Michael Young - US grants

We have been studying the molecular control of circadian behavioral rhythms using Drosophila as a model system. Homologues of genes initially characterized in the fly, have now been linked to the control of rhythmic behavior and physiology in vertebrates, including fish, frogs, mice and humans. A central component of the fly clock is a feedback circuit in which two clock proteins, PERIOD (PER) and TIMELESS (TIM), repress their own transcription. Temporal delays in this feedback promote oscillatory gene expression. We have recently discovered novel cellular features controlling one such delay. Additional studies have identifed new genes and proteins affecting periodicity of the circadian clock. In this proposal we will examine the following: (1) PER and TIM appear to be physically modified in response to their interaction in the cytoplasm, allowing their subsequent, independent nuclear accumulation. We will identify and characterized modifications of these proteins that are associated with this regulation. (2) We will determine whether a newly discovered, PER/TIM cytoplasmic interval timer contributes to temperature compensation of the circadian clock. (3) We will conduct a high-throughput screen for new genes and proteins regulating the timed nuclear accumulation of PER and TIM in cultured cells. (4) A locomotor activity screen involving several hundred transgenic RNAi stocks has shown that reduction of a specific karyopherin substantially lengthens the period of the fly clock. The molecular pathway underlying this protein's contribution to rhythmicity will be explored in flies and S2 cells. (5) Cryptochrome (CRY) has a key role in the light-dependent degradation of TIM. We have produced new mutations that affect physical interactions of the CRY C-terminal tail with the CRY photolyase homology domain (PHD). Preliminary studies indicate that some of these mutations alter CRY stability only on exposure to light. We will determine whether light induces dissociation of the CRY C-terminal tail and the PHD. RELEVANCE (See instructions): Candidate gene approaches, originating in the forward genetic screens of Drosophila, allowed mutant orthologs of human PERIOD protein and casein kinase 1 to be connected to inborn errors of sleep. The early functional studies of these genes and proteins in Drosophila have also been used as the basis for exploring specific mechanisms underlying aberrant patterns of human sleep. We believe our proposed genetic, biophysical, and biochemical studies of Drosophila's circadian clock will continue to reveal new principles of organization and function that promote an understanding of human circadian rhythms.

Animal Behavior Program

Non-technical Abstract



Title: Entropy and same-different conceptualization

PI: Wasserman, Edward A.

Proposal #: 9904569


Dr. Wasserman and Dr. Young will study the acquisition and application of an abstract
concept by a nonprimate species - the pigeon. Pigeons will be taught to
choose one key when the items of a multi-item display are all the same as
one another and to choose a second key when the items are all different
from one another - a "same-different" discrimination. Previous
experimentation has suggested that the pigeon's discrimination performance
is a function of the variability, or more precisely the entropy, of the
visual displays. In ten experiments, the will seek to better understand the
acquisition of the same-different concept, to explore the generality of the
acquired same-different concept, to study the role of spatial organization
in same-different discrimination learning, and to elucidate the role of
entropy in same-different conceptualization.

This has the potential to disclosing new and important parallels between human and animal cognition, and in demonstrating that even the most advanced forms of cognition can be given precise and rigorous explanations. Documenting that even pigeons are capable of abstraction and that deterministic computational principles may lie at the root of this complex cognitive process should help stimulate neuroscientists to uncover the biological mechanisms of this amazing ability.

This award is made under the high performance connections portion of ANIR's "Connections to the Internet" announcement, NSF 98-102. It provides partial support for two years for a DS-3 connection to the vBNS. Applications include projects in studying educational outcomes of networked multimedia, networked-based monitoring and fault diagnosis, distributed services telemedicine, interconnecting distributed biological databases to establish a "virtual computational resource center"; network-based scheduling and supply chain coordination and networking controls for network edge multimedia appliances. Collaborating institutions include the Jackson Laboratory, the Institute of Genomic Research, Lawrence Livermore National Laboratory, Lawrence Berkeley National Laboratory, Los Alamos National Laboratory, Brookhaven National Laboratory, Oak Ridge National Laboratory, and the National Human Genome Research Institute, the Jefferson Laboratory at the University of Virginia and others.

