Grants

National Institutes of Health

BRAIN Initiative: Reagent Resources for Brain Cell Type-Specific Access to Broaden Distribution of Enabling Technologies for Neuroscience (U24 Clinical Trial Not Allowed)

National Institutes of Health

BRAIN Initiative: Research Resource Grants for Technology Integration and Dissemination (U24 Clinical Trial Not Allowed)

National Institutes of Health

BRAIN Initiative: Theories, Models and Methods for Analysis of Complex Data from the Brain (R01 Clinical Trial Not Allowed)

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY: Ischemic heart disease is the leading cause of death in U.S. and timely reperfusion of the occluded coronary artery after myocardial infarction (MI) is the most effective therapy currently available. However, additional ischemia/reperfusion (I/R) injury occurs in ~25% of patients who suffer MI and these patients often develop heart failure (HF). We recently demonstrated that activation of the brain leptin-melanocortin system pathway greatly improves cardiomyocyte energy metabolism and contractility, preserves cardiac function, and prevents progression of HF following I/R injury. Intracerebroventricular (ICV) infusion of leptin for 4 weeks, at a low dose that did not alter blood leptin concentration, improved cardiac function and metabolism after I/R injury. We also observed that these cardiac protective effects were absent in melanocortin 4 receptor (MC4R) deficient rats and that direct activation of brain MC4R using synthetic agonists (e.g. MTII), circumventing leptin signaling, also protected the heart from progressive cardiac dysfunction after MI. How the brain communicates with the heart during leptin-melanocortin system activation is still unknown. Our preliminary data suggest that the cardioprotective effect of ICV leptin or MTII infusion after I/R may be mediated by brown adipose tissue (BAT) since BAT surgical removal and BAT sympathectomy markedly attenuated the effects of central leptin or MTII administration to improve heart function post-I/R. Since obesity, a major cause of cardiovascular diseases, may induce leptin resistance, we will focus on activation of central MC4R pathway, bypassing leptin resistance. Therefore, we propose that activation of brain MC4R, via infusion of MTII directly into the brain, increases BAT activity through the sympathetic nervous system; once activated, BAT releases extracellular vesicles (EVs) containing cardioprotective microRNAs that reach the heart via the circulation and improve cardiac function and metabolism post-I/R. Our Research Strategy is organized in two aims. Aim 1 will test the hypothesis that BAT-derived EVs are essential for the cardioprotective actions of activating brain MC4R after cardiac I/R injury. Aim 2 will test the hypothesis that chronic activation of brain MC4R increases BAT-derived EVs that protect the heart from I/R injury by delivering cardioprotective microRNAs, including miR- 125b-5p. We will use state-of-the-art chronic in vivo protocols with high-resolution ultrasound techniques for imaging cardiac function in rats and mice combined with sophisticated molecular techniques for identification of the BAT-derived EVs cargo. Outcomes from this study could lead to novel and more effective therapeutic approaches for I/R and HF, and will provide a new target for MC4R agonists which are currently being used to treat rare forms of genetic obesity in humans.

NCCIH - National Center for Complementary and Integrative Health

Project Summary Improved treatments for chronic neuropathic pain are needed but hindered by an incomplete understanding of the biological mechanisms of pain development. Sleep disruptions are associated with increased chronic neuropathic pain. Thus, understanding processes critical to sleep may be the key to understanding chronic pain. The glymphatic system is a network of perivascular spaces alongside blood vessels, which facilitates cerebrospinal fluid (CSF) movement into, and interstitial fluid through the brain, ultimately draining into the meningeal lymphatic system. CSF movement between the glymphatic system and the cervical lymphatic system follows circadian (~24h) timing. During sleep, CSF influx and brain solute clearance increase, while direct CSF drainage to peripheral lymphatics predominates during the active phase. The glymphatic system presents a novel therapeutic target for neuropathic pain. This proposal introduces the hypothesis that circadian timing governs CSF movement between the glymphatic and lymphatic systems, driving cytokine redistribution across neuroimmune tissues, regulating nociception and the development of chronic pain. Aim 1 will test whether the daily glymphatic/lymphatic CSF switch deteriorates during the development of chronic pain, altering cytokine distribution across neuroimmune tissues and increasing nociception and hyperalgesia. Aim 2 will test whether the molecular clock controls daily glymphatic/lymphatic CSF distribution and cytokine distribution across neuroimmune tissue, influencing nociception across the day. Aim 3 will assess whether reinforcing circadian timing through food restriction attenuates chronic pain. Aligning peripheral rhythms with central timing provides a non-invasive therapy for chronic pain. These experiments will reveal new insights into chronic pain pathology and explore non-pharmacological interventions for a critical unmet need.

