to test surfaces within a parallel
plate flow cell or a radial stagnation point flow cell. The lab is also equipped with an Electrokinetic
Analyzer for streaming potential measurements and a ZetaPal machine for particle electrophoretic
mobility and dynamic light scattering (both pieces by Brookhaven Corp.).
Northwestern University:
The Hersam Laboratory (3000 sq. ft.) houses five fume hoods and the following major pieces of
instrumentation: (i) 2 Thermomicroscopes CP Research Atomic Force Microscopes (AFMs): characterize
mechanical (force-distance spectroscopy) and electronic (electric force microscopy and scanning
potentiometry) properties of materials at the nanometer scale in ambient, controlled atmosphere, and
liquid environments; (ii) 2 Room Temperature Ultra-high Vacuum (UHV) Scanning Tunneling
Microscopes (STMs): These home-built multi-chamber systems are used to prepare pristine surfaces,
which are then characterized at the atomic-scale with STM and scanning tunneling spectroscopy.
Feedback controlled lithography has also been implemented to isolate and pattern individual molecules
on surfaces in atomically precise geometries. The UHV chambers (base pressure ~ 2×10-11 Torr) are
directly interfaced to a controlled atmosphere glove box (oxygen and water concentrations < 1 ppm) to
enable combined UHV and wet chemical processing with minimal contamination; (iii) 1 Cryogenic
Variable Temperature UHV STM: this system controls the temperature of the sample and the
microscope between 10 K and 400 K, ideal for cryogenic studies and high resolution scanning tunneling
spectroscopy; (iv) 1 Nanoelectronic Charge Transport Measurement Apparatus: Enables electrical
characterization of nanoscale devices and sensors. The apparatus includes a wafer prober, hall
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measurement apparatus, high sensitivity source-measure unit, spectrum analyzer, current preamplifier,
lock-in amplifier, and 4-channel digital oscilloscope. (v) 3 Density Gradient Ultracentrifugation (DGU)
Apparatuses: Used to sort carbon nanotube and graphene samples by their physical and electronic
structure. Each apparatus includes a horn ultrasonicator, a Beckman Coulter Optima L-90 K Preparative
Ultracentrifuge, and a BioComp Piston Gradient Fractionator.
University of New Mexico/Sandia National Lab:
Brinker's Biocharacterization laboratory integrates biological organisms/components with engineered
platforms. Capable of handling Biosafety Level 2 organisms and cell lines and the isolation and analysis
of DNA, RNA, and proteins. Methods used to incorporate biological organisms/components onto
engineered platforms: vesicle fusion; multiple tethering schemes; and plugged flow packing. Other
capabilities include: ellipsometry for film characterization; electrochemistry; a PCR instrument for DNA
amplification; a laser connected to an inverted microscope for fluorophore interrogation; and a
hyperspectral microarray scanner for microarray analysis. The AML facility contains standard
microbiological and biochemical equipment and supplies for handling the microorganisms and cell lines
proposed for use on this project: Class II flow bench; standard and CO 2 incubators; cryo-storage;
freezers and refrigerators; autoclave; and a fluorescence microscope. The laboratory includes a new
Asylum Research MFP-3D-BioAFM integrated with a Nikon TE2000-U inverted fluorescence microscope,
which combines molecular resolution imaging and picoNewton force measurements on an inverted
optical microscope to allow: in situ imaging of the surfaces of living cells upon exposure to NMs;
measurement of adhesive forces of proteins/NMs on cell surfaces; single-molecule force spectroscopy
of single NPs; and nanolithography and manipulation of samples on the nanometer and picoNewton
scale.
University of Texas, El Paso:
Gardea-Torresdey’s laboratory: 3100 Perkin–Elmer flame atomic absorption spectrometer; 4100 ZL
Perkin–Elmer Zeeman graphite furnace atomic absorption spectrometer; 4300 DV Perkin–Elmer ICP OES;
Perkin–Elmer Elan DRC IIe Laser ablation/HPLC/ICP-MS; EG&G Model 394 electrochemical trace
analyzer; Hewlett–Packard 5890 GC; Hewlett–Packard 5972 GC/MS; Perkin–Elmer Spectrum 100 FTIR
spectrometer coupled to a Perkin–Elmer Spectrum spotlight 300 FTIR microscope; Nano-ZS 90, Malvern;
Fisher XRF. Additional shared resources: Bruker 250-MHz NMR spectrometer; Bruker 300-MHz multinuclei NMR spectrometer; Electroscan 2020 environmental SEM; Kevex omicron X-ray
microfluorescence spectrometer; Hitachi S-4800-II SEM with EBSD; EDAX/TSL X-ray analyzer and
electron backscatter diffraction imaging equipment; Zyvex Nanomanipulator and Nanoprobe; Hitachi H8000 TEM; Fluorescence microscopy; confocal microscope; conductivity meter; AFM. The XAS studies
planned for this project will be performed at Stanford Synchrotron Radiation Laboratories (SSRL),
Stanford, CA, where Gardea-Torresdey has received beam time the duration of this project.
University of Bremen:
Foundation Institute for Materials Science material characterization equipment available: X-ray
diffraction (with extended Rietveld analysis); TEM and SEM; surface adsorption analysis (adsorption
isotherms), UV-vis spectroscopy, Dynamic Light scattering, Zeta-potential und centrifugal particle sizer.
Mädler’s laboratory has state-of-the-art flame spray pyrolysis reactors for the synthesis of various metal
oxide-based NMs, including their functionalization with noble metals as well as double flame reactors.
107
14. Personnel
Management and Organization Strategy
The UC CEIN organizational strategy is to maintain a strong infrastructure that supports and integrates our
research, technology development, educational, outreach and diversity efforts.
By facilitating
communication across our participating communities, our organizational structure allows for selection,
prioritization, distribution, and management of resources within a multi-institutional structure. By
combining management of our financial operations with our programmatic operations, UC CEIN has been
able to create an infrastructure designed to streamline the Center's activities while meeting the reporting
requirements of the funding agency and the University.
Leadership
Andre Nel (UCLA) serves as the Center Director and Principal Investigator. As Director, Dr. Nel is
responsible for the integration of the Center’s overall research, education and outreach activities. Arturo
Keller (UCSB) is the Associate Director, responsible for coordinating the research integration, seminars,
student training, and outreach activities at UC Santa Barbara to provide seamless integration with the
activities at UCLA. Focused leadership for the education and outreach components of the Center is
provided by Hilary Godwin (UCLA). This faculty management team provides complimentary expertise and
strategic leadership to ensure the Center’s vision and mission.
Research Themes
UC CEIN research is organized into seven themes, each under the leadership of a CEIN faculty member.