0002993
Torgersen

Educational research supports the critical importance of creating a realistic context in the classroom that is engaging to students. Theories of situated learning, instructional approaches such as anchored instruction, and successful high school, UG geoscience efforts, all recommend that students be engaged in a "macro-context" that situates learning in the authentic practices of scientists, politicians, and/or citizens. This increases the probability that students will detect the usefulness of geoscience knowledge as a tool for solving problems in their own real world; that is, they will detect the information's raison d'etre and be able to transfer learning from the classroom to their own lives. In order to 1) provide opportunities to learn, 2) provide the tools to extrapolate from personal experience (the best learning tool) 3) appreciate the scientific/economic couplings and feedback loops that affect their daily lives and 4) appreciate the temporal response of coupled systems, and 5) mindfully engage both undergraduate and high school students in construction of understanding concerning coupled dynamic environments across multiple scales (lab water, pond water, and the waters of Long Island Sound), the PIs will acquire and install an Instrumented Environmental Laboratory (InEnLab) at the University of Connecticut. Commercially available environmental probes will be installed in campus ponds that clearly demonstrate (on a daily timescale) the coupled interactions of chem./bio/phys within these small, commonplace ponds. The data streams (T, cond., O2, pH, etc., every 15 minutes) from these in situ probes will be directly connected to the Internet and available in real time through (e.g., www.myPond.uconn.edu) modeled after an existing www.mySound.uconn.edu . An anchored problem involving water issues in and around the University community will serve as a context for students to develop, identify and quantify the dynamics of this coupled system. This web-accessible data stream (with scientist diary comments) will then serve as a context for UG and HS classroom problems/examples, demonstrations of coupled system dynamics and independent inquiry as well as create unique opportunities for undergraduate honors theses. Such experiences will afford students an opportunity to inter-relate these experiences with observations they make during controlled laboratory experiments that quantify discrete processes and lead to an appreciation of the magnitude and temporal response of environmental systems over larger time scales and larger space scales. Transfer of knowledge will be stimulated by comparison of the processes and time scales in Mirror Pond to Bridgeport Harbor and Long Island Sound using streamed data from www.mySound.uconn.edu. Project management will take a management-by-objectives approach. Formative evaluation dependent measures will include completion of objectives and timelines, online website statistics, instructor variables (implementation fidelity) and student variables (knowledge, attitudes, and behaviors including interest, self-efficacy, and geoscience content achievement). Formative evaluation methods will include teacher and student surveys, artifacts of student problem solving on the scenario, course grades, teacher interviews and student interviews. The formative evaluation will be conducted by project team members and the summative by an external evaluator.

People face numerous decisions throughout the day, but nowhere are these decisions as critical as when they occur under conditions of stress, complexity, and time pressure. Choosing among a range of possible causes of explosions, weird noises, malfunctioning machinery, or unusual readings on instruments is difficult, especially when there are multiple competing candidates with varying time signatures, likelihoods, and intensities. Previous research on causal judgment has focused on controlled experiments, but everyday decision making occurs under less pristine conditions. To examine the extent to which prior approaches apply in complex dynamic situations, the proposed studies examine behavior within the context of a video game that involves multiple causal candidates, many visual perspectives, and varying degrees of complexity. Participants in the study will be faced with battlefield decisions regarding the source of enemy fire or other threats.

The theoretical basis for these studies is that causal judgments rely on the subjective certainty regarding whether an effect will occur and when it will occur. The experiments are designed to (a) evaluate the relative effectiveness of various methods of bridging delays between causes and their effects (given that delays are known to be detrimental to effective source identification), (b) assess theoretical predictions relating to the integration of information about contingency, endogenous temporal variability, and exogenous temporal variability, and (c) determine whether a proposed theoretical model extends to situations in which a cause and its effect are continuously related (e.g., the proximity of a cause determines the magnitude of its effect). A critical contribution of this project is the creation of a video game environment for studying decision making. This platform will be shared with other scientists to encourage the development of theories of dynamic decision making.

The rhizosphere, the zone of soil immediately surrounding plant roots, plays a prominent role in supplying plants with water and nutrients. However, surprisingly little is known about rhizosphere physical properties and how they affect root growth, water and nutrient uptake. The lack of non-invasive and non-destructive imaging techniques necessary to observe living roots growing in undisturbed soil have been a main reason for this shortcoming. Recent advances in synchrotron X-ray microtomography, or CMT, provide the potential to directly observe soil physical properties around living roots in-situ. The goal of this research is to quantify rhizosphere physical properties by (1) employing CMT to visualize physical root-soil structure interactions, (2) using computer models to simulate root-induced structural alterations to the rhizosphere using micro-mechanical approaches, and (3) estimating changes in rhizosphere hydraulic properties, such as water retention and hydraulic conductivity, based on CMT imaging and inverse modeling.

