Joel Beinin, History

Popular Struggle and the New Internationalism in Israel/Palestine

Michelle Lee (student research assistant) will work with Joel Beinin (faculty member) on a project of contemporary history and political sociology investigating the dynamics of two intertwined social movements in Israel/Palestine since the failure of the July 2000 Camp David summit and the collapse of the Oslo “peace process.” The success or failure of efforts to resume Palestinian-Israeli negotiations in 2010 is irrelevant to the project, because it focuses on the mobilization of local communities rather than high politics. The first is a joint movement of Israeli Jews and Palestinians which grew up in response to Israeli police shooting of thirteen Arab citizens of Israel in the first ten days of October 2000 as they were engaged in unarmed demonstrations in solidarity with the 2nd Palestinian intifada in the West Bank and the Gaza Strip. This movement, centered around an organization called Ta‘ayush (Living Together), was formed to provide protection for Arab citizens of Israel in the event of further acts of police violence against them. It soon morphed into a sustained effort to break the siege the Israeli army imposed on most of the West Bank – organizing caravans of food and medical supplies to besieged villages, picking olives in groves the army declared as “closed military zones” physically removing barriers in access roads to them, and acting as human shields to allow villagers to return to locations which they had abandoned due to depredations by extremist settlers. Research on this aspect of the project has been virtually completed and written up in draft form. The second movement – the one whose study will engage Michelle Lee – is based among dozens of grass roots popular committees in dozens of villages throughout the West Bank. These committees were formed as an effort to halt the construction of the separation barrier Israel has been constructing largely inside the West Bank since 2002. The barrier (in its current state of construction) effectively annexes 9.5 % of the West Bank to Israel and cuts many villages off from their agricultural lands on its western side. These popular committees emerged without sustained organizational or political support from the Palestinian Authority (PA) or Palestinian NGOs. They typically unite all the political factions in a given village: Fateh, Hamas, and even Islamic Jihad – a political accomplishment the PA, Israel, and the United States have worked hard to prevent at the macro-political level. I have divided this second movement into three distinctive regions: the northern and central West Bank, the caves of the South Hebron Hills, and in urban East Jerusalem. In principle the Gaza Strip would comprise another region, but it is simply too dangerous and logistically fraught to conduct any

kind of regular research there. Following Palestinian usage, I define this movement as “popular resistance” or “popular struggle” rather than “nonviolent.” Activist memoirs and many other accounts of this movement romanticize its “nonviolence.” In contrast, I fully acknowledge that, while there is no use of firearms or other weapons, stone-throwing by teenagers is a regular feature of demonstrations in some (not all) locales. Most (not all) leading Palestinians openly affirm their strategic rather than faith-based commitment to non-violence. An analytical chapter of the projected book historicizing the issue of violence/non-violence will argue that this has been an aspect of the social tension between urban-based Palestinian elites and rural villagers since the 1930s. The final chapter of the book discusses the “new internationalism” that has emerged around support for the Palestinian movement. The first, and most important aspect of this “new internationalism” for the future of Israel/Palestine, is the participation of thousands of Israelis from Ta‘ayush, Rabbis for Human Rights, the Coalition of Women for Peace, Anarchists against the Wall, and others in persistent efforts to prevent the Israeli separation barrier from destroying the livelihoods of Palestinian farmers and to block the Israeli government’s plans to consolidate Jewish control over East Jerusalem. The joint struggle of Israelis and West Bank Palestinians is an entirely new phenomenon in the history of the Palestinian Israeli conflict. The second aspect is the active participation of foreigners organized by the International Solidarity Movement and a myriad of church-based organizations in support of the Palestinian movement. There have been earlier forms of such internationalist idealism - the International Brigades of the Spanish Civil War and Americans participating in development work in Nicaragua or El Salvador in the 1980s, while guerillas fought against the dictatorial regimes. I explore the motivations of foreigners to risk their lives on behalf of the Palestinian people in a period when few people can believe that such actions place them on “the right side of history” as was the case, for example, during the Spanish Civil War This project is framed by the analytical perspective of social movement theory (SMT). In the Palestinian context, SMT focuses our attention on the dynamics of grassroots politics in the face of the collapse of a coherent Palestinian national leadership. At the same time, local political, social and cultural processes are deeply affected by global forces (for example, residents of the West Bank village of Bil‘in reenacting the film “Avatar” in a February 2010 demonstration), but in entirely different ways than the diplomatic maneuvers which occupy the attention of most scholars and (especially) journalists. Moreover, rather than simply apply the trio of classical SMT concepts, I take seriously the auto-critique and revision of those concepts by three of the leading scholars of SMT.1

Evidence from the social movement of Palestinians, Israelis, and internationals of the last decade challenges and enhances the conceptual range of SMT. For example, the protests against the separation barrier seem to have been motivated more by an immediate threat than a change in the structure of political opportunities; and the resources Palestinians can mobilize now are far fewer than during the 1990s. As I have argued in recent work, it may be that weakly institutionalized movements of subalterns based on local networks present the most opportunities for developing democratic norms in the contemporary Arab world.2

Michelle’s Arabic is now at a relatively advanced level. This will enable her to assist me in sorting through about 35 hours of interviews I conducted over the summer. I will conduct additional interviews during a research trip during the winter break. Based on her initial pass through the interviews Michelle will help to refine the categories according to which they will be coded (motivation, character of the action, relationship, if any, to Palestinian national institutions, strategic/principled commitment to nonviolence, geographic variables, etc) This exercise will improve and expand the range of Michelle’s Arabic. Her oral knowledge of Arabic is primarily Modern Standard Arabic and Egyptian dialect. The interviews are in Palestinian dialect. Michelle will also be searching through Arabic and English websites for documentary evidence in Arabic and English to support the narrative historical account which forms the empirical base of this project. Michelle anticipates enrolling in a research seminar I will be teaching in the spring. During her work as my research assistant this fall and winter we will develop an independent line of research she can pursue and write up as a paper for this course. Proposed Budget 85 hours @ $14/ hour – fall quarter $1,190 100 hours @ $14/ hour – winter quarter 1,400 100 hours @ $14/hour – spring quarter 1,400 three weeks of full-time summer work $1,680 TOTAL $ 5,670

1 McAdam, Doug, Sidney G. Tarrow, and Charles Tilly. Dynamics of Contention, Cambridge

Studies in Contentious Politics. Cambridge: Cambridge University Press, 2001.

2 See, The Struggle for Worker Rights in Egypt (Washington, DC: Solidarity Center, 2010); “Workers’ Protest in Egypt: Neo-Liberalism and Class Struggle in the 21st Century,” Social Movement Studies 8 (no. 4, Nov. 2009); and “A Workers’ Social Movement on the Margin of the Global Neoliberal Order, Egypt 2004-08” in Joel Beinin and Frédéric Vairel (eds,) Social Movements, Mobilization and Contestation in the Middle East and North Africa (Stanford University Press, forthcoming).

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LEARNING ANALYTICS: LEVERAGING THE TOOLS

OF ARTIFICIAL INTELLIGENCE TO BETTER

UNDERSTAND LEARNING A proposal to the VPUE Faculty Grants for Undergraduate Research

Paulo Blikstein

School of Education and (by courtesy) Computer Science

PROJECT SUMMARY Assessing learning has always been a complex task. There are a number of approaches that educators employ to ensure students are progressing satisfactorily: standardized tests, portfolios, free response, etc; but many of these approaches fail to sufficiently capture, in a holistic fashion, what and how students learn. More importantly, these traditional forms of assessment fail to represent learning in project-based learning environments. A VPUE Grant would support two undergraduate students as they explore a variety of machine learning and artificial intelligence techniques to better quantify student learning. These researchers would be involved in designing and implementing ongoing investigations, in addition to furthering their knowledge of statistical methods and data mining through the analysis of the data. They will also have several opportunities to engage the learning sciences and computer science communities through seminars and group meetings. At the end of this work, these students will have a strong understanding of how to enact user studies, extract pedagogically relevant features from a variety of media (speech, video and text) and also how to apply rich data mining and machine learning algorithms to these data.

PROJECT DESCRIPTION Politicians, educators, business leaders, and researchers are unanimous to state that we need to redesign schools to teach the so-called 21st century skills: creativity, innovation, critical thinking, problem solving, communication, collaboration, among others. None of those skills are easily measured using current assessment techniques, such as multiple choice tests or even portfolios – and, as Lord Kelvin famously said, “if you can't measure it, you can't improve it.” As a result, our schools are paralyzed by the push to teach new skills, and the lack of reliable ways to assess those skills. One of the difficulties is that current assessment instruments are based on products (an exam, a project, a portfolio), and not on processes (the actual cognitive and intellectual development while performing a learning activity), due to the intrinsic difficulties in capturing detailed process data for large numbers of students. However, new sensing and data mining technologies could make it possible to capture and analyze massive amounts of process data of classroom activities. This project investigates the use of biosensing, text mining, signal- and image-processing, and machine learning to explore multidimensional process-based student assessments.

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For the last two years, researchers in the Transformative Learning Technologies Lab have been studying the use of artificial intelligence and machine learning in assessing student knowledge development. More specifically, the group has observed the capability for performing novel assessments based on student speech and student-generated computer programs. In one study, we used automated text mining to analyze students describing and building engineering mechanisms and machines, and were able to tease apart experts and novices solely based on the algorithm. In another study, we logged second-by-second interactions with the computer as students created computer programs, and detected patterns, strategies, and styles of learning which differed across the level of previous experience. Furthermore, the group recently developed a framework for doing multi-modal data analysis using student speech, drawings and gestures. It is our belief that the intersection of these novel techniques will usher in a new way for recognizing and assessing the way students learn in hands-on learning environments.

Additionally, the Transformative Learning Technologies Lab is situated at an ideal intersection of engineering and education. The group has several connections with diverse-SES middle and high-school students, and undergraduate researchers would be able to implement their research across a diverse student population, having a contact with the underprivileged student population in East Palo Alto. Moreover, the group is responsible for running the Stanford Learning Fabrication Lab, the Makers’ Club and the Beyond Bits and Atoms class, all of which represent prototypical project-based learning experiences with a large collection of resources for developing innovative hardware and software. Finally, the Transformative Learning Technologies Lab consists of members that have expertise in the areas of education, computer science, engineering and psychology, which could provide students seeking further graduate training with a great experience.

SPECIFIC STUDENT RESPONSIBILITIES AND OPPORTUNITIES The students will be involved in several aspects of academic research. This will include designing and critiquing user studies, conducting interviews and focus groups, extracting features from the data, and analyzing the data. More specifically, the student will have the opportunity to create interview protocols and participate in the interview process. Once these interviews have been completed, the students will divide up the data to do feature selection and feature extraction in the different mediums. But this does imply in doing “traditional” video data analysis or discourse analysis. On the contrary, the research novelty of this project is the automation of the data analysis. For example, students may work on developing an algorithm to automatically recognize certain actions, gestures, or parts of speech within the recorded videos or transcripts. Another may work with designing a technique for determining the level of collaboration in a given learning task using computer vision. After feature extraction has been completed, students will combine the features and perform data mining to look for relevant patterns.

Implicit to what is indicated above will be opportunities for completed literature reviews and developing new tools for doing research in this space. For example, after completing the first iteration of a study, the student may realize that we need to develop a new piece of software to accommodate an additional modality. In this way we anticipate that the student will have the chance to iterate on the research design to propose improvements.

Lastly, students will have the opportunity to learn a great deal about rapid prototyping and fabrication in the Stanford Learning Fabrication Lab. Using tools like the laser cutter, 3D printer, vinyl cutter and CNC, the students will be able to develop new skills in developing physical infrastructure, and explore how this hardware can be combined with custom software to create useful educational tools and research tools. For example, we have been using the lab to create 3D-printed objects to facilitate data collection, such as devices to attach cameras to research subjects, special tables for capturing students’ drawings and sketches, and low cost audio and video instrumentation.

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MENTORSHIP The students will work closely with Paulo Blikstein and graduate student Marcelo Worsley, who is conducting research on Learning Analytics as part of his PhD. The students will work closely with Blikstein and Worsley to discuss algorithm implementations, research protocols and learning theory. Furthermore, the students will engage Worsley, and his research colleagues, Daniel Greene and Michelle Hutton, both PhD. students, in analyzing data and interpreting results. They will also have the chance to present their work at regular research group meetings. Additionally, students will have individual weekly meetings with Blikstein to discuss progress, share ideas and receive feedback. Finally, the students will work with Blikstein and Worsley to develop conference presentation and journal publications.

STUDENT RECRUITMENT We intend to recruit through our connections with the Engineering Diversity organizations (SBSE, SWE, SSCLES and SHPE) and through communication with CS106 and CS107 section leaders. We will also solicit recommendations from other computer science faculty, and send an announcement to former Beyond Bits and Atoms and Stanford Makers’ Club students.