Each theme engages several faculty, postdoctoral researchers, research staff, and graduate students. Key
to the success of the CEIN is the integration of research within and across themes. Theme leaders (who are
also members of the CEIN Executive Committee) are responsible for setting priorities, allocating resources,
and tracking progress towards achievement of the theme's goals. Frequent formal communication
between theme leaders is key to ensuring that progress is made across all groups, and the findings of one
theme are rapidly disseminated other themes. Projects submit periodic progress updates to their theme
leader, the results of which are shared and discussed by the UC CEIN Executive Committee.
Executive Committee
The Executive Committee is composed of the Director, Associate Director, Education/Outreach Director,
Co-PIs, Theme leaders, and the Center Chief Administrative Officer. In fall 2012, CEIN faculty member Jorge
Gardea-Torresday (University of El Paso Texas) joined the Executive Committee to provide additional input
and guidance. The Executive Committee meets at least once per month and is responsible for assisting the
Director with integration and coordination of research and education, overall resource allocation, and
outreach to the scientific, industrial, and policy community. Several times a year, the Executive Committee
reviews long-term directions of the Center and possible strategic redirections. Prior to any Research
Reviews, Site Visits, and External Science Advisory Committee meetings the EC focuses on strategic
planning. Research progress for all projects is reviewed on an ongoing basis, with projects submitting
Quarterly progress updates.
Allocation of Center resources is based on the following metrics: (i)
contribution of the proposed work to the CEIN’s core goals; (ii) productivity, publication, and product
delivery record; (iii) novelty; (iv) integration and cooperation with other funded CEIN projects; (v)
availability of resources and facilities to carry out proposed projects; and (vi) timely delivery of tangible
results.
One to two times per year, the Executive Committee meets for a day long research retreat. The retreat
focuses on the review of overall Center priorities and is a forum for discussing and establishing key short
and long term goals for the Center, with particular focus on strengthening integration across all Themes.
108
External Science Advisory Committee
The UC CEIN has convened an External Science Advisory Committee (ESAC) comprised of scientists,
technologists, industry members, and policy and education specialists. The ESAC advises the Center’s
Executive Committee with respect to CEIN strategic directions and management policies. The ESAC
provides feedback on the focus and direction of CEIN research, progress made toward achieving Center
goals, and illuminating new research and educational opportunities. The diversity of this group provides a
comprehensive perspective on the major advances in nanotechnology and key issues with regards to
potential environmental implications. In response to the most recent Site Visit comments, we expanded
the ESAC committee in 2013 to include a more diverse pool of advisors. The ESAC meets twice a year by
teleconference and holds an in-person meeting at UCLA every other year. In addition to the group
meetings, UC CEIN Executive Committee members engage ESAC members on an individual basis throughout
the year based on their expertise. Additionally, ESAC members are invited to Center public events,
including our Outreach workshops and scientific meetings. The composition of the ESAC is reviewed by the
Executive Committee every two years.
Current External Science Advisory Committee member:
• Pedro Alvarez, Rice University
• Ahmed Busnaina, Northeastern University
• Sharon Dunwood, University of Wisconsin-Madison
• C. Michael Garner, Retired (formerly Intel)
• Agnes Kane, Brown University
• Mark Lafranconi, Tox Horizons
• Kent Pinkerton, UC Davis
• Rick Pleus, Intertox
• Omowunmi Sadik, SUNY Binghamton
• Ron Turco, Purdue University
• Isiah Warner, Louisana State University
• Jeff Wong, CA Department of Toxic Substances Control
• Paul Zimmerman, Intel
Student-Postdoctoral Advisory Committee
A Student-Postdoctoral Advisory Committee (SPAC) continues to be active and key role within the CEIN.
The committee includes graduate student and postdoctoral scholar representatives from each of the
Center's themes. The SPAC provides ongoing input into the development of the CEIN education program
(including development of undergraduate mentoring opportunities), development of full-day annual
leadership workshops (next scheduled for May 2016), and formulation of goals for future Center workshops
and seminar series. With input from the SPAC, the Education/Outreach Director and Coordinator have
refined our annual evaluative survey which among other topics, documents educational and training
achievements of Center trainees, results of which are discussed with the SPAC.
Support Cores
The UC CEIN has identified four key Core function areas that form the basis for the Center's research
infrastructure and provide support to enable the execution of research of the highest caliber. The Core
areas interact across the Center's projects to enable smooth cross-disciplinary integration. The Cores are
key in the ability to expand the scope of research within the Center and to maintain the flexibility necessary
to conduct complex multidisciplinary research across a range of themes. Each of the Cores is housed
within the California NanoSystems Institute (CNSI) facility at UCLA. Each of the Center's Core functions to
109
provide the infrastructure and key support needed to carry out the wide range of multidisciplinary activities
within the Center. Each Core serves a unique and necessary function. Cores B, C, and D are all adaptations
of previously existing research projects with the Center. The interactions with the Cores and the Themes
are essential to the scientific research advances of the Center. As the Center's mission leads to the
exploration of new questions about the environmental implications of nanomaterials, whether that
involves new materials, new environmental conditions, or new types of data collected, the Cores will
continue to play a key integrated role in the mission of the Center. The Cores are led by research staff who
have the technical skills to interact across Center projects. Ideas for future development of Core activities
arise through ongoing discussion with theme leaders based on the direction and findings of the Center's
overall research agenda.
• Core A:
Administrative Core
• Core B:
ENM Acquisition, Characterization, and Distribution
• Core C:
Data Management Core
• Core D:
Molecular Shared Screening Resource
Core A: Administrative Support
An administrative staff has been compiled at UCLA to support streamlined operations of the Center. Since
establishment of the Center in September 2008, the administration of the Center has operated under
continuous management of the Center's Chief Administrative Officer (CAO). Utilizing experience in
managing other large federally funded research, the CEIN administration is organized to provide maximized
support to all Center projects in the most efficient manner possible. The CAO assists the Director by
overseeing the general administration, cooperation, communication, planning, financial implementation,
goals setting, and development of Center activities. The CAO is supported by the following dedicated staff:
o Financial/Budget Coordinator – responsible for financial management and reporting
systems across partner institutions
o Administrative Assistant – provides general support for all Center activities including
meeting coordination
o Education Coordinator – under joint supervision of the CAO and Education/Outreach
Director, organizes the training, communication, diversity, and evaluation components of
the program.
o Outreach Coordinator - in Spring 2012, CEIN recruited an Outreach Coordinator who works
under the direction of the CAO, the Director, and the Education/Outreach Director to
develop and implement our Center's outreach activities targeted towards stakeholders in
academia, industry, and policy makers.
o To assist in the administrative coordination of the UC Santa Barbara activities, a half time
administrative support staff position has been allocated to UCSB.