This research seeks to provide transformative insights into the role of rhizosphere physical properties for water and nutrient uptake by living plants. It serves as a stepping stone for better understanding the role of plants in the critical zone at the soil-atmosphere interface. The project cuts across disciplinary boundaries of biology, soil physics, and soil mechanics to offer new insights on surface runoff, soil compaction and erosion, losses to agricultural productivity, land reclamation, and principles of soil-plant interactions. Doctoral students and a post-Doctoral associate will be trained through this project.

This exploratory project will investigate the utility of social networking as a learning environment to motivate and improve the performance of high school students, especially Hispanic students, and college students in the areas of math, science, and engineering. The Learning Enabled Social Network (LESN), a joint project between the University of Connecticut?s Schools of Engineering and Education, seeks to discover how these inherently motivating environments can be adapted to enhance motivation and interest in engineering education and how to harness the power of project-based learning and social networking to enhance learning and promote the science, technology, engineering, and math disciplines. LESN is based on a strong theoretical framework of communities of practice to engage students in authentic problem solving activities. The structure of the technology allows vertical integration from elementary school to professional engineering as well as horizontal participation across various cultures and disciplines. The tool?s student-centered design seeks to facilitate student-centered learning and transform faculty teaching. Collaboration between the University of Connecticut and Windham high school will seek to identify features of the online social network that lend themselves to improved engineering problem solving. This project will also advance the understanding and skills of participating engineering faculty and administrators as related to innovative pedagogy as a result of working with the project.

Engineering education must be transformed if it is to meet the needs of the 21st century. Academic performance and motivation must be addressed at the K-12 level if we are going to improve recruitment and expand the diversity of incoming engineering enrollment. Critical thinking skills to solve real-world problems must also be improved if our graduates are to be capable of working in multi-disciplined and multi-cultured communities, which are increasingly becoming common forums for engineering work. Social networking can effectively boost academic performance and eventually lead to improved recruitment and retention in science and engineering disciplines.

RAPID: Fire-Induced Changes of Soil Structure: Implications for Soil Hydraulic Properties and Coupled Erosion by Water and Wind

David Shafer, Associate Research Professor, Division of Hydrologic Sciences, DRI
Michael Young, Associate Research Professor, Division of Hydrologic Sciences, DRI
Dave DuBois, Associate Research Professor, Division of Atmospheric Sciences, DRI
Markus Berli, Assistant Research Professor, Division of Hydrologic Sciences, DRI
Scott Tyler, Research Professor, Department of Geological Sciences and Engineering, UNR

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

Project Abstract: The Gleason Controlled Burn, to be conducted near Ely, Nevada, provides an opportunity to quantify the effects of fire on soil structure, and to test hypotheses on how fire-induced changes in soil structure can lead to coupled water and wind erosion by collecting data at the same locations prior to and after the burn. The burn will be conducted by the U.S. Bureau of Land Management in August 2009. Because the burn is a planned event, pre- and post-burn measurements can be conducted on pre-determined sites. The funding awarded by NSF, along with internal funds from DRI, will be used to collect a set of pre-fire measurements. The area to be burned in the Gleason Fire has strongly-developed, coarse crumbled, soil structure in unburned areas. However, where other controlled burns have been done nearby, this structure has collapsed into a structureless soil, rich in fine particles that are most likely prone to erosion. Pre-fire measurements will include soil morphology and structure, water infiltration, air permeability, and wind-shear required to induce aeolian transport of soil particles. Hypotheses include: 1) the fire will destroy soil structure, increasing soil bulk density, and decreasing soil hydraulic conductivity and air permeability, a set of conditions that would increase the potential for soil erosion by water due to precipitation input; and, 2) the loss of soil structure will disaggregate soil material that would be more prone to suspension by wind at lower wind velocities, when compared to pre-burn conditions. Most studies on post-fire effects lack a true comparison to pre-fire conditions. This research will allow changes in soil structure to be quantitatively described and linked to post-fire hydraulic and aeolian transport properties that strongly influence the susceptibility of post-fire soil erosion. Although limited in scope, this research will provide the data needed for post-fire comparisons, and allow testing of some of the field and laboratory methods that the researchers will propose to use in a more comprehensive proposal to NSF on pre- and post-fire soil properties and erosion potential. The follow-on proposal will include collection of post-fire data from the Gleason Fire.