BUDGET Student Stipends

2 students for Winter and Spring, ($14/hour, $1,400 each): $5,600

2 students for the Summer, full-time @5,600 each: $11,200

Student Travel expenses

2 Conferences @$1200 each: $2,400

Project Materials

Lab and research supplies (materials for manufacturing data-collection devices, sensors, custom video-capture apparatus), $300 per student/year: $600

Total: $19,800

Degradation and Long Term Reliability for Organic Photovoltaic Technologies  

Prof. Reinhold Dauskardt Department of Materials Science & Engineering 

 Admin. Contact: Jane Edwards, edwardsj@stanford.edu, 650‐723‐2615 

 I. Executive Summary  Photovoltaic  (PV)  technologies  are  fast  emerging  as  one  of  the  most  important  forms  of environmentally  sustainable  and  renewable  energy.    During  use,  however,  PV  devices  are exposed  to  some  of  the most  severe  operating  conditions  of  any  complex  high  technology. Despite extremely optimistic  forecasts  for  low cost and efficient PV modules, device reliability and  lifetimes  may  present  very  significant  barriers  for  the  success  of  these  promising  and environmentally sound new technologies.    Damage of the organic PV devices occurs by exposure to environmental species (typically H2O, O2, other  active  ions), which diffuse  and  interact  chemically with  the polymer molecules.    In addition, UV light from the sun has enough energy (3 ‐ 4 eV per photon) to break covalent bonds in  polymer  chains  and  induce  further  photochemical  damage.  Although  frequently  reported, virtually nothing is understood regarding the fundamental degradation processes of the organic PVs.  The fundamental nature of these degradation processes is the focus of our research.  The  undergraduate  (UG)  student,  Ricardo  Corona,  will  employ  our  recently  developed micromechanical techniques to quantitatively characterize the kinetics of defect propagation in solar cell devices that include the effects of environmental species and in‐situ UV irradiation.  A VPUE  faculty  grant  will  support  his  lab  work  and  the  registration  cost  of  one  scientific conference.    II. Student Activities  The student will measure the effects of a series of chemically reactive environments in both the gas and  liquid phase on materials and  interfaces relevant to PV technologies.     Specifically, he will employ fracture mechanics techniques to measure adhesion and cohesion of interfaces and layers  at  the device  and module  level of different  prospective  photovoltaic  cells.  In order  to accomplish this, the student will be introduced to both software and equipment that is relevant to the techniques in current use.    III. Mentoring Strategies  The student will meet at  least once a week with Prof. Dauskardt to discuss the progress of his research and will be continuously mentored by  third year Ph.D. student Fernando Novoa. The mentor  specializes  in  photovoltaics  reliability  at  large  and  has  previously  supervised  other undergraduates working  in  this  field.   The UG  student will  also be expected  to participate  in 

weekly research group meetings where he will receive feedback on the direction of his research and will be exposed to a broader selection of scientific projects.   The  research  activities of  the undergraduate  student will  take place  in  the unique  and novel experimental  capabilities  in our group. His  research will be part of  the  collaborative effort of more  than  16  principal  investigators  who  constitute  the  Center  for  Advanced  Molecular Photovoltaics at Stanford.   As a member of  this center, he will participate  in weekly meetings and  bi‐annual  symposia which will  greatly  enrich  his  research  experience.    The  collaboration between  students  and  professors  in  this  center,  (mostly  graduate  students)  is  continuously increasing, and the UG student will form part of this growing scientific community.     IV. Student Final Products  The undergraduate will be engaged in a self contained project and the results of his experiments will go to a research publication.   Similar goals have been achieved  in previous undergraduate endeavors. Two research  journal publications have already been published and four additional papers  in preparation or under review  include VPUE supported undergraduate students as co‐authors.    In  particular,  last  summer,  the  research  of  another  undergraduate  student,  Scott Takahashi, supervised by the same mentor yielded results which will be  included  in a scientific journal publication this year.  The student will also complete a final report that reflects progress of their project.   Depending upon  the  quality  of  the  results  and  the  approval  of  the  respective  committee,  the undergraduate  student  might  present  his  poster  at  the  MRS  Spring  meeting  held  in  San Francisco.   V. Evaluation  The results of the UG student research will be evaluated by Prof. Dauskardt.   Weekly meetings between  the  student and  the professor will be used  to assess  the quality of his  research, his approach and his commitment.  The mentor will also continuously monitor the performance of the UG student to make sure he is making good use of the resources and that he is getting the best educational experience.    Prof. Dauskardt will also grade the final report of the UG student and will provide feedback on the quality of the scientific findings and the student’s ability to write a scientific report.  VI. Relation to Student’s Educational Program  This project is adequate for a college junior in our materials science program because it requires a strong command of the cross disciplinary fundamentals of the MatSci curriculum. The student will be applying the essentials of mechanics, chemistry, and physics that will have relevance to validate the applicability of our newly developed techniques and instruments.  

 A number of students have elected materials science and engineering as their major based on their  research  experience  in  our  group.  Additionally,  the  UG  projects  have  the  potential  to 

evolve  into more extensive projects  related  to a  senior project or honors  thesis.   Two of our previous VPUE  supported UG  students  continued with Masters  level  research  projects  in  co‐terminal MS degrees.  VIII. Plan for Student Recruitment  Our  solar  cell  reliability  research area has been very popular among UG  students and we get requests from many UG students to join our projects.  We have selected Ricardo Corona for this project due  to his excellent  research and academic  record. Ricardo has previously  interned  in our group for two quarters. He has already learned the specific techniques that will allow him to engage in a more committed project.  This is why we are confident that Ricardo’s performance will be outstanding and he will be able to achieve the goals of his project. Ricardo is a junior in the materials science department who  is focusing on photonics and photovoltaics. He has also had  extensive  experience  in  industry  doing  materials  science  research  focusing  on  both biomaterials and  inorganic crystalline materials. Previous  to his participation  in  the Dauskardt lab,  Ricardo  was  involved  in  Prof. Mark  Brongersma’s  lab  where  he  worked  on  developing nanostructured solar cells in the Stanford Nanofabrication Facility.   XIX. Outcomes of past student projects  As part of our research effort, we have hosted and mentored Stanford undergraduates  in our lab, both during the academic year and over summers.  9 students have been supported through the VPUE program.   These students contributed significantly to the greater research objectives of the group by conducting an extensive set of experimental and modeling studies.   They have all been very successful in completing their projects.  As already noted, their involvement in our research is not only stimulating, but brings an added energy and productivity to our research.   X. Budget  Student Stipend ‐ $ 5 600 

(40 weeks,10 hours a week, $14 per hour)      

Project Materials ‐ $ 250   (poster printing, conference registration and lab supplies)      

Undergraduate  Research  Faculty  Grant  Application  

Project  title:  Improving  water  management,  sanitation,  and  hygiene  in  east  Africa  

Submitted  by:  Prof.  Jenna  Davis  (Civil  &  Environmental  Engineering  and  the  Woods  Institute  for  the  Environment)  

Project Overview. Diarrheal and respiratory infections are among the top ten illnesses contributing to the global disease burden, causing 5.5 million deaths and 99.2 million disability-adjusted life years lost annually. A variety of pathogens that cause diarrhea and respiratory illnesses are transmitted via contaminated hands among individuals practicing inadequate hand hygiene, as well as through contaminated water and food. The risk of these illnesses is highest among households with limited water supplies for personal hygiene, such as the majority of those living in sub-Saharan Africa and Asia. For these households, water must be fetched from a distance and stored in the home, limiting the volume of water available for personal hygiene and creating opportunities for the contamination of stored drinking water by hands and cups. A variety of randomized controlled trials have demonstrated that improvements in household water management, as well as in sanitation and hygiene practices, can reduce the incidence of diarrheal and respiratory illness. The challenge remains, however, to identify interventions that motivate the adoption and consistent practice of these health behaviors. The current study, with field sites in Kenya and Tanzania, is testing two different approaches to reducing the risk of water- and sanitation-related disease. In Kenya, we are testing the impacts of promoting alcohol-based hand sanitizer—a waterless hand cleanser that is relatively common among health care facilities in high-income countries, but that has received limited attention for use in the developing world—in primary schools of low-income communities. The use of hand sanitizer does not require water, needs less time for successful use than handwashing, and does not require drying hands with potentially contaminated towels. It is thus a potentially appropriate way to improve hand hygiene practices in settings with limited water supplies and a lack of materials for hand drying. The three main goals of this field site are to evaluate the acceptability and feasibility of providing waterless hand sanitizer in schools; to obtain observational data on how access to waterless hand sanitizer affects teacher and student hand hygiene behavior; and to evaluate the use of CCTV surveillance as a method of measuring hygiene behavior by comparing it to the gold standard of measuring behavior: structured observation. This study is currently being carried out in the community of Kibera, located in Nairobi. The research is employing an interdisciplinary approach, using both qualitative and quantitative data collection methods. Two methods are being used to obtain observational data of hand hygiene behavior. Closed circuit television devices (CCTVs) have been installed at schools and set to record hand hygiene behavior at specific times in public locations at schools located near latrines and eating areas. Concurrently to CCTV recordings, study staff are also conducting structured observations (3 hours/day) of student and teacher hand hygiene behavior. Surveys with teachers, administrators, and students have been conducted to determine knowledge, beliefs, and social norms in relation to hand hygiene. Student absenteeism is being tracked daily by teachers using personal digital assistants (PDAs), and diarrheal and respiratory illness symptoms of those students in attendance are also being recorded using the PDAs. In-depth interviews

with teachers, administrators, and students to evaluate perceptions of waterless hand sanitizer as an alternative to handwashing with soap and water, to determine user preferences for dispenser design and other product characteristics, and to assess any changes in knowledge, beliefs, and social norms in relation to hand hygiene behavior. In Tanzania, we are focused on the household rather than the school as the entry point for our work. We have designed a unique informational intervention and are testing its effects on the adoption and sustained practice of improved water management, sanitation, and hygiene behaviors among households that include at least one child under the age of five. We have been following approximately 1100 households since January 2010 and are tracking the health of family members, as well as levels of contamination with fecal indicator bacteria of stored water, source water, and hands of the female head of household. For a subset of the participating households we have shared the water and hand test results and explained their meaning. Other households have received general health messaging regarding the links between water, sanitation, hygiene (WASH), and health, or no intervention at all (the control cohort). Our hypothesis is that households who received their test results will remember and respond to the WASH messages to a greater extent, and for a longer duration, as compared to households that received either generic information or no information. This project thus provides a test of health behavior theory which posits that more tailored or individualized messages tend to “stick” with individuals to a greater extent than non-specific messages. At the same time, we are also investigating two spatially driven research priorities. The first is exploring spatial patterns of contamination with fecal indicator bacteria in the study area. The second is modeling uptake and dissemination of the health messages as a function of household characteristics, geospatial factors such as density and isolation, and community features. Student objectives & activities. We seek two students to contribute to the research goals of the project. The students will be involved in collecting, processing, cleaning, and analyzing of primary data in a variety of formats (video, survey, and GPS); and organizing and presenting research findings in the form of graphs, tables, and maps. The students will join an existing project team that includes three graduate students in addition to the faculty mentor. The student working with the Kenya team will watch CCTV footage from study schools and log observed hand hygiene behavior captured by the CCTVs into a structured form on a personal digital assistant (PDA). The student will thus play a valuable role by transforming the CCTV footage into quantitative data that can be analyzed and compared with structured observation data collected at the same schools. S/he will develop skills in analyzing video footage, programming and using PDAs for data collection, summarizing and presenting data in graphic and tabular form, and statistical analysis. S/he will also develop facility with the software packages Survey System and SPSS. The student will be held responsible for the following deliverables:

• Watching an agreed-upon number of hours of CCTV footage; • Recording hand hygiene behavior observed in the video footage onto a PDA; • Downloading the data onto a field laptop and managing the database of video footage; • Carrying out data cleaning on observational data obtained by the Kenyan field team; • Completing statistical analyses such as generating descriptive statistics and tests of

hypotheses with the observational data;

• Subjet to the student’s interest, s/he will also be invited to process qualitative data (in-depth interviews) obtained during the study to identify themes with respect to adoption and acceptance of the hand sanitizer by students and teachers;

• Preparing and delivering a presentation summarizing his/her work and the results thereof; and

• Logging his/her hours spent on the above tasks. The student working with the Tanzania team will review GPS and survey data that are sent daily from the field, assist with the development of the geographic information system from this site, and carry out mapping and spatial analysis using collected data. S/he will develop skills in reviewing and manipulating spatial data, summarizing and presenting data in graphic and tabular form, making maps, interpolating geographical data from satellite imagery, and spatial statistical analysis. S/he will also develop facility with the software packages ArcGIS, Survey System, and SPSS. The student will be held responsible for the following deliverables:

• Carrying out data review two days per week, including the provision of feedback to the Tanzanian field team and cleaning collected data based on responses received;

• Appending collected GPS and survey data to the existing GIS; • Generating summary tables of collected data; • Creating maps of the study area, including the location of households, community

features, and water points; • Supporting graduate students and faculty in the carrying out of spatial statistical analyses

of collected data; • Preparing and delivering a presentation summarizing his/her work and the results thereof;

and • Logging his/her hours spent on the above tasks.

Mentorship. The students will be mentored in order to develop the knowledge, strategies and skills required to manage various types of data in pursuit of a research question. Each student will work under the guidance of Prof. Davis, and will also work closely with an advanced graduate student. Weekly project meetings will be convened to monitor progress, provide support and feedback, and trouble-shoot emerging challenges. Each student will also prepare and deliver a presentation of his/her work to Prof. Davis’ research group meeting. Recruitment. The position will be advertised through Prof. Davis’s water and sanitation research group email listserv, as well as through CEE student mail listings. Students with a strong interest in environmental and international health will be prioritized.

RESEARCH PROPOSAL: DETERMINANTS OF FOOD-CHAIN LENGTH IN TROPICAL ISLANDS Rodolfo Dirzo (PI), Hillary S. Young (Postdoctoral Fellow, co-PI)

We propose to involve 2 (ideally 3) early stage undergraduate students in an ongoing research project examining the relative role of productivity, ecosystem size, and habitat complexity in structuring food webs, and specifically in determining food-chain length. The funding from this grant would primarily support student salary and expenses, to process and analyze samples, and perform basic data analysis. The funding would also support quarterly student meetings to discuss progress and results, and funding to facilitate students presenting their results in meetings, poster sessions, or peer reviewed journals. Research Questions Understanding the factors that influence food-chain length is fundamental to understanding ecological communities. Food chain length has important effects on ecosystem function and ecosystem structure; it influences bioaccumulation of toxins, and may be representative of broader changes in ecosystem health and diversity. Yet, there is still much unknown about the drivers of food chain length in terrestrial communities. The primary three hypotheses of factors driving food chain length are ecosystem level productivity, ecosystem size, and ecosystem complexity. While evidence from the marine system suggests that ecosystem size alone is the major driver, my lab is involved in efforts to test the relative importance of these hypotheses in terrestrial systems. We are working in a series of small islets of different sizes in the Line Island chain of the central Pacific; these islands are eco-climatically similar and are of the same parent material (limestone), but exist along a 10 fold gradient of productivity (driven by differential occupy by seabird colonies, and thus differential nutrient subsidy levels) and habitat complexity (driven by differential invasion histories of plant communities). Using these natural gradients, we have been sampling soil, plant and animal communities to 1) quantify productivity and habitat complexity gradients, 2) examine variability in abundance and diversity of consumer communities in these habitats, and 3) look at changes in trophic position of individual consumers, and of the aggregated consumer community to identify changes in food chain lengths across these naturally occurring gradients. We propose to involve students in all aspects of these goals (specifics detailed below), and also to be involved in verifying the validity of stable isotope methodologies for use in food length analysis of arthropod-driven food webs, by working on a greenhouse project assessing effects in changes in plant nutrient levels on arthropod isotopic fractionation rates. Student Responsibilities and Deliverables: We propose to involve undergraduates to help us quantify changes in productivity in insect consumer community, measure and changes in food chain length, and validation of insect fractionation rates. Student participation would greatly facilitate the completion of this project, as it is labor intensive in sample preparation and analysis. To quantify changes in productivity students would perform chemical analysis of soil nutrients and plant litterfall inputs (both already taken in the field). Specifically, students would assist with nitrate, ammonium, and phosphate extractions of soil, with subsequent analysis on SmartChem Discrete Analyzer; and with bulk analysis of C and N of soils and leaves on the Alpkem Environmental Analyzer. To quantify changes in consumer communities (abundance and diversity), students would be trained in basic insect taxonomy in order to sort insects to lowest possible taxonomic level, at which point they will count and weigh all insect groups. To measure changes in food chain length, students would prepare soil, leaves, and consumer tissue for isotopic analysis (grinding, acidifying, and foil balling samples) on the mass spectrometer. Finally, to help validate insect fractionation rates in controlled feeding trials, students would assist with basic animal and plant husbandry and would sample both plants and insects and prepare for isotopic analysis (as detailed above). While students will ultimately focus on one or two of the research objectives, depending on their interests, all students involved in this project will gain exposure to and training in multiple basic ecological tools (nutrient analyses, taxonomy, and isotopic analyses). Yet, since the project has many smaller questions embedded within the larger conceptual framework, students will have the opportunity to see an entire question through from concept to data analysis, and even to writing up results. Student Selection: We would aim to recruit 2-3 early stage students (freshman and sophomores) with an interest in ecology, in order to give them initial exposure to ecological research and techniques; these students would also then have the time and skills in order to continue with the project, with the possibility of developing associated independent research projects. We will work the Biology and Earth Systems Student Services office to advertise available positions. Students that began research on this project with the lab in summer 2010, but are unable to continue due to lack of support would be prime candidates for this support. Students would be expected to commit 7-10 hours weekly for a minimum of two quarters. Student Mentorship To foster student intellectual engagement in the project, we will encourage them to participate in data analysis and write up of the portion of the project they have assisted with. Students will also receive close guidance from myself, and from my postdoctoral researcher (H. Young), who will directly supervise work. We will

