Robert Frank - US grants

We are continuing our studies to attempt to develop a model of diabetic retinopathy in rats made diabetic with streptozotocin, and in addition to investigate other aspects of the pathologic anatomy and physiology of other tissues in the eyes, brains, and other organs of these animals. In addition to diabetes, other conditions are superimposed in our attempt to promote the development of retinopathy. These include systemic hypertension in a strain of rat in which this is a genetic lesion, and diets high in sucrose. The role of aldose reductase is investigated by observing the effects of the drug CP-45634, an inhibitor of this enzyme and by feeding some animals diets rich in galactose. The role of diabetes is investigated by use of insulin therapy in some animals. After one year on these regimens, animals are sacrificed, and flat mounts of the retinal vessels are prepared by trypsin digestion. The anatomical configuration and permeability of the retinal vessels and of the retinal pigment epithelium are investigated by electron microscopy using the tracers horseradish peroxidase and microperoxidase. In addition, we will examine by light and scanning and transmission electron microscopy cerebral vessels, sciatic nerves and kidneys of animals on the various regimens. Observations will be recorded by several individuals who are masked as to the identities of the experimental animals to avoid bias. In this way, we can objectively determine what abnormalities are present that are related to diabetes.

In order to develop new drugs for use in the treatment of behavioral disorders and central nervous system dysfunction, a battery of behavioral tests must be available for the assessment of the psychoactive properties of these substances. One behavioral paradigm that has been employed for this purpose has examined the effect of various pharmalogical agents on the self-administration of brain stimulation reward (BSR). In particular, this approach has proven useful in determining the addiction potential of drugs and in investigating the behavioral effects of anti-psychotic agents. However, the potential of this paradigm for characterizing the multitude of behavioral effects that might be produced by a drug has not been fully exploited. For example, although there is evidence that the effect of a drug on self-stimulation may depend on the joint effects of the stimulation site and response requirements, no systematic attempt has been made to explore this relationship. The proposed studies would examine the influence of response topography and differences in electrode placement on drug-induced changes in intracranial self-stimulation. Self-stimulation thresholds, response rates and response patterns will be assessed using a novel measurement strategy that manipulates brain stimulation train durations. Since little or no account is taken of differences in response topographies or stimulation site in most self-stimulation reserach, the results of the proposed studies may indicate that significant changes are needed in the methods currently used to assess the behavioral effects of pharmacological agents on BSR. They may also initiate a rethinking of how central reward and response control mechanisms jointly regulate goal directed behavior.

EVALUATE EARLY TREATMENT OF DIABETIC RETINOPATHY

We will continue to investigate the biochemical and physiological properties of freshly isolated retinal microvessels, and of their constituent cells grown in culture. Specific topics of investigation will include: (a) The macromolecular components of the microvascular basement membrane obtained from intact vessels isolated from fresh tissue and also synthesized by retinal capillary cells in culture. These include collagens and proteoglycans, and noncollagenous proteins such as laminin and fibronectin. The effect on the synthesis of these macromolecules of elevated levels of glucose, galactose, and xylose, and of the aldose reductase inhibitor Sorbinil will be studied. (b) The properties of receptors on the cell membranes of retinal vascular cells for hormones that induce smooth muscle contraction or relaxation; these include Alpha- and beta-adrenergic agents and angiotensin II. The purpose of this investigation is to determine, first, if pericytes are contractile cells analogous to the smooth muscle cells of larger vessels; second, if there are differences in the behavior of pericytes and endothelial cells to these agents, and third, whether the response of retinal vascular cells to these hormones is altered in the presence of elevated concentrations of glucose or other sugars, or in the presence of any of these sugars together with an aldose reductase inhibitor. (c) We will investigate, by transmission electron microscopy, the morphological differentiation of retinal capillary cells in culture, paying particular attention to the development of such features as intercellular junctions, as well as to the appearance of apparent vascular "lumina". Additional morphologic studies will include localization of a fluorescein labeled lectin probe (Ulex europaeus I lectin) as a marker for cultured capillary endothelium and morphometric analyses of scanning electron micrographs of cultured capillary endothelial cells incubated with platelets as a measure of platelet adhesiveness under normal, high glucose and high galactose culture conditions. The overall aims of this research are to understand better how this normal physiology may be altered by conditions simulating diabetes mellitus.