Core B: ENM Acquisition, Characterization, and Distribution
Core B is closely tied to the activities of Theme 1 and operates under the direction of Theme 1 leader
Jeffrey I. Zink, who oversees the technical director, Dr. Zhaoxia Ivy Ji. Core B maintains the Centers
nanomaterials library and coordinates the synthesis or acquisition and the distribution of ENMs across
research projects and themes. This process necessitates close interaction with the toxicity groups to
understand the major findings of current ongoing studies and to work with the material synthesis projects
to redesign materials as needed to affect material properties. In order to conduct material characterization
under relevant exposure conditions, Core B is closely affiliated with the cellular and environmental study
investigators to determine the relevant range of characterization procedures and media to be conducted
for each material. Characterization parameters that are key to our ongoing studies are: size and
distribution analysis in relevant media, agglomeration kinetics, sedimentation studies, and surface charge
analysis.
110
Core B has four main responsibilities:
1. The standard reference and combinatorial nanomaterial libraries are the sources of materials for
mechanistic and high-throughput studies designed to probe environmental fate and transport of these
materials as well as their cellular, organism, and ecosystem toxicity. Currently more than 100 different
nanomaterials, varying from metals, metals oxides, to carbon nanotubes, have been introduced into
the library.
2. The major “service” function of Core B involves characterization of the nanomaterials as they are
synthesized or acquired. Its goals are to thoroughly characterize nanoparticles of commercial
importance and make them available in usable forms and quantities for in vitro and in vivo studies.
“Conventional” particles of commercial importance and scientifically-important high value particles are
characterized by Core B.
3. Development of methods of dispersing nanoparticles in biologically relevant media is another major
service function. Important insight has been gained by the Center, particularly regarding the influence
of cell culture media as they influence dose metrics. For each type of particle introduced into the
Center, Core B explores the best method of dispersion and documents these methods.
4. Core B is also responsible for the distribution and tracking of materials across Center projects. The
inter- and intra-campus distributions of both the particles and the characterization information
associated with them have been very reliable and efficient.
Core C: Data Management Core
The UC CEIN Data Management Team, under the supervision of Theme 6 leader Cohen, is responsible for
development and maintenance of the computational infrastructure and data management system of the
Center. Core C provides core support for data management, data storage, IT support, the web-based
collaborative infrastructure and the computational needs of the Center. The technological infrastructure of
the Center was developed to keep pace with the data generated by Center projects and to meet the
computational needs of the Center's data analysis and modeling projects. Core C has implemented a
center-wide file and data repository, hosts the Center's public website, and hosts software that allows for
the searching/organizing/mining of research data uploaded to the system. The data manager (Bacsafra)
works with each project's investigators to facilitate the uploading of data and to adapt the data repository
system to meet the specific data needs of each project. The CEIN Data Management group plays a key role
in the national Nanoinformatics effort. Our computational capabilities have enabled collaborations with
external groups, including the EPAs ToxCast Program and NSF's iPlant Collaborative.
Core D: Molecular Shared Screening Resource
Core D provides scientific and technical consultation in the planning and execution of high throughput
experiments conducted by UC CEIN researchers. The Molecular Shared Screening Resource (MSSR), under
the direction of MSSR Scientific Director Robert Damoiseaux, assists in the translation of existing low
throughput assays and the de novo establishment of novel assays. The expertise and technical capabilities
available through the MSSR make this facility uniquely suited to handle a wide variety of assays, including
those aimed at exploring the interaction between nanomaterials and bacteria, yeast, animal cells, and
whole animals (zebrafish).
Core D (MSSR) is most closely linked to the research in Themes 2 and 5, working with projects to develop
and validate HTS techniques for the screening of cells, bacteria, yeast, and whole animals (zebrafish) for the
effects of interactions with nanomaterials. MSSR staff work closely with project researchers to translate
existing assays to high throughput format, which includes adaptation of the assays for implementation on
the robotics systems and providing assistance in conducting validation studies and data analysis. Once
111
assays have been validated for HTS, screens may be conducted using additional Center library
nanomaterials as dictated by the ongoing research project hypotheses.
Organization Chart
Changes in Personnel
During the past year, Theme 5 Leader/UCSB Investigator Hunter Lenihan opted to resign from the CEIN to
focus on his other research endeavors.
The Executive Committee unanimously selected Theme 5
investigator and Executive Committee member Roger Nisbet as the new theme leader for Theme 5.
Responsibilities for ongoing theme 5 projects that were under the oversight of Lenihan were shifted to
UCSB investigator Robert Miller and UCD investigator Gary Cherr. No significant change in the scope of
Theme 5 occurred as a result of this personnel change.
As part of its annual review of projects and ongoing progress, the Executive Committee has wrapped up
project support for the work at Columbia University, effective September 2015. The project in Theme 3
under the direction of Professor P. Somasundaran has reached its natural conclusion and funds were
reallocated to other projects within Theme 3 keeping with the mission and scope of the Center.
112
Table 4a: NSEC Personnel - All, irrespective of Citizenship
Gender
Personnel Type
Total
Leadership, Administration/Management
Subtotal
Director(s)
1
Thrust Leaders
1
Administrative Director and Support Staff
Research
Subtotal
Senior Faculty 1
Junior Faculty
1
Research Staff
Visiting Faculty 1
Industry Researchers
Post Docs 1
Doctoral Students
1
Race Data
Ethnicity:
Hispanic
Disabled
% NSEC
Dollars
0
3
0
100%
0
1
0
100%
0
0
1
0
100%
0
0
0
1
0
-
68
1
1
6
31
0
99%
4
0
0
0
1
0
87%
100%
Mixed - incl.
AI/AN, B/AA, Mixed - W/A
NH/PI
Male
Female
AI/AN
NH/PI
B/AA
W
A
21
9
12
0
1
0
17
3
0
0
2
2
0
0
0
0
2
0
0
0
7
4
3
0
0
0
7
0
0
12
3
9
0
1
0
8
3
170
95
73
1
2
6
83
15
14
1
0
0
0
11
Not
Provided
3
3
0
0
0
0
1
2
0
0
0
0
0
20
12
8
0
1
1
10
8
0
0
0
3
0
-
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
0
0
0
0
0
0
0
0
0
0
0
0
0
-
25
17
8
0
0
1
10
14
0
0
0
1
0
100%
100%
40
18
22
0
0
2
20
16
0
0
2
10
0
Master’s Students 1
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
Undergraduate Students (non-REU) 1
65
31
34
1
1
2
31
24
1
1
4
16
0
100%
High School Students
2
0
0
0
0
0
0
0
0
0
0
0
0
50%
Curriculum Development and Outreach
Subtotal
3
1
2
0
0
0
3
0
0
0
0
0
0
Senior Faculty 1
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
Junior Faculty 1
1
0
1
0
0
0
1
0
0
0
0
0
0
100%
Research Staff
Visiting Faculty 1
1
1
0
0
0
0
1
0
0
0
0
0
0
-
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
0
0
0
0
0
0
0
0
0
0
0
0
0
-
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
1
0
1
0
0
0
1
0
0
0
0
0
0
0%
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
0
0
0
0
0
0
0
0
0
0
0
0
0
-
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
0%
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
0%
Post Docs 1
Doctoral Students 1
Undergraduate Students (non-REU)
1
High School Students
REU Students
Subtotal
REU students participating in NSEC Research 1
NSEC Funded REU Students
Precollege (K-12)
Subtotal
0
0
0
0
0
0
0
0
0
0
0
0
0
Students
0
0
0
0
0
0
0
0
0
0
0
0
0
-
Teachers—RET
0
0
0
0
0
0
0
0
0
0
0
0
0
-
Teachers—Non-RET
Total 1
0
0
0
0
0
0
0
0
0
0
0
0
0
-
194
105
87
1
3
6
103
71
1
1
6
34
0
81%
1 The percentage of people in the personnel category receiving at least some salary or stipend support from NSF NSEC Program must be provided in the far right
column, "% NSEC Dollars." Details are described in the Instructions section for this table.
