Grants

Brandywine School District - Brandywine Operations Center

Non-Profit

Rose Hill Community Center

Non-Profit

YMCA of Delaware - Sussex

Non-Profit

PNC Bank Center

Commercial

NCI - National Cancer Institute

PROJECT SUMMARY Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman’s disease. KS causes significant morbidity and mortality worldwide, particularly in people living with HIV (PLWH) and in sub-Saharan Africa (SSA) where KSHV seroprevalence is high. It is estimated that 80% of the KS burden in SSA, where the impact of KS is heaviest, is attributable to HIV infection. KS most often develops in the setting of T-cell deficiency or dysfunction, such as in KSHV-seropositive individuals with HIV infection or KSHV-seropositive recipients of solid organ or allogeneic hematopoietic cell transplants. In these settings KS can remit following initiation of antiretroviral therapy (ART) or withdrawal of immune suppression. In SSA, primary infection with KSHV is thought to occur in childhood, but most cases of KS and other KSHV-associated disease in both PLWH and people without HIV infection develop many years, often several decades, later. These observations suggest that loss or impairment of a T-cell component of pre- existing KSHV-specific immunity underlie the development of these diseases. Strategies that preserve or restore the T-cell component of KSHV-specific immunity in PLWH and others at risk should, therefore, have potential for the prevention or treatment of KSHV-associated disease. Our studies of tumor biopsies and blood samples from people in Uganda living with HIV and KS (epidemic KS) as well as adults with KS but no concurrent HIV infection (endemic KS) have identified a large repertoire of T- cells that are likely to be specific for KSHV. We have begun to identify the antigenic targets of these putative KSHV-specific T-cells and find that they demonstrate high avidity for KSHV-encoded peptides, recognize KSHV- infected cells, are detectable in KS tumors, circulate in blood, and persist across time. Additional preliminary data from whole exome sequencing and transcriptional profiling of KS tumors reveal a sparse mutational landscape but consistent expression of latent and lytic cycle KSHV genes, supporting the concept that immune interventions that preserve, enhance, or restore the T-cell response to KSHV could prove effective for the prevention or treatment of KS, particularly in PLWH who are at greatest risk. Comprehensive definition of the targets of the KSHV-specific T-cell response in KSHV-seropositive individuals and of how that T-cell response is impaired or disabled in individuals who develop KS will provide the blueprint for such immune interventions. The studies in this application will lay the foundation for specific immune therapy for KS by identifying the major targets of the T-cell response to KSHV, identifying those that are naturally presented by KSHV-infected cells, and defining mechanisms by which KSHV attempts to evade that response.

FDA - Food and Drug Administration

SUMMARY: OVERALL PROJECT The chronic disease epidemic and continuing exposure of Americans to harmful environmental toxins in their foods constitute a public health crisis. The last line of defense for protecting Americans is food testing for harmful chemicals and contaminating microbes that can cause life-threatening and life-long complications. During the prior 5-year cooperative agreement with FDA, the Maryland Department of Health (MDH) Laboratories Administration systematically built-up its food testing capabilities across nearly the full spectrum of current and emerging threats. Through diligent investment in people and resources, MDH Laboratories Administration has achieved major strategic advances that resulted in 18 harmful-product recalls, and most from imported foods. It now proposes to leverage these cutting-edge capabilities to test foods for dangerous contaminants with two areas of focus. First, MDH Laboratories Administration seeks to strengthen and expand its chemical testing of foods for known, and identification of unknown, chemicals. Second, it seeks to offer its comprehensive across-the-board testing capabilities, supported by its new direct electronic data connections for real-time reporting to FDA, to provide a low- cost means to shift large-scale food testing from grocery store shelves to ports of entry and domestic processing facilities. These state-of-the-art capabilities promise to ensure the safety of the food supply, prevent illness, lower testing costs, and combat the chronic disease crisis.

