Grants

NIA - National Institute on Aging

Abstract Lewy body dementia (LBD) is the second most common form of dementia after Alzheimer’s disease (AD), affecting over 1.4 million Americans. The causes of LBD remain largely unknown, and there is currently no cure. This application aims to explore the mechanisms that underlie the genetic link between LBD and mutations in GBA1, the gene that encodes the lysosomal enzyme glucocerebrosidase (GCase). Homozygous recessive mutations in GBA1 cause Gaucher disease, the most common lysosomal storage disorder, which is often associated with parkinsonism and cognitive impairment. Heterozygous GBA1 mutations, however, represent the strongest genetic risk factor for both LBD and Parkinson’s disease (PD), and are linked to more severe cognitive impairment and more rapid cognitive decline. Despite the role of GBA1 mutations in promoting α-synuclein (αSyn) pathology, little is known about how these mutations contribute to the pathophysiology of LBD. Using an astrocyte specific Gba1 conditional knockout (Gba1CKO) mouse model, we have found that astrocyte Gba1 deficiency induces hippocampus dependent mild cognitive impairment. By crossing Gba1CKO mice with the well- characterized Thy1-αSyn (Line 61) mouse model of LBD, which overexpresses human wild-type αSyn, we provide evidence that astrocyte Gba1 deficiency exacerbates LBD-related αSyn accumulation, cognitive impairment and motor symptoms. Gba1CKO mice further demonstrate an increase in levels of hippocampal astrocyte GABA transporter GAT-3, a reduction in extrasynaptic GABAAR-mediated tonic inhibition in CA1 pyramidal neurons, and a defect in autophagy-lysosome degradation. Based on these preliminary findings, we hypothesize that GBA1 deficiency disrupts astrocyte GAT-3-mediated GABA uptake and tonic inhibition, leading to increased neuronal excitability and more severe αSyn accumulation during the prodromal phase of LBD. Three specific aims are proposed: Aim 1 will determine whether GAT-3 upregulation contributes to impaired tonic inhibition and neuronal hyperexcitability in Gba1CKO mice; Aim 2 will assess whether GAT-3 upregulation is caused by autophagy-lysosome dysfunction in Gba1CKO mice; Aim 3 will examine whether impaired tonic inhibition exacerbates neuronal hyperexcitability and αSyn pathology in the Gba1CKO:Thy1-αSyn LBD model mice. The successful completion of this project will reveal a novel astrocyte-mediated mechanism for LBD pathogenesis and inform the development of more effective therapies.

U.S. National Science Foundation

Astronomy and Astrophysics Research Grants

NIBIB - National Institute of Biomedical Imaging and Bioengineering

Abstract The quantitative detection of nucleic acids plays an increasingly important role in the early detection and screening of cancers. Although the real-time quantitative PCR method has become the gold standard for nucleic acid quantification, its reliance on expensive equipment and trained personnel limits its use in resource-limited settings. Recently, CRISPR technology has emerged as a simple and powerful tool for highly sensitive and specific nucleic acid detection when combined with nucleic acid pre-amplification. However, due to the incorporation of the pre-amplification step, CRISPR-based detection methods require multiple operations and lack the quantitative detection capabilities needed for nucleic acid targets. Therefore, developing a simple and sensitive CRISPR approach for the quantitative detection of nucleic acid biomarkers (e.g., microRNAs) remains a challenge. Recent studies have demonstrated that exosomal microRNAs (exo-miRNAs) are promising liquid biopsy biomarkers for detecting cancer progression and assessing therapy efficacy with high sensitivity and specificity. However, current methods for exo-miRNA detection often require expensive equipment and specialized expertise, hindering their widespread clinical application. Here, we propose to study an asymmetric CRISPR approach for the quantitative detection of nucleic acids (e.g., exo-miRNAs). Furthermore, we will integrate the asymmetric CRISPR assay into a microfluidic chip to develop an asymmetric CRISPR diagnostic platform for exo-miRNA profiling in clinical blood samples. As an example application, we will adapt our asymmetric CRISPR diagnostic platform for the non-invasive early detection of breast cancer—the most commonly diagnosed cancer in the world—and rigorously validate its clinical application. Ultimately, the success of our proposed project will enable clinical translation, facilitating the development of a simple, sensitive, nucleic acid-based molecular detection method for early cancer detection and personalized medicine.

