International Assessment of Research and Development in Physical Sciences

and Engineering Advances in Life Sciences and Oncology (APHELION)

Kickoff Meeting

NIH Natcher Building 45, Conference Rooms E1 & E2

February 1, 2012

Briefing Book

Sponsor’s

Logo

World Technology Evaluation Center, Inc. 4600 N. Fairfax Drive #104

Arlington, VA 22203

International Assessment of Physical Sciences and Engineering Advances in Life

Sciences and Oncology (APHELION)

Kickoff Meeting, February 1, 2012

NIH, Natcher Building 45, Conference Room E1/E2 (Lower Level)

AGENDA

8:00 AM Continental breakfast 8:30 AM Welcome (Nastaran Kuhn, NCI; Duane Shelton, WTEC)

• Self-introduction of attendees • Overview of meeting agenda, model reports, briefing book, (including panelist contracts)

8:45 AM Proposed scope of study (Paul Janmey, University of Pennsylvania, Study Chair) • Overview of study • Scope of study, issues to be researched • Introduction of study panelists and advisors

9:30 AM Sponsor comments on plan 9:45 AM Organization of study and additional logistics (Paul Janmey)

• Assignment of panelists, backup authors to report chapters/themes • Introductions to hosts by panelists • Set procedures to prepare itinerary and questions to be presented to hosts

10:30 AM Select geographic scope of study (Paul Janmey and Duane Shelton) • Preliminary bibliometric study (Grant Lewison)

11:00 AM Schedule / Resources (Duane Shelton)

• Set study tour(s) schedule and choose alternative fall-back date(s) • Set final 1-day (plus previous evening) workshop schedule for panel presentation with fall-back

date • Schedule final report delivery • Resources available (determines number of panelists, baseline workshop, geography, book)

11:30 AM Working Lunch / What Next? (Paul Janmey) • Set dates for conference calls to identify sites to be visited and questions to be presented to

overseas hosts • Remaining issues wrap-up

12:30 PM Study procedures/logistics (Frank Huband, WTEC) • Details of WTEC study methodology, WTEC’s project manager, coordination of site report

drafts, chapter drafts, etc. • Public and private websites for study reports and discussions • Advance arrangements • Structure of final report • Travel policies, reimbursement methods, consultant contracts • Best way to contact panelists (phone, email, address, secretary, etc.)

2:00 PM Adjourn

NCI-NSF IAA SOW APHELION DRAFT Dated 01-27-12 1

INTER-AGENCY AGREEMENT BETWEEN DEPARTMENT OF HEALTH AND HUMAN SERVICES

NATIONAL INSTITUTES OF HEALTH NATIONAL CANCER INSTITUTE

AND THE NATIONAL SCIENCE FOUNDATION

STATEMENT OF WORK

Assessment of PHysical sciences and Engineering

advances in LIfe sciences and ONcology (APHELION)

PROJECT SUMMARY This document describes a plan for the National Cancer Institute (NCI) Office of Physical Sciences – Oncology (OPSO) to participate in and co-sponsor a study led by the National Science Foundation (NSF) to conduct an international Assessment of PHysical sciences and Engineering advances in LIfe sciences and ONcology (APHELION). The APHELION is aimed at determining the status and trends of research and development whereby physical sciences and engineering principles are being applied to cancer research and oncology in leading laboratories and organizations via an on-site peer review process in Europe and Asia. The NSF has an existing contract with the World Technology Evaluation Center (WTEC), Inc. under which the study will be conducted. The mission of the NCI is to conduct and foster cancer research; reviewing and approving grant-in-aid applications to support promising research projects on the causes, prevention, diagnosis, and treatment of cancer; collecting, analyzing, and disseminating the results of cancer research conducted in the United States and in other countries; and providing training and instruction in the diagnosis and treatment of cancer. Over the years, NCI has evolved into the world's pre-eminent cancer research organization. Under the leadership of the NCI Deputy Director, the Center for Strategic Scientific Initiatives (CSSI) coordinates several efforts both within and outside of NCI to carry-out its function of supporting timely execution and implementation of activities that have trans-NCI benefit. Within the NCI, the CSSI houses (1) The Cancer Genome Atlas (TCGA) Program Office; (2) Office of Cancer Nanotechnology Research; (3) Office of Cancer Clinical Proteomics Research; (4) Office of Physical Sciences-Oncology; (5) Office of Biorepositories and Biospecimen Research; (6) Office of Cancer Genomics; (7) Knowledge Management and Special Projects Branch; (8) Center for Global Cancer Health Research. These offices support extramural research programs and lead standards and policy development initiatives with the goal of accelerating advances in biomedical technology and furthering the vision of personalized medicine. The NCI Office of Physical Sciences-Oncology (OPSO) (1) serves as a nexus for the development and implementation of physical science-based initiatives to enable progress in cancer research for NCI and its integration across trans-NCI, trans-NIH, and inter-agency activities; (2) enables the development of discoveries and new fields of study based on the application of aspects of the physical sciences

NCI-NSF IAA SOW APHELION DRAFT Dated 01-27-12 2

approaches to cancer research; (3) and facilitates the exploration of novel and innovative approaches to advance our understanding of the physical laws and principles that shape and govern the emergence and behavior of cancer at all scales. The NSF has long had a role in maintaining the general health of science and education across a range of universities and other organizations and has been deeply involved in funding research in engineering and the physical sciences. Recently, the NSF and the NCI have collaborated on a funding opportunity titled Physical and Engineering Sciences in Oncology (PESO) Awards [also known as the Physical and Life Sciences Early Research (PLIER) Awards]. The rationale for the NCI OPSO participation in the APHELION with NSF is based on the premise that significant advances may be expected as the result of continued investments in inter- and multi-disciplinary research at the intersection of the engineering/physical sciences and the life sciences. The field of cancer biology is one that has been dominated, historically, by researchers with classical training in the basic and clinical life sciences. More recently, the field has expanded to include physical and engineering scientists, whose background and expertise are complementary to those possessed by life scientists, leading to the recognition that significant advancements in the fundamental understanding of cancer diseases are possible through multidisciplinary research that involves experts in chemistry, physics, materials science, and manifold engineering disciplines. Emerging and burgeoning opportunities for collaborative research at the intersection of the physical/engineering sciences and the life sciences have been identified through several NSF workshops over the past few years. Furthermore, the NCI launched a program to bring new perspectives from the physical sciences to cancer biology and oncology in 2009. The Physical Sciences – Oncology Centers (PS-OCs) Program is in its third year of implementation and the OPSO will use the study to help develop relevant and novel funding concepts to further the mission of the NCI. Specifically, the OPSO seek novel research concepts at the interface of engineering/physical sciences and the life sciences with a focus on advancing the fundamental understanding of cancer biology to underpin translational research that promotes the prevention, detection, and treatment of cancer diseases. PROJECT BACKGROUND

In 1971 President Nixon declared war on cancer, and much effort has been invested in learning more about this complex system of diseases, and in developing treatments. However, despite considerable progress in treatment of certain forms of cancer, progress in reducing its mortality by conventional biomedical approaches is disappointing. Thus, in addition to new biomedical approaches, such as those based on the human genome, some researchers are using concepts from the physical sciences. In the U.S. much of the research that applies physical sciences and engineering concepts to cancer biology and oncology is supported by the Office of Physical Sciences – Oncology (OPSO) at the National Cancer Institute. The OPSO is exploring innovative new approaches to better understand and control cancer by encouraging the convergence of the physical sciences with cancer biology and oncology. Building on stunning progress in the molecular sciences, it supports new research themes based on the application of physical sciences concepts and approaches to the major barriers in cancer research. Examples of concepts being explored by the OPSO through its Physical Sciences – Oncology Centers (PS-OCs) Program are: (1) Applying physics and engineering laws and principles to cancer by defining the role of thermodynamics and mechanics in metastasis and determining how this knowledge might be employed in new intervention strategies; (2) Applying evolution and evolutionary theory to cancer by developing a comprehensive theoretical inclusive construct that would provide a foundation for understanding and predicting cancer heterogeneity; (3) Applying information theory to cancer by pursuing theoretical and supportive experimental approaches that define what information is and how it

NCI-NSF IAA SOW APHELION DRAFT Dated 01-27-12 3

is decoded and managed in terms of cell signaling and contextual information translation in cancer; and (4) Deconvoluting cancer’s complexity by pursuing theoretical and experimental approaches from the physical sciences to cancer complexity that will inform a new fundamental level of understanding of cancer that may facilitate prediction of viable pathways to develop novel interventions. The NSF currently has an umbrella contract awarded to the World Technology Evaluation Center (WTEC), Inc. to facilitate the assessment of research in engineering and science worldwide with the aim of maintaining U.S. leadership in these areas. WTEC is a non-profit research institute, which conducts international research assessment studies for the NSF, NIH, DOD, and other Federal agencies--more than 60 to date. Recent related studies include Nanotechnology Research Directions for Societal Needs in 2020, Brain-Computer Interfaces, Catalysis by Nanostructured Materials, Simulation-Based Engineering and Science, Rapid Vaccines Manufacturing, Tissue Engineering, and Systems Biology. PURPOSE

The objective of this joint study with the NCI OPSO and the NSF is to utilize an expert panel consisting of prominent scientists in the field of applying physical sciences and engineering perspectives/principles to oncology and other biomedical areas to conduct site visits at overseas institutions to conduct an international Assessment of PHysical sciences and Engineering advances in LIfe sciences and ONcology (APHELION). The findings of the APHELION will result in briefings to the sponsors, public workshops and a final report that will collectively provide a comprehensive, peer-reviewed set of evaluations of physical sciences-oncology research overseas in comparison to research being conducted in the United States. AUTHORITY This agreement is entered into under the authority of the National Science Foundation Act of 1950 as amended (42 USC 1861 et seq, specifically 1873(f) and section 241A and 301 of the Public Health Services Act, as amended. These authorizations for these agencies, together with the internal policies and procedures of each agency, define the authority of the agencies to enter Into this agreement and to manage this joint program focused on physical, mathematical, and engineering sciences or some combination of such the biological sciences. SCOPE OF WORK WTEC shall conduct the international assessment of the current status and the trends of the application of physical sciences and engineering concepts to cancer biology, oncology and other biomedical areas. The objectives of an international assessment would be to:

• Guide and justify U.S. research investments • Look for good ideas abroad (technology transfer, improving U.S. programs) • Look for opportunities for cooperation and collaboration • Compare U.S. R&D with that abroad

The study panel, under the guidance of the sponsors, will be instrumental in helping to develop a definitive scope of the study. Among these objectives related to the proposed study are:

NCI-NSF IAA SOW APHELION DRAFT Dated 01-27-12 4

• Information Transfer in Cancer and other Biomedical research areas through an Evolutionary Lens

o Can novel therapeutic strategies be developed based on increasing the genetic load of mutations in diseased cell population (e.g. cancer) that will lead to extinction of this population?

o What genetic and epigenetic features define a cancer stem cell? o Do oncogenic mutations confer self-renewal to cells? o What is a gene and how is it regulated in time and space?

• Time Domain of Cancer Metastasis and other Diseases with Therapy o Is the fluid phase biopsy of solid tumors an accurate real-time representation of the

disease over the course of the patient’s lifetime? o How does the heterogeneity of a tumor or other diseased tissue impact drug response?

• Mechanics in Health and Disease o Is Mechano-therapy of disease such as cancer possible? o “Follow the genes” is the dominant paradigm. Can we develop a complementary “follow

the physics” approach? o What is role of forces in cancer metastasis? o Can lessons learned from the roles that cell and tissue mechanics play in developmental

biology be applied to disease initiation and progression (e.g. in cancer)? • Physical Parameters of Cells, Microenvironment, and Host

o How does a cell change its genetic, epigenomic and metabolomic signature, as it becomes "successful" e.g. invasive, metastatic?

o How do physical cues derail a cell’s evolution into disease (e.g. cancer, heart, lung)? o Can approaches used in tissue engineering such as decellularized tissues be used as in

vitro or in vivo model systems to study disease (e.g. decellularized tumors to study cancer or metastasis)?

o Is the transport oncophysics of the microenvironment what really matters? o What is the energy budget of a diseased cell (e.g. cancer) compared to a developing cell

and a mature normal cell? • Understanding Physical Emergent Properties During Pathogenesis of Disease

o How can we change the physical microenvironment (selective pressures) to prevent cancer?

o Is cancer curable? Can it be controlled through manipulation of the microenvironment? o Why do tumors ultimately make a phase transition to a metastatic phenotype? o Could physical science tools be used to understand the molecular mechanisms of

cellular collective behaviors in disease initiation and progression? The oscillatory dynamics? Pattern formation? Instability and fluctuations of biological phenomena?

• Heart and Lung Disease – Connections to Cancer o What are the effects of shear stress from blood flow on the development of

cardiovascular disease? How do patterns of shear stress, flow, and flow rates affect cell movement throughout the circulation?

o What are the effects of pressure on lung epithelium in health and disease? Do changes in lung pressure affect cancer metastasis to the lung?

o Can computational models of flow patterns of circulating tumor cells be used to predict sites of cancer metastasis?

The above list of topics will be refined by the panel members in consultation with the sponsors at the study kick-off meeting.

NCI-NSF IAA SOW APHELION DRAFT Dated 01-27-12 5

TASKS Task 1 WTEC, in consultation with study sponsors, shall select a panel of six (6) U.S. experts (including the panel chair) in the field, who are familiar with international activities in the field. The panel chair shall have sufficient stature in this field to command respect in recruitment of panelists, and make presentations of results to peers. The chair also will have the necessary skills at leading a panel to efficiently conduct the study. Task 2 The Contractor shall organize a sponsor meeting to be held in the Washington, DC metro area in January/February 2012 at which interested sponsors will attend along with the panel chair if they are available. Task 3 After the sponsor meeting, the Contractor shall organize a kick-off meeting to be held in the Washington, DC metro area in February 2012 at which the expert panel, any scientific advisors, and interested sponsors will attend. At the kick-off meeting, the chair will define the scope of the study (with guidance from all of the agency sponsors) and assign each panelist a section of the final report. During the preliminary study, WTEC shall assist the panelists by conducting electronic literature searches. Password protected and public Web sites will be maintained by the WTEC during the study to facilitate the work of the panel. Task 4 WTEC shall organize a fact-finding trip to Europe for the panel to visit centers of excellence in physical sciences and engineering for oncology and other biomedical areas. The sites will include sponsoring organizations, as well as top labs. Government observers will accompany the expert panel, to assist and gather information first hand. Task 5 WTEC shall provide template site visit reports for each site visited to the study panel members and obtain draft site visit reports from the panel by July 2012. Task 6 WTEC shall organize a workshop in the Washington, DC area for the presentation of the results in a timely fashion such that the final report may be produced in August 2012. Approximately 50 key participants from government and the private sector would be expected to attend a one-day discussion of the results. Each panelist will make a 30-minute presentation with visual aids, and the chair will give an overall summary. The workshop will be webcast to broaden its dissemination, including posting of the video for at least three years. Task 7 WTEC shall provide a template analytical report to the study panel members and obtain a comprehensive draft analytical report from the panel by the beginning of August 2012. Task 8 WTEC shall produce a final written report in August 2012, print and distribute 100 B&W bound hardcopies to study participants, hosts, and sponsors, and post the full report in color on the WTEC website.

NCI-NSF IAA SOW APHELION DRAFT Dated 01-27-12 6

Task 9 If sufficient funds are available to conduct a subsequent study in another continent, WTEC shall organize a fact-finding trip to Asia in the spring or early summer of 2013 with a second final written report that shall be produced no later than August 2013. DELIVERABLES The schedule for the study will be determined at the kick-off meeting by mutual agreement of the sponsors, the WTEC staff, and the panel members. However, the first phase of the timeline shall be driven by a report deadline of August 1, 2012 for study that will be conducted in Europe. Deliverable Deadline Task 1: Selection of chair, panel members, and scientific advisors January 2012 Task 2: Sponsor Meeting February 2012 Task 3: Kick-off Meeting March 2012 Task 4: Fact-finding trip to Europe June 2012 Task 5: Draft site reports from study in Europe July 2012 Task 6: Final workshop phase 1 July 2012 Task 7: Draft analytical report from study in Europe August 2012 Task 8: Final written report from study in Europe August 2012 Task 9: Fact-finding trip to Asia (if sufficient funds allow) May 2013 Draft site reports from study in Asia June 2013

Final workshop phase 2 July 2013 Draft analytical report from study in Asia July 2013

Final written report from study in Asia August 2013 DURATION, AMENDMENT, AND TERMINATION This IAA is in effect for FY 2012 – FY 2013 and may be amended by signed written agreement between the NCI/NIH and NSF. The NCI/NIH or NSF may terminate this agreement by signed written notice provided, at least ninety days in advance. The IAA may be terminated immediately by the signed written agreement of all parties. RESOLUTION OF DISAGREEMENTS Should disagreement arise under this agreement, or amendments and/or revisions thereto, which cannot be resolved at the Assistant Director (NSF/ENG) and Deputy Director (NCI) level, the area(s) of disagreement shall be slated in writing by each Party and presented to the other Party at the Director or equivalent level for consideration.

Welcome ::::::

Assessment of Physical Sciences andEngineering Advances in Life Sciences andOncology (APHELION)

PROJECT SUMMARYThis document describes a plan for the National Cancer Institute (NCI) Office of PhysicalSciences – Oncology (OPSO) to participate in and co-sponsor a study led by the NationalScience Foundation (NSF) to conduct an international Assessment of PHysical sciencesand Engineering advances in LIfe sciences and ONcology (APHELION). The APHELIONis aimed at determining the status and trends of research and development wherebyphysical sciences and engineering principles are being applied to cancer research andoncology in leading laboratories and organizations via an on-site peer review process inEurope and Asia. The NSF has an existing contract with the World Technology EvaluationCenter (WTEC), Inc. under which the study will be conducted.

The mission of the NCI is to conduct and foster cancer research; reviewing and approvinggrant-in-aid applications to support promising research projects on the causes, prevention,diagnosis, and treatment of cancer; collecting, analyzing, and disseminating the results ofcancer research conducted in the United States and in other countries; and providingtraining and instruction in the diagnosis and treatment of cancer. Over the years, NCI hasevolved into the world's pre-eminent cancer research organization.

Under the leadership of the NCI Deputy Director, the Center for Strategic ScientificInitiatives (CSSI) coordinates several efforts both within and outside of NCI to carry-out itsfunction of supporting timely execution and implementation of activities that have trans-NCIbenefit. Within the NCI, the CSSI houses (1) The Cancer Genome Atlas (TCGA) ProgramOffice; (2) Office of Cancer Nanotechnology Research; (3) Office of Cancer ClinicalProteomics Research; (4) Office of Physical Sciences-Oncology; (5) Office ofBiorepositories and Biospecimen Research; (6) Office of Cancer Genomics; (7)Knowledge Management and Special Projects Branch; (8) Center for Global CancerHealth Research. These offices support extramural research programs and lead standardsand policy development initiatives with the goal of accelerating advances in biomedicaltechnology and furthering the vision of personalized medicine.

The NCI Office of Physical Sciences-Oncology (OPSO) (1) serves as a nexus for thedevelopment and implementation of physical science-based initiatives to enable progressin cancer research for NCI and its integration across trans-NCI, trans-NIH, and inter-agencyactivities; (2) enables the development of discoveries and new fields of study based on theapplication of aspects of the physical sciences approaches to cancer research; (3) andfacilitates the exploration of novel and innovative approaches to advance ourunderstanding of the physical laws and principles that shape and govern the emergence

and behavior of cancer at all scales.

The NSF has long had a role in maintaining the general health of science and educationacross a range of universities and other organizations and has been deeply involved infunding research in engineering and the physical sciences. Recently, the NSF and the NCIhave collaborated on a funding opportunity titled Physical and Engineering Sciences inOncology (PESO) Awards [also known as the Physical and Life Sciences Early Research(PLIER) Awards].The rationale for the NCI OPSO participation in the APHELION with NSF is based on thepremise that significant advances may be expected as the result of continued investmentsin inter- and multi-disciplinary research at the intersection of the engineering/physicalsciences and the life sciences. The field of cancer biology is one that has been dominated,historically, by researchers with classical training in the basic and clinical life sciences.More recently, the field has expanded to include physical and engineering scientists,whose background and expertise are complementary to those possessed by life

THE PANEL

PAUL JANMEY

(Panel Chair), University of Pennsylvaniamore>

SHARON GERECHT , Johns Hopkins Universitymore>

CYNTHIA REINHART-KING Cornell Universitymore>

PARAG MALLICK Stanford Universitymore>

OW EN MCCARTY

Oregon Health & ScienceUniversitymore>

LANCE L. MUNN

Harvard Medical Schoolmore>

DANIEL A. FLETCHER

Lawrence Berkeley NationalLaboratorymore>

The Panel Summary Purpose Scope

whose background and expertise are complementary to those possessed by lifescientists, leading to the recognition that significant advancements in the fundamentalunderstanding of cancer diseases are possible through multidisciplinary research thatinvolves experts in chemistry, physics, materials science, and manifold engineeringdisciplines. Emerging and burgeoning opportunities for collaborative research at theintersection of the physical/engineering sciences and the life sciences have beenidentified through several NSF workshops over the past few years. Furthermore, the NCIlaunched a program to bring new perspectives from the physical sciences to cancerbiology and oncology in 2009. The Physical Sciences – Oncology Centers (PS-OCs)Program is in its third year of implementation and the OPSO will use the study to helpdevelop relevant and novel funding concepts to further the mission of the NCI. Specifically,the OPSO seek novel research concepts at the interface of engineering/physical sciencesand the life sciences with a focus on advancing the fundamental understanding of cancerbiology to underpin translational research that promotes the prevention, detection, andtreatment of cancer diseases.

PROJECT BACKGROUNDIn 1971 President Nixon declared war on cancer, and much effort has been invested inlearning more about this complex system of diseases, and in developing treatments.However, despite considerable progress in treatment of certain forms of cancer, progressin reducing its mortality by conventional biomedical approaches is disappointing. Thus, inaddition to new biomedical approaches, such as those based on the human genome,some researchers are using concepts from the physical sciences. In the U.S. much of theresearch that applies physical sciences and engineering concepts to cancer biology andoncology is supported by the Office of Physical Sciences – Oncology (OPSO) at theNational Cancer Institute. The OPSO is exploring innovative new approaches to betterunderstand and control cancer by encouraging the convergence of the physical scienceswith cancer biology and oncology. Building on stunning progress in the molecular sciences,it supports new research themes based on the application of physical sciences conceptsand approaches to the major barriers in cancer reearch.

Examples of concepts being explored by the OPSO through its Physical Sciences –Oncology Centers (PS-OCs) Program are: (1) Applying physics and engineering laws andprinciples to cancer by defining the role of thermodynamics and mechanics in metastasisand determining how this knowledge might be employed in new intervention strategies; (2)Applying evolution and evolutionary theory to cancer by developing a comprehensive

theoretical inclusive construct that would provide a foundation for understanding andpredicting cancer heterogeneity; (3) Applying information theory to cancer by pursuingtheoretical and supportive experimental approaches that define what information is andhow it is decoded and managed in terms of cell signaling and contextual informationtranslation in cancer; and (4) Deconvoluting cancer’s complexity by pursuing theoreticaland experimental approaches from the physical sciences to cancer complexity that willinform a new fundamental level of understanding of cancer that may facilitate prediction ofviable pathways to develop novel interventions.

