PI: Aboushala, Ayman
Title: Safer Chemicals Management: An Economic Development Perspective
Abstract: The purpose of this study is to investigate the apical sealing properties of EndoRez and Epiephany systems by quantitatively determining of the leakage with radioactive isotopes.

Leakage has been assessed using varying experimental designs. Most commonly dye penetration has been used to evaluate the apical seal, but other techniques include scanning electron microscopy, bacterial penetration studies, pressurized fluid measurements, electrochemical methods, radioactive isotopes detected by autoradiography, scintillation spectrometry, and gamma counters.

In this study, apical leakage will be analyzed quantitatively using radio labeled tracers that will be detected and measured using a new method "liquid scintillation counting". For each tooth, samples will be immersed for periods of time in the radioactive solution so that changes in the quality of the seal over time could be analyzed. Radioisotopes micro leakage technique is particularly of importance, it can provide a quantitative numbers of the leaked radioisotope particles instead of rate and percentage.

PI: Ackerman, Frank
Title: Safer Chemicals Management: An Economic Development Perspective
Abstract: In this proposal the Global Development and Environment Institute (GDAE) at Tufts University offers to perform a study of the links between safer chemicals management and economic development. This study is intended to help place chemical issues on the agenda of decision makers involved in planning international development programs, and to lay the groundwork for establishing safer chemicals management as a component in Sweden's international poverty reduction programs.

Exposure to toxic chemicals can cause severe and sometimes irreversible damage to human health, including cancers, endocrine and neurological disorders, birth defects, and learning disabilities. In addition to the human suffering produced by avoidable toxic exposures, these exposures have economic effects. The costs of treating environmentally induced illnesses deplete the resources of individual families and can strain the capacity of government agencies that provide health and social services. When fetal, infant, or childhood exposure to toxic chemicals impairs the ability of children to learn and develop normally, the long-term costs to an economy can be enormous. The economic problems associated with toxic exposures have been explored in more detail in the context of the developed world, but the problems are often even more severe in developing countries.

The public health effects of chemical exposures, and the attendant economic impacts, make it particularly important for economic development plans to include a chemicals management component. In the study, we will make the case that better chemicals management and stronger chemicals control can have significant economic benefits and contribute to economic growth, social welfare and poverty reduction. The study will review and interpret results from existing case studies that have been carried out in the developed as well as the developing world. Our study will draw an explicit link between chemicals management decisions and the overarching goal of poverty reduction.

PI: Afsar, Mohammed
Title: Dielectric Spectroscopy in the Millimeter Wave Frequency Range
Abstract: The primary objective of this feasibility study is to determine if there are unique signatures for materials of interest that can be determined by dielectric spectroscopy in the MMW frequency range. This study will create a library of such spectra and assess their specificity. An associated objective is to determine penetration of MMW energy through common container materials. A concept for searching mail, bottles, packages, using these or similar measurement techniques will be developed.

Tufts University shall use existing laboratory MMW equipment to determine the transmission and reflection spectra of appropriate materials of interest that one might find in a security screening application. These materials are to include: simulants of hazardous materials; benign materials that might be used as hoaxes, common packaging materials; and other common benign materials that might be found in containers. All materials to be tested must be approved for use within Tufts University lab spaces. Also, Tufts University will determine penetration through common packaging material and containers. Spectra for these materials should be determined over the MMW frequency range.

Proposed tasking is as follows:

• Develop a materials list for testing and submit for review and concurrence by the Government. This list should comprise a common sub-set of materials that can be tested in the Tufts University lab. These materials should be similar in nature (similar MMW dielectric signatures) to materials that might be found in a security screening application. The list of materials to test is limited to 12 items as defined in the Statement of Work C.3.6 Parts 1 and 2.
• Develop a methodology to determine the dielectric properties for the materials identified above. This should include an assessment of what data already exists for these materials, what part of the spectrum is of most interest or useful, and what measurement techniques to employ.
• Measure the MW/MMW dielectric spectra of various materials/stimulants independent of the requirement of closed containers. Provide the spectral data as a deliverable.
• Develop a report that describes the results of the spectral measurements. Include recommendations on the feasibility of making these spectral measurements to support a screening scenario for detection of hazardous materials and contraband.

PI: Agyeman, Julian
Title: Urban Audiences and Environmental Education
Abstract: The researcher, through the services of Julian Agyeman in his capacity as principal investigator, as well as other university faculty and student interns shall conduct a study at Mass Audubon's Boston Nature Center, in Mattapan, and Broad Meadow Brook Wildlife Sanctuary I in Worcester. The research will address these questions:

• To what extent do these sanctuaries currently engage socio- economically and culturally diverse audiences in sanctuary-based activities?
• What currently employed practices at these sanctuaries contribute to engaging socio- economically and culturally diverse audiences?
• What are the barriers that keep under-represented audiences from engaging in sanctuary-based activities at these sanctuaries?
• What are the most effective strategies, existing or new, to engage socio- economically and culturally diverse audiences in an inclusive manner?

PI: Balaban, Naomi
Title: Quorum Sensing and Staphylococcus Aureus Pathogenesis
Abstract: This proposal is responsive to PA-03-080 on "Biodefense and emerging infectious disease research opportunities". Our aim is to better understand how virulence is regulated in Staphylococcus aureus and to further develop immunotherapy to staphylococcal infections. S. aureus cause food poisoning, sepsis, device (Biofilm) related infections, and multiple diseases like endocarditis and pneumonia. The numerous toxins produced by the bacteria are at the heart of these diseases and cause more than 50,000 deaths each year in the US alone. As food and device-associated infectious organism that can survive in multiple environments, S. aureus is a potential target for bioterrorism. Many of the infective strains are resistant to conventional antibiotics and alternative methods to prevent and treat such infections are mandatory. We discovered that the production of toxins is regulated by quorum sensing mechanisms, where proteins such as RNAIIl activating protein (RAP) are secreted by the bacteria and induce virulence. RAP (native or recombinant) activates S. aureus pathogenesis through the histidine-phosphorylation of TRAP in a still unknown manner. TRAP has been shown to be membrane-associated, but it lacks a predicted transmembrane domain and a kinase domain typical of two component system sensors. Our first hypothesis is that TRAP is bound to the membrane through another protein and that this protein acts as the actual receptor to RAP. Studies proposed in Specific Aim 1 are focused on identifying this receptor. RAP has been shown to serve as an effective vaccine to prevent S. aureus infections. Our second hypothesis is that monoclonal anti RAP antibodies may be used for immunotherapy. This will be tested under Specific Aim 2, using a panel of clones already available. Such immune intervention would greatly benefit people suffering from acute drug resistant infections or surgery-related infections often associated with implantable medical devices.

