John Fowler - US grants

The Triangle Coalition of Science and Technology Education held a conference on Local Alliances for Science and Technology Education at the Wingspread Conference Center, Racine, Wisconsin. One of the most important outcomes of this conference will be a Handbook on Local Alliances, which will contain guidelines and suggestions for the development and operation of local or regional support groups. This Handbook will include descriptions of existing local organizations which could provide nuclei for local alliances, lists of cooperating professional organizations, examples of local alliance activities, budgets, sources of funding, do's and don'ts for the formation of such alliances, and suggestions for long-range alliance goals and strategies.

This project will test the feasibility of recruiting, training, an deploying a cadre of volunteers who are competent scientists and/or engineers and who will work in the schools as teacher aides. Five sites, all locations of existing Triangle Coalition collaboratives, will serve as the recruiting and training centers. Science teachers from cooperating schools will specify tasks for the volunteers and will assist in conducting the training workshops. For one academic year, the volunteers will work in the schools. During that year, data will be collected on the effectiveness of the service provided by the volunteers. The goal is to recruit a total of 25 volunteers (5 per site) who will contribute a total of 9000 hours of service (360 hours per volunteer). The project will be conducted under the general supervision of John Fowler of the National Science Teachers Association. Significant assistance in the recruiting and training procedures will be provided by the National School Volunteer Program.

Electronic networks, ranging from local to national in scope, have been developed for a variety of purposes. Persons involved in science and mathematics education at the K-12 level have increasingly been identifying ways in which such networking could be useful, and experimenting with the creation of such networks. It now seems appropriate to draw on the experience of both educators and electronics experts to define optimum characteristics of such networking activities and systems, including the hardware, software, databases, and interconnects. These guidelines should be useful to educators in facilitiating the efficient establishment of new networks and to funding agencies in deciding how best to allocate funds for networks. A small working conference of persons experienced in the electronics of networking and in the educational applications of networking will draft guidelines for the design and operation of networks for the K-12 science and mathematics education community. These will subsequently be refined and compiled into a report which can be broadly distributed. The objective will be to provide practical guidance to anyone interested in linking K-12 schools and teachers electronically in the most effective and economical way.

DESCRIPTION (Investigator's Abstract): The overall objective of this proposal is to understand factors that determine the extracellular levels of endogenous adenosine during conditions of cerebral hypoxia and/or ischemia.Adenosine acts as a potent endogenous neuroprotectant and augmentation of adenosinergic tone appears to be a reasonable basis for therapeutic intervention in cerebral ischemia. To model various states of metabolic stress, the rat hippocampal slice is exposed to conditions of hypoxia, hypoglycemia and in vitro ischemia which is combined hypoxia + hypoglycemia. We correlate electrophysiological indices of neuronal responsiveness with HPLC and isotope measurements of adenosine influx. In the last grant period, we show that a moderate elevation in levels of the inhibitory neuromodulator adenosine contributes to the early, reversible depression of synaptic transmission during hypoxia, hypoglycemia and in vitro ischemia. When exposed to extended conditions of in vitro ischemia, adenosine efflux abruptly rises four to sixfold in close temporal association with an anoxic depolarization whose occurrence is strongly correlated with the irreversible loss of synaptic transmission. The stimulus or trigger for this relatively large release of adenosine is not known. In vitro ischemia is associated with a number of events including: '1) increased intracellular Ca2+,2) excessive release of excitatory amino acids, particularly glutamate, 2) an anoxic depolarization, and 4) ATP depletion. Under normoxic conditions each of this stimuli may affect extracellular adenosine levels. Based on our work and that of others we propose the following working, hypothesis: The anoxic depolarization induces the release of glutamate which, through activation of glutamate receptors, initiates a large Ca2+ influx. The Ca2+ influx triggers, perhaps through ATP depletion, a substantial release of adenosine. The proposed studies will provide insight into the acute neuronal response to ischemic conditions and will provide an increased understanding into adenosine's role as an endogenous neuroprotectant and its potential use in therapeutic 'intervention of cerebral ischemia.

The Triangle Coalition for Science and Technology Education has requested support for a two-year project to expand a pilot project designed in 1988 into a systematic and replicable mechanism nationally that advances institutional change locally through a collaboratively planned and implemented volunteer program in science, mathematics, and technology. They propose a two-stage expansion: Phase I involving 20 - 30 project sites, perfecting pilot training procedures and materials. Phase II involving an additional 100 sites using the procedures and materials developed in Phase I. The Foundation's support represent less than 10% of the anticipated project costs, with the private sector contributions estimated to be on the order of several million dollars.