NIGMS - National Institute of General Medical Sciences

Project Summary This proposal centers on developing new deoxygenative functionalization of alcohols and carboxylic acids for accessing medicinally valuable chiral amines and fluorinated compounds through new sequential, stereo- controlled reactions. Alcohols and carboxylic acids are ubiquitous, structurally diverse, and stable feedstock chemicals, making the asymmetric deoxygenative diversification of their C–O bonds a highly attractive strategy for exploring new chemical space and discovering new therapeutics. While seminal approaches have demonstrated converting alcohols and carboxylic acids to pharmaceutically relevant chiral products, these methods often require multiple steps, undergo slow C–O bond activation, are limited in nucleophile scope, and lack stereo-control. To overcome these challenges, the Kim Group will employ a sulfonyl fluoride as a SuFEx (Sulfur Fluoride Exchange) clickable reagent for alcoholic C–O bond activation and a catalytically versatile base metal that will facilitate multiple C–O bond functionalizations of carboxylic acids. Our methods will allow one- step, rapid asymmetric C–O bond derivatization to construct C(sp3)–N/C bond formations between unfunctionalized starting materials and diverse nucleophiles with predictable stereochemical outcomes. Herein, we will develop the following Research Programs: (1) One-step, stereospecific and site-selective deoxygenative amination and perfluoroalkylation of alcohols via SuFEx, allowing direct installations of pharmaceutically relevant free amines, N-heterocycles, and perfluoroalkyl groups into alcohols, and (2) enantioselective deoxygenative diversification of carboxylic acids, providing a new platform for chiral amine synthesis via sequential geminal C– O bond functionalizations of a carboxyl group. Together, the successful realization of the goals described in these research programs will provide a new set of robust tools for rapid asymmetric derivatization of C–O bonds within widely available feedstock chemicals and complex molecules, which will expedite synthetic access to medicinally valuable products.

NSF

Many biological and physical systems exhibit high degrees of internal complexity that resist direct mathematical description. Examples include ecological dynamics in a varied environment and fluctuating flame fronts in combustion. Nonetheless, such systems often exhibit tractable behavior when viewed at large or fine scales. This "asymptotic" behavior plays a major role in applications, and often has a universal character that unites the study of disparate systems. In this project, the principal investigator (PI) will combine several mathematical methods to identify and justify asymptotic phenomena in partial differential equations (PDEs) originating in the sciences. This work has the potential to shed light on a variety of systems including ecological invasion, atomic deposition, and fluid shock formation. The PI is committed to undergraduate and graduate mentorship, with the particular aim of supporting students from underrepresented backgrounds. This project will explore the asymptotic behavior of various deterministic and stochastic PDEs in significant limiting regimes. The project comprises three interconnected lines of work. (1) The PI will study the long-time propagation speed and front structure of solutions to reaction-diffusion equations in heterogeneous and random environments. This investigation encompasses a dual analysis of associated branching particle systems. (2) The PI will combine analytic and probabilistic methods to study long-time and white-noise limits of several physically motivated stochastic PDEs, including stochastic conservation laws and stochastic heat equations near criticality. (3) The PI will investigate the action of weak viscosity on internal shock formation in the compressible Navier--Stokes equations. This involves a delicate coupling between hyperbolic and parabolic approximations. 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 project seeks to advance the mathematical analysis of plasma physics and rotating fluids. Plasmas are ubiquitous in astronomy and in geophysical fluids. They are also central to many challenges and opportunities facing the modern world, from neon lamps to fusion reactors. The many scales involved, and the very unstable nature of plasmas represent formidable challenges and require many different levels of description whose precise relationship (when to use one instead of the other, and which to believe if the results disagree) is still poorly understood. Since the Earth spins, all questions involving geofluids, such as weather predictions, necessitate delicate analysis of rotating fluids. One of the throughlines of this project is that, in some special cases, the more complicated settings may actually be better behaved or more stable than one would a priori expect; for example, a fluid in rotation may be more predictable than a fluid (almost) quiescent. Isolating such favorable situations in rotating fluids and plasma physics, and understanding how and why predictions are easier then, is one of the main goals of the project. Some of the problems addressed relate to the interaction between a charged, hot gas and a solid wall bounding it; how, in the absence of boundary, a hot plasma may be stabilized under a reversible phenomenon called ``Landau damping'' or whether a faster spinning Earth would have a simpler weather system. The project provides research training opportunities for graduate students and postdoctoral scholars. This project studies partial differential equations inspired by physics. The first part of the project concerns the description of the asymptotic behavior of solutions to non-collisional kinetic equations. The Principal Investigator (PI) studies the stability of homogeneous equilibria for the Vlasov-Poisson system, starting with the case of fat-tail equilibria, as well as the stability of vacuum for the same system in the presence of boundaries. Extensions to more involved models (e.g. Vlasov-Maxwell), will also be considered. The second part of the project addresses problems related to quasilinear dispersive equations. The PI studies the derivation of the Euler-Poisson system for ions from the two-fluid model in the case of confined domain and also investigates the stability of a constant background at rest for the compressible Euler equations in a rotating environment. These problems are addressed using tools from finite dimensional Hamiltonian dynamical systems, harmonic analysis, atomic spaces, functional analysis and more standard partial differential equations tools like the maximum principle, energy estimates, bilinear estimates and precise dispersion analysis. 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.