PI: Beinfeld, Margery
Title: CCK in Generating Enzyme - Structure, Location and Role
Abstract: Prohormone convertases PC1, PC2 and PC5 are good candidates for the enzymes responsible for the post-translational processing of CCK in rodent brain. PC2 is essential for normal pro CCK processing in some mouse brain regions, although there is clearly another enzyme(s) that processes pro CCK in place of PC2. Knowing the extent of colocalization of PC1 and PC5 with CCK will indicate whether they are candidates for the enzyme(s) that work in concert with PC2. We have made significant progress toward understanding how the sequence of pro CCK determines where it is cleaved and what cleavages are required for production of amidated CCK in an endocrine cell line. Proposed site-directed mutagenesis and expression studies would extend our understanding of this process. Tumor cells have been very useful to study pro CCK processing, but they are not good models for pro CCK processing in rodent brain. The use of antisense strategies to inhibit the expression of these enzymes in organotypic rat brain slices will allow us to learn more about their role in CCK processing. Together these experiments represent an integrated and novel approach to understanding the biosynthesis and processing of pro CCK in endocrine tumor cells and in rodent brain. The experiments test the following hypotheses: 1). PC1, PC2 and PC5 comprise a redundant system to insure production of active CCK in rodent brain. 2). Pro CCK has 3 dimensional structure that influences where it is cleaved. This structure changes as it is processed, making other sites more accessible to subsequent cleavage. The overall goal of this work is to understand the mechanism and enzymology of post-translational processing of pro CCK. CCK is known to be an important element in the neurochemical balance that is essential for normal nervous system function. The following Specific Aims are proposed: 1. The distribution and co-localization of PCI, PC2 and PC5 mRNA with CCK mRNA will be determined using in situ hybridization histochemistry in rat brain. In parallel, the colocalization of PCI, PC2 and PC5 enzyme protein with CCK immunoreactivity will be determined using immunohistochemistry. 2. Ongoing studies on the effect of altering the sequence of rat pro CCK on its processing in pituitary At-T20 cells will be continued. 3. The importance of PCI, PC2 and PC5 for pro CCK processing will be determined using organotypic rat brain slices in culture. Inhibition of enzyme expression will be achieved by incubation with peptide nucleic acid compounds, specific antisense oligonucleotides, double stranded RNA, DNA transfection and/or treatment with viral vectors expressing antisense cDNAs. The effect of this inhibition on the processing of pro CCK will be determined.

PI: Bers, Marina
Title: Communities of Learning and Care: Multi-User Virtual Environments that Promote Positive Youth Development
Abstract: We live in a society where concepts of self and community are constantly changing. This context makes it challenging for young people to construct a sense of self and grow into contributors to civil society. This becomes even more challenging for youth suffering from a severe chronic illness that requires medical interventions such as heart and kidney transplant. In the past, most of this young people wouldn't survive. Today, the current advances in medicine make it possible not only to extend their length of life, but also their quality. However, major life style changes and compliance to demanding medication and dietary regiments are needed. Technology can tackle this challenge by integrating already existing face-to-face psycho-educational programs with virtual environment aimed at fostering community building and social support.

My career goal is to develop a groundbreaking research program and teaching career in the area of technologies to foster youth positive and healthy development. My first step is to work at Boston's Children's Hospital with young people suffering from severe renal and cardiac failure that wouldn't survive without an organ transplant and who, are at risk of developing mental-health related problems. Later on, I plan to extend this work to other settings for young people at risk, such as community-based organizations and after-school programs. I will investigate how multi-user virtual environments specifically designed to foster new kinds of communities of learning and care can lead to positive youth development. I coined the term identity construction environments (ICE) to refer to these technologies.

The applied developmental science model provides a framework to design ICE. It also provides a model for doing research in complex real-world settings. It is my career goal to build on this framework by exploring three general hypotheses. First, ICE promotes positive youth development, measured in regard to the development of the six C's of positive development: competence (i.e. compliance and technological fluency), connection, character, confidence, caring and contribution to civil society. Second, ICE complement and augment the effects of face to face psychosocial interventions. Third, the positive effects are due to the design features of ICE and the nature of the on-line activities that engages youth in cognitive, social and emotional development.

Exploring these hypotheses involves conducting interdisciplinary research, developing new technologies, such as the Zora graphical multi-user environment, and a set of assessment and professional training strategies, and critically evaluating them in the complexities of a real-world setting, such as Boston's Children Hospital. This three-fold program makes 1) theoretical contributions by providing an interdisciplinary framework to enable collaboration between computer scientists and child development experts; 2) innovative designs of technologies that can be scalable and sustainable to promote positive youth development; and 3) empirical research to evaluate results of interventions using these technologies in real-world settings.

PI: Blumsack, Marilyn
Title: Tufts Institute for Lifelong Learning
Abstract: Founded in fall 2000, The Tufts Institute for Lifelong Learning (TILL) is now a mature, proven center of life-long learning for the retired and near-retired population in the greater Boston area. During calendar year 2004, it served 230 participants who accounted for 435 course enrollments. It offers study groups of varying length, a Lunch and Learn series, and regular off-campus special event. It maintains a collaborative relationship with Lexington's Brookhaven retirement community.