The NSF currently has an umbrella contract awarded to the World Technology EvaluationCenter (WTEC), Inc. to facilitate the assessment of research in engineering and scienceworldwide with the aim of maintaining U.S. leadership in these areas. WTEC is a non-profit research institute, which conducts international research assessment studies for theNSF, NIH, DOD, and other Federal agencies--more than 60 to date. Recent relatedstudies include Nanotechnology Research Directions for Societal Needs in 2020, Brain-Computer Interfaces, Catalysis by Nanostructured Materials, Simulation-BasedEngineering and Science, Rapid Vaccines Manufacturing, Tissue Engineering, andSystems Biology.PURPOSE

The objective of this joint study with the NCI OPSO and the NSF is to utilize an expert panelconsisting of prominent scientists in the field of applying physical sciences andengineering perspectives/principles to oncology and other biomedical areas to conductsite visits at overseas institutions to conduct an international Assessment of PHysicalsciences and Engineering advances in LIfe sciences and ONcology (APHELION). Thefindings of the APHELION will result in briefings to the sponsors, public workshops and afinal report that will collectively provide a comprehensive, peer-reviewed set of evaluationsof physical sciences-oncology research overseas in comparison to research beingconducted in the United States.

Consultants

ANTONIO TITO FOJO , Medical Oncology Branch andAffiliatesmore>

IMPORTANT LINKS

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Submit

conducted in the United States.

AUTHORITY

This agreement is entered into under the authority of the National Science Foundation Actof 1950 as amended (42 USC 1861 et seq, specifically 1873(f) and section 241A and 301of the Public Health Services Act, as amended.

These authorizations for these agencies, together with the internal policies and proceduresofeach agency, define the authority of the agencies to enter Into this agreement and tomanagethis joint program focused on physical, mathematical, and engineering sciences or somecombination of such the biological sciences.

SCOPE OF WORK

WTEC shall conduct the international assessment of the current status and the trends ofthe application of physical sciences and engineering concepts to cancer biology, oncologyand other biomedical areas. The objectives of an international assessment would be to: • Guide and justify U.S. research investments

• Look for good ideas abroad (technology transfer, improving U.S. programs)• Look for opportunities for cooperation and collaboration• Compare U.S. R&D with that abroadThe study panel, under the guidance of the sponsors, will be instrumental in helping todevelop a definitive scope of the study. Among these objectives related to the proposedstudy are:• Information Transfer in Cancer and other Biomedical research areas through anEvolutionary Lens o Can novel therapeutic strategies be developed based on increasing the genetic load ofmutations in diseased cell population (e.g. cancer) that will lead to extinction of thispopulation?o What genetic and epigenetic features define a cancer stem cell?o Do oncogenic mutations confer self-renewal to cells?o What is a gene and how is it regulated in time and space?• Time Domain of Cancer Metastasis and other Diseases with Therapyo Is the fluid phase biopsy of solid tumors an accurate real-time representation of thedisease over the course of the patient’s lifetime?o How does the heterogeneity of a tumor or other diseased tissue impact drug response?• Mechanics in Health and Disease o Is Mechano-therapy of disease such as cancer possible?o “Follow the genes” is the dominant paradigm. Can we develop a complementary “followthe physics” approach?o What is role of forces in cancer metastasis?o Can lessons learned from the roles that cell and tissue mechanics play in developmentalbiology be applied to disease initiation and progression (e.g. in cancer)?• Physical Parameters of Cells, Microenvironment, and Hosto How does a cell change its genetic, epigenomic and metabolomic signature, as itbecomes "successful" e.g. invasive, metastatic?o How do physical cues derail a cell’s evolution into disease (e.g. cancer, heart, lung)? o Can approaches used in tissue engineering such as decellularized tissues be used as invitro or in vivo model systems to study disease (e.g. decellularized tumors to study canceror metastasis)?o Is the transport oncophysics of the microenvironment what really matters?o What is the energy budget of a diseased cell (e.g. cancer) compared to a developing celland a mature normal cell?• Understanding Physical Emergent Properties During Pathogenesis of Diseaseo How can we change the physical microenvironment (selective pressures) to preventcancer?o Is cancer curable? Can it be controlled through manipulation of the microenvironment?o Why do tumors ultimately make a phase transition to a metastatic phenotype?o Could physical science tools be used to understand the molecular mechanisms ofcellular collective behaviors in disease initiation and progression? The oscillatorydynamics? Pattern formation? Instability and fluctuations of biological phenomena?• Heart and Lung Disease – Connections to Cancer

• Heart and Lung Disease – Connections to Cancero What are the effects of shear stress from blood flow on the development ofcardiovascular disease? How do patterns of shear stress, flow, and flow rates affect cellmovement throughout the circulation?o What are the effects of pressure on lung epithelium in health and disease? Do changesin lung pressure affect cancer metastasis to the lung? o Can computational models of flow patterns of circulating tumor cells be used to predict

sites of cancer metastasis?

The above list of topics will be refined by the panel members in consultation with thesponsors at the study kick-off meeting.

TASKS

Task 1WTEC, in consultation with study sponsors, shall select a panel of six (6) U.S. experts(including the panel chair) in the field, who are familiar with international activities in thefield. The panel chair shall have sufficient stature in this field to command respect inrecruitment of panelists, and make presentations of results to peers. The chair also willhave the necessary skills at leading a panel to efficiently conduct the study.

Task 2The Contractor shall organize a sponsor meeting to be held in the Washington, DC metroarea in January/February 2012 at which interested sponsors will attend along with thepanel chair if they are available.

Task 3After the sponsor meeting, the Contractor shall organize a kick-off meeting to be held inthe Washington, DC metro area in February 2012 at which the expert panel, any scientificadvisors, and interested sponsors will attend. At the kick-off meeting, the chair will definethe scope of the study (with guidance from all of the agency sponsors) and assign eachpanelist a section of the final report. During the preliminary study, WTEC shall assist thepanelists by conducting electronic literature searches. Password protected and publicWeb sites will be maintained by the WTEC during the study to facilitate the work of thepanel.

Task 4WTEC shall organize a fact-finding trip to Europe for the panel to visit centers ofexcellence in physical sciences and engineering for oncology and other biomedical areas.The sites will include sponsoring organizations, as well as top labs. Government observerswill accompany the expert panel, to assist and gather information first hand.

Task 5WTEC shall provide template site visit reports for each site visited to the study panelmembers and obtain draft site visit reports from the panel by July 2012.

Task 6WTEC shall organize a workshop in the Washington, DC area for the presentation of theresults in a timely fashion such that the final report may be produced in August 2012.Approximately 50 key participants from government and the private sector would beexpected to attend a one-day discussion of the results. Each panelist will make a 30-minute presentation with visual aids, and the chair will give an overall summary. Theworkshop will be webcast to broaden its dissemination, including posting of the video forat least three years.

Task 7

WTEC shall provide a template analytical report to the study panel members and obtain acomprehensive draft analytical report from the panel by the beginning of August 2012.Task 8WTEC shall produce a final written report in August 2012, print and distribute 100 B&Wbound hardcopies to study participants, hosts, and sponsors, and post the full report incolor on the WTEC website.Task 9

Task 9If sufficient funds are available to conduct a subsequent study in another continent, WTECshall organize a fact-finding trip to Asia in the spring or early summer of 2013 with asecond final written report that shall be produced no later than August 2013.DELIVERABLESThe schedule for the study will be determined at the kick-off meeting by mutual agreementof the sponsors, the WTEC staff, and the panel members. However, the first phase of thetimeline shall be driven by a report deadline of August 1, 2012 for study that will beconducted in Europe.

Deliverable DeadlineTask 1: Selection of chair, panel members, and scientific advisors | January 2012Task 2: Sponsor Meeting | February 2012Task 3: Kick-off Meeting | March 2012Task 4: Fact-finding trip to Europe | June 2012Task 5: Draft site reports from study in Europe | July 2012Task 6: Final workshop phase | 1 July 2012Task 7: Draft analytical report from study in Europe | August 2012Task 8: Final written report from study in Europe | August 2012Task 9: Fact-finding trip to Asia (if sufficient funds allow) | May 2013Draft site reports from study in Asia | June 2013Final workshop phase | 2 July 2013Draft analytical report from study in Asia | July 2013Final written report from study in Asia | August 2013

DURATION, AMENDMENT, AND TERMINATIONThis IAA is in effect for FY 2012 – FY 2013 and may be amended by signed writtenagreement between the NCI/NIH and NSF. The NCI/NIH or NSF may terminate thisagreement by signed written notice provided, at least ninety days in advance. The IAA maybe terminated immediately by the signed written agreement of all parties.RESOLUTION OF DISAGREEMENTSShould disagreement arise under this agreement, or amendments and/or revisionsthereto, which cannot be resolved at the Assistant Director (NSF/ENG) and DeputyDirector (NCI) level, the area(s) of disagreement shall be slated in writing by each Partyand presented to the other Party at the Director or equivalent level for consideration.

Assessment of Physical Sciences and Engineering Advances in Life Sciences and Oncology. Sponsored by National Cancer

Institute, NSF || For further information contact: Hassan Ali, WTEC Project Manager, hali@scienceus.org

January 27, 2012

Panelists for the Assessment of Physical Sciences and Engineering Advances in Life Sciences and Oncology (APHELION Study)

Chair: Paul Janmey, PhD, Associate Director, Institute for Medicine and Engineering, Professor of Physiology, School of Medicine, University of Pennsylvania; janmey@mail.med.upenn.edu http://www.med.upenn.edu/physiol/p_janmey_bio.html Institute for Medicine and Engineering 1010 Vagelos Laboratories 3340 Smith Walk Philadelphia, PA 19104 Tel. 215-573-7380

Paul Janmey received an A.B. degree from Oberlin College in 1976 and a Ph.D. in Physical Chemistry from the University of Wisconsin in 1982, working in the lab of J.D. Ferry on fibrin polymerization. A post-doctoral fellowship in the Hematology Unit of Massachusetts General Hospital motivated application of methods of polymer physics to the cytoskeleton. Since then his lab has studied the viscoelastic properties of biopolymer networks and the regulation of cytoskeletal and extracellular matrix assembly. Current work is focused on the response of cells to the viscoelastic properties of their environment and on developing new soft biocompatible materials for tissue engineering and wound healing. Sharon Gerecht, PhD, Assistant Professor, Department of Chemical and Biomolecular Engineering, Johns Hopkins University; gerecht@jhu.edu http://www.jhu.edu/chembe/gerecht/ The Department of Chemical and Biomolecular Engineering Johns Hopkins University 221Maryland Hall 3400 North Charles Street Baltimore, MD 21218 Tel. 410-516-2846

Sharon Gerecht is an Assistant Professor, Department of Chemical and Biomolecular Engineering, Johns Hopkins University. She is also a lead investigator at the Johns Hopkins Physical Sciences-Oncology Center and a member of the Institute for NanoBioTechnology at Johns Hopkins. Dr. Gerecht earned bachelor’s and doctoral degrees from the Technion - Israel Institute of Technology and a master’s degree from Tel Aviv University. Dr. Gerecht is the recipient of the 2008 Allan C. Davis Medal from the Maryland Academy of Sciences, the North America Vascular Biology Organization Junior Investigator Award (2009), the Basil O’Connor Starter Scholar Research Award from the March of Dimes Foundation (2009-2011), the National Scientist Development Award from American Heart Association (2008-2012), and the NSF CAREER award (2011-2016). Dr. Gerecht’s research focuses on employing engineering fundamentals to study basic questions in stem cell biology and how to apply them for blood vessel regeneration and repair and the limitation of cancer progression. Cynthia Reinhart-King, PhD, Assistant Professor, Department of Biomedical Engineering, Cornell University;

cak57@cornell.edu http://www.bme.cornell.edu/people/profile.cfm?netid=cak57 302 Weill Hall Cornell University Ithaca, NY Tel. 607-255-8491

Cynthia Reinhart-King is an assistant professor in the department of Biomedical Engineering at Cornell University and a member of the graduate faculty in the department of Mechanical and Aerospace Engineering, the Cornell Center on Microenvironment and Metastasis and the Cornell Nanobiotechnology Center. She obtained undergraduate degrees in chemical engineering and biology at MIT. While there, she was awarded the Randolph G. Wei Award for “research at the interface of the life sciences and engineering.” As a graduate student at the University of Pennsylvania in the Department of Bioengineering, she received a Whitaker Foundation Graduate Fellowship to support her thesis work on endothelial cell mechanobiology. She then completed postdoctoral training as an Individual NIH NRSA postdoctoral fellow in the Cardiovascular Research Institute at the University of Rochester. Dr. Reinhart-King’s current research interests are in the areas of cell mechanics and cell migration specifically in the context of cancer and atherosclerosis. Her lab uses a multidisciplinary approach, drawing from cell and molecular biology, biophysics, and biomechanics to quantitatively examine the mechanisms of tissue formation and disease progression. Her lab is funded by the American Heart Association, the National Institutes of Health, the National Science Foundation and the American Federation of Aging Research. She has been awarded the Rita Schaffer Young Investigator Award by BMES and an NSF CAREER Award. She has also received the 2010 Sonny Yau ‘72 Excellence in Teaching Award, the highest award for teaching in Cornell’s College of Engineering. Parag Mallick, PhD, Assistant Professor, Department of Radiology, Stanford University; paragm@stanford.edu http://med.stanford.edu/profiles/Parag_Mallick/ Canary Center for Cancer Early Detection Stanford University 1501 S California Avenue, Room 2212 Palo Alto, CA 94304 Tel. 650-723-2300

Parag Mallick graduated from Washington University in St. Louis with a BS in Computer Science. He then obtained his Ph.D. from UCLA in Chemistry & Biochemistry, where he worked with Dr. David Eisenberg. At UCLA he received both an NSF IGERT Fellowship and an NSF Biotechnology fellowship. He completed Post-Doctoral studies at The Institute for Systems Biology, in Seattle, WA with Dr. Ruedi Aebersold. He is now faculty with the Canary Center for Cancer Early Detection at Stanford University where he is developing quantitative multi-scale to better prioritize potential biomarker candidates and to accurately describe cellular regulation and dysregulation. In addition, he is the principle investigator of ProteoWizard, an open-source platform for accelerating the development of tools to analyze Proteomics Data. Owen McCarty, PhD, Associate Professor, Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University; owenmccarty@yahoo.com http://www.ohsu.edu/xd/education/schools/school-of-medicine/departments/basic-science-departments/biomedical-engineering/people/owen-mccarty.cfm Center for Health and Healing Mail code: CH13B 3303 SW Bond Avenue, Rm #13033 Portland, Oregon 97239-3098 Tel. 503-418-9307

Owen McCarty is an Associate Professor of Biomedical Engineering at the Oregon Health & Science University. He holds a joint appointment as an Associate Professor in Cell & Developmental Biology, and serves as the Biomedical Engineering Director of Graduate Education. Dr. McCarty received his Ph.D. degree in Chemical & Biomolecular Engineering from Johns Hopkins University. His graduate work focused on the identification and characterization of novel tumor cell receptors for blood platelets and leukocytes. He performed his postdoctoral research with Steve Watson at the University of Oxford, where he focused on elucidating the role of the Rho GTPases in regulating platelet function. He was the first to show that Rac plays a critical role in platelet lamellipodia formation and is required for thrombus stability under shear flow. Dr. McCarty joined Oregon Health & Science University as an Assistant Professor of Biomedical Engineering in 2005. His research centers on characterizing the role of platelets in thrombosis, inflammation and cancer metastasis. His work has been featured by Science Daily and United Press International. Dr. McCarty was named the 2009 Karl Link New Investigator in Thrombosis by the American Heart Association, and has been twice been awarded the “paper of the year” by the Journal of Thrombosis and Haemostasis for his work to characterize the mechanisms that drive platelet cytoskeletal reorganization. Lance L. Munn, PhD, Associate Professor of Radiation Oncology Harvard Medical School; Associate Biologist Edwin L. Steele Laboratory for Tumor Biology. munn@steele.mgh.harvard.edu http://www.massgeneral.org/cancer/research/researchlab.aspx?id=1213 Edwin L. Steele Laboratory Massachusetts General Hospital 100 Blossom Street, Cox-7 Boston, MA 02114 Tel. 617-726-8143

Lance L. Munn, received his PhD in Bioengineering from Rice University, and is currently Associate Professor in the Department of Radiation Oncology at The Massachusetts General Hospital. His research focuses on the mechanobiology of tumors and blood vessels using in vivo models, mathematical simulations and microfabricated tissue analogs. These systems allow analysis of the dynamics of cell cooperation during the formation and remodeling of blood vessels as well as tumor invasion and has led to discoveries of novel mechanisms of vascular anastomosis and tumor invasion.

e-mail addresses: janmey@mail.med.upenn.edu, gerecht@jhu.edu, cak57@cornell.edu, mallick@usc.edu, owenmccarty@yahoo.com

Daniel A. Fletcher

Professor, Department of Bioengineering Faculty Scientist, Lawrence Berkeley National Laboratory Deputy Division Director, Physical Biosciences Division, LBL

608B Stanley Hall mailcode: 1762 (510) 643-5624 fax: (510) 642-5835 fletch@berkeley.edu http://fletchlab.berkeley.edu

Dan Fletcher is Professor of Bioengineering and Biophysics at UC Berkeley and Faculty Scientist at the Lawrence Berkeley National Laboratory, where his research focuses on understanding how cells are organized to sense and respond to their physical environment. Dr. Fletcher received a B.S.E. from Princeton University and a D.Phil. from Oxford University. He received a Ph.D. from Stanford University and was a Postdoctoral Fellow at the Stanford University School of Medicine. Dr. Fletcher is currently the Associate Chair of the Bioengineering Department at UC Berkeley and Deputy Director of the Physical Biosciences Division at LBNL.

EXPERT ADVISORS

Antonio Tito Fojo, M.D., Ph.D.

Medical Oncology Branch and Affiliates

Head, Experimental Therapeutics Section Senior Investigator Building 10, Room 12C103 10 Center Drive Bethesda, MD 20892 Phone: 301-496-2631 Fax: 301-402-1608 E-Mail: fojot@mail.nih.gov

Biography Dr. Fojo was born in Havana, Cuba, moved to the United States with his family in 1960, and became a U.S. citizen in 1970. He received his M.D. and Ph.D. from the University of Miami. He completed 3 years of training in internal medicine at Washington University/Barnes Hospital in St. Louis, and after a year as chief resident came to the NCI as a clinical associate in the Medicine Branch, now the Cancer Therapeutics Branch. After 3 years with Drs. Ira Pastan and Michael Gottesman, he assumed the position of senior investigator in the Cancer Therapeutics Branch.

PAUL JANMEY, PH.D.Professor of Physiology

Institute for Medicine and Engineering1010 Vagelos Laboratories

3340 Smith WalkPhiladelphia, PA 19104

janmey@mail.med.upenn.edu

Phone: (215) 573-7380Fax: (215) 573-68151

Other Perelman School of Medicine AffiliationsCell and Molecular Biology Graduate GroupPennsylvania Muscle Institute

DegreesPh.D., University of Wisconsin, 1982A.B., Oberlin College, 1976

HonorsRotschild-Yvette Mayent Award, Institut Curie, 1999

Professional AffiliationsAmerican Society for Cell BiologyBiophysical Society

Research Description Our lab studies several aspects of cell mechanics. In oneproject, we produce soft materials, usually hydrogels, towhich cell adhesion proteins are linked to study how thestiffness of surfaces alters cell structure, function, andgrowth. Endothelial cells, fibroblasts, neurons andastrocytes each show unique dependence on substratestiffness, and we seek to understand how they sense andrespond to this mechanical cue. In related work we measurethe structure and viscoelasticity of cytoskeletal polymernetworks using a variety of imaging, scattering, andrheologic methods. Further studies examine how changes incell membrane structure mediated by inositol phospholipidslead to production of signals that remodel the cytoskeleton.?

Representative PublicationsFlanagan, L. A., Ju, Y. E., Marg, B., Osterfield, M., andJanmey, P. A. (2002). Neurite branching on deformablesubstrates. Neuroreport 13, 2411-5

Yin, H.L., and P.A. Janmey. 2003. Phosphoinositideregulation of the actin cytoskeleton. Annu Rev Physiol.65:761-89

Bucki, R., Pastore, J.J., Giraud, F., Sulpice, J.C. andJanmey, P.A. 2003. Flavonoid inhibition of plateletprocoagulant activity and phosphoinositide synthesis. JThromb Haemost 1:1820-8.

Wong, G. C. L., Lijn, A., Tang, J. X., Li, Y., Janmey, P. andSafinya, C. R. (2003). Lamellar Phase of Stacked Two-Dimensional Rafts of Actin Filaments. Phys. Rev. Lett. 91,018103.

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Sharon GerechtAssistant Professor

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Office: MD 116Phone: (410) 516-2846 Email: gerecht@jhu.eduCurriculum Vitae

Research Interests

Our research is focused on employing engineering fundamentals to study basic questions in stemcell biology and applying these for tissue repair and regeneration.

Specifically, we study the interactions between stem cells (SCs) and their microenvironment w ith thelong term goal to engineer artificial SC microenvironments capable of guiding vascular differentiation,delivery and regeneration. Our research program is based on the integrated and advanced use oftissue engineering system components and is grounded in fundamentals of interfacial science andengineering and SC biology.

Publications

Gerecht-Nir S, Dazard J-E, Golan-Mashiach M, Osenberg S, Botvinnik A, Amariglio N, Domany E, RechaviG, Givol D and Itskovitz-Eldor J. Vascular gene expression and phenotypic correlation duringdifferentiation of human embryonic stem cells. Dev Dyn 2005; 232:488-498.

Gerecht S, Burdick JA, Ferreira LS, Townsend SA, Langer R, and Vunjak-Novakovic G. Hyaluronic acidhydrogel for controlled self-renewal and differentiation of human embryonic stem cells. Proc Natl Acad SciU S A. 2007; 104:11298-11303.

Gerecht S*, Bettinger* CJ, Zhang Z, Borenstein J, Vunjak-Novakovic G, Langer R. The effect of actindisrupting agents on contact guidance of human embryonic stem cells. Biomaterials. 2007; 28:4068-4077.

Figallo E*, Cannizzaro C*, Gerecht S*,Burdick JA, Langer R, Elvassor N, Vunjak-Novakovic G.Microbioreactor arrays for controlling cellular microenvironments. Lab Chip. Special issue on Cell andTissue Engineering in Microsystems. 2007; 7: 710 - 719

Gerecht S, Townsend SA, Pressler H, Zhu H, Nijst C.L.E, Broggeman J, Nichol J, Langer R. A porousphotocurable bioelastomer for cell encapsulation and culture. Biomaterials.doi:10.1016/j.biomaterials.2007.07.039.

