John White, PhD - US grants

The small intestine actively secretes HCO-3 and actively reabsorbs HCO-3 (or secretes H+). These processes are important in the normal function of the small intestine and in pathophysiological circumstances such as diarrhea. Nevertheless, the underlying ion transport events are unresolved and the intercellular and extracellular control mechanisms are not known. Moreover, the transporting cells responsible have not been identified. A subpopulation of mucosal cells in the jejunum of the urodele (Amphiuma) has been found to contain acid vesicles when exposed to the fluorescent stain acridine orange (AO). pH and K+ sensitive microelectrodes will be employed to measure the ion content of the vesicles and cytoplasm of the secretory cells of in vitro intestinal segments. Hypotheses regarding the cellular mechanisms of acid secretion will be tested. Scanning and transmission electron microscopy will be used along with AO flurosescence to determine the morphology of the secretory cells and their associated vesicles and to distinguish whether the changes in acid secretion result from changes in acid storage of H+ transport. The identity of the cells responsible for the enhanced acid secretion caused by catecholamines such as epinephrine will be determine and the ion transport events induced by catecholamines including, apparently, Na-H exchange studied in detail. The effect of cholinergic agents to reduce acid secretion will be examined. The ability of cholinergic agonists to stimulate HCO-3 secretion in the duodenum and adrenergic agents to block the effect will be documented using the pH stat technique. The effect of these agents on Na and C1 transport will be determined. The possibility that methacholine acts through elevation of cyclic AMP will be examined. These studies will provide the first electrophysiological and morphological analysis of an identified acid secretory cell in the intestinal mucosa. Whether the catecholamine-driven acid secretion is from the same or a different cell will be determined. The ion transport mechanisms responsible for spontaneous and epinephrine-stimulated acid secretion will be determined.

Microelectrodes including ion-sensitive microelectrodes will be used in conjunction with isotopic tracer techniques to investigate, in vitro, how the large enterocytes of the amphibian duodenum are able to effect transepithelial secretion of HCO3- or its equivalent) and absorption of Cl-, the way in which these parallel transport processes are linked in the transporting cells and the manner in which the level of cyclic AMP in the cells influences the rate of these parallel transport events. Two hypotheses will be tested. First, that the rate of HCO3- secretion is a function of intracellular HCO3- activity (aiHCO3-) or pH. Secondly, that the level of Cl- accumulation achieved by the enterocyte is a function of intracellular (HCO3-) activity or pH. In order to define the transmembrane driving forces for HCO3- secretion aiHCO3 will be assessed by employing microelectrodes sensitive to HCO3- or pH. In the same way intracellular Cl- activity will also be assessed. Different experimental manipulations will be employed to determine 1) the relationship between intracellular HCO3- activity and the secretory HCO3- flux. The response of villus and intervillus cells to elevation of cyclic AMP will also be determined. 2) the relationship between the level of Cl- accumulation achieved by the active mucosal uptake mechanism and the intracellular HCO3- activity and pH. The mucosal events in electrogenic Cl- absorption will be studied further by measuring the mucosal membrane potential, transepithelial potential and voltage divider ratio while electrogenic Cl- absorption is induced by addition of the anion to the medium. The role of luminal NaC1 cotransport will be examined by measuring labeled fluxes of Na+ and Cl- while electrogenic Cl- absorption is induced. Lastly, to examine the possibility that actively transported sugars stimulate intestinal Na+ absorption by lowering cell K+ the correlation between net Na+ absorption and cell K+ activity will be studied. The objective is to understand the mechanism of active Na+ absorption, active Cl- absorption and the related process of HCO3- secretion as it occurs in the normal intestine and in pathological states such as diarrhea and congenital alkalosis as a prelude to the development of effective therapies against these disorders.

Precisely controlled milliwatt levels of CO2 laser energy can fuse the protein-collagen matrix of tissues. The following proposal is designed to test the hypothesis that this method of tissue fusion used for vascular repair may provide better anatomic and functional results compared to conventional hand-sewn controls. The technical problems and functional alterations of conventional vascular repair methods of small vessels are well recognized: narrowing of the lumen, intimal tears, and stimulation of smooth muscle cells from repetitive transmural suture placement, leading to early thrombosis or prolonged functional alterations. The milliwatt CO2 laser may provide a useful method of tissue fusion because its energy is absorbed in a chromagen-independent uniform manner with a shallow depth of penetration. This study will evaluate the application of milliwatt CO2 laser tissue fusion techniques to the carotid artery and aorta of the rabbit. Methods, laser power, power densities, and energy fluence levels necessary to fuse the protein-collagen matrix of the media and adventitia will be established. Strength of the tissue fusion bond will be determined by slowly raising peak systolic pressures wih an epinephrine infusion to the point of anastomotic disruption or a maximum pressure of 300 mm Hg. Patency and anastomotic morphology in both the laser fused and hand sewn vessels will be evaluated non-invasively with B-Mode ultrasonic imaging. The nature of the laser-induced injury and the pattern of healing will be analyzed with sequential histology and scanning and transmission electron microscopy and compared to that generated by conventional transmural suture technique. These studies will provide a technical and functional analysis of the laser-created tissue fusion vascular anastomosis. The establishment of a method of tissue repair, particularly one which can be used for small vessel anastomosis and minimize disruption of the endothelial flow surface, may permit improved immediate technical results and less distortion of the blood-vessel wall interaction.

This grant in the Organic and Macromolecular Chemistry Program will support a series of three annual "Workshops on Reactive Intermediates." These workshops have the dual purposes of (1) providing an effective forum for informal discussion by active scientists of current research in topical areas of organic dynamics, and (2) assisting the Program staff in identifying areas of research in organic dynamics which require incorporation into the Program's long-range planning. Each workshop will bring together approximately 18 active scientists from around the United States for discussions of current research in mechanisms of organic chemical reactions, with an emphasis on critical evaluation of research in progress. The informal discussion format is intended to stimulate challenge and criticism, to facilitate the development of collaborative research approaches to common problems, and to prevent unproductive duplicative efforts. The participants are drawn widely from the community of physical, organic, and organometallic chemists working on the chemistry of reactive intermediates, and a particular effort is made to incorporate young investigators, women and minority scientists into the mainstream of research activity in the areas of organic dynamics. The topics chosen for discussion are selected to complement, not compete with, other established and more formal conferences.