TILL seeks support from The Bernard Osher Foundation for two purposes: to increase its membership and to broaden the scope and number of its core eight-session and four-session study group offerings. These objectives are not mutually exclusive. Both are essential to achieving the financial strength that will ensure the Institute's future. To that end, a first-year grant of $99,000 and any subsequent yearly grants of similar amounts from the Foundation will be used to invest in membership and program development by:

• Hiring a professional-level fulltime associate director with primary responsibility for developing and implementing an enhanced and expanded marketing program.
• Supporting this larger marketing effort with adequate resources and focusing it on attracting members from TILL's "home town" communities of Medford and Somerville and on the suburbs north and west of Boston.
• Supplementing TILL's cadre of volunteer study group leaders each academic year with from four to six faculty or graduate students who will receive stipends of $2,000 to $3,000 per study group. These faculty members will teach subjects of known interest to TILL's members but in which no member possesses the expertise to serve as a volunteer study group leader. They will be drawn only from Tufts faculty, faculty emeriti, and graduate students and will be used sparingly so as not to undermine TILL's ongoing, fundamental commitment to peer learning.

Our goal will be an active membership of 300 in no more than three years.

PI: Bohm, Andrew
Title: Molecular Basis for Inhibition of Edema Factor
Abstract: The objective of this project is to find small molecule inhibitors of the anthrax protein Edema Factor (EF). This toxin is secreted by Bacillus anthracis in a catalytically inactive state. When the toxin is transported into the cellular cytoplasm of anthrax victims by the anthrax-derived transporter, Protective Antigen, it forms a complex with calmodulin (CAM) - the key intracellular calcium-binding protein in vertebrates. This association activates EF, and converts it into an adenylyl cyclase with 1000 times greater catalytic activity than the victim's own cyclic AMP-producing enzymes. Conventional anthrax therapies (which target the anthrax bacterium, not the anthrax toxins) are highly effective, but are insufficient to save all anthrax victims. EF inhibitors represent a completely distinct, and wholly complementary approach to combating anthrax. Such inhibitors will, by treating the downstream effects of the disease, help restore cellular equilibrium, and are likely to slow the course disease. By allowing more time for conventional treatments and the immune system to work, these inhibitors may significantly increase anthrax survival rates. We have solved crystal structures of EF (the inactive state) and the EF/CaM complex (the active state). Using these structures as a guide, and in close consultation with pharmaceutical researchers, we will use structure-based, computational drug discovery methods to identify small molecules representing two distinct types of EF inhibitors; Type A, inhibitors that occlude the active site, and Type B, those that maintain EF in its CAM-free, catalytically inactive state. We already have assays for inhibitors of Type A. We will complete the development of a simple assay for inhibitors of Type B, and then apply these assays to the top approximately 1000 compounds suggested by our computational drug screens. We will also determine the crystal structures of EF in complex with those small molecules identified by this screening procedure, so that the pharmaceutical properties of these inhibitors may be improved through rational drug design methods.

PI: Bratt, Rachel
Title: Women’s Institute for Housing and Economic Development: 1981-2006
Abstract: The mission of the Women's Institute is to build affordable housing that fosters economic security for low-income women and families. For nearly 25 years, they have worked with community-based organizations to create affordable housing and programs for low- income and homeless women and families. Recognizing that families benefit from community-based programs and thrive in environments where they can develop peer supports, WIHED has have worked in partnership with over 50 community-based organizations that provide programs and activities to increase women's economic and family stability. Their more than 420 completed units of innovative housing include community spaces that promote skill development and family well-being. In short, WIHED has created programs that give women the tools to make sound economic choices for their families.

As part of their efforts to increase their internal capacity, and in order to "deepen and extend their impact in Boston and nearby communities, WIHED has indicated an interest in partnering with the Department of Urban and Environment Policy and Planning (UEP). The UEP faculty has longstanding relationships with Boston-area nonprofit organizations and a commitment to community-based development. UEP also combines a unique focus on housing, community development, and child and family issues.

As part of WIHED’s 25th anniversary celebration, it will be useful and informative to develop a history of their organization, tracing their formation, changes in orientation over the years, major accomplishments, and challenges. This will involve delving into organizational records, interviewing past and present personnel and board members, as well as interviewing key public officials and other nonprofit organizations with which WIHED has interacted most closely.

An important part of the case study will involve a qualitative and quantitative examination of a select number of projects (maximum of three) developed by WIHED, including the impacts on families, where this information is readily available. Another major focus of the case study will be on the steps and decisions that led to the creation in 2002 of WIHED’s Center for Supportive Communities and on the achievements of this center, to date.

As WIHED has evolved, and as the development process has become more complex, it is increasingly important to develop accurate ways of tracking their activities, thereby creating an ongoing vehicle for monitoring their projects and chronicling what they have learned. To this end, under this contract Tufts researchers will develop a comprehensive plan for evaluating their current and future projects. As part of this effort, we will develop a series of evaluative questions that pertain to the development process and appropriate instruments for collecting the necessary data. We anticipate that these instruments will be usable by WIHED staff, and that annual reports will be easily generated.

PI: Brenner, Brian
Title: Developing a Library of Bridge Models
Abstract: This proposal is an extension of work by the Tufts University Civil and Environmental Engineering Department, working with fellows of the NSF funded Tufts Engineering the Next Steps (TENS) GK-12 Project, to develop buildable model bridges of different structural types. The models are used for outreach in Massachusetts classrooms, grades 1-6. The working models demonstrate different types of bridge design, architecture, and construction methods as they are assembled by grade school students in a way that simulates the actual construction process. This library of bridge models will be used to foster outreach to schools, interest in k-12 education by current college students, and awareness of architecture and design in our communities.