DEPT OF DEFENSE.DEPT OF THE NAVY.NAVSUP.NAVSUP OTHER HCA.BUMED.NAVY MEDICINE WEST.NAVAL MEDICAL RESEARCH CENTER

Comprehensive full-service maintenance/repair plan for Illumina Nova/Seq 6000

NCI - National Cancer Institute

PROJECT SUMMARY/ABSTRACT Combination immune-oncology (IO) using immune checkpoint blockers (ICB) with or without vascular endothelial growth factor (VEGF) targeting agents have emerged as first-line treatments for patients with advanced renal cell carcinoma (RCC). Although the initial response rates to treatment range from 40%–60%, the rates of treatment resistance are high. Given the need to better optimize therapy selection for patients and minimize exposure to ineffective treatments, identifying which patients are destined to progress on treatment and those who can obtain long-term benefit and potentially cure is an urgent need plaguing clinical practice. Currently, no biomarkers are used in the clinic to help inform therapy selection for patients. Against this backdrop, we have pioneered a minimally invasive comprehensive blood-based liquid biopsy platform that can integrate analysis of CTC protein and DNA—necessary for improved treatment selection for patients with RCC and other cancers. The key aims of this project are to: 1) clinically validate early on-treatment CTC dynamics as prognostic biomarkers in metastatic RCC, 2) clinically validate early on-treatment CTC dynamics as predictive biomarkers to IO therapy in metastatic RCC, and 3) determine if early on-treatment CTC dynamics predict benefit to stereotactic ablative radiotherapy (SABR), which is increasing being utilized in RCC management. We will use our liquid biopsy platform to identify predictors of response and resistance to systemic therapy and radiotherapy among two clinical groups of advanced RCC patients: (1) a multi-institutional cohort of patients with RCC from University of California San Diego Moores Cancer Center, University of Wisconsin Carbone Cancer Center, and University Hospitals Seidman Cancer Center, and (2) RCC patients enrolled on a nationally-accruing, National Cancer Institute Cooperative Group trial of IO combination therapy with or without SABR. The outcomes of this project will transform how we select patients for treatment and monitor for resistance in metastatic RCC. Our team is led by Dr. Rana R. McKay, an early-stage investigator and medical oncologist at the University of California San Diego. Together with Dr. Zhao, Lang, and Emamekhoo from the University of Wisconsin, and Dr. Barata from University Hospitals, we have the clinical and translational expertise necessary to lead the studies featured in this project. We are confident that our innovative, minimally invasive, liquid biopsy approach will provide real-time molecular information for clinical decision-making that will optimize therapy selection of patients and improve patient well-being by maximizing the therapeutic benefit of treatment and limiting exposure to ineffective treatments. Additionally, our approach is scalable allowing for broad clinical application. Our proposed comprehensive clinical-grade liquid biopsy platform will revolutionize developing biomarkers for RCC and can serve as a roadmap for other cancers.

Town of Grantsville

Comprehensive Plan Revisions

Town of Willards

Comprehensive Plan Revisions

Mayor & Town Council of Oakland

Comprehensive Plan Revisions

Town of Pittsville

Comprehensive Plan Revisions

Town of Grantsville

Comprehensive Plan Revisions

Town of Loch Lynn Heights

Comprehensive Plan Revisions

Town of Willards

Comprehensive Plan Revisions

Town of Loch Lynn Heights

Comprehensive Plan Revisions

Mayor & Town Council of Oakland

Comprehensive Plan Revisions

Town of Pittsville

Comprehensive Plan Revisions

Employment and Training Administration

This is a Notice of Intent Only. The U.S. Department of Labor, Employment and Training Administration intends to provide funding for a cooperative agreement with the National Governors Association, Center for Best Practices (NGA Center) to provide a comprehensive program of support to American Apprenticeship grantees. This comprehensive program of support will conduct state policy academies, learning institutes and offer grantees the opportunity to share lessons learned, learn from subject matter experts and peers, and access implementation support on specific topics. Together these efforts will further the development of a uniquely American Apprenticeship system.

NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

Project Summary/Abstract Encopresis (fecal incontinence) and enuresis (urine incontinence) are prevalent in autistic youth and can have a negative impact on quality of life (Kroeger et al., 2009). Evidence supports behavioral interventions for enuresis. However, encopresis persists despite successful intervention for enuresis for a subset of autistic youth (Lomas Mevers et al., 2018). Unfortunately, the timeline for achieving fecal continence after successfully completing enuresis treatment is unclear and there is no available evidence on which individuals are likely to acquire fecal continence independently after urine treatment versus those who will continue to experience encopresis and require additional intervention. For those individuals who do require specific intervention for encopresis, our group has developed and tested the Multidisciplinary Intervention for Encopresis (MIE), which integrates physiological mechanisms (resolution of constipation before treatment and use of suppositories in treatment, if needed) and behavioral mechanisms (reinforcement of continent bowel movements). Randomized clinical trials (RCTs) of MIE have demonstrated feasibility, acceptability, and efficacy for improving encopresis with minimal side-effects when implemented in a specialty clinic with trained therapists. Unfortunately, this service model poses access barriers - especially for children in rural areas. This study aims to address these research gaps by assessing the progression from urine treatment to BM continence and evaluating a novel caregiver-mediated service model of MIE (CM-MIE) to improve accessibility. We will recruit two groups of participants: (a) autistic youth with both enuresis and encopresis and (b) autistic youth with encopresis alone. Those with both enuresis and encopresis (N=70) will enter a pre-randomization phase consisting of enuresis treatment and a monitoring period to assess fecal continence. This pre- randomization phase will allow determination of what proportion of youthbecome continent for bowel movements following enuresis treatment without additional intervention and how long after enuresis treatment this fecal continence emerges (Aim 1). We will also analyze participant characteristics that might relate to acquiring fecal continence in this phase (Aim 2). Those who continue to experience fecal incontinence in the pre-randomization period will join the participants who entered the study with encopresis alone and enter the randomized phase of the study (N=60; 30 per group) comparing CM-MIE to a parent education (PE) program focused on encopresis. Outcomes of the RCT (Aim 3) are the Clinical Global Impression – Improvement Scale rated by a treatment- blind Independent Evaluator and caregiver stress measured by the Caregiver Strain Questionnaire. An exploratory aim will evaluate participant characteristics that impact response to encopresis treatment. This innovative study will be the first to evaluate the progression from enuresis treatment to fecal continence in well- characterized autistic youth and the first to evaluate a caregiver-mediated intervention for encopresis.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY / ABSTRACT Alphaviruses are mosquito-borne pathogens that are capable of causing significant outbreaks of severe clinical disease. Currently, for many alphaviruses there are no approved antiviral therapies, or safe and effective vaccines. Therefore, research which seeks to determine the mechanisms by which the alphaviruses evade or dysregulate the host innate immune response is essential and critically important to systematically defining alphaviral biology and the development of innovative antiviral strategies. The overarching research objective of this proposal is to comprehensively define the impact of a novel interaction between the alphaviral Capsid (CP) protein and the host IRAK1 protein. The rationale and scientific premises supporting this objective are based on the importance of the IRAK1 protein to host innate immune and inflammatory signaling pathways, and a robust body of preliminary evidence that indicates that the CP/IRAK1 interaction is highly conserved amongst the members of the genus Alphavirus, crucial to limiting the induction of type-I interferon, and essential to Sindbis (SINV) virus neuropathogenesis in vivo. Nonetheless, the precise impacts of the CP/IRAK1 interaction on alphaviral infection and pathogenesis remain fully unrealized, constituting a critical gap in the knowledgebase. Thus, we propose the following specific aims- i) To delineate the impact of the CP/IRAK1 interaction on alphaviral pathogenesis in vivo; ii) To define the molecular impacts of the CP/IRAK1 interaction on host cellular biology; and iii) to determine the impact and consequences of the CP/IRAK1 interaction on the alphaviral CP protein. Over the course of the first aim, we will utilize highly tractable mouse models of alphaviral infection and pathogenesis to specifically probe the role of the CP/IRAK1 interaction on the evasion of Toll-Like Receptor (TLR) signaling and induction of an innate immune response, and the dysregulation of IL-1 family cytokine signaling. The second aim uses robust cellular models to discern the mechanism by which the CP/IRAK1 interaction negatively impacts signaling and to define the precise impacts of the CP/IRAK1 interaction on the host response to IL-1 stimulation. Finally, the third aim uses robust cellular models of alphaviral infection to rigorously determine the molecular consequences of IRAK1-mediated phosphorylation of the CP protein. This proposed work is highly significant in that it will comprehensively assess the importance of the novel CP/IRAK1 interaction to alphaviral infection and pathogenesis. Moreover, these efforts are conceptually, and technically innovative as robust tried-and-true and state-of-the-art approaches, techniques, and models of infection will be used to rigorously define the biological and molecular importance of the CP/IRAK1 interaction. The successful completion of these efforts will serve to fundamentally expand the understanding of alphaviral biology and lay the foundation for the development of meaningful therapeutic interventions.