have an initial meeting with each student selected to discuss theoretical framework of these questions, and show them all preliminary data. We will then have quarterly project meetings with all involved researchers to discuss project progress, findings, and any questions and concerns that may arise. Involved students will present the results from their focal projects at these meetings. Students will also be encouraged to participate in lab meetings and discussion groups to foster broader intellectual development on issues of community ecology. Relationship to Departmental VPUE Funding: While the Biology Department does have an existing VPUE departmental grant for undergraduate research, this is available for summer months only. We have involved many students in field research through this program (with uniformly outstanding reviews) including one student in 2010; however, this does not support academic year lab work. Without this support it is difficult to involve new students and retain summer students in completing the lab work that is necessary to carry the project through from concept to completion. Results from Previous Student Research Past student projects from my lab have been extraordinarily successful in developing lab associated projects into independent research, honors theses, and, ultimately, published scientific works. Related specifically to our work in the Line Islands in particular, four undergraduates have completed or are completing honors theses based on their field or lab work on these projects, and three have already authored or coauthored peer reviewed papers. Students have also presented the results of their work at international conferences. Budget: We request salary ($13.50 per hour) for 25 hours per week for 40 weeks ($13,500). We include $500 to support student specific research costs (safety equipment, and duplicates of sample preparation materials), and $1,200 to cover travel to professional meetings and meeting fees, and poster preparation materials for students to be able to present results from their involvement in this work in conferences (presentations in poster sessions).

Eric Dunham, Geophysics Physics-based Models to Quantify Ground Shaking from Earthquakes Project summary: Few records exist of ground shaking close to large earthquakes, making it challenging to accurately assess seismic hazard in many highly populated regions adjacent to major faults. Computer simulations—with inputs constrained by geologic studies of faults, experimental studies of friction, and seismic observations of past earthquakes—can be used to generate synthetic seismograms from scenario earthquakes to supplement the existing ground motion records. This VPUE grant will support an undergraduate student to further develop our simulation capabilities, particularly for high frequency ground motion modeling as described in detail below, and to validate the methodology by comparing synthetic seismograms with recorded data. The student will learn about seismic wave propagation, earthquake source physics, numerical solution techniques for partial differential equations, and the use of high performance computing in the geosciences. Project description: Currently, computer simulations of earthquake ruptures and seismic wave propagation can be used to accurately model ground motion at frequencies less than 1 Hz. The predicted peak ground velocity from two such simulations (conducted by the Southern California Earthquake Center, Olsen et al., 2006) is shown in the figure to the right. The top panel is for a rupture that propagates from the north to the south; the bottom panel is for a rupture that propagates in the opposite direction, but is otherwise identical. It is quite clear that shaking is largest in the direction of propagation, an effect known to seismologists as directivity (but which is essentially identical to the well-known Doppler shift of radiation from a moving source that leads to narrower pulses of larger amplitude in the forward direction). Other than magnitude and distance to the fault, directivity is the single most important earthquake source property in determining the amplitude of ground motion at a particular

site. Despite the obvious importance of directivity, it is only just now being incorporated, in a very approximate way, into the ground motion prediction equations used to set building codes and insurance rates. This is because directivity effects, which are so obvious in low frequency ground motion (< 1 Hz), vanish at high frequencies (>1 Hz) in a manner that is difficult to parameterize. The underlying cause of this remains unknown, and this issue must be resolved before directivity can be properly accounted for. Understanding the 1-10 Hz frequency band is critical from an engineering perspective, however, as the resonance frequencies of all but the tallest buildings lie within it (e.g., the Hoover Tower resonates at ~1 Hz and single-story homes resonate at ~10 Hz). One hint at what might explain the loss of directivity effects at high frequencies is the related observation that around 1 Hz, shaking begins to assume a stochastic character that becomes increasingly pronounced as frequency increases. The loss of coherence and diminution of directivity effects at high frequencies is thought to arise from either scattering of waves from material heterogeneities along the propagation path from source to station, or irregular rupture propagation. Both of these mechanisms limit the constructive interference of waves from various parts of the fault that causes directivity. However, there is no consensus on which of these mechanisms is most important. We specifically seek to make testable predictions that can be used to quantify the relative importance of these two mechanisms. Irregular rupture propagation is thought to arise from the interaction with geometric complexities of the fault such as bends, branches, and activation of secondary faults. Our group has recently developed provably stable and accurate numerical methods that permit us to model spontaneous rupture propagation through geometrically complex fault systems. The codes have been parallelized and we routinely run them on hundreds or thousands of processors. For the first time, we can use these physics-based models to generate ground motion at frequencies up to ~10 Hz. Our specific plan is to quantify directivity effects as a function of frequency on fault systems having varying degrees of geometric complexity. In some cases, geologic mapping provides specific examples we can investigate (e.g., the set of faults that ruptured in the 1992 M 7.2 Landers earthquake), but we will also supplement these cases with synthetically generated fault systems. Specific student responsibilities and opportunities: The student will be responsible for running a set of computer simulations to generate synthetic seismograms that will then be analyzed to quantify directivity effects as a function of frequency. This will involve learning about parallel computing using MPI (Message Passing Interface) to communicate between processors. Analyzing the synthetic data will involve signal processing skills. Gathering data on fault system geometries will expose the student to geologic mapping techniques. Throughout the project, the student will need to be mindful that one of the end products should be a simple quantification of directivity effects that could be used by earthquake engineers to set building codes and insurance rates.

Mentorship: The student will work with Assistant Professor Dunham and participate in weekly research group meetings. The group meetings will provide an informal venue for the student to develop presentation skills and receive feedback from other group members. The meetings will also provide exposure to the broader research directions in the group. Student recruitment: The selected student, Hoon Cho, is currently a sophomore computer science major. He began working with our group in the spring quarter last year when he was still a freshman and continued at 40 hours/week over the summer with the support of funding from the School of Earth Sciences. Hoon displayed a remarkable talent for all aspects of this project. He presented preliminary results of the project at the Southern California Earthquake Center meeting in September 2010. We expect to write up this preliminary research over the next quarter or two for publication in the Bulletin of the Seismological Society of America or Geophysical Research Letters. Outcomes of past projects: Assistant Professor Dunham has had no previous awards from the VPUE. Budget: Student stipends: Autumn quarter $700 ($14/hr, 5 hr/wk, 10 wk) Winter quarter $1400 ($14/hr, 10 hr/wk, 10 wk) Spring quarter $1400 ($14/hr, 10 hr/wk, 10 wk) Total $3500

PAULLA EBRON, ANTHROPOLOGY

Heritage Preservation Along The US Sea Island Coast Project background: The Sea Islands lie at the intersection between Africa and African America. It is the site where scholars have best shown that the agency and cultural heritage of Africans made a difference in the making of the North American political economy. African American history, linguistics, folklore, photography, art, film, and literature are all focused on this small region as the site of the most authentic New World African culture. This project addresses the relations between representations and material histories in the making of transatlantic ties between Africa and African America. As a region, the Sea Islands have a long history of scholarly and popular representations of African agency in the New World. As an interdisciplinary object, the fields of African American history, linguistics, folklore, photography, art, film, and literature have drawn attention to this small region as the site of the most authentic New World African culture. Following federal recognition of the area as a the Gullah-Geechee National Heritage Corridor in 2006, a coastal area 400 mile long and 30 miles wide, that encompasses the four states of North Carolina, South Carolina, Georgia, and Florida, has generated even more interest and an increasing range of “cultural experts” try to represent the contemporary Sea Island culture. It asks: What is the relationship between representations and material histories? What is the “big story” that can be told about where representations and material histories meet? Three areas, landscape, memory and social up-lift have served as analytic containers for the research of others on the region. The landscape aspect builds on the scholarship of Sea Island-oriented historians and geographers; however, it adds several new questions to their work. We trace the travels and responses of plants and microorganisms to help to animate the landscape, showing a new dimension of Sea Island regionality. This is complemented by a consideration of the technology of memory projects, such as the WPA, recordings of Sea Island residents, and films. Finally, social uplift looks at the activist projects that have made the region historically important, as for example citizenship schools and legendary figures such as Septima Clark, Esau Jenkins and Bernice Robinson and their role in establishing citizenship schools and the civil rights movement. As part of this project we are engaged in data collection from multiple sources. These include historical maps and plats, photographs, newspaper reports, texts and other material from the Avery Research Center for African American History, the South Carolina Historical Society, and other archives. They also include field notes, bibliographies and material gathered from online news sources. We are in the process of developing a repository that combines qualitative and quantitative ethnographic information with spatial data. A central piece in this collection is the mapping of the Sea Islands that provide a spatial reference for the data collection. No detailed map of the islands of the Gullah-Geechee Heritage Corridor currently exists, so we are undertaking a digitization project of the islands. It will allow us to gain a better understanding of the history of the landscape that constitutes the Sea Island region. Bringing together a combination of ethnographic, demographic and other relevant datasets and archival material and geographically visualize information will help to unravel some aspects of the complexity of this historical landscape and how it was shaped over time.

Student responsibilities and opportunities: Students will contribute to the faculty research in the following ways. One student will continue the digitization of the islands in ArcGIS, which is already under way. Another student will assist in the sorting and archiving of collected archival material, bibliographic references, and conduct online research following the websites and network of people interested in Gullah-Geehee culture, collating and organizing material associated with the contemporary cultural heritage management part of the project. This also involves creating a resource inventory of the on-line sources to compliment a bibliography that was published a number of years ago. A third student will focus on ethical citizenship, and looking for sources of public campaigns for civil rights and voters. Two students will also accompany the faculty on a visit to the Highlander Research Center in Tennessee to assist in archival search for photos and other materials on the citizenship schools. They will participate in the preparation of a formal interview with civil rights activists in Tennessee, where they will also sit in on. Methodologically, students will learn about data collection for cultural anthropological research and be involved in the analytical process of how to 'make sense' of multiple data sources and use them to address theoretical questions. How, for example, can we make use of visuals as evidence, how can we read information from historical plantation plats? Students will have a chance to play an active role in the design of the repository. Students also will be trained in how to appropriately use online sources, an area that is only beginning to be explored for anthropological research. Closely linked to methodology it raises a number of questions regarding analysis, developing ways of judging credibility, corroboration of evidence with other sources. Students also will be exposed to ethical issues of virtual work. Two students will shadow the faculty for an ethnographic interview and will work with the faculty in preparation for the interview. Lastly, students will learn how to develop spatial questions and interpret evidence spatially, something not often addressed in anthropological education. Mentorship: The students will be in close communication with me as well my collaborator in this project, Dr. Claudia Engel, Academic Technology Specialist for the Anthropology department, who is responsible for the GIS components and the development of the data repository. Dr. Engel will serve as a co-mentor and particularly be responsible to train students in GIS and digitization, online research and the database aspects of the project. Students will report on the progress of their work and participate in meetings with me and Dr. Engel. In those meetings research will be discussed and students are expected to contribute the discussion. We will brainstorm potential solutions to any challenges that have arisen, and reflect on the relation of the evidence to the broader conceptual and theoretical frameworks of the project. We will also encourage the students to think critically with the evidence. The students know each other, have worked together and with my team, which we expect to positively influence the working relationship. Recruitment: The three students that will collaborate with us on the project, Camira Powell, Devney Hamilton and Daniel Towns, all in their second year now, were participants in the VPUE funded Sea Island Field School in summer 2010 (http://www.stanford.edu/~pebron/fieldschool). Being already familiar with the larger scope of the research project as well as the study region, including the local community and collaborators makes them ideally suited as collaborators for this project. No startup time would be required. Students would be well positioned to corroborate evidence or assess archival materials, since they have been at the

scene. Knowledge of the landscape will be valuable asset for digitization, which is one off satellite imagery of the area. All three students have demonstrated excellence in their work conducted during the field school and have all expressed a keen interest in a continued involvement in the project. Not only did students tell us how much they learned during the 4 week long field school in South Carolina, but they also gained tremendous respect from attendants of their final presentations and praised their performance. These students have critically thought about the issues involved in the project and are able to contribute an independent perspective that we expect to be an important contribution to the team discussion. While the work being performed by students will not be a continuation of their individual research projects we will take advantage of their specific expertise that they acquired during the summer field school. Thus, they will be able to immediately focus on the tasks at hand. The summer research of Devney Hamilton on the significance of landownership makes her well suited to work on the digitizing of the islands. Camira Powell's summer research on Esau Jenkins makes her particularly fit to work on the civil rights documents. And Daniel Towns' research about the Gullah-Geechee Heritage Corridor proves useful in the collection of material around this topic. A VPUE Faculty Grant for Undergraduate Research would provide Camira Powell, Deveney Hamilton and Daniel Towns with a unique opportunity to work within a team and alongside a senior faculty. It would build on their already existing knowledge of the study area and provide them with an opportunity to further develop their skills they started to build during the field school. It would contribute to a solid foundation for these promising young scholars to become future independent and critical researchers. Budget: Student Stipends: 1 student, 10hrs/week, Winter and Spring Quarters $2,800 2 students, 5hrs/week, Winter and Spring Quarters $2,800 Student Travel Expenses: 2 students, travel expenses to Tennessee $2,800 Total Requested: $8,400