This Small Business Innovation Research (SBIR) Phase I project aims to develop efficient manufacturing of nanostructured flexible transparent conducting electrodes (TCEs) with low resistivity and high durability. Flexible nanostructured TCEs will be produced by using the proprietary surface-embedding technology in flexible transparent polymers. It is anticipated to demonstrate superior flexibility, conductivity, and comparable transparency to the current technologies.

The broader/commercial impact of this project will be the potential to provide a highly conductive and highly transparent conducting electrode that is flexible, durable, and inexpensive for applications in flexible thin-film photovoltaics (TFPVs). Existing TCEs, including other transparent conducting oxides, either are relatively inflexible and brittle, or if flexible, do not offer high conductivity and transparency, which has limited the adoption of many flexible TFPV technologies. Advances made through this project will have a significant long-term commercial impact by enabling the widespread adoption of flexible TFPVs.

The Fall 2012 MIdwestern GrapH TheorY LIII (MIGHTY LIII) conference will be hosted at Iowa State University in Ames, Iowa on September 21-22, 2012. MIGHTY is a long-running conference series which draws graph theorists from across the country to one- or two-day conferences to disseminate new ideas in a wide variety of topics related to graph theory. Topics typically represented include chromatic graph theory, directed graphs, hypergraphs, and applications of graph theory (i.e., to biological and social networks).

This conference provides a rare opportunity to bring together a large number of researchers in graph theory from the Midwest. The broad appeal of the plenary speakers, Ron Graham and Persi Diaconis, will attract many participants including students and junior investigators. Most of the funds from this award will support the travel costs of such participants. More information about the conference is available at the conference website: http://www.math.iastate.edu/mighty2012/.

This Small Business Innovation Research (SBIR) Phase II project aims to develop high-performance transparent conductors as a replacement to Indium Tin Oxide (ITO) in touchscreens. ITO suffers from a number of disadvantages, including being one of the most expensive components of a touchscreen device, complex manufacture, and inflexibility. In this project, a transparent conductor will be developed using solution-based conventional coating equipment. Two key features of this novel transparent conductor are: (1) ease of processing, which eliminates many conventional processing steps involved in coatings; and (2) extreme durability, which enables the creation of next-generation touch devices that are otherwise impossible to realize with ITO or other ITO-alternative materials. The tradeoff between photonic transmission and electronic conduction will be theoretically and experimentally studied by extracting effective optical parameters of transparent conductor films. The printed touchscreen sensors will be integrated into functional multi-touch projected-capacitive devices, which are expected to show mechanical flexibility, higher signal to noise ratios, and faster response times.

The broader/commercial impacts of this project will be the potential to enable enhanced performance of touchscreens at disruptively lower costs. The total addressable market of patterned transparent conductor materials for touchscreen industry is about $1.3 billion today. Currently, material and processing costs of ITO represent a growing portion of the bill of materials for touchscreen devices. Transparent conductors to be developed through this project offer low-cost, high-performance, and high production throughput benefits, which will address the ITO-related challenges in touchscreen industry. Other applications of this technology includes liquid crystal displays, organic light emitting diodes, e-paper, flexible displays, thin film photovoltaics, electromagnetic shielding, defrosting windshields, low-emissivity architectural glass, and smart windows.

Bridgewater State University (BSI) will examine how flexibility in the workplace, meaning flexible hours and conditions of work, may improve the representation and advancement of women faculty in Science, Technology, Engineering, and Mathematics (STEM). BSU will conduct a series of interviews and a survey to better understand how women in STEM, especially women faculty of color, who work either full time or part time at teaching-intensive institutions, may be supported in the academic environment. Both men and women faculty, especially at teaching-intensive institutions, will benefit from the findings because the project will result in recommendations on changing the work place environment to achieve better work-life integration and a more supportive environment.