9713750 Fowler This grant provides funding for the development of methods for optimizing the design and operation of semiconductor wafer fabrication facilities. Descriptive issues concerning performance evaluation, as well as prescriptive issues concerning scheduling and planning will be studied. The goal of the research on performance evaluation is to develop methodologies for determining the impact of process time variabilities, release policies, scheduling policies, hot lots, equipment failures, product mix, and cluster tools on the cycle-time performance of the plant. In the area of scheduling, the goal is to design and analyze policies for making real-time decisions concerning when to release new wafer lots into the plant, and how to schedule the large numbers of stations in re-entrant fabrication lines in the presence of equipment failures, set-up time constraints, batching considerations, and operator availability constraints. In the area of planning, the goal is to study the issues of yield learning, equipment utilization over time, effects of adding equipment over time, ramp-up, and non-stationary behavior. Also, problems of managing capital outlays over time in the face of demand uncertainty will be studied. If successful, the results of this research will lead to improvements in the design and operation of semiconductor fabrication facilities. They will provide methods for the prediction of the performance of large fabrication facilities before they are built. They will also provide methods for efficiently scheduling the complex operations of expensive fabrication plants so as to improve their cycle-time performance. The research work will thus contribute to the understanding of how to design and operate large wafer fabrication facilities.

DESCRIPTION: (Verbatim from the Applicant's Abstract) The long-term goal of this research is to understand the (patho) physiologic role of the inhibitory neuromodulator adenosine in the brain's early resp0onse to stroke. Understanding adenosine's contribution is important because adenosine-based pharmacological interventions show promise in reducing neuronal hypoxic/ischemic injury in a number of animal models [31,34,83,87,117]. The specific focus if this proposal is to extend to an in vivo model of the PI's previous series of studies performed in the in vitro hippocampal slice. These in vitro studies detailed adenosine's substantial mediation of the early reversible depression of synaptic transmission and adenosine's interaction with the anoxic depolarization in response to ischemic-like conditions [39-42,44]. Surprisingly, in spite of an extensive literature describing adenosine's role I in vitro slice preparations [9,24,52,69,89,90,142], there has yet to be, to the best of our knowledge, a demonstration of adenosine's role in vivo. The following specific aims, therefore, focus on examining the contribution of salient observations made in vitro to an in vivo hypoxic/ischemic rat hippocampal model. The following specific aims will be addressed: Specific Aim 1. Determine the role of adenosine receptors in the in the early hypoxic/ischemic depression of synaptic transmission in vivo. Specific Aim 2. Examine the relationship between adensone receptor activation, inhibition of evoked synaptic potentials and tissue pO2 in vivo. Specific Aim 3. Determine the influence of adenosine receptor activation on development of the anoxic depolarization during extended hypoxia/ischemia in vivo. And, examine adenosine receptor function in the post-ischemic period after the anoxic depolarization.

The semiconductor manufacturing supply chain is very complex spanning multiple manufacturing sites in various locations around the globe. This grant provides funding that will allow the multidisciplinary research team to use experience gained in factory control to develop control regimes for semiconductor supply chains. The goal is to efficiently and effectively a) model and simulate the physical entities, b) model and simulate the range of decision algorithms, and c) interface the two. The research team has taken a first step toward this. To depict the physical system a basic module was developed that could be used to represent a factory, a transportation link, or a warehouse. The basic module is made up of capacity and delay sub-modules. A supply chain is modeled by connecting basic modules together in series or parallel. This approach provides reasonable execution times while still capturing the qualitative behavior of these systems. Therefore, the research team will first determine reasonable ways to parameterize the basic module. Next, software architectures to support the modeling and analysis of semiconductor supply chains and ensure scalability will be investigated. Real semiconductor supply chain problems (supplied by the industrial participants) will be used in addressing both the parameterization and architecture issues. Finally, how the approach can be implemented in next-generation ERP systems will be studied.

If successful, this research will have an impact on the System Architecture of next-generation ERP systems by determining how to include scalable "what-if" capabilities in these systems. It will also facilitate Collaborative Decision Making in scalable enterprise systems by allowing one group of people to describe the way their factories work and another group of people to specify enterprise decision policies. Finally, it will allow for the analysis of various Supply Chain Design issues by providing new modeling and analysis capabilities.

This Small Grant for Exploratory Research (SGER) will investigate methods for evaluating and comparing heuristically derived solutions to multi-objective combinatorial optimization problems. Almost all such problems are NP-Hard, so characterizing the Pareto-optimal efficient set is computationally intractable. The research will draw on heuristic and approximate solution methods for these models, and structure a approach to comparing them based on distance to the (possibly) unknown Pareto set. Drawing on promising preliminary results for small models, the research will seek to develop and extend the methods to higher dimension.