Proposal for a 2010-2011 Faculty Grant for Undergraduate Research

Jon A. Krosnick

Department of Communication

October, 2010 Proposal Content My research team is engaged in a series of studies exploring the psychology of political behavior by American citizens. For example, one study is examining the impact of the order of candidates' names on the ballot on election outcomes. Another study entails a review of the literature on the causes of voting. Another is examining how political judgments manifest subadditivity. Another project is exploring how news media coverage of global warming influences public attitudes on the issue. Undergraduates participate in carrying out all of these studies and often play principal roles. A wide range of methodologies will be used. For example, our study of name order entails working with elections officials and state archives around the country to obtain precinct-level vote returns and create databases of them for statistical analysis. Our study of news media influence entails locating video recordings of television news stories that fit what we need, editing them to produce different versions, designing a questionnaire to measure effects, working with a survey data collection firm to collect data from a representative sample of Americans, and analyzing the data statistically. The students will have regular work schedules and will be overseen in their daily activities by me and by graduate student members of my research team. Each undergraduate will be paired with a graduate student on each project for oversight and consultation and advising. In addition, I will meet regularly with the undergrads individually and as a group to plan their activities. And their work will be monitored closely, and feedback will be provided weekly. I will also be available to the students to provide advice on any issues of interest (e.g., their education, career development). Students will generate materials for data collection, databases, literature reviews, statistical data analyses, and written reports of their findings. In addition, the students will make regular oral presentations of their work to our research team. Through regular meetings, we will be sure that student accomplishments are in line with faculty expectations and that the students are enjoying the work and getting the experiences they want from it. Here is a description of one of our projects: Some attitudes are resistant to change, are stable over time, and have powerful impact on a person's think and action (called "strong attitudes"), whereas other attitudes are flexible and inconsequential (called "weak attitudes"). Social scientists have identified a dozen attributes of attitudes that

differentiate the strong from the weak. Strong attitudes are ones that people consider more personally important to them, that come to mind quickly and effortlessly, that are held with great certainty, that are accompanied by large volumes of relevant knowledge stored in long-term memory, and more. Considerable disagreement exists regarding the relations among these attributes: some scholars have suggested that the attributes reflect a few latent constructs. These researchers have conducted factor analyses, identified clusters, averaged measures of attitudes in a cluster into an index, and conducted analyses with that index. However, each such investigation has identified a different clustering structure that is not replicated in any other investigation. Other scholars have suggested that each strength-related attitude attribute is a distinct construct in its own right. Theses researchers have built measures of each construct and treated them individually in multivariate statistical analyses, at the expense of parsimony. But evidence generated by this approach has not yet convinced those interested in building clusters that they should abandon their analytic strategy. To help resolve this controversy, we will apply new research methods to compare the causes and consequences of each strength-related attribute, in an effort to identify clusters of attributes more convincingly. If we find two or more attributes that have the same origins and effects, this would support the claim that they can sensibly be treat as surface manifestations of a single latent construct. But if we find no such instances, this will support the separate-constructs notion. To do so, we will be analyzing a variety of existing datasets. A group of undergraduates will join our research team to study these issues. Here is a description of another of our projects: During the last ten years, we have conducted a series of national surveys tracking American public opinion on issues related to climate change. And during this time, Americans have come to accept the views of mainstream scientists on many relevant issues: whether the planet has been heating up gradually during the past 100 years, whether humans are responsible for this warming, how serious the effects of climate change will be if nothing is done to mitigate them, what should be done to deal with the problem, and much more. But at the same time, there has been a growing split between Republicans and Democrats on this issue. While Democrats have been moving steadily in the direction of the views of mainstream scientists, Republicans have not manifested any notable changes in this direction. Although Democrats and Republicans differed only minimally in their views in the late 1990s, Democrats are now much more likely to endorse mainstream scientists' views on this issue. This raises a fascinating question: why has this gap grown? Literatures in political science and psychology suggest a possible answer: perhaps people's views have been importantly influenced by visible and trusted leaders and supporters of their parties, and perhaps those leaders expressed increasingly different views on the issue over the course of the last ten years. Specifically, it could be that news media coverage of the issue has provided increased visibility to many natural scientists and to Democratically-inclined leaders who expressed

the beliefs that climate change is real, threatening, and merits mitigation, while Republican-included leaders (such as President Bush) maintained the view for many years that the jury was out and more research was needed to resolve these issues. This project is designed to test this hypothesis. Specifically, we propose to do an in-depth content analysis of news media coverage of climate change, randomly selecting a set of major news media stories on the issue (to make the data processing task manageable in size) and content analyze the news stories. The undergraduate research assistants would develop a set of procedures for implementing the content analysis, carry it out, evaluate the reliability of their results, and conduct statistical analyses of their data. My research team's activities with undergraduate assistants in the past have led to the students writing honors theses with me. Two years ago, three such theses were completed, one of which has already been accepted for publication in a major journal, and the others of which certainly will be. Our work always trains students in how to do real social science research of top quality, and we often lure students to spend their careers in the social sciences. Some students who joined us as freshmen worked with us consistently throughout their time at Stanford. The students' time with the graduate students is an important part of their professional socialization. And seeing their work gain national visibility is inspiring to the students and energizes them to do their best work. Some students have already been recruited to work with me this year because they qualify for federal work study and will earn the maximum allowed through that program. But those funds would run out relatively soon after the students start working with me, because work study money is very limited this year. And because of Stanford’s generous financial aid this year, many fewer students quality for work study at all. So I am seeking VPUE support to allow work study students and non-work study students to work for the entire academic year (and a few to work during next summer) to fill out our team and allow the students to see their projects through to completion. We will advertise research assistant positions to non-work study students via email announcements, which has been successful in recruiting students to our team in the past. Past student project outcomes have included: Acquired election returns from all California elections since the beginning of name order rotation on ballots, built a huge database, and carried out statistical analyses, yielding op-eds in the NY Times and Mercury News, conference presentations, and an academic article. Collected decades of survey data on presidential approval, gasoline prices, unemployment rates, interest rates; conducted time series analysis, yielding conference presentations and articles. Located and edited tv news stories suitable for use in experiment, organized conferences of major political psychologists on campus, etc. etc. Two years ago, one of my VPUE undergrads was the first author of a journal article in the Journal of Social Issues on the causes of voter turnout – this was a broad literature review that integrated a huge amount of past research and proposed a new theoretical framework for understanding the findings of that work. Two of the senior honors these written by our students are currently being combined into a single article for submission to a top journal by one of the authors, who

is now enrolled at the Stanford Law School and is collaborating with our current undergrads. Budget 10 academic year students, 10 hours per week, 30 weeks academic year, $14 per hour = $42,000 - $5,600 matching funds from federal work study = $36,400 5 summer students, 40 hours per week, 10 weeks, $14 per hour = $28,000 TOTAL REQUEST: $64,400

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Office of the Vice Provost for Undergraduate Education VPUE Faculty Grants for Undergraduate Research, Academic Year 2010-2011

THE VIRTUAL HEART

A COMPUTATIONAL TOOLBOX TO MODEL HEART FAILURE o Tyler O’Brien Shultz, undergraduate student (sophomore) o Corey Lynn Murphey, undergraduate student (junior) o Manuel K. Rausch, PhD student in Mechanical Engineering (Tyler’s student mentor) o Jonathan Wong, PhD student in Mechanical Engineering (Corey’s student mentor) o Ellen Kuhl, Associate Professor in Mechanical Engineering and Bioengineering (Faculty mentor)    BROADER SCHOLARLY AGENDA MOTIVATING THE PROJECT The overall goal of our Computational Biomechanics lab is to move heart disease therapies from empirical to predictive by using fundamental laws of physics. To achieve this goal, we design interactive, simulation environments that will advance our understanding of complex bio-electro-mechanical pathways in heart disease. Heart disease is the primary cause of death in industrialized nations, claiming more than 16 million lives worldwide each year. Without early diagnosis and appropriate treatment, this dysfunction of the heart can have devastating physiological consequences. Historically, clinical therapies for heart disease have been developed by trial and error, as opposed to a systematic therapy design through scientific understanding of the functional and structural mechanisms of electrical excitation and mechanical contraction. Continuum mechanics-based models in combination with modern computer simulation technologies now allow us to provide greater insight into the complex pathways of rhythm and contraction disturbances, and thereby guide the design of novel successful therapies for heart failure. SPECIFIC STUDENT PROJECT OBJECTIVES Tyler O’Brien Shultz is a second year undergraduate student at Stanford who has been working in the Computational Biomechanics lab for the past five months. He has teamed up with a current PhD student, Manuel Rausch, to study the functional mechanisms underlying leaking heart valves. Under Manuel’s close guidance, Tyler has now taken the lead on the experimental aspects of this project. He is explanting mitral valve leaflets from ovine hearts. After tissue histology, Tyler is characterizing fiber orientations within these leaflets using optical microscopy. The ultimate goal of this study is to correlate mitral leaflet microstructure, for example collagen fiber orientation, to mechanical function, for example maximum principal strain. Our collaborators in the Department of Cardiothoracic Surgery are providing Tyler with data sets from in vivo sheep experiments in which they have, for the first time, characterized mitral leaflet strains in the beating heart. Tyler’s student adviser Manuel has recently submitted a manuscript about the engineering interpretation of these unique clinical data sets. We are now in the process of collecting the final data of Tyler’s imaging study that will then turn into a follow-up manuscript. This funding will allow Tyler to be engaged in the entire process of data collection, data evaluation, manuscript preparation, and scientific publishing.

Corey Lynn Murphey is a third year undergraduate student at Stanford who has been working in the Computational Biomechanics lab for the past five months. She has teamed up with a current PhD student, Jonathan Wong, to study the fundamental characteristics of rhythm disturbances in the

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heart. Jonathan had previously developed a computational toolset to predict electrocardiograms on a patient-specific basis. Within this project, Corey will continue to explore the impact of ventricular fibrillation, a common and extremely dangerous rhythm disorder in the heart. Throughout the summer, Corey has familiarized herself with the mathematics and the computational algorithms underlying these predictions. She is now at a stage, where she is independently running simulations of healthy and diseased hearts based on magnetic resonance images from arrhythmia patients taken by our collaborators in Cardiology. This support will provide her the opportunity to finalize her patient-specific studies of ventricular fibriallation and biventricular pacing. If successful, we envision to mentor Corey to publish her work in a peer-reviewed internationally recognized journal. We have successfully done this in the past with a previous undergraduate student in our lab and believe it will expose Corey to the process of scientific writing, reviewed research, and publishing. SPECIFIC STUDENT ACTIVITIES, TECHNIQUES, AND DELIVERABLES Both students, Tyler and Corey, will continue to work closely with PhD students in our lab. They have successfully started this teamwork over the summer. Both PhD students, Manuel and Jonathan, are excited to continue working with Tyler and Corey. This funding will allow Tyler to finalize his tissue histology studies on mitral valve leaflets and Corey to finalize her computational research on rhythm disturbances in the heart. While Tyler’s work is primarily experimental, Corey’s work is more mathematical and computational. Our lab is committed to mentor them towards scientific publications that will give them exposure to the scientific community at an early stage of their career. Their individual contributions will consist of collecting scientific results, summarizing their results in graphs and images, interpreting the results, and embedding their work in a bigger scientific picture. STRATEGIES FOR PROVIDING MENTORSHIP Since Tyler and Corey have joined the Computational Biomechanics lab through the SURI program in summer 2010, they have developed unique skill sets from which all members of our lab benefit. Tyler and Corey are regularly participating in the weekly group meetings of the Kuhl lab where they are giving regular progress reports to all lab members. As part of this project, Tyler and Corey will also attend the biweekly meetings of the Cardiovascular Tissue Engineering Group at Stanford where they will have the opportunity to actively interact with Radiologists, Vascular Surgeons, Cardiothoracic Surgeons, Material Scientists, and Mechanical Engineers. Tyler is closely working with a PhD student in the lab, Manuel Rausch, and Corey is working with another PhD student, Jonathan Wong. Both teams are actively mentored by Ellen Kuhl, and meet on a weekly basis to provide feedback on their research activities. To engage Tyler and Corey in the activities of the lab, they are provided desk space in the Durand building sharing the office with their student advisers. PLANS FOR STUDENT RECRUITMENT AND SELECTION Tyler O’Brien Shultz and Corey Lynn Murphey have been working in the Kuhl lab as SURI summer research undergraduate students. They have started their projects and would like to continue their research activities throughout the academic year. OUTCOMES OF PAST STUDENT PROJECTS Previous VPEU grants have sponsored two undergraduate students working in the Kuhl lab:

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Anton Dam was sponsored in the academic year 2008-2009. He has finalized his research project and we have submitted a manuscript that summarizes his work which is currently under review: Rausch MK, Dam A, Göktepe S, Abilez OJ, Kuhl E. Computational modeling of growth: Systemic and pulmonary hypertension in the heart. submitted for publication. 2010. Olivia Jackson was sponsored in the academic year 2009-2010. She has designed new educational and outreach materials around cardiac function which are publicly available on our lab website: http://biomechanics.stanford.edu/ animations.

BUDGET

Student Stipends o Corey Lynn Murphey Fall 2010/11 10 weeks, 10 hours/week $ 1,400 o Corey Lynn Murphey Winter 2010/11 10 weeks, 10 hours/week $ 1,400 o Corey Lynn Murphey Spring 2010/11 10 weeks, 10 hours/week $ 1,400 o Corey Lynn Murphey Summer 2010/11 10 weeks, 40 hours/week $ 5,600

o Tyler O’Brien Shultz Fall 2010/11 10 weeks, 10 hours/week $ 1,400 o Tyler O’Brien Shultz Winter 2010/11 10 weeks, 10 hours/week $ 1,400 o Tyler O’Brien Shultz Spring 2010/11 10 weeks, 10 hours/week $ 1,400 Student Travel Expenses o Tyler O’Brien Shultz

ASME Summer Bioengineering Conference Nemacolin Woodlands Resort Farmington, Pennsylvania, June 22-26, 2011 $ 1,500

o Corey Lynn Murphey ASME Summer Bioengineering Conference Nemacolin Woodlands Resort Farmington, Pennsylvania, June 22-26, 2011 $ 1,500

The budget will cover conference fee, travel, and accommodation. Tyler and Corey will participate in the ASME undergraduate student poster competition. They will be accompanied by Ellen Kuhl, Alkiviadis Tsamis, post doc in the Kuhl lab, and their student advisers Manuel Rausch and Jonathan Wong, PhD students in the Kuhl lab.