The Department of Chemical and Biomolecular Engineering, Johns Hopkins University221Maryland Hall 3400 North Charles Street, Baltmore, MD 21218 410-516-7170 (phone) | 410-516-5510 (fax) | chembe@jhu.edu

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Parag Mallick

Assistant Professor (Research), Radiology - Diagnostic Radiology

Academic Offices

Profile http://med.stanford.edu/profiles/Parag_Mallick/http://med.stanford.edu/profiles/Parag_Mallick/

email

Personal Information

paragm@stanford.edu

email

Alternate Contact

Pat Riley

periley@stanford.edu

Professional OverviewProfessional Overview

Professional Education

PostDoc: Institute for Systems Biology, Proteomics & Systems Biology

Ph.D.: University of California, Los Angeles, Chemistry & Biochemistry

B.S.: Washington University in St. Louis, Computer Science & Biochemistry

Postdoctoral Advisees

Dario Amodei

Internet Links

ProteoWizard (http://proteowizard.sourceforge.net)

Scientific FocusScientific Focus

Current Research Interests

Our general hope is to apply systems biology's complimentary computational and experimental

methods in hopes that experimental results motivate large-scale computational studies, w hich initiate

new experimental explorations. We hope this synergistic combination w ill provide insight into the

relationship betw een molecular phenomena and organismic phenomena.

Organismic states, such as healthy and diseased, are hypothesized to arise from the alteration of a

systems normal cell-netw ork structures through a combination of endogenous genetic modif ications

and exogenous environmental agents. Whole-cell and w hole-organism analyses of gene expression,

protein expression and related differential analyses have been w idely applied to study biological

processes and disease states. These techniques have permitted the examination of cellular

processes and their relationship to physiologic effects in a greater detail than previously possible,

enabling better characterizations of pathologic states, such as cancer.

As our understanding of cellular processes has developed, so has our understanding that cancer,

even in a single patient, is not one disease, but instead hundreds of heterogeneous diseases unif ied

by the single common gross phenotype of de-regulation of cell-grow th. Consequently, diagnosis

becomes a complex challenge it is insuff icient to merely determine that someone has cancer; instead

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Owen J.T. McCartyE-mail: mccartyo@ohsu.eduPhone: 503-418-9307Fax: 503-418-9311Alt Phone: 503-418-9350

Current AppointmentsAssociate Professor, Department of Biomedical Engineering Associate Professor, Department of Cell & Development Biology

OfficeCenter for Health and Healing3303 SW Bond Avenue Mail code: CH13B

Rm #13033Education

BS, Chemical Engineering, State University of New York at Buffalo, 1997Ph.D, Chemical & Biomolecular Engineering, Johns Hopkins University, 2002

Department(s)Biomedical Engineering

BiographyDr. McCarty received his Ph.D in Chemical & Biomolecular Engineering from Johns Hopkins Universitywith dissertation work focused on the role of platelets in cancer metastasis and thrombosis. As aWellcome Trust Postdoctoral Fellow, he continued his research in the area of thrombosis, examiningthe signaling pathways governing platelet cytoskeletal reorganization, at the Department ofPharmacology, Oxford University and Centre for Cardiovascular Sciences, University of Birmingham,UK.

Research InterestsDr. McCarty's research is focused on understanding the interplay between cell biology and fluidmechanics in the cardiovascular system. In particular, his research into the balance betweenhydrodynamic shear forces and chemical adhesive interactions has great relevance to underlyingprocesses of cancer, cardiovascular disease, and inflammation.

Research Project(s)Thrombosis and Hemostasis

Research Group(s)Cardiovascular and Blood ResearchVascular Biology and Vascular Tissue Engineering

Selected Publications

1. McCarty OJ, Mousa SA, Bray PF, Konstantopoulos K. Immobilized platelets support human coloncarcinoma cell tethering, rolling and firm adhesion under dynamic flow conditions. Blood 2000 Sep;96(5): 1789-1797

2. Abulencia JP, Tien N, McCarty OJ, Plymire D, Mousa SA, Konstantopoulos K. Comparativeantiplatelet efficacy of a novel nonpeptide GPIIb/IIIa antagonist (XV454) and abciximab (c7E3) in flowmodels of thrombosis. Arteriosclerosis Thrombosis & Vascular Biology. 2001 Jan; 21(1): 149-156

3. Burdick MM, McCarty OJ, Jadhav S, Konstantopoulos K. Cell-cell interactions in inflammation andcancer metastasis. IEEE Engineering in Medicine and Biology 2001 May; 20(3): 86-91

4. Mousa SA, Abulencia JP, McCarty OJ, Turner NA, Konstantopoulos K. Comparative efficacy betweenthe GPIIb/IIIa antagonists, roxifiban and orbofiban, in inhibiting platelet function in flow models ofthrombosis. Journal of Cardiovascular Pharmacology 2002 Apr; 39(4): 552-5560

5. McCarty OJ, Jadhav S, Burdick MM, Bell WR, Konstantopoulos K. Fluid shear regulates the kineticsand molecular mechanisms of activation-dependent platelet binding to colon carcinoma cells.Biophysical Journal 2002 Aug; 83(2): 836-48

6. McCarty OJ, Tien N, Bochner BS, Konstantopoulos K. Exogenous eosinophil activation convertsPSGL-1-dependent binding to CD18-dependent stable adhesion to Platelets in shear flow. AmericanJournal of Physiology: Cell Physiology 2003 May; 284(5): C1223-34

7. Hanley W†, McCarty OJ†, Jadhav S, Tseng Y, Wirtz D, Konstantopoulos K. Single-moleculecharacterization of P-selectin/ligand binding. Journal of Biological Chemistry 2003 Mar; 278(12):10556-61. †equally contributing first authors

8. McCarty OJ, Abulencia JP, Mousa SA, Konstantopoulos K. Evaluation of platelet antagonists in in-vitro flow models of thrombosis. Methods of Molecular Medicine 2004 Aug; 93: 21-34

9. McCarty OJ, Zhao Y, Andrew N, Machesky LM, Staunton D, Frampton J, Watson SP. Evaluation of therole of platelet integrins in fibronectin-dependent spreading and adhesion. Journal of Thrombosis

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Munn LabResearch topics include: leukocyte mechanics andtumor physiology

OVERVIEW GROUP MEMBERS PUBLICATIONS CONTACT

PROGRAM AFFILIATIONS

Radiation Oncology Research

Edwin L. Steele Laboratory forTumor Biology

Lance L. Munn, PhDAssociate Professor of Radiation OncologyHarvard Medical School

Associate BiologistEdwin L. Steele Laboratory for Tumor Biology

Research Summary

As part of the Edwin L. Steele Laboratory for Tumor Biology, research at the Munn Laboratory focuses on blood vessel structureand function in normal and pathological conditions. Within this broad area, I have projects that address:

Leukocyte Trafficking and Blood Dynamics

A physiological inflammatory response requires margination, adhesion and extravasation of leukocytes which then migrate tothe region of insult. Some aspects of this process occur in tumors, but in general, the immune response is ineffective. Usingmathematical modeling validated by experiments, we have characterized the physical mechanisms that encourage leukocyteadhesion in normal vasculature. These mechanisms are inefficient in tumor vessels due to the abnormal flow conditions andnetwork topology. We are investigating the possibility of altering the fluid dynamics in tumors to encourage infiltration of blood-borne immune cells. Because our tools for studying blood dynamics are fundamentally robust, we can also use them toanalyze thrombosis, sickle cells and the mechanics of atherosclerosis.

Transvascular Transport

Heterogenous permeability of tumor vasculature makes it difficult to deliver drugs via systemic injection to all cells in a tumor.The goal of this project is to determine the mechanisms of spatial and organ-specific dependence of vascular leakage intumors. A better understanding of the mechanisms of barrier modulation will allow the development of strategies for improvingdrug delivery to all regions of solid tumors.

Cell and Vessel Morphogenesis During Angiogenesis

In many normal physiological responses, endothelial cells and the blood vessel networks they form undergo dramaticchanges in morphology and function. Examples include angiogenesis in wound healing, vessel dilation/hyperpermeability ininflammation, and endometrial angiogenesis in the female reproductive cycle. Endothelial cells, in cooperation with otherstromal cells, have to accomplish these diverse changes by responding to a limited number of growth factors including VEGF,PlGF and bFGF. We are using a systems biology approach to understand how the various growth factors and cells cooperateto produce these seemingly diverse functions. Because tumor angiogenesis relies on many of these same growth factors andcellular mechanisms (but in an abnormal, poorly controlled way), these studies will allow a better understanding of tumorangiogenesis and anti-angiogenic therapy.

Cancer Cell Intravasation

During the initial stage of metastasis, cancer cells must breach the vessel wall and enter the circulation. Despite intenseresearch in this area, the cellular mechanisms by which this occurs are poorly understood. Some tumors seem tometastasize as single rogue cells, while others travel in groups or clusters; some seem to actively migrate into the vessel,while others may be passively pushed. Using gene array analysis and carefully designed coculture systems, we areassessing the mechanical and cellular determinants of the initiation of metastasis.

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Cynthia A. Reinhart-KingDept: Biomedical Engineering

Title: Assistant Professor

Address: 302 Weill Hall

Phone: 607 255-8491

email: CAK57@cornell.edu

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CYNTHIA A. REINHART-KINGBiography

Cynthia Reinhart-King is an Assistant Professor in theDepartment of Biomedical Engineering at CornellUniversity, and a member of the graduate faculty inMechanical and Aerospace Engineering and the CornellNanobiotechnology Center. She obtained undergraduatedegrees in chemical engineering and biology at MIT.While there, she was awarded the Randolph G. WeiAward for "research at the interface of the life sciencesand engineering." As a graduate student at theUniversity of Pennsylvania in the Department ofBioengineering, she received a Whitaker FoundationGraduate Fellowship to support her thesis work onendothelial cell mechanobiology. She then completedpostdoctoral training as an Individual NIH NRSApostdoctoral fellow in the Cardiovascular ResearchInstitute at the University of Rochester. Dr. Reinhart-King's current research interests are in the areas ofcell-biomaterial interactions, cell mechanics, cancermetastasis and vascular cell signaling. Her lab uses amultidisciplinary approach, drawing from cell andmolecular biology, biophysics, and biomechanics toquantitatively examine the mechanisms of tissueformation and disease progression. Her lab is funded bythe National Institutes of Health, the National Scienceof Foundation, the American Heart Association, and theAmerican Federation for Aging Research. Additionally,she is a project leader in the NIH-funded U54 CornellCenter on the Microenvironment and Metastasis. Shehas received the Rita Schaffer Young InvestigatorAward, the Biomedical Engineering Society's highest recognition for a young faculty member,and the 2010 Sonny Yau '72 Excellence in Teaching Award from the Cornell College ofEngineering.

Research Interests

The research conducted by Cynthia Reinhart-King focuses on elucidating the basic principles ofcell adhesion and cell-biomaterial interactions for applications relating primarily to thecardiovascular system. The central mission of this work is to understand the mechanisms thatdrive tissue formation. This work uses a multidisciplinary approach involving principles from cellbiology, biophysics, biomaterials and biomechanics to guide the development of materials fortissue engineering applications and the development of novel therapeutics. Of particularinterest are the physiology of blood vessel formation and the pathophysiology of vasculardisease.

At a molecular level, this work involves characterizing the role of intracellular structural andsignaling proteins in governing cell adhesion and tissue development specifically as it pertains toblood vessel formation. At the cellular level, the properties of the extracellular matrixenvironment, both chemical and mechanical, are manipulated and exploited to controlendothelial cell behaviors such as growth, adhesion and migration. At the tissue level, this workincludes elucidating the properties of the extracellular matrix that foster healthy tissueformation from individual cell populations. Biophysical and biochemical techniques are exploitedto quantitatively characterize cell behavior in both normal and diseased states. Using TractionForce Microscopy, our group was the first to quantify the forces exerted by endothelial cells ontheir substrate in response to both chemical and mechanical cues during cell spreading andadhesion, providing key insights into the molecular mechanisms of cell-biomaterial interactions.The ultimate goal is to determine governing parameters that can used to predict and controlcell behavior in order to form new tissues. Knowledge gained in these areas will provide insight

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Daniel A. Fletcher

Professor, Department of Bioengineering

Faculty Scientist, Lawrence Berkeley National Laboratory

Deputy Division Director, Physical Biosciences Division, LBL

608B Stanley Hall

mailcode: 1762

(510) 643-5624

fax: (510) 642-5835

fletch@berkeley.edu

http://fletchlab.berkeley.edu

Joined the UC Berkeley Faculty in 2002

Research Interests

My laboratory studies the mechanics and dynamics of cell movements on the purified protein, single cell, and

tissue levels. For these studies, we are developing new instruments to quantify cell and molecular

mechanics based on optical microscopy, force microscopy, and microfabrication.

Education

2002 Postdoctoral Fellow, Stanford University, Biochemistry

2001 Ph.D., Stanford University, Mechanical Engineering

1997 D.Phil., Oxford University, Engineering Science

1994 B.S.E., Princeton University, Mechanical & Aerospace Engineering

Major Awards

2008-2009 White House Fellow, Washington, DC

2008 Vodafone Wireless Innovation Challenge

2008 Intel Inspire-Empower Challenge

2005 Hellman Faculty Fund Award, UC Berkeley

2004 National Science Foundation CAREER Award

2004 National Collegiate Inventors and Innovators E-Team Award

2003 UC Berkeley Presidential Chair Fellow

2001 National Inventors Hall of Fame Collegiate Inventors Award

1996 National Science Foundation Graduate Research Fellowship

1995 American Society of Mechanical Engineering Arthur L. Williston Medal

1994 Rhodes Scholarship

Professional Experience

2010-present Professor, Bioengineering, UC Berkeley

2007-present Deputy Division Director, Physical Biosciences, Lawrence Berkeley National Lab

2007-2010 Associate Professor, Bioengineering, UC Berkeley

2002-2007 Assistant Professor, Bioengineering, UC Berkeley

2003-present Faculty Scientist, Physical Biosciences, Lawrence Berkeley National Laboratory

2003-present Member, Nanoscale Science & Engineering Graduate Group, UC Berkeley

2002-present Member, Bioengineering Graduate Group, UC Berkeley & UCSF

2002-present Member, Biophysics Graduate Group, UC Berkeley

2002-present Faculty Affiliate, QB3, UC Berkeley

Selected Publications

D.N. Breslauer, R.N. Maamari, N.A. Switz, W.A. Lam, D.A. Fletcher, "Mobile Phone Based Clinical M icroscopy

for Global Health Applications", PLoS ONE 4(7): e6320, 2009.

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 1

Site Location Research Focus Contact Information Rank / Visit StatusInstitute Curie Paris, France Modeling cancer growth

In this work, we model biological tissues using a simple, mechanistic simulation based on dissipative particle dynamics.We investigate the continuum behavior of the simulated tissue and determine its dependence on the properties of the individual cell.We measure the dependence of the homeostatic state on the microscopic parameters of our model and show that homeostatic pressure, rather than the unconfined rate of cell division, determines the outcome of tissue competitions.Simulated cell aggregates are cohesive and round up due to the effect of tissue surface tension, which we measure for different tissues.Using a variety of shear and creep simulations, we study tissue rheology by measuring yield stresses, shear viscosities, complex viscosities as well as the loss tangents as a function of model parameters.We find that cell division and apoptosis lead to a vanishing yield stress and fluid-like tissues.The effects of different adhesion strengths and levels of noise on the rheology of the tissue are also measured.Finally we study growth of tissue spheroids under external stress.Similar to experiments we find that growth is highly localized to a proliferating rim.External pressure reduces growth rates at the

f d b lk

Jens Elgeti PHYSICAL APPROACH OF BIOLOGICAL PROBLEMSGroup leaders : Pr Jean-François Joanny, Jacques ProstPHYSICS AND CARCINOGENESISDoes Homeostatic Pressure Explain Tumor Growth? Jens ElgetiRole of fascin in invadopodia formation and turnover of focal adhesionsNadia Elkhatib, Marie Schoumacher, Danijela VignjevicMorphogenesis and Intracellular Signalling, Institut Curie, 26 rue d'Ulm, 75248 Paris cedex 05, FranceContact: danijela.vignjevic@curie.fr | Website

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 2

Paris Diderot Paris, France Laboratory of Complex Matter and Systems, Physics of Single Cell MechanosensingMany mechanical cues, such as forces and the rigidity of living tissues, control the biological functions and fate of living cells. In particular, substrate rigidity was shown to direct cell spreading, migration, and stem cell differentiation. Our aim is to understand the physical processes allowing cells to detect and adapt to the rigidity of its environment. Thus, we develop original setups combining single cell mechanical measurements (rheometry, traction force, [1]) and visualization of the evolution of the cell structure (cell shape in phase contrast, stress fibers in confocal microscopy, and adhesion complexes in TIRFM).

Atef AsnaciosBenoit Ladoux

Lyon

Ralf EveraersINS Paris and UCLA Paris, France David Bensimon

ENS paris

Francoise LivolantUniversity of Edinburgh, MRC Centre for Inflammation Research

UK Matrix Stiffness Modulates Proliferation, Chemotherapeutic Response, and Dormancy in Hepatocellular Carcinoma Cells

John P. Iredale, D.M., F.R.C.P., F.Med.Sci.,Fax: þ44 131 2426682

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 3

DundeeUniv Dundee

UK I was trained as a theoretical physicist, but for the past 10 years or so have performed research on living systems. My interests span all of biology, from enzymes to cells to embryos to populations, and from basic research questions to translational applications in biomedicine. The tools I bring to biology are 1. theoretical formulation and analysis of fluctuations, and 2. computer simulation of interacting agents.

Timothy NewmanTheory of living systemsInke Nathke inke@lifesci.dundee.ac.uk mechanics of intestinal cancer

Oxford UK Institute of Biomedical Engineering (IBME)

The Institute of Biomedical Engineering (IBME) is a research institute of the Department of Engineering Science, which is located on the University's medical campus in Headington.

Opened in April 2008, the IBME offers a world-class venue for engineers and clinicians to work together on addressing unmet needs in the prevention, early diagnosis and treatment of major diseases. The Institute’s core mission is to develop novel medical devices, technology and systems capable of delivering substantial healthcare benefit.

The IBME is directed by Professor Lionel Tarassenko CBE, FREng, who is also the Chair of Electrical Engineering.

Phil Maini

Karolinska InstituteDepartment of Oncology-Pathology

Dzevad Belkic

EPFL Switzerland Reconstructing the brain piece by piece and building a virtual brain in a supercomputer—these are some of the goals of the Blue Brain Project. The virtual brain will be an exceptional tool giving neuroscientists a new understanding of the brain and a better understanding of neurological diseases.

Melody Swarz, Blue Brain Neurologist

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 4

CECAM-HQ-EPFL Switzerland Computational Physics Methods for CancerJune 27, 2012 to June 29, 2012Location : CECAM-HQ-EPFL, Lausanne, SwitzerlandOrganisersStefano Zapperi (CNR-IENI, Italy)Caterina La Porta (University of Milano, Italy)Physics Of CancerESF Exploratory Workshop - PESC - EMRCConvened by: Stefano Zapperi (IT), Caterina La Porta (IT)

ETH Zurich Switzerland Dr. Viola Vogel is a Professor in the Department of Materials heading the Laboratory for Biologically Oriented Materials at the Swiss Federal Institute of Technology (ETH) in Zürich. After completing her graduate research at the Max-Planck Institute for Biophysical Chemistry, she received her Ph. D. in Physics at Frankfurt University, followed by two years as postdoctoral fellow at the University of California Berkeley. As faculty member she joined the Department of

Viola Vogel

University of Basel Switzerland The Blue Brain project began in 2005 with an agreement between the EPFL and IBM, which supplied the BlueGene/L supercomputer acquired by EPFL to build

Cora-Ann Schönenberger

German Cancer Research Center

Helmholtz, Germany

Lichter: 3D genome; Gladilin: Cell mechanicsDivision of Molecular Genetics Prof. Dr. Peter Lichter In the great majority of cases, cancer arises as a consequence of alterations in a cell’s genetic makeup. Our work focuses on the correlation between such alterations and the formation of tumors. In addition to investigating single genes, we look at how the multitude of a cell’s genes – the genome – is involved in these processes. To this end, we develop special technologies to characterize the genome, e.g., in regard to...

Peter Lichter, Evgeny Gladilin

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 5

Universitat Lepzig Germany Josef A. Käs Research Interests and Expertiselaser physics, optics, scanning probe techniquesbiological physics, condensed matter physics of soft matter, polymer physics, medical physics, and nonlinear dynamics

cell and molecular biology, neuroscience, oncology, genetics, regenerative medicine

optical imaging of the motions of individual polymer chains in polymer networks with nano-

Josef A. Käs (Biophysics), Lars-Christian Horn MD,Principal Investigator & Head of DivisionUniversity of Leipzig Faculty of Physics and Earth Science Institute for Experimental Physics I Soft Matter Physics Divisione mail jkaes@physik uniMPI Dresden Germany Structure formation in cells and tissues Frank Jülicher(MPI Dresden) Dynamics of Tissues[Podcast][Aud][Cam]

TU Dresden Germany Most of what we know in Physics has been derived from experience with the inanimate world. One remaining challenge represents the transfer of these concepts to living objects such as cells, tissues, and entire organisms, where it is not certain if they are appropriate or even relevant. We investigate the mechanical and optical properties of living cells and tissues using novel photonic tools to test their relevance and importance for biological function. Our ultimate goal is the transfer of our findings to medical application in the fields of improved diagnosis of diseases and novel approaches in regenerative medicine with an impact on clinical practice.

Jochen Guck (moving from Cambridge to Dresden)

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 6

University Bremen Germany AFM and cell mechanicsOur research focuses on the characterisation and understanding of cellular and molecular processes. The instrument of choice is the atomic force microscope (AFM), due to its unique sensitivity (in terms of forces), spatial resolution, and the possibility of investigating biological samples under physiological conditions. The AFM is supplemented by optical microscopy in many variants, cell culture and biochemical investigations of the samples. The research focuses on several issues.

Manfred Radmacher

Friedrich-Alexander Universitat Erlangen-Nurnberg

Germany The Faculty of Medicine at the University of Erlangen-Nürnberg is a major player in the field of interdisciplinary research in Molecular Medicine in Germany. Starting with the academic year 1999/2000, the Faculty of Medicine in Erlangen implemented a four-year full-time degree programme in Molecular Medicine , leading to the 'Diploma' level qualification. The German 'Diploma' compares to the international Master of Science degree, and permits admission to a three-year doctoral programme. The Diploma programme was converted into a 3-year Bachelor of Science programme and a consecutive 2-year Master of Science programme in 2007.

Ana-Suncana Smith

University of Saarlandes Germany Biological Experimental Physics GroupsBiological systems are intriguing. Their features emerge from many different interacting components in a way that we do not understand. We develop new experimental and statistical tools in order to tackle well-chosen questions concerning emergent biological functions. Albrecht Ott

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 7

Hemholtz Zentrum Munchen Germany German Research Center for Environmental Health, Institute of Biomathematics and BiometryMy main interests are focussed on the development of methods and programs for segmentation, feature extraction, -evaluation and -display. The quantitation of more or less

Karsten Robenacker

University of Heidelberg Germany German Virtual Liver NetworkThe Virtual Liver will be a dynamic mathematical model that represents, rather than fully replicates human liver physiology, morphology and function, integrating quantitative data from all levels of organisation, from sub-cellular levels to the whole organ.The model will be composed of those pathways, networks and functions, the details of which are necessary and sufficient to generate a dynamic view of liver function, validated in the context of whole organ function and anatomy, and capable of generating experimentally testable predictions that are relevant to the physiology of the liver, as well as the function of the organism, and how this is disturbed in disease.

