Deborah Johnson - US grants

The creation of university research centers to encourage collaboration among academe, industry and government in the conduct of science and technology is a relatively new phenomenon in this country. The aim of this project is to explore what happens to the values of these three sectors when they come together in these settings. This effort itself is a collaboration between four scholars from the disciplines of philosophy, political science and sociology. They will use their disciplinary perspectives and methods, including normative, organizational, structural and ethnographic analysis, in an intensive, on-site examination of the negotiation of values, including concerns for professional success, control, and management, in two research centers located at Rensselaer Polytechnic Institute, the Center for Manufacturing Productivity and Technology Transfer and the Center for Composite Materials and Structures. A four-member board incorporating business, government, and public interest perspectives, will advise the project; and the study will be augmented by an exchange of ideas and data with an investigation of other university-industry interactions currently underway in RPI's Center for Science and Technology Policy. Results will be disseminated in articles for disciplinary and interdisciplinary journals. Special mailings of "Working Papers" will be made to administrators and policymakers, and the findings should also be appropriate for sessions at meetings of the American Association for the Advancement of Science and the Society for Social Studies of Science. Involvement at the centers should also lead to channels of publication to audiences interested in the centers' activities. This project can make a unique contribution to the development, application, and evaluation of collaborative research agendas and methods in science and technology studies. It will also provide the first intensive, longitudinal examination of the processes and products of negotiating values in these new institutional settings. The investigators are exceptionally well qualified; graduate students are involved; institutional support and cooperation is excellent. The use of an advisory board and interaction with another related investigation will help to assure broader relevance and balance. This is a good example of the kind of cross-disciplinary research EVS should encourage. Results are likely to be useful and widely disseminated. Costs are reasonable. Total support in the amount of $164,374 is recommended, of which $96,000 is awarded now, from the Directorate for Engineering and the Directorate for Mathematical and Physical Sciences.

This study will characterize an important protein, TFIIIC, that is essential for the expression of a large class of genes in eucaryotic cells which are transcribed by RNA polymerase III. Specifically, one of the first critical steps in the transcription process will be examined: the direct interaction of TFIIIC with the DNA template. To this end, a partially purified fraction containing the yeast Saccharomyces cerevisiae TFIIIC will be used to determine the specific nucleotides within the two internal promoter regions of the tRNA gene required for its binding. Since the yeast system also exhibits a dependence for 5'flanking sequence for efficient tRNA gene transcription, the additional contribution of these sequences on TFIIIC binding will also be assessed. These studies will use a variety of mutant templates previously derived from two tRNA genes. Nuclease-protection assays will qualitalively determine the site of TFIIIC binding to these templates. Gel retardation analysis of TFIIIC-DNA complexes will quantitate how these mutations affect the affinity of TFIIIC for these templates. These studies will also examine the structure of the TFIIIC polypeptide responsible for this specific interaction. Recently, using a protein blotting procedure, a 150,000 dalton molecular weight protein has been identified which specifically interacts with tRNA genes and constitutes the DNA binding function of TFIIIC. This study will elucidate whether this protein contains functional DNA binding domains which are responsible for its interaction with one or both of the internal promoter regions. Further purification of TFIIIC by conventional and affinity chromatography methods will allow for the generation of monospecific antibodies and protein sequence information. Yeast genomic libraries will be screened using immunological and hybridization methods for isolating the gene encoding the TFIIIC protein. Overproduction of the TFIIIC polypeptide will be accomplished using a yeast expression system. Potential DNA- binding and protein-binding domains on this protein will be delineated by assaying its ability to bind specifically to tRNA genes and to reconstitute tRNA transcription in vitro with TFIIIB and RNA polymerase III. Future studies will involve mutagenesis of the TFIIIC gene and the production of mutant TFIIIC proteins. These studies will determine the structure function relationship of the TFIIIC polypeptide and delineate ordered interactions which define TFIIIC's role in the mechanism of RNA polymerase III transcription.

This study will characterize an important protein, TFIIIC, that is essential for the expression of a large class of genes in eucaryotic cells which are transcribed by RNA polymerase III. Specifically, one of the first critical steps in the transcription process will be examined: the direct interaction of TFIIIC with the DNA template. To this end, a partially purified fraction containing the yeast Saccharomyces cerevisiae TFIIIC will be used to determine the specific nucleotides within the two internal promoter regions of the tRNA gene required for its binding. Since the yeast system also exhibits a dependence for 5'flanking sequence for efficient tRNA gene transcription, the additional contribution of these sequences on TFIIIC binding will also be assessed. These studies will use a variety of mutant templates previously derived from two tRNA genes. Nuclease-protection assays will qualitalively determine the site of TFIIIC binding to these templates. Gel retardation analysis of TFIIIC-DNA complexes will quantitate how these mutations affect the affinity of TFIIIC for these templates. These studies will also examine the structure of the TFIIIC polypeptide responsible for this specific interaction. Recently, using a protein blotting procedure, a 150,000 dalton molecular weight protein has been identified which specifically interacts with tRNA genes and constitutes the DNA binding function of TFIIIC. This study will elucidate whether this protein contains functional DNA binding domains which are responsible for its interaction with one or both of the internal promoter regions. Further purification of TFIIIC by conventional and affinity chromatography methods will allow for the generation of monospecific antibodies and protein sequence information. Yeast genomic libraries will be screened using immunological and hybridization methods for isolating the gene encoding the TFIIIC protein. Overproduction of the TFIIIC polypeptide will be accomplished using a yeast expression system. Potential DNA- binding and protein-binding domains on this protein will be delineated by assaying its ability to bind specifically to tRNA genes and to reconstitute tRNA transcription in vitro with TFIIIB and RNA polymerase III. Future studies will involve mutagenesis of the TFIIIC gene and the production of mutant TFIIIC proteins. These studies will determine the structure function relationship of the TFIIIC polypeptide and delineate ordered interactions which define TFIIIC's role in the mechanism of RNA polymerase III transcription.