LEGEND:
AI/AN NH/PI B/AA WAMixed - incl. AI/AN, B/AA, NH/PI Mixed - W/A US/Perm Non-US -
White
Indian or Alaska Native, Black or African American, or Native Hawaiian or Other Pacific Islander
113
Table 4b: NSEC Personnel - US Citizens and Permanent Residents
Gender
Personnel Type
Total
Race Data
Ethnicity:
Hispanic
Disabled
% NSEC
Dollars
0
3
0
100%
0
1
0
100%
0
0
1
0
100%
0
0
0
1
0
-
34
1
1
1
20
0
100%
3
0
0
0
0
0
100%
0
2
0
0
0
0
0
100%
9
2
0
0
0
1
0
-
0
0
0
0
0
0
0
0
0%
0
0
0
0
0
0
0
0
0
-
0
0
4
0
0
0
0
0
0
100%
0
0
1
16
5
0
0
0
4
0
100%
0
0
0
0
0
0
0
0
0
0
0%
29
1
1
1
31
22
1
1
1
15
0
100%
79%
Mixed - incl.
AI/AN, B/AA, Mixed - W/A
NH/PI
Male
Female
AI/AN
NH/PI
B/AA
W
A
21
9
12
0
1
0
17
3
0
0
2
2
0
0
0
0
2
0
0
0
Thrust Leaders 1
7
4
3
0
0
0
7
0
0
Administrative Director and Support Staff
12
3
9
0
1
0
8
3
112
64
48
1
2
3
69
12
11
1
0
0
0
9
Junior Faculty 1
2
2
0
0
0
0
Research Staff
Visiting Faculty 1
13
8
5
0
1
1
0
0
0
0
0
Post Docs 1
0
0
0
0
4
2
2
0
22
11
11
0
0
0
59
30
Leadership, Administration/Management
Subtotal
Director(s)
1
Research
Subtotal
Senior Faculty 1
Doctoral Students 1
Undergraduate Students (non-REU)
1
Curriculum Development and Outreach
Subtotal
Not
Provided
3
1
2
0
0
0
3
0
0
0
0
0
0
Senior Faculty 1
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
1
1
0
1
0
0
0
1
0
0
0
0
0
0
100%
Junior Faculty
Research Staff
Visiting Faculty 1
Post Docs 1
1
1
0
0
0
0
1
0
0
0
0
0
0
-
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
0
0
0
0
0
0
0
0
0
0
0
0
0
-
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
1
1
0
1
0
0
0
1
0
0
0
0
0
0
0%
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
Undergraduate Students (non-REU) 1
0
0
0
0
0
0
0
0
0
0
0
0
0
0%
136
74
62
1
3
3
89
37
1
1
1
23
0
80%
Doctoral Students
Total 1
1 The percentage of people in the personnel category receiving at least some salary or stipend support from NSF NSEC Program must be provided in the far right
column, "% NSEC Dollars." Details are described in the Instructions section for this table.
LEGEND:
AI/AN NH/PI B/AA WAMixed - incl. AI/AN, B/AA, NH/PI Mixed - W/A US/Perm Non-US -
White
114
15. Publications and Patents
Primary Publications
1. Adeleye, A. S., Conway, J. R., Garner, K., Huang, Y., Su, Y., & Keller, A. A. (2016). Engineered
nanomaterials for water treatment and remediation: Costs, benefits, and applicability. Chemical
Engineering Journal, 286, 640-662. doi: http://dx.doi.org/10.1016/j.cej.2015.10.105
2. Ananthasubramaniam, B., McCauley, E., Gust, K. A., Kennedy, A. J., Muller, E. B., Perkins, E. J., &
Nisbet, R. M. (2015). Relating suborganismal processes to ecotoxicological and population level
endpoints using a bioenergetic model. Ecological Applications, 25(6), 1691-1710. doi:
10.1890/14-0498.1
3. Bandyopadhyay, S., Mukherjee, A., Rico, C. M., Peralta-Videa, J. R., & Gardea-Torresdey, J. L.
(2015). Differential Effects of CeO2 and ZnO Nanoparticles on Chlorophyll and Secondary
Metabolites in Alfalfa (Medicago sativa). Science and Technology Journal, 3(1), 7-13.
4. Bandyopadhyay, S., Plascencia-Villa, G., Mukherjee, A., Rico, C. M., José-Yacamán, M., PeraltaVidea, J. R., & Gardea-Torresdey, J. L. (2015). Comparative phytotoxicity of ZnO NPs, bulk ZnO,
and ionic zinc onto the alfalfa plants symbiotically associated with Sinorhizobium meliloti in soil.
Science of The Total Environment, 515–516, 60-69. doi: 10.1016/j.scitotenv.2015.02.014
5. Baptista, M. S., Miller, R. J., Halewood, E. R., Hanna, S. K., Almeida, C. M. R., Vasconcelos, V. M., .
. . Lenihan, H. S. (2015). Impacts of Silver Nanoparticles on a Natural Estuarine Plankton
Community. Environmental Science & Technology, 49(21), 12968-12974. doi:
10.1021/acs.est.5b03285
6. Barrios, A. C., Rico, C. M., Trujillo-Reyes, J., Medina-Velo, I. A., Peralta-Videa, J. R., & GardeaTorresdey, J. L. Effects of uncoated and citric acid coated cerium oxide nanoparticles, bulk
cerium oxide, cerium acetate, and citric acid on tomato plants. Science of The Total
Environment. doi: http://dx.doi.org/10.1016/j.scitotenv.2015.11.143
7. Beaudrie, C. E. H., Kandlikar, M., Gregory, R., Long, G., & Wilson, T. (2015). Nanomaterial risk
screeining: a structured approach to aid decision making under certainty. Environment Systems