Public Health Agency of Canada | Agence de la santé publique du Canada

The Office of Audit and Evaluation (OAE) Departmental Evaluation Plan for PHAC describes the Program Evaluation Division's scheduled work for the five-year period from 2021-22 to 2025-26. The Plan was developed to meet PHAC's commitments under the Policy on Results (2016), which requires that each department prepare a five-year plan, annually updated. The projects included in this Evaluation Plan were selected to ensure full coverage of all Grant and Contribution spending over $5 million annually over a five-year period, prior commitments in Treasury Board Submissions, the information needs of program management, and program risks, and optimal use of resources. The Departmental Results Framework (DRF), program inventory, and performance information profiles developed by PHAC have formed the basis for this plan.

NSF

Miami Dade College’s (MDC) Advanced Technologies in Supply Chain Logistics and Education (AT-SCaLE) project will aim to modernize MDC's supply chain education program by integrating advanced technologies such as Cloud Computing, Artificial Intelligence (AI), Robotics, and the Internet of Things (IoT) into the traditional supply chain curriculum. This project will provide students with the knowledge, skills, and hands-on experience required to thrive in a rapidly evolving workforce and support the nation's economic competitiveness and workforce development. Over the three-year project, MDC anticipates that 103 students will be recruited through AT-SCaLE Summer Camps, Lunch & Learn Events, Lab Tours, and Continuing Education opportunities. These efforts will lead to enrollment in credit-bearing courses within the Associate of Science (AS) in Supply Chain program or the Logistics and Transportation Specialist College Credit Certificate (CCC), equipping students with the skills to enter and excel in the supply chain and logistics field. The project will include a range of activities designed to address evolving workforce needs and modernize supply chain education. MDC will obtain state-of-the-art equipment for the AT-SCaLE Lab and partner with Quanser to provide a one-week training program for the Principal Investigators in addition to ongoing technical support. Prologis, a global leader in logistics, will provide Subject Matter Experts (SMEs) who will share insights on advanced technologies and best practices, guide internships and placement opportunities, and meet with MDC students at least once per semester. The project will establish a modernized curriculum with input from an existing Industry Advisory Board, which will offer feedback on new course modules. Flexible learning pathways, including updated weekend courses and stackable credentials will be developed to support incumbent workers seeking to upskill and advance their careers. There is significant potential to advance understanding of modernizing the supply chain workforce and advance knowledge within the field of supply chain and logistics through the enhancement of educational methodologies by incorporating specific advanced technologies and continuous real-time industry feedback into the revised MDC supply chain curriculum. The goal of the project is to address the technician-level workforce needs by incorporating advanced technologies into the existing supply chain curriculum. The project will create a state-of-the art AT-SCaLE Lab to provide hands-on training with industry-standard tools, increase program enrollment and retention; and develop flexible learning pathways for incumbent workers. This project is funded by the Advanced Technological Education program that focuses on the education of technicians for the advanced-technology fields that drive the nation's economy. 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.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT This Phase II SBIR will de-risk a new class of antivirals that can be developed to target any RNA virus from SARS-CoV-2 to influenza. The effort will specifically translate a lead, platform-derived SARS-CoV-2 candidate (AT191) designed to be self-administered and to prevent hospitalizations or deaths by any SARS-CoV-2 variant. Despite vaccines and 2 blockbuster antivirals marketed to prevent hospitalizations, 900,000 Americans were hospitalized due to SARS-CoV-2 in 2023. Beyond vaccine hesitancy and durability concerns, existing antivirals only reduce hospitalizations and deaths by 40–50%. SARS-CoV-2 antivirals are further limited by contraindications (e.g. Paxlovid) and safety concerns (e.g. molnupiravir). Moreover, there is a risk that SARS- CoV-2 acquires resistance to all existing classes of antivirals—as occurred with all SARS-COV-2 monoclonal antibodies prior to 2024. There is a clear unmet need for new classes of antivirals, especially antivirals that can: (i) be used at-home to prevent hospitalizations, and (ii) maintain (variant-proof) efficacy as novel variants emerge. Encrypted RNA (encRNA) is a new class of RNA developed by Autonomous Therapeutics. The plug-and-play platform technology can develop antivirals against any RNA virus and can encode any therapeutic protein. Unlike state-of-the-art mRNA, each platform-derived encRNA only activates its (broad-spectrum) antiviral payload in targeted virus-infected cells. More specifically, encRNA only translate encoded proteins when bound, transcribed, and amplified by targeted viral RNA polymerase (RdRp) complexes conserved across a viral species. Thus, encRNA remain translationally inactive and safe in uninfected cells (e.g. as prophylactics). AT191 is our lead, first-in-class encRNA therapeutic candidate developed to confer inhaled and variant-proof efficacy against all variants of SARS-CoV-2 (and SARS-CoV-1). AT191 confers precision and pan-sarbecovirus efficacy—because AT191’s antiviral payload (IFN-β) is only activated and translated by sarbecovirus RdRp. In Phase I-equivalent studies, we developed: (i) the encRNA platform technology, (ii) the AT191 lead candidate, and (iii) an inhalable lipid nanoparticle (LNP) for encRNA self-administration using marketed nebulizers. We further demonstrated the (iv) variant-proof efficacy of AT191 against every tested SARS-CoV-2 variant in vitro, and the (v) preliminary in vivo safety and efficacy of AT191 in both mice and hamsters. Here we propose to develop AT191 into a GLP-ready candidate ready for IND-enabling studies. We propose to test the pan-sarbecovirus efficacy (SARS-CoV-1 & 2) of AT191 in vivo and to perform critical CMC, inhalation, dose-timing, and dose-finding studies in hamsters. We will also test safety/efficacy in non-human primates. The effort will culminate in a pre-IND. If successful in follow-on clinical studies, AT191 could be used at-home as a prophylactic or therapeutic: e.g. for immediate use after exposure to an infected child or family member. Beyond SARS-CoV-2, the same encRNA-LNP platform technology could be used to develop precision and variant-proof candidates for any RNA virus—including viruses for which no safe and effective antivirals exist.