The major transcriptional activities in eukaryotic cells are devoted to the synthesis of rRNAs and tRNAs by RNA polymerases I and III. The in vitro transcription systems derived for Pol I and III, compared to those for Pol II, are efficient, specified by fewer proteins, and more often mimic the transcription events observed in vivo. We have made substantial progress in purification and characterization of the Drosophila Pol I and Pol III transcription components. The species specific nature of these components and the unique features of these Drosophila transcription systems have led us to examine the role of these proteins in specific regulatory effects. Our results are the first to show that serum, TPA (A tumor-promoting phorbol ester), and a calcium ionophore can up-regulate rRNA and tRNA gene expression in Drosophila. Furthermore, we have been able to derive cell extracts that reproduce this transcription increase in vitro. Using transcription reconstitution assays and partially purified protein factors, we will determine the relative activity levels of Pol I, TFIC, TFID, and Pol III, TFIIIB, and TFIIIC in non-stimulated and stimulated cell extracts. Stable transcription formation and gel shift assays will be used to analyze alterations in the DNA binding functions of TFID and TFIIIC. These results will define, for the first time, Pol I and III regulatory events mediated by serum, TPA and calcium ionophore, and the relationships among these events. Since the induction of specific genes by phorbol esters in Drosophila has not been previously demonstrated, our studies will provide new insights as to its mechanism for gene regulation in this system. Once we have defined which of the factors are involved in these regulatory processes, we will further determine the structural modifications in specific polypeptides which give rise to their altered activities. Qualitative and quantitative differences in the polypeptides which are shared by Pol I and III, and those polypeptides which comprise the factor subunits will be examined by immunological approaches. We will use both currently available antibodies and antibodies derived from purified Drosophila components. We will expand our purification protocols to more completely purify these components, focusing on those proteins which we find to be altered in the regulatory events. In total, these experiments can offer unique insights into gene regulation in Drosophila, into the control of Pol I and III gene expression, and into potential novel mechanisms of the co-regulation of these two systems.

Computerized decision models are increasingly being used in the public and private sector for decisions that affect everyone. Pension funds are invested on the basis of computer models; medical student interns are matched with hospitals on the basis of a computer model; air traffic is controlled on the basis of a computer model; income tax laws are changed on the basis of models; and so on. Yet, often those who make decisions on the basis of a computer model do not understand the algorithms used, or the assumptions made, in the model. They cannot critically assess the model's output. Moreover, decisions made using computer models are often not accessible to the public that is affected by them. Hence, increasing use of, and dependence upon, computer models raises important ethical questions. The most serious issues center on the effects of the use of models on the democratic process, the responsibilities of the model designers to their clients and to the public, and the treatment of risk that is often buried in a model. While a good deal of research has been done in recent years on the social impact of computers and on the ethical issues surrounding computers, only rarely have the ethical issues arising from the use of computer decision models been addressed. The investigator will collaborate in identifying and analyzing the ethical issues surrounding the use of computer models. The analysis will lead to recommendations for change in the way models are designed and used, and in the way modelers function in their professional roles. This project furthers VPW program objectives to provide opportunities for women to advance their careers in science or engineering through research, and to encourage other women to pursue careers in these areas through the investigator's enhanced visibility as a role model on the host campus. The proposed activities which contribute to the second objective include: presenting seminars; arranging informal discussion groups for women faculty and students; and teaching/co-teaching a course.

This study is the first phase of a longitudinal study of organizational and contextual influences on academic research groups in U.S. science and engineering. The study will examine how research groups are organized and how they change over time; how contextual variables influence group structure, functioning, and performance; and how contextual and group variables together influence members' careers, work-related attitudes and values, and research behavior (including problem selection, research style, productivity, quality, and risk tolerance). The main purposes of Phase I are to operationalize major concepts and develop measures, field test data-gathering techniques, devise a sampling plan, design data management and analysis systems, and address and refine the research questions through analysis of preliminary data, This will be done through face-to-face interviews, questionnaires, and an examination of documents for approximately fifty-five researchers and their teams, drawn from a national sample of scientists and engineers in four fields. This project addresses fundamental questions about the social organization of academic research and thus should be of interest to a wide audience, including federal decision makers, scholars interested in the social organization of science, the community of researchers and practitioners concerned with higher education, and social scientists interested in groups, organizations, and work life. The immediate products of Phase I will be a detailed final report, an executive summary, and a one-page abstract of the project (25 copies of each) for NSF, and an academic paper (based on cross- sectional data) reporting on differences in group characteristics and performance among research teams.

This grant will support an interactive distance video workshop on Ethics in Modeling. The purpose of the workshop is to explore the use of this new technology as a means to focus attention on ethical issues in the development and use of computer-based decision models for the modeling community that develops models; the potential users and those who may be affected by the use of models; and educators and researchers in applied ethics and the disciplines of modeling: operations research, statistics, management science, and systems engineering. The workshop will involve individuals at four sites, in the Netherlands, Massachusetts, Maryland, and New York. One goal of the workshop is to find out what modes of interaction using this technology will be most effective. The second research goal is to generate awareness, discussion, and scholarship on the ethical issues involved in modeling. For this purpose, the participants will discuss four cases. Each site will have a facilitator, and the workshop will be videotaped for analysis. Participants will complete pre- and post- workshop questionnaires. The principal investigators will prepare a report on the findings.