and Decisions, 35(1), 88-109. doi: 10.1007/s10669-014-9529-y
8. Chowdhury, I., Mansukhani, N. D., Guiney, L. M., Hersam, M. C., & Bouchard, D. C. (2015).
Aggregation and Stability of Reduced Graphene Oxide: Complex Roles of Divalent Cations, pH,
and Natural Organic Matter. Environmental Science & Technology, 49(18), 10886-10893. doi:
10.1021/acs.est.5b01866
9. Conway, J. R., Beaulieu, A. L., Beaulieu, N. L., Mazer, S. J., & Keller, A. A. (2015). Environmental
Stresses Increase Photosynthetic Disruption by Metal Oxide Nanomaterials in a Soil-Grown
Plant. ACS Nano, 9(12), 11737-11749. doi: 10.1021/acsnano.5b03091
10. Du, W., Gardea-Torresdey, J. L., Ji, R., Yin, Y., Zhu, J., Peralta-Videa, J. R., & Guo, H. (2015).
Physiological and Biochemical Changes Imposed by CeO2 Nanoparticles on Wheat: A Life Cycle
Field Study. Environmental Science & Technology, 49(19), 11884-11893. doi:
10.1021/acs.est.5b03055
11. Garner, K. L., Suh, S., Lenihan, H. S., & Keller, A. A. (2015). Species Sensitivity Distributions for
Engineered Nanomaterials. Environmental Science & Technology, 49(9), 5753-5759. doi:
10.1021/acs.est.5b00081
12. Gavankar, S., Anderson, S., & Keller, A. A. (2015). Critical Components of Uncertainty
Communication in Life Cycle Assessments of Emerging Technologies. Journal of Industrial
Ecology, 19(3), 468-479. doi: 10.1111/jiec.12183
13. Ge, Y., Priester, J. H., Mortimer, M., Chang, C. H., Ji, Z., Schimel, J. P., & Holden, P. A. (2016).
Long-term effects of multi-walled carbon nanotubes and graphene on microbial communities in
dry soil. [Early online]. Environmental Science & Technology. doi: 10.1021/acs.est.5b05620
115
14. Hernandez-Viezcas, J. A., Castillo-Michel, H., Peralta-Videa, J. R., & Gardea-Torresdey, J. L.
(2016). Interactions between CeO2 Nanoparticles and the Desert Plant Mesquite: A
Spectroscopy
Approach.
ACS
Sustainable
Chemistry
&
Engineering.
doi:
10.1021/acssuschemeng.5b01251
15. Hong, J., Wang, L., Sun, Y., Zhao, L., Niu, G., Tan, W., . . . Gardea-Torresdey, J. L. (2015). Foliar
applied nanoscale and microscale CeO 2 and CuO alter cucumber (Cucumis sativus) fruit quality.
Science of The Total Environment. doi: 10.1016/j.scitotenv.2015.08.029
16. Jiang, W., Lin, S., Chang, C. H., Ji, Z., Sun, B., Wang, X., . . . Nel, A. E. (2015). Implications of the
Differential Toxicological Effects of III–V Ionic and Particulate Materials for Hazard Assessment
of Semiconductor Slurries. ACS Nano. doi: 10.1021/acsnano.5b04847
17. Kaweeteerawat, C., Chang, C. H., Roy, K. R., Liu, R., Li, R., Toso, D., . . . Godwin, H. A. (2015). Cu
Nanoparticles Have Different Impacts in Escherichia coli and Lactobacillus brevis than Their
Microsized and Ionic Analogues. ACS Nano, 9(7), 7215-7225. doi: 10.1021/acsnano.5b02021
18. Liu, H. H., Bilal, M., Lazareva, A., Keller, A., & Cohen, Y. (2015). Simulation tool for assessing the
release and environmental distribution of nanomaterials. Beilstein Journal of Nanotechnology,
6(1), 938-951. doi: 10.3762/bjnano.6.97
19. Liu, R., Ge, Y., Holden, P. A., & Cohen, Y. (2015). Analysis of soil bacteria susceptibility to
manufactured nanoparticles via data visualization. Beilstein Journal of Nanotechnology, 6(1),
1635-1651. doi: 10.3762/bjnano.6.166
20. Liu, R., Jiang, W., Walkey, C. D., Chan, W. C. W., & Cohen, Y. (2015). Prediction of nanoparticlescell association based on corona proteins and physicochemical properties. Nanoscale, 7(21),
9664-9675. doi: 10.1039/c5nr01537e
21. Liu, R., Liu, H. H., Ji, Z., Chang, C. H., Xia, T., Nel, A. E., & Cohen, Y. (2015). Evaluation of Toxicity
Ranking for Metal Oxide Nanoparticles via an in Vitro Dosimetry Model. ACS Nano, 9(9), 93039313. doi: 10.1021/acsnano.5b04420
22. Liu, R., Rallo, R., Bilal, M., & Cohen, Y. (2015). Quantitative Structure-Activity Relationships for
Cellular Uptake of Surface-Modified Nanoparticles. Combinatorial Chemistry & High Throughput
Screening, 18(4), 365-375. doi: 10.2174/1386207318666150306105525
23. Liu, R., & Cohen, Y. (2015). Nanoinformatics for environmental health and biomedicine. Beilstein
Journal of Nanotechnology, 6, 2449-2451. doi: 10.3762/bjnano.6.253
24. Liu, S., Jiang, W., Wu, B., Yu, J., Yu, H., Zhang, X.-X., . . . Cherr, G. N. (2015). Low levels of
graphene and graphene oxide inhibit cellular xenobiotic defense system mediated by efflux
transporters. Nanotoxicology, Early Online 1-10. doi: 10.3109/17435390.2015.1104739
25. Low-Kam, C., Telesca, D., Ji, Z., Zhang, H., Xia, T., Zink, J. I., & Nel, A. E. (2015). A Bayesian
regression tree approach to identify the effect of nanoparticles’ properties on toxicity profiles.
