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Seattle Poetry Slam

Seattle Poetry Slam will host an all-ages three-day celebration of LGBTQ arts and community on December 8-10 at Capitol Hill venues. The Queer Resurgence on Capitol Hill Poetry Festival will include panel discussions, workshops, and a poetry slam competition. Seattle Poetry Slam will partner with key organizations like Seattle Spit (Seattle's only LGBTQ open mic) and Gay City (Seattle's LGBTQ Center).

NCI - National Cancer Institute

SUMMARY/ABSTRACT Cranial radiotherapy remains a cornerstone for treating primary and metastatic brain tumors. However, it is frequently associated with long-term cognitive decline, particularly in patients who survive beyond six months post-treatment. Despite advances in radiation delivery and neuroprotective strategies, no effective interventions currently exist to prevent or reverse radiation-induced neurotoxicity. The studies outlined in this proposal are based on a novel hypothesis that radiation disrupts neural lineage commitment in the developing human brain, driving aberrant cellular plasticity and transdifferentiation of neural stem/progenitor cells into endothelial-like phenotypes, which is supported by preliminary and published data. These fate shifts impair neurodevelopment and alter synaptic function, contributing to long-term cognitive deficits. The overall hypothesis is that radiation-induced cellular reprogramming in the human brain alters both cellular identity and functional connectivity, and that these effects can be mitigated through targeted inhibition of endothelial-inductive pathways (e.g., VEGF, FGFR, Notch). To test this, we will use mature human iPSC-derived cortical organoids subjected to fractionated radiation and apply single-cell and spatial transcriptomic approaches to define lineage transitions (Aim 1), followed by functional assays including calcium imaging and multielectrode array recordings to assess neural network activity in the presence and absence of pathway inhibition (Aim 2). This R21 project leverages cutting-edge 3D human brain models and state-of-the-art technologies to address a major gap in understanding the cellular mechanisms underlying radiation-induced cognitive impairment. Because the targeted pathways have existing pharmacologic inhibitors already in clinical use, this research has high translational potential for developing radiation mitigators to preserve brain function in cancer patients undergoing radiotherapy.

Friends of Rainier Valley Creative District

The Friends of Rainer Valley Creative District are hosting the 2023 Rainier Valley Community Arts Resource Fair (Arts Resource Fair) will take place on Sunday, August 20, 2023 in Columbia Park (located at the north end of Rainier Valley) from 11AM to 7PM. This is a full day multi-purpose event that will provide arts, culture, education, health, legal, housing, and business resources to the general public with a particular focus on the needs of creative businesses in the Rainier Valley.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ ABSTRACT Although World Health Organization (WHO) guidelines now recommend once‐daily tenofovir‐lamivudine‐ dolutegravir (TLD) for antiretroviral therapy (ART), adherence challenges in taking daily oral ART persist. The rates of virologic suppression (VS) worldwide for those on ART are around 70%, with a lower rate (65%) approximately three years after starting ART. Pharmacologic adherence metrics, where ART levels are directly measured in a biomatrix ‐ such as plasma, urine, dried blood spots (DBS), or hair‐ reflect actual pill‐taking and predict virologic suppression more accurately than self‐reported adherence. Our UCSF research group has helped pioneer the use of small hair samples to measure adherence to ART, but most methods to analyze ART drugs in any matrix involve liquid chromatography/tandem‐mass spectrometry (LC‐MS/MS) which is expensive and cannot be performed in real‐time. Point‐of‐care (POC) adherence monitoring requires the development of a highly selective antibody and subsequent development of an immunoassay to ART. Evidence from other disease states show that real‐time monitoring of drug levels to the needed medication, followed by supportive feedback to the patient, increases adherence and improves outcomes. Our UCSF group has now developed one of the first immunoassays (antibody‐based assay) to detect tenofovir (TFV) in urine, a matrix easily‐accessible for point‐of‐care testing. Work by our team among people with HIV (PWH) in Namibia assessed the effect of the urine assay on VS rates among persistently virally non‐ suppressed adults on ART, despite the application of WHO‐recommended enhanced adherence counseling (EAC). In a pre‐post analysis, we found that VS rates increased from 0% to 92% after urine testing and counseling at monthly ART refills over six months. Now is the time to perform a large, randomized trial to explore the ability of counseling informed by results from the urine TFV assay to increase VS versus standard‐of‐care EAC to provide evidence for incorporating the urine POC test into clinical practice. Aim 1 of this renewal R01 application proposes a large randomized trial (n=500) comparing use of the POC urine test for TFV with tailored counseling versus standard‐of‐care EAC among participants with documented virologic failure on TLD at clinics in South Africa. The primary outcome is VS at six months; secondary outcomes include assessing the sustainability of the 6‐month intervention on VS out to 24 months; development of viral resistance in each arm; and positive urine tests by arm. Aim 2 examines implementation outcomes including acceptability and feasibility, with Aim 3 assessing cost‐effectiveness of the intervention. If the trial is successful, we will have demonstrated that an easy‐to‐use inexpensive POC urine adherence test will increase VS among populations with virologic failure on TLD, which will benefit patients, decrease the development of viral resistance, and prevent forward transmission. The aspiration of this grant is to move the low‐cost urine assay into clinical care and inform WHO ART guidelines (WHO letter of support included).

SPRINGVILLE CENTER FOR