This project is to engage undergraduate faculty in a set of activities that will prepare them to teach courses or course modules on ethical and professional issues in computing. Twenty-five undergraduate faculty from a diversity of disciplines and types of institutions are participants. They are required to do pre-workshop assignments; attend a 5-day workshop during the summer, participate in an on-line forum, and attend a two day follow-up meeting in February. The activities are designed to address pedagogical issues as well as subject matter. The subject matter topics to be covered include proprietary rights in computer software, privacy, responsibility and liability, hacking, risk and reliability, democracy, access, and autonomy, and professional ethics for computer professionals. The project responds to the growing need for faculty trained in this area as the accreditation requirements in computer science and engineering recommend coverage of "social, ethical, and professional issues in computing."

ADVANCING THE STATE OF KNOWLEDGE ON SOCIAL AND ECONOMIC OUTCOMES OF FUNDAMENTAL RESEARCH WORKSHOP ABSTRACT In a competitive global environment where the allocation of scarce resources is a matter of intense interest and debate, it is important that policy-makers have a clear picture of the social and economic outcomes of public expenditures for fundamental scientific and engineering research. Since World War II, policy-makers and the public have come to expect social and economic returns from public investment in fundamental research. The National Science Foundation has responded to these expectations by supporting research aimed at understanding the contributions of science and engineering to the U.S. economy and society at large. Such research has been conducted predominately by economists, who have developed several methodologies which measure the influence of research and development (R&D) on outcomes. While economic studies have confirmed a strong relationship between R&D and growth of output and productivity, they are limited in their focus on economic outcomes. Consequentially, many other putative benefits that may result from investments in science and engineering research have scarcely been investigated, including quality-of-life outcomes in the areas of public health, food and nutrition, environmental quality and sustainability, the development of human capital and its relation to socio-economic mobility, communications and transportation, education, neighborhoods and communities, and the nature of work and recreation. This over-reliance on economic outcomes has resulted in the underestimation of the full-range of benefits that are derived from fundamental research. Furthermore, results from economic studies are accompanied by a high degree of uncertainty that makes interpretation difficult, and limits their utility for policy purposes. An expansion of the body of knowledge concerning the interrelationships between science, engineering, and society as they pertain to the impact of new research activities would enable a more complete understanding of the social and economic outcomes of fundamental research. Advances in the state of knowledge in this area require that we move beyond our historic focus on economic outcomes, and toward alternative conceptualizations and measurements of outcomes in other areas that are important to Americans and their quality-of-life. The purpose of this grant is to support a workshop focused on developing these alternative concepts and measures of the social and economic outcomes of fundamental research.

The Association for Practical and Professional Ethics, in collaboration with the Poynter Center for the Study of Ethics and American Institutions, and Association members who are leading scholars and educators in the ethics of scientific research, will provide instruction in ethical issues in scientific research for a selected group of graduate students and postdoctoral fellows in engineering and the natural and physical sciences. The objective is to equip these researchers with skill in ethical thinking, understanding of the historical context of scientific misconduct and awareness of the multidisciplinary nature of major issues in scientific research. An intensive four day workshop will provide 15 participants in each of three years with tools for self-directed development in these areas and a network of support. The workshop will introduce participants to ethical theory and reasoning in the context of discussions on topics such as data sharing and ownership; responsible conduct of research; conflicts of interest; professional relations with colleagues; ethical issues in computing; protection of human subjects; variations in standards of conduct; responsibilities of engineers and scientists to the larger society. The aim is to enable them to provide leadership in ethical issues in the scientific community and enhanced ethics education for their own future students. Participants will be nominated by science and engineering faculty at research universities and through solicitations to a wide variety of professional associations, and selected for their promise as leaders and mentors. In advance of the workshop, they will begin to read historical cases and introductory material, to inform themselves of standards of conduct in their own fields, and to develop a case study for distribution and comment. During the workshop, participants will discuss presentations and case studies, continue to work on their own cases and those contributed by others, and review and evaluate standards of conduct. Case studies prepared in the workshop will be made available to faculty nationwide for use in their own courses, and participants will be expected to share their work at their home institutions. They will join a network of concerned scientists and engineers from the Big Ten and other universities and receive a complementary three year membership in the Association which will enable them to maintain the contacts needed to continue to work in the field. Project staff and an outside evaluator will assess the project.

The proposed study will investigate parental socialization processes related to the development of children's racial coping skills. For African Americans, daily living experiences and the stressful life event of other Americans are additionally encumbered by the chronic and mundan stressors associated with racism and discrimination (Pierce, 1975; 1990) Black families, painfully aware of the racial imbalance and their concomitant devalued status in the society, adjust their parenting practices to include socialization geared toward protecting their children and their psyches' from anticipated race prejudice and explicit discriminatory events. Three hypotheses will be considered. Hypothesis 1: Parental interactional processes (negotiation strategies, declaratives, questions imperatives, turn-taking, etc.) which facilitate and encourage child problem solving will be related to proactive racial coping in children. Hypothesis 2: Among parents where interactional process are not observed to be optimal, proactive racial coping among children will be mediated by other personality attributes or perceptions of the child, i.e., age, positive feeling of competence, good general coping skills, low school anxiety, perceived social support from other adults or peers. Hypothesi 3: Parental contextualization of non-specific conflict as racial conflic will be associated with the increased number of child racial coping strategies (RCS) articulated, while decontextualization or diminished racial meaning will result in fewer articulated RCS. Microanalysis of will examine videotaped sessions of 80 parent-child dyads regarding the race related socialization of African American children in grades 3-4 and 5-6. Children will be divided into two tasks conditions, in one condition stories with explicit racial content will be used, in the second similar stories devoid of racial content will be used. Independent variables, include the scored domains of interaction and contextualization or decontextualization of each story (tasks referred to above), the dependent variable is the child's racial coping strategies.