The Annals of Applied Statistics, 9(1), 383-401. doi: 10.1214/14-AOAS797
26. Majumdar, S., Trujillo-Reyes, J., Hernandez-Viezcas, J. A., White, J. C., Peralta-Videa, J. R., &
Gardea-Torresdey, J. L. (2015). Cerium biomagnification in a terrestrial food chain: Influence of
particle size and growth stage. Environmental Science & Technology. doi:
10.1021/acs.est.5b04784
27. Majumdar, S., Almeida, I. C., Arigi, E. A., Choi, H., VerBerkmoes, N. C., Trujillo-Reyes, J., . . .
Gardea-Torresdey, J. L. (2015). Environmental Effects of Nanoceria on Seed Production of
Common Bean (Phaseolus vulgaris): A Proteomic Analysis. Environmental Science & Technology,
49(22), 13283-13293. doi: 10.1021/acs.est.5b03452
28. Mansukhani, N. D., Guiney, L. M., Kim, P. J., Zhao, Y., Alducin, D., Ponce, A., . . . Hersam, M. C.
(2015). High-Concentration Aqueous Dispersions of Nanoscale 2D Materials Using Nonionic,
Biocompatible Block Copolymers. Small, n/a-n/a. doi: 10.1002/smll.201503082
116
29. Mukherjee, A., Sun, Y., Morelius, E., Tamez, C., Bandyopadhyay, S., Niu, G., . . . GardeaTorresdey, J. L. (2016). Differential toxicity of bare and hybrid ZnO nanoparticles in green pea
(Pisum sativum L.): A life cycle study. Frontiers in Plant Science, 6. doi: 10.3389/fpls.2015.01242
30. Muller, E. B., Lin, S., & Nisbet, R. M. (2015). Quantitative Adverse Outcome Pathway Analysis of
Hatching in Zebrafish with CuO Nanoparticles. Environmental Science & Technology, 49(19),
11817-11824. doi: 10.1021/acs.est.5b01837
31. Nel, A. E., Parak, W. J., Chan, W. C. W., Xia, T., Hersam, M. C., Brinker, C. J., . . . Weiss, P. S.
(2015). Where Are We Heading in Nanotechnology Environmental Health and Safety and
Materials Characterization? ACS Nano, 9(6), 5627-5630. doi: 10.1021/acsnano.5b03496
32. Oh, E., Liu, R., Nel, A., Gemill, K. B., Bilal, M., Cohen, Y., & Medintz, I. L. (2016). Meta-analysis of
cellular toxicity for cadmium-containing quantum dots. [Early online]. Nature Nanotechnology.
doi: 10.1038/nnano.2015.338
33. Osborne, O. J., Lin, S., Chang, C. H., Ji, Z., Yu, X., Wang, X., . . . Nel, A. E. (2015). Organ-Specific
and Size-Dependent Ag Nanoparticle Toxicity in Gills and Intestines of Adult Zebrafish. ACS
Nano, 9(10), 9573-9584. doi: 10.1021/acsnano.5b04583
34. Pokhrel, S., Birkenstock, J., Dianat, A., Zimmermann, J., Schowalter, M., Rosenauer, A., . . .
Mädler, L. (2015). In situ high temperature X-ray diffraction, transmission electron microscopy
and theoretical modeling for the formation of WO 3 crystallites. CrystEngComm, 17(36), 69856998. doi: 10.1039/C5CE00526D
35. Rico, C., Barrios, A., Tan, W., Rubenecia, R., Lee, S., Varela-Ramirez, A., . . . Gardea-Torresdey, J.
(2015). Physiological and biochemical response of soil-grown barley (Hordeum vulgare L.) to
cerium oxide nanoparticles. Environmental Science and Pollution Research, 22(14), 1055110558. doi: 10.1007/s11356-015-4243-y
36. Song, H.-M., Zink, J. I., & Khashab, N. M. (2015). Engineering the Internal Structure of Magnetic
Silica Nanoparticles by Thermal Control. Particle & Particle Systems Characterization, 32(3), 307312. doi: 10.1002/ppsc.201400118
37. Song, H.-M., Zink, J. I., & Khashab, N. M. (2015). Seeded growth of ferrite nanoparticles from Mn
oxides: observation of anomalies in magnetic transitions. Physical Chemistry Chemical Physics,
17(28), 18825-18833. doi: 10.1039/C5CP01301A
38. Song, H.-M., Zink, J. I., & Khashab, N. M. (2015). Selective Magnetic Evolution of MnxFe1-xO
Nanoplates. The Journal of Physical Chemistry C. 119(19), 10740-10748. doi:
10.1021/acs.jpcc.5b01938
39. Taylor, A., Marcus, I., Guysi, R., & Walker, S. (2015). Metal Oxide Nanoparticles Induce Minimal
Phenotypic Changes in a Model Colon Gut Microbiota. Environmental Engineering Science, 32(7),
602-612. doi: 10.1089/ees.2014.0518
40. Taylor, A. A., & Walker, S. L. (2016). Effects of copper particles on a model septic system's
function
and
microbial
community.
Water
Research,
91,
350-360.
doi:
http://dx.doi.org/10.1016/j.watres.2016.01.014
41. Torres-Duarte, C., Adeleye, A. S., Pokhrel, S., Mädler, L., Keller, A. A., & Cherr, G. N. (2015).
Developmental effects of two different copper oxide nanomaterials in sea urchin (Lytechinus
pictus) embryos. Nanotoxicology, 1-9. doi: 10.3109/17435390.2015.1107145
42. Wang, H., Adeleye, A. S., Huang, Y., Li, F., & Keller, A. A. (2015). Heteroaggregation of
nanoparticles with biocolloids and geocolloids. Advances in Colloid and Interface Science. doi:
10.1016/j.cis.2015.07.002
43. Wang, H., Dong, Y.-n., Zhu, M., Li, X., Keller, A. A., Wang, T., & Li, F. (2015). Heteroaggregation of
engineered nanoparticles and kaolin clays in aqueous environments. Water Research, 80, 130138. doi: http://dx.doi.org/10.1016/j.watres.2015.05.023
117
44. Wang, X., Mansukhani, N. D., Guiney, L. M., Ji, Z., Chang, C. H., Wang, M., . . . Nel, A. E. (2015).
Differences in the Toxicological Potential of 2D versus Aggregated Molybdenum Disulfide in the
Lung. Small, 11(38), 5079-5087. doi: 10.1002/smll.201500906
45. Wu, B., Torres-Duarte, C., Cole, B. J., & Cherr, G. N. (2015). Copper Oxide and Zinc Oxide
Nanomaterials Act as Inhibitors of Multidrug Resistance Transport in Sea Urchin Embryos: Their
Role as Chemosensitizers. Environmental Science & Technology, 49(9), 5760-5770. doi:
10.1021/acs.est.5b00345
46. Zhang, H., Wang, X., Wang, M., Li, L., Chang, C. H., Ji, Z., . . . Nel, A. E. (2015). Mammalian Cells
Exhibit a Range of Sensitivities to Silver Nanoparticles that are Partially Explicable by Variations
in Antioxidant Defense and Metallothionein Expression. Small, 11(31), 3797-3805. doi:
10.1002/smll.201500251
47. Zhao, L., Sun, Y., Hernandez-Viezcas, J. A., Hong, J., Majumdar, S., Niu, G., . . . Gardea-Torresdey,
J. L. (2015). Monitoring the Environmental Effects of CeO2 and ZnO Nanoparticles Through the
Life Cycle of Corn (Zea mays) Plants and in Situ μ-XRF Mapping of Nutrients in Kernels.