MPI-Göttingen Max Planck Research Group for Biophysics and Evolutionary Dynamics, MPI for Dynamics and Self-Organization

Göttingen, Germany

Spatial structure increases the waiting time for cancerErik A Martens , Rumen Kostadinov , Carlo C Maley and Oskar Hallatschekerik.martens@ds.mpg.de, oskar.hallatschek@ds.mpg.deNew J. Phys. 13 115014 doi:10.1088/1367-2630/13/11/115014 (http://dx.doi.org/10.1088/1367-2630/13/11/115014)

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 8

German Cancer Research Center

Heidelberg, Germany

Mechanical cell phenotyping using microscopic imaging and computational modelingEvgeny Gladilin1, Paula Gonzalez2, Roland Eils1,2 1German Cancer Research Center, Heidelberg, Germany2BioQuant, University Heidelberg, Germany

e.gladilin@dkfz.de | Website

Institute for Science and Technology Austria

Klosterneuberg, Austria

Topics related to embryo morphogenesis using zebrafish as a model system. Quantitative descriptions of morphogenetic processes of interest, formulating a working hypothesis based on this descriptive analysis, and functionally addressing the working hypothesis using a combination of genetic, cell biological, biophysical and imaging techniques.

Carl Philipp-Heisenberg and others

Leiden-Amsterdam Center for Drug Research

AmsterdamToxicology Leo Price

Leiden Univ. LeidenHelmut Schiessel(Leiden Univ.) DNA and Chromatin[Slides][Podcast][Aud][Cam]

Structure formation in cells and tissues Frank Jülicher(MPI Dresden) Dynamics of Tissues[Podcast][Aud][Cam]

Helmut Schiessel

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 9

NanoNed The Netherlands NanoNed is a national nanotechnology R&D initiative that combines the Dutchstrengths in nanoscience and technology in a national network with scientifically,economically and socially relevant research and infrastructure projects.

Technical University – Delft

Amsterdam

The Biofilm Research Group BIOFILM MODELINGDuring biofilm development, a large number of phenomena occur simultaneously and interact over a large range of length and time scales. As a result of nutrient conversions, the biofilm expands based on bacterial growth and production of extracellular polymers. Chemical species need to be continuously transported to and from the biofilm system by physical processes such as molecular diffusion and convection. Fluid flow drives biofilm growth by regulating the concentrations of available substrates and products. On the other hand, the flow also shears the biofilm surface, and determines biofilm detachment processes. All these linked phenomena create a dynamic picture of the biofilm three-dimensional structure. Mathematical models can prove useful because they allow testing of hypothesis and, in addition, can direct experimental efforts to complex regions of operation that can easily confound the general intuition.

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 10

Hubrecht Institute Netherlands Clevers groupWnt signaling and cancerOriginally focused on T lymphocyte transcription factors, we cloned Tcf1 in 1991. With the discovery that Tcf factors are the final effectors of Wnt signaling, we changed our interests to the biology of Wnt signaling in intestinal self-renewal and cancer. We identified a series of adult tissue stem cells with the novel Lgr5 marker, currently our major focus of research. For a more detailed overview, click here.van Rheenen groupCancer biophysicsComplication of metastasis, the process in which cells detach from the primary tumor to form new distant tumor sites, is the primary reason why women die from breast cancer. The metastatic behavior of tumor cells is highly dependent on the cell’s intrinsic characteristics and on the tumor microenvironment, such as stromal cells and the extracellular matrix. We study both by combining conditional mouse models that recapitulate human breast tumors and intravital imaging techniques (high resolution imaging of metastasis in living animals in real time). By these experiments we hope to indentify new drug targets that combined with current clinical approaches may lead to new therapies.de Rooij groupDynamics of cell adhesionThe focus in our lab is the regulation of cell-cell adhesion. We use high-resolution live-cell imaging and biochemical techniques to investigate how cell-cell adhesion receptors (E-cadherin, Claudin, Nectin) are coupled to the actin

t k l t W t d h thi li k i i d t

Hans Clevers, Jacco van Rheenen, Johan de Rooij

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 11

Radboud University Nijmegen Medical Center

Netherlands Peter Friedl holds the Chair for Microscopic Imaging of the Cell in the department of Cell Biology, which includes the Core Facility for Microscopy at the Radboud University Nijmegen Medical Centre. In addition, he fulfills the role of the head of the Cell Dynamics Laboratory. Peter's research interest is the visualization of cell-matrix interactions and dynamic cell patterning during immune cell interactions and tumor invasion. He, therefore, uses 3D extracellular matrix (ECM) based cell culture models and advanced imaging procedures as well as intravital microscopy. Peter has won the prestigious VICI award in 2010.

Peter Friedl

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 12

Centro de Investigacion Principe Felipe

Valencia, SpainStructural Genomics Laboratory Marc A. Marti-Renom

We are interested in the molecular mechanisms that regulate cellfate. To study such mechanisms, we employ the laws of physics and the rules of evolution to develop and apply computational methods for predicting the 3Dstructures of macromolecules and their complexes. Our current lines of research are:

Protein-Ligandinteractions.We develop methods for comparative docking of small chemical compounds and their target proteins. Such methods are applied to identify drug targets genomes that cause tropical diseases. This work is part of the Tropical Disease Initiative (TDI, http://www.tropicaldisease.org).

Comparative RNA structureprediction.The recent interest in RNA, specially non-coding RNA molecules, has prompted us to develop a series of tools for the alignment of RNA structures and the prediction of their functions. Our main goal for this line of researchis to develop a software pipeline for comparative RNA structure prediction.Structure determination of genomic domains and genomes.More recently, we have engaged collaboration with experimentalists to study the 3D organization of the chromatin. Such work is resulting in the first ever structures of genomic domains in the cell nucleus, including the alpha-globin domain in the Human

th ti f C l b t

Marc A. Marti-Renom

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 13

Institute for Bioengineering of Catalonia

Barcelona, Spain Research TopicsCell motility and tissue dynamics / Cytoskeletal fragility / Cell-Cell adhesion / Cell Mechanics / Nanobiotechnology

Cell motility and tissue dynamicsThe ability of eukaryotic cells to migrate within living organisms underlies a wide range of phenomena in health and disease. When properly regulated, cell migration enables morphogenesis, host defense, and tissue healing. When regulation fails, however, cell migration mediates devastating pathologies such as cancer, vascular disease and chronic inflammation. Our research focuses in understanding the fundamental biophysical mechanisms underlying migration both at the single cell level and at the tissue level.

Cytoskeletal fragilityWith every beat of the heart, inflation of the lung, or peristalsis of the gut, cell types of diverse function are subjected to substantial mechanical forces. How cells sense and respond to such forces underlies fundamental biological functions including differentiation, proliferation, polarization, locomotion, invasion, gene expression, and pattern formation. We recently identified a new class of universal cellular responses to mechanical forces we termed “cytoskeletal fluidization” (Trepat et al, Nature, 2007). The existence of this response class implies that the cytoskeleton of the living cell should no longer be regarded as a robust and stable scaffold but as a fragile one that is able to fluidize and quickly reorganize to adapt to its active mechanical environment. Our

t h f b tt d t di th

Xavier Trepat

National Technical University of Athens

Greece In Silico Oncology Group In Silico Oncology Group is a research module of the Laboratory of Microwaves and Fibre Optics

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 14

Henryk NiewodniczaŸski Institute of Nuclear Physics

Poland Currently, cancer diagnosis relies mostly on morphological examination of exfoliated, aspirated cells or surgically removed tissue. As long as standard diagnosis is concerned, this classical approach seems to be satisfactory. In the recent years, cancer progression has been shown to be accompanied by alterations in mechanical properties of cells. This offers the detection of otherwise unnoticed cancer cell disregarded by histological analysis due to insignificant manifestations. One of techniques, sensitive to changes in mechanical properties, is the atomic force microscopy, which detects cancer cells through their elastic properties. Such measurements were applied to tissue sections collected from patients suffering from various cancers. Despite of heterogeneity and complexity of cancer cell sections, the use of the Young's modulus as an indicator of cell elasticity allow for detection of cancer cells in tissue slices.

P. Laidler

Academy of Sciences of the Czech Republic, Institute of Photonics and Electronics

Prague, Czech Republic

Cancer diagnostics based on damped cellular elastoelectrical vibrations in microtubules

O. Kucera

Department of Molecular Cell Biology, Weizmann Institute of Science

Israel Cell adhesion and migration in cancerWide screens for genes involved in the regulation of cell migration are carried by Suha Naffar Abu-Amara, using high-

Prof. Benny Geiger

Institute of Photonics and Electronics, Academy of Sciences of the Czech Republic

Czech Republic Eur Biophys J. 2011 Jun;40(6):747-59. Epub 2011 Mar 11.Cancer physics: diagnostics based on dampedcellular elastoelectrical vibrations in microtubules.Pokorn˘ J, Vedruccio C, Cifra M, Kučera O.

Potential Sites WTEC APHELION Study - Jan 2012-4 Last update: 1/31/2012

APHELION SITES - EUROPE 15

Université de Mons Belgium MECHANOBIOLOGY & SOFT MATTERMechanism of the Spatial Coordination Between Cell and Nuclear ShapeM.Versaevel, T. Grevesse and S. GabrieleNature Communications, in press (2012)

Sylvain Gabriele

1/30/2012 5:24:00 PM AUSTRIA Vienna - Institute of Science and Technology Austria Carl Philipp-Heisenberg Zebrafish embryo morphogenesis BELGIUM Mons - Université de Mons Sylvain Gabriele Mechanobiology & soft matter CZECH REPUBLIC Prague - Institute of Photonics and Electronics, Academy of Sciences of the Czech Republic Kučera O Cancer physics: diagnostics based on damped cellular elastoelectrical vibrations in microtubules. FRANCE Paris - Inst. Curie Jean-François Joanny, Jacques Prost Physical approach of biological problems. Physics and carcinogenesis Jens Elgeti Modeling tissue growth Nadia Elkhatib, Marie Schoumacher, Danijela Vignjevic Role of fascin in invadopodia formation and turnover of focal adhesions

- Univ. Paris VII. Denis Diderot Atef Asnasios Benoit Ladoux Mechanosensing and nano/micro topography - INS Paris David Bensimon New Results on ISWI Chromatin - ENS Paris

Francoise Livolant DNA Condensation in a Confined Environment (the Bacteriophage Capsid) Lyon Ralf Everaers Structure and Dynamics of Interphase Chromosomes GERMANY Heidelberg - German Cancer Research Center Evgeny Gladilin Mechanical cell phenotyping using microscopic imaging and computational modeling Peter Lichter 3D genome German Virtual Liver Network The Virtual Liver will be a dynamic mathematical model Göttingen – MPI Research Group for Biophysics and Evolutionary Dynamics Oskar Hallatschek Spatial structure increases the waiting time for cancer Leipzig Josef A. Käs Feeling for Cancer with Light Dresden -MPI Frank Jülicher Structure formation in cells and tissues

- TU Jochen Guck (now in Cambridge) Cell mechanics, diagnostic devices Bremen Manfred Radmacher Cell mechanics – AFM GREECE Athens - National Technical University of Athens

In silico Oncology group ISRAEL Rehovot - Weizmann Institute of Science Benny Geiger Cell adhesion and migration in cancer Sam Safran Soft matter approaches to model cell-ECD and cell-cell mechanosensing Italy Milan - University of Milano Stefano Zapperi Statistical materials modeling Caterina La Porta Population Dynamics and Cancer Stem Cells NETHERLANDS Leiden - Leiden Univ. Helmut Schiessel DNA and chromatin structure

Amsterdam - Leiden-Amsterdam Center for Drug Research Leo Price Toxicology, tissue morphology Utrecht – Hubrecht Inst. Hans Clevers, Jacco van Rheenen, Johan de Rooij Wnt signaling and relation to cytoskeleton Nijmegen - Radboud University Nijmegen Medical Center Peter Friedl Mechanics of tumor cell movement and ECM remodeling NanoNed is a national nanotechnology R&D initiative that combines the Dutch strengths in nanoscience and technology in a national network with scientifically, economically and socially relevant research and infrastructure projects.

POLAND Kraków - Henryk Niewodniczański Institute of Nuclear Physics Cell mechanics methods for cancer diagnosis SPAIN Barcelona - Institute for Bioengineering of Catalonia Xavier Trepat Cell motility and tissue dynamics Valencia - Centro de Investigacion Principe Felipe Marc A. Marti-Renom Evolutionary principles to determine cell fate Computational methods for predicting the 3Dstructures of macromolecules and their complexes SWEDEN Stockholm – Karolinska Inst. Dzevad Belkic High energy radiation SWITZERLAND Lausanne – EPFL Melody Swartz Lymphatic system mechanics Dendritic cells – vaccine production Zürich – ETH Viola Vogel Biologically Oriented Materials Angiogenesis Mechanosensing Basel Cora-Ann Schönenberger UK Edinburgh - MRC Centre for Inflammation Research, University of Edinburgh

John P. Iredale Matrix Stiffness Modulates Proliferation, Chemotherapeutic Response, and Dormancy in Hepatocellular Carcinoma Cells Dundee - Univ Dundee Timothy Newman Theory of living systems Inke Näthke Mechanics of intestinal cancer Oxford Phil Maini Institute of Biomedical Engineering (IBME)

RECENT AND FUTURE EUROPEAN CONFERENCES IN PHYSICS AND CANCER Computational Physics Methods for Cancer June 27, 2012 to June 29, 2012 Location: CECAM-HQ-EPFL, Lausanne, Switzerland Organisers Stefano Zapperi (CNR-IENI, Italy) Caterina La Porta (University of Milano, Italy) Physics Of Cancer ESF Exploratory Workshop - PESC - EMRC Convened by: Stefano Zapperi (IT), Caterina La Porta (IT) Location: 13-15 September 2012, Varenna, Italy Stefano Zapperi Institute for Energetics and Interphases (IENI) CNR Via R. Cozzi 53 20125 Milano Italy Caterina La Porta Department of Biomolecular Science and Biotechnology University of Milan

Monday, January 30, 2012

SITE Research Focus/Special Equipment URL Contact Information

Rank/Visit Status 3: must see 2: target of opportunity

Suggested by

The National Institute for the Control of Pharmaceutical and Biological Products (NICPBP)

A must see site (Jack Zhang).

Beijing Institute of Biological Products

"Beijing Institute of Biological Products should be added as it is nominated as National Vaccine Research Center. " (Jack Zhang)

Sinovac "George told me that Chinese New Year is February 14 and that most places close for the following week. Some people take 2 weeks off at that time, so we need to keep this in mind for scheduling visits." (Mary)

http://www.sinovac.com/ "Sinovac is a must. George has a contact there who has a good command of English. Her name is Helen Yang, Manager of International Development, yangg@sinovac.com, tel: 86-10-6296-3661." (Mary)

3 Terry

Joe will call Margaret in GSK http://www.gsk.com/research/index.html

"Vaccine facility in Shanghai while other one is to be started in Taizhou , Jiangsu province in partnering with one local company" (Jack Zhang)

http://www.gsk.com/contactus-careers.htm

Shanghai Institute of Biological Products

Subsidary of CNBG. Cyril will look into this. "Shanghai Institute of Biological Products would be a good place to visit (also associated with CNBG). They are large and have relevant products. "Although a CNBC site, it does appear to be R&D intensive and has modern vaccine production capabilities. If we can arrange a GSK visit in Shanghai with Shenzhen Neptunus and WalVax, then SIBP is a 3." (Terry)

http://www.siobp.com/index_e.htm 8621-62803189 shsys@online.sh.cn

3

CHINA

Potential Asia Sites for Vaccine Manufacturing (W/O India) (as of December 21, 2009)

GSK (JV with Shenzhen Neptunus and WalVax)

URL 1; leads to the research page URL 2: has different tabs where have contact information

3 Terry

Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd.

Zhejang Tianyuan and Change Shen are newer, with less than 500 employees each and if not geograhically convenient, may not be worth the extra travel." (Mary) "Good one, should be among primary sites, recently acquired by Novartis (80% share at the cost of USD120million). " (Jack Zhang)

http://www.ty-pharm.com/en/index.asp Tianhe Road 56, Linping, Yuhang District, Hangzhou City, Zhejiang Province, ChinaPC 311100 86571- 26286888 typharm@mail.hz.zj.cn

1

Public Health Commission ?

Either Joe or Steve will check with John Boslego. 3

Regulatory Commission ? 3

Wuhan Biological Institute

&

Chinese National Biological Group (CNBG) (7 government run facilities)

"Wuhan may be the government- favored; PATH will know...Bill Wainright consults for PATH, is an engineer and knows the Chinese sites." (Steve). "After looking at the CNBG website, it seems that we should try to meet with the CNBG with representatives of the 6 biologicals companies and then make plans to visit Chengdu and or Wuhan." (Mary) "CNBC is State owned. They have a large vaccine portfolio. I would rate them a 3 for a Beijing visit." (Terry) "I am quite familiar with CNBG and two of its manufacturing facilities – Wuhan and Chengdu. These government facilities do quite well on large scale manufacturing once technology is developed and in place. Their R&D capabilities are improving but they have a long way to go. Their manufacturing systems are also improving but have a long way to go to achieve cGMP. PATH has been working quite extensively with Chengdu (JE and Pneumo conjugate) and Wuhan (rotavirus). PATH has an office in Beijing headed by Jack Zhang, who spent 20+ years in the CNBG system and knows most of the vaccine players (public and private) in China. ...Jack would be able to make some introductions for you in China as well, although I ask that you be mindful of his time. " (From Boslego to Joe) "Just merged with Sinopharm. All 6 Institutes are the subsidiaries of original CNBG now Sinopharm." (Jack Zhang)

http://www.cnbgint.com/Contact/index.asp Dr. Bing Zeng (VP, manufacturing?), a contact from George Siber, my former supervisor at Wyeth, bingzeng@cnbg.com.cnMs Meng Li (Business Development), mengli@cnbg.com from Bill Waintwright

Dr. Xiaoming Zhang, Managing Directorxmyang@wibp.com.cn

Gelin Xu, Head of Viral Vaccine Productionxugelin@yahoo.com.cn

26th floor,Fusheng Building,No.4Hui-xin East Street,Chaoyang District，Beijing, P.R.China. District,Beijing,China Postcode:100029 Tel:8610-84663377/8610-84663388 Fax:8610-84663311Email: cnbgint@cnbg.com.cn

3 Mary and Steve

Contact people provided by Mary

http://www.biken.osaka-u.ac.jp/e/research.php

http://www.ifrec.osaka-u.ac.jp/en/access/index.php

JAPANTerryBiken Biken is intergrated with Osaka University. URL1: Staff names, sort by research groups. Main

director: Hitoshi Kikutanigeneral email address: www@biken.osaka-u.ac.jp

URL 2: Immnunology Research Center website

Integrated Life Science Building, Osaka University3-1 Yamadaoka, Suita, 565-0871, Osaka, JapanTEL General Affairs:+81-6-6879-4275FAX +81-6-6879-4272E-mail ifrec-office@ifrec.osaka-u.ac.jp

3

Denka Seiken clinical chemistry, immunochemistry, and infectious disease IVD reagents. "Denka: not much on vaccines. The website did not entice me to want to visit." (Mary)

http://www.denka-seiken.co.jp/english/index.html Masatarou Satsuka (President)DENKA SEIKEN CO., LTD.3-4-2, Nihonbashi,Kayabacho,Chuo-ku,Tokyo 103-0025,JAPANseiken@denka-seiken.co.jpPhone: +81-3-3669-9421Fax: +81-3-3669-9390

2?? Terry

Ministry of Health, Labour and Welfare (Public Health Commission?)

* Research and Development Division, Health Policy Bureau* Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau "It seems that the Pharmaceutical and Food Safety Bureau is responsible for Vaccine manufacturing. " (Remi)

1-2-2 Kasumigaseki Chiyoda-ku Tokyo, 100-8916 +81-3-5253-1111 (main switchboard)

3

Pharmaceuticals and Medical Devices Agency (Regulatory Commission?)

"This is the agency that regulates drugs and biologicals in Japan. " (Mary) "I've just called the PMDA to ask about their activities. They said they focus on reviewing process of new drugs for approval from the Ministry of Health,Labour and Welfare,including offering consultation services before application to manufacturers, as shown [at their] site" (Remi)

http://www.pmda.go.jp/english/service/outline_s.html3

National Inst. Infectious Diseases, Tokyo

"Equivalent to CDC" (Remi's Japan contact) http://www.nih.go.jp/niid/index-e.html Masato Tashiro, director of the Department of Viral DiseasesToyama 1-23-1, Shinjuku-kuTokyo, 162-8640, Japanemail: info@nih.go.jp

3 Grant PP

Kitosato Institute (Research Center for Bilogicals), Tokyo

3

Okuda, K; Xin, KQ

http://www.yokohama-cu.ac.jp/index-e.html

https://ycursc.yokohama-cu.ac.jp/drams/search.do?type=top03_e

http://www.osaka-u.ac.jp/en

http://www.biken.osaka-u.ac.jp/kenkyu/kansen/Protozool/index.html

Nagahara, S; Sano, A

Osaka University, Osaka Name Masahiro TANEMURABirthDay 1964.2Research Keyword transplantation, immunology, xenotransplantation, carbohydrate, cancer immunotherapyE-mail mtanemuragesurg.med.osaka-u.ac.jpTEL 06-6879-3251FAX 06-6879-3259

Name Toshihiro HORIIResearch Keyword development of malaria vaccine, molecular biological research for Plasmodium, parasitologyE-mail horiibiken.osaka-u.ac.jpTEL 06-6879-8280FAX 06-6879-8281URL 2: Horii Group

3

Yokohama City University, Yokohama

Joe will check URLs. URL 1: Yokohama U. General infURL 2: Researcher Database

?? Grant PP

Sumitomo Pharmaceutical Co. Ltd, Osaka

Manufacture, sale/purchase, and import/export of pharmaceuticals, veterinary products, food additives,

Kenjiro Miyatake,Chairman 3 Grant PP

http://www.ds-pharma.co.jp/english/index.html

Chemo-Sero-Therapeutic Research Inst., Kumamoto

drug manufacturing and vaccine development. "Lots of vaccines, including veterinary vaccines. I think this one would be worth a visit." (Mary)

http://www.kaketsuken.or.jp/eng/index.html Akinobu Funatsu, General Director

1-6-1 Okubo, Kumamoto-shi, Kumamoto 860-8568, Japan TEL.096-344-1211 FAX.096-345-1345

3 Grant PP

"We should involve Dr. Chung Keel Lee, formerly at the Salk Institute in Swiftwater, and WHO, and now the key technical advisor to the head of the KFDA. He has good influence, knows a lot about vaccines and is a friend of Don's. chungklee@kfda.go.kr" (Don Gerson to Mary)

Korea Green Cross "Green Cross is a must Don's contact is Dr. BG Rhee, bgrhee@greencross.com, at the head office in Seoul. He has very good English and can help arrange travel to the plant in the south. The Sr Managing Director of the flu facility is Dr. MinCho, mcho@greencross.com. The Mogam Research Institute is part of Green Cross and has a number of interesting projects, so they would be good to visit. Green Cross is a pre-qualified WHO supplier and Mogam is a WHO reference lab." (Don Gerson to Mary)

http://eng.greencross.com/ Park Chang-Un, Chief Executive (contact provided by Bhawani Mukherjee) Tel: 011-82-312609300

3 Terry, Cyril, and Marycontact person provided by Mary

Korea Vaccine http://www.koreavaccine.com/e_about/about.php 3 Terry and CyrilInternational Vaccine Institute

Headed by John Clemems jclemens@ivi.int http://www.ivi.org/about_us/staff/Senior_staff.html#john

http://www.ivi.org/ 3 Cyril

Mogam Biotechnology Research Institute

Dr. Yoon is willing to host your group (from Hyun Lillehoj, Cyril's contact). "I also suggest you visit Mogam and Greencross Veterinary product only since your stay is only one day" (Hyun)

Dr. Yeup Yoon, Director Cell phone number: 031-260-9833

SOUTH KOREA

Co. Ltd, Osaka pharmaceuticals, veterinary products, food additives, industrial chemicals, and other chemical products, etc. "Mention of only one veterinary vaccine. Did not seem worth visiting. " (Mary)

Address ZIP code 553-00011-5-51 Ebie, Fukushima-ku, Osaka, Osaka, JapanTEL (06) 6454-8151FAX (06) 6458-8640

1

WTEC, Inc. Suite 201

4800 Roland Avenue Baltimore, MD 21210

410-467-9832 (fax 9848)

Technology to transform mobility for people with a disability

European Study Tour, 16 – 24 October 2010

Information for Host Research Organizations The United States’ study panel is grateful to your organization for agreeing to receive our delegation. We hope the following information about our purpose and the information we seek will be helpful in preparing for our meeting. Goals of the Mobility Study This study is intended to gather information on the worldwide status and trends in technology that will transform mobility for people with a disability, for the benefit of government decision makers and the research community. The study panelists will gather hands-on information on mobility research abroad that will be used by the U.S. Government to modify its own programs. The study will critically analyze and compare the research in the United States with that pursued in Europe. This information will serve the following purposes:

• Identify good ideas overseas worth exploring in U.S. R&D programs • Clarify research opportunities and needs for promoting progress in the field • Identify specific opportunities (persons and organization) for international collaboration • Evaluate the position of foreign research programs relative to those in the U.S.