The study has a two-pronged approach to understanding workplace flexibility by 1) investigating full-time faculty members' access to, and experiences with, workplace flexibility, and 2) by examining how to better support part-time faculty so that part-time work is a more viable path to workplace flexibility using a mixed methods approach. Special attention will be paid to the perspectives of women faculty of color, given their severe underrepresentation on campus. Previous published research on women in STEM has focused almost entirely on research institutions, so this study will offer a significant contribution to the literature by systematically documenting the experiences of women faculty in STEM at a teaching-intensive university. Previous research has shown that women scientists often experience identity interference, which occurs when the norms and expectations of being a woman interfere with those associated with being a scientist. However, faculty at teaching-intensive universities may have a strong teacher identity that can bridge the gap between their woman identity and scientist identity, so long as they are provided the workplace flexibility to explore different facets of their professional lives and achieve effective work-life integration. This study will test this hypothesis while empirically exploring how to increase workplace flexibility for both full- and part-time faculty members. This study is specifically designed to provide empirical support that will motivate institutional transformation to support the advancement of women in STEM at BSU. Results of this study are expected to impact the experiences of women in STEM across the state university system. Furthermore, because there is a dearth of information in the scientific literature regarding faculty in STEM beyond research-intensive institutions, disseminating the results of this study can inspire other teaching-intensive institutions to consider the ways that they can support the advancement of women in STEM. While this study is focused solely on faculty experiences, supporting faculty at teaching-intensive universities can have a positive effect on a large number of students, given the close relationships between faculty and undergraduate students at teaching-intensive universities. Finally, because previous research has suggested that workplace flexibility is crucial to the advancement of women of color in STEM, transformations motivated by this project could increase the racial and ethnic diversity of STEM fields.

Combinatorics is a growing and important area of mathematics. The focus of combinatorics is the structure of discrete (as opposed to continuous) sets of objects. Combinatorics is critical to many areas of mathematics, and plays a key role in computational, scientific, and engineering applications. In part due to the legacy of Paul Erdos, combinatorics is a research field driven by collaboration. In order to provide graduate students in combinatorics a collaborative research opportunity and nurture long-lasting research collaborations, we will organize the Rocky Mountain-Great Plains Workshop Graduate Research Workshop in Combinatorics.

This award will support the Rocky Mountain-Great Plains Workshop Graduate Research Workshop in Combinatorics (GRWC), which will be held in Denver, CO from July 28th-August 8th, 2014, will involve approximately 30 graduate students, 4 postdoctoral researchers and 10 faculty in an intense two-week collaborative research experience. Participants will work to solve important, relevant problems from graph theory, enumeration, combinatorial matrix theory, finite geometry and other modern sub-disciplines of combinatorics. Students will prepare open problems prior to the workshop under the guidance of a faculty mentor from the organizing committee, which consists of faculty from the University of Colorado Denver, University of Denver, Iowa State University, the University of Wyoming and the University of Nebraska Lincoln. These problems will then either be presented at the workshop by their proposers or hosted on the workshop's secure problem wiki, and will be worked on by small groups of participating students, postdocs and faculty. For more information about the GRWC, including a detailed description of the workshop format please see the workshop website at http://sites.google.com/site/rmgpgrwc .

? DESCRIPTION (provided by applicant): This project assesses associations between ambient air pollution exposures and vascular phenomena, integrating air pollution epidemiology, exposure assessment, and applied statistical techniques. The proposal aims to further understanding of the patterns and biologic mechanisms underlying the relationship between air pollution and cardiovascular disease. This project will investigate acute and chronic effects of ai pollution on cellular adhesion molecules and on the microvasculature, as measured via retinal photographs. This research utilizes a large, existing, multi-center US cohort with well-characterized health measures and state-of-the-art air pollution exposure predictions. Design of the study allows assessment of microvasculature longitudinally as well as characterization the interrelationship between air pollution exposure, microvascular changes, adhesion molecules, and cardiovascular events via mediation analysis (causal modeling). This research and corresponding training plan will provide experience in advanced statistical methods, biological measurement techniques, and cardiovascular pathophysiology through a combination of formal coursework, independent study, and applied research.

The Rocky Mountain-Great Plains Graduate Research Workshop in Combinatorics (GRWC), will be held in Laramie, WY (2016), Denver, CO (2017) and Ames, IA (2018), building upon successful NSF-funded workshops in 2014 and 2015. Each workshop will involve approximately 39 graduate students and postdoctoral researchers, and 10 or more faculty members in an intense two-week collaborative research experience. Participants will work to solve important, relevant problems from graph theory, enumeration, combinatorial matrix theory, finite geometry, and other modern sub-disciplines of combinatorics. Students will prepare open problems prior to the workshop under the guidance of faculty mentors from the organizing committee, which consists of faculty from Iowa State University, the University of Colorado Denver, the University of Denver, the University of Nebraska Lincoln, and the University of Wyoming. These problems, presented at the workshop by their proposers or hosted on the workshop's secure problem wiki, will be worked on by small groups of participating students, postdocs, and faculty. For more information about the GRWC, including a detailed description of the workshop format, please see the workshop website at http://sites.google.com/site/rmgpgrwc