Environmental Science & Technology, 49(5), 2921-2928. doi: 10.1021/es5060226
48. Zhao, L., Hu, J., Huang, Y., Wang, H., Adeleye, A., Ortiz, C., & Keller, A. A. (2016). 1H NMR and
GC–MS based metabolomics reveal nano-Cu altered cucumber (Cucumis sativus) fruit nutritional
supply. [Article in press- available on line]. Plant Physiology and Biochemistry. doi:
http://dx.doi.org/10.1016/j.plaphy.2016.02.010
49. Zuverza-Mena, N., Medina-Velo, I. A., Barrios, A. C., Tan, W., Peralta-Videa, J. R., & GardeaTorresdey, J. L. (2015). Copper nanoparticles/compounds impact agronomic and physiological
parameters in cilantro (Coriandrum sativum). Environmental Science: Processes & Impacts,
17(10), 1783-1793. doi: 10.1039/c5em00329f
50. Zuverza-Mena, N., Armendariz Jr., R., Peralta-Videa, J. R., & Gardea-Torresdey, J. L. (2016).
Effects of silver nanoparticles on radish sprouts: Root growth reduction and modifications in the
nutritional value. Frontiers in Plant Science, 7. doi: 10.3389/fpls.2016.00090
Leveraged Publications
51. Aruoja, V., Pokhrel, S., Sihtmae, M., Mortimer, M., Madler, L., & Kahru, A. (2015). Toxicity of 12
metal-based nanoparticles to algae, bacteria and protozoa. Environmental Science: Nano, 2(6),
630-644. doi: 10.1039/c5en00057b
52. Butler, K. S., Durfee, P. N., Theron, C., Ashley, C. E., Carnes, E. C., & Brinker, C. J. (2016).
Protocells: Modular Mesoporous Silica Nanoparticle-Supported Lipid Bilayers for Drug Delivery.
Small. doi: 10.1002/smll.201502119
53. Chan, W. W. C., Glotzer, S., Gogotsi, Y., Hafner, J. H., Hammond, P. T., Hersam, M. C., . . . Weiss,
P. S. (2015). Grand plans for nano. ACS Nano, 9(12), 11503-11505. doi:
10.1021/acsnano.5b07280
54. Chiu, H.-W., Xia, T., Lee, Y.-H., Chen, C.-W., Tsai, J.-C., & Wang, Y.-J. (2015). Cationic polystyrene
nanospheres induce autophagic cell death through the induction of endoplasmic reticulum
stress. Nanoscale, 7(2), 736-746. doi: 10.1039/C4NR05509H
55. Copeland, L., & Bimber, B. (2014). Variation in the Relationship Between Digital Media Use and
Political Participation in U.S. Elections Over Time, 1996–2012: Does Obama’s Reelection Change
the Picture? Journal of Information Technology & Politics, 12(1), 74-87. doi:
10.1080/19331681.2014.975391
56. Ivask, A., Titma, T., Visnapuu, M., Vija, H., Kakinen, A., Sihtmae, M., . . . Kahru, A. (2015). Toxicity
of 11 metal oxide nanoparticles to three mammalian cell types in vitro. Current Topics in
Medicinal
Chemistry,
15(18),
1914-1929.
doi:
http://dx.doi.org/10.2174/1568026615666150506150109
118
57. Jakus, A. E., Secor, E. B., Rutz, A. L., Jordan, S. W., Hersam, M. C., & Shah, R. N. (2015). ThreeDimensional Printing of High-Content Graphene Scaffolds for Electronic and Biomedical
Applications. ACS Nano, 9(4), 4636-4648. doi: 10.1021/acsnano.5b01179
58. Lee, D. G., Roehrdanz, P. R., Feraud, M., Ervin, J., Anumol, T., Jia, A., . . . Holden, P. A. (2015).
Wastewater compounds in urban shallow groundwater wells correspond to exfiltration
probabilities
of
nearby
sewers.
Water
Research,
85,
467-475.
doi:
http://dx.doi.org/10.1016/j.watres.2015.08.048
59. Li, X., Xue, M., Raabe, O. G., Aaron, H. L., Eisen, E. A., Evans, J. E., . . . Pinkerton, K. E. (2015).
Aerosol droplet delivery of mesoporous silica nanoparticles: A strategy for respiratory-based
therapeutics. Nanomedicine: Nanotechnology, Biology and Medicine, 11(6), 1377-1385. doi:
http://dx.doi.org/10.1016/j.nano.2015.03.007
60. López-Moreno, M., Avilés, L., Román, F., Rosas, J., Hernández-Viezcas, J., Peralta-Videa, J., &
Gardea-Torresdey, J. (2015). Sludge and Compost Amendments in Tropical Soils: Impact on
Coriander (Coriandrum sativum) Nutrient Content. International Journal of Biological,
Biomolecular, Agricultural, Food and Biotechnological Engineering, 9(4), 353 - 359. Retrieved
from http://scholar.waset.org/1999.1/10001053
61. Malloy, T., Blake, A., Linkov, I., & Sinsheimer, P. (2015). Decisions, Science, and Values: Crafting
Regulatory Alternatives Analysis. Risk Analysis, 35(12), 2137-2151. doi: 10.1111/risa.12466
62. Nisbet, R. M., Martin, B. T., & de Roos, A. M. (2015). Integrating ecological insight derived from
individual-based simulations and physiologically structured population models. Ecological
Modelling. doi: 10.1016/j.ecolmodel.2015.08.013
63. Noureddine, A., Lichon, L., Maynadier, M., Garcia, M., Gary-Bobo, M., Zink, J. I., . . . Wong Chi
Man, M. (2015). Controlled multiple functionalization of mesoporous silica nanoparticles:
homogeneous implementation of pairs of functionalities communicating through energy or
proton transfers. Nanoscale, 7(26), 11444-11452. doi: 10.1039/c5nr02620b
64. Padilla-Rodríguez, A., Hernández-Viezcas, J. A., Peralta-Videa, J. R., Gardea-Torresdey, J. L.,
Perales-Pérez, O., & Román-Velázquez, F. R. (2015). Adsorption of Arsenic(V) Oxyanion from
Aqueous Solutions by Using Protonated Chitosan Flakes. Separation Science and Technology,
50(14), 2099-2111. doi: 10.1080/01496395.2015.1040123
65. Su, Y., Adeleye, A. S., Keller, A. A., Huang, Y., Dai, C., Zhou, X., & Zhang, Y. (2015). Magnetic
sulfide-modified nanoscale zerovalent iron (S-nZVI) for dissolved metal ion removal. Water
research, 74, 47-57. doi: http://dx.doi.org/10.1016/j.watres.2015.02.004
66. Sun, B., Pokhrel, S., Dunphy, D. R., Zhang, H., Ji, Z., Wang, X., . . . Xia, T. (2015). Reduction of
Acute Inflammatory Effects of Fumed Silica Nanoparticles in the Lung by Adjusting Silanol
Display through Calcination and Metal Doping. ACS Nano, 9(9), 9357-9372. doi:
10.1021/acsnano.5b03443
67. Wang, Z., Xia, T., & Liu, S. (2015). Mechanisms of nanosilver-induced toxicological effects: more
attention should be paid to its sublethal effects. Nanoscale, 7(17), 7470-7481. doi:
10.1039/C5NR01133G
68. Yu, J., Liu, S., Wu, B., Shen, Z., Cherr, G. N., Zhang, X.-X., & Li, M. (2016). Comparison of
cytotoxicity and inhibition of membrane ABC transporters induced by MWCNTs with different
length and functional groups. [Early online]. Environmental Science & Technology. doi:
10.1021/acs.est.5b05772
Books and other publications
69. Chernyshova, V., Ponnurangam, S., & Somasundaran, P. (2015). Nanoparticles: Particle size and
shape effects on electrochemical properties. In P. Somasundaran (Ed.), Encyclopedia of Surface
and Colloid Science (3 ed.). New York: CRC Press.