This proposal involves five new, long-term goals: 1) we will study the biochemical mechanism of capillary basement membrane thickening, resembling that of diabetes, which we have found occurs in the retinal and cerebral microvessels of rats with galactosemia induced by diet, and is prevented by an aldose reductase inhibitor. Quantitative and qualitative aspects of basement membrane collagen, proteoglycan (PG), and laminin synthesis will be evaluated following (3H)-proline and (35S)-sulfate administration, using biochemical analysis and enzyme-linked immunosorbent assay. 2) We will compare the biosynthesis of PGs of the interphotoreceptor matrix (IPM) in spontaneously hypertensive (SHR) rats, which develop a photoreceptor dystrophy, and in genetically closely related Wistar-Kyoto (WKy) animals, which do not. We have found that the dystrophy in SHR animals is greatly retarded with a 30% galactose diet which, we propose, may alter PG aynthesis in the IPM. (35S)-sulfate and (3H)-glucosamine will be administered for autoradiographic and biochemical analyses of retinal PGs in SHR and WKy animals on high galactose and normal diets. 3) We will evaluate the proposed contractile function of pericytes in the retinal and cerebral circulation of normal, diabetic, and galactosemic rats by comparing them in the normal state and following administration of agents that induce vascular smooth muscle contraction. Electron microscope morphometric methods will be used to assess contractility of pericytes and/or endothelial cells. 4) We will evaluate the integrity of the blood-brain and blood-retinal barriers in diabetic, galactosemic, and normal rats following production of acute hypertension pharmacologically. This will be done by evaluating gross leakage of Evans blue dye, and microscopic leakage of horseradish peroxidase. The studies in (3) and (4) will test the hypothesis that dysfunciton of pericytes may occur early in diabetes and galactosemia, well before pericyte loss occurs. The consequences of this dysfunction may be more prominent in the retinal microcirculation than in the cerebral because of the much larger proportion of pericytes to endothelial cells in the retina. 5) We will attempt to develop models of retinovitreal neovascularization in the rat with much higher prevalence than we observed in dystrophic SHR animals during the previous funding period. By sequential ophthalmoscopic observation and photography, and by (3H)-thymidine autoradiography, we will attempt to provide further evidence that these truly are new vessels, comparable to those of various human disease states.

Acid fog, composed chiefly of H2SO4 and HNO3, occurs on a seasonal basis in Los Angeles and elsewhere in the country. The following physicochemical properties of acid fog have been reported: pH as low as 1.7, total acid mass in excess of 100 ug/m3, hypo-osmolar liquid water content of about 0.2 g/m3, and a mass median diameter of the fog droplets on the order of 15 um. We hypothesize that these fog droplets are irritating to the respiratory system. Our specific aims are to generate and characterize H2SO4-fog for the acute exposure of human volunteers. The fog will be administered in a small-volume head dome. Two groups of adults will be studied: healthy non-smokers and asthmatics. The functional end-points will include: airway reactivity, maximal expiratory flow-volume curves, respiratory flow resistance, and bronchopulmonary deposition and clearance of a radiolabeled aerosol. The possible roles of post-ganglionic nerve stimulation and mast cell mediator release in the response to acid fog will be studied.