PI: Brodeur, Peter
Title: Organization and Expression of V Genes
Abstract: Antigen specific receptors of B and T lineage cells require the somatic assembly of V, D, and J gene segments during lymphocyte development. Immunoglobulin and T cell receptor loci are targeted by a common V(D)J recombinase in a cell type- and developmental stage-specific manner. The fundamental control of this process occurs at the level of alterations in chromatin structure that confer locus "accessibility" to the RAG1/2 complex. The immunoglobulin heavy chain locus (Igh) is the first to rearrange during B cell differentiation and accessibility at different stages is limited to discrete domains. The cis-acting elements and signaling pathways that regulate accessibility throughout the Igh locus are yet to be fully elucidated. Since V(D)J recombination is required for normal lymphocyte development, defects in the process result in both subtle and catastrophic immune deficiencies. Thus, understanding the underlying mechanisms has obvious implications to health and disease. Our long term goals are focused on the control of Igh locus accessibility within the nearly 3 megabase region containing approximately 200 Vh gene segments. In this application, we propose to extend our studies of a candidate control region in the 5' boundary of the lgh locus that exhibits early B cell specific chromatin remodeling. This novel region interacts, both in vitro and in vivo, with factors that have been implicated in Igh accessibility and rearrangement. We propose to examine sorted early B cell subsets from bone marrow to determine the precise stage of B cell development at which this element is active. Gel shift and chromatin immunoprecipitation approaches will be used to define the factors that are recruited to the multiple sites mapped within this region. The function of this putative regulatory element will be tested by both genomic deletion and studies of BAC transgenes containing putative control regions and Vh segments of the 5' region of the locus. We will use a novel cell line model as well as primary bone marrow cells to determine the mechanism through which IL-7 receptor signaling selectively mediates D-distal (5') Vh gene accessibility.

PI: Bullock, Peter
Title: Initiation of SV40 DNA Replication and Its Regulation
Abstract: Many DNA tumor viruses encode "initiators" proteins that site specifically bind to viral origins of DNA replication. Upon binding to their respective origins, the initiators assemble into DNA helicases that are capable of melting duplex DNA. Initiators also recruit cellular proteins required for synthesis of nascent DNA. We are attempting to understand these processes by characterizing in depth an initiator encoded by Simian Virus 40, termed T-antigen (T-ag). Using the Simian Virus 40 system and simple band shift experiments, a fundamental question in biology will be addressed: "how does the cell cycle machinery control the assembly of initiators on viral origins of replication?" Recent experiments with T-ag derived peptides, whose ability to bind to DNA is regulated by phosphorylation of Thr 124, are providing significant insights into this process. Experiments are proposed to determine if similar mechanisms are operating in the context of T-ag. Related aspects of T-ag assembly and regulation will be considered, such as locating a site on T-ag whose interactions with the flanking sequences in the core origin is necessary for T-ag binding. Collectively, these studies will provide information that may allow us to solve the mechanism of DNA unwinding. Once the SV40 origin is unwound, the pol alpha-primase complex initiates the synthesis of nascent DNA strands. Exactly what sequences constitute the initiation sites for the pol alpha-primase complex is the topic of an additional series of experiments. Given that many basic processes are conserved throughout evolution, we are confident that the information we obtain from these studies will be pertinent to the initiation of DNA replication at other viral origins of replication. Furthermore, they may help us to understand how the cell cycle machinery controls initiation events at cellular origins. Given that uncontrolled DNA replication is thought to be a component of many diseases, including cancer, it is very important to understand how DNA replication is initiated and how it is controlled.

PI: Cao, Caroline
Title: Adapting to Technology in Minimally Invasive Surgery
Abstract: In the project "Adapting to Technology in Minimally Invasive Surgery", we proposed to involve undergraduate students as summer interns on small projects within the main research activities. There is evidence in the literature to support the importance of early exposure of undergraduate students to research. Our previous experience with REUs further support this. The work with these students produced 2 scientific conference posters, one presented at the annual meeting of the Society of American Gastroenterology and Endoscopic Surgeons (SAGES), the other at the annual meeting of the Human Factors and Ergonomics Society. One student continued with the work in the lab following her summer experience and submitted an honors thesis. She is now a graduate student in our program, continuing this research.

The summer project for the undergraduate students this year will be well-defined and will complement the on-going research activities which include an evaluation of new technology for training minimally invasive surgical skills. We are continuing with our study of a new genre of technology related to minimally invasive surgery -surgical skills training simulators. Surgical simulators promise to be the next revolution in surgical training, as flight simulators revolutionized pilot training. Contrary to the popular belief that virtual simulators is the key to a flexible and comprehensive technical skills training program for surgical residents, our research thus far has indicated that a real simulator (SAGES FLS) is more sensitive than a virtual simulator (MIST -VR) as a surgical skills assessment tool. This may be a function of the lack of maturity of the virtual technology. Our goal is to combine the best of both worlds and develop a training module that employs augmented reality (real + virtual features). We have recently acquired an augmented reality system and are ready to carry out an evaluation of this simulator. In addition, we are interested in developing new modules to train dynamic surgical skills.

The systems are housed in the Tufts-New England Medical Centre (NEMC). The research lab has full access to the surgeons and residents who work at NEMC. This research setting, as well as the research activity, provides an excellent opportunity for undergraduate students to learn about the research and acquire hands-on experience in conducting their own research projects. In addition, NEMC is the official SAGES training and testing center for all surgeons who practice minimally invasive surgery in the New England area. We have a unique opportunity to recruit surgeons from all over New England to participate in our study on surgical skills training.

PI: Catley, Andy
Title: Case Study on Emergency, Pastoralists and Food Security in South Sudan
Abstract: There is an increasing recognition that complex emergencies and man-made disasters have become the most important causes of food insecurity and famine. Responses to such emergency situations are generally of a humanitarian/emergency nature that, while contributing to saving lives and (sometimes) to protect livelihoods, are generally inadequate in addressing in a sustainable manner the complex root causes of the problem. This may be partly attributable to a dearth of long-term policies and strategies for addressing food security problems in a sustainable manner in protracted emergency contexts. Such policy gap was highlighted during the 'International Workshop on Food Security in Complex Emergencies: building policies frameworks to address longer-term programming in complex emergencies' organized by FAO- ESA (Tivoli 23-25 September 2003).

A series of case studies were thus launched by FAO-ESA to contribute to such on-going research process in three countries under complex emergencies conditions: RDC, Somalia and Sudan. In the cases of Sudan a preliminary review was undertaken during the months of June and July 2004 that: a) defined and tested a framework for analysis of food security in complex emergencies context; b) provided an overview of the food security situation in Sudan (with a focus on south Sudan) and related responses and of the links of the responses with stakeholders strategies and information flows; c) extracted some preliminary hypothesis and lessons with respect to the existence and the limitations of the responses by donors' agencies, local institutions and local people that though undertaken in an emergency context may have long-term potential effects on food security; d) identified research areas that may deserve further attention and define the related frameworks for analysis.