New NY Broadband 15-16 Capital

ATC Phase 2 Broadband Capital

SP APPROP Chautaqua Erie High Tech Mfg

Athenex Dunkirk Capital

STATE, DEPARTMENT OF.STATE, DEPARTMENT OF.AMERICAN EMBASSY ATHENS

ATHENS_Photography and Videography Services for the U.S. Embassy in Athens, Greece

DEEP

Athletic field improvements including upgrade of ball field and soccer field to behind the town hall and relocation of batting cages

DECD

Athletic Field Reconstruction

St. Athanasius Youth Program, Inc.

Youth

New NY Broadband 15-16 Capital

ATI Phase 2 Area 1 Broadband Capital

New NY Broadband 15-16 Capital

ATI Phase 2 Area 2 Broadband Capital

New NY Broadband 15-16 Capital

ATI Phase 2 Area 3 Broadband Capital

Atkinson Foundation

The Atkinson Foundation focuses on social and economic justice including decent work, civic engagement, and journalism in Canada.

Department of Commerce

Atlanta FY 2021 – FY 2023 EDA Planning and Local Technical Assistance

Atlantic Canada Opportunities Agency

ACOA is a federal regional development agency providing grants for economic growth, innovation, and community development across New Brunswick, Nova Scotia, PEI, and Newfoundland & Labrador.

Atlantic Housing Foundation Inc

Atlantic Housing Foundation Inc is an active grantmaking foundation based in Dallas, TX. Focus: community development. Contact the foundation directly for current funding opportunities.

DEPT OF DEFENSE.DEPT OF THE ARMY.US ARMY CORPS OF ENGINEERS.ENGINEER DIVISION SOUTH ATLANTIC.ENDIST WILMINGTON.W074 ENDIST WILMINGTON

ATLANTIC INTRACOASTAL WATERWAY (AIWW) SNOWS CUT BANK STABILIZATION

City of Seattle — Technology Matching Fund

Update the Family Resource Center’s outdated technology lab in Rainer Beach. Add Chromebooks and Jetpacks for mobile use and internet access for clients at home.