NIA - National Institute on Aging

The process of delivering antibody-based therapeutics drugs to the brain is complicated by the need to penetrate the blood-brain barrier (BBB), prompting interest in BBB-penetrating strategies for antibody therapeutics. However, the methods to test brain penetration of these drugs are inadequate due to the intermingling of blood vessels and brain tissue, which confounds the signal of drug penetration. Current methods for measuring the distribution of antibody drugs in the brain are inadequate, lacking in accuracy, reliability and the capacity for three-dimensional, high-resolution, quantitative analysis. Addressing this technological shortfall, Translucence Biosystems is enhancing its proprietary 3D brain imaging and analysis platform to create a specialized Vasculature Subtraction Parenchymal Quantification (VSPQ) workflow. This tool aims to isolate and measure only the therapeutically relevant antibody drug within the brain parenchyma. The Phase II goal is to refine this approach to ensure precise measurement, leveraging the company’s experience and expertise in neuroscience, artificial intelligence (AI), and technology commercialization. The specific aims of the project are to develop and qualify the VSPQ workflow using machine learning algorithms to distinguish between vasculature and parenchyma signals, targeting 95% sensitivity and specificity relative to human assessments; integrate the VSPQ workflow into the existing 3D imaging platform, ensuring that the AI-generated data correlates strongly with manually partitioned regional data; validate the utility of the software through blind analysis of data provided by strategic partners, demonstrating its robustness and accuracy in real-world conditions; and validate a cloud- based version of the pipeline, ensuring that it is stable, reliable, and performs consistently with the local version. The impact of this research is poised to be significant, providing a vital tool for Alzheimer's disease drug discovery and potentially improving the rate of successful treatment development. By offering the VSPQ workflow as a cloud-based software-as-a-service, Translucence Biosystems is aiming to make this innovative technology widely accessible, thereby streamlining the drug development pipeline and bringing new therapies to patients more efficiently.

NSF

Dynamics in heterogeneous and random environments arise in a broad range of scientific fields, from economic growth and fluid turbulence to diffusion models in machine learning. These systems are often modelled by nonlinear partial differential equations and stochastic processes involving multiple temporal and spatial scales. To mitigate this complexity, researchers frequently use approximate macroscopic effective models or simplified systems that inherit essential qualitative properties of the dynamics of the larger system. This project seeks to study the validity and behavior of such approximations in applications across the physical sciences, macroeconomics, and machine learning. The project also contributes to the training and development of junior researchers in active areas of applied mathematics. The research is structured around three main themes. The first part of the project develops new tools and better understanding of the connection between branching processes, mean field games, and knowledge diffusion in macroeconomic models, with particular attention to their long-time behavior. The second part concerns the mathematical foundations of diffusion models used in machine learning, focusing on their convergence rates and regimes of validity in sampling and generative tasks. The third part investigates the long-time behavior of the solutions to systems of reaction-diffusion equations. Together, these efforts aim to advance both theoretical insight and practical methodologies in modeling systems influenced by randomness and heterogeneity. 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.

Ridgefield

Branchville Elementary School Project

Market NY - RC6 - DED Local Cash

Brand USA NYS International Cooperative Working Capital

Friends of Market to MOHAI Corridor

Friends of Market to MOHAI Corridor will lead a community input process to develop design standards for a pedestrian corridor from the waterfront to Lake Union along Bell Street and Terry Avenue - the 'Market to MOHAI' corridor. Landscape architectural services will be used. Promenade elements for design will include a logo, sidewalk markers, pedestrian lighting, way-finding signs, and street furniture. This corridor will connect several neighborhoods and parks.

Brandon Street Safe Routes to School Project

Brandon Street Safe Routes to School Project would like to increase pedestrian safety, walkability, and safe routes to school by reducing traffic speed on S. Brandon Street between 46th and 48th Ave S. by installing wheel stops to narrow the road. Seattle Department of Transportation (SDOT) will install the wheel stops and hire a design contractor to instruct the group on planting low maintenance landscaping to help resolve puddle issues that occur during rains. The group will host a planting party event in December with snacks and refreshments.