This award is made in the Materials Chemistry and Chemical Processing Initiative in support of the collaborative research of Professors Cowley, Jones, Ekerdt and White at the University of Texas/Austin. Joint funding is provided by the Divisions of Chemistry, Materials Research, and Chemical and Thermal Systems. The principal objective is to achieve precise control of the physical and electronic properties of epitaxially grown semiconductor thin films through the rational design and chemical synthesis of single-source precursors. Novel single-source precursors will be prepared and their structures and stabilities determined. Thin films will be grown by chemical beam epitaxy and the adsorption, decomposition and surface desorption kinetics of the precursors will be studied by advanced surface science techniques. The relationship between precursor structure, surface reactions and materials properties will be explored in order to develop an atomistic description of how the precursors react at the interface and how film growth progresses.

The research, in the general area of Analytical and Surface Chemistry, focuses on surface chemistry. The work promises to lead to an understanding of the mechanisms by which the energy of a photon or electron is converted to electronic excitation that leads to bond breaking whithin chemical species attached to a metal surface. Such experiments improve our understanding of surface chemistry which can lead to better catalysts and thus cheaper and better chemical products. Metals such as platinum and silver will be used as substrates and alkyl halides used as model systems for species attached to these substrates. Photon-induced reactions among coadsorbed species (such as oxygen and ethylene) will be examined, as will the effect of laser-induced desorption of chemisorbed species on the metal surface.

This award will support the Science and Technology Center for the Synthesis, Growth and Analysis of Electronic Materials at the University of Texas, Austin. The research program of the Center is organized into two thrust areas--compound semiconductors and silicon-based materials. Within each thrust area chemists will synthesize molecular precursors and determine their surface and gas phase reactivities, and engineers and physicists will grow and analyze thin films of electronic materials made from these precursors, and construct and test new devices made from these films. A major component of the research will be the synthesis, purification and surface reactivity measurements of novel precursors, containing group III and group V elements in a single molecule, that have low toxicity and are suitable for film growth by advanced OMCVD and CBE techniques. Electronic materials, and the structures and devices derived from them, lie at the heart of numerous advanced technologies that have strategic and economic relevance. Through an integrated and collaborative research program, which links scientists and engineers at the University with scientists and engineers at Sandia National Laboratory, Texas Instruments Inc., and Motorola Inc., the Center will develop and demonstrate new concepts for electronic materials, structures and devices, which will lead to smaller, faster and more densely integrated electronic devices with tailored optical and electronic properties.

9319640 White This research project is in the general area of Analytical and Surface Chemistry and in the subfield of surface dynamics. During the tenure of this three-year continuing grant, Professor White and his students will investigate the kinetics and dynamics of photon- and electron-driven processes in molecular adlayers. From the photon-driven processes, both photochemical and photophysical events, as well as the competition between them, will be investigated. Using low energy electrons, comparable bond breaking and energy transfer processes will be studied. The objective of the project is to increase our understanding of both the kinetics and dynamics that are operative in nonthermal systems at surfaces. %%% The primary objective of this research is to investigate the interactions of photons and electrons with molecules adsorbed on solid surfaces. Improved understanding of such systems is important to progress in many technologically important areas of research including catalysis, separations, and environmental chemistry. ***

This renewal award is made in the Organic Dynamics Program in support of the research of Dr. Marye Anne Fox. The structure, chemical properties, photoreactivity, and new routes for the generation of stable radicals, biradicals, radical ions and carbenes will be investigated. Structure will be established by a comparison of solution phase and solid state NMR spectroscopy, by electrochemical techniques, and by transient and steady state photochemical probes for excited state reactivity. The effect of structure on the efficiency of photoinduced electron transfer and whether novel photoreactivity can be initiated by long wavelength visible or infared light will be explored. The effect of phase and local environment on selective partitioning among competing reaction pathways from a common excited state will be studied. This work will focus on understanding differences in typical photochemical behavior elicited by constraining a photoactive molecule within a size-constrained zeolite, within a self-assembled monolayer, within molecular solids, and in supercritical fluids. Progress in understanding the key reactions organic chemistry depends on the knowledge of the properties, stabilities and structures of reactive intermediates. Such knowledge is required for understanding the efficient utilization of light-adsorptive organic dyes in mechanistic chemistry, for the design of molecular conductors, semiconductors, and magnets, in the synthesis of surface-modified catalysts, and as a vehicle for understanding aggregation effects in controlling chemical reactivity. f8 Û-ª þ ; + S u m m a r y I n f o r m a t i o n ( ++++++++++++ ( Û ++++++++++++ ++++++++++++ ++++++++++++ + Ûª? ÑOh ª' +'ª?0 Ý + ] $ H l + ¢ ? D h + ++++++++++++++++++++++++++++++++ R:\WWUSER\TEMPLATE\NORMAL.DOT

The hippocampal formation, important for the process of laying down new memories, contains large amounts of zinc, located in synaptic vesicles and released with high-frequency stimulation. Furthermore, zinc exerts effects on many ion channels, some of which may be unique to the hippocampal region. Thus, it has been postulated, but not confirmed, that synaptic zinc and specialized zinc-sensitive ion channels act as a novel neuromodulatory system. As the next steps in testing this postulate, experiments are proposed here to test the following four hypotheses: Hypothesis A. The kinetics of zinc-induced block of voltage-dependent conductances are consistent with a neuromodulatory role. The kinetics of Zn2+-induced block of ion channels are crucial for determining whether this pharmacological effect has physiological significance. Using rapid solution-exchange and whole-cell patch-clamp techniques, these kinetics will be measured in dissociated neurons from the medial entorhinal cortex (MEC). Hypothesis B. Zinc-sensitive ionic conductances co-localize with Zn2+- positive nerve terminals in the hippocampal region. If specialized, Zn2+ -sensitive ion channels are the postsynaptic "receptors" of a novel neuromodulatory system, they are likely to be expressed in regions of the hippocampal formation other than the MEC. This hypothesis will be tested by recording from dissociated neurons from two additional Zn2+-rich regions: hippocampal region CA3 and the lateral entorhinal cortex (LEC). Hypothesis C. Zinc-sensitive Na+ channels of the MEC are structurally similar to cardiac Na+ channels. Demonstrating that Zn2+-sensitive ion channels are structurally related to cardiac Na+ channels, and hence different from known brain channels, would argue strongly that these channels are indeed "specialized." The structure of these channels will be probed using well-understood pharmacological manipulations in dissociated neurons. Hypothesis D. Endogenous, synaptically released Zn2+ modulates neuronal voltage-dependent conductances in the hippocampal region. To argue that Zn2+ modulates voltage-gated conductances in the MEC, LEC and region CA3, one must demonstrate that endogenous synaptically released Zn2+ reaches and affects these conductances. This demonstration will be attempted in recordings from hippocampal-entorhinal brain slices. The overall goal of this project - an understanding of the role zinc plays in the functioning of the hippocampal region - may prove crucial in understanding several devastating neurological disorders. Examples of brain disorders to which zinc metabolism in the hippocampal region has been linked include Alzheimer's disease, temporal lobe epilepsy, and stroke-related cell death.