This interesting project examines the basic behavioral foundations of economic analysis. The fundamental concept underpinning economic theory regarding the purchase of consumer goods and services, participation in the labor market, and the establishment of contracts between people or institutions is the maximization of utility. That is to say, people make choices which they perceive will bring them the most satisfaction, and in doing so they forgo other choices. This seeming truism is both self-evident and profound at the same time. The approach has provided insights into many important questions. For instance, faced with a given wage rate, how much will people work? What fraction of their incomes will they save? What effect will a tax on gasoline have on the purchase of automobiles or on the number of miles driven. Clearly these are important questions to policy makers, producers, consumers, and other economic agents. The approach of utility maximization is, however, sometimes not readily applicable to observed human behavior. Many times people continue in behavior which to an observer appears irrational. Economists and psychologists who study such behavior often explain it as the result of human beings' inability to process effectively the ocean of information available to them. Thus they implicitly derive rules of thumb, or other shortcuts which allow for reasonably rapid decision making, but might not result in the choice which truly gives the most satisfaction over the long run. Economic agents enter into long term contracts with each other, even though in the short term each agent might be able to do better by acting independently. That is to say, each party to a contract might have the incentive to cheat, particularly if the cheating cannot be detected. This very innovative project explores the incentives to cheat on contracts, the types of information conveyed by individuals entering into contracts, and mechanisms which might diminish the incentive to cheat. Professor Frank uses a game theoretic framework to analyze the so- called prisoner's dilemma in a variety of interesting settings. In this manner he gains a great deal of insight into the information processing mechanisms of human behavior, and ultimately into the ability of economic agents to act in a rational manner.

Cocaine abuse has risen sharply over the past 10 years, and with this increase has come a commensurate increase in the health and social problems associated with chronic cocaine use. Effective strategies for dealing with this problem depend on an appreciation of the factors that contribute to drug use. In the case of cocaine, it is generally believed that drug-induced changes in affect (both euphoria and dysphoria) are important determinants of the pattern of drug self-administration. However, few studies have attempted to evaluate the time course of cocaine's mood-altering effects. The research described in this proposal explores the time course of cocaine-induced changes in affect using an intracranial self- stimulation paradigm. Fluctuations in train durations thresholds will be used to investigate the effects of chronic cocaine administration of central reward mechanisms. In addition, the ability of drugs coadministered with cocaine (i.e., ethanol and morphine) will be evaluated for their ability to modify cocaine- induced changes in self-stimulation. Finally, the influence of imipramine on cocaine's effects will be assessed to determine whether this drug, which has been proposed as a treatment for cocaine dependence, alters cocaine-induced euphoria and/or dysphoria.

biomedical equipment purchase;

The goals of this research include, first, evaluation of factors restrain proliferation and enhance differentiation of cultured retinal cells, including pericytes and endothelial cells of the retinal microvessels, the retinal pigment epithelium (RPE), and retinal glia. Factors to be evaluated include basement membrane macromolecules; interactions with other, neighboring cells; and a substance present in aqueous extracts of bovine retina that promotes morphologic differentiation of neuroglia. The interaction of disease states (diabetes and galactosemia, simulated by elevated levels of glucose and galactose in the culture medium) with the above factors will be evaluated. The types, and quantities, of extracellular matrix macro-molecules synthesized by retinal vascular, RPE, and retinal glial cells cultured on a basement membrane matrix under normal conditions and with elevated glucose or galactose, with or without an aldose reductase inhibitor, will be studied. The role of RPE and choroidal vascular cells in modifying one another's behavior will be studied by histologic, autoradiographic, and immunocytochemical methods in a model of human subretinal neovascularization produced in pigmented rats by mild krypton laster photo-coagulation. The "glial modulating factor" from retina will be further purified, monoclonal antibodies prepared to it, and biochemical and immunological comparisons will be made with acidic fibroblast growth factors from retina and brain, and the "glial maturation factor" of Lim, isolated from bovine brain. Immunocytochemical localization of this factor in the retina will be attempted. A second goal of this research is to determine factors that stimulate contraction of retinal pericytes, cells whose abnormality may be critical in diabetic retinopathy. This will be approached using vasoactive agents (norepinephrine, angiotensin II, and vasopressin), and variations in the O2 and CO2 levels in the culture medium, on pericytes grown on deformable matrices, and the determining whether these agents produce an elevation in cytoplasmic free Ca++ in cultured pericytes, using fluorescent Ca++-binding probes and microspectrofluorimetry. A third goal of this project is to initiate additional long-lived non-neoplastic human retinal cell lines from epiretinal membranes excised during vitrectomy surgery on infants with stage 5 retinopathy of prematurity. Cells obtained through these cultures will be defined immunocytochemically and used in the retinal cell culture experiments described above.