The goal of the collaborations at the heart of the GRWC is to produce high-quality, publishable research on a variety of topics. Another longer-term goal of the workshop is to help student participants expand their professional research networks. A strong research network is often a crucial part of building a generative and sustainable research program, and establishing these connections at an early career stage can have a long-term positive effect on the quality, impact, and depth of a professional's research portfolio. Participation in the GRWC will allow students to cultivate a large professional network of peers from the combinatorics community with whom they will be able to interact and collaborate throughout their careers. The GRWC will also offer professional development workshops to help students and postdocs prepare for job searches and future careers in academia, industry, or government.

In this NSF INCLUDES Design and Development Launch Pilot the institutions of "Building on Strengths" propose to build and pilot the infrastructure, induction process, and early implementation of the Mathematician Affiliates of Color network. This network will consist of mathematicians of color from across academia and industry who want to invest time in, share their expertise with, and learn from students of color and their teachers. Building on Strengths will draw on basic needs cognitive theory to support these interactions and will focus narrowly on short and moderate term collaborations (from one month to a semester) between visiting mathematicians, students, and collaborating teachers that will involve three specific types of interactions: doing mathematics together as a habits-of-mind practice, talking about the discipline of mathematics and the experiences of mathematicians of color in that discipline, and relationship-building activities. The foundational infrastructure developed in the project will include systems for recruitment, selection and induction, a process for pairing affiliate mathematicians with classrooms, and support structures for the collaborations. To support the goals of the network a prototype virtual space will be developed in which real-time artifacts can be collected and shared from the classroom interactions. While Building on Strengths will pilot this program in the secondary context, once a viable model is established, scaling to K-16, as well as to other STEM fields, will be possible.

The research study in the project uses an exploratory sequential mixed-methods design and will be conducted in two phases. In the first, quantitative, phase of the study the following questions will be addressed: (1) Is the teacher-mathematician collaboration associated with a change for students in perception of basic human needs being met, mathematical or racial identities, or beliefs about mathematics or who can do mathematics? (2) Is the teacher-mathematician collaboration associated with a change for adults in perceptions of the role of basic needs or in adults' identities or beliefs about mathematics or who can do mathematics? In the second, qualitative, phase of the study, two types of interactions will be selected for in-depth qualitative study, identifying cases where groups of students experienced changes in their needs, identity, and beliefs. In this qualitative case-centered phase, the following questions will be explored: (1) What is the nature of the mentor-student interaction? (2) What aspects of the intervention do students feel are most relevant to them? (3) How did the implementation of the intervention differ from the anticipated intervention? The results of the study will help improve the infrastructure for, and better support the interactions between, mathematicians of color, students of color and their mathematics teachers; the outcomes will also shed light on how students experience their interactions.

The concept of networks is a mathematical term used to analyze relationships between objects (e.g. people, places, and things). Of particular importance is the study of how influence propagates throughout networks, especially how one can deduce the influence of an entire network by monitoring a few members. The objective of this project is to establish a comprehensive knowledge base for developing, implementing, and applying computational methods related to this phenomenon. As a result, this research has strong connections to applications related to social networks, electrical power networks, and quantum systems. This project also supports a concerted effort to engage underrepresented groups within the research. Hence, the impact of this educational component includes the development of underrepresented groups within the next generation of STEM researchers.


The main technical contribution of this project is the integration of combinatorial optimization, spectral graph theory, and numerical analysis techniques to examine zero-forcing in networks. In particular, the research team will incorporate branch decomposition techniques and linear and integer programming techniques to significantly increase the computational efficacy of algorithms to solve zero-forcing problems on graphs. The models and algorithms that result from this study will be validated using experimental data and also by data attainable publicly like electrical grid data. This research will significantly advance the knowledge base of combinatorial optimization, integer programming, and spectral graph theory while also contributing to the increased scalability and efficiency for solving computationally hard problems related to the aforementioned applications.