INT 9722819 White This U.S.-Hungary research project between J. Michael White of the University of Texas, Austin, and Frigyes Solymosi of the Hungarian Academy of Sciences' Institute of Solid State and Radiochemistry, Szeged, will examine heterogeneous catalytic oxidation reactions of hydrocarbon and fluorocarbon molecules on single crystal transition metal surfaces. Specifically, Hungarian participants will study reactivity of surface complexes that are key intermediates in catalytic reactions. To accomplish this they will employ ultra-high vacuum chambers. The U.S. team will focus on the dynamics of photon-driven oxidation reactions involving adsorbed reaction precursors by using a suite of surface sensitive spectroscopic methods. Results are expected to contribute to our basic understanding of a broad range of oxidation reactions that occur between hydrocarbons and fluorocarbons at heterogeneous interfaces that have considerable societal impact on a global scale. This project in analytical and surface chemistry fulfills the program objective of advancing scientific knowledge by enabling leading experts in the United States and Central Europe to combine complementary talents and pool resources in areas of strong mutual interest and competence. ??

0085177
White
Introduction. Electrical activity in nerve and muscle cells is generated by populations of ion channels that "gate" (open or close) in response to changes in transmembrane voltage and/or the concentrations of crucial chemicals. In studies of the biophysical processes underlying electrical activity, scientists and engineers rely upon two basic recording configurations. In the first recording configuration, commonly referred to as current clamping, the researcher controls the amount of net transmembrane current (i.e., current across the cell membrane) and measures transmembrane voltage. In the second recording configuration, called voltage clamping, the researcher uses an electrical feedback circuit to control transmembrane voltage and measures transmembrane current. Current clamping is useful for characterizing the patterns of electrical activity generated by a given nerve or muscle cell; voltage clamping is useful for studying the biophysical mechanisms underlying a particular pattern of electrical activity.

More recently, a third very useful recording configuration has been developed, in which neither transmembrane current nor transmembrane voltage is the controlled variable. Instead, the researcher uses a sophisticated recording system to mimic in real time the electrical conductance associated with a given population of virtual ion channels. This recording mode, called dynamic clamping, allows the researcher to block native ion channels, and replace them with virtual analogs, the properties of which can be controlled precisely. Dynamic clamping and other real-time-computing-based protocols enable entirely new classes of experiments, in which (for example) the applied stimulus can mimic the behavior of a (blocked) dynamic component of the system, and thus be used to determine unequivocally the effects of the mimicked component of overall behavior.

Dynamic clamping and other real-time experimental techniques show enormous promise as important research tools. Dynamic clamping could be used, for example, to study the electrical effects of computer-designed pharmaceutical agents even before the agents are developed in the laboratory. So far, however, the impact of this technique has been educed by three interrelated difficulties. First, the technical complexities of its design are beyond the skills of most end-users, and no one has yet provided a flexible, powerful, turn-key system. Second, existing dynamic clamp systems do not account for the seemingly stochastic (i.e., probabilistic) nature of voltage-gated ion channels. Adding this capability would allow researchers to attack entirely new sets of exciting problems that are as yet unapproachable. Third, existing dynamic clamp systems cannot account for measured or assumed spatial distributions of ion channels.

Specific Aims. The specific aims of this proposal are (1) to complete construction of a stochastic dynamic clamp (SDC) system that can be used to study the actions of noisy virtual voltage- and ligand-gated ion channels in living cells; (2) to create a web-based system of support to help end-users adopt and use the SDC system for dynamic clamping and other real-time experimental applications; (3) to develop methods for representing virtual ion channels that are remote from the recording site in the cell body, and (4) to use the new SDC system to test specific hypotheses regarding the relative importance of noise from synaptic sources and noise from voltage-gated ion channels in limiting neuronal reliability.

The project will have educational impact at both the graduate and undergraduate levels, in the context of the classroom and research projects. Innovations from Specific Aims 1 and 3 will extend the dynamic clamp method to account for stochastic and spatially distributed channels. The investigators' support (Aim 2) will be a crucial step in developing a turn-key system. The system will be easily adaptable to apply techniques of real-time computation in many biomedical engineering applications. Field tests of the device (aim 4) will push the field of neurobiology in a more quantitative, information-oriented direction. In particular, they will advance the study of the biophysical underpinnings of neuronal reliability, which play a fundamental role in the understanding of coding strategies used by the nervous system. Such advances are not practically achievable without real-time computing technology.

The research project entitled "Surface Photochemistry and Interfacial Charge Transfer" will be conducted by Dr. J. Michael White from the University of Texas, Austin and is supported by the Analytical and Surface Chemistry program. The research is focused in two areas. (1)The study of photodissociation dynamics of adsorbed alkyl nitrite species on metals, and (2) the study of charge transfer reactions of organic systems which function as light emitting diodes (OLEDs). Dr. White has found that there are 3 pathways associated with the photodissociations. Each pathway is affected by the surface substrate (metal), the adlayer structure, energy and method of excitation and the presence of coadsorbed species. The first part of the research program will focus on elucidating the effects and separating the pathways. The second part of the research program seeks to characterize the structure and electronic properties of adsorbed OLEDs and correlating these properties to luminescent characteristics. Both of these projects will be carried out using state of the art surface characterization techniques. Both projects will provide an important and fundamental understanding of photodissociation mechanisms and OLEDs.

The results of this research will have an impact on the area of fundamental photochemistry of adsorbed species on metals and on the understanding of luminescence and how it is affected by structure and electronic properties. The OLED studies could potentially have a broad impact on the development of new materials and devices.

The microscope has been a widely used tool of biological research for over two hundred years, but interest and developments in microscopy have waxed and waned over the years. Extraordinary advances in genomics over the past few years, however, which have helped identify more physical components of cells and organisms thus creating a new challenge in determining how these parts function together as a living ensemble, have fueled a new demand for microscopy. This project develops an integrated software suite that is used to capture, archive, visualize, analyze and distribute multifocal plane, time-lapse (4-D) microscopic recordings of embryonic development. Advanced visualization aids including roaming space and time, 3-D rendering and arbitrary plane slicing facilitates perception of complex structural dynamics. A comprehensive annotation system enables extensively labeled canonical developmental sequences to be established in a database thereby providing a powerful educational resource for students of embryology.