health science research support; university;

The goals of this research include, first, evaluation of factors restrain proliferation and enhance differentiation of cultured retinal cells, including pericytes and endothelial cells of the retinal microvessels, the retinal pigment epithelium (RPE), and retinal glia. Factors to be evaluated include basement membrane macromolecules; interactions with other, neighboring cells; and a substance present in aqueous extracts of bovine retina that promotes morphologic differentiation of neuroglia. The interaction of disease states (diabetes and galactosemia, simulated by elevated levels of glucose and galactose in the culture medium) with the above factors will be evaluated. The types, and quantities, of extracellular matrix macro-molecules synthesized by retinal vascular, RPE, and retinal glial cells cultured on a basement membrane matrix under normal conditions and with elevated glucose or galactose, with or without an aldose reductase inhibitor, will be studied. The role of RPE and choroidal vascular cells in modifying one another's behavior will be studied by histologic, autoradiographic, and immunocytochemical methods in a model of human subretinal neovascularization produced in pigmented rats by mild krypton laster photo-coagulation. The "glial modulating factor" from retina will be further purified, monoclonal antibodies prepared to it, and biochemical and immunological comparisons will be made with acidic fibroblast growth factors from retina and brain, and the "glial maturation factor" of Lim, isolated from bovine brain. Immunocytochemical localization of this factor in the retina will be attempted. A second goal of this research is to determine factors that stimulate contraction of retinal pericytes, cells whose abnormality may be critical in diabetic retinopathy. This will be approached using vasoactive agents (norepinephrine, angiotensin II, and vasopressin), and variations in the O2 and CO2 levels in the culture medium, on pericytes grown on deformable matrices, and the determining whether these agents produce an elevation in cytoplasmic free Ca++ in cultured pericytes, using fluorescent Ca++-binding probes and microspectrofluorimetry. A third goal of this project is to initiate additional long-lived non-neoplastic human retinal cell lines from epiretinal membranes excised during vitrectomy surgery on infants with stage 5 retinopathy of prematurity. Cells obtained through these cultures will be defined immunocytochemically and used in the retinal cell culture experiments described above.

Since the 1970s, increasing numbers of buildings have been designed and constructed to conserve energy and reduce air conditioning costs by minimizing air leakage through the building envelope. However, concern has arisen that such construction practices may compromise indoor air quality and thereby pose a threat to worker health. The term "sick building syndrome" (SBS) has been used to describe epidemics of symptoms or illness that occur in such workplaces and lack a specific etiology as in Legionnaires Disease or hypersensitivity pneumonitis. There have been relatively few attempts under controlled laboratory conditions to study SBS. We hypothesize that the autonomic nervous system plays a key role in modulating a number of SBS symptoms and propose to investigate the role of olfaction and other sensory cues in driving SBS. In this pilot study, we will test the feasibility of measuring changes in physiological, biochemical and cytological parameters that might underlie the symptoms of SBS and in neurobehavioral performance during controlled exposure of volunteers to volatile organic compounds (VOC). We also propose to test a method of masking the odor of VOC over a period of several hours.