This is the second phase of a longitudinal study of academic science and engineering research groups in the United States. The study is concerned with: 1) the social organization, functioning, and life course of research groups; 2) the research performance of the group, including properties of the group's research system (that is, the set of materials, methods, instruments and ideas used in the research process), its risk profile, and published productivity; 3) the influence of group characteristics on the work-related attitudes, values, and behaviors of member scientists and engineers.

DESCRIPTION: (adapted from the investigator's abstract) The hepatitis B virus (HBV) is an infectious agent affecting over 300 million people world-wide. Chronic infection can lead to liver necrosis and hepatocellular carcinoma. One of the HBV gene products, the X protein, transactivates a large number of cellular and viral genes, yet the mechanism by which this occurs is still not understood. Compelling evidence supports the view that the X protein has a critical role in establishing infection and a direct role in the development of hepatocellular carcinoma. Therefore, uncovering the function of this protein in the transactivation of cellular genes is critical to our understanding the role of X in pathogenesis. The investigator has recently demonstrated that X mediates an increase in the cellular levels of the TATA-binding protein (TBP), a factor involved in the transcription of all cellular genes, and that this protein is limiting for the expression of RNA pol III genes. Both X-mediated increases in RNA pol III gene expression and TBP are dependent upon X-activation of cellular protein kinases. The investigator's aim is to define the signaling pathway activated by X and the consequence of this event on gene activity and TBP levels. The proposed studies will determine: (1) at what level X regulates the cellular increase in TBP; (2) whether both the X-mediated events are dependent upon the activation of the Ras signal transduction pathway; (3) whether X activates Sos-Grb2 complexes and whether this is necessary for gene induction; and (4) whether RNA pol III gene induction and the increase in cellular TBP is mediated exclusively by activating signaling proteins. The proposed studies will comprehensively assess the relationship between X-activation of RNA pol III genes, X-mediated increases in TBP, and the activation of Ras. The investigator will also examine whether X can activate RNA pol I gene expression. These results could demonstrate, for the first time, a whole new class of cellular genes that are induced by X. If so, the investigator will also determine whether induction by X is also dependent upon Ras activation and increased TBP levels. The proposed experiments will be carried out using rat 1 cells and/or Drosopholia S-2 cells that are transiently transfected or genetically altered to express expression vectors for X or other genes. The goal of the studies will potentially be to define a key function of the X protein that allows HBV to intrude into the cellular transcription machinery and ultimately alter the growth properties of the cell. These basic studies will directly impact treatment of HBV-infected patients. With the many new anti-Ras therapeutic agents under investigation, these studies could lead the way for a potential new use of these compounds: by inhibiting X mediated Ras activation to prevent pathogenesis in individuals chronically infected with HBV.

This award is a planning/pilot graduate training project to involve one faculty member and three graduate students for one year in laying the groundwork for the development of a science and technology studies graduate program in design. STS scholars have recognized how technologies embody cultural, social and political values. But seldom have they applied such perspectives that inform actual design projects. The award will allow for the teaching of an interdisciplinary course on design involving STS and Engineering faculty, the development of a series of interdisciplinary courses on design, and the participation of three graduate students. The project will explore ways to integrate STS and design, as well as on-campus design and industry design. Moreoever, the project will explore ways of building bridges to engineering faculty. Activities for graduate students will not only involve classes, but also field work to non-academic sites and a colloquium series.

This project addresses one of the most abiding and important topics in science and technology studies - the historical relations of science, technology and industry. Its purpose is to show that a definable and critical phase in these relations was marked by the emergence of scientific consulting - a new and hitherto unexamined scientific practice of the mid-nineteenth century. The project focuses on the careers of the most prominent consultants of the time, geologists and chemists, and their interactions with the development of the coal and petroleum industries. It discusses the scientific and commercial contributions of these consultants as well as the ethical and legal consequences of this new professional scientific practice. The results of the project will contribute to several areas of scholarship. In the history of geology and chemistry, the project highlights theoretical and empirical contributions by American scientists to the studies of coal and petroleum which will provide a balance to predominantly European accounts of these sciences. In scientific ethics, the project shows how the norms of professional conduct for American scientists were shaped by the commercial practices of consultants. In the relations of science and the law, the project outlines the emergence of scientific expert witnessing and the changes in the legal code that allowed for the patenting of scientific research. And finally, by systematically investigating this new practice of consulting the project explains how science became an essential component of technological and industrial development.