Project Summary/Abstract Our genetic screens in Drosophila previously identified several mutations with strong effects on patterns of sleep. Recently we found that three of these genes, insomniac, cullin3 and nedd8, are expressed in the blood-brain-barrier-forming subperineurial glia of the fly, and that the morphological and biophysical properties of the barrier are altered in inc, cullin3, and nedd8 mutants. In our proposed studies we will test the effects of classical barrier mutants on sleep, evaluate barrier function across the entire range of available sleep mutants and in aged vs young flies, and explore evidence for regulatory interactions among sleep and classical barrier-regulating genes. Most Drosophila sleep mutants severely reduce longevity. We will determine whether mutations that increase longevity also improve barrier function and sleep duration in sleep mutants. In a second branch of our proposed research we will examine the role of circadian clock genes in commonly encountered disorders of human sleep. We recently discovered a mutation of the circadian clock gene CRY1 that is associated with a form of delayed sleep phase disorder (DSPD) that affects ~1 in 100 individuals worldwide. The results of our study suggest a novel approach for exploring the heritability of similarly common sleep disorders: Predictive algorithms will be applied to several large human exome databases to select candidate circadian variants for cellular phenotyping. Prevalent alleles that are associated with altered circadian rhythmicity in cell culture assays also will be studied by behavioral phenotyping of carrier subjects identified by collaborators at Bilkent University in Ankara, Turkey. Disordered sleep is often accompanied by chronic diseases including diabetes, obesity, or certain mood and anxiety disorders. Although causality in such instances has been difficult to establish by traditional approaches, we will employ deep physiological and behavioral phenotyping of individuals sharing specific genetic variations affecting sleep in tests for linkage to specific co-morbidities. These studies may significantly enrich our understanding of biological pathways regulated by circadian clocks in humans as well as fundamental disease etiologies.

Iowa State University (ISU) in partnership with researchers at the Education Development Center (EDC) and the University of North Carolina Charlotte will implement an NSF EHR Core Research (ECR) project to study the experiences, perspectives, and stories of successful doctoral students and recent PhDs from underrepresented groups in mathematics. The project will develop interview instruments and conduct in-depth, semi-structured interviews with four cohorts: newly accepted students, early graduate students (pre-qualifying exams), advanced graduate students (dissertation level), and recent PhDs (0-5 years since graduation). The interview instruments could be useful to the field beyond this project and the use of these four cohorts will add to the current literature. The research questions in the study are: What are lived experiences of successful underrepresented students who are pursuing mathematics PhDs? and What formal and informal structures are perceived by doctoral students as effective supports?

The research will build knowledge to inform decisions about changing mathematics department cultures and practices to better recruit, retain and graduate mathematicians from underrepresented groups. The project will result in survey results from 100 graduate students and recent graduates and twelve composite counterstories illustrating the student experiences and support systems that result in success for students from underrepresented groups. The counterstories and other results are expected to disrupt current perceptions about who can be successful in graduate school, and how. The project includes plans for strategic dissemination of the research results to stakeholders and practitioners.

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

Project Summary ? Michael C. Young ? University of Toledo Developing more general strategies for late stage functionalization of complex molecules is an important and much needed area of research. Using natural products that can be produced via sustainable fermentation technology is the most expedient method to prepare complex therapeutic agents, and although semi-synthesis can be a viable strategy to further derivatize these natural products to achieve new and potentially more useful drugs, the majority of unreactive C?H bonds on these molecules are not able to be selectively functionalized with current technology. To circumvent this challenge to producing next generation antibiotic, anticancer, and other much needed drugs, we propose using a simple hydrogen bonding interaction to position reactive transition metal catalysts in close proximity to a single C?H bond on complex substrates bearing a hydrogen bond acceptor. By installing a tunable linker between the hydrogen bond recognition domain and that of the metal catalyst, we anticipate that a library of different catalysts can be accessed that will allow functionalization at a defined distance from the directing handle of the substrate. The long term goal of this research is to develop libraries of different transition metal catalysts to achieve C?C, C?N, C?O, C?S, and C?B bond formation from inert C?H bonds on complex steroid and macrolide structures, thereby allowing rapid access to new therapeutic targets, especially new antibiotics and anticancer agents. During the funding period, we intend to demonstrate proof of principle by performing iron-based C?H amination and rhodium-based C?H alkylation, and using piano stool complexes we intend to expand towards photochemical-mediated C?borylation. Using a hydrogen bond-directing approach to performing biomimetic C?H activation is expected to revolutionize late stage functionalization by providing a more general strategy for directed C?H activation, and will dramatically increase the types of semi-synthetic procedures that can be performed on complex molecules. Furthermore, the catalyst and product libraries will be made readily available to members of the scientific community, ensuring maximum adoption of the catalysts as well as increasing the likelihood of quickly demonstrating the viability of the approach to access new biologically active molecules.