The objective of the project is to provide empirical evidence, based on hands on experience to the research process through a case study on Emergency, pastoralists and food security in south Sudan. The case study will focus on livestock as a key component of the livelihoods of south Sudan people and the lessons that could be learned from an experience that although undertaken in an emergency context presents a number of "developmental" elements.

PI: Cebe, Peggy
Title: Polymer-Based Nanocomposites: An Opportunity for Deaf and Hearing-Impaired Students
Abstract: The objective of this proposal is to provide an opportunity for deaf and hard of hearing students, which involves participation in classroom and laboratory research in the field of polymers. A small group of college-age students will perform an internship at Tufts University for six weeks during the summer. The educational opportunity is arranged in two parts, the classroom component, and the laboratory component. Sign language interpreters will be provided for all the classroom lessons and the group laboratory instrument training sessions. A field trip to the National Plastics Center and Museum will be undertaken.

The classroom component will address: 1. basic polymer science needed to conduct the laboratory research work, and 2. aspects of participating and communicating within a scientific environment. From the polymer science lessons, students will learn about the chemistry and physics of polymer molecules, crystallization and melting of polymers, the interaction of X-rays and light with polymers, mechanical properties of polymers, and the connection between thermal processing, structure, and ultimate properties of polymers. To prepare the students for participation in the scientific community, a strong component of pre-professional training will be incorporated. This training will include discussion of situational ethics pertaining to proper conduct in the laboratory (integrity in the performance of research) and ethics of writing and presenting results (integrity in scholarship).

Deaf and hard of hearing students face obstacles in communicating with the hearing world. A major portion of the classroom component will center on teaching the students how to communicate, including how to write a scientific report, how to maintain a laboratory notebook, how to make a group meeting presentation, and how to organize a poster presentation. The students will present their results at a weekly group meeting, and will write a summary report at the end of the internship.

In the laboratory component, the students will be making and characterizing polymer-based nanocomposite films. The goals of the laboratory research component are to: expose the students to the laboratory environment; introduce them to the concepts of formulating and testing hypotheses; assist students to conduct systematic studies while controlling variables; illustrate the use of modem analytical equipment; and demonstrate the connection between processing variables, structure, and properties.

PI: Chaisson, Eric
Title: Educational Tools for Chandra Mission
Abstract: The Chandra X-Ray Observatory was designed to be the next great leap forward in x-ray astronomy. Mainly a NASA mission, this Hubble-class vehicle was launched into high-Earth orbit on July 23, 1999. Its resolution and sensitivity makes this telescope the premier device for high-energy astronomy into the twenty-first century.

The Chandra X-Ray Observatory Center, operated by the Smithsonian Astrophysical Observatory, the Chandra X-Ray Observatory Center control science and flight operations of Chandra for NASA from Cambridge, MA. The operation center consists of two facilities and has a staff of over two hundred people. The operation and control facility in Kendall Square is electronically linked to the science support facility at the Harvard-Smithsonian Center for Astrophysics. Scientists from the CFA and MIT have played key roles in designing the mirrors and scientific instruments for the telescope.

The Wright Center has partnered with the Chandra X-Ray Observatory Center (1) to create broadcast-quality video animations of the spacecraft in orbit and of the main science results resulting from the spacecraft's observations of a variety of cosmic objects, and (2) to plan and organize a series of teacher workshops, including the construction of a suite of educational modules for use by pre-college teachers, in order to disseminate the main science findings of this x-ray mission.