In collaboration with leading scholars, scientists, engineers, and educators from university-based centers and fields with expertise in the ethics of scientific research, the Association for Practical and Professional Ethics will provide instruction in ethical issues in scientific research, training in teaching research ethics, and an opportunity for research collaboration for a selected group of graduate students and post-doctoral fellows in engineering and the natural and physical sciences. The project will nurture a community of young researchers who show promise of leadership and an interest in research ethics, providing them with skills in ethical thinking, understanding of the historical context of scientific misconduct, and an awareness of the mutidisciplinary nature of major ethical issues in science and engineering. A related objective is to train them in teaching research ethics. The goal is to enhance the ethical quality of participants' own research careers, that of their colleagues and of the generations of students they will teach. The project will also exploit the resources already created in previous work, by collaborating with prior participants to: 1) Develop a set of more effective teaching materials and techniques for instruction in research ethics, with an emphasis on best practices. 2) Produce a set of narratives that capture the ethical environment and ethical problems of graduate students and postdoctoral fellows, and a set of recommendations for improving graduate research ethics education, from the perspective of participants trained in ethics. 3) Produce scholarly papers on issues in research ethics, especially those encountered in the graduate education experience. Finally, the project will provide a network of support to assist the students in providing leadership in ethical issues in the scientific community. The first project component will involve 15 participants a year, for each of three years, in eight months of activity, including an intensive 4.5 day workshop on research ethics, a 1.5 day teaching seminar, the development of a case and commentary on a topic in research ethics, and experience in teaching research ethics at their home institution. The second component will involve collaborating with up to 51 former participants of the program to develop more effective teaching materials in graduate research ethics, including a focus on best practices; to develop recommendations for improving the research ethics experience in the graduate setting; and to engage in scholarly work on issues of research ethics, particularly those related to the graduate school environment. This component will involve work over four years and include four 1.5 day working conferences. This project will directly impact the understanding and teaching of research ethics for 96 young researchers and will indirectly affect their peers, students, graduate departments and universities. It will contribute to understanding of the task of graduate research ethics education and provide some tools for that effort.

DESCRIPTION: (Adapted from the investigator's abstract) The Hepatitis B virus (HBV) is a common infectious agent. The HBV protein product, X, has shown to be essential for viral replication, and it is strongly implicated in the development of hepatocellular carcinoma in chronically infected HBV patients, yet its role in these events is not well-understood. Our previous work has comprehensively defined the mechanism for how X transactivated RNA polymerase I and III promoters. We made the interesting discovery that X induces the promoters by activating the Ras signal transduction pathway which then increases the cellular levels of the central transcription factor, TATA-binding protein (TBP). Increases in cellular TBP augment RNA pol I and III transcription and differentially regulate RNA pol II promoters. Our research plan will clearly delineate how X, an oncogenic Ras, increase cellular TBP levels. The proposed aims will rigorously investigate each event in the TBP gene expression process that gives rise to the final TBP product. By examining the individual contribution of each process, and how it differs when either X or oncegenic Ras is expressed in cells, we will obtain a good quantitative picture of how this X- and oncogenic Ras-mediated increase in TBP occurs. We have promising new data indicating that a key step leading to the increase in TBP is due to an increase in TBP promoter activity. Therefore, a major focus of the proposed studies will be to examine how the TBP promoter is regulated by X and by oncogenic Ras. We will comprehensively define the X-mediated signaling events downstream of Ras to the promoter that modulate TBP promoter activity. Since X has been shown to transform cells, and Ras is strongly oncegenic, we will also determine how alterations in the cellular levels of TBP can affect the transformation potential of cells. Focus formation, growth in soft agar, and mouse tumorigenesis assays will be used to assess whether directly overexpressing TBP can enhance transforming activity or whether down-regulating its production in cells can prevent Ras-induced transformation. Using mutant TBP proteins that are specifically defective in RNA pol II or pol III transcription, we will define specific changes in cellular gene expression occurring in TBP-overexpressing cells that contribute to transformation. These studies promise to make unique and important new contributions to our understanding of the function of the HBV X protein and oncegenic Ras, the regulation of TBP, and their consequences on cellular gene activity that leads to cellular transformation.

This endeavor examines the implications of recent work in Science and Technology Studies (STS) for understanding the connection between ethics and technology. It involves integration of insights from two fields of research that have significantly evolved in the last two decades:
Social studies of technology; and
Applied and practical ethics related to technology.
STS theories of technology provide a rich foundation for understanding the connection between ethics and technology insofar as they reveal the intimate connections between technology and society, and especially the social shaping of technology. STS scholars have rejected the idea that technologies simply appear and then have social impacts. They now favor more complex, co-creation models of technology and society. However, many ethicists continue to use a model of technology arriving intact and then having impacts, i.e., threatening particular social values or raising ethical issues. When the seamless connection between technology and society is better understood, many new and promising directions for research on ethics and technology become apparent.
This project aims to develop, articulate, illustrate, and disseminate a theoretical account (or accounts) of the connection between ethics and technology, an account that incorporates and builds on STS social shaping/co-creation theories. The major task of the project will be to draw out the implications of STS theory for ethics. Three directions will serve as starting places for this endeavor. STS theory suggests that technology should be understood to be not just material objects but material objects together with social institutions, social practices, and human relationships. In this view, ethical and value issues may be present at any point in the life cycle of a technology, from design, to manufacture, to marketing and distribution, to adoption and use. Second, a good deal of STS literature addresses the values embodied in the design of material objects and this has enormous implications for understanding the possibility of moral values being 'in' material objects. Third, understanding the connection between ethics and technology opens up the possibility of better understanding the role of human agency in technology-mediated activities and consequently the accountability of humans for such activities.
The project is philosophical and theoretical in nature, not empirical. While the research to be done will draw on empirical studies of technology, the methodology of the project is conceptual, thematic, and analytical. The investigator is a philosopher who has worked both in STS and in the field of applied/ practical ethics, especially ethical issues in computer technology. Two post-doctoral research associates, one post-doc with a background in STS and one with a background in ethics are involved. Each will be trained to understand the other field so that both can assist in the development of the theoretical account and work on an individual project.