Project Materials and Supplies o Materials and Supplies, Tyler O’Brien Shultz $ 500 o Materials and Supplies, Corey Murphey $ 500

The budget will cover experimental equipment and usage of shared imaging facilities for tissue histology, immunohistochemistry, scanning electron microscopy, and transmission electron microscopy.

Budget Summary o Tyler O’Brien Shultz, Fall, Winter, Spring, Tavel, Materials $ 6,200 o Corey Murphey, Fall, Winter, Spring, Summer, Travel, Materials $11,800

The overall requested budget to support Tyler O’Brien Shultz and Corey Murphey is $18,000.

Application for a VPUE Grant for Undergraduate Research

Nicholas Jenkins (English and PWR), njenkins@stanford.edu, 13 October 2010

Project Title: Family: A Site About Culture (http://fam.stanford.edu)

Scholarly agenda "Family" began two years ago as a small-bore investigation into the genealogical background of the poet W. H. Auden. Wondering if and how I could read social history into poetry, I wanted to know very simply who Auden's ancestors were and where they came from. Ultimately I discovered a great deal that is interesting to me about Auden's personal history, about for instance his radically split family circumstances. Auden's father came from a very modest world of provincial tenants and farmers; his mother was distantly descended from British and European royalty. Such a tense, socially emblematic imbalance is ciphered into some of the most marked characteristics of Auden's poetry. But as I worked I started to notice more and more provocative or surprising links (links that often had little to do with Auden) between important political and cultural figures, between church and state, between military realities and aesthetic tendencies, between empire and homeland. Harnessing the power of the genealogical software I was using, I saw untold stories coming into focus for me almost day by day. I saw for instance how the son of the Victorian poet Alfred Tennyson, enabled by the prestige accruing to his father from poems such as "The Charge of the Light Brigade", married into the aristocratic world that included the Earl of Lucan, who ordered the Light Brigade's charge and the Earl of Cardigan who led it. And I saw in turn how this famous lyric about a headlong military assault was a kind of allegory of Tennyson's own "charge" into the redoubt of the British aristocracy. (See http://goo.gl/ulYt) Eventually I realized that what I was seeing form in front of me was a strange, powerful social map of English culture. I kept working. This was no longer simply something about Auden. I kept adding more and more important figures to my database. For example, I integrated 813 out of the 816 individuals Noel Annan identified, in what is probably the most famous essay in British social history of the last 60 years, as his "intellectual aristocracy". In order to connect Annan's 813 intellectual aristocrats into my social tree I had to put in 6,500 people (parents, aunts, brothers, sisters). As of this writing, my "Family" database has very close to 18,000 individuals (each of whom is connected in some way, either immediately or distantly, to the other 17,999 or so people listed). At this point I am surrounded by myriad questions about British culture that my research has thrown up -- what is the relationship between family and culture? what is the relationship between different kinds of cultural expression and different family connections? how in the British case does social prestige intersect with artistic or intellectual achievement? are certain kinds of literary expression (such as poetry) tied closely to a particular class in British culture? My intricate, cell-by-cell, person-by-person assembly of this very large set of inter-relationships has left me in the midst of some of the largest and most interesting historical questions.

Jenkins, Oct 2010 application for VPUE grant, p. 2

Student project objectives "Family" (http://fam.stanford.edu), my project's website, is already available in a basic form online. I need student help now to enrich its presentation through some intensive picture research, through research on basic biographical details of some of the major figures (poets, generals, political hostesses, novelists). I do not envisage the database growing in size much further, but I would also like to intensify the degree of interconnection between figures already in the database. With this too, I need student research help. In other words, while I write about what I have uncovered I need help from an undergraduate to put some more flesh on the bones of the research I have done. I envisage this project as a rare opportunity for a Stanford student to become deeply, intimately familiar with vast stretches of British cultural and political history, refracted through the lens of "family", predominantly in the period from the 18th through to the 20th century. My experience in working on the project, largely alone until now, is that the website brings to light a wealth of unsuspected material, a plethora of arcane stories, an overflowing abundance of specific historical questions and problems that no one person, and certainly not myself, will ever be able to explore adequately. I therefore see the work an undergraduate would do with me on this website as providing a large number of intriguing research possibilities for the student to follow up on their own behalf in, for example, an Honors essay. Student responsibilities A student working with me on this project would be responsible for such typical tasks as: independent research on visual sources to be incorporated into the website tabulation of biographical information, gleaned from scholarly sources such as the Oxford Dictionary of National Biography research in libraries into information concerning dates, places, people etc that is not currently accessible online analytical study of the database to reveal flaws or problems and to locate opportunities for cross-linking between individuals listed Strategies for providing mentorship My aim would be to have an open channel of communication, to be used as often as necessary, between my student researcher and myself. But that fluid arrangement would rest of the bedrock of a weekly sit-down consultation with the student to assess progress, to talk through problems and to inspect work.

Jenkins, Oct 2010 application for VPUE grant, p. 3

Plans for student recruitment I would aim to recruit a student through advertising in the English and History departments and through recommendations from colleagues there and in PWR. Budget Student stipend Fall quarter 2010: 10 hrs per week for 10 weeks @ $14/hour

$1400 Winter quarter 2011: 10 hrs per week for 10 weeks @ $14/hour

$1400 Spring quarter 2011: 10 hrs per week for 10 weeks @ $14/hour

$1400 Summer quarter 2011: 10 hrs per week for 10 weeks @ $14/hour

$1400 Miscellaneous supplies, publications

$400 Total requested $6000

Liao, Y. Joyce VPUE Grant Application 

 

Research Proposal: Regenerative Therapy for Vision Restoration in the Adult

Y. Joyce Liao, M.D. Ph.D. Department of Ophthalmology

I. Project Description Introduction and Summary This grant proposal will establish the feasibility and optimal conditions for successful central nervous system stem cell therapy in adults for the treatment of anterior ischemic optic neuropathy (AION). AION is the most common acute optic neuropathy in patients over 50 years old and leads to significant, permanent vision loss. There is no effective treatment. We have encouraging preliminary data for transplantation of neural progenitor cells derived from embryonic stem cells (ES-NPCs) into the brain and the eye. With the help of the VPUE Faculty Award, we will use retinal lasering, a well established therapy for diabetic retinopathy, to increase the efficacy of stem cell transplantation into the eye to re-constitute retinal neurons and glia in an animal model of AION. The restoration of visual information processing—one of the most valued and quantifiable central nervous system behaviors—using regenerative approaches will likely transform the therapeutic approach following central nervous system injury. Preliminary Data

Experimental AION. We have established a reliable model of experimental AION in our laboratory using photochemical thrombosis. We have performed extensive in vivo and in vitro morphometric analyses during the acute and chronic phases of experimental AION using ocular coherence tomography and microscopy (manuscripts submitted and in preparation). We have also performed functional assessment of vision following experimental AION using serial intracranial flash visual evoked potential recording.

Stem cell transplantation. We have successfully transplanted green fluorescent protein (GFP)-positive ES-NPCs into over 200 adult mice, using retinal lasering, a proven therapy in patients with diabetic retinopathy, to coaxed the adult retina to uptake a significant number of ES-NPCs and extend elaborate processes (manuscripts in preparation). Figure Right shows an examplar of a retinal whole mount prepared from a lasered eye 1 month following transplantation. There are many transplanted cells, which appeared green due to presence of GFP. More severe laser parameters correlated with better transplantation efficacy. At 1 and 2 months, many transplanted cells expressed neuronal marker (class III -tubulin) and glial marker glial fibrillary acidic protein (GFAP) but not both. In Figure Right next page, whole mount retinal preparation showed many transplanted ES-NPCs (green) with processes that expressed neuronal marker -tubulin (red) but not glial marker GFAP (blue). These ES-NPCs co-localized among native retinal ganglion cells and processes which express -tubulin

Liao, Y. Joyce VPUE Grant Application 

 

(red). Some processes were so dense that they formed a nerve-like bundle (not shown). These ES-NPCs expressed neuronal marker but did not extend processes into the optic nerve. In optic nerve injury model such as AION, the normal barrier for exogenous axonal extension is disrupted, possibly facilitating ES-NPC extension into the optic nerve.

Research Aims Aim 1. Modification and characterization of ES-NPCs to generate retinal progenitors. To optimize generation of retinal ganglion cells from ES-NPCs, we will characterize the effects of noggin, dkk1, and IGF-1 on culture ES-NPCs, we will perform RT-PCR on serial time points (days 1-8). We will use RT-PCR to assess expression of forebrain, retinal, and other markers at days 1-7 in vitro of the ES-NPCs, compared to that in developing mouse retina E14-20 (positive control) and untreated cells (negative control). We will look for expression of Oct3/4, SSEA1, nestin, NeuN, fox-G1, Rx, class-III -tubulin, Pax6, Chx10, Mitf, Zoe, and Notch 1; markers of post-mitotic retinal neurons including peripherin, recoverin, calretinin, S-opsin, and Brn3; markers of excitatory and inhibitory neurons; and markers of non-neuronal cells including astrocytes, microglia, and endothelial cells. Treatment protocol that most closely resembles developing mouse retina and in particular retinal ganglion cells will be used in future transplantation experiments. We do not anticipate any technical difficulties with the RT-PCR since this has been performed. We may need to adjust the culture conditions to optimize the retinal ganglion cell fate, such as additional treatment with Lefty and Shh. Following transplantation (see Aims 2-3), we anticipate the expression pattern of to correlate with the success of generating retinal ganglion cells. Aim 2. Laser-assisted transplantation of retinal progenitors to treat animal model of ischemic optic neuropathy. To determine the feasibility of stem cell transplantation to treat AION, we will perform experimental AION in the right eyes in adult mice per standard protocol first and, one-day later, perform retinal lasering and bilateral intravitreal transplantation of ES-NPCs. We will assess transplantation efficacy using retinal whole mount preparations and horizontal frozen retinal sections at 1- and 2-months following transplantation using immunohistochemistry and light microscopy. Controls include no retinal lasering and no AION. We will evaluate the possibility of fusion using BrdU labeling of ES-NPCs prior to transplantation. A minimal of 10 mice per experimental arm and at least 2 experiments will be performed per data point. We will perform morphometric quantification under masked conditions using Image J and statistical analysis using Student’s t-test and one-way ANOVA. Aim 3. Differentiation of transplanted ES-NPCs. To determine the fate of transplanted cells, we will use whole mount retinal preparation and frozen horizontal retinal sections to perform morphometric studies of the retina and optic nerve at 1-2 months following transplantation using antibodies against known retinal ganglion cell markers, including -tubulin, neurofilament, and Brn3, vs. markers of other cells including photoreceptors (recoverin), bipolar cells (calbindin), horizontal and amacrine cells (GAD65), and astrocytes (GFAP). We will also look for microglial activation (Iba-1), although our preliminary studies showed that there was no evidence of rejection following

Liao, Y. Joyce VPUE Grant Application 

 

transplantation. A minimal of 10 mice per experimental arm and at least 2 experiments will be performed per data point, and we will use Student’s t-test and one-way ANOVA for statistical analyses.

II. Student Objectives and Contribution

A. Learn scientific method and approach to the study of the optic nerve and diseases B. Become educated about regenerative and other approaches to disease treatment C. Use microscopy and morphometric analysis D. Participate in all aspects of the research project, including learn techniques such as

preparation of whole mount retina, retina lasering, polymerase chain reaction, immunohistochemistry, and in vivo morphometric assessments of the retina and optic nerve

E. Gain appreciation for the scientific method and preparation of laboratory findings for publication

III. Student Activities, Techniques, Responsibilities, and Deliverables

A. Learn the scientific method and statistical analysis B. Learn how to conduct animal research C. Learn to assess mouse retina and optic nerve in vivo using microscopy and ocular coherence

tomography D. Learn techniques including retinal lasering, photochemical thrombosis model of optic nerve

head ischemia, whole mount retinal preparation, histological preparation, immunohistochemistry, microscopy, and morphometric analyses

E. Present at group meetings and journal clubs, including critical interpretation of scientific publications

F. Participate in writing manuscripts and constructing figures for publication G. Attend ophthalmology department and Stanford research activities H. Present at the weekly ophthalmology research seminar and at two international meeting on

vision research. Apply for student research awards associated with meetings IV. Mentorship The students will work in the laboratory directly with me to carry out all aspects of the experiments (see above). I will provide feedback on average twice per week and following each formal presentation during lab meeting and to members of the Ophthalmology Department. The students will present the findings using powerpoint presentation, after the data has been analyzed. V. Student Recruitment and Selection Undergraduate students Madison Stanford, a junior Chemical Engineering major, and Melissa Ada, a sophomore Human Biology major, have already been recruited into my laboratory. They both plan to work an average of 10 hours per week during the 2010-2011 academic year and 40 hours per week for 10 weeks during the 2011 summer. VI Outcomes of Past Student Projects

Liao, Y. Joyce VPUE Grant Application 

 

My previous students include Madison Stanford, a Stanford Chemical Engineering sophomore. Ms. Stanford’s work with me last year has resulted in 2 manuscripts which are being prepared for publication. In addition, she will be the lead author on 2 optic nerve projects which will be completed and submitted for publication in 2010-2011. A second student Xue Hu, a senior Computer Science major, was funded during part of summer 2010 to write MATLAB programs for data analysis. She will be an author, most likely second, on a manuscript when the data analysis is completed.

I have also received funding through the Medical Scholars Program at Stanford. Kiran Kaur was a fourth year medical student, who spent 6 weeks full-time with me. Her work led to a second author basic science study on the effect of a small heat shock protein on neuroprotection of optic nerve following ischemia, which is submitted for publication. She is also the first author on a clinical paper on ischemic optic neuropathy. Another student Yi-Ren Chen has worked with me in the last 2 years. He won a student travel award of the Association of Research in Vision and Ophthalmology and the 2010 AOA Student Research Award. He is the first author on 3 different projects; one is submitted and 2 are being written for publication.