PI: Chan, Daniel
Title: Determination of Plasma Amino Acid in Critically Ill Dogs
Abstract: Critical illness resulting from trauma, surgery or sepsis is associated with catabolism, negative nitrogen balance, wasting oflean body mass, immunosuppression, and compromised wound healing in people. 1-7 Under certain conditions, such as after trauma or during critical illness, amino acids are redistributed from the peripheral tissues to serve as substrates for vital functions such as oxidation, gluconeogenesis, and protein synthesis in the intestinal mucosa, the liver, and in the immune system.8-1O Animal studies have shown a decrease in muscle protein synthesis, and an increase in whole body protein synthesis after trauma or sepsis, implying an increase in protein synthesis in tissues other than muscle. II The up-regulation of protein synthesis by the liver, intestines and immune cells in the face of negative nitrogen balance may lead to relative deficiencies in specific amino acids that may contribute to lean body wasting, immunosuppression and decreased healing.
Of particular interest are the changes in glutamine metabolism associated with critical illnesses such as severe trauma, major surgery, and sepsis. Circulating plasma glutamine is derived primarily from synthesis in skeletal muscle, lungs, and adipose tissue. During periods of stress, muscle proteolysis further provides an increased flux of glutamine trom skeletal muscle to the circulating amino acid pool. 12 Glutamine utilization on the other hand, can only be processed by glutaminase-expressing tissues such as the liver, kidney, intestine, lymphocytes and monocytes/macrophages.13 Despite glutamine efflux trom skeletal muscle during critical illness, glutamine consumption exceeds glutamine production, resulting in a marked depletion of plasma and tissue glutamine concentrations.I2 This overall depletion of glutamine has been correlated with increased morbidity and poor survival.14-J6 Glutamine deprivation leads to cellular energy depletion, along with reduced levels of the antioxidant glutathione and the important cell survival factor, 70 kD Mr heat-shock protein. 17-19 These cellular changes are believed to be key events contributing to organ dysfunction and increased mortality.
The integrity of the gut barrier is intricately linked with glutamine metabolism and is particularly vulnerable during critical illness. Enterocytes utilize glutamine almost exclusively for energy production, protein synthesis, and DNA and RNA synthesis. 10 Following stress of injury or surgery glutamine uptake across the brush border of surface enterocytes is increased, providing an important metabolic fuel source.9,I0,20 However, during periods of stress or critical illness, there is often a decreased enteral nutrient intake resulting in glutamine and energy depletion of these cells. While surface enterocytes are dependent on luminal sources of nutrition, the deeper rapidly-proliferating crypt cells depend on plasma glutamine to support DNA and RNA synthesis required for cell division.2O The combination of decreased luminal and plasma glutamine is likely responsible for the observed villous atrophy, decreased mucosal cellularity, compromised gastrointestinal immune function, and increased gut permeability associated with critical illness and malnutrition.15,20,22 This dual dependence on luminal and plasma glutamine by cells of the gastrointestinal system may explain the increased risk of bacterial translocation associated with critical illnesses.
Along with glutamine, other amino acids are mobilized during critical illness trom skeletal muscle to the circulating pool, where they may be consumed by the process of gluconeogenesis or are lost in the urine compounding a negative nitrogen balance. Branched-chain amino acids (BCAA) such as leucine, isoleucine, and valine are important regulators of body protein synthesis and represent the major nitrogen source for glutamine and alanine synthesis in muscle tissue. 23-26 During catabolic conditions, BCAA are increasingly oxidized in skeletal muscle and released into the circulation. This process of proteolysis leads to severe muscle wasting associated with critical illness. As the demands by the gastrointestinal tract, liver, and immune cells for glutamine increase, muscle proteolysis attempts to supply the necessary precursors, namely BCAA for glutamine synthesis.26
The association of amino acid depletion during critical illnesses has led to investigations focusing on repletion of such amino acids and possible effects on the host. Recent data suggests that supplementation of glutamine and BCAA can have dramatic positive effects in critically ill human patients.2,4,25,27-29 Marked improvements in nitrogen balance and reduction of muscle protein catabolism have been achieved with BCAA supplementation to septic and chronic renal failure patients? Parenteral administration ofBCAA have also been shown to decrease mortality in small number of septic patients.25 Glutamine supplementation has been shown to decrease the rate of mobilization of BCAA into the circulation and even improve clinical outcome in some studies of critically ill human patients. 4,28,30,31 Improved gastrointestinal barrier function, decreased bacterial translocation, shorter hospitalization and improved survival have also been associated with glutamine supplementation.28,30,31
However, to date, depletion of such key amino acids has not been demonstrated in critically ill dogs with naturally occurring diseases. Furthermore, without confirmation and better characterization of the changes in amino acid profile during critical illness in dogs, recommendations for amino acid supplementation remain speculative. While nutrient requirements have been established for healthy dogs during different life stages, currently there are no studies describing specific nutrient requirements for critically ill dogs. By identifying which amino acids are depleted during critical illness, we will be better able to direct future research in designing nutritional strategies for the treatment of catabolic critically ill dogs.

PI: Chapra, Steven
Title: Improved Science and Decision Support for Managing Watershed Nutrient Loads
Abstract: This project focuses on two major gaps in that presently impede the effective management of nutrients in watersheds: (I) inadequate characterization of sediment- water interactions and fixed plant activity in current receiving water quality models and (2) lack of a decision oriented framework for managing nutrient loads in a watershed. A decision support system (DSS) will be developed which integrates scientific models of watershed nutrient loads and their fate in receiving waters, into a decision-oriented optimization framework. The DSS model development process will allow stakeholders, scientists and regulators to define and prioritize watershed nutrient management objectives at the early stages of the project. This process will lead to an initial screening level DSS by the end of year one, based on simple nutrient loading function models, GIS information, a simple receiving water model and a decision model driven by a genetic algorithm. The initial DSS will be tested and evaluated by local scientists, stakeholders and regulators and used to formulate a more realistic DSS in subsequent project years, by incorporating more sophisticated runoff and receiving water models into the framework. The proposed DSS will be used to develop a TMDL program and to design a water quality monitoring network for the Mystic River Watershed. The Mystic River watershed is attractive because it is made up of both agricultural and urban land-uses and consists of a network of streams and lakes. In addition, the river is an impaired waterway and contains a current USGS NA WQA station. An existing collaborative partnership and close relationship already exists between the research project team, Tufts University and the Mystic River Watershed Association.

PI: Coffin, John
Title: Retrovirus Evolution
Abstract: Retroviruses display a remarkable variety of interactions with their hosts, well beyond that known for any other virus group. This variety is a consequence of special features of the virus life cycle, including a high mutation rate during replication, the unique ability (and necessity to integrate their DNA at every replication cycle, and special features of certain parts of the genome, including the envelope gene and the LTR, that allow rapid adaptation to host cells displaying different surface receptors and in different transcription programs. For a number of years, our laboratory has been studying a number of different aspects of the evolutionary interaction of retroviruses with their host. These areas include: the mechanisms and role of genetic variation - point mutation, homologous and illegitimate recombination in genetic variation in vitro, the way in which LTR and env sequences are able to vary their patterns of expression and receptor usage; the nature and evolution of endogenous proviruses. Future studies will continue along the same lines. Our aims are: To study mutation and selection, we will continue development of our approach toward quantitation of very low-frequency; use these approaches to test models for retrovirus evolution (accumulation of point mutations and recombination) in simple culture; and develop and extend mathematical models for retrovirus variation and short-term evolution. To study evolution of env genes, we will analyze avian retrovirus env gene variants isolated by in vitro selection for extended host range; we will determine the evolutionary pathway by which such variants; we will determine the functional properties of "ancestral" env genes in endogenous; and we will test the possibility of evolution of env genes from normal cellular genes. We will study the evolution of endogenous proviruses by continuing to dissect the coevolution of endogenous MLV's and wild mice; using se sequences of endogenous human proviruses to test models of primate evolution; and testing why the large numbers of human endogenous proviruses do not give rise to infectious virus.