The purpose of this innovative working conference is to more deeply address cultural variations in research on parenting and socialization in diverse families. The working conference will provide the opportunity to present a number of collaborative research projects that begin to remedy gaps in the literature on diverse families and deepen the study of culture and parenting processes. The projects discussed at this conference will be developed from a cross-section of more than 20 existing data sets accessible to members of the Study Group on Race, Culture and Ethnicity (SGRCE), a diverse group of scholars who have collectively been working toward advancing research on family functioning and child development. The primary activity of the group will be to develop a series of studies/papers that share constructs within two main areas of study-- parenting and, ethnic identity and socialization. During the conference collaborators will present findings from the various studies conducted and discuss the convergence across data sets and cultures. Finally, plans will be made to fuse data sets based upon what we have learned from the research and presentations to guide future research. More broadly, the conference is meant 1) to further the development of a more in-depth and inclusive study of diverse families, which we are calling an excavation of culture; 2) to incorporate and embrace an approach to research on families of color that is responsive to policy and practice concerns; 3) to advance each particular set of joint analyses through consultation with expert statistical consultants; and 4) finally, to publish the resulting group of papers on these issues.

DESCRIPTION (provided by applicant): Deregulation of epidermal growth factor receptor (EGFR)-mediated signaling is key to the pathogenesis of many human cancers. As new therapeutic agents are being developed that target these receptors, it is crucial that we define their downstream targets to better understand the function of these drugs, allowing the design of more selective therapeutic agents. The TATA-binding protein, TBP, is a central transcription factor used by all cellular genes. Our previous work revealed that oncogenic Ras increases TBP expression, producing selective but pleiotrophic effects on cellular transcription. Furthermore, increased concentrations of TBP can promote cellular transformation. Although all EGFRs activate Ras, our preliminary results suggest that EGFR1, HER-2 and the EGFR1 variant, EGFRvlll differentially regulate TBP expression. Our proposal will test the hypotheses that: (1) Expression of TBP is differentially regulated by members of the EGFR family, and that (2) EGFR-mediated induction of TBP expression contributes to the transforming function of EGFR. Our proposed studies will (1) Identify the signaling events activated by individual EGFRs that are responsible for their abilities to regulate TBP expression; (2) Identify the transcription components targeted by these EGFR-mediated signaling events that directly regulate the TBP promoter; (3) Test whether cellular TBP concentrations are critical for the phenotypic changes induced by EGFRs or their downstream signaling events. These studies will significantly impact our understanding of how cells become transformed. The results of these studies will define TBP as a new target of these receptors and signaling molecules, and establish the first link between a general transcription initiation factor and transformation. This information will form the basis for future genetic tests in mice that will address the role of TBP in oncogenesis.

PTEN is a tumor suppressor and the first phosphatase identified to be frequently mutated/deleted somatically in a variety of human cancers. Substantial evidence supports that loss of PTEN promotes the development of human cancer. PTEN normally serves to repress the activation of the PIS kinase signaling pathway. However, little is yet known regarding PTEN-mediated changes in gene expression that are lost in cells that lack PTEN. Our studies will examine the novel idea that PTEN, and PIS kinase/Akt signaling, regulates RNA polymerase (pol)Ill-dependent gene expression and that this regulatory event is lost in human carcinoma cells that exhibit reduced PTEN expression. As RNA pol III products, tRNAs and 5S rRNAs, determine the translational capacity of cells, repression of RNA pol III transcription by PTEN is likely to be fundamental to its tumor suppressing function. Our studies will identify new targets of PTEN, and elucidate in detail, the mechanism for how loss of PTEN leads to deregulation of RNA pol III transcription in several different human cell lines. By comparing cells that contain alterations in the levels of functional PTEN, we will: (1) Determine whether PTEN represses transcription of the three major classes of RNA pol III promoters;(2) Determine the PTEN/Akt-regulated signaling pathways involved in this response;and determine whether PTEN may also function in the nucleus to directly repress the transcription process. (3) Identify quantitative and/or qualitative changes in factor(s) of the RNA pol III transcription machinery that is/are specifically targeted by PTEN;and (4) Determine how these changes in the transcription components alters their function and the formation of transcription initiation complexes in vivo. From these studies, we will identify novel downstream targets of PTEN that are important for its function as a tumor suppressor and provide the first evidence that the deregulation of RNA pol III genes is a consequence of the loss of PTEN. Defining the PTEN-mediated signaling pathways and targets that are aberrantly regulated in cells that have lost PTEN function, giving rise to these specific consequences gene expression, will provide a valuable nexus for investigation of therapeutic agents that mimic PTEN function.

This award provides funding for a 3 year continuing award to support a Research Experiences for Teachers (RET) in Engineering Site program at the University of Maryland (UMD)College Park in partnership with the University of Virginia (UVA) entitled, "Research involving Design, Innovation and Invention Experiences for Teachers (Research DIIET)," under the direction of Dr. Leigh Abts.