119
70. Cohen, Y. (2015). Environmental Multimedia Distribution of Nanomaterials. In Quantifying
Exposure to Engineered Nanomaterials (QEEN) from Manufactured Products: Addressing
Environmental, Health, and Safety Implications. Arlington, VA. National Nanotechnology
Institute
71. Han, X., Engeman, C., Appelbaum, R., & Harthorn, B. H. (June 2015). Proceedings from
Democratizing Technologies: Assessing the Roles of NGOs in Shaping Technological Futures.
University of California, Santa Barbara: Center for Nanotechnology in Society.
72. Harthorn, B. H. (2016). Unifying ethical conceptions. In W. Sims Bainbridge & M. C. Roco (Eds.),
Handbook of science and technology convergence (1 ed.). Switzerland: Springer International
Publishing.
73. Nameth, C. (2015, April 23). Internal evaluation . . . and other responsibilities [Web blog
post]. Retrieved from: http://aea365.org/blog/catherine-nameth-on-internal-evaluation-andother-responsibilities/
74. Peralta-Videa, J. R., Medina-Velo, I. A., Zuverza-Mena, N., Tan, W., Hernandez-Viezcas, J. A., &
Gardea-Torresdey, J. L. (2015). Biophysical Methods of Detection and Quantification of Uptake,
Translocation, and Accumulation of Nanoparticles. In C. Kole, D. S. Kumar & M. V.
Khodakovskaya (Eds.), Plant Nanotechnology- Principles and Practices. Berlin: Springer-Verlag.
75. Truong, C., Stevenson, L., Krattenmaker, K., & Nameth, C. (2015, November). Looking
Downstream: Could Nanosilver in Consumer Products Affect Pond Life?. Retrieved
from http://www.sciencebuddies.org/science-fair-projects/project_ideas/EnvSci_p064.shtml
76. Wang, Y. (2015). Comparative effects of carbonaceous nanomaterials on soil-grown soybeans
2015 ERI Summer Fellowship Report. Bren School of Environmental Science & Management.
Retrieved from http://admin.eri.ucsb.edu/ERI-Fellowships/2015/WangYing.pdf
16. Biographical Information
No new Center Faculty to report.
120
UC Center for Environmental Implications of Nanotechnology Year 8 Progress Report 17. Honors and Awards  Mark Hersam (Northwestern, Faculty) – named one of 5 U.S. Science Envoys to engage internationally at the citizen and government level to foster increased scientific cooperation.  Galen Stucky (UCSB, Faculty) and C. Jeffrey Brinker (UNM, Faculty) – named 2015 Fellows of the National Academy of Inventors (NAI).  C. Jeffrey Brinker (UNM, Faculty) – Awarded University of New Mexico 2015 Presidential Award of Distinction.  Jeffrey Brinker (UCLA, Faculty), Joshua Schimel (UCSB, Faculty) – Named 2015 Thompsons Reuters Highly Cited Researchers, ranking them amongst the top 1% most cited in their cited field and year of publication, earning them the mark of exceptional impact.  Arturo Keller (UCSB, Faculty) – Awarded Agilent Thought Leader Award for his contributions to environmental science.  C. Jeffrey Brinker (UNM, Faculty) – Named 2015 University of New Mexico Innovation Fellow for his efforts of commercialization of nanoparticle based drug carriers.  Priyanka Jain (UNM, High School Student) – Winner, 2016 Regional Science & Engineering Fair ‐ advancing to Nationals under mentorship of Brinker. 18. Fiscal Information Statement of Residual Unobligated Funds Allocations were made to all UC CEIN projects according to the final approved budget for Year 8, which began on September 1, 2015. Funds were allocated across projects at UCLA, UC Santa Barbara, UC Davis, UC Riverside, University Texas El Paso, University of New Mexico, Northwestern University, and the University of Bremen – these transfers were made in early September shortly after receipt of incremental funding for Year 8. At this time, any unobligated funds at the end of Year 7 for each institution were reviewed and plans for allocation according to the originally approved scope of research were reviewed by the Executive Committee. Progress is monitored by the CEIN executive committee through bi‐annual progress reports and discussed at monthly executive committee meetings. Funding balances are continuously monitored by the CEIN Chief Administrative Officer, and any potential concerns about unobligated funds will be brought to the attention of the CEIN Director and Executive Committee for review. Any unobligated funds remaining in either the main award or the subawards at the end of the current funding period will be handled in accordance with NSF policy. Budgets On the pages that follow, please find the following summary information:  Current year actual expenditures for the Year 8 budget period for each awardee. These totals include actual expenses through February 29, 2016.  Proposed Year 9 budgets by institution, including authorized institutional approval signatures. Allocations reflect an anticipated cut in funding of $400,000 as a result in the reduction of EPA support for FY2016. The Executive Committee has opted to absorb the cuts proportionally across Themes and the attached budgets reflect new allocations by Institution as a result of the anticipated reduced funding. 121 Total Number of Non-academic Partners
II. Non-academic Partnering Institution(s)
Total Number of Academic Partners
I. Academic Partnering Institution(s)
Institution Type
Table 6: Partnering Institutions
Y
Contributes
Financial
Support To
Center
Y
Minority
Serving
Institution
Partner
0
Female
Serving
Institution
Partner
0
National
Lab/ Other
Govt.
Partner
0
Industry
Partner
0
Museum
Partner
Y
International
Partner
Y
Y
California Science Center
143
0
0
6
4
Y
Santa Monica Public Library
Y
Y
Y
0
4
Institute of Occupational Safety an
0
1
Y
Y
Y
nal Institute of Standards and Techn
otection Agency Office of Research
8
Y
11
Y
0
2
Y
Y
0
4
University of California, Davis
University of California, Riverside
Y
Y
niversity of California, Santa Barba
Y
Y
University of Birmingham
Y
Y
Y
Receives
Financial
Support From
Center
Name of Institution

UC CEIN Annual Report 2016

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