Increases in psychomotor stimulant abuse have lead to a national effort to curtail use of these substances. For the most part, recent efforts have focused on stemming the tide of cocaine abuse. Attempts have been made to reduce both the supply of and demand for cocaine. In addition, the search has begun for effective treatment programs for those who have developed chronic patterns of cocaine abuse. Pharmacological treatments are being viewed as a potentially important adjunct to behaviorally-oriented treatment strategies. Given recent evidence that the reinforcing effects of many drugs of abuse are mediated through a common neural substrate, drugs developed for the treatment of cocaine abuse may be useful for treating the abuse of other substances. The long-term objectives of the proposed research are an elucidation of the neural substrates/mechanisms which mediate psychomotor stimulant reinforcement, and the development of pharmacological treatments for psychomotor stimulant abuse. These objectives will be pursued in the following experiments. 1. One series of experiments will evaluate the role of the nucleus accumbens (and possibly other dopamine terminal fields) in the self- stimulation threshold-lowering effects of amphetamine and cocaine. These experiments are intended to identify the neuroanatomical loci that mediate cocaine and amphetamine's reinforcing effects by assessing the influence of 6-hydroxydopamine (6-OHDA) lesions on amphetamine and cocaine-induced enhancement of brain stimulation reward. 2. A subsequent series of experiments will focus on the capacity of mixed D2/5-HT2 antagonists to reverse amphetamine and cocaine-induced decreases in self-stimulation thresholds. Preliminary evidence suggests that these drugs attenuate the reinforcing properties of psychomotor stimulants. The proposed experiments will systematically investigate the ability of compounds with varying specificity for the D2 and 5-HT2 receptor subtypes to antagonize cocaine and amphetamine's effects on brain stimulation reward. The relative contribution of dopamine and serotonin mechanisms will be clarified by using antagonists that differ in their spectra of dopaminergic and serotonergic activity. 3. A set of neurochemical and electrophysiological experiments will be performed based on the outcomes of the 6-OHDA and antagonist studies. These experiments will be conducted to elucidate the mechanism(s) by which an antagonist reverses cocaine or amphetamine's effects. Drug-induced changes in dopamine metabolism an release will be measured using in vivo microdialysis, while extracellular recording techniques will be used to measure dopamine cell activity. The neuroanatomical loci for the microdialysis and recording studies will be determined by the 6-OHDA experiments, and the antagonists will be selected based on their ability to reverse cocaine or amphetamine's effects on self-stimulation thresholds. The combination of behavioral, neurochemical and electrophysiological techniques used in the proposed experiments should provide insights into dopaminergic and serotonergic modulation of psychomotor stimulant reinforcement. In addition, these experiments will provide information concerning the potential value of D2 and 5-HT2 antagonists as pharmacotherapies for psychomotor stimulant abuse.

Increases in psychomotor stimulant abuse have lead to a national effort to curtail use of these substances. For the most part, recent efforts have focused on stemming the tide of cocaine abuse. Attempts have been made to reduce both the supply of and demand for cocaine. In addition, the search has begun for effective treatment programs for those who have developed chronic patterns of cocaine abuse. Pharmacological treatments are being viewed as a potentially important adjunct to behaviorally-oriented treatment strategies. Given recent evidence that the reinforcing effects of many drugs of abuse are mediated through a common neural substrate, drugs developed for the treatment of cocaine abuse may be useful for treating the abuse of other substances. The long-term objectives of the proposed research are an elucidation of the neural substrates/mechanisms which mediate psychomotor stimulant reinforcement, and the development of pharmacological treatments for psychomotor stimulant abuse. These objectives will be pursued in the following experiments. 1. One series of experiments will evaluate the role of the nucleus accumbens (and possibly other dopamine terminal fields) in the self- stimulation threshold-lowering effects of amphetamine and cocaine. These experiments are intended to identify the neuroanatomical loci that mediate cocaine and amphetamine's reinforcing effects by assessing the influence of 6-hydroxydopamine (6-OHDA) lesions on amphetamine and cocaine-induced enhancement of brain stimulation reward. 2. A subsequent series of experiments will focus on the capacity of mixed D2/5-HT2 antagonists to reverse amphetamine and cocaine-induced decreases in self-stimulation thresholds. Preliminary evidence suggests that these drugs attenuate the reinforcing properties of psychomotor stimulants. The proposed experiments will systematically investigate the ability of compounds with varying specificity for the D2 and 5-HT2 receptor subtypes to antagonize cocaine and amphetamine's effects on brain stimulation reward. The relative contribution of dopamine and serotonin mechanisms will be clarified by using antagonists that differ in their spectra of dopaminergic and serotonergic activity. 3. A set of neurochemical and electrophysiological experiments will be performed based on the outcomes of the 6-OHDA and antagonist studies. These experiments will be conducted to elucidate the mechanism(s) by which an antagonist reverses cocaine or amphetamine's effects. Drug-induced changes in dopamine metabolism an release will be measured using in vivo microdialysis, while extracellular recording techniques will be used to measure dopamine cell activity. The neuroanatomical loci for the microdialysis and recording studies will be determined by the 6-OHDA experiments, and the antagonists will be selected based on their ability to reverse cocaine or amphetamine's effects on self-stimulation thresholds. The combination of behavioral, neurochemical and electrophysiological techniques used in the proposed experiments should provide insights into dopaminergic and serotonergic modulation of psychomotor stimulant reinforcement. In addition, these experiments will provide information concerning the potential value of D2 and 5-HT2 antagonists as pharmacotherapies for psychomotor stimulant abuse.