Liao, Y. Joyce VPUE Grant Application 

 

Budget

2 students for 2010-2011 academic year and summer

1) Madison Stanford, junior, Chemical Engineering

2) Melissa Ada, sophomore, Human Biology

Total Salaries* $19,600

Travel** $5,600

Research $1,000

Total $26,200

*Academic year: $14 x 10 hrs/week x 10 weeks/quarter x 3 quarters = $4,200/student ($8,400 for 2)

Summer: $14 x 40 hrs/week x 10 weeks = $5,600/student ($11,200 for 2)

**Travel to two conferences (NANOS and ARVO) $2,800/student ($5,600 for 2)

VPUE Faculty grant for undergraduate research ----PROPOSAL Richard P. Martin

Antony and Isabelle Raubitschek Professor of Classics Room 105, Bldg 110, Main Quad

The study of Homeric religion, the topic of a large book project on which I am embarking, requires the use of methods and findings from philology, linguistics, epigraphy, archaeology, anthropology and religious studies. I believe it is the perfect introduction for an undergraduate to the inherently interdisciplinary nature of the study of the ancient world. I am applying for a VPUE faculty grant for undergraduate research in order to train and collaborate with a Classics student who can participate in getting a major project off the ground and learning the trade from the ground up. The broader scholarly framework for this project is that of a long overdue, late- 20th century re-integration of the fragmented specialist studies of textual, intellectual, and material cultures in the ancient Mediterranean. While the early 19th century could envision a robust and holistic approach, an all-embracing Altertumswissenschaft along the lines proposed by August Boeckh and Friedrich Wolf, the explosion in knowledge about antiquity (partly abetted by this vision) over the course of the 19th and 20th centuries (new papyri, inscriptions, sites, questions) had led by the 1990s to a scholarly landscape pocked with expert bunkers and intellectual foxholes. Those who studied and interpreted Homeric poetry, for example (of which guild I remain a member) most often had little regular scholarly contact with those who interpreted the material remains of Greek ritual practices (sacrifice pits, bone and ash deposits, votive offerings, temples). Dirt and word (in the apt phrasing of Emily Vermeule) were increasingly divorced. [On this problem, I have written in a recent issue of the Transactions of the American Philological Association.1] The study of the religious phenomena represented in the Homeric poems—whether divine intervention or horse sacrifice—had remained stuck in the theological modes of the mid-19th century, using rigid almost catechistic classifications spun out of listings of passages in the Iliad and Odyssey. Meanwhile, anthropologically oriented and informed studies, like those of the Swiss expert in ancient religion Walter Burkert, had not made headway with Homerists, who considered the realms of “actual” Greek religion to be the domain of “dirt” Classicists. A seminar taught in conjunction with my colleague Ian Morris in 2006 convinced me that a total revamping of our view of Homeric religion (both words should be in scare quotes) is needed, and I began in 2007 to collect data and secondary sources as I could in the brief intervals between writing several other book projects. Now I am ready to begin the structuring, precise research, data analysis, and drafting of the book. I need someone to help me sort out and organize the mass of bibliographic resources in the fields mentioned above, where relevant to the project. The researching undergraduate would: •Think through with me the full range of resources to be explore, in as many language as needed •Locate and scan/download/Xerox/check out the print resources

1 Martin, R., “Words Alone are Certain Good(s): Philology and Greek Material Culture,” TAPA 138 (2008) 313-49.

•Read and summarize selected articles and book chapters to flag me as to argument and to get a broad sense of the issues •Critique said sources with his own views based on reading I assign Thus far, the range of tasks would seem fairly ordinary. What makes my request distinctive—and I think highly useful for an undergraduate education—is the added features: •Data will be culled from the Greek texts of Homeric epic at the level of formula and interpreted, first with attention to poetics, then in all dimensions related to ritual and cult. This involves training the undergraduate in the precise analytical methods of identifying and isolating lexical and phrasal elements. At the simplest level, the phrase “all the gods” e.g. can be found, all of its occurrences can be listed (via the online Thesaurus Linguae Graecae), and a list can be presented. But the true intellectual work begins as the undergraduate is shown how to cluster the occurrences, around such variables as speaker/narrator; narrative situation; relevance to type-scene (e.g. rites of sacrifice, oaths, welcoming); and rhetorical purposes of the phrase in context. In short, I will train the student in discourse analysis of Homeric Greek. Somewhere in the vicinity of 75 such phrases will be assigned and more are expected to be discovered in the process, by the undergraduate who will investigate these narrative kernels,. •The “deliverable” (to use a word properly relevant only to industry but unfortunately creeping into universities) will be a detailed document (appx. 80 pages) that interprets Homeric phraseology in terms of the above-listed features and forms the data set for further comparative and archaeological work to be done by me, and, if time permits, the undergraduate. Appendices to this will list the entire formulaic data set used (this may well be another 200 pages but is mostly TLG cut-and-paste material). I wish to have the work done this academic year, starting immediately. I plan to meet regularly—ideally every week—with the student in order to map out the project, keep him in constant discussion, and oversee his collection of dictional materials and directions for interpreting them. As I am Chair this year and constantly on site, this will not be difficult. I will of course be in electronic communication with him as well. I already have approached a student, who has tentatively agreed (based on funding). Ben Radcliffe is perfect because he knows Greek and Latin, and also has begun with our lecturer Fred Porta the study of Hittite. As the analysis of Homeric religion requires reference to the Indo-European heritage, and to studies of pre-Homeric myth and cultures, these skills are absolutely invaluable, and I do not know of another student who can offer them. I will supplement these by introducing Ben to relevant work on and texts in Vedic and Medieval Irish poetics and culture. The work of the student will fit into the broader agenda of my project by enabling us to answer such questions as whether the Homeric representations of ta hiera (“the holy things”) is: 1) stratified—i.e. are some phrases linguistically older than others or formulaically “older” in the oral tradition. This will involve a new presentation (and learning by Ben) of the methods of Milman Parry and Albert Lord concerning oral poetics; and 2) whether it is at all connected with “real” religious practices as attested in archaeology or later epigraphic contexts. How fictional is Homer? How “real”? Or—better yet—how does the poetic imagination of the past and its gods interact with and

even drive the practices one can reconstruct of actual Greeks in the 12th through 6th centuries BC (the long gestation period for Homeric epic). I do not envision social activities, presentations, travel, or other add-ons—just simple one-to-one tutorial-style mentoring, intensely, with full written products required at suitable stages (every 6 weeks, at most). Experience of the past 30 years (unfunded) has taught me that this works best.

BUDGET Student stipend: $14 per hour x 10 hours/week x 25 weeks (1/2 Fall 2010; Winter-Spring 2011 quarters) = $3500. $14 per hour x 20 hours/week x 5 weeks summer 2011 = $1400. Student travel: $0. Project materials: Books (Homeric dictionary, Oxford Classical Texts (5), Homeric grammars): $400. Xeroxing appx. 2000 pages @ $.05 page = $100. TOTAL: $5400

Magnetic Imaging of Individual Biologically Derived Nanomagnet Chains Submitted for the October 13, 2010 call

for VPUE Faculty Grants for Undergraduate Research Faculty Mentor: Kam Moler, Applied Physics and Physics

Undergraduate Researcher: Bo Dwyer, Sophomore, Physics Summary:

Magnetotactic bacteria comprise a large group of distinct prokaryotic species

linked by the biological synthesis of small magnetic particles within the cell body. These magnetic particles, called magnetosomes, are arranged into long lines within the cells and are used for navigational purposes. These bacteria, or the magnetic particles they produce, could have broad applications in medical fields such as cancer therapy and MRI contrast enhancement. In addition, our collaborators in the medical school are seeking to genetically engineer other cell lines (including mammalian cancer and stem cell lines) to produce similar magnetosomes for multiple purposes including single-cell MRI tracking.

Project Description: The field of nanotechnology has made exciting advancements in recent years.

Some of the most interesting advances have come in the field of medicine. Quantum dots can be injected into patients to create exceptionally clear images of tumors. Nanoparticles with many functional groups attached to them will bind to certain tumor cells.

While most nanomaterials are created in labs, some are naturally occurring. Several species of gram negative bacteria, for example, form small crystalline chains of iron oxide. These bacteria are anaerobic and are found primarily in muddy sediment layers in fresh bodies of water. Using these magnetite chains, the bacteria are able to differentiate up from down so that they can swim into oxygen poor regions.

These magnetite chains are of medical interest for several reasons. Irradiated bacteria could potentially be injected into a patient and guided to a tumor using an external magnetic field. Nanomagnets from bacteria could be stimulated to vibrate in a magnetic field, providing a possible treatment for hypothermia. Most importantly, it has been shown that these magnets have the ability to enhance MRI contrast positively or negatively, depending on the size of the particles that make up the chains.

This project spans several departments. A. C. Matin’s group in the Department of Microbiology and Immunology at the School of Medicine seek to express well-characterized magnetotactic bacterial genes magA, mms6, or both in the brain-metastasizing human breast cancer cell line 231BR, with the hope that the cells will produce intracellular magnetite particles. Brian Rutt’s group in the Department of Radiology is attempting to detect magnetite-expressing 231BR cells in vivo. Nu/nu mice will be injected intra-cranially with increasing number of 231BR cells encoding either magA, mms6, or both, and single cell-sensitive mouse brain MRI will be used to track them. Kam Moler’s group in the Department of Physics, wishes to investigate magnetite particle production in vitro in transformed 231BR cells expressing magA, mms6, or both. Increase in iron uptake generated by these genes will be quantified in vitro. Micro-

Superconducting Quantum Interference Devices (micro-SQUIDs) and Magnetic Force Microscopy (MFM) will be used to assess conditions that optimize the magnetic moment of the resulting magnetite. The student for which this application is intended will be working in Kam Moler’s lab.

Cellular MRI integrates the ability to obtain high resolution MR data with the use of contrast agents for labeling specific cells, thereby enhancing their delectability. Due to the unique aspects of MRI, e.g., high spatial resolution, excellent soft tissue contrast, and enhancement of the contrast by exogenous labels, great potential exists for utilizing MRI to non-invasively detect and track cancer cells within organisms. For MR cell-tracking studies, cells are typically labeled with iron oxide-based magnetic nanoparticles before their injection or transplantation. This form of cell labeling provides high cellular detection sensitivity with MRI.

The magnetite particle size and additional characteristics are strong determinants of the MRI signal. An important aspect of the proposed research is to manipulate and optimize the relevant properties and thereby the resulting MRI effectiveness. The Moler group has developed scanning micro-Superconducting Quantum Interference Devices (micro-SQUIDs) to measure the tiny magnetic fields generated by mesoscopic electronic structures. The Moler group’s smallest detectable moment is about ten billion times smaller than the smallest moment that can be detected by the commonly used commercial magnetic detection systems (e.g., the Quantum Design Magnetic Property Measurement System), and is presently the world record for magnetic dipole moment sensitivity in a scanning micro-SQUID.

The Moler group will use a range of techniques to characterize the magnetic properties of magnetite-generating mammalian cells. The MRI contrast generated by each individual cell will not be simply a function of iron mass but will depend on magnetite size, shape, and structure. We will therefore conduct nano-characterization of magnetite generated in 231BR cells both at magnetic and structural levels; theoretical modeling and comparison of MRI and physical characterization data should inform us as to how these differences may relate to MRI contrast. Iron-oxide particle formation will be examined by ultra-high-resolution SEM and particle size and shape will be characterized by ultra-high-resolution TEM. A bulk SQUID magnetometer will be used to measure iron-oxide particle magnetic properties in cell populations (~107 cells). As this instrument has limited sensitivity, cell populations that show promising magnetic properties will be further studied using scanning micro-SQUID susceptometry to measure iron-oxide particle magnetic properties in single cells. The micro-SQUID can detect the total dipole moment of a single cell and can also provide information about the internal magnetic structure (e.g., broken chains), but it does not have the sub-50-nm spatial resolution needed to resolve the magnetic configuration of the individual magnetosomes in a chain. We will therefore explore two alternative magnetic imaging methodologies: Magnetic Force Microscopy (MFM) and Scanning Transmission X-Ray Microscopy with X-ray Magnetic Circular Dichroism (STXM-XMCD) for spatially resolved images of the magnetic fields of individual magnetosomes. MFM will be used in conjunction with the magnetically coated carbon nanotubes sharp MFM tips developed by the Moler group to image magnetite particles in the cells. X-ray Magnetic Circular Dichroism (XMCD) is a relatively new technique used primarily at synchrotrons to detect magnetic properties of materials. In combination with

Scanning Transmission X-Ray Microscopy (STXM), this technique can image magnetic domains with very high spatial resolution while providing chemically specific information. The Moler group has on going collaboration with the Durr group at SLAC to explore STXM-XMCD as an alternative technique for spatially resolved imaging of the magnetic fields of individual magnetosomes.

Specific student responsibilities and opportunities:

A VPUE grant will support an undergraduate student as he assists in the magnetic characterization of these organisms. The student will develop sample preparation techniques for Scanning Electron Microscopy (SEM) and Superconducting Quantum Interference Device (SQUID) measurements. The student has also been trained in the use of the Stanford Nanofabrication Laboratory’s SEM and will use this device locate magnetosomes within these bacteria so that the images can be cross referenced with magnetic dipole measurements. In addition to gaining knowledge regarding magnetotacitc bacteria and mammalian cells, the student will also learn how to operate several useful tools used in the field of magnetic physics. The student will learn how to take measurements on a SQUID, a Magnetic Force Microscope (MFM) and a Magnetic Property Measurement System (MPMS). Because SQUID operation is very technical, the student will begin the use of this tool as an assistant under the close supervision of another lab member, as described below in Mentorship.

Specific student deliverables: Bo has already surveyed the literature, developed processes for preparing bacteria

samples, and learned how to operate an SEM to characterize these samples. Bo will continue to develop and test sample preparation techniques. This support will enable him to learn how to operate a scanning SQUID microscope. I (Kam Moler) expect him to continue to play an important role as a member of the team by preparing samples and characterizing them through SEM and MPMS measurements, but I think he is ready to start learning to acquire and analyze his own magnetic data this year.

Mentorship: The student will work closely with graduate student Lisa Qian and postdoc Beena

Kalisky, both of whom have been working on this project for some time. The student will work with Lisa on sample preparation, taking SEM images, and making MPMS measurements. He will work with Beena on a SQUID so that he might learn how to operate it under supervision. The Moler group is a world leader in scanning SQUID microscopy, holding the world record on spin sensitivity by two orders of magnitude, and Dr. Beena Kalisky is one of a handful of people in the world who knows how to operate these instruments. She is more than willing to work closely with sophomore Bo Dwyer after being impressed by his abilities and work ethic during his first summer in the lab, and their partnership is a very attractive element of this project.

Student Recruitment:

The student in question (Bo Dwyer) is a declared physics major and has

completed the introductory physics 60 series at Stanford. He began working in the Moler lab during the summer of 2010 under the Stanford Undergraduate Physics Research Program. He was attracted to this particular project because of a past experience in a microbiology laboratory at Boston University. His interests in physics and biology are well suited for this project.

Outcomes of Past Projects The faculty mentor last year applied for a grant (Thank you!) that was used to

support freshman Anand Natarajan last year during the winter and spring of 2009-2010. Anand did some helpful calculations. At the present time Anand is a sophomore and is pursuing his research interests in computer science after a summer internship at Google.