Project Summary/Abstract Genetic screens in Drosophila have identified mutations that significantly reduce both night- time and daytime sleep. Genes affected by these mutations are expressed in the blood-brain- barrier-forming subperineurial glia of the fly and alter the morphological and biophysical properties of the barrier. We have discovered novel genetic interactions among some of these mutations: surprisingly, certain mutant combinations restore both sleep and blood-brain-barrier function. We propose further studies that could reveal molecular pathways connecting their gene products and clarify their contributions to sleep and barrier function. We discovered that in wild type Drosophila the blood-brain barrier opens and closes with a rhythm that requires a circadian clock. We have also found that barrier permeability is closely connected to sleep need: sleep deprivation opens the barrier, but rebound sleep closes it. What is being exchanged across the barrier in such a dynamic fashion? Nervous system function is protected by a steep concentration gradient of K+ separating the haemolymph and brain. In our proposed studies we will develop tools to quantify K+ flux across the blood brain barrier with high temporal resolution in living flies. Are episodes of sleep and wakefulness correlated with these ion exchanges? Do such measurements reveal features of wake/sleep behavior that are not evident using standard locomotor activity monitoring? Our studies have also shown that sleep mutants reduce lifespan, but in a fashion that can be reversed by time-controlled access to food. These effects require a circadian clock and we will determine which tissues are responsible for this response and whether lifespan restoration depends on sleep recovery. Chronic exposure to psychogenic stressors can have profound, long-lasting effects on both physical and mental health and is often accompanied by a profound loss of sleep. Chronic social isolation provides a means by which a psychogenic stressor can be easily applied for an extended period, and we observe significant reductions in total sleep, day-time sleep, and night-time sleep in isolated flies when compared to sleep in siblings that are group reared. To search for genetic pathways that might respond to isolation-induced stress and depress sleep, comparative RNAseq assays were performed using Drosophila heads collected from group- reared flies, or from flies stressed through chronic isolation. Among the most highly responding genes are those thought to regulate appetite. These map to a small neuronal circuit which we will further characterize to determine its possible role in isolation-induced stress responses affecting sleep and hunger.

With support of the Directorate of Mathematical and Physical Sciences (MPS) Drs. Michael Young of Carnegie Mellon University, Pamela Harris of Williams College, Jennifer Ross and Moses Ntam of Tuskegee University and Tera Jordan of the Iowa State University form the core leadership team that will provide mentorship and other support to the first two cohorts of the MPS-Ascending Postdoctoral Research Fellows. The MPS-Ascend funding mechanism (NSF 21-573 and NSF 22-501) is intended to recognize beginning investigators of significant potential and provide them with experience in research that will broaden perspectives, facilitate interdisciplinary interactions, and help broadening participation within MPS fields. The purpose of the MPS-Ascend External Mentorship program is to support these postdoctoral Fellows who will broaden the participation of groups that are underrepresented in MPS fields in the U.S. including Blacks or African Americans, Hispanics, Latinos, Native Americans, Alaska Natives, Native Hawaiians and other Native Pacific Islanders. This team will develop a network of mentors and sponsors who will enhance the Fellows’ professional preparation and equip them for leadership roles as equity-focused scholars. The community will function using a layered mentor approach that connects the fellows with one-on-one, peer, and volunteer expert mentors. Through professional development and learning activities, as well as interaction with mentors, the Fellows will be prepared for career success.<br/><br/>This effort will bring together a diverse group of educators with experience in math and physical sciences (MPS) as well as social sciences to provide MPS postdoctoral fellows with mentoring experiences that will strengthen their career preparation. The knowledge gained through this project will help to contribute to higher education and science literature regarding promising practices related to preparing postdoctoral fellows for successful professional experiences and seamless transition into the academic arena. This project will develop future faculty and industry leaders who will understand the importance of providing holistic mentoring to support postdoctoral fellows. The planned professional experiences of the postdoctoral fellows will equip them to interact with people from all backgrounds and contribute to broadening the participation of individuals from historically underrepresented groups.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.