Multi-objective optimization problems model important tradeoffs that decision makers face in many settings. For example, in strategic facilities location problems, decision makers must trade off minimizing cost and maximizing service. Most of these problems are also combinatorial, in that discrete decisions such as build or don't build require choice of one option or another without the opportunity to compromise the difference. Such models are so common in engineering practice that advances in methods for treating them have great potential significance to the broad field of operations research.

This grant provides funding for the development of efficient and effective tools for the estimation of cycle time-throughput (CT-TH) curves via computer simulation. Unlike analytical queueing models, computer simulation can be used to represent almost any manufacturing system regardless of how complex. Unfortunately, simulation allows for the evaluation of only one point at a time on the CT-TH curve, so tools are needed to guide the simulation for development of the full curve. Since the CT-TH curve for real manufacturing systems is subject to variability, this research will identify and derive appropriate models and tools to represent not only the mean of the curve, but also its variance and selected percentiles, especially in the region of maximum system capacity. The tools for constructing the CT-TH curves will be adaptive and selective both in terms of the models used and the precision required by the user. Accurate model determination will be directed under both fixed-budget and fixed-precision settings. Experiments to evaluate the methods developed will be conducted on a test bed of tractable queueing models and a large-scale simulation of a semiconductor manufacturing facility.

If successful, the results of this research will provide methods for efficiently generating the CT-TH curves associated with simulation models of semiconductor manufacturing facilities. Since CT-TH curves can be used to quantitatively evaluate different scenarios of product mix, production targets and capital expansion, the primary goal of this work will be to develop simulation methods for generating accurate CT-TH curves given finite resources. Compared to existing methods, this work will increase the number and complexity of manufacturing system evaluations that can be conducted leading to improvements in production facilities. Production improvements will lead to subsequent reductions in production cost and/or increases in throughput. The proposed work will also contribute to the tools available for model fitting, variance reduction and fixed sample allocation in large-scale simulation models.

This grant aims to improve the design and operation of surgical delivery systems (SDSs). There are four primary research goals. First, develop new models and methodologies for determining the optimal investment and configuration of surgical resources under uncertainty. Second, construct advance scheduling systems that allocate surgeries in a multi-OR setting. Third, develop robust real-time scheduling systems that consider the impact of unanticipated events on initial schedules. Fourth, develop a sophisticated discrete-event simulation model to evaluate the models described above, and compare them to existing policies.

The broader impacts of this project will affect all Americans by improving the efficiency of a critical part of the health-care delivery system. ORs account for more than 40 percent of a hospital's revenues, and preliminary research indicates that these scarce resources are not being optimally deployed. Faster access to care will directly improve patient outcomes, and more efficient allocation of ORs will reduce health care costs, and permit health care providers to focus on other activities.

PI: Matthew Evans (Carnegie Institution of Washington)
CoPIs: Donald Auger (South Dakota State University; subawardee), John Fowler and Scott Givan (Oregon State University; subawardees), Erik Vollbrecht (Iowa State University; subawardee)

Collaborator: Kelly Beck, Gabriel Garcia (Stanford University; subawardees)

An understanding of the genetic basis of gametophyte function will have important implications for agriculture, as gametophytes are central to plant reproduction. The female and male gametophytes make up the haploid phase of the angiosperm life cycle, which immediately succeeds meiosis and precedes formation of the seed (embryo and endosperm). Although gametophytes are small and undergo few cell divisions, they are crucial for reproduction, as they produce gametes, control the fertilization process, and influence development of the seed. However, because mutations that are deleterious to these haploid tissues are difficult to recover and maintain, relatively little is known about the genetic and cellular mechanisms underlying gametophyte function and development, especially in crop plants. This project seeks to overcome this limitation using genetic tools unique to the model crop Zea mays (maize) to accomplish a genomic-scale investigation of gametophytically-required genes. Trisomic stocks that transmit duplicate chromosomal regions through the gametophyte will be used to screen for Activator transposon-tagged gametophyte-lethal mutants. The phenotype of these mutants will be characterized in male and female gametophytes, and the corresponding DNA sequences of the mutated genes identified. Verification of the identity of a select group of candidate genes will be accomplished using multiple alleles and RNA expression analyses. Complementary aims in expression profiling of gametophytes and in bioinformatics - to identify orthologous genes in other plant models and integrate the data generated by the project - will allow an assessment of the genetic basis of gametophyte function. Finally, the ability to predict gametophytic functions across species boundaries will be tested using RNA interference to target select genes in the dicot model Arabidopsis thaliana.