Scope of Study The study emphasizes technology to transform mobility for people with a disability, increasing health, participation, and independence at all ages, at home and at work, through prevention of motor impairment, or maintenance and improvement of motor function. Mobility is defined as posture, balance, and transfers; manipulation; walking, stair climbing, and other locomotion tasks; and using transportation. The following strategies are covered by the study:

• joint and limb prostheses • functional electrical stimulation • assistive devices, including robotic aides, wheelchairs and other vehicles, orthoses, and

exoskeletons • health monitoring, including pervasive and wearable systems for fall detection and activity

monitoring • movement training, exercise, and rehabilitation therapy, including robotic, computer,

biofeedback, and virtual-reality based approaches, • strategies that combine drug or cell-based therapeutics with the above strategies.

The study is also interested in organizational and translational issues related to these strategies. Please note that the study is not focused on brain-computer interfaces because WTEC recently completed a separate study on this technology. Agenda for the Visit

• We have prepared a 15 minute slide presentation about the study, the panel, the panel’s research directions, and the current research focus of the sponsoring agencies (National Science Foundation, Department of Veterans Affairs, National Institutes of Health) (attached). We would be happy to present these slides.

• We have assembled a list of questions (attached) intended to improve our understanding of your organization’s research activities.

• We would be happy to hear presentations about your research, or simply to discuss the questions. We would be delighted to see any demonstrations of your work.

Model of Questions for Hosts

Taken from Mobility study

2

Technology to transform mobility for people with a disability European Study Tour, 16 – 24 October 2010

Questions for Host Research Organizations

The following is a list of questions intended to help guide conversations during our visit: 1. Grand Challenges of Mobility Science and Technology:

a. Please identify what you feel are the grand challenges in the field of mobility technology. b. What scientific or technological advances must be made to achieve these grand challenges,

and what are the roadblocks to achieving these advances?

2. Laboratory-specific Issues Related to Mobility Research a. Please state the major objectives of your laboratory’s research and development effort with

respect to transforming mobility for people with a disability. b. What are three key accomplishments of your laboratory in the past ten years? How have these

results influenced the field of mobility from (a) a scientific perspective, and (b) an applications perspective? If possible, please provide copies of written reports and references that document these projects.

c. What percentage of your work is being directly applied to clinical applications vs. basic science and engineering development efforts? What clinical partners or user groups do you work with to test your technology? What performance and quality of life measures are you using to assess efficacy of the systems?

d. Does any of your research have involvement in any way with the military or veterans? e. Do any members of your research team have disabilities?

3. Technology Transfer, Commercialization, and Regulatory Issues:

a. Are there any commercial products resulting from your research? b. How many mobility-related patents has your laboratory or institution generated, what

countries are these patents for, how many have been licensed, and are the patents critical for the commercialization?

c. What human subjects and regulatory approvals are required for your research? 4. Funding – Government and Commercial Sponsorship:

a. What are your current funding mechanisms for mobility science and technology? b. To what extent do these mechanisms involve government, private, and commercial sources? c. Are funding mechanisms typically single-investigator, multi-investigator, or multi-

institutional? In your opinion, what do you think works best? 5. International Collaborations and Comparisons:

a. What do you see as the strengths of European mobility research programs relative to those in the U.S., and vice versa?

b. If relevant, identify research and development areas worth exploring as future collaborations with U.S. mobility science and technology programs.

6. Training and Education:

a. What types of training programs in mobility science and technology exist at your institution? b. To what extent do these training programs involve industry?

INTERNATIONAL ASSESSMENT OF RESEARCH AND

Model Presentation to Hosts

Taken from Vaccine2 Study

INTERNATIONAL ASSESSMENT OF RESEARCH ANDDEVELOPMENT IN

VACCINE MANUFACTURING

Sponsors:

WTEC IS CONDUCTING THE INTERNATIONALASSESSMENT OF RESEARCH ANDDEVELOPMENT IN VACCINE MANUFACTURING,

World Technology Evaluation Center, Inc.

COSPONSORED BY THE U.S. NATIONALSCIENCE FOUNDATION (NSF), THE U.S. DEPARTMENT OF AGRICULTURE (USDA), THEU.S. DEPARTMENT OF HEALTH AND HUMANSERVICES (DHHS), AND THE NATIONALINSTITUTES OF HEALTH (NIH).

WTEC IS THE LEADING ORGANIZATION IN THEWTEC IS THE LEADING ORGANIZATION IN THEU.S. CONDUCTING INTERNATIONALTECHNOLOGY ASSESSMENTS VIA EXPERTREVIEW, AND HAS CONDUCTED OVER 60 SUCHSTUDIES SINCE 1989

HTTP://WWW.WTEC.ORG/VACCMFG/

Open sources and open dissemination(http://www wtec org)

Key Principles of WTEC StudiesKey Principles of WTEC Studies

(http://www.wtec.org)

Mutually beneficial exchange of ideas among host institutions and U.S. delegations

Review of draft reports by hosts prior to Review of draft reports by hosts prior to public dissemination; proprietary considerations honored

SCOPE/OBJECTIVES OF THE STUDY

Assessment of science and engineering R&D for flexible, scalable, modular vaccine manufacturing that could provide rapid response to the needs of both the general public and to p p g psmaller regional outbreaks of disease.

Gaps discovered in the course of the study will facilitate the articulation of new initiatives.

The sponsoring agencies will assess new information gathered by the visiting panelists as a basis for new programs and initiatives

Agricultural vaccine will be considered as well because of the Agricultural vaccine will be considered as well because of the demands for massive inoculation of domestic fowl and animals from which applicable lessons may be learned.

Further details on the study are available at http://www.wtec.org/vaccmfg/

greatest relianceon new science and methodology

Why engineering?

science

greatest reliance on engineering and new technology

discovery development commercialization

technology

Vaccine manufacturingHow can engineering help?

AgileFl iblFlexibleModularResponsive

Vaccine development timesVaccine development times13 to 29 years

THE PROJECT TEAM

Expert PanelExpert Panel

•• Joseph T. Joseph T. BielitzkiBielitzki (Chair) (Chair) University of Central Florida University of Central Florida •• Stephen W. DrewStephen W. Drew Science Partners LLCScience Partners LLCpp•• Cyril Gay Cyril Gay United States Department of United States Department of

AgricultureAgriculture•• NarayanNarayan IyerIyer Biomedical Advanced Research and Biomedical Advanced Research and

Development Authority (BARDA), U.S. Development Authority (BARDA), U.S. Department of Health & Human Department of Health & Human ServicesServices

•• Sheldon Howard JacobsonSheldon Howard Jacobson University of Illinois at UrbanaUniversity of Illinois at Urbana--ChampaignChampaignChampaignChampaign

•• Terrance LeightonTerrance Leighton Children’s Hospital Oakland Children’s Hospital Oakland Research Institute (CHORI)Research Institute (CHORI)

•• Mary RitcheyMary Ritchey RitcheyRitchey Associates, Inc.Associates, Inc.

Other MembersOther Members•• RemiRemi KumagaiKumagai WTEC Representative WTEC Representative

Joseph T. Bielitzki, MS, DVMOffice or Research and CommercializationUniversity of Central Florida, Orlando , Florida

In a past life:Chief Veterinary Officer/NASAProgram Manager/DARPA/DSO

These are the programsI worked with:

Accelerated AnthraxAccelerated Anthrax

RestorativeInjuryRepair

STEPHEN W. DREW, PHDCONSULTANTS TO THE BIOTECHNOLOGY & PHARMACEUTICAL INDUSTRIES

Strategic Development of Biologics

Strategies for Regulatory Approval Merck Sharp & Dohme Vaccines Merck Sharp & Dohme Vaccines RNA Aptamer for Macular Degeneration

Process Design for Bulk and Formulated Biologics

Therapeutic Enzymes for Pancreatic Insufficiency

Conjugated Polysaccharide Vaccines Live Viral Vaccines and Subunit Vaccines

Quality Control and Quality Assurance Systems

Manufacturing Strategies and Facilities Design

CYRIL G. GAY, DVM, PH.DNATIONAL PROGRAM LEADER, ANIMAL HEALTHNATIONAL PROGRAM STAFF, ANIMAL PRODUCTION AND PROTECTIONAGRICULTURAL RESEARCH SERVICE, UNITED STATES DEPARTMENT OF AGRICULTURE

Prior Positions Director, New Product Technical Development, Pfizer Chief, Biotechnology, Center for Veterinary Biologics, USDA

Relevant Publications C.G. Gay, R. Zuerner, J.P. Bannantine, H.S. Lillehoj, J.J Zhu, R. Green & P.P. Pastoret (2007).

Genomics and Vaccine Development. Rev. sci. tech. Off. int. Epiz., 26 (1), in press Brown R.A., Blumerman, S., Gay C., Bolin C., Duby R., Baldwin C.L. (2003). Comparison of

three different leptospiral vaccines for induction of a type 1 immune response to Leptospira borgpetersenii serovar hardjo. Vaccine 21, pp 4448-4458G C G S lt J B l ki C (2003) Ch ll d O t iti i D l i d Gay, C.G., Salt, J., Balaski, C. (2003). Challenges and Opportunities in Developing and Marketing Vaccines for OIE List A and Emerging Animal Diseases. Dev Biol. Basel, Karger, vol 114, pp 209-216.

Gay, C.G. (1994). A Risk Analysis Model for Experimental Veterinary Vaccines. Biotechnology 11: 826-827.

Roth, H.J., Gay, C.G., Espeseth, D.A., (1995). Risk Analysis for the Importation of Veterinary Biologics. Rev. sci. tech. Off. int. Epiz., 14 (4): 1061-1071.

NARAYAN IYER, PHDBIOMEDICAL ADVANCED RESEARCH AND DEVELOPMENT AUTHORITY (BARDA), U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES (HHS)

Experience and Expertise Active in the biotech and vaccine industry for over 10 years.

Acting Chief of the Anthra Vaccines Section of the Di ision of CBRN Acting Chief of the Anthrax Vaccines Section of the Division of CBRN Countermeasures at BARDA.

Responsible for the execution and oversight of anthrax vaccines programs authorized under Project BioShield Act of 2004 and the Pandemic and All Hazards Preparedness Act of 2006.

Managed both early and advanced product development of two product lines: Anthrax vaccine as part of the Biodefense portfolio and vaccine against Travelers Diarrhea at Iomai Corporation (now Intercell USA).

Worked in Bioprocess development for drug substance and product o ed op ocess de e op e t o d ug substa ce a d p oductmanufacturing as well as applications of QbD to late-stage processes, ensuring compliance for licensure requirements.

At Corning Inc, he managed product development of oligonucleotide-based microarrays for monitoring regulation of gene expression.

He has received awards and citations for his contributions to advanced product development.

SHELDON H. JACOBSON, PH.D.

Professor, Willett Faculty Scholar Director, Simulation and Optimization Laboratory College of Engineering, University of Illinois at Urbana-Champaign shj@uiuc.edu https://netfiles.uiuc.edu/shj/www/shj.html https://netfiles.uiuc.edu/shj/www/shj.html

Areas of Research- Industrial Engineering and Operations Research- Pediatric Vaccine Economics and Formulary Design- Pediatric Vaccine Stockpiling and Distribution- Recent Publications Sewell, E.C., Jacobson, S.H., 2003, "Using an Integer Programming Model to Determine the Price of

Combination Vaccines for Childhood Immunization,” Annals of Operations Research, 119, 261-284. Jacobson, S.H., Karnani, T., Sewell, E.C., 2003, “Analyzing the Economic Value of the Hepatitis B -

Haemophilus Influenzae Type B Combination Vaccine by Reverse Engineering a Formulary SelectionAlgorithm,” Vaccine, 21(17-18), 2169-2177.

Jacobson, S.H., Sewell, E.C., Allwine, D.A., Medina, E.A., Weniger, B.G., 2003, “Designing PediatricVaccine Formularies and Pricing Pediatric Combination Vaccines using Operations Research Models andAlgorithms,” Expert Review of Vaccines, 2(1), 15-19.

Jacobson, S.H., Karnani, T., Sewell, E.C., 2004, “Assessing the Impact of Wastage on Pediatric VaccineImmunization Formulary Costs Using a Vaccine Selection Algorithm,” Vaccine, 22(17-18), 2307-2315.

Jacobson, S.H., Sewell, E.C., Karnani, T., 2005, “Engineering the Economic Value of Two PediatricCombination Vaccines,” Health Care Management Science, 8(1), 29-40.

Jacobson,, S.H., Sewell, E.C., Proano, R.A., Jokela, J.A., 2006, “Stockpile Levels for Pediatric Vaccines:How Much is Enough?” Vaccine, 24(17), 3530-3537.

Jacobson, S.H., Sewell, E.C., Proano, R.A., 2006, “An Analysis of the Pediatric Vaccine ShortageProblem,” Health Care Management Science, 9(4), 371-389.

TERRANCE LEIGHTON - SENIOR SCIENTISTCENTER FOR IMMUNOLOGY & VACCINE DEVELOPMENT

Research Interests

• Molecular evolution of bacterial sporulation• AFM & NanoSIMS single bacterial or viral particle

digital imaging under physiological conditions• Pathogen vaccines - Genomics of surface antigens,

formulation and delivery technologiesy g• Single molecule antigen:antibody nanogold AFM

imaging on native pathogen surfaces• Pathogen medical countermeasures – Genomics

and structure-based drug design• Broad-band PCR detection of viral and bacterial

pathogen signatures by mass spectrometry

MARY B. RITCHEY, PH.D.RITCHEY ASSOCIATES, INC., PHARMACEUTICAL CONSULTING

Areas Of Expertise Biologicals Development and Manufacturing Strategies Quality Control and Assurance Systems Development Quality Control and Assurance Systems Development Investigations and Problem Solving

Experience Held Various VP Positions with Responsibilities for Development,

Manufacturing, Quality and Technical Services for Vaccines and Biologicals at Lederle Laboratories and Wyeth Pharmaceuticals

Responsible for Global Vaccine Supply and Capital Programs Directed Supply Chain Development and Technology Transfer for

Conjugated Polysaccharide VaccinesQ C Q O Built Quality Control and Quality Assurance Organizations

Developed Processes for Both Bacterial and Viral Vaccines Including Influenza, Polio, Pertussis, Diphtheria, Tetanus, and Various Polysaccharide/Conjugated Vaccines

Prepared Investigational New Drug and License Application Materials

Basic Research on Influenza Viruses

NORTH AMERICAN BASELINE WORKSHOPWorkshop with leading industry and university

experts, held in Washington, D.C., January 23, 2007

Designed to assess the state-of-the-art in Vaccine Manufacturing R&D and applications in North America to provide a baseline for comparing U.S. and other countries’ work in Vaccine Manufacturing.

Major issues discussed: Can Current Vaccine Manufacturing Strategy Meet Future

Vaccine Needs? Can Vaccine Manufacture be Agile, Modular and

Responsive? Incorporating Innovation in Bioprocessing The Changing Face of Vaccine Development

EUROPEAN SITES VISITED IN 2007(1)AUSTRIA Baxter BioScience, Vaccines, Orth an der Donau

BELGIUM GlaxoSmithKline Biologicals, Rixensart Pfizer Global Manufacturing, Louvain-la-Neuve Federal Public Service Health, Food Chain Security and

Environment, Scientific Institute of Public Health (SIPH), Brussels

ITALY Novartis, Siena Novartis, Siena University of Siena

The NETHERLANDS Intervet Nederland B.V., Boxmeer

EUROPEAN SITES VISITED IN 2007(2)UNITED KINGDOM Oxford University

National Instit te for Biological Standards and Control Potters National Institute for Biological Standards and Control, Potters Bar

Health Protection Agency, London PowderMed, Oxford National Institute for Medical Research (NIMR), London Institute for Animal Health, Compton Laboratory

GERMANY Mikroglas chemtech GmbH, Mainz

SWEDEN Karolinska Institute, Stockholm ECDC (European Center for Disease Control), Stockholm Swedish Institute for Infectious Disease Control, Stockholm

KEY RESULTS OF EUROPEAN STUDY (1)REGULATIONS

• Requirements for Human and Animal Vaccines are Harmonized The potential exists to manufacture human vaccines in a facility that

routinely manufactures animal vaccines and vice versa, as a means of rapidly building expanding capacity in the face of emerging disease

• A Framework for Reviewing Adjuvants Alone is AvailableUse of these compounds that can enhance vaccine effectiveness or

reduce the amount of antigen required is facilitated

• A Pandemic Preparedness Plan for Influenza is In PlaceExperimental H5N1 vaccines have been preparedp p p

• Because Vaccines are intended for Healthy Populations, Requirements Are Complex for Initial Testing and LicensureSmall organizations with novel ideas have difficulty proceeding beyond

the research stage

KEY RESULTS OF EUROPEAN STUDY (2) TECHNOLOGY

• Vaccine Manufacturers Are Working on Platforms Capable of Supporting Multiple Vaccine AntigensC ll lt t V b d t l lCell culture systems, e.g. Vero can be done at large scale

• Microtechnology Is Under Development for Both Manufacturing Optimization and Laboratory Evaluation of Antigens “Lab on a Chip” offers promising results

• New Vaccine Delivery Systems Offer PromiseDelivery of DNA vaccines to the immune system via gold particles is under

development

Bacterial ghosts and virus like particles are also in development

• Use of disposable systems is increasing as a means of reducing costs and increasing flexibilityWAVE bioreactors can be used for some cell culture systems

• A Better Understanding of the Immune System Is Required for Vaccine Development in the FutureA study of “Structural Immunology” has been suggested as a path forward

KEY RESULTS OF EUROPEAN STUDY (3)ECONOMICS AND DELIVERY:

• Vaccine Stockpiles for Pre-Pandemic Vaccines Are Being Developed Location of the stockpile and import/export rules can impact the

effective use of stockpiles

• Ancillary Supplies and Logistics Are Key to Effective Immunization During a Pandemic The volume of supplies needed, e.g. syringes and biowaste disposal

can become bottlenecks

• Costs for New Vaccines and Improving Current Vaccines Are High Return on investment often favors new products over improvements

ASIAN SITES TO BE VISITED: CHINA The National Institute for the Control of

Pharmaceutical and Biological Products (NICPBP)

Sinovac

Ministry of Health

Beijing Institute of Biological Products (NVSI)

PATH

Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd.

Sinopharm

ASIAN SITES TO BE VISITED: JAPAN Biken (The Research Foundation for Microbial

Diseases of Osaka University)

National Inst. Infectious Diseases

Osaka University

Ministry of Health, Labour and Welfare

Kitosato Institute (Research Center for Biologicals) (off-site meeting with representative)

Chemo-Sero-Therapeutic Research Institute (off-site meeting with representative)

ASIAN SITES TO BE VISITED: S. KOREA

Korea Green Cross

Mogam Biotechnology Research Institute

AUSTRALIAN SITES TO BE VISITED

Bioproperties, Ltd (Melbourne and Sidney)

University Melbourne

Public Health Commission (TGA)

STUDY SCHEDULE

2007January 23 N. American Workshop

2009 October 28 Kickoff Meeting for

Asia/Australia Study2010 Feb. 21-Mar 5 Asia/Australia site visits

May 5th Final Workshop

Autumn 2010 Final Report

FINAL WORKSHOP OF THE STUDY

The final workshop of the Asia and Australia Study ill b h ld i W hi t D C M 5 2010will be held in Washington, D.C. on May 5, 2010

Registration information for the final workshop is at: http://www.wtec.org/vaccine2/

You are invited to attend or to send a representative.

Thank You!

APPENDICES

AGRICULTURAL RESEARCH SERVICE (ARS) MISSION

ARS conducts research to developand transfer solutions to agriculturalproblems of high national priority.

ARS PROFILE

8,000+ employees Intramural Research 8,000 employees 2,000+ scientists 100+ laboratory locations $979 million annual budget

(FY02) Partnerships with

universities and industry

a u a esea c Farm to table research

scope 22 National programs 1,100+ research

projectsy

A Promising FutureWho We Are

Animal Health (NP 103)

•Healthy animals are critical to our ability to maintain a wholesome and safe food supply and prevent the

The National Animal Disease Center, in Ames, IA, is the largest federal animal disease research center in the U.S. We conduct research to solve animal health and food safety problems faced by livestock producers and the public.

transmission of pathogens to people

•We will utilize the power of genomics (both animal and microbe) to better control host-pathogen interactions

•We will provide new tools in the continuing eradication of animal diseases of economic importance

•We will improve the detection of pathogens to detect animal diseases before they begin

•We will increase the understanding of the animal immune system to increase resistance to infections and develop highly effective vaccines

•We will increase our understanding of the mechanisms of

The mission of the Animal Parasitic Diseases Laboratory in Beltsville, MD is to reduce the economic cost of parasitism in livestock and poultry and to reduce the risk of transmission of parasite zoonoses to humans.

The Plum Island Animal Disease Center in Greenport, NY is responsible for research and diagnosis to protect the nation's animal industries and exports from catastrophic economic losses caused by foreign animal disease (FAD) agents accidentally or deliberately introduced into the U.S.