The Moler lab has not historically had very many undergraduate researchers. Two notable exceptions were Cynthia Keeler, who built her own research apparatus because she wished to do a very independent project and is now a postdoc at Harvard, and Josh Leu, who worked together with two graduate students to design a new kind of magnetic nanosensor. He was a coauthor on two papers during his undergraduate research, and is now a graduate student at MIT in EE.

Budget

student stipends or wages $14/hour x 10 hours/week x 10 weeks/quarter x 3 quarters $14/hour x 40 hours/week x 10 weeks/quarter x 1 quarters (summer) $9800 total wages travel $1400 travel to APS March Meeting Student Research Supplies $500 Student Research Supplies

ProposalforVPUEFacultyGrantforUndergraduateResearch The scholarly agenda that will motivate the undergraduate student project is the scholarly work that we do in my lab. The lab specializes in the study of human brain from a clinical and system neuroscience perspective. The general theme of our research is the relationship between clinical phenotypes and brain anatomy and physiology as well as the neural correlates of human expression and experience. The main impetus for our research is to understand the anatomical and functional correlates of cognition and stereotyped behavior in the human brain. Our methods include simultaneous fMRI/EEG, intracranial electrophysiological recording, and electrical stimulation of the human brain. The human subjects in our research are patients who are implanted with intracranial electrodes as part of their epilepsy surgery. Patients are implanted only and only for clinical reasons. The work has been reviewed and approved by the Stanford University IRB office. The proposed undergraduate research project will be in line with the larger theme of scholarly work in my lab and also in line with the methods that we have gained expertise in. In my lab, there are two postdoc fellows, one graduate student, and two international visiting scholars, and a full time research assistant. We have expertise in the methods of electrophysiological recording and brain stimulation. The student project objectives are to 1) learn how to interact and collaborate with other team members in the lab, 2) administer a cognitive task to patients admitted to Epilepsy Monitoring Unit at Stanford University Medical Center, 3) record electrophysiological data from patients implanted with intracranial electrodes while patients perform the cognitive task (see below), 4) analyze the recorded electrophysiological data using easy-to use algorithms that we have developed in the lab, and 5) interpret the findings in light of what is known in the literature. We will use a cognitive task that is in line with the previous work in this lab, namely understanding the neural basis of laughter and positive emotional expression and experience. For this, we will administer a task that contains funny, sad, and neutral images. These images are standardized images and we have normative data about how funny they are or how sad they are. The task will be repeated twice in each patient, and will take about 20 minutes each time. The aim of the study is to identify regional brain activity induced by presentation of emotionally salient stimuli. Our goal is to identify the regional activity within specific sub-regions of the human amygdala during positive emotional stimuli. The student will be encouraged to participate in the procedure of brain mapping with electrical brain stimulation that is performed solely for clinical reasons. Student will be responsible to record the perceptual and behavioral phenomena induced by electrical stimulation of the brain reported by patients. The student will shadow me in the clinic once weekly to learn about the clinical practice of medicine and the clinical condition of patients with refractory epilepsy, which will lead to invasive intracranial monitoring. I will encourage the student to work towards a poster presentation in a national meeting and prepare for a more independent research study. Moreover, the student will be

required to prepare two oral presentations in the lab. First the student will present data from literature research and will highlight what is known and what is unknown in the field. The student will write up the summary of literature search. In the second meeting, the student will describe the methodology of research and the preliminary findings of the study and will discuss its implications. Each lab member, including myself, will give feedback to the student after each presentation. In addition, the student will have weekly meetings with myself to review the plan and progress of the project. The student will continue the research Depending on the level of funding, one or two students will be selected by application. A flyer will be sent out as an email attachment to the list of Student Interest Group in Neuroscience (SIGN) (see attachment). Students will be selected in the basis of criteria specified on the flyer. Although I personally have not received VPUE grant yet, I have been involved with mentoring many students at Stanford. Most gratifying to me has been my experience with undergrad students. They are the smartest I have worked with and the most curious ones. It is fascinating to work with enthusiastic students who are passionately engaged with learning new things about the human brain. I also like to teach and I have been very fortunate that students and neurology residents have appreciated my teaching and awarded me the Lysia Forno Award for Excellence in Teaching the year I got to Stanford. I hope you will give me the opportunity to afford mentoring more students in the years to come. Thanks for your attention,

Josef Parvizi MD PhD Assistant Professor Department of Neurology and Neurological Sciences School of Medicine LBCN.stanford.edu

Student Research OpportunityLaboratory of Cognitive & Behavioral Neurology

Who: Undergraduate students interested in neuroscience, medicine, or psychology

When: Flexible work hours during the academic year - full time in the summer

Where: Laboratory of Behavioral and Cognitive Neurology - Boswell Building - Main Hospital

What: The project entails electrophysiological studies of the brain function during different cognitive tasks. We record electrophysiological signals from electrodes implanted over the surface of the brain in conscious human subjects undergoing epilepsy surgery. We administer cognitive tasks and analyze the event-related potentials in each specific brain region. Students who produce meaningful data are encouraged to present their findings as a poster in a national meeting (with paid travel expenses). More about the available projects: http://lbcn.stanford.edu

How: Send a copy of your resume and a short paragraph describing your career goals to jparvizi@stanford.edu

Must haves: Eager to learn about the brainInterested in being engaged in pursuing a larger scholarly agenda to learn about the structure and function of the brain and relevant clinical problems. Knowledge of MATLAB

Vahe’ Petrosian, Physics and Applied Physics

Project Summary

Understanding the underlying physical mechanisms for emissions from astro-nomical objects is essential for understanding their structure and the stateof the faraway regions of the cosmos. Especially interesting are clusters ofgalaxies, the largest structure in the universe. One aspect of these objects istheir non-thermal emissions by high energy particles (or cosmic rays). Themechanisms for energizing of these particles and their emission processes iscurrently subject of intense research. These emissions come from the intracluster medium (ICM) in form of radio and hard X-ray radiation, on topof dominant and well understood thermal soft X-ray emission from the hotplasma. Many attempts to explain the hard X-ray emission from ICM havepreviously been suggested and rejected. The subject of this project is arigorous investigation of the mechanism of acceleration of the non-thermalradiating particles. Unlike past studies which have dealt with accelerationand emission of electrons, here we propose to also consider the processesfor protons (and other less abundant ions), and more importantly, investi-gate the interplay between these two species. We will develop a computerprogram that determines the time evolution of the energy spectrum of theprotons and electrons in the ICM and compare their radiation with theobserved radio and hard X-ray spectra from several clusters of galaxies.

Project Description

The two most probable mechanisms for the hard X-ray emission from ICMare non-thermal bremsstrahlung radiation and inverse Compton scattering.Previous results from our research group has shown that the electron non-thermal bremsstrahlung radiation would cause catastrophic heating of theICM if it were to generate the observed hard X-ray spectrum. This is be-cause of their fast energy loss rate by Coulomb collisions. For protons,however, the overall energy loss timescale is expected to be much longerthan that for electrons. Also, new energy loss processes, such as proton-electron Coulomb collision and proton-proton interaction, come into play.Last summer, Byungwoo investigated this subject and derived the energyloss rates of the proton due to the all relevant processes (both elastic andinelastic proton-proton and proton-electron). He also simulated the time

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evolution of the energy spectrum of the protons subject to these energy lossprocesses while accelerated by turbulence, which is expected to be present inthe ICM. The result showed that, unlike the electron case, the protons wereable to develop a promising non-thermal tail, without causing unaccept-able increase of the temperature of ICM gas. We have developed numericalcodes for solving the Fokker-Planck equations describing the relevant pro-cesses for acceleration of electrons and protons separately. In the projectproposed here, we will consider the interactions between the protons andelectrons by solving their coupled Fokker-Planck equations simultaneously.We will compute the time evolution of the energy spectra of the protonsand electrons that interact with each other and are subject to accelerationby turbulence and the above mentioned energy loss processes. This will al-low us to rigorously verify the possibility that the hard X-ray emission fromICM is generated by the proton non-thermal bremsstrahlung radiation. Thiswork can be also used to investigate possible mechanisms for the gamma-rayspectra that will be observed by Fermi Telescope in the future.

Student Recruitment

The sole student working in this project will be Byungwoo Kang a thirdyear Physics major who worked with me last two summers on the initialphases of this project. Byungwoo made good progress specially in the lastsummer. This grant will be important motivation for him to continue thiswork during the academic year. With 5 to10 hours per week for the restof the academic year he can continue this progress and complete most ofthe required research so that this summer we can prepare the work forpublication in the Astrophysical Journal, the premier astronomical journalwhere we publish most of our research results. It is very likely that theresult of this research will be the main part of his honors thesis if he decidesto go that route.

The principal location where the research will take place will be in theVarian building where he will have a desk in a shared office with graduateand other undergraduate students in my research group next to my office.

Mentorship

Byungwoo will participate in our activities like the graduate students andpost docs. This will provide numerous encounters and discussion of his

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progress and future directions. In his research work Byungwoo is at thestage of first year graduate students and we have weakly discussion of hisresearch progress. He will be encouraged to also participate in our twiceweekly astrophysics gatherings, where many research topics are discussed,as much as his academic schedule allows.

Outcome of Past Projects

Two years ago the research work of William East, another undergraduatestudent in similar situation as Byungwoo, was supported by the VPUEprogram. That support led to a publication in the Astrophysical Journal(Petrosian & East 2008, ApJ, 682, 175) and an honors thesis. I expectsimilar achievements from Byungwoo. William East is continuing his careerat Princeton.

Budget

Student stipend: $1,400, for about 100 hours of work at $14/hr.Publication and Materials. $1,000 mainly for a 8 to 10 page paper forpublication.Total $2,400.

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Suzanne Pfeffer, Biochemistry

Transfer of cholesterol between NPC1 and NPC2 proteins

Summary:

Low density lipoproteins (LDLs) deliver cholesterol to cells by binding to cell surface receptors that internalize the plasma lipoproteins. LDL is transported to lysosomes where it’s cholesterol esters are cleaved by lipoprotein lipase and cholesterol is released for cellular use. Two proteins in lysosomes can bind cholesterol and are needed to transfer that cholesterol from inside lysosomes to the cytoplasm, where it is used for membrane synthesis, steroid hormone synthesis, metabolic signaling and other cellular needs. The proteins are named NPC1 and NPC2 for the so-called Niemann Pick Disease that ensues in patients carrying mutations in either protein. NPC2 is a small soluble protein that binds cholesterol; NPC1 is a much larger, transmembrane protein that spans the bilayer 13 times and binds cholesterol via its lumenal N-terminus. Studies from Brown and Goldstein at the University of Texas Southwestern Medical School have shown that NPC2 can transfer cholesterol to NPC1, but these scientists could not show direct interaction between these proteins (1,2). This lab has shown that another domain of NPC1 can bind directly to NPC2. The goal of this summer project is to identify the precise residues on NPC2 protein that interact with NPC1. This is important, as it will provide precise molecular detail regarding a fundamental and essential cellular process.

Project description: At left is a diagram showing the membrane topology of NPC1 protein. There are three large portions of the protein that face the lumen of lysosomes. Because this protein has 13 transmembrane domains, it is very hard to work with in the laboratory: it must be studied in detergent, which often interferes with interactions of other binding partners. We have bypassed this limitation by replacing the two transmembrane domains that flank lumenal domains #2 and #3 with antiparallel, coiled coil sequences that are expected to fold as depicted at left. These

soluble constructs are produced in animal cells; we have added a signal sequence to permit transit through the secretory pathway, and a 6-histidine tag to permit rapid purification of the domains by Ni-NTA chromatography. We have been able to purify domain #2 in milligram quantities from the conditioned medium of HEK293F cells (see below left) and we have used surface plasmon resonance to show binding directly to NPC2 protein purified from raw bovine milk (see gel below). The goal of this project will be to identify precise residues in NPC1 and NPC2 proteins that mediate their interaction.

VPUE Faculty Grant

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#1 #2 #3

Shown above left is a gel of the proteins we purified. We have shown that NPC1 domain 2 binds NPC2 (above middle panel), and our model is that this binding facilitates cholesterol transfer from NPC2 to NPC1 domain 1 which also has a cholesterol binding site (1). Matthew Scott and Dennis Ko (Stanford, ref. 3) previously identified a number of mutations on NPC2 protein that are needed for it’s function but not for cholesterol binding (see figure below). We will explore the importance of NPC2 residues D72, K75, K32 and D7 on binding. The binding we detect is pH sensitive with tighter binding observed at the lower pH normally found in lysosomes. The amount of charge present on charged amino acid residues will be influenced by pH and thus these residues are top candidates to mediate the interaction. The experimental approach will be to use site directed mutagenesis to generate mutations in NPC2; the proteins will be purified from the conditioned medium of cultured cells. Binding to NPC1 domain 2 will be tested by surface plasmon resonance by the PAN facility in the Beckman Center.

NPC2:

We also want to identify the precise residues in NPC1 domain 2 that mediate the binding, and we will test first a set of charged residues that cause NPC disease in patients (R404Q; R518Q). We have already generated these mutations in the context of our secreted, soluble domain 2 loop. The proteins will be purified from cultured cells and binding tested as before, by surface plasmon resonance. If the above candidate mutant versions of either protein do not show loss of binding, we will then carry out an alanine-scanning mutagenesis of all charged residues in the NPC1 domain 2 loop, as well as charged residues on the surface of NPC2 protein.

VPUE Faculty Grant

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Specific Student Responsibilities: The student (Emma Powell, now a Sophomore) will carry out site directed mutagenesis of NPC2 plasmids and will learn to grow and transfect mammalian HEK293F cells and purify the mutant NPC2 proteins that are secreted from cells. [Unfortunately, the published constructs are no longer available.] The student will learn surface plasmon resonance data analysis and interpretation. In addition, the student will learn conventional biochemical purification techniques that permit NPC2 to be isolated from raw milk: ammonium sulfate precipitation, ion exchange chromatography and gel filtration chromatography, followed by SDS-PAGE analysis. Deliverables: mutant proteins and vectors that encode them; purified NPC2 protein; hopefully, binding results for mutant proteins with wild type partners.

Mentorship: The student will work directly with Dr. Maika Deffieu, a postdoctoral fellow who has generated all of the preliminary data for this project. The faculty member will also interact with the student on a daily basis. The student will be expected to present research results at our weekly lab meetings and participate in weekly journal clubs, during which research articles are discussed and evaluated. The findings can develop into an independent honors thesis in subsequent quarters, with future analysis of domain 3 as a focus. Also for the future are establishment of cholesterol binding and transfer assays and tests thereof.