Town Of Branford

Non-Priority

DEEP

Branford Town Green Revitalization

OPM

Branford Train Station TOD Master Plan.

Portland

Bransfield Park Parking Area Safety Improvements

Brazil Center

BrasilFest will take place on Sunday, August 16, 2020 from 11:00 a.m. 7:00 p.m. at the Seattle Center Mural Theatre, Armory Loft and the Fisher Pavilion Rooftop. For the 2020 event, there will be music, food, an interactive children's library with traditional Brazilian books, dancing performances, a zumba workshop, theater productions and a new partnership with the Seattle Forum Film Festival!

Friends of BrasilFest

BrasilFest will be celebrating its 25th anniversary on Sunday, August 20th, 2023, from noon - 7 pm at the Seattle Center Mural Theatre, Armory, Armory Lofts, and the Fisher Pavilion Rooftop. The event will include music, food, exhibits, dancing, workshops, and children's activities all activities delivered with fun, participation, and opportunities to educate with inclusion and diversity.

Brazil Center

Brazil Fest, a celebration of the people, food and culture of Brazil will be held on Sunday, August 19th from noon - 7 pm at three locations in the Seattle Center; the Mural Theatre, Amory Loft and the Fisher Pavilion Rooftop. The event will include music, food, dancing, workshops and children's activities all done in a big Brazilian way.

NSF

Vortex ring interactions with solid and deformable surfaces abound in nature and engineering flows. This situation is particularly relevant to the problem of replacement speech following a laryngectomy, where unsteady flow exiting a tracheoesophageal prosthesis produces pulsatile vortex rings that impinge on the curved wall of the esophagus. The resultant esophageal pressure field is responsible for successfully producing tracheoesophageal (i.e., replacement) speech. As such, understanding the mechanics that arise as vortex rings impact curved surfaces, in particular the pressure loading that is produced, could lead to improved success rates of replacement speech. This work is also more broadly applicable to both biological and engineering flows, such as cardiac hemodynamics, fluidic energy harvesting, wall-bounded turbulence, etc. The physics of these interactions will be investigated via flow visualization and both two-dimensional and tomographic particle image velocimetry. Acquisition of the velocity fields will enable determination of vorticity topologies, pressure field estimation, and identification of pressure source terms, as well as the resultant wall loading that arises during these interactions. This proposal blends the research efforts with a novel outreach plan to help high-school choral students envision how an interest in artistic expression in voice can lead to a career in science and engineering. The proposed work plan will explore the mechanics of vortex ring-surface interactions with both hemispherical and cylindrical cavities. Flow visualization and particle image velocimetry will be utilized to explore how a primary vortex ring approaching a cavity induces flow on the surface of the cavity, and subsequently causes the flow to separate and roll-up into a secondary vortex ring, and potentially develop azimuthal instabilities. This interaction will be investigated in both axisymmetric (hemispherical) and two-dimensional cavity geometries as a function of cavity radius relative to the primary vortex ring radius. The pressure loading that develops on the concave surface will also be quantified to provide insight into the fluid-structure interaction. The outcomes from this research plan will improve success rates of tracheoesophageal speech. The project will also facilitate the training and education of one graduate and multiple undergraduate students. Finally, the outreach program will inspire high-school students to pursue careers in science and engineering fields, while also providing paid summer research experiences for two of them. 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.

NYC Department of Cultural Affairs

Brave New World Repertory Theatre, Inc.

Braver Players Musical Theater Foundation

Braver Players Musical Theater Foundation is an active grantmaking foundation based in Costa Mesa, CA. Focus: arts. Contact the foundation directly for current funding opportunities.

DEPT OF DEFENSE.DEPT OF THE NAVY.NAVSEA.NAVSEA SHIPYARD.PUGET SOUND NAVAL SHIPYARD IMF

Bravo Dive Boat 65DS1101

Brawley Community Foundation

Brawley Community Foundation is an active grantmaking foundation based in Brawley, CA. Focus: community development. Contact the foundation directly for current funding opportunities.

City of Gainesville

Brazilian Cultural Arts Exchange