The research program of the Animal Disease Research Unit in Pullman, WA is to solve basic and applied problems concerning persistent infectious diseases of domestic animals.The mission of the Poultry Research Unit in Starkville, MS is to improve poultry production efficiency and product quality.

Scientists at the Roman L. Hruska U.S. Meat Animal Research Center in Clay Center, NE are developing scientific information and new technology to solve high priority problems for the U.S. beef, sheep, and swine industries.

The mission of the Arthropod Borne Animal Diseases Research diseases to develop better control strategies

ARS

RESEARCH

The Southeast Poultry Research Laboratory in Athens, GA provides scientific solutions to national and international exotic and emerging poultry disease problems that impact poultry and human health.

The mission of the Poultry Production and Products Safety Research Laboratory in Fayetteville, AR is to investigate ways to reduce the impact of poultry production problems in turkeys and broilers, ensure a wholesome product for the consumer, and reduce the negative environmental impact of poultry production.

The mission of Avian Disease Oncology Laboratory in East Lansing, MI is to provide leadership in solving current and future problems in neoplastic and other viral diseases of poultry using basic and applied multidisciplinary team approaches thereby benefiting the poultry industry and consumers.

The mission of the Arthropod-Borne Animal Diseases Research Laboratory in Laramie, WY is to conduct basic and applied studies on the arthropod transmitted viral diseases of domestic animals.

PRIORITIES

St t i bj ti Strategic objectives1. Establish ARS laboratories into a fluid, highly effective

research network, to maximize use of core competencies and resources

2. Access to specialized high containment facilities to study zoonotic and emerging diseases

3 Develop an integrated animal and microbial genomics3. Develop an integrated animal and microbial genomics research program

4. Establish centers of excellence in immunology 5. Launch a biotherapeutic discovery program providing

alternatives to animal drugs

PRIORITIES

St t i bj ti Strategic objectives6. Build a technology-driven vaccine and diagnostic

discovery research program7. Develop core competencies in field epidemiology and

predictive biology8. Develop internationally recognized OIE expert

collaborative laboratoriescollaborative laboratories9. Establish best in class training center for our nation’s

veterinarians and scientists10. Develop a model technology transfer program to

achieve the full impact of our research discoveries

WTECINTERNATIONAL ASSESSMENT OF RESEARCH ANDDEVELOPMENT IN VACCINE MANUFACTURING

Terrance LeightonS i S i ti tSenior ScientistCenter for Immunology & Vaccine Development

TERRANCE LEIGHTONRESEARCH INTERESTS

Combinatorial vaccines Protection against all forms of

pathogen disease etiology Pulmonary inhalational phase

Spore surface antigens Cot, BclA & other exosporium

targets Toxinemic phase

rPABacteremic phase Bacteremic phase Cap 35 kDa SAP EA1

Terrance Leighton – Research InterestsAFM Nanometer Scale Resolution of Native

Bacterial Spore Surface Structures Under Physiological Conditions

Outer Coat:Honeycomb structure

B. thuringiensis

Bacterial Spores

5.0 x 5.0 m

B. atrophaeus

Exosporium

350 x 350 nm

600 x 300 nm 400 x 400 nm

Outer Coat:Rodlet structure

300 x 300 nm 130 x 130 nm

Outer Coat:Rodlet structure

Inner Coat:Honeycomb structure

B. cereus

AFM reveals strikingly different species-specific spore coat ultrastructure

These studies establish AFM as a powerful new tool for revealing bacterial spore structure and variation at nm-to-mm scales

Terrance Leighton – Research InterestsAFM Visualization of Immunolabeled

B. anthracis Spore Surface Structures Under Physiological Conditions

5.0 x 5.0 m

NanotaggedAnti-surface Ab

Spore Surface Ag:Ab Panel

Control Sera Nanotagged Ag:Ab Panel

Nanotagged Ag:Ab Complexes

DRAFT -- Appendix D. Site Reports—Europe 1

Site: Cardiff University Cardiff, Wales, UK, CF10 3XQ http://www.cf.ac.uk/ Date Visited: September 28, 2007 WTEC Attendees: G. W. Huber (report author), R. J. Davis, V.V. Guliants, R. Sharma Hosts & Research Professor Gary Attard (Electrochemistry, surface science, catalysis) Interests: Email: Attard@Cardiff.ac.uk Professor Michael Bowker (Catalysis, surface science, nanoscience)

Email: Bowkerm@cardiff.ac.uk Dr. Albert Carley (Surface analysis, catalysis, surface science)

Email: Carley@Cardiff.ac.uk Dr. Philip Davies (Surface science, nano-imaging)

Email: DaviesPR@Cardiff.ac.uk Professor Graham Hutchings (Catalysis)

Email: Hutch@Cardiff.ac.uk Dr. Stuart Taylor (Catalysis)

Email: TaylorSH@Cardiff.ac.uk Dr. David Willock (Theory/modeling)

Email: WillockDJ@Cardiff.ac.uk

BACKGROUND

The total number of people at Cardiff University studying catalysis and surface science include 65 researchers, among them, 7 academics (the hosts for the WTEC team’s visit); 13-post-doctoral researchers, and 45 research students. This is one of six groups in the UK that studies catalysis and surface science. In 2004/2005 these researchers published 77 papers. The current grant-holding for these researchers is £5.5 million/yr ($11.2 million/yr). Approximately 60% of the grants come from government and 40% from industry. The university negotiates with industry prior to doing research, and all intellectual property issues are open for negotiation. Some current major instrumentation for these research groups include: XPS, AFM, STM/AFM/XPS/LEED/EPR, SEM, and in situ XRD.

A past weakness for all groups in the UK system has been the lack of technical support for research; the Heterogeneous Catalysis and Surface Science group at Cardiff is currently addressing this problem in various innovative ways. It is also getting more graduate students from abroad; currently 30 % of its PhD students are foreign. The time required for a PhD is 3 years.

There are three major themes to these research groups:

1. Heterogeneous Catalysis 2. Nanoscience 3. Surface Science

RESEARCH AND DEVELOPMENT ACTIVITIES

During our visit the WTEC panelists heard presentations from our hosts that described the research that they are doing. Some of the research projects are described below.

Michael Bowker (http://www.cf.ac.uk/chemy/contactsandpeople/academicstaff/bowker.html)

The Michael Bowker group is at the interface between surface science and catalysis with an emphasis on surface science (see Bowker 2007 for a recent review that covers most of the group’s recent surface science work). Figure 1 shows an image from the Bowker Research Group of a Pd/TiO2 model catalyst before and after exposure to oxygen. This figure illustrates the structural changes that can occur with a catalyst.

MODEL SITE REPORT

taken from Catalysis Study

2 DRAFT -- Appendix D. Site Reports—Europe

A)

B)

Figure 1. Image of Pd/TiO2 (110) model catalyst before and after exposure to 900 L of O2 at

673 K (courtesy of Bowker Research Group).

There are four major themes in the Bowker group:

1. Oxide Surfaces and Selective Oxidation 2. Au surfaces and Catalysis/Photocatalysis 3. Automotive Catalysis and Surfaces 4. Nanoparticle Surface Science

The Bowker group claims that as nanoscience becomes more important, surface science will also become more important. Future areas of research in the Bowker group include

1. Controlled fabrication (Can we make controlled clean nanostructures by vacuum methods? Thermal stability is crucial.)

2. Identification of oxygen storage mechanism on Pt/CeOx at the atomic scale 3. The role of peroxide in NOx storage 4. Fabrication of Pt nanoparticles onto thin-layer BaO to investigate NOx storage. 5. Model catalysts by wet preparation techniques. 6. Bio-surface interactions

Gary Attard (http://www.cf.ac.uk/chemy/contactsandpeople/academicstaff/attard.html)

The focus of the Gary Attard research group is on electrocatalysis at metal surfaces. This includes fuel cell research studying hydrogen evolution, hydrogen oxidation, oxygen reduction, and CO tolerance. Figure 2 shows cyclic voltammetry of Ru/Pt layers from the Attard Research Group.

In situ electrochemistry experiments are also being done to study well-defined nanoparticle catalysts under “real conditions.” This includes combining Raman spectroscopy with voltammetry and in situ STM with GC-MS monitoring of products. Another area of research for the Attard group is bio-nanoscience, which is the controlled formation of nanomaterials using bacteria

Albert Carley (http://www.cf.ac.uk/chemy/contactsandpeople/academicstaff/carley.html)

The Albert Carley research group is using TAP with isotopic labeling to study CO oxidation with Au catalysts, supplemented by fundamental studies on model planar catalysts prepared in situ. Researchers in this group are using XPS to study catalysts for H2O2 synthesis, including TiO2-supported Au, Au/Pd, and Pd catalysts. They have found that the most active catalyst for H2O2 synthesis is an Au-Pd/TiO2 catalyst. This research indicates the importance of bimetallic catalysts. Important variables that go into designing catalysts for H2O2 synthesis include support, Au-Pd composition, calcination conditions, stability-leaching, and aging.

DRAFT -- Appendix D. Site Reports—Europe 3

Figure 2. Cyclic voltammetry of Ru/Pt{100} film (black line) and the platinum adlayers at 20 mV s-1.

Inset displays CO oxidation peaks for selected Pt adlayers at 50 mV s-1 (courtesy of Gary Attard).

Philip R. Davies (http://www.cf.ac.uk/chemy/contactsandpeople/academicstaff/davies.html)

The Philip Davies research group uses a number of surface science techniques on model catalysts, to include STM, DFT, XPS, and LEED. During the WTEC visit Dr. Davies discussed his work on understanding amine basicity on the role of reaction pathways over Cu catalysts; substrate/adsorbate mobility in the presence of Cl over Cu catalysts; and the reactivity relationships on Fe and Au catalysts. Figure 3 shows how various surface science and theoretical techniques can be combined to give insight into the reaction surface chemistry for amine conversion over a Cu model catalyst.

Graham J. Hutchings (http://www.cf.ac.uk/chemy/contactsandpeople/academicstaff/hutchings.html)

There are three major themes for the Graham Hutchings research group:

1. Catalysis by gold 2. Oxidation with oxide catalysts 3. Enantioselective catalysts

The Hutchings research group is known worldwide for its work in the area of selective oxidations. Hutchings researchers have developed tunable gold catalysts that are able to oxidize hydrocarbons under mild conditions and also oxidize glycerol to glycerate (Carretin et al. 2002). They have also developed Pd-Au catalysts for H2O2 production from H2 and O2, as shown in Figure 4 (Edwards et al. 2007). The highest productivity they have achieved for H2O2 synthesis is 900 mole H2O2/h-kgcat. Pd-Au catalysts are also good catalysts for the selective oxidation of alcohols to aldehydes without solvents (Enach et al. 2006). The reaction for H2O2 synthesis takes place via –OOH species. These species are also effective for the oxidation of alcohols. This is why Au-Pd catalysts are effective for both H2O2 synthesis and selective alcohol oxidation.

4 DRAFT -- Appendix D. Site Reports—Europe

Figure 3. Role of amine basicity in controlling reaction pathway for Cu(110): R3N(g) + O(a) H2O +

RN(a). Results are from a combination of techniques including STM, XPS, DFT (courtesy of Philip Davies).

0

10

20

30

40

50

60

Au Pd

Pro

duct

ivity

, mol

/h/K

g

Au/Pd Au/Pd Figure 4. Rate of H2O2 formation from H2 and O2 over TiO2 supported Pd-Au catalysts

(courtesy of Graham Hutchings).

Figure 5 shows some of the Hutchings group work on identifying the active phase and reaction mechanism for oxidation reaction with vanadium phosphate catalysts (Conte et al. 2006).

CH3CH2NH2 CF3CH2NH2

15.6 nm

C6H5NH2

DRAFT -- Appendix D. Site Reports—Europe 5

Figure 5. Summary of w-VOPO4 transformations observed between 50º and 600ºC. w-VOPO4

transforms to d-VOPO4 when exposed to a variety of reactants at 400ºC. A further transformation of d- VOPO4 into a disordered material was observed when butane or acetic acid was added in the absence of oxygen. d-VOPO4 recrystallized to w-VOPO4 when calcined at 600ºC in air. The disordered material obtained in the butane experiment recrystallized to w-VOPO4 when calcined at 600ºC in air. w-VOPO4 transforms irreversibly to g-VOPO4 when exposed to butane in air at 600ºC (Conte et al. 2006).

Stuart Taylor (http://www.cf.ac.uk/chemy/contactsandpeople/academicstaff/taylor.html)

The Stuart Taylor group is currently studying the following areas:

1. Total oxidation (Ambient temperature CO and VOC oxidation) 2. Selective oxidation of hydrocarbons 3. Catalyst preparation (co-precipitation, supercritical preparation) 4. Fischer-Tropsch Synthesis 5. Hydrogenation reactions

Researchers in this group have found that nanocrystalline CeO2 is also active for total polyaromatic hydrocarbon oxidation. They are studying selective propane oxidation with Co-oxide catalysts and have observed that nanocrystalline Co3O4 is extremely active for hydrocarbon oxidation. At low temperature, Co3O4 has a high selectivity towards propylene. These catalysts do deactivate but are easily regenerated.

David J. Willock (http://www.cf.ac.uk/chemy/contactsandpeople/academicstaff/willock.html)

The David Wilcox group uses computational chemistry to understand heterogeneous catalysis. Researchers in this group use quantum chemistry methods to understand the reaction profiles of complexes and adsorption and reaction at metal and oxide surfaces. They also use force field methods such as Monte Carlo simulations. This group has conducted studies for acetone adsorption on Pt surfaces. They have also studied methane activation on MoO catalysts (Coquet and Willock 2005). Their research indicates the important role of defect Mo sites, and without defects no activation is seen. They also teach an MS course in molecular modeling and scientific computing.

SUMMARY/CONCLUSIONS

There is a wide range of world-class catalysis activities occurring at Cardiff University, spanning surface science with model catalysis to theoretical calculations to catalysis under industrial conditions. This integrated approach allows insights into fundamental chemistry and advances in real world catalysis to be made. It is likely that Cardiff University will continue to make significant advances in catalysis in the future.

REFERENCES Bowker, M. 2007. Catalysis resolved using scanning tunnelling microscopy, Chem. Soc. Rev. 36:1656.

6 DRAFT -- Appendix D. Site Reports—Europe

Carrettin, S., P. McMorn, P. Johnston, K. Griffin and G.J. Hutchings, 2002. Selective oxidation of glycerol to glyceric

acid using a gold catalyst, Chem. Commun. (2002) 696-697.

Conte, M., G. Budroni, J.K. Bartley, S.H. Taylor, A.F. Carley, A. Schmidt, D.M. Murphy, F. Girgsdies, T. Ressler, R. Schlögl, and G.J. Hutchings. 2006. Chemically induced fast solid-state transitions of {omega}-VOPO4 in vanadium phosphate catalysts. Science 313:1270-1273.

Coquet, R., and D.J. Willock. 2005. The (010) surface of alpha-MoO3, A DFT + U study. Phys. Chem. Chem. Phys. 7:3819-3828.

Edwards, J. K., A. F. Carley, A. A. Herzing, C. J. Kiely and G. J. Hutchings, 2007. Direct synthesis of hydrogen peroxide from H2 and O2 using supported Au–Pd catalysts, Faraday Disc. 138. DOI: 10.1039/b705915a.

Enache, D.I., J.K. Edwards, P. Landon, B. Solsona-Espriu, AF. Carley, A.A. Herzing, M. Watanabe, C.J. Kiely, D.W. Knight, and G.J. Hutchings. 2006. Solvent-free oxidation of primary alcohols to aldehydes using Au-Pd/TiO2 catalysts. Science 311:362-365.

MODELFinal Workshop PresentationFinal Workshop Presentation

Taken fromMobility Research Study

WEARABLE SENSOR TECHNOLOGY

Bonato & Chan

Overview

Describe clinical need for wearable sensors

f Discuss sensor functionality

Present technical aspects of sensor/system implementation (e-textile and wireless)

Provide specific examples of sensors/systems developed by European groups Gloves

Shirts

Bed linen

Motivation

Health Care Reform (Independence at Home Medical Practice Demonstration Program) Medical Practice Demonstration Program) electronic health information systems, remote

monitoring, and mobile diagnostic technology

Less intrusive patient monitoring Improve diagnoses

Enhance safety

Increase community participation

Maintain independence

Motivation

Community Based researchT k h i l b f h h i l Take the gait lab out of the hospital

Measure research phenotyping

Medication titration N of 1 trials

EUROPEAN COMMISSION

Peter Wintlev-Jensen and Andreas Lymberis

P t f 14

Motivation

Percentage of GDP (EU27)

2

4

6

8

10

12

142007 2060

0

2

Source: EC '2009 Ageing Report: economic and budgetary projections for the EU-27 Member States (2008-2060)'

Framework Programme 7 ICT

Motivation

Framework Programme 7 ICT research

ICT & Aging Advanced Prototypes for independent

living/active aging (Ambient Intelligence, Robotics)

Open Systems, Reference Architectures, p y , ,Platforms

Support: roadmaps, ethics, standards, Int’l cooperation

Currently~30 projects, ~90 M€ funding

TELECARE IN SCOTLAND

Motivation

• 46,500 hospital bed days saved by facilitating early hospital discharge

• 225,000 care home bed days saved by delaying the requirement for people to enter care homes

• 46,000 nights of sleep-over care and 905,000 , g p ,home check visits saved by substitution of remote monitoring arrangements

• Collectively, these savings are valued at around £43 million - an anticipated benefit to program funding cost ratio of 5:1.

Utility

Physiological Monitoring ECG ECG

Body Temp

Blood pressure

Respiratory Rate

Oxygen saturation

Surface EMG

Biomarkers (sweat)

Sympathetic/parasympathetic balance (e.g. mood)

Utility

Movement monitoring Body position (e g falls) Body position (e.g. falls)

Activity monitoring

Energy expenditure

Geolocation Track activities

Localize people in need of urgent clinical care

Fuse with sensors embedded in the environment

Merging with survey data gathering in the fieldMerging sensor and survey data

Related clinical conditions

Cardiac arrhythmias - 15 million

A M Sleep Apnea- Millions

Sudden Infant Death Syndrome 2,000/year

Nursing home

Falls 10%/year

Wearable Sensor Categories

Ambulatory SystemsFi i b d di i l First generation systems based on traditional sensor technology and data loggers (similar to Holter systems) with limited capability.

Cloth-Based Systems Second generation systems based on sensors integrated

in garments and relying on either wireless technology in garments and relying on either wireless technology or e-textile solutions for data gathering.

First Generation (Ambulatory) Systems

NASA Lifeguard (2004)

Second Generation (Wearable) Systems

Systems based on wireless technology or e-textile sol tions to gather and rela data to a remote sitesolutions to gather and relay data to a remote site.

Internet

Location (GPS) Communication Gateway

Cell phone network

Cell

Emergency ECG & Respiration

e-textileData Glove Bluetooth/WLAN

Family/Caregiver

Clinician

Motion

Second Generation (Wearable) Systems

Sensor Technology

Electrical resistancePi l i Piezoelectric

Hall Sensors

Foam based

Wires wrapped around thread

Traditional Electrodes

Wireless controls

Examples

Zurich

Pisa

Madrid

Twente

UNIV OF ZURICH (BALGRIST HOSPITAL)

Prof. Gregoire Courtine

Instrumented Glove•• To date, the To date, the gloves developed, as far as now, present drawbacksgloves developed, as far as now, present drawbacks

- sensor saturation- sensor signal drift- not being able to record all finger joints

•• To overcome these drawbacks, a new sensorized glove has been developed: the To overcome these drawbacks, a new sensorized glove has been developed: the NeuroAssess GloveNeuroAssess Glove

NeuroAssess Glove

Instrumented Glove

• Specifications:

- 6 resistive bend sensors- 0.5° resolution- 0.9° repeatability error- ± 3° accuracy- 100 Hz sampling rate

SMARTEX AND UNIVERSITY OF PISA

Prof. DeRossi and Dr. Paradiso

Overview

Smartex (spin-off of University of Pisa) - Goal is to se te tiles as a platform for nobtr si e monitoringuse textiles as a platform for unobtrusive monitoring

Devised a novel way of “printing” piezoelectric sensors onto elastic cloth at very low cost

10 years old-company with 10 staff

Funding Milan textile industry, DARPA, NIH

Functional focus-manipulation, posture, balance, transfers and locomotion

Smartex Capabilities

Smartex products

Shirt (commercialized) with ECG and

respiratory rate sensors.

Jumpsuit/pants with position sensors.

Products

Bed sheet (ECG, Resp Rate, Movement)

Elbow Sleeve (EMG, FES in development)

Glove (conductive elastomers, microbubbles for force measurement in development)

TREMOR PROJECT

Prof. Jose Pons

TREMOR Project

Consortium of 8 European partners

Prof José L Pons (Project Coordinator) Consejo Superior de Prof. José L. Pons (Project Coordinator), Consejo Superior de Investigaciones Científicas, Madrid, Spain along with 8 other European institutions http://www.iai.csic.es/tremor/index.htm

“An ambulatory BCI-driven tremor suppression system based on functional electrical stimulation”

“Tremor is most common movement disorder”

Managed with drugs, surgery (thalamotomy), and deep brain stimulation

Treatments are ineffective in 25% of patients

TREMOR PROJECT

Uses EEG and EMG along with IMUs to detect voluntary motion and tremor, using a sensor fusion approach

Use FES to either Cancel tremor with out-of-

phase stimulation

Stiffen the limb by co-contraction, to reduce tremor amplitudetremor amplitude

Project at an early stage

Interesting use of FES making use of wearable sensors

UNIVERSITY OF TWENTE - MIRA

Prof. Peter Veltink

Wearable Motion Analysis Laboratory

Human Movement Sensing

Inertial & magnetic sensors

10+ years of research Now commercially

available (Xsens) Utilized in peer-

i d bli tireviewed publications Enables community,

institution, and home based evaluations

Monitoring Dynamic Interactions

Foot – Ground interaction Instrumented shoe Two 6 DOF sensors

2 inertial sensors

Hand – object In development

Instrumented Shoe

Ground Reaction Forces Center of Mass

Leidtke et. al., 2007

Schepers et al, 2009

XSENS 3D MOTION TRACKING

Dr. Per Slycke

Company Overview

Founded 10 years ago - University of Twente spin-off. Focus is 3D motion tracking Focus is 3D motion tracking. 65 employees with 50% in research & development. Focus is on 3 industries: 1) Industrial applications

(unmanned vehicles), 2) Entertainment/training & simulation (movie special effects and video games), and 3) Movement science (how they started).

First Generation Sensor Technology

Real-time motion capture system.

Wi d it ith k i d Wired suit with power packs required.

Usable indoors or outdoors (difficult for video motion capture) with no marker occlusion issues.

Integration drift an issue for position estimates.

First Generation Sensor

Second Generation Sensor Technology

Real-time motion capture.

N i k i d No wires or power packs required.

Increased accuracy.

Usable indoors or outdoors with no occlusion issues.

Integration drift resolved through UWB RF technology.