Anticipated Outcome: Co-authorship on a research article is possible, which will be of great help to the student when applying to graduate programs. This lab has not received VPUE funding for many years, but all undergraduates who have trained here have gone on to very successful postgraduate careers: Victor Velculescu, MD/PhD Johns Hopkins; Kristin Kwan, Harvard PhD; John Hanna, Harvard MD/PhD; Collin Melton, UCSF PhD program; Sagar Bapat, UCSD MD/PhD program.

Budget: Student stipend: $5600 ($14 per hour, 40 hours per week, 10 weeks over the summer)Project materials: $500 surface plasmon resonance PAN core facility charge

References:

1. Kwon HJ, Abi-Mosleh L, Wang ML, Deisenhofer J, Goldstein JL, Brown MS, Infante RE. Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol. Cell. 2009 Jun 26;137(7):1213-24.

2. Wang ML, Motamed M, Infante RE, Abi-Mosleh L, Kwon HJ, Brown MS, Goldstein JL. Identification of surface residues on Niemann-Pick C2 essential for hydrophobic Handoff of cholesterol to NPC1 in lysosomes. Cell Metab. 2010 Aug 4;12(2):166-73.

3. Ko DC, Binkley J, Sidow A, Scott MP. The integrity of a cholesterol-binding pocket in Niemann-Pick C2 protein is necessary to control lysosome cholesterol levels. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2518-25.

VPUE Faculty Grant

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Undergraduate Research Supporting Faculty Digital Theatre Words (DTW) An Internet Accessible, Interactive Dictionary of Theatrical Terms and Concepts in Forty Languages Michael Ramsaur, Department of Drama Michael Rooney, Civil Engineering major, and Jacob Boehm Music major will work as research assistants with Michael Ramsaur on a vast writing and editing project – a lexicon and dictionary of 2,400 theatre design, technical and performance terms in forty languages called Digital Theatre Words (DTW). Michael and Jacob will take on the task of receiving and organizing material (terms, descriptions and images) from over 150 contributors from around the world. These contributions, after editing, will be made available on an Internet web page provided by the International Organization of Scenographers, Theatre Architects and Technicians (OISTAT). Rather than structuring the DTW project database around words in English with translations of those terms into other languages, the database is structured from a description of each term described in each country’s own language, often with three-dimensional and sometimes interactive illustrations. Thus DTW will be able to present a significant understanding of the term within its cultural origin and practice from which the term is derived. The students will be performing individual research on finding or creating images for many of the terms. These images will be of value in the understanding of each term. The images will become a reference for the interactive aspect of the project which allows DTW users to search the database by image, as well as searching by word. For ease of gathering information, DTW is organized into 11 specific word groups: Performance, Lighting, Sound, Media and Protocols, Special Effects, Architecture and Building, Scenery, Rigging and Machinery, Electric, Administration and Management, and Costume. Michael and Jacob will be responsible for specific word groups. This is a project facilitated through the many contacts I have made over the last fifteen years working with OISTAT, and researching international trends in theatrical lighting design. The DTW project involves collaboration among a group of outstanding colleagues from institutions around the word including Royal Welch College of Music and Drama, RITS School Brussels, Central Academy of Drama Beijing, Shanghai Drama Academy, Institut del Thetre Barcelona, University of Novi Sad Serbia, University of Tel-Aviv, National Academy of Art Sofia, The Arts University College at Bournemouth Dorset, Moscow Art Theatre School, Lithuanian National Opera, Royal Danish Opera, Opera de Montréal, Scottish Opera, Malmo Opera Sweden, English National Opera, Hong Kong Academy of Performing Arts, Taiwan National University of the Arts, La Scala Opera, Makerere University Uganda, and (as you can imagine for a project of this scope) many more. A valuable component of this project is that all information will be accessible worldwide through the Internet. Each theatrical term will be accessed via a sophisticated multi-lingual interface designed in Belgium by Jerome Maeckelberg, my

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major colleague in this project. The operational interface is designed so that each user will be able to navigate DTW in his or her native language. Michael Rooney and Jacob Boehm are highly experienced in theatrical production and active in lighting design both with the Drama Department and with other student groups on campus. They will meet weekly with Michael Ramsaur for coordinating and advising sessions. The two students will each work 10 hrs. a week for winter and spring quarters to bring this project to completion. The students will then join the OISTAT World Congress and DTW contributors in Prague to celebrate the release of the project which will go “live” at the Congress, June of 2011. The Congress will takes place concurrently with the Prague Quadrennial Student Scenofest. By attending the World Congress, Michael and Jacob will also be able to interact with students from around the world, some of which have acted as research support for their teachers who have contributed to DTW. Assisting on this project will provide Michael and Jacob a unique opportunity to meet and network with world leaders in the various aspects of the theatrical discipline. They will be a part of an international project that will aid thousands of theatre practitioners and researchers, and they will gain a boundless knowledge of the workings of many theater cultures. An example of the DTW project can be seen at http://www.youtube.com/watch?v=AHcd9pYFRG8 Budget: 1 student working 10 hours/week Winter and Spring Quarters 2,600 1 student working 10 hours/ week Winter and Spring Quarters 2,600 2 students hotel & per diem costs Prague at the 1,200 OISTAT Congress DTW release ceremony 2 student air travel to Prague 4,800 Total Project 11,200

Joseph C. Wu, MD, PhD VPUE Grant Application

Clinical Hurdles to Stem Cell Therapy

Progress Summary from Previous Cycle

During the academic year and summer 2009-2010, our laboratory received support from VPUE

to fund two undergraduate students (Wendy Zhang and Divya Nag; both current Stanford

sophomores). Due in large part to the support provided by VPUE, over the past ten months

Wendy and Divya have been able to dedicate significant amounts of time to the laboratory. They

have developed a strong initial basis for methods of scientific inquiry and built a basic level of

expertise in experimental techniques involving stem cell biology and non-invasive molecular

imaging. The contributions of Wendy and Divya have resulted in three co-authorships in

manuscripts published in peer reviewed journals (Wilson KD et al, Cancer Research 2010;

Nguyen PK et al, Advanced Drug Delivery Reviews 2010; Nguyen PK et al, Journal of Nuclear

Cardiology, in press). This is especially impressive considering that both Wendy and Divya

entered the laboratory as freshmen in the Fall of 2009.

From my individual conversations and regular mentorship sessions with these two students, I

strongly believe Wendy and Divya are on track to establish a strong foundation for their future

careers in biomedical science and academic medicine. For this next cycle, I hope to support a

total of three students (Wendy Zhang, Divya Nag, Nam Nguyen) with help from VPUE. Given

their previous track record of excellence and dedication to the laboratory, I am excited to watch

these students continue to develop toward becoming independent researchers and scientists.

Introduction

Our laboratory focuses on utilizing human embryonic stem (hES) cells to regenerate tissues and

organs. In contrast to adult stem cells, hES cells are capable of unlimited self-renewal and are

pluripotent, meaning they can differentiate into any cell type of the human body. This capacity of

hES cells to form cells traditionally considered "post-mitotic" such as cardiomyocytes, neurons,

and pancreatic beta island cells has stimulated hope that ES cell based therapy will one day be

able to treat ischemic heart disease, stroke, diabetes, and other causes of morbidity and mortality.

Joseph C. Wu, MD, PhD VPUE Grant Application

Indeed, a number of reports in the past ten years have demonstrated that hES cells have the

capacity to act therapeutically in the heart, brain, skeletal muscle, pancreas, liver, and blood.

Before the potential of hES cells can be realized in the clinic however, a number of hurdles must

first be addressed. My laboratory uses molecular imaging and basic molecular biology to study

two of these issues: 1) immunogenicity of hES cells and their therapeutic derivatives and 2) the

capacity of undifferentiated hES cells to form tumors (teratomas) in patients. I currently have 11

postdoctoral fellows and 2 graduate students. I have funding support from the NIH Director’s

New Innovator Award (2008-2013) and the NIH Transformative Roadmap R01 Award (2009-

2014) to execute these studies.

Immune rejection of hES cells is due to the fact that hES cells and their derivatives are not “self-

derived”, but instead originate from a donor blastocyst. Animals that receive therapeutic cells

derived from ES cells in allogeneic transplant models will often mount an aggressive immune

response to these cells resulting in poor engraftment and survival of delivered cells. The potential

for teratoma development in patients that receive ES cell based therapies is a second critical

issue. Teratomas are complex tumors composed of derivatives of all three germ layers. Failure of

ES cells to properly differentiate into therapeutic derivatives can result in the development of

these tumors in animals or patients that receive these cells. A recent case of stem cell derived

teratoma formation was reported last year in PLoS Medicine in which a young boy receiving

fetal neural stem cell transplantation in Russia for treatment of ataxia telangiectasia developed a

brain tumor. As the issues of immunogenicity and teratoma formation are two significant clinical

hurdles to the implementation of ES cell based therapies that have not been fully addressed it is

imperative that exceptionally innovative, high-risk, and original strategies be developed to

address these critical issues.

By training three highly motivated sophomore undergraduate students to become independent

investigators in basic science, I hope to contribute to the future development stem cell research

by the early addition of new and young researchers to the field of regenerative medicine.

Specifically, I aim to augment their educational experience at Stanford through exposure and

participation in two main project areas outlined below.

Joseph C. Wu, MD, PhD VPUE Grant Application

Immunogenicity

Divya Nag and Nam Nguyen will investigate immunogenicity of hES cells and their derivatives.

This project was initiated in the Fall of 2009 and is ongoing. The aims and deliverables are:

Specific Aim 1: To characterize the immunogenic surface marker profile of hES cells and

hES cell derived endothelial cells and cardiomyocytes.

Specific Aim 2: To test several candidate immunosuppressive drug cocktails to induce

peripheral tolerance to hES cells and their therapeutic derivatives in an allogeneic cell

transplant model.

Divya and Nam have made significant progress toward both these aims over the past year. For

this coming year, Nam and Divya will be supervised by two of my postdoctoral research fellows

Patricia Almeida, PhD, and Ning Sun, PhD, a well as graduate students Jeremy Pearl and

Andrew Lee. Given the current rate of progress, I anticipate this project will be finished by the

end of 2011 and ideally lead toward a subsequent honors thesis projects for both Nam and Divya

once they enter their junior and senior years at Stanford.

Tumorigenicity

The potential for post-transplantation formation of teratomas in patients receiving ES cell based

therapies is a critical issue that has yet to be addressed. It is thus extremely important that novel

methods of imaging teratoma formation are developed for the early detection of these tumors

following delivery of ES cell derived therapeutic cell populations into patients. Wendy Zhang

will work on novel methods of detecting ES cell derived tumors via positron emission

tomography (PET) radionuclide imaging.

Specifically, Wendy will have two deliverables:

Specific aim 1: To screen a library of clinical and custom developed PET probes for

detection of teratoma formation in immunodeficient animals.

Specific aim 2: To test the capacity of probes specific for teratoma surface markers to

carry chemotherapeutic drugs for targeted delivery to the tumor.

Joseph C. Wu, MD, PhD VPUE Grant Application

In the past year, Wendy has generated significant data toward the above aims, part of which has

resulted in her publishing a co-author paper (Wilson KD et al, Cancer Research 2010). Wendy

Zhang will continue to work under the guidance of my postdoctoral fellow Feng Lan, PhD, and

graduate student Andrew Lee to screen a library of existing PET probes for binding specificity to

protein motifs uniquely expressed on the surface of teratoma tumors. I am confident she will

continue to make accelerated progress toward completing the aims of this project again with the

hope this project will lead to her own individual honors thesis project as an upperclassman.

Mentorship

Wendy, Divya, and Nam have performed very well in the past year both intellectually and in

terms of data generation. My interactions with these students have been both personally and

pedagogically rewarding. I have a number of structured teaching and mentoring mechanisms in

place to develop the research capability of these three students. These include group meetings

and individual advising sessions. We have weekly lab meetings which typically last two hours

and include a short progress report from each person in the laboratory plus a formal and more

detailed presentation of recent data and proposed studies from one or more individual lab

members. Given the interrelated nature of the various projects in the lab, these meetings have

been an excellent opportunity for critical review of primary data and mentoring in experimental

design and data interpretation.

For their past year in the laboratory, Wendy, Divya, and Nam have presented formal updates of

their progress in group meeting sessions every two months, and met with me on a bi-weekly

basis for personal mentorship and advising sessions. During these sessions, I have discussed and

analyzed their recent results, helped them troubleshoot any technical problems, and addressed

specific questions they have regarding their projects.

For the coming year, Nam, Divya, and Wendy will attend several scheduled interdepartmental,

multidisciplinary collaborative meetings and classes in addition to lab meetings. These include

auditing Dev Bio 296 (Stem Cell and Regenerative Medicine) for which I am a lecturer, and the

MIPS weekly molecular imaging and stem cell biology program seminars, which feature

renowned academicians from a variety of disciplines. In conjunction with the above described

training plan, Nam, Divya and Wendy will attend several scientific meetings during the year,

Joseph C. Wu, MD, PhD VPUE Grant Application

including the AHA and Keystone meetings on regenerative medicine. This past year both Wendy

and Divya attended the ICCSR meeting in San Francisco.

For technical guidance, Nam, Divya, and Wendy will be matched with several postdoctoral

research fellows and graduate students. Nam and Divya will work with postdoctoral fellows

Patricia Almeida and Ning Sun each of whom has a multi-year track record of publication on

stem cell biology. They will also work closely with Jeremy Pearl, an MD/PhD student studying

stem cell immunology. Wendy will work with a synthetic chemistry fellow Feng Lan, and

Andrew Lee, a graduate student who has an expertise in molecular imaging of stem cells.

Through the guidance of these senior research fellows Nam, Divya, and Wendy should become

proficient in an array of techniques ranging from hES cell culture to fluorescence activated cell

sorting to PET imaging. At the end of their fellowship year, they will be equipped with many

state-of-the-art research techniques and an understanding of the nuances that render each one

challenging. More importantly, they will have learned how to utilize the appropriate molecular

tools to answer relevant scientific questions.

Joseph C. Wu, MD, PhD VPUE Grant Application

Budget Proposal

1. Student Stipend or Wage Description:

Three students for academic year 2010-2011, total of 3 quarters at 10 hours/wk for 10 wks/quarter: $4,200 per student x 3 = total of $12,600 for 3 students

2. Student Travel Expense Description

Keystone Conference for Molecular Cardiology: Disease Mechanisms and Experimental Therapeutics in Keystone, Colorado. Student Registration: $500 for two students, Travel+Lodging: $600 = total of $1,600 for 2 students.

3. Student Research Supplies Description

Flow cytometry booking reservations, reagents for cell culture, animals for stem cell transplant models: $500 per student, total of $1500 for 3 students.