This project is being funded through the Learning and Intelligent Systems (LIS) initiative. It is interdisciplinary research in the knowledge, processing, and learning of language. It proceeds from a framework utilizing results from mathematical statistics, adaptive systems, and formal learning theory which provide a means of treating language as a kind of statistical optimization. Previous work by the principal investigator on the integration of linguistic theory with optimization principles in neural networks has led to this new grammar formalism, optimality theory, which has had considerable impact on many aspects of the study of human language, including learning. Recently developed methods of psychological experimentation now provide reliable data on the process of language learning, even in infants. This research brings together these experimental methods for observing real-time processing and learning of language, computational methods of research on optimization and automatic language processing, and linguistic methods for studying the structure of the representations essential for human language. The investigators bring not only expertise in the contributing disciplines, but also considerable experience in interdisciplinary collaboration. The results of this research will help us to explain the mystery of how humans - and possibly artificial systems - can learn to use and understand languages.

Throughout modern linguistic theory, it has been assumed almost without exception that sentences are best represented in terms of certain types of abstract graphs called trees. The choice of trees as underlying sentence structure captures a number of intuitions about the building blocks of sentence structure, what are called constituents: they are contiguous; each constituent has a unique structural position; every independent sentence comprises a single constituent; etc. A grammatical theory must have some way of selecting those trees that represent well-formed sentences. Consequently, it must make use of some primitive vocabulary for talking about properties of linguistically relevant tree structures. The question of what enters into this primitive vocabulary has been relatively neglected. While the domination relation has been widely assumed as a primitive, this project proposes that c-command, a highly grammatically relevant structural relation, is a better choice and should instead play the the central role of characterizing well-formedness. The proposed research will address the following issues: (1) What is the precise nature of c-command? What is the range of structural objects that it allows us to define? (2) Is c-command expressive enough to define the constructs of grammatical theory, while not being overly permissive as to allow the definability of linguistically irrelevant structures? (3) To what degree can the use of primitive c-command elucidate the otherwise puzzling dichotomy between segments and categories that has been introduced in recent work to distinguish different ways of relating constituents together? (4) In what respect are views of grammar that build structural representations using sequences of derivational steps simplified in the context of primitive c-command, in particular Chomsky's minimalist proposals as well as Tree Adjoining Grammars, a system which has achieved significant results both in theoretical and computational li nguistics? (5) What are the implications of c-command for models of human sentence processing? In particular, to what degree can the assumption that the parser manipulates c-command relations account for the relative acceptability of certain local ambiguities while explaining the existence of processing difficulty for others? This project also aims to show that the use of c-command in sentence processing can unify two competing strands of work in the development of sentence processing models based on semantic dependencies and on structural configurations, maintaining the advantages of each.

It is a commonplace observation that children, in contrast to non-human primates or sophisticated computers, are able to learn a language in what seems to be an effortless fashion. Yet, the basis of this ability remains a point of contentious debate. Some theorists emphasize the importance of nature, focusing on the exquisitely abstract and subtle generalizations that form part of a child's linguistic knowledge. Others stress the importance of nurture, highlighting the remarkable ability of child language learners to detect and exploit subtle statistical properties of the language input they receive. While there is no incompatibility between these two perspectives on language learning, there has to date been little systematic investigation of the relative contributions of nature and nurture in an empirically rich domain. With support from the National Science Foundation, Drs. Robert Frank, William Badecker, and Donald Mathis will explore this middle ground, focusing on a diverse and crosslinguistically variable set of phenomena in the domain of sentence structure (syntax). This research project will use computational simulations of artificial neural networks to probe the precise character of the generalizations that emerge when statistical learning is applied to such complex syntactic data. These generalizations will be compared to patterns of human linguistic behavior via a parallel set of psycholinguistic studies, allowing the identification of contexts in which human linguistic knowledge is a close reflection of statistically-induced patterns and contexts in which it bears the stamp of a learner's innate nature.