Broader Impacts:

This project is relevant to many agricultural objectives seeking to influence plant reproduction - for example, controlling pollen fertility for hybrid seed production, limiting pollen-mediated transgene flow, and inducing apomixis. Because the tools and stocks created, and sequences generated, will be freely available to the scientific community, the project will enable other researchers to better investigate gametophytes through creation of a gametophyte-specific sequence-indexed mutant collection. All stocks created by the project will be deposited in the Maize Coop Stock Center (maizecoop.cropsci.uiuc.edu). All Ac transposon flanking sequences will be searchable by BLAST, both at PlantGDB (www.plantgdb.org), and at the project''s database: ZGamDB (maizegametophyte.org). Phenotypic and expression data will also be accessible at ZGamDb. For long-term storage and broad community access, phenotypic and genetic data will be incorporated into MaizeGDB (www.maizegdb.org), and expression data will be deposited at the Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo) and the Plant Expression Database (www.plexdb.org).


The project will help train 10 undergraduates to serve as science mentors for K-12 students, through exposing them to plant science research. In partnership with Stanford University''s Haas Center for Public Service, these undergraduate mentors will be placed in communities with large populations from under-represented groups, and help develop science experiences for K-12 students. In addition, the project will train two postdoctoral researchers and a graduate student in genomic-scale approaches to plant biology, and will introduce undergraduates and high school students to genomic science.

This award provides funding for the support of student travel to the Winter Simulation Conference 2012, Berlin, Germany, 9-12 December 2012. Specifically, the students will be attending the PhD Colloquium (workshop) followed by the technical conference. The abstracts of the students' work will be published in the WSC2012 proceeding, which has wide distribution. The WSC PhD colloquia have been highly successful in providing a forum for the initial socialization into the field of young doctoral scholars; many of today's leading simulation researchers participated as students in earlier colloquia.

This travel grant will encourage the interaction of the US emerging scholars with their counterparts and senior researchers from Europe and elsewhere, increasing the international awareness of the participating US students. The PIs will work with the conference organizers to identify and include the broadest possible group of highly qualified PhD students, especially those coming from under-represented groups.

INTELLECTUAL MERIT
This project seeks to understand the mechanisms by which plant cells control the delivery of proteins and other functional molecules to their outer surface, the region defined by the plasma membrane and surrounding cell wall. This process is known as vesicle trafficking, as proteins are produced within the cell, packaged into small, membrane-bound carriers (vesicles), and then moved to the plasma membrane for final delivery. This process is important because: 1) it is the primary mechanism used to build and to control the plant cell interface with its outside environment, which can affect how the plant interacts with harmful or beneficial microbes; 2) it is crucial for cell growth; 3) it is a regulator of cell-cell communication between cells; and 4) it is crucial for the acquisition of nutrients from the surrounding environment via specialized plasma membrane-localized protein transporters. The molecular mechanisms regarding how vesicle trafficking are controlled are not well understood. One player that appears likely to control this process in plant cells is the eight-protein exocyst complex, which provides spatial regulation at the plasma membrane for vesicle trafficking. This project uses the Arabidopsis root hair as a model and investigates the exocyst-mediated vesicle trafficking pathway (EMVT). EMVT is required for proper growth of the root hair, a key structure for nutrient acquisition. The project seeks to understand how root hair growth relies on EMVT through: 1) Characterization of exocyst interactions with other known components of the vesicle trafficking system; and 2) Molecular identification of a new gene (NERD1) which interacts functionally with the exocyst in the Arabidopsis root hair. The project should build a deeper understanding of how the function of plasma membrane-targeted molecules is enabled and controlled, and how precise patterns of cellular growth are affected.

BROADER IMPACTS
The knowledge generated in this project may have broad implications for plant physiology and development. Due to its hypothesized connection to the plasma membrane, EMVT may help mediate interactions between root and soil. Thus, this work could inform applied work that seeks to manage plant responses to abiotic stress induced by the surrounding environment (e.g. drought, salinity, and nutrient-poor soils), to pathogens, and to interactions with the rhizosphere microbial community. In addition, the project will train a postdoctoral researcher in integrating genetic, cell biological and next-generation sequencing approaches, and will mentor undergraduate students in plant genetic research. Finally, this project will support outreach efforts to high school students through the Apprenticeships in Science and Engineering program at Oregon State University.