Web site: http://www.loci.wisc.edu/cambio

DESCRIPTION (provided by applicant): The long-term goal of the proposed work is to use coordinated electrophysiological, computational, and applied mathematical techniques to understand the biophysical underpinnings of synchronous activity in the brain. Because synchronous activity is linked to the behavioral state, seems important for learning and memory, and shows clear abnormalities in clinically important conditions like temporal lobe epilepsy, the results gained from this program should make important contributions to human health. The specific goal of the proposed research is to characterize neurons from brain slices of the hippocampal formation in terms of their abilities to generate coherent population activity via mutual excitation and/or inhibition. To this end, we will adapt and use "mapping" techniques from applied mathematics, along with custom-built "dynamic clamp" technology. Work will focus on the mechanisms underlying two EEG rhythms that appear together during active exploration and learning: the 4-12 Hz theta rhythm and 30-80 Hz gamma rhythm. The effects of known neuromodulatory agents (acetylcholine, norepinephrine, and serotonin), as well as those of a putative neuromodulator (zinc), will be assessed. This appraisal will focus on how the biophysical effects of neuromodulators may alter cellular synchronization properties and hence, change the population driving synchronous activity. Computational and experimental methods will be used to verify the validity of mapping measurements in predicting network behavior. Because the techniques to be used in the proposed work are generally applicable, with clear underlying assumptions, both the results and the newly developed techniques should be broadly pertinent for work in many brain structures that show coherent network activity. Work will be organized around two hypotheses: (A) The biophysical properties of excitatory neurons in excitation-dominated structures support synchronization by mutual excitation; the converse is true for inhibition-dominated structures. (B) Neuromodulators can change the functional architecture of the hippocampal formation by altering cellular properties that determine synchronization behavior.

DESCRIPTION(adapted from applicant's abstract): Single nerve cells are often unreliable: repeated presentations of identical stimuli can generate significantly different trains of action potentials. Because this response variability limits the accuracy of encoding by the nervous system, its biophysical underpinnings are of great interest. The immediate goal of this project is to understand how two major sources of neuronal noise - synaptic noise in the signal received from presynaptic cells and channel noise caused by the probabilistic gating of ion channels - contribute to and interact with the dynamics of excitatory neurons of the hippocampal formation, a brain region implicated in learning and memory. Excitatory neurons of the medial entorhinal cortex (MEC) and hippocarnpus provide a powerful test-bed for these experiments for several reasons. For example: some of these neurons exhibit prominent channel noise that may limit response reliability and shape network responses; different classes of these neurons have contrasting rhythmic properties that imply contrasting stimulus preferences under noisy conditions; and these neurons play a critical role in human memory in the healthy and compromised brain. Electrophysiological experiments will be conducted using standard methods and newly developed stochastic dynamic clamp technology. The latter approach allows direct exploration of the causal roles of specific biological noise sources in shaping neuronal electrical dynamics and reliability. Four hypotheses will be tested: A. Excitatory neurons in MEC and hippocampus exhibit significant levels of channel noise B. Properties of reliability differ significantly among principal cells of the hippocampal formation C. Channel and synaptic noise influence electrical dynamics and reliability in the MEC D. Biological noise influences the behavior of biologically-inspired network simulations The long-term goal of this project - to enhance our understanding of how molecular-level events contribute to excitability, rhythmicity, and encoding properties in nerve cells - is important for improving human health. A mechanistic understanding of this connection may lead to novel diagnoses and treatments for several debilitating neurological disorders that disrupt the information-processing capabilities of the hippocampal region, including temporal-lobe epilepsy and stroke-related cell death.

The investigator and her colleagues collaborate in a group
project at the Center for BioDynamics (CBD) to provide
interdisciplinary education and training for graduate students
and postdoctoral-level investigators in the context of a vigorous
interdisciplinary research program that focuses on areas of
mutual interest in mathematics (especially dynamical systems),
biology, and engineering. Disciplines include mathematics,
biomedical engineering, aerospace/mechanical engineering,
biology, psychology, and physics. Training extends beyond the
usual classroom activities by engaging participants in a variety
of research projects as well. One of the major topics is dynamics
of the nervous system. The projects, which involve experiments,
modeling, and analysis, all deal with the variety of rhythms in
the nervous system and the potential functions of these rhythms
in key cognitive states and processes such as attention,
awareness, learning, and recall. A second major topic is
dynamics of gene expression. Progress in genomic research is
leading to maps of the building blocks of biology and fueling the
study of gene regulation, where proteins often regulate their own
production or that of other proteins in a complex web of
interactions. CBD projects focus on using techniques from
nonlinear dynamics, statistical physics, control theory, and
molecular biology to model, design, and construct synthetic gene
regulatory networks, and to probe naturally occurring gene
regulatory networks. The third major topic is the dynamics of
patterns and waves. Training activities include two weekly
working seminars, extra journal clubs and reading groups,
seminars to educate the CBD members in the research going on
within the Center, and a CBD-initiated team-taught course.
The Center for BioDynamics (CBD) helps to advance
understanding of difficult interdisciplinary problems at the
intersection of mathematics, biology, and engineering, and it
trains mathematicians, scientists, and engineers for the 21st
century workforce. It does this by combining traditional
classroom education with significant engagement of students and
postdocs in interdisciplinary teams working on current problems.
The disciplines involved are mathematics, biomedical engineering,
aerospace/mechanical engineering, biology, psychology, and
physics. One of the major topics is dynamics of the nervous
system. The projects in this topic seek to shed light on the
origin of the electrical activity in the brain, and how the brain
uses this activity to process sensory information, to think, and
to regulate movement. A second major topic is dynamics of gene
expression. The web of interactions among the proteins that are
produced by genes is complex; the projects associated with this
topic involve the design and construction of artificial gene
regulatory networks, and techniques to better understand
naturally occurring gene regulatory networks. The third major
topic is the dynamics of patterns and waves, occuring in a
variety of applications. Training activities include two weekly
working seminars, regular sessions to read scientific journals,
seminars to educate the CBD members in the research going on
within the Center, and a CBD-initiated team-taught course. The
project is supported by the Computational Mathematics, Applied
Mathematics, Computational Neuroscience, and Biological Databases
and Informatics programs and by the MPS Office of
Multidisciplinary Activities.