The broader impacts of this project include an understanding of factors that might distinguish between the processes normal and abnormal language development and point to possible lines of intervention, as well as a potential characterization of certain types of language breakdown. The interdisciplinary character of this work, encompassing ideas from linguistics, psycholinguistics, and computer science, will enhance the integration of research and education both through the unique research opportunities the project will provide for undergraduate and graduate students as well as through the development of innovative courses on the mental structure of language that will incorporate a laboratory component to be made publicly available on the web.

For generations, uncovering the nature of human language has challenged researchers across a range of disciplines. Breakthrough progress requires a highly multidisciplinary yet integrated research effort, necessitating a new kind of language scientist capable of working across traditional disciplinary boundaries. This IGERT award facilitates the development of such scientists, further developing the Problem-Centered Training approach pioneered at Johns Hopkins. Through the programs Computational and Experimental Tracks, trainees will learn to deploy the diversity of methods and perspectives of linguistics, experimental psychology, computer science, cognitive neuroscience and mathematics in the attack of a single problem in the domain of language. Through an international component, trainees will gain experience in the laboratories of foreign pioneers in multiple disciplines, and will engage in research on languages other than English.

Linguistics has been undergoing a revolutionary transformation, expanding its horizons to embrace the full cognitive science of language. Trainees in this IGERT will, through their graduate work and beyond, play a vital role in completing this transformation, and in bridging a number of fundamental schisms currently dividing language science. Breakthroughs arising from a unified science of language will have major long-term impact on language education. In the short term, scientists trained in the Computational Track will transfer insight from linguistic theory to language engineering, impacting commercial and security technology. Through a suite of special outreach mechanisms targeting not only Ph.D. applicants, but also their faculty mentors and a broader undergraduate population, the program promotes the involvement of underrepresented minorities in scientific research. IGERT is an NSF-wide program intended to meet the challenges of educating U.S. Ph.D. scientists and engineers with the interdisciplinary background, deep knowledge in a chosen discipline, and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to catalyze a cultural change in graduate education by establishing innovative new models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries.

This project investigates a question fundamental to social and economic interactions: Can individuals accurately assess the trustworthiness of unfamiliar others and, if so, through what mechanisms? Decisions to trust constitute a necessary element for the development of stable partnerships and societies. Yet, in the face of the many benefits that come with delayed exchanges, the decision to trust another is often a precarious one. The individual who first extends effort or provides resources is necessarily in the unenviable position of risking that the other will not reciprocate. Consequently, adaptive functioning relies not only on trusting others, but also on the ability to decide if one's partner is worthy of trust. Interestingly, however, previous efforts designed to uncover the signals of trustworthiness have been relatively unsuccessful. Building off initial research by members of the project team which demonstrates that trustworthiness of new partners can be discerned at greater than chance levels, the current project explores a novel route by which individuals may assesses the intentions of potential partners. Rather than looking for specific cues to trustworthiness in isolation, the process of assessing trust will be reconceptualized as a dynamic and iterative one. In short, the project will examine whether decisions to trust are not based simply on reading the cues of others, but rather on a dynamic "dance" whereby partners engage in nonconscious mimicry, and in so doing, are able to use perceptions of their own bodily states to infer their partner's feelings and, thereby, predict their motivations. To investigate this possibility, the research team will conduct experiments examining the interplay of emitted nonverbal signals and mimicry on decisions to trust within the context of behavioral economic games. Moreover, given that many facets of these phenomena often occur outside of human awareness and control, newly developed social robots will be used as interaction partners for humans in several experiments. These robots provide not only exacting control over relevant expressive parameters that is not possible in humans, but also the opportunity to test proposed models by allowing the robot to predict the trustworthiness of human partners. Taken as a whole, this project not only holds potential to increase understanding of the processes the underlie the initial emergence of trust-based relationships, but also to refine the physical and computational architecture that enable robots to infer motives and predict actions of humans and, thereby, increase their utility and value as interaction partners.