Second Generation SensorRecharge Station

UWB RF Receiver

Wearable Technology Gaps

Technology is not yet reliable for enough safety applicationsapplications EKG applications will need to be as good as standard

electrodes to get traction

Kinematic technology not yet accurate enough for precise research applications (gait lab)

X (1/10th l l f ) Xsens (1/10th level of accuracy)

Wearable Technology Gaps

System integration not yet adequate for commerciali ation and clinical applicationcommercialization and clinical application Technical and data security issues

Wellness vs. medical applications

Unclear if end users are adequately involved in the design process

Conclusions

Wearable sensors hold great promise to: Improve diagnostics Monitor treatment Enhance research outcomes Increase independence and participation Reduce healthcare costs

However, technology is only in its “second generation”

Will need to improve accuracy, reliability and system integration for true translation to occur

1

CHAPTER 2

SYNTHESIS OF NANOSTRUCTURED CATALYSTS

Raul F. Lobo

INTRODUCTION

As defined in Chapter 1, “a heterogeneous catalysis is a molecular event occurring at a solid-fluid interface [where] the nanostructure surrounding the reactive interface, known as the active site, can significantly influence the observed rate of reaction (referred to as catalytic activity) and the distribution of observed products (known as selectivity).” This definition points to the need to control the molecular structure of a heterogeneous catalyst at the nanometer length scale to successfully prepare catalysts that are both active and selective. The catalysis community endeavors to accomplish this objective by the creative use of diverse synthesis methods. This chapter describes important examples of successful control of catalyst nanostructure and its impact on catalytic activity and selectivity, as observed by the WTEC panel during its visits to laboratories in Asia and Europe. When appropriate, the chapter will reference research activities conducted in the United States to highlight similarities or differences between the three regions. The aim of this review is not to be exhaustive, but rather to illustrate the innovative ways in which scientists and engineers are successfully controlling atoms and molecules to self-organize in cooperative assemblies with meaningful catalytic functions. The selected examples of nanostructured catalysts described here are ones that have shown interesting or unique activities.

The definition of heterogeneous catalysis given above does not reveal the difficulty of the task that is the preparation of successful and novel catalysts. In particular, in addition to catalytic activity and selectivity, practical catalytic materials must be very stable at reaction conditions. Practical industrial reaction conditions often require high temperatures and strong oxidizing or reducing environments—environments that must be withstood for extended periods of time by the nanostructured catalysts. In addition to structural stability, long-term catalytic activity requires that impurities (either in the feed or by-products of the reaction) do not accumulate on the catalyst surface and block access to the active site. This chapter discusses mainly the activity and selectivity of novel nanostructured catalytic materials because these are the properties readily controlled through synthesis. The issues of stability are nevertheless important and are discussed in more details in other chapters.

First, some context and definitions are provided here for some of the ideas discussed later by describing an example of a nanostructured industrial catalyst already used in industry, platinum (Pt) nanoparticles supported on zeolite K-L (Treacy 1999). This example epitomizes the importance of nanoscopic length scales in catalytic materials and is one to which other materials described below can be compared. Zeolite L has a one-dimensional pore system with pore windows of ~7.5 Å and cages between the windows of ~11 Å. This material is an excellent catalyst for the reforming of n-hexane and n-heptane into benzene and toluene (McVicker et al. 1993), and it is used commercially for this purpose in several oil refineries. The presence of Pt nanoparticles in the pores of this zeolite is revealed by Z-contrast TEM in the left image of Figure 2.1. This figure also illustrates the diversity of Pt clusters in the zeolite pore (right image of Figure 2.1) in the fresh catalysts. After time-on-stream, the smaller particles aggregate to make particles similar to type B or H.

Model

Final Report Chapter Taken from

Catalysis Study

DRAFT -- 2. Synthesis of Nanostructured Catalysts 2

The right side of Figure 2.1 also illustrates that a portion of the active sites can be inaccessible to reacting molecules if two large clusters block the one-dimensional pores of the zeolite. There is then an optimal loading of metal on the catalysts that depends on the average crystal size of the zeolite support. In the best-case scenario, there will be one metal cluster per pore in each of the crystal pores.

Figure 2.1. (Left) A Z-contrast TEM image of zeolite Pt/K-L after reduction and reaction in oil; (right) illustration of the location and variable size of Pt clusters in the zeolite pores. In the optimum catalyst, each pore will contain only one particle (of the type B or H) in the pores to maximize access to the active metal surface (Treacy 1999). As depicted, clusters B and H block access to the clusters C-G.

Pt/Zeolite L catalysts are prepared by impregnation, where cationic mononuclear Pt species are dissolved in water and added to the zeolite support. The nanoparticles are formed upon heating this sample in a reducing atmosphere (McVicker et al. 1993). During the heating and reduction, the cationic species migrate into the zeolite pore, decompose, and are reduced. Platinum clusters are formed by migration and aggregation of Pt atoms. Where is the nanostructure “design” in this synthesis? In this case, it is the selection of the zeolite with the precise pore size and shape, and the composition needed to stabilize metal clusters in the pores. The Pt clusters do indeed self-assemble from the molecular species during the activation process. Choosing the “right” zeolite and the proper activation protocol are essential steps to make this nanostructure possible. It must be recognized, too, that in this system the thermodynamically favored state is the formation of large metal particles on the outside of the zeolite crystal. The synthesis process is crucial to capture the metastable disperse nanoparticle phase for long periods of time and to avoid the direct conversion of the precursors into large metal particles.

In the examples of catalyst synthesis that follow, self-assembly of inorganic precursors on a nanostructured support, or the use of self-assembled moieties (such as micelles and rods), are exploited in various ways to achieve materials with novel structures and with interesting catalytic properties arising from the new structure. Self-assembly plays a role in almost every case and can be thought of as the paradigm that connects the diverse materials and synthesis methods discussed throughout.

RHENIUM CLUSTERS IN ZEOLITE ZSM-5

Prof. Iwasawa at the University of Tokyo (see site report, Appendix C) recently reported a new rhenium-based catalyst with exceptional selectivity for benzene hydroxylation to form phenol using molecular oxygen as the oxidant (Bal et al. 2006). The catalyst is prepared by a chemical vapor deposition method using trioxomethylrhenium as the precursor. This rhenium precursor reacts with the acid sites of the zeolite, forming isolated species of rhenium trioxide bound to the zeolite framework. The catalyst is then activated in the presence of ammonia, leading to a reorganization of the intracrystalline rhenium forming isolated Re

Raul F. Lobo 3

clusters. The highest selectivity is obtained by flowing a small amount of ammonia along with benzene and oxygen, and the only by-product detected is CO2.

Both zeolite structure and composition are very important to form the selective Re clusters. Zeolites beta, mordenite, ZSM-5, and USY were investigated, and only the catalysts prepared on zeolite ZSM-5 showed high activity and selectivity. The composition is also very important, because the selectivity of the catalysts increases as the amount of aluminum in the ZSM-5 framework increases (from 48% to 88% selectivity) (Tada et al. 2007). An extended-X-ray absorption spectroscopy investigation of the samples and their evolution with pretreatment revealed that the initially mononuclear species aggregates upon heating and—in the presence of ammonia—forms a very well defined rhenium oxinitride cluster (Figure 2.2). The rhenium assemblies are edge-sharing octahedra with nitrogen atoms in the center and oxygen atoms capping the corners.

Figure 2.2. Rhenium oxinitride clusters form in H-ZSM-5 zeolites in the presence of ammonia (Bal et al. 2006).

The complex has formally a positive charge and is anchored to the zeolite by electrostatic forces. This structure shows why a small ammonia pressure is required to maintain high activity and selectivity with the cluster. The ammonia provides enough nitrogen background pressure to keep the stabilizing nitrogen atoms in the cluster from leaving the active sites. If the flow of ammonia is stopped, the clusters eventually decompose and catalytic activity is lost. Again, it is important to recognize that only ZSM-5 gives acceptable catalysis levels. It is a zeolite that incidentally turned out to have the most suitable channel dimensions to allow the growth and assembly of the rhenium in a 10-unit cluster—but no bigger. Could this have been predicted from the outset? Probably not, because it was not known a priori what the structure was of the active site. The catalyst was prepared following a hint from previous reports suggesting rhenium inside zeolites could be a selective catalyst for benzene hydroxylation (Kusakari, Sasaki, and Iwasawa 2004). By combining various synthesis techniques (CVD, impregnation, etc.) and activation protocols, Iwasawa’s group found this very interesting material. It was the combination of good chemical intuition and a systematic and well-organized synthesis research plan that allowed them to find this outstanding example of nanostructured catalysis.

NOVEL PROPENE PARTIAL OXYDATION CATALYSTS

The selective oxidation of hydrocarbons accounts for about 25% of the organic chemical products manufactured worldwide. One of the most important types of heterogeneous catalysts used for these oxidations are mixed metal oxides. Mitsubishi Chemicals has developed a new mixed metal oxide catalyst of composition MoVTe(Sb)NbO, a material capable of catalyzing the selective oxidation of propane to acrolein (Grasselli et al. 2003). In a recent report (Sadakane et al. 2007), Ueda and coworkers at Hokkaido University (see site report, Appendix C) describe the synthesis of a new material with many structural similarities to the Mitsubishi catalyst. The basic structure of the Mitsubishi catalyst is depicted in Figure 2.3a. Here, 6 and 7 rings of {MO6} octahedral and pentagonal {(M)M5O27} units are comprised of a heptagonal {MO7} unit surrounded by edge-sharing {MO6} octahedral units (DeSanto et al. 2004). Each unit cell contains four 7-ring pores and four 6-ring pores.

DRAFT -- 2. Synthesis of Nanostructured Catalysts 4

The new structure discovered by Ueda’s group is comprised of the same building units arranged with a different connectivity. The result (Figure 2.3b) is a material also containing 6- and 7-rings. The new structure has three 7-ring pores and only two 6-ring pores per unit cell, the result of a different concentration of the {MO6} octahedra with respect to the pentagonal units. The catalytic tests performed on both catalysts show that their activities are remarkably similar for the acrolein–to-acrylic-acid reaction (the 2nd step in the propene oxidation process). These similarities indicate that the layered structure and the presence of both 6 and 7 rings are important to achieve high activity and selectivity at low temperatures. Crude MoxVy oxides were much less active for this reaction.

A Raman and UV/Vis investigation of the synthesis and assembly of the tetragonal and trigonal catalysts reveals important details about the formation of intermediate building units during the synthesis process. These studies show that by controlling the pH carefully during the synthesis of the materials, pentagonal units {Mo(Mo)5} are formed in the precursor solution. This conclusion is inferred from the Raman signatures of the solution, consistent with the formation of polyoxomolibdates that contain the pentagonal unit. UV/Vis spectra are also consistent with the presence of polyoxomolibdates containing the pentagonal unit. These studies show that synthesis of the tetragonal and trigonal catalysts depends on the formation of nanoscale building blocks that can self-assemble into an ordered solid upon the hydrothermal treatment of the synthesis solution.

Figure 2.3. (a) Tetragonal structure of mixed metal oxide Mitsubishi catalyst; (b) newly discovered trigonal mixed metal oxide discovered by Ueda at Hokkaido University (Sadakane et al. 2007).

MESOPOROSITY DESIGNED INTO MICROPOROUS CATALYSTS

Selective heterogeneous catalysts usually operate with high selectivity only within a narrow temperature window. Below some minimum temperature, chemical reactions proceed too slowly to be of practical value. Above an effective maximum temperature, secondary reactions become kinetically dominant and make the catalyst impractical. In zeolites and other microporous catalysts, the temperature window of operation for catalytic chemistry is coupled to transport (physical) processes. That is, sometimes the reactants or products diffuse slowly within the catalyst particles, greatly reducing the effectiveness of the catalyst.

This problem is widely recognized as a practical limitation to the application of zeolites, and many attempts and strategies have been devised to overcome it. The obvious one is to reduce the size of the crystallites. This often works, but crystal size reduction also decreases the thermal stability of the zeolite and increases the ratio of external/internal surface areas, promoting unselective reactions that occur on the crystal exterior. Recently, much effort has gone into developing materials that are microporous at one level but also mesoporous at another level, such that the resistance to diffusion is drastically reduced. During visits to Asia and Europe, the WTEC panel observed various strategies to form meso-microporous materials, a promising approach to solve this problem.

Raul F. Lobo 5

Micro-Mesoporous Zeolites by Design of Organic-Inorganic Surfactants

The group of Prof. Ryoo of the Korea Advanced Institute of Science and Technology (KAIST; see site report in Appendix C) has developed an innovative strategy for the synthesis of zeolite crystals containing within them mesoporous channels (Choi et al. 2006). The key developments are the design of a new structure-directing agent containing an alkoxysilane moiety to anchor the molecule to the zeolite, a quaternary ammonium group to provide solubility in the synthesis gel, and an alkyl chain to promote aggregation of the organic structure directors. Scheme 1 shows an example of a prototypical molecule used by the Ryoo’s group.

Si NMeO

MeOMeO

Alkoxysilane

Alkylammonium

Alkane chain

Scheme 1. Prototypical molecule.

Using this approach, the Ryoo group has been able to prepare several zeolite materials with extraordinary crystal mesostructure. Figure 2.4 shows a typical example of the dramatic change that is obtained in crystal mesostructure.

Figure 2.4. Example of the crystal morphology of zeolite ZSM-5 obtained using an organic structure-directing agent similar to the one depicted in Scheme 1.

Analysis of the mesoporosity of these materials using adsorption studies clearly shows highly monodisperse pores, consistent with aggregation of the surfactant structure-directing agents into rods as the zeolite crystal grows towards its final shape. Further indication of the order of the mesoporosity is obtained from X-ray powder diffraction studies that show a relatively narrow peak at low angles (less than 1° 2). This peak arises because of the correlation between center-to-center distances of contiguous mesopores.

DRAFT -- 2. Synthesis of Nanostructured Catalysts 6

Perhaps the most dramatic effect is observed on the catalytic selectivity and activity of these materials (Srivastava, Choi, and Ryoo 2006). One of the reactions where these new materials have shown promise is in the synthesis of jasminaldehyde. Scheme 2 shows the reaction of interest starting from benzaldehyde and heptanaldehyde. A mesoporous ZSM-5 zeolite shows excellent activity and selectivity (98% and 98%, respectively) towards the formation of jasminaldehyde (Choi et al. 2006; Srivastava, Choi, and Ryoo 2006). These numbers can be compared to traditional H-ZSM-5 zeolites (3.9% and 69%, respectively) and mesoporous aluminosilicates (MCM-41-type materials) that have still lower activity (25%) and lower selectivity (79%) than the mesoporous zeolites. This difference in activity indicates not only that the mesoporosity of the material helps increase catalytic activity, but also that there is some structural change on the mesoporous crystal surface (external to the micropores, but internal to the mesopores) that allows for this large improvement in catalytic selectivity. The synthetic approach developed by the KAIST group is very flexible. At this point, it seems that only a small portion of many structural variations of the molecules have been explored. This is a promising route to discovering new nanostructured catalysts with improved selectivity and activity.

CHO

+ OHC

CHO

Scheme 2. Synthesis of jasminaldehyde using mesoporous zeolites.

Micro-Mesoporous Zeolites from Carbon Templates

Christensen and coworkers at the Technical University in Denmark (see site report in Appendix D) have developed a completely different approach to making zeolite catalysts containing mesopores (Kustova, Hasselriis, and Christensen 2004; Christensen et al. 2005; Christenson et al. 2007). The approach is called the carbon templating method, whereby zeolites are synthesized using a highly concentrated gel in the presence of carbon materials such as carbon black particles (~12 nm in diameter), carbon fibers, carbon nanotubes, etc. During crystal growth, zeolite crystals grow around the carbon structures in the synthesis gel, engulfing the carbon particles. After the zeolite synthesis has been completed, the samples are heated in the presence of oxygen and the carbon is burned completely, leaving spaces within the crystal with irregular orientations and locations but relatively uniform in size. The TEM image in Figure 2.5 is of a crystal of ZSM-5 after calcinations and removal of the carbon. The mesopores can be observed clearly in the image. This method is very flexible and is widely applicable to the synthesis of many zeolite structures. It can yield a large fraction of mesoporous volume (up to 1.0 cc/g).

Figure 2.5. (Left) TEM image of zeolite silicalite-1 prepared using carbon black particles in the synthesis gel; (right) diagram illustrating the concentration profile of benzene (A), ethylene (B) and ethylbenzene (C) on a conventional zeolite crystal and a mesoporous zeolite prepared by the carbon templating process (Christensen et al. 2007).

Raul F. Lobo 7

Recently, Christensen et al. (2007) have investigated simultaneously the catalytic activity and diffusion rates of benzene and ethylbenzene in mesoporous ZSM-5 crystals. The catalytic tests show that for zeolites of nominally the same crystal size, the reaction rate for benzene alkylation is much faster for the mesoporous zeolite than for the conventional zeolite crystal. Using the classical ideas of diffusion-controlled transport in catalyst pellets, they derive activation energies for the diffusion of reactants and products. Their analysis indicates that the effect of the mesopores is to accelerate the transport of reagents into the crystal (and products out of the crystal). Their analysis provides an explanation for increases in both selectivity and activity for the reaction investigated.

Micro-Mesoporous Catalysts by Assembly of Nanoparticles

The group of Feng-Shou Xiao at Jilin University (see site report in Appendix C) has devised a still different approach (Li et al. 2005; Tang et al. 2007; Wang et al. 2005). In this case, the investigators first prepare a solution of zeolite precursor nanoparticles by mixing, for example, water, tetraethylorthosilicate, and tetrapropylammonium. This particular mixture, when heated to ~100°C for short periods of time, gives rise to nanoparticles that are a few nanometers in diameter. These nanoparticles are then put in contact with a mixture of surfactants: Pluronic P123 and (C3F7O-C3F6O)2CFCF3CONH (CH2)3N

+(C2H5)2 and water. This mixture is stirred and heated under hydrothermal conditions at 180°C. The product contains a very well-defined mesoporous structure similar to the one of mesoporous silica USB-1. The composite material is called JLU-20 (Figure 2.6).

Figure 2.6. TEM image of JLU-20 showing the hexagonal arrangement of mesopores and the internal zeolite structure (Li et al. 2005).

Using a combination of nitrogen adsorption isotherms, nuclear magnetic resonance, and infrared spectroscopy and catalytic tests, the researchers at Jilin University show convincingly that the materials they prepare contain both mesoporosity and microporosity reminiscent of the properties of ZSM-5 crystals. Unfortunately, at this time there is no report describing the catalytic chemistry of the JLU-20 samples, and these cannot be compared to the two previous examples.

These three examples of mesoporous zeolites show the diversity of approaches that can be used to reach a common goal. Self-assembly, keen understanding of the aqueous chemistry of inorganic oxides, and the colloidal chemistry of charged particles in an aqueous environment are all elements needed to successfully prepare these complex materials.

DRAFT -- 2. Synthesis of Nanostructured Catalysts 8

SYNTHESIS OF EXTRA-LARGE-PORE ZEOLITE ITQ-33

The group of Avelino Corma at the Institute de Tecnología Química (ITQ) de Valencia (see site report, Appendix D) recently reported a new zeolite material with two important new structural characteristics (Corma et al. 2006). This material contains channels with 18-ring pores (Figure 2.7) ~12.5 Å in free diameter in one crystal direction, and in two perpendicular directions contains 10-ring (5.5 Å) channels. Prior to the synthesis of ITQ-33, several extra-large-pore zeolites (containing more than 12 rings as the minimum pore dimension) had been synthesized. In particular, ECR-34, a gallium silicate, contains one-dimensional pores of similar size to ITQ-33. However, ITQ-33 has pores in three dimensions, and it is prepared with a simple structure director, hexamethonium cations.

Figure 2.7. Structure of the new 18-ring zeolite ITQ-33 (courtesy ITQ, Valencia).

The successful synthesis of ITQ-33 requires four ingredients. The first ingredient is a structure director (hexamethonium) that fills in the pore space not occupied by the silica framework. The second ingredient is the presence of some fluorine ions in the synthesis gel. These ions are incorporated in the as-synthesized material to balance (in part) the charge of the organic structure director and end up typically occluded in some of the small cages of the zeolite structure. In this form, the fluoride anion has both a stabilization effect for small cages and a structure-directing effect by selecting structures that have these cages. The third ingredient for the synthesis of ITQ-33 is the addition of some germanium oxide (in addition to silicon dioxide) to the synthesis gel. The larger Ge-O bond distances also stabilize cage structures that are different from the ones usually observed in pure silicates. The final crucial ingredient in the synthesis of ITQ-33 is the use of high-throughput synthesis methods. Originally, ITQ-33 was found as a small impurity in a set of exploratory synthesis compositions (Corma et al. 2006) investigated by the Spanish group. By the combination of statistical design of experiments techniques and high-throughput experimentation, Corma and collaborators found narrow synthesis conditions that allow for the preparation of this material in pure form. It is especially interesting that a small and flexible organic molecule such as hexamethonium is capable of stabilizing such a large and open structure.

N+

N+

Scheme IV: Hexamethonium

The catalytic tests conducted with this zeolite indicate that the acidity of ITQ-33 is of similar strength compared to the acidity of other high-silica zeolites. For instance, in the alkylation of benzene with propene to make cumene, ITQ-33 gives high selectivity at high conversions (with less than 0.01% by-products at 99% conversion), and the rate of deactivation is slower than the rate of deactivation of comparable commercial catalysts such as zeolite beta. ITQ-33 has also been tested for the cracking of vacuum oil, where it has shown several important qualities. First, it gives a conversion higher than zeolite beta and similar to zeolite USY.

Raul F. Lobo 9

Second, it gives higher diesel selectivity without loss of the yield of butanes and propene. Because ITQ-33 can be prepared using a simple and inexpensive organic structure director, and because it has unique catalytic properties while maintaining good stability, it is quite possible that this rather exotic material will find industrial applications. This material is very new, and much can be expected from further study of its catalytic properties.

HETEROPOLYANIONS AS PRECURSORS FOR DESULFURIZATION CATALYSTS

Hydrodesulfurization is a very important catalytic process used to remove sulfur from oil feedstocks by the selective hydrogenation of carbon-sulfur bonds. The catalysts are usually prepared by impregnation of alumina with ammonium heptamolibdate and cobalt nitrate. This precursor material is sulfided to yield MoS2 crystallites (a layered material) with cobalt atoms decorating the edges of the layers. It has been found empirically that a Co/Mo ratio of 0.5 gives the most active catalysts.

In order to improve over the existing catalysts, the Catalysis Laboratory at Lille and IFP in France (Martin et al. 2005; Mazurelle et al. 2008) have developed a new route to the preparation of hydrodesulfurization catalysts based on heteropolyanions (HPA) of molybdenum and cobalt. The basic idea is to use HPA with atomically mixed Co and Mo as a way to enhance the formation of small crystallites upon sulfidation. The starting point was Anderson HPAs of composition CoMo6O24H6(NH4)3. Since the ratio of Co/Mo is below the optimal value, the Lamonier laboratory developed a synthesis of the dimer of this HPA (Co2Mo10O38H4)

6– and then exchanged the ammonium form with cobalt to form a compound with the desired Co/Mo ratio.