Abstract

This proposal was received in response to Nanoscale Science and Engineering initiative, NSF 01-157, category NIRT. It focuses on organic semiconductor based nanoscale transistors, a particularly important area of activity where much remains to be understood and discovered. Organic nanoscale transistors make use of fabrication approaches ranging from molecular self-assembly to advanced nanolithography. This, together with the considerable flexibility in designing and synthesizing a range of semiconducting materials offers hope that such devices may one day be components in a new generation of electronic circuits. The ability to confine and manipulate electric charges on the spatial scale of a molecule is an important advantage for molecular electronics. The proposed project aims at combining self-assembly and advanced nanolithography to realize two families of nanoscale transistor devices that will enable the systematic evaluation of these devices as components in electronic circuits. Crucial to the study is the use of advanced high k dielectrics in organic nano-transistors. This will lower the operating voltage of the devices as well as permit the induction of very large densities of charge, which in turn has been shown to open up new domains in charge transport with associated applications. The project will involve device characterization by conventional methods as well as by scanning probe methods. Additionally, it will involve extensive characterization of interfaces between organic semiconductors and gate insulators, and morphological characterization of self-assembled organic layers with a lateral resolution down to 1 nm. Large-area organic transistors have been shown in the recent past to have unique properties such as chemical sensing and light-emission. The chemical sensing aspects of nanotransistors will be examined in detail for the first time This study will combine chemical design of semiconductors with receptor groups to bind specific analytes with detailed characterization of the chemical nature of the interaction between semiconductor and analyte. Among other properties of nanoscale transistors that will be explored is superconductivity. Superconductivity has been observed recently in large-area polymer transistors and among the suggested applications of such transistors includes quantum information processing. Finally, a new approach to fabricate circuits is proposed in which the organic nano-transistor circuitry is compatible with Si-circuitry. This architecture permits (in principle) the sharing of functionality between the Si circuitry and the organic circuitry. The key aspect of the fabrication scheme is the use of an up-side down approach to fabricate organic circuitry, in which the interconnects are defined first followed by the gate level and finally the source-drain level. Thus the fragile molecular materials are not exposed to harsh processing environments.

This project formulates a strategic plan for the development of the national center for pulp and paper technology through the partnership of the four two-year colleges and with strong backing and support from industry. The center is going to establish and perpetuate a technology program and network providing students around the nation an effective education and training program. The center is also going to provide the pulp and paper sector of the U. S. forest products industry with a globally competitive, technologically advanced workforce. Alabama Southern Community College (ASCC) and Auburn University alliance continues in this project with the addition of four two-year colleges strategically located throughout the United States. These institutions include: (1) Kennebec Valley Technical College, a rural college in Fairfield, Maine, (2) Fox Valley Technical College in a more urban area in Appleton, Wisconsin, (3) Century Community Technical College in White Bear Lake, Minnesota, and (4) Lower Columbia College in a more urban area in Longview, Washington.

The project includes participation of several national pulp and paper industry organizations under an industry-academia-governmental initiative called Agenda 2020. These national organizations consist of (1) The American Forest and Paper Association (AF&PA), (2) The Technical Association of the Pulp and Paper Industry (TAPPI), and (3) The Paper, Allied-Industrial, Chemical & Energy Workers International Union (PACE). This initiative enables focusing the industry's technology vision, sets the industry's technology agenda, and provides science and technology foundation for the industry. A major focus of Agenda 2020 is the development of a technologically advanced workforce (TAW) to operate and maintain the new technologies of today, and more importantly, in the coming years. The planning for this center is going to closely coordinate the workforce development needs of today and in the future as new and sophisticated technology is ushered in for purposes of efficiency and quality improvement so that our nation's pulp and paper industries can successfully compete internationally.

The proposed project presents a new, creative approach to address student understanding of related material in different courses through the use of a multi-semester interwoven project to reinforce basic STEM material critical to solving engineering problems. A strong laboratory component with multimedia and hands-on application of STEM material will reinforce theoretical concepts.
Through the use of a common problem for dynamic systems that spans across several courses (basic math skills, laboratory measurement and model development to predict dynamic system response), students are better equipped to solve a real dynamic system problem which requires the use of many STEM tools. A strong laboratory component measuring a real system using a web-based data acquisition system requires the students to "think outside the box" and apply theoretical concepts through practical hands-on learning. An open ended project forces the students to take ownership of learning material which integrates several themes and underlying STEM material promoting a life-long, self-learning process.

This interwoven project contains basic core STEM material that is easily transferable to all engineering disciplines as well as other institutions. Since the project will
result in educational material online, geographic, ethnic and gender barriers will be overcome and will allow for universal access to the material. This multi-semester, interwoven project concept with an online experiment is the salient feature of this program; integration of STEM material is accomplished in a relevant, meaningful way for student comprehension and retention.

Alabama Southern Community College, Auburn University, and the Charter Member Colleges are developing an ATE National Center of Excellence called the National Center for Pulp and Paper Technology. The Charter Member Colleges include: (1) Kennebec Valley Community College (Fairfield, Maine); (2) Mid-State Technical College (Wisconsin Rapids, Wisconsin); and (3) Lower Columbia College (Longview, Washington). The mission of the National Center, with the support of other two-year colleges, universities, and a national array of pulp and paper companies and mills and national organizations, is to establish and perpetuate a technology program to give students around the nation exciting and effective education and training opportunities and to provide the pulp and paper sector of the United States forest products industry with a globally competitive, technologically advanced workforce (TAW). In turn, the mission of the National Center is being conducted through 8 goals and 36 objectives. The broad array of services to be provided through the National Center has been identified as critical for the pulp and paper workforce by a comprehensive consortium of industry, trade and professional organizations, colleges, universities, and governmental entities under the auspices of Agenda 2020.

The intellectual merit of the Center includes continuous contributions to advancing knowledge in the areas of education and training for technicians and operations in the pulp and paper industry through several elements that may be applied to other disciplines and industries. These elements include: (1) a broad collaborative model that serves as the prototypical schematic for industry-education-government collaboration to show other industries and educational organizations how to move toward the goal of having a TAW so they too can successfully compete in global economy, (2) an education and training model that through the National Pulp and Paper Technician and Operator Certification Program incorporates skills standardization and verification based on international standards, (3) an ongoing research based analysis that helps colleges, universities, and the pulp and paper industry measure the effectiveness of education and training programs through return on investment model, and (4) education and training research that is reported through monthly journals and an annual book series published in paper and e-book formats.

By providing an array of services, the broader impacts of the Center include: standardized and certified programs, outcomes-based instruction, advanced training and education methods and delivery, research and application of new teaching methods, academic- industry-government partnerships, dual focus on entry level and incumbent workers, quantitative measurement of effectiveness, labor-management cooperation, community college-university linkages, and outreach to K-12 teachers and students. Also, the developers are working to ensure that the activities have provisions to recruit and help students enter the workforce from groups that have been traditionally underrepresented in the pulp and paper industry.

Abstract
CHE-0412609
White/Texas

With the support of the Analytical and Surface Chemistry Program, Professor White and his coworkers at the University of Texas at Austin are investigating the photo and thermal induced chemistry of small oxygen containing molecules on nanostructured oxide and bimetallic surfaces. Using a novel hydrophobic/hydrophilic patterning method, they are depositing nanometer sized titanium and molybdenum oxide particles, as well as Au/Cu bimetallic particles on planar TiO2 surfaces. Scanning tunneling microscopy, thermal desorption spectroscopy, and X-ray photoelectron spectroscopy are used to examine the kinetics and mechanisms of the reactions on these structured surfaces. Information from this fundamental research is important for developing an understanding of the reactivity of nanoparticles of oxide and bimetallic materials.