NSF

This project is set at the interface of two areas in the foundation of mathematics, computability theory and reverse mathematics. Computability theory, which traces its history to the pioneering work of Alan Turing in the 1930s on the formal definition of an algorithm, is broadly concerned with the question of which mathematical problems can be solved by a computer, and among those that cannot be, in measuring precisely how far away these problems are from being thus solvable. Reverse mathematics instead looks to understand how complicated mathematical theorems are, by determining the minimal axioms necessary to carry out the logical arguments in the proofs of these results. Although these areas are distinct, they are deeply related, with ideas and results in one often leading to ideas and results in the other. Together, they provide deep insight across all areas of mathematics, revealing connections between previously disparate areas, and often leading to novel and more computationally efficient methods. This project involves graduate students. A longstanding focus of research in computability theory and reverse mathematics has been combinatorics, especially Ramsey’s theorem and related combinatorial results. But more recent work has exposed fascinating new connections with other areas, including set theory and topology, which the PI is building on and exploring in this project. More precisely, the PI addresses a suite of problems concerning two important generalizations of Ramsey’s theorem: Milliken’s tree theorem, which comes from work in structural Ramsey theory, and the Ginsburg–Sands theorem, which is a purely topological result. Investigation of these theorems in computability theory and reverse mathematics over the past few years has already produced some significant developments, yet some of the most fundamental questions remain open. This project will seek to answer these questions, including through the development of new techniques and conceptual tools with which to approach problems in computable combinatorics more generally. In this way, the project will also further develop the interplay between computability theory, combinatorics, and topology. 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.

NSF

With the surge of artificial intelligence (AI) and data science, increasing data and parameters of machine learning models come with high-order structures, also known as tensors. Tensor decomposition (TD) is commonly used to compress the data and analyze the underlying information. This project aims to develop both theoretically justified and practically efficient TD algorithms, as well as algorithms for low-rank tensor approximations and tensor completions. Such tools have wide applications in data science, statistics, engineering, and industry, including multi-view learning, convolutional neural networks (CNNs), and large language models (LLMs). The project also includes training of undergraduate and graduate students studying in scientific computing and data science. This project studies a range of challenging research tasks centered on the computation and analysis of tensor decompositions. A major goal is to overcome limitations of existing algebraic-based and optimization-based methods, which are either computationally expensive or theoretically insufficient. The tensor decomposition algorithms utilized in this project are based on generating polynomials to reformulate and understand the non-symmetric TD. The developed TD algorithms will have the following advantages: computationally efficient in terms of speed and memory, easy to implement in linear algebra friendly software, have theoretical guarantees, can be used to detect certain tensor ranks, and support higher tensor ranks. For generic tensors satisfying certain rank bounds, the approach in this project is to construct the TD by solving linear equations. When the tensor rank is higher, the problem is reformulated as a nonlinear optimization with linear constraints and can be solved using modern optimization methods. The generating polynomial-based framework can also be utilized to reformulate and solve low-rank tensor approximation and tensor completion problems, which are widely used in data science applications. 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.

NSF

This research project advances the development of next-generation liquid nanosensors using surface-enhanced Raman spectroscopy (SERS), a powerful technique that enables highly sensitive detection of molecular signatures. These sensors have transformative potential for early detection of environmental pollutants in water supplies and non-invasive diagnosis of diseases such as cancer and neurodegenerative disorders. However, current SERS probes face major limitations in sensitivity and reproducibility due to the complexity of detecting trace biomolecules in liquid samples. This award supports a cost-effective, computation-guided approach to the design, synthesis, and application of high-performance SERS nanoprobes. By integrating multiscale simulations with experimental synthesis, the project reduces reliance on traditional trial-and-error methods. Computational models will guide the structural design of plasmonic nanostructures and predict optimal synthesis conditions, accelerating discovery while conserving resources. This interdisciplinary collaboration between engineering and the physical sciences supports NSF’s mission to promote the progress of science and advance national health and welfare. The project also fosters STEM education and expands the workforce by providing hands-on research opportunities for students, helping to train the next generation of scientists and engineers. This award supports the rational design and synthesis of metal-insulator-metal (MIM) nanoprobes for enhanced SERS-based liquid sensing. The project combines continuum-scale finite element analysis (FEA), colloidal theory, and atomistic molecular simulations to model field enhancement, nanoparticle assembly, and interfacial interactions. Simulation outputs will directly inform the experimental fabrication of MIM nanoprobes with tunable core shape, silica thickness, and surface ligand chemistry. The project includes three integrated tasks: (1) development of a multiscale modeling framework to design optimal MIM nanostructures and predict solution-phase assembly conditions; (2) synthesis of MIM nanoprobes with tailored morphology and surface functionality based on computational guidance; and (3) evaluation of SERS performance across a range of analytes, including in silico screening and experimental detection of biological and chemical targets in liquid media. This integrated approach aims to establish generalizable design principles for reproducible, high-sensitivity SERS nanoprobes and accelerate their application in diagnostic and environmental monitoring technologies. 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.