This Research Experiences for Teachers (RET) in Engineering Site involves a rigorous six-week summer research schedule of active learning activities for a total of 39 middle and high school science teachers,13 each year for three years at both the UMD and the UVA campuses. The program also includes an academic year action research project. The teachers will be recruited from the Montgomery County, Maryland Public School System, the Danville and Pittsylvania Public Schools in Virginia and the Washington D.C. Friendship Public Charter School. The teachers will explore the 'abstract notion of innovation'-from basic scientific discovery to applied product development and will create classroom modules.

Computer Science (31)

This project is building on the success of an existing software laboratory to support a computer science course on Electronic Commerce Technologies developed under a prior NSF award (DUE 0127300) to expand e-commerce education by developing and disseminating materials that focus on a key element of e-commerce technology: security. The goal of this project is disseminate materials from the previous project and to respond to one of the grand challenges in the field of computer science - writing secure software. The prior project was devoted to developing materials to be used in training students to program components of e-commerce stores. This project is developing, testing, and refining teaching materials that emphasize the security requirements of e-commerce software. The PIs are developing coordinated lecture materials and supporting software laboratory exercises ("virtual labs"), in the following critical areas:

(1) Cryptography - the mathematics of security;
(2) Professional ethics - a sense of responsibility should precede knowledge and empowerment;
(3) Detecting and defending against attacks - the technology of hacking;
(4) Wireless access - the enabler for mobile commerce;
(5) Web services - a new approach to e-commerce security;
(6) Authentication, authorization, and federation - the crucial web service components that facilitate identity management and trust sharing among disparate systems.

This technical approach differs markedly from the business/legal approach taken in many extant e-commerce courses. Project emphasis areas include:

- security and on secure coding philosophies, strategies, tools, and techniques;
- collaboration between a computer scientist and philosopher (ethicist) leading to an emphasis on professional ethics;
- use and evaluation of six types of interactive staff support: office hours, email, NetMeeting, IM, FAQs, and student-operated message boards;
- a "teach-the-teachers" workshop for 20-25 faculty in the three summers, to include faculty from community colleges, liberal arts colleges, and science and engineering programs;
- a well-designed effort to recruit women and minorities in every aspect of the proposed work;
- an emphasis on "programming in context" in which students can see the practical application and social value of their artifacts;
- providing staff to support faculty at other schools with their adoption, implementation, use, and evaluation of these materials; and
- a multi-institution qualitative and quantitative evaluation of whether and how these materials changed learning outcomes for the students.

This interdisciplinary research project, funded by the Science, Technology, and Society Program, seeks to better understand the social consequences of surveillance. The growing prevalence of surveillance, facilitated by increasingly sophisticated information technologies, is well documented. However, the social implications for democratic societies of so much tracking, monitoring, and sorting of individual behavior is less well-understood. At the same time, interest in transparency policies is growing in calls for more transparency of government and corporate practices. Transparency is seen as a remedy for the negative effects of surveillance. This project reframes surveillance and transparency in viewing them both as systems of accountability. Accountability provides a novel lens through which to view the normative structures of these two systems and will be understood to involve: (1) an individual or organization; (2) an account of that individual or organization, focused on a particular domain of activity; and (3) a group, organization, or individual that uses the account to make decisions. Further, surveillance and transparency will be analyzed as sociotechnical systems: the social structures and cultural meanings constitute, and are in turn constituted by, the information technology systems in which they are realized. This framework will guide the creation of five case studies which will provide the basis for analysis and cross-comparison. The five cases cover government, corporate and non-profit organizations. An interdisciplinary team of scholars will analyze the cases and do the cross-case comparisons, yielding both new insights into transparency and new understandings of the social implications of surveillance. These analyses will examine how the rationales for creation of systems gets translated into their actual workings; how IT has an impact on that translation; and how the systems affect underrepresented groups in science and engineering.

This award to the US National Academy of Engineering establishes a Phase I Climate Change Education Partnership (CCEP) in collaboration with Arizona State University, Museum of Science-Boston, University of Virginia, Colorado School of Mines, and the Phoenix Union High School District. The overall goal of CCEP Phase I is to establish a coordinated national network of regionally- or thematically-based partnerships devoted to increasing the adoption of effective, high quality educational programs and resources related to the science of climate change and its impacts. This award focuses on the impacts of climate change for engineered systems. The goal is to catalyze and transform engineering education in K-12, science museums, and undergraduate engineering departments to prepare current and future engineers, policymakers, and the public to meet these challenges.

In coming decades, climate change and society's responses to it will require enormous transformation of the nation's technological infrastructure. Current US education falls short of preparing the country for this challenge. Educational platforms must focus on the multiple, complex interactions between engineered systems and the Earth's climate system. At the same time, transformation raises societal challenges, including trade-offs among benefits, costs, and risks, and opportunities for building public trust, confidence, and engagement. New education must integrate technical and normative learning, knowledge, and skills, in formal and informal educational venues.

This partnership will develop a comprehensive vision focused on three themes: (1) climate impacts on engineered systems and their adaptation; (2) changes in engineered systems required to mitigate greenhouse gas emissions; and (3) the creation of novel technological systems to engineer the Earth's climate system. Cutting across themes, it will examine challenges of: (1) governance; (2) justice; (3) sustainability; and (4) public engagement and trust. It will reach out to engineering professional societies, educators and deans, K-12, informal science institutions, industry, non-governmental organizations, media, and policymakers. Working with the Phoenix Union High School District, whose 25,000 students are 78% Hispanic, 10% African American, and 3.2% Native American, allows the Partnership to devise appealing programs for students of diverse backgrounds.