The surface chemical reactivity of nanometer sized materials is likely to differ in important ways from the surface reactivity of bulk oxide and bimetallic materials. This research project, carried out by Professor White and his group at the University of Texas, addresses this important question. Using a hydrophobic/hydrophilic patterning method, nanostructured surfaces of titanium and molybdenum oxides, as well as Au/Cu bimetallic nanoparticles are prepared and characterized. The surface chemistry of these materials is then examined using standard UHV surface chemistry probes. This fundamental information is crucial for developing an understanding of the reactivity of nanomaterials for use in many technical applications.

[unreadable] DESCRIPTION (provided by applicant): The 2nd annual GTReal workshop will be held in May or June 2006 at the campus of Boston University. The meeting will be attended by around 120 scientists at a range of levels of experience (students, postdoctoral fellows, faculty members). The meeting will include 3 invited speakers, 12-15 contributed talks, and 2-4 "breakout" sessions, in which attendees will discuss topics of mutual interest. There will also be a hands-on tutorials. Depending on the number of submissions, there may be posters as well. Following on the success of the first event, held in May 2005 at the Georgia Tech, GTReal will focus on the following topics: (1) Exchanging scientific results. Because of the technical hurdles involved, only a handful of investigators are using real-time "dynamic clamp" systems to mimic membrane conductances in excitable cells. These investigators have gone to this level of trouble because dynamic clamp techniques provide the best method to test specific, computationally based hypotheses in living systems. Invited and contributed talks will focus on exciting examples of dynamic clamp and other real-time applications in neurophysiology and other disciplines, as well as technical means used to obtain such results. (2) Building a community of developers and end-users. Over a decade after the seminal work on dynamic clamp, no turn-key system exists, but several groups have devised systems that seem promising. A major goal of the breakout sessions will be to continue to build a community of developers and end-users of real-time technology, based on the principles of open-source software development. The attendees of GTReal will constitute much of the core of this community. Tutorials and informal interactions will add to the cadre of skilled users and developers. (3) Extending the real-time approach to new types of experiments. Real-time techniques allow an unprecedented degree of quantitative hypothesis testing in biological experiments. A number of extensions of the technique would increase its impact dramatically. For example, within cellular neurophysiology, it should be possible to combine real-time technology and optical techniques for recording and stimulation. Real-time techniques also have the potential to revolutionize systems physiology and behavioral studies of sensory systems. [unreadable] [unreadable] [unreadable]

This project will advance the creation and support of a community of scholars, from undergraduate to faculty, working at the interfaces among dynamical systems and biological applications. The three main areas of focus are: 1. Analysis of systems with multiple length and time scales, including applications to pattern formation; 2. Mathematical neuroscience, including analytical methods for working with small networks and reduction of dimension techniques; 3. Gene regulatory networks, including the development of RNA switches, transcriptional bursting and programmable cells. These areas have major applications to issues concerning health and medicine. The project will build on the previous research and training experience of the Center for BioDynamics, co-directed by the Principal Investigator and one of the other senior faculty members. Trainees will be pre- and post-doctoral students who will take part in a wide variety of formal and informal activities, including special seminars, working groups, mini-symposia, laboratory work, journal clubs and social events, which will enable them to acquire the multiple scientific cultures needed to work in a trans-disciplinary manner. The pre-doctoral students will be from the departments of Mathematics or Biomedical Engineering; the postdoctoral associates will be drawn from a wide range of backgrounds, with a focus on applied math. In addition to their research activities, trainees will obtain experience teaching at different levels. Math department faculty and trainees will be involved in the construction of new interdisciplinary curricula for undergraduates in other departments, including Biology; the faculty will mentor the trainees in teaching the new curricula.

choice; stimulus /response

The WGBH Educational Foundation together with the Association of Computing Machinery (ACM) and dozens of partners, proposes a major new initiative to reshape
the image of computing among college-bound high school students, with a special focus on Latina girls and African-American boys. Image is seen as an important factor in the lack of interest in computing majors among high school and college students, who often see computer scientists as geeks and nerds with boring jobs and equally boring lives. Latina girls and African-American boys ? among the most underrepresented groups in computing ? represent particularly important and challenging audiences. The New Image for Computing project will research and design a ?communications make-over?? a new set of messages that will accurately and positively portray the field and will be widely tested for their emotional appeal to and intellectual connection with the targeted audiences. Experienced marketing professionals will help create the messaging campaign using proven marketing and communications strategies. WGBH, a leading producer of programming for public television and non-broadcast educational media, is uniquely positioned to lead this initiative, as they have a current, similar project called Engineer Your Life that aims to encourage academically prepared high school girls to consider engineering as an attractive option for both post-secondary education and as a career choice.

This SGER project will examine how river flood pulsing controls freshwater residence time in coastal wetland basins of Louisiana, and how this control regulates biogeochemical processing of nitrogen (N). The central hypothesis is that the pulsed event of river floods will decrease N retention and removal by wetlands (via denitrification) by drastically decreasing water residence times in entire wetland basins. This, in turn, will lead to increased N loading to the Gulf of Mexico, where anthropogenic N loading has long been implicated in coastal hypoxia and the Northern Gulf Dead Zone. It will take advantage of The Mississippi River flood of 2008, which will be one of the largest pulses of freshwater for wetlands in coastal Louisiana in almost a century. This study will use managed river diversions into the study basins to examine this relationship between freshwater inputs and nitrogen retention.

This research will provide ecosystem managers, who manage valuable, large wetland systems like the Mississippi River Delta and the Florida Everglades, with critical water quality information. One management goal is to prevent excess N from reaching the coastal ocean where many economically important fisheries are located and where excess N causes toxic algal blooms, low dissolved oxygen, and massive fish kills. This experiment will also provide important data on how well coastal wetlands respond to very large pulses of freshwater.