PI: Damassa, David
Title: TUSK: Tools to Integrate and Share Health Knowledge
Abstract: Knowledge management is becoming an increasing important factor in the education of health professionals as both faculty and students wrestle with the explosive growth of information and growing time constraints. TUSK, the Tufts University Scientific Knowledgebase (formerly HSDB) is a database-driven software system developed over the past 8 years that is used extensively by the medical, dental, veterinary schools at Tufts and has recently been installed at the New York Medical College (NYMC). Built using open source tools and with an architecture based on open standards, TUSK supports local content sharing and personal knowledge management. Although extremely effective in supporting integrated medical curricula, both faculty and students have expressed the need for easier access to a wider range of external content resources, particularly those relevant to the clinical years of training. The overall goal of this project is to enable seamless local and inter-institutional sharing of medical content in a discretionary and secure manner through a common TUSK interface. The first aim of this project is to extend the TUSK system to integrate external as well as internal content interface, forming coherent connects between all sources of content. This will involve the representation of content from diverse sources as searchable "nodes" within TUSK and the implementation of system that associates all content nodes against a common medical vocabulary (the UMLS). The second aim is to implement automated authorization and rights managements to facilitate the cross-institutional use of content. The Internet2/NSF authentication and authorization middleware (Shibboleth) as well as digital rights management standards will be integrated into the TUSK system enabling controlled access to content among schools using TUSK and other Shibboleth-enabled systems. The results of this project will provide immediate and direct benefits to current users of TUSK-based systems by providing access to a wider range of clinically relevant content, facilitating the controlled sharing of curricular material and enhancing the use of the TUSK knowledge management features particularly during the clinical years of training. In addition, the experiences gained in the implementation of standards-based cross-institutional authentication and digital rights management are expected to have broader impact on the development and application of these services to health sciences education.

PI: Dawson, Dean
Title: The meiotic role of SIK19p in yeast
Abstract: A fundamental difference between meiotic and mitotic chromosome segregation is that in meiosis I, sister chromatids move as a unit to one pole of the spindle rather than separating as they do in mitosis. Sustained linkage of sister chromatids through meiosis I is accomplished by association of the chromatids at the centromere region and development of kinetochores that allow both chromatids to be moved as a unit to one pole of the spindle. The localization of the meiosis-specific cohesin, Rec8p, to the centromeres is essential for maintenance of sister chromatid cohesion through meiosis I, and Mam1p is necessary for kinetochore development, but the molecular basis for the regulation of cohesion and sister kinetochores in meiosis remains a mystery. Recently, it has been demonstrated that the S1k19 protein of Saccharomyces cerevisiae is essential for the maintenance of sister chromatid association through meiosis I. Two possible roles have been suggested for Slkl9p in meiosis. The first is to promote sister chromatid cohesion at the centromeres, perhaps by protecting Rec8p in this region from degradation at the metaphase I to anaphase I transition. The second is to control sister kinetochore development, such that sister chromatids share a single functional kinetochore throughout meiosis I. This proposal addresses these models through four sets of experiments. First, experiments are proposed that use the chromatin immuno-precipitation method to explore the centromeric localization of Slkl9p and Mamip, and their dependence upon each other for association with the centromere. The role of the CDEII centromere element in meiotic kinetochore function will be explored genetically and through studies of its association with Slkl9p. Second, we will test whether Slk 19p controls sister chromatid centromere cohesion by monitoring its relationship with Rec8p and by using cell biological assays to monitor the establishment and maintenance of sister chromatid centromere association in slkl9 mutants. The third set of experiments is designed to determine the identities of the proteins that interact with Slkl9p in meiosis. A two-hybrid screen will be performed. Affinity chromatography will be used to purify Slkl9p and associated proteins from meiotic cells. A genetic approach will used to identify high copy suppressors of slkl9 partial loss-of-function mutants. Finally, we will explore the regulation of Slkl9p by: 1) Spo 13p 2) possible conjugation to ubiquin or ubiquitin-like proteins, 3) targetting for degradation by Cdh 1p and Amaip and 4) degradation by Espip, the protease that triggers anaphase I by clipping cohesin proteins.

PI: Easterbrooks, Ann
Title: Evaluation of the Touchpoints Early Child Care and Education Initiative Intervention
Abstract: This evaluation of the Touchpoints Early Child Care and Education initiative has been developed by a Tufts evaluation team, directed by Professors Ann Easterbrooks (Eliot-Pearson Department of Child Development) and Fran Jacobs (Eliot-Pearson Department of Child Development/Department of Urban and Environmental Policy and Planning). It contains initial plans for undertaking both an outcome study (to determine the possible results of the program) and a process study (to document aspects of the program's implementation, and participants' responses to them).

Since its inception, the Brazelton Center's Touchpoints Program (TP) has garnered much public and professional acclaim. The Touchpoints Program, built on Dr. Brazelton's vast clinical experiences helping parents manage their young children's often bewildering and stressful developmental transitions, trains a wide variety of child-serving professionals; its primary goals are to increase professionals' knowledge of child, parent, and family development, and to expand professionals' repertoire of respectful, collaborative, and strengths-oriented strategies for working with parents. Improved relationships between professionals and parents, and between parents and children, should result, and these in turn should yield enhanced child well-being.

Admirably, Touchpoints principals have been interested in evaluation for a number of years, appreciating the often-ignored truth that even a conceptually well- supported program does not always produce the desired results. This can be the case for a wide variety of reasons. Sometimes the problem is related to program operations, and the extent to which the program is being faithfully implemented --that is, delivered as designed. Other times, £or example, the program's intervention theory is correct, but only in certain circumstances, with certain populations. By systematically collecting information on program implementation and on the effects achieved £or participants - "process" data and "outcome" data - evaluation can provide feedback to programs to validate their approaches and/ or direct them to promising modifications 0£ theory and practice that might improve their success.