Phase I involves working groups organized by theme and target audience. One or more content working groups focus on developing an inventory of climate education materials integrating technical and normative education. By the end of Phase I, the Partnership will have marshaled a broad network of stakeholders from the target audiences and submitted a proposal to NSF for Phase II. It will have published and disseminated material from the three thematic meetings, as well as results from the project working groups, so content and approaches needed to initiate new formal and informal educational efforts are widely available. More information on this project is available at http://www.nae.edu/21302.aspx, or by contacting the PI, Rachelle Hollander at rhollander@nae.edu.

DESCRIPTION (provided by applicant): In the previous grant period, we made the unexpected discovery that members of the epidermal growth factor receptor family differentially regulate expression of the central transcription initiation factor, TBP, and defined new signaling pathways and transcription factors that regulate TBP expression. In addition to identifying positive regulators of TBP, we discovered a novel human protein, Maf1, which represses TBP transcription. Maf1 is an important transcriptional repressor that uniquely targets both RNA pol II- and pol III-transcribed genes that promote oncogenic transformation. Our new results support the idea that Maf1 is a key target of PTEN that is critical for its tumor suppressor function. Loss of PTEN results in a marked decrease in Maf1 expression; increased Maf1 expression suppresses cellular transformation in PTEN- deficient cells; and nuclear Maf1 expression is diminished in both mouse and human prostate cancers that are PTEN-deficient. Our overall goal is to understand the molecular and biological function of Maf1, and to use mouse models to determine whether the resultant decrease in Maf1 expression, by loss of PTEN, contributes to the development of prostate cancer. Aim 1 will identify Maf1 occupied regions genome- wide in primary human prostate epithelial cells. Given our newly identified interaction between Maf1 and the transcription factor Mediator CDK8 subcomplex, we will further test the novel hypothesis that Maf1 blocks the ability of this subcomplex to induce both RNA pol II- and III-dependent gene expression. These studies will define new paradigms by which transcription from different RNA polymerases are co-repressed, thus elucidating important gene repression pathways. Given that CDK8 is a potent oncoprotein, Aim 2 will further assess whether Maf1 abrogates CDK8-mediated oncogenic transformation. A transgenic mouse model will be established to test the idea that restoring Maf1 expression in PTEN-deficient mouse prostate will block or delay prostate intraepithelial neoplasia and tumorigenesis. Characterization of Maf1 will provide a new paradigm for how cells suppress a transformed phenotype and define a novel PTEN target whose loss is critical to the development of prostate cancer.

Moral notions and practices shape and are shaped by new technologies. Ethics for developing technologies involves identification and analysis of the ethical issues associated with a new technology in ways that can influence its design and use. Bringing ethical perspectives into the early stages of technological development is the best opportunity for those perspectives to have an influence.

This project examines the discourse around artificial agent technology--computer systems that are described as autonomous decision-making entities--in order to understand how moral concepts and practices shape and are shaped by new technologies. Concepts of agency and autonomy are central to morality; they underpin the very possibility of morality and are strongly linked to concepts of responsibility and accountability. This project will examine how computer scientists and engineers conceptualize issues of responsibility with regard to artificial agents.

The project will focus on two case studies: 1) the discussion centered around artificial moral agents, and 2) the discourse about autonomous military robots. The overarching descriptive research question for each case is: How are notions of responsibility, agency, and autonomy being negotiated? The overarching normative question is: How should artificial agents be conceptualized and designed? The methodology combines discourse analysis, philosophical analysis, and in-depth interviews with computer scientists and engineers. The project will have broader impact by training a postdoctoral fellow in ethics in science research and qualitative social science research methods. The results will be disseminated broadly to scholars as well as those who are engaged in the development of artificial agent technology.

Introduction

This postdoctoral fellowship will support research on water infrastructure in Panama; it focuses specifically on the networked infrastructures that supplies water for both shipping and municipal use. The project has three phases focusing respectively on installation, maintenance, and use. Each phase is structured in terms of a core question. The first phase asks how the water management infrastructure that links the canal with the two cities at its endpoints, Panama and Colon, shaped system development and regional water distribution problems. It will be answered through historical research at archives in the US and Panama. The second asks how expectations and practices of infrastructure maintenance compare between the two institutions that manage water in the study region. This question will be answered through participant observation and interviews with work crews and administrators at both water management institutions. The third asks how urban water users perceive delivery problems and develop household strategies to cope with them. This question will be answered through semi-structured interviews and participant observation in urban Panama.

Intellectual Merit

The project will advance scholarship in three areas. It will merge STS scholarship on infrastructure and political ecology in a novel manner resulting in a new, powerful framework that will benefit both fields. It will utilize the new framework to advance scholarship in the emerging Science and Technology Studies subfield, Water Studies. Finally, it will provide evidence to better theorize how infrastructure functions across geographical and cultural differences, illuminating how these systems work when irregular maintenance and service interruption are a part of everyday life.

Potential Broader Impacts

Infrastructures have become visible sites of economic anxiety, political struggle, and ecological crisis in recent years. Communities worldwide face problems of service delivery associated with aging infrastructure and state budgetary shortfalls. The research will generate new knowledge about technology, society, and ecology under these conditions that is relevant to engineers, planners, and administrators who seek to design and manage socio-technical systems in more culturally appropriate, equitable, and sustainable ways. The project will illuminate how urban water problems are produced and might be ameliorated. Findings will be disseminated to multiple audiences through academic conferences, publications in peer-reviewed journals, public workshops, and the training of engineering students.