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (15): Translational Science and specific Challenge Topic, 15- NS-104: Early-Stage Therapy Development. The major goal of the proposed work is to develop novel technical and theoretical means to understand the mechanisms underlying temporal lobe epilepsy (TLE) and to assess new classes of possible treatments for this devastating disorder. TLE is often difficult to treat using currently available approaches and entails an economic cost of $12 billion dollars per year within the United States alone. The proposed work is transformative on several fronts. First, the work focuses on the putative role of glial support cells (specifically, astrocytes) in TLE. Although there is a convincing body of evidence that astrocytes are involved in epileptic dysfunction, this evidence has not yet gained wide acceptance, leaving approaches that focus on astrocytes underappreciated and underutilized. Second, the proposed approach depends on a novel imaging technique, called targeted path scanning (TPS), which allows recordings of neuronal and glial calcium transients in up to 100 cells simultaneously, with single-cell spatial resolution and excellent temporal resolution. The TPS approach allows the proposed research program to study mechanisms and putative treatments of TLE in interacting neuronal and glial networks, with spatiotemporal resolution that permits simultaneous analysis at both the cellular and network levels. The proposed study has two specific aims. Aim 1 addresses whether the properties of astrocytic population calcium transients are altered in brain slices derived from animals that have been subjected to the kainic acid (KA) model of TLE. These transients will be characterized, and compared with data from age-matched controls, in slices from animals during both the latent period (after induction of status epilepticus but before spontaneous seizures) and after spontaneous seizures have begun. Relevant properties to be studied include temporal frequency, magnitude, and spatial extent throughout the astrocytic network. Aim 2 focuses on interactions between astrocytic calcium transients and spike-driven calcium transients in nearby neurons. Specific questions to be addressed in this aim include: Are calcium transients in astrocytes and neurons spatially and/or temporally correlated? If so, which cell type in a given area leads the other? How do known anti-epileptic drugs affect calcium transients in astrocytes, calcium transients in neurons, and the potential interactions between the two cell types? Finally, can this ground-breaking technology be used as a network- based assay for the identification of novel anticonvulsant molecules for the treatment of pharmacoresistant epilepsy? The proposed project-a pioneering effort between a pharmacologist/epileptologist and a bioengineer-is translational in its focus and intent. The major goal of the proposed work is to develop new theories and approaches that could be invaluable in discovering new pharmacological treatments for the devastating seizure disorder, temporal lobe epilepsy. PUBLIC HEALTH RELEVANCE: Temporal lobe epilepsy is a seizure disorder with devastating effects, particularly in the large number of patients for whom current treatments are ineffective. The purpose of the proposed work is to use ground- breaking imaging technology to study this disease in interacting networks of both nerve cells and glial metabolic support cells. A likely outcome of the proposed work will be entirely new ways to assess potential pharmacological therapies for epilepsy.

DESCRIPTION (provided by applicant): To understand brain function mechanistically, and thus to take principled approaches in repairing damaged brains, biomedical scientists face the daunting task of bridging the gap between the electrophysiological properties of single cells and the emergent properties of neuronal networks. The proposed experiments will help bridge this gap for a problem of great relevance in cognition and learning and memory: the cellular bases of the coherent theta rhythm in the hippocampus. The central hypothesis is that a particular class of hippocampal inhibitory interneurons, called oriens lacunosum-moleculare (O-LM) cells, plays a crucial role in amplifying the theta rhythm in vivo and generating theta-rhythmic activity in vitro. Proposed brain-slice experiments rely upon a recently developed real-time dynamic clamp system to study the integrative properties of O-LM cells and to immerse living neurons in computer-simulated microcircuits. Building such hybrid microcircuits-small brain circuits containing biological and simulated neurons that interact in real time- allows one to test precise hypotheses of microcircuit function with unprecedented quantitative rigor. Additional proposed studies focus on the consequences of O-LM-cell projections to the distal dendrites of pyramidal cells, as well as the consequences of O-LM-cell loss for the theta rhythm in vivo and in vitro. The proposed research program has five aims: (1) To study the input-output properties of O-LM cells in response to artificial synaptic barrages that mimic the in vivo state. (2) To study how phase-locked, distal and proximal inhibitory inputs can lead to phase-locked sparse firing in excitatory pyramidal cells. (3) To study the effects of distal O-LM-based inhibition on phase-dependent selection of dendritic inputs to pyramidal neurons. (4) To study how input from oriens-lacunosum moleculare (O-LM) interneurons to pyramidal cells and fast- spiking interneurons contributes to self-organized theta and gamma rhythms in closed-loop networks. (5) To study the importance of synchronization of O-LM cells for rhythmic activity under manipulation of feedback input, artificial rhythmic drive from the septum, and other factors. The long-term goal of this research program is to understand, with quantitative and mechanistic rigor, the mechanisms by which both normal and abnormal rhythmic behaviors emerge in the hippocampus and other cortical regions. The work will be immediately relevant to understanding the theta and gamma rhythms. These two patterns of coherent activity seem crucial for normal cognition and learning and memory, and are disrupted in a broad range of conditions including epilepsy, schizophrenia, Parkinson's disease, and Alzheimer's disease. Because the proposed approach can show how specific membrane mechanisms contribute to network function, it is particularly useful for identifying new drug targets. An added bonus of the proposed approach is that the dynamic clamp technology developed for these studies may prove useful for therapeutic, feedback-controlled electrical stimulation of the brain.

RAPID: Sediment, water, and nutrient flux and fate in Lake Pontchartrain from the 2011 Bonnet Carre Spillway Opening

EAR-1139997
Samuel Bentley, Sibel Bargu, Chunyan Li, Nan Walker, John R. White
Louisiana State University

ABSTRACT
The lower Mississippi River Delta (MRD), inhabited by >2 million people, is a critical national resource in terms of maritime transport, fisheries, and energy. MRD wetlands and waters are degrading at alarming rates, losing wetlands equivalent to the area of Delaware since the 1930?s, and more over the next century. The health of coastal waters and the fate of wetlands are strongly governed by the flow of fresh water and accompanying sediments and nutrients, which are now largely controlled by engineered structures along the river. For these reasons, conservation and restoration of the MRD is one of the outstanding environmental and socioeconomic challenges faced by our country over the next century. Understanding and managing water, sediment, and nutrient flux and fate into the MRD coastal zone is central to this challenge.
The Spring 2011 hydrograph of the Mississippi River is reaching levels exceeding the Great Flood of 1927 in many locations in Louisiana. To provide relief to river levees, water is being released through the Bonnet Carré Spillway (BCS) into Lake Ponchartrain (LP), a large mostly enclosed estuary within the MRD (Fig. 1). BCS opening on May 9 is now producing record fluxes of water (>8800 m3 s-1, 126% of design capacity) into LP, likely along with record fluxes of sediment and nutrients. Understanding the dynamics and impact of this plume in LP is important for several reasons: (1) nutrient loading to the lake will produce potentially toxic algal blooms; (2) fresh water flux will cause strong exchange of the fresher lake with the saltier coastal ocean; and (3), measurement and study of sediment supply and deposition will provide important information for use of sediment in engineered diversions for delta restoration.
PIs will sample water, sediment, nutrients, and plankton over time to understand impacts to the lake, in order to better understand impacts from future manmade diversions for delta restoration. Because LP has strong similarities to other MRD estuaries, and engineered diversions of river water and sediment are primary tools planned for MRD conservation and restoration, results of this work will be directly applicable to large regions of the MRD in need of conservation and restoration.