PI: Feig, Larry
Title: Function of the Ras Related Ral Proteins
Abstract: The overall goal of this proposal is to gain a better understanding of the functions of the Ras related Ral- GTPase family. RalA and RalB have been implicated in diverse cell functions including the control of vesicle sorting, gene expression and cell proliferation. As GTPases, Ral proteins function as molecular switches to transmit extracellular signals to specific intracellular signaling cascades. Ral proteins reach the active GTP bound state in cells by interacting with one of a family of Ral-specific guanine nucleotide exchange factors (Ral-GEFs). One class of Ral-GEFs binds to and is activated by GTP-bound Ras, and a growing body of evidence supports the idea that elevated Ral-GEF/Ral signaling has the potential to contribute to human oncogenesis. This proposal will attempt to reveal the mechanisms underlying two newly identified processes by which the Ral-GEF, Ral-GDS, is regulated. One process positively regulates Ral-GEF activity through interaction with the PDK1 protein kinase, and the other negatively regulates Ral-GEF activity through protein kinase D-mediated phosphorylation. Active GTP-bound Ral proteins bind to and alter the activity of a set of downstream "effector" proteins to influence cellular processes. Studies in this proposal will expand upon our recent finding that RalA but not RalB functions in the maintenance of cellular polarity by enhancing the rate of delivery of membrane proteins to the basolateral surface of epithelial cells through its newly identified effector, the exocyst, and possibly through an exocyst-independent mechanism. Thus, one set of goals is to define the biochemical basis for the difference in activities of these two closely related Ral family members. Another goal is to identify the additional RalA "effector" that participates in basolateral membrane delivery. We also plan to define how RalA binding to the exocyst or other Ral effectors promotes membrane delivery in MDCK epithelial cells. Understanding how Ral functions in this process is important because faulty delivery and polarization of membrane proteins can lead to serious diseases including cystic fibrosis, I cell disease, familial, polycystic kidney disease and possibly cancer. Finally, there is a growing appreciation that Ral-GEFs contribute to downstream signaling from GTPases by mechanisms that are independent from their ability to activate GTPases. Therefore, another aim of this proposal is to evaluate the contribution of Ral-GEF binding proteins for their ability to contribute functions that complement those of active Ral in cell processes mediated by the Ral-GEF/Ral signaling cascade.

PI: Forrester, Janet
Title: Nutritional Status in HIV Hispanic Drug Abusers
Abstract: The BIENESTAR study is a longitudinal cohort study of the effect of drug abuse on nutritional status and outcomes among Hispanics with HIV infection. The cohort is comprised of 3 groups: HIV+ drug abusers, HIV- drug abusers, and HIV+ non-drug abusers. Efforts will focus on expanding and maintaining this unique cohort. New hypotheses addressed in this competitive renewal reflect current trends, as HIV becomes a chronic disease. Liver disease is an increasingly common complication in patients with HIV. While it is generally accepted that HCV is largely responsible for liver disease in HIV infection, studies suggest that drug abuse itself is a risk factor for liver disease among persons with HCV. Animal studies have shown that cocaine can cause liver toxicity by the induction of oxidative stress with tissue damage. Hispanics of the NE USA preferentially inject cocaine more than other races, and therefore may be at increased risk of oxidative stress and liver dysfunction. Low serum antioxidant micronutrient levels are common in drug abusers, further increasing the risk of oxidative tissue damage. This study proposes to examine antioxidant status, oxidative stress, and liver dysfunction in Hispanic drug abusers with HIV infection. There are 4 specific aims: 1) To examine the association between the type (cocaine versus heroin) and frequency of drug abuse with plasma antioxidant capacity and oxidative stress. The specific interest is to know if cocaine differs from heroin in its ability to alter antioxidant capacity and cause oxidative stress; 2) To examine the association between the type and frequency of drug abuse and liver dysfunction. If cocaine or heroin cause oxidative stress to hepatic tissues this may result in detectable alterations in liver function; 3) To examine the association between oxidative damage and liver dysfunction. An association between oxidative stress and liver dysfunction will imply that drug abuse alters liver function through a mechanism involving oxidative stress; and 4) To examine the influence of infection with HIV, infection with HCV, and alcohol consumption on the associations described in specific aims 1 to 3. This will determine if drug abuse is an independent risk factor for liver dysfunction or whether, like alcohol, it is an accelerator of liver dysfunction in persons with HIV and/or HCV infection. The proposed study will build on the infrastructure of the BIENESTAR study (NIDA DA 11598) and the BIENESTAR-micronutrient study (NIDA DA 14501).

PI: Freeman, Lisa
Title: Interdisciplinary Research Training for Veterinarians
Abstract: Well-trained comparative medical scientists are needed to meet the research needs of the 21st Century. Veterinarians currently are underrepresented in biomedical research but can make a unique contribution because of their expertise in clinical practice and fundamental biology, as well as their knowledge of spontaneous animal models of human disease. The goal of the proposed education program is to attract veterinarians to NIDDK-relevant research. This program is focused primarily on veterinary residents, a highly motivated group for which research training usually is not provided. This program is designed to first create the desire to pursue research and then to nurture these candidates with strong mentoring and programs, as well as by providing readily accessible research opportunities. Finally, common barriers to research will be addressed. A major aspect of the program will be biannual symposia on spontaneous animal models of human disease to disseminate information to the scientific community on the vast array of models available and to create new opportunities for collaboration. This program will utilize the strengths and resources of Tufts University to develop an untapped resource for research scientists. This will be achieved under the mentoring of a program faculty that has been recruited specifically to provide an interdisciplinary team of collaborative scientists in a variety of disciplines and that provides experienced and positive role models. The program faculty consists of 17 faculty from 9 departments on three different campuses, providing a network of research training in nutrition and endocrine, digestive, kidney, urologic, and hematologic diseases. Veterinary residents will be actively recruited, with particular attention paid to minority candidates. The program will consist of six parts: 1) Biannual symposia on spontaneous animal models of human disease to provide greater interaction with researchers from other disciplines and to increase opportunities for collaborative research; 2) A multi-function website to facilitate research, including two web-based courses on laboratory techniques and applied statistical methods; 3) A resident research and development (R&D) seminar series that will include topics to foster an interest in research and to facilitate research training; 4) Short-term introductory research electives; 5) Intensive research training electives; and 6) An active mentoring program. The inclusion of a specialist in outcomes assessment on the program faculty will ensure timely and accurate assessment of the program. Short-term evaluations will be used to guide development in the early stages of the program. Mid-range impact of the program will be evaluated by the number of participants, research presentations, grants, and papers. Long-term outcomes will be assessed by the number of Tufts-trained residents that do postdoctoral training and pursue research careers, and by using existing and novel outcomes assessment instruments. These evaluations, continued refinement, and the commitment of the program faculty will help to ensure that this becomes a self-sustaining program.