Generally, the researachers found that the use of simple HPA (with a Co/Mo ratio different from the optimal) already showed improved activity over the materials prepared with heptamolidbate and cobalt nitrate. The new Co-exchanged Anderson HPA dimer resulted in even better activity than all previous samples. The origin of this enhanced activity can be explained based on TEM images of the standard catalysts and of the HPA-catalyst (Figure 2.8). The images show that the use of the HPA reduces the effective size (diameter) of the MoS2 layers, generating more active sites per unit mass of catalysts. In the figure, disordered individual layers of the MoS2 are the most commonly observed structure on the HPA-based catalysts. On the traditional catalysts, the MoS2 layers are more organized in stacks of crystals, and in fact, the MoS2 single layers can be observed to surround some of the alumina particles. This structure leads to low levels of layer edges, the structures where the active site of the catalysts is believed to be located.

Figure 2.8. TEM images of sulfided HDS catalysts prepared using an Anderson dimer HPA (left), and conventional ammonium heptamolibdate, and cobalt nitrate (right) (Lamonier et al. 2007)

DRAFT -- 2. Synthesis of Nanostructured Catalysts 10

FINAL REMARKS

This chapter has described recent international advances in the synthesis of nanostructured catalysts that have shown promise to improve upon the activity or selectivity of existing catalysts. Multiple times in visits to labs in Europe and Asia, WTEC panelists observed the use of preformed nanostructures as starting blocks upon which the final structure is formed or developed. Panelists also observed that the characterization techniques developed for the nanotechnology revolution have been extremely helpful to the characterization of novel catalysts with nanostructures and have promoted an intensification of efforts across the world to improve important catalysts already in use or under development.

REFERENCES

Bal, R., M. Tada, T. Sasaki, and Y. Iwasawa. 2006. Direct Phenol Synthesis by Selective Oxidation of Benzene with Molecular Oxygen on an Interstitial-N/Re Cluster/Zeolite Catalyst. Angew. Chem. Int. Ed. 45:448-452.

Choi, M., H.S. Cho, R. Srivastava, C. Venkatesan, D.H. Choi, and R. Ryoo. 2006. Amphiphilic organosilane-directed synthesis of crystalline zeolite with tunable mesoporosity. Nature Materials 5:718-723.

Christensen, C.H., I. Schmidt, A. Carlsson, K. Johannsen, and K. Herbst. 2005. Crystals in crystals: Nanocrystals within mesoporous zeolite single crystals. J. Am. Chem. Soc. 127:8098-8102.

Christensen, C.H., K. Johannsen, E. Toernqvist, I. Schmidt, H. Topsoe, and C.H. Christensen. 2007. Mesoporous zeolite single crystal catalysts: Diffusion and catalysis in hierarchical zeolites. Catal. Today 128:117-122.

Corma, A., M.J. Díaz-Cabañas, J.L. Jordá, C. Martínez, and M. Moliner. 2006. High-throughput synthesis and catalytic properties of a molecular sieve with 18- and 10-member rings. Nature 443:842-845.

DeSanto, P., D.J. Buttrey, R.K. Grasselli, C.G. Lugmair, A.F. Volpe, B.H. Toby, and T. Vogt. 2004. Structural aspects of the M1 and M2 phases in MoVNbTeO propane ammoxidation catalysts. Zeitsch. Kristall. 219:152-165.

Grasselli, R.K., J.D. Burrington, D.J. Buttrey, P. DeSanto, C.G. Lugmair, A.F. Volpe, and T. Weingand. 2003. Multifunctionality of Active Centers in (Amm)oxidation Catalysts: From Bi–Mo–Ox to Mo–V–Nb–(Te, Sb)–Ox. Topics Catal. 23:5-22.

Kusakari, T., T. Sasaki, and Y. Iwasawa. 2004. Selective oxidation of benzene to phenol with molecular oxygen on rhenium/zeolite catalysts. Chem. Commun. 992-993.

Kustova, M.Y., P. Hasselriis, and C.H. Christensen. 2004. Mesoporous MEL-type zeolite xingle crystal catalysts. Catal. Lett. 96:205-211.

Lamonier, C., C. Martin, J. Mazurelle, V. Harlé, D. Guillaume, and E. Payen. 2007. Molybdocobaltate cobalt salts: New starting materials for hydrotreating catalysts. Appl. Catal. B: Env. 70:548-556.

Li, D.F., D.S. Su, J.W. Song, X.Y. Guan, K. Hofmann, and F.S. Xiao. 2005. Highly steam-stable mesoporous silica assembled from preformed zeolite precursors at high temperatures. J. Mater. Chem. 15:5063-5069.

Martin, C., C. Lamonier, M. Fournier, O. Mentré, V. Harlé, D. Guillaume, and E. Payen. 2005. Evidence and characterization of a new decamolybdocobaltate cobalt salt: An efficient precursor for hydrotreatment catalyst preparation. Chem. Mater. 17:4438-4448.

Mazurelle, J., C. Lamonier, C. Lancelot, E. Payen, C. Pichon, and D. Guillaume. 2008. Use of the cobalt salt of the heteropolyanion [Co2Mo10O38H4]

6− for the preparation of CoMo HDS catalysts supported on Al2O3, TiO2 and ZrO2. Catal. Today 130:41-49.

McVicker, G.B., J.L. Kao, J.J. Ziemiak, W.E. Gates, J.L. Robbins, M.M.J. Treacy, S.B. Rice, T.H. Vanderspurt, V.R. Cross, and A.K. Ghosh. 1993. Effect of sulfur on the performance and on the particle size and location of platinum in Pt/KL hexane aromatization catalysts. J. Catal. 139:48-61.

Sadakane, M., N. Watanabe, T. Katou, Y. Nodasaka, and W. Ueda. 2007. Crystalline Mo3VOx mixed-metal-oxide catalyst with trigonal symmetry. Angew. Chem. Int. Ed. 46:1493-1496.

Srivastava, R., M. Choi, and R. Ryoo. 2006. Mesoporous materials with zeolite framework: Remarkable effect of the hierarchical structure for retardation of catalyst deactivation. Chem. Comm. 4489-4491.

Tada, M., R. Bal, T. Sasaki, Y. Uemura, Y. Inada, S. Tanaka, M. Nomura, and Y. Iwasawa. 2007. Novel re-cluster/HZSM-5 catalyst for highly selective phenol synthesis from benzene and O2: Performance and reaction mechanism. J. Phys. Chem. C 111:10095-10104.

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Tang, T.D., C.Y. Yin, L.F. Wang, Y.Y. Ji, and F.S. Xiao. 2007. Superior performance in deep saturation of bulky aromatic pyrene over acidic mesoporous Beta zeolite-supported palladium catalyst. J. Catal. 249:111-115.

Treacy, M.M.J. 1999. Pt agglomeration and entombment in single channel zeolites: Pt/LTL. Micropor. Mesopor. Mater. 28:271-292.

Wang, L.F., K.F. Lin, Y. Di, D.L. Zhang, C.J. Li, Q. Yang, C.Y. Yin, Z.H. Sun, D.Z. Jiang, and F.S. Xiao. 2005. High-temperature synthesis of stable ordered mesoporous silica materials using mesoporous carbon as a hard template. Micropor. Mesopor. Mater. 86:81-88.

WTEC Highlights

Duane Shelton

February, 2012

August 27, 2008

Acknowledgements

…and over 400 expert panelists, thousands of foreign hosts

NCI (need permission to use logo)

WTEC Past

• WTEC is a non-profit that leads in international R&D assessments by peer review

• 70 studies funded by peer-reviewed NSF awards• Studies are jointly funded by several agencies• ITRI is the small business subsidiary of WTEC• Both were spun off from Loyola University

Maryland in 2001

Related Studies (Sponsors)• Systems Biology (NCI, NIBIB, NSF, DARPA,

DOE, EPA, NASA, NIST)• Biosensing (NIBIB, NSF, NASA, USDA, ARO)• Brain-Computer Interfaces (NSF, NINDS,NIBIB,

TATRC, et al.)• Simulation-Based Engineering & Science(NSF,

NASA, DOE, NIST, NIBIB)• Nanotechnology Progress and Opportunity

(NSF, USDA)• Rapid Vaccines Manufacturing (NSF, NIST,

NIBIB, HHS/BARDA, USDA)

WTEC Future: New in FY2012

• Converging Technologies for Societal Benefit (NSF, EPA, et al.) 12/15/11

• APHELION (NCI, NSF) 1/18/12, 2/1/12• Systems Engineering and Education for

Manufacturing (4 NSF divisions) 1/19/12• BioImaging R&D (NSF, et al.) 2/7/12• Bidding on NNCO and NITRD contracts

Purposes of Studies

Guide and justify U.S. research investmentsLook for good ideas abroad (tech transfer)Look for opportunities for cooperation and collaborationCompare U.S. R&D programs and status with those abroad

WTEC Methods

Write grant proposals that can pass peer reviewEstablish a coalition of sponsors who have resources to make it happenRecruit a great panel from sponsor nominationsConduct the study effectively; sponsors participate in decisions—like where to goMaintain good host relations, so we can return in future studiesPublish an outstanding report

Report Editing

Our reports are of academic quality with full citations, etc.Analytical chapters written by experts Site reports are merely an appendixThey are edited several timesWe always have to extract chapters from holdoutsPublished in 9 books; we now have Springer series with 4 publishedDistribution by paper media pales in comparison to Web downloads

WTEC Staff for This Study

Frank Huband, PhD, VP for OperationsHassan Ali, MS, Project Manager (POC)Grant Lewison, PhD, EU Advance

ContractorHaydon Rochester, PhD, Senior EditorHemant Sarin, MD, International Science

Policy Fellow

More Information

Briefing books for this meetingHassan Ali at 301-461-2109 or hali@ScienceUS.orghttp://wtec.orghttp://wtec.org/aphelion/ (public)http://wtec.org/private/aphelion/(password available from Hassan)

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Milestones for WTEC Milestones for WTEC International Studies

• Preliminary Phase• Study Tour Planning PhaseStudy Tour Planning Phase• Study Tour Phase• Working Reports Phase• Final Report Phase

Acknowledgments

…and over 400 expert panelists, thousands of foreign hosts

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Milestones for WTEC International Studies Preliminary Phase

• Fund raising – solicit resources necessary for the study, WTEC contacts program officers in the field of study to invite them to project p g y p jmeetings

• Sponsors’ meeting – potential sponsors discuss scope and Statement of Work (SOW) for project, determine if there is enough funding available to begin a study, and nominate panelists and panel chair

• Chair’s meeting – study chair presents benefits of study to potential sponsors, including draft scope of project, names of panelists and of other potential sponsors (sometimes addressed at Sponsor’s meeting)

• Kickoff meeting – introduce study panelists, update draft scope, ff g y p , p p ,assign technical topics to panelists, provide preliminary bibliometric study, decide if U.S. baseline workshop is necessary (if so, schedule workshop and speakers), choose U.S. research to be presented to foreign hosts, schedule foreign study tour and workshop dates, and define process for preparing a list of questions for foreign hosts; WTEC engages advance contractor(s), creates public and private websites for information exchange, and schedules monthly conference calls with panelists; study chair defines structure of final report; WTEC project manager assumes responsibilities, including serving as a general point of contact (POC)

Milestones for WTEC International Studies Study Tour Planning Phase

• Baseline workshop – study panelists (an approximately ten selected U.S. researchers) present the state of art in the U.S. or North America; draft

t f di i d li d t th k h d d t d t report of proceedings is delivered at the workshop and updated to serve as a quid pro quo for foreign hosts; WTEC reimburses speakers for travel and lodging

• Advance work – bibliometric study identifies sites with significant number of publications to supplement expert panel knowledge; panelists and sponsors introduce advance contractor to as many hosts as possible; advance contractor sends panelist bios and lists of questions to foreign hosts, schedules itinerary, and arranges travel and lodging (one or more conference calls provide coordination); advance contractor provides detailed itinerary one-week before departure; panelists make their own

l i f h i l i f h i htravel reservations from their own travel reservations from their home across the Atlantic or Pacific, but advance contractor makes arrangements in foreign locations

• Literature survey – in parallel with advance work, panelists survey recent literature, especially papers and websites of the sites to be visited; WTEC and advance contractor help provide information; to attract audience for the final workshop, WTEC publicizes workshop via online calendars and sends postcards to memebers of targeted professional society lists

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Milestones for WTEC International Studies Study Tour Phase

• Study tour week – panelists fly to a common arrival location (e.g., Frankfurt to Tokyo) on Friday/Saturday; on Sunday, panelists meet with Frankfurt to Tokyo) on Friday/Saturday; on Sunday, panelists meet with advance contractor to receive final itineraries; panelists usually divide into two groups; each group selects a head of delegation and a scribe for each site to be visited; head of delegation presents to foreign hosts the purpose of study, U.S. baseline information, and a brief bios of panelists; each site’s scribe records minutes of meeting, collects handout materials provided by hosts, and copies host’s electronic presentations on a memory stick; each group will be issued an international cell phone and a digital voice recorder; most delegations meet for breakfast daily to compare notes; the schedule is intense (panelists will be stressed but they will learn a lot)

• Closing meeting - after a week on tour, the panel reassembles on Friday i h d i h l l i i i h d l devening at the departure airport hotel; a closing meeting is scheduled on

Saturday morning:1. Scribes present as 5-minute review of main points of interests at each site

(takes 1-2 hours)2. Panelists list the most interesting preliminary findings of the week3. A schedule is determined for delivery of site reports to other panelists via

project manager4. Any changes to the workshop or report assignments are considered

Panelists may depart for home on Saturday afternoon or Sunday

Milestones for WTEC International Studies Working Reports Phase

• Site reports drafted and distributed – two weeks after the end of the study tour; these reports serve as data for panelist to write about sites of the study tour; these reports serve as data for panelist to write about sites that they did no visit; a bonus is paid to scribes for timely delivery; WTEC final reports have standard site report formats that include : site visited, data of visit, names of U.S. visitors, names of host participants, background, funding sources and commercialization, R&D activities, and summary and conclusions; WTEC edits and sends site reports to individual hosts for review; as an interim product, WTEC usually points a bound booklet of draft site reports for sponsors

• Final workshop – approximately two months after the last site visits, a one day public meeting with a webcast that will be publicly broadcast is held at NSF from 8am 4pm Panelists will come the evening before for a held at NSF from 8am -4pm. Panelists will come the evening before for a working dinner to review consensus findings for the chair's exec summary presentation. Panelists will send a power point presentation a week before for the webcast files; WTEC will compile them into a conference proceedings and posts proceedings on public Web site (Missing presentations will be shown with a blank page with that person's name;) panelists can change their .ppt slides, as long as they don't insert additional ones. WTEC director of Publications assumes project responsibilities as POC for editing final report

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Milestones for WTEC International Studies Final Report Phase

• Each panelist drafts a chapter – technical chapters are due one month after the final workshop; study chair writes an executive one month after the final workshop; study chair writes an executive summary and introductory chapter on the study process; each panelist writes an analytical chapter on a subtopic of the field (the page quota is 10 pages, including figures and references); previous WTEC reports serve as style guides; figures should have source citations, usually from host presentations captures on memory sticks; panelists receive a bonus for timely delivery of chapters

• Draft analytical report completed – site reports are included in an appendix; WTEC edits and sends draft reports to sponsors and hosts sometimes to peer reviewers; study chair sponsors and hosts, sometimes to peer reviewers; study chair receives a bonus if the overall manuscript is compiled in a timely manner; WTEC posts the draft report on the private website for review and prints a paper draft for sponsors.

• Final report – WTEC edits to academic specifications, prints 100 paper copies, and posts report in PDF format on public Web site; if resources are available, WTEC will seek publication of final report by a commercial publisher

WTEC Project Management

• Frank Huband, Vice President for Operations, fhuband@scienceus.org, 202-290-5230, fax 703-527-4805

• Hassan Ali, Project Manager, hali@scienceus.org, office 301-461-2109. Hassan should be copied on all emails and should be able to give a status check on the project at any time

• Faith Wang, Panelist Contracts, fwang@scienceus.org, f 717-299-7130, fax 717-299-7131

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Travel Arrangements

From/To USPanelists may make their own travel arrangements with Panelists may make their own travel arrangements with Travelocity.com (or the like) and WTEC will reimburse them. If they use our agents, airline tickets are charged directly to WTEC. Our agents are: Kristin Friant, Frosch Travel: kristin.friant@frosch.com, 410-433-9300, and Joan Porte, Joan’s Travel Partners: Joanstravel@verizon.net, 703-533-2210 Coach class only

Travel In EuropeDr. Grant Lewison, Advance Contractor: grantlewison@aol.co.uk, 44-20-8878-5646. Grant usually grantlewison@aol.co.uk, 44 20 8878 5646. Grant usually performs bibliometric studies to provide metrics on which countries are ahead in the field; Grant helps identify the best people and places to visit abroad.

Travel in Asia Dr. David Kahaner, Advance contractor: kahaner@atip.or.jp

Travel Reimbursement

Reimbursement Formhttp://www.wtec.org/travel/2010AprWTECTravelReimbursementForm.xls

For timely reimbursement, please download form and submit the completed form via mail, fax, or email to:

WTEC, Inc.Att: Christopher McGee, cmcgee@scienceus.org1653 Lititz Pike #417Lancaster, PA 17601717-299-7131 (fax)

Travel Reimbursement PoliciesSee http://www.wtec.org/travel/

Potential Attendees at APHELION Kick off Meeting (alphabetical order) (as of Jan. 27)

Joe Akkara NSF/MPS jakkara@nsf.gov 703-292-4946 Radhakishan (Kishan) Baheti

NSF/ECCF rbaheti@nsf.gov 703-292-8339

David Berkowitz NSF/MPS/CHE dberkowi@nsf.gov 703- 292-8171 Krastan Blagoev NSF/MPS/PHY kblagoev@nsf.gov 703-292-4666 David Brant NSF/MPS/DMR dbrant@nsf.gov 703-292-4941 Dennis Carter NSF/ENG/CMMI dcarter@nsf.gov 703-292-2162 Richard Conroy NIH/DHHS conroyri@mail.nih.gov 301-402-1486 Ted Conway NSF/CBET tconway@nsf.gov 703-292-7091 Clark Cooper ENG/CMMI CCOOPER@nsf.gov 703-292-7899 Semahat Demir NSF/ BES sdemir@nsf.gov 703-292-7950 Theresa Good NSF/ENG/CBET tgood@nsf.gov 703-292-7029 Sean Hanlon NIH/NCI sean.hanlon@nih.gov Chris Kelley NIH/DHHS kelleyc@mail.nih.gov 301-451-4778 Karen Jo NIH/NCI karen.jo@nih.gov Jonathan Franca-Koh

NIH/NCI jonathan.franca-koh@nih.gov

Nastaran Kuhn NIH/NCI nastaran.kuhn@nih.gov 301-451-2472 Sandra Laney Dept. of State LaneySJ@state.gov 202-663-3244 Jerry Lee NIH/NCI leejerry@mail.nih.gov Cathy Lewis NIH/NIGMS lewisc@nigms.nih.gov Eric Lin NIST eric.lin@nist.gov 301-975-6743 Peter Lyster NIH lysterp@nigms.nih.gov 301-451-6446 Martha Lundberg

NIH/NHLBI lundberm@nhlbi.nih.gov 301-435-0513

Nicole Moore NIH/NCI nicole.moore@nih.gov 301-435-2486 Larry Nagahara NIH/NCI nagaharl@mail.nih.gov 301-594-9018 Grace Peng NIH/NIBIB grace.peng@nih.gov Anne Plant NIST anne.plant@nist.gov Mike Roco NSF/ENG/OAD mroco@nsf.gov 703-292-7032 Sofi Bin-Salamon AFOSR Sofi.Bin-

Salamon@afosr.af.mil

Kaiming Ye NSF/CBET kye@nsf.gov 703-292-2161 Other Agencies

Nancy Sung Burroughs Welcome Fund

nsung@bwfund.org

Panelists Paul Janmey (Chair)

U. Pennsylvania janmey@mail.med.upenn.edu

Owen McCarty Oregon Health & Science University

owenmccarty@yahoo.com

503-418-9307

Sharon Gerecht Johns Hopkins University

gerecht@jhu.edu

410-516-2846

Cynthia Reinhart-King

Cornell University cak57@cornell.edu

607-255-8491

Parag Mallick Stanford University paragm@stanford.edu 650-723-2300 Lance Munn Harvard Medical

School munn@steele.mgh.harvard.edu 617-726-8143

Daniel Fletcher

Lawrence Berkeley National Laboratory

fletch@berkeley.edu

510- 643-5624

Expert Advisors Antonio T. Fojo NIH/NCI fojot@mail.nih.gov 301-496-2631

WTEC

Duane Shelton WTEC shelton@scienceus.org 717-299-7130 Frank Huband WTEC fhuband@scienceus.org 202-290-5230 Hassan Ali WTEC hali@scienceus.org 301-461-2109 Hemant Sarin WTEC hemantsarin74@gmail.com 301-648-6458 Matt Henderson WTEC mhenderson@scienceus.org 717-299-7130

Connect to the NIH Wireless Network as a Guest

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The NIH provides patients and visitors of the NIH campus temporary access to the Internet and NIH public resources via NIH Wireless Guest Services. Guests accessing the NIH wireless network do not have the ability to access internal NIH resources.

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o The SSID and WEP Key is needed for proper configuration of the wireless client.

Once a Wireless Device is Properly Configured

1. Open a Web browser and attempt to access any Web resource (ex. www.nih.gov). A login page will appear.

2. Enter the Guest Login Account username and password provided. 3. Once the account information is verified, access to the Internet will be granted.

o An authenticated guest has access to any resources available through the Internet, including public NIH Web pages.

Resources

• NIHnet Wireless Network Service website

For additional information, please contact:

NIH IT Service Desk Phone: 301-496-4357 866-319-4357 301-496-8294 (TTY) Web: http://itservicedesk.nih.gov

FIRST NAME LAST NAME username passwordJoe Akkara wlan_xb53 wppMQG58!Kishan Baheti wlan_7dvs upgUYH64!David Berkowitz wlan_nww4 bfvTQV57!Krastan Blagoev wlan_ukea gwkRGH43!David Brant wlan_4emj bvrVJS62!Dennis Carter wlan_bqc6 ckpDAC68!Ted Conway wlan_u4p3 dymMSN67!Clark Cooper wlan_9khd enhVHW56!Semahat Demir wlan_98hb gcfDYG55!Theresa Good wlan_u5em sjhWWS64!Sandra Laney wlan_632e txeENC63!Eric Lin wlan_kf93 nwmJQM82!Ann Plant wlan_dm4t jvwXAY55!Mike Roco wlan_q65r kktFSJ54!Sofi Bin-Salamon wlan_9q9k wrvYPT63!Kaiming Ye wlan_hk4g bvfCKB85!Nancy Sung wlan_mafe cjdKCK74!Paul Janmey wlan_ef5g jbsJTX67!Owen McCarty wlan_45tu fnxCJF72!Sharon Gerecht wlan_vtca gcvKBR67!Cynthia Reinhart-King wlan_h49v shwDXA77!Parag Mallick wlan_ju45 txuNPK75!Lance Munn wlan_crcn ddwFKV84!Duane Shelton wlan_d2y2 arcYCC87!Frank Huband wlan_hm6u snuWNP75!Hassan Ali wlan_netg tbsEEX74!Hemant Sarin wlan_sx4c cuvJNJ27!Matt Henderson wlan_cwvx yueXXW73!Dan Fletcher wlan_bj8m yvfVKU86!

Guest User SSID: NIH-Visitors-WLANWep Key: 56697369746F72416363657373