DESCRIPTION (provided by applicant): Temporal lobe epilepsy (TLE), a devastating seizure disorder that is difficult to control with anticonvulsant drugs, often develops following an initia insult to the CNS. In order to better understand the process of epileptogenesis and to develop innovative therapeutic approaches for the management of TLE, animal models have been developed that exhibit some of the hallmarks of this seizure disorder: a period of status epilepticus (SE) which serves as the initial insult to the CNS, a variable latent period during which seizures do not occur, and the eventual development of recurrent, spontaneous seizures of temporal lobe origin. Recently we used the kainic acid (KA) model of TLE to investigate 'reactive' astrocytes in the hippocampus (HC), a brain region known to be involved in seizure generation. There is a significant increase in gap junction coupling between astrocytes following KA-induced status epilepticus (SE). Therefore, the astrocytic network architecture is altered in brain regions associated with seizure generation. We also discovered that astrocytes express kainate receptor (KAR) subunits following SE and hypothesize that activation of KARs can result in calcium (Ca2+) transients that induce the release of signaling molecules that modulate neuronal activity in the HC. The present application will use targeted path scanning 2-photon microscopy (TPS) to simultaneously evaluate rapid Ca2+ transients in large networks of astrocytes in brain slices obtained from animals treated with KA to induce SE. We employ in utero electroporation to target a genetically encoded Ca2+ indicating protein (Lck- GCaMP3) to the rat HC so that we can use brain slices obtained from adult animals to determine 1) if activation of KARs induces somatic Ca2+ signaling in networks of reactive astrocytes in the HC and 2) if KAR- induced and/or other agonist-induced Ca2+ signaling in the fine processes of reactive astrocytes induces the release of signaling molecules that directly influence network activity in HC brain slices obtained from KA- treated rats during both the latent period and chronic epilepsy. Finally, we will use electron microscopy to determine if there are ultrastructura changes in KAR expression, gap junction coupling, and dendritic ensheathment in the astrocyte compartment of the tripartite synapse of the CA1 and CA3 regions of the HC following KA-induced SE. The combined use of TPS with the stable expression of Lck-GCaMP3 in cells of the HC is a technical achievement that will contribute to our understanding of the functional role of KAR expression in astrocytes following status epilepticus (SE), both in the latent period and in chronic epilepsy. The proposed experiments will also determine how pathologic glial/neuronal interactions, both structural and functional, influence circuit activity during the development and persistence of epilepsy. Finally it is anticipated that the proposed experiments will lead to the identification of novel molecular targets for innovative therapeutic approaches for the treatment, prevention, and/or cure of this devastating seizure disorder.

Genetically-encoded reporters of neural activity are a transformative tool for understanding brain function because they allow for the simultaneous measurement of activity across many neurons defined by genetic and anatomical criteria. The current generation of such reporters use light to signal activity, which limits their ability to be used deep in brain tissue and across the full range of neuronal activity. The goals of the project are to overcome these limitations by developing reporter proteins that can be engineered to emit unique electrical or magnetic signals in response to neural activity. The project will also develop sensors that are optimized for detecting these signals from individual neurons in intact brain tissue in the freely-behaving animal. The proposed 'electrogenetic' toolbox will allow neural activity to be recorded with high fidelity from defined cell types across the entire physiological range of neuronal firing rates, from any location in the mammalian brain, and in the freely-behaving animal. This strategy leverages existing and widely available technology for recording electromagnetic signals in the brain, and thus has the potential to be rapidly adopted for a wide range of neuroscience applications.

This project will develop a new strategy for measuring neural activity from genetically-targeted neurons in the intact brain. An interdisciplinary team of investigators will first use gene therapy techniques to express candidate proteins in particular neurons, then will screen for electrical or magnetic signals using conventional electrodes or nanoscale magnetometer probes. Understanding how neurons of a particular type are activated in the behaving animal is crucial for understanding the neural basis of sensation, cognition and behavior. Indeed, the lack of tools for interrogating identified neurons while they are in action is a major impediment to understanding functional neural circuits in the brain. In addition to breaking this impasse in basic science, a potential broader impact of this project is that the tools to be developed in this proposal may provide information leading to improved diagnosis and treatment of nervous system disorders including mental illness, autism, addiction and epilepsy.

Coastal Louisiana is currently experiencing net sea level rise at rates higher than most of the world's coastlines and within the global range predicted to occur in the next 65 - 85 years, making Louisiana an ideal site to study potential future impacts of rising sea level on coastal systems. This project will use field collection and controlled tank experiments to study the changing organic carbon cycle resulting from erosion of marsh soils along with its impact on associated biogeochemical processes. The hypothesis tested in this study is that the majority of eroded soil organic carbon is converted to carbon dioxide (CO2) and released to the atmosphere, representing an addition to the anthropogenic input of CO2. This process has not been quantified and could be an important missing component in predictive models of atmospheric CO2 changes. While this process may be of only regional importance today in comparison to other sources of CO2, this study of the Louisiana coast will greatly enhance our full understanding of the potential impacts on the global carbon cycle that may result from coastal erosion as global sea level continues to rise.

The project will train graduate and undergraduate students in interdisciplinary research involving marine and wetland biogeochemistry, microbiology, and ecological modeling. It will also fund development of an interactive, educational display on the loss of coastal wetlands for the Louisiana Sea Grant's annual Ocean Commotion educational event attended by area middle and high school students, teachers, and parents. Results from this study may also inform community planners both regionally and worldwide as they prepare for sea level rise in coastal communities.

Eustatic sea level rise and regional subsidence have created a much greater rate of coastline loss in Louisiana than is being experienced in most of the world's coastal regions, reaching global rates that are predicted to occur worldwide in 65 - 85 years. This provides a unique potential to extrapolate data from Louisiana's changing coastal carbon cycle to both regional and global models of the future impact of sea level rise and coastal erosion. By quantifying and modeling the importance of CO2 emissions resulting directly from mineralized soil organic matter from eroding coastlines, a missing element can be added to climate change models. The PIs here plan to investigate the fate of the coastal wetland carbon pool as it erodes using field sampling, laboratory analysis, mesocosm manipulations, and the creation of a coupled physical-biogeochemical model for the basin being studied. Beyond quantifying increased CO2 emission, the PIs will also address the potential for increased eutrophication due to input of nutrients from eroded soils, as well as the potential for future contribution to existing hypoxic zones in the northern Gulf of Mexico that result from excessive nutrient input from the Mississippi River watershed.