PI: Matthew M. S. Evans (Carnegie Institution of Washington)

CoPIs: Donald L. Auger (South Dakota State University), John E. Fowler (Oregon State University), R. Keith Slotkin (The Ohio State University) and Erik W. Volbrecht (Iowa State University)

Senior Collaborators: Allison Phillips (Wisconsin Lutheran College) and Jennifer Eustaquio (Stanford University)

This project comprises foundational research on epigenetics and gene expression, and thus may have broad implications for the manifestation of important plant traits, particularly in crops with large numbers of transposons in their genomes. More specifically, gametophytes are central to plant reproduction; thus this project is directly relevant to several agricultural objectives (e.g., controlling pollen fertility, limiting pollen-mediated transgene flow, inducing apomixis), particularly given the project's focus on a crucial crop plant, maize. Additionally, the project will provide a data framework for other researchers to determine how gametophytes function and how they can be manipulated to generate improved crop plants. This project will train a number of undergraduate, graduate and post-graduate scientists in an interdisciplinary fashion through frequent exchanges between the partnering laboratories. Undergraduates will gain experience in modern laboratory techniques as well as computational analysis of large-scale data sets. Undergraduate students will simultaneously be trained as researchers and educators through Stanford University's Science in Service Program. Undergraduates learn to be Science Mentors for high school students and develop laboratory curricula that are then performed by local high school programs under the supervision of the undergraduate mentors. As part of the project, students from the high school programs also participate in the project, getting exposure to genetics and image analysis.

Within the floral tissues of flowering plants, multicellular haploid female and male gametophytes produce the gametes that undergo fertilization to produce seeds. Although gametophytes are small and undergo few cell divisions, they are crucial for producing the next generation, and execute diverse biological processes. Plant seed formation and reproduction, and thus global agriculture, are dependent on gametophyte function. In spite of their critical role in plant reproduction, gametophyte function and development has largely been overlooked due to their small size and imbedded location within the parental tissue. The maize genome, like many crop plant genomes, harbors a large number of mobile DNA elements, called transposons, and control of these elements, often through regulation of epigenetic states, is critical for maintenance of gene function and genome structure. Gametophytes help set epigenetic states in the next generation, however little is known, especially in the female gametophyte, about how transposon expression is regulated, and how that control impacts the concurrent expression of protein-coding genes. This project will use tissue micro-dissection techniques and whole genome analysis to understand the mechanisms that underlie developmental regulation of epigenetic states and cellular functions in the gametophytes of both sexes in maize. This project will screen for new mutants and genes that function in gametophyte development; perform genome-wide analysis of expression of genes, transposons, and different classes of RNAs with cellular detail; generate visual reporters for transposon activity; and characterize transposon expression in developing gametophytes. This project will determine the spatial and temporal expression pattern for genes and transposons in developing gametophytes, as well as define how they function to program gametophyte development. The effect of relevant mutants on transposon expression is expected to increase understanding of the interaction between basic gametophyte development and control of transposon activity in the important crop plant, maize. The sequence gene expression data generated from this project will be widely accessible through the project website (www.maizegametophyte.org) and the National Center for Biotechnology Information Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo), and the Maize Genetics and Genomics Database (maizegdb.org). Seed stocks will be deposited with the Maize Genetics Cooperation Stock Center.

Pollen is made of two cell types, sperm cells and pollen vegetative cells, each with different sets of active genes. Pollen vegetative cells carry the sperm cells inside them on their journey first through the air and then through the female reproductive structure to fuse with eggs and make seeds. During this process, the pollen vegetative cells use a large number of genes to grow and develop and to protect their cargo of sperm cells. Robust pollen that can survive adverse environmental conditions is essential for high yield in crops like corn (maize). Especially in regard to heat tolerance, pollen is an important consideration in crop improvement. Recent discoveries have revealed that enzymes called DNA glycosylases, which change the structure of DNA, are important for activating genes in pollen vegetative cells. This project aims to investigate the function of these enzymes in corn pollen. The results will yield new knowledge about pollen genetics and new tools for putting that knowledge to use in plant reproduction.

DNA methylation generally represses repetitive DNA. In certain situations, however, DNA methylation can regulate developmental gene expression. In plants, DNA glycosylases remove methylation and can mediate epigenetic inheritance. The goal of this project is to identify both genes and intergenic regions of the genome that are targeted for demethylation and to determine the functional significance of demethylation in pollen. This will involve a novel approach to determine the effects of demethylation on gene expression at single-cell resolution in mixed populations of normal and glycosylase-defective pollen. The capstone of the project will be testing the potential of engineering glycosylases to demethylate specific genetic elements. This will be an initial step toward a larger goal of creating experimental resources for studying the consequences of methylation as well as for epigenetically controlling gene expression in pollen, with potential for heritability into the next generation.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.