The past two decades have witnessed the exploration of a range of grammatical formalisms by computational, theoretical, and psycho linguists, for their utility in building natural language interfaces and machine translation systems, characterizing the nature of human linguistic knowledge, and constructing models of language processing. Because many of these formalisms share important formal and linguistic properties (most prominently, mild context-sensitivity and lexicalization), there are many potential synergies, computational, theoretical and psychological, that can be gotten by considering ideas that stem from work outside of particular formalism. Moreover, though theoreticians, computationalists, and psychologists are concerned with solving different problems, ideas that derive from one community often turn out to have a significant consequences for the others.

The goal of this NSF-sponsored workshop, which will take place at Yale University on June 10-12, 2010, is to foster both of these types of connections: across the formalism divide and the theoretical-computational-psycho divide. The Tree-Adjoining Grammar community has a history of exploring these connections, and this workshop aims to expand the community of researchers involved in such cross-pollination even further. The workshop will bring together researchers from the Tree-Adjoining Grammar, Minimalism, Categorial Grammar, Dependency Grammar, HPSG, and LFG communities to look at the similarities and differences of the formalisms, with the goals of developing shared, broad-coverage grammars, transferring parsing and machine learning algorithms from one formalism to another. and gaining new insights into the properties of different formalisms and their capacity for linguistic and psycholinguistic explanation.

This award provides support crucial to attract to the workshop not only prominent researchers, who will give invited presentations and tutorial lectures, but also, and perhaps even more importantly, PhD students. By introducing junior researchers to the fruitfulness of cross-framework and cross-disciplinary interactions at an early stage in their careers, our hope is that the award will have a transformative effect on the kind of work they will engage in during their entire careers, potentially leading to a broader, more integrated perspective in the field at large.

This Partnerships for Innovation project from Kent State University, which is partnering with two knowledge-enhancement partner companies and five other academic, industrial and non-profit partners, will establish a broad platform on liquid crystal (LC) - polymer interfaces. LC - polymer interfaces have been of vital importance in the liquid crystal display (LCD) industry since its inception. The recent advent of flexible LCDs using plastic substrates is generating renewed and urgent interest in interface design and associated behavior. The move from glass to soft flexible substrates not only raises new technical problems, but also illuminates old ones. These problems and questions of basic science are exceptionally close and are inextricably linked; the goal of the project is to connect device and manufacturing issues in industry to the frontiers of academic research. The project aims to identify the technical issues in real products of the partner companies and to offer solutions based on the state-of-the-art characterization, computational materials science, and novel materials development. The proposed platform will not only solve key problems in currently emerging technologies, but it will also enable new LC-on-plastic (LCOP) technologies and thereby provide to U.S. industry new opportunities with the potential for strong economic development based on LCOP products.

The broader impacts of this research are potentially large-scale economic opportunities for U.S. display and related industries. A dramatic technological change today is the move of LCDs from glass to plastic substrates. This change represents a tremendous opportunity for U.S. industry to again establish a leadership position and develop and benefit from the emerging LCOP technology. The partnership will disseminate project results through networks in the LC-polymer community and provide a model for future industry-university collaboration in practical problem solving. If the current challenges are overcome, the U.S. will have the opportunity to harness, develop, and cultivate this emerging new technology, with vast technological and economic promise.

Partners at the inception of the project include the Knowledge-Enhancement Partnership (KEP) unit, consisting of Kent State University (Liquid Crystal Institute) and two small businesses: AlphaMicron (AMI) (Kent, OH), and Kent Displays (KDI) (Kent, OH), both of which are the pioneers responsible for the breakthrough demonstrations that LCOP technology is possible. In addition, there are other partners. These partners include other academic institutions: University of Akron and University of Oklahoma; a private sector organization (non-profit): Bridgestone Americas Center for Research Technology; and public sector organizations: Nortech/FlexMatters and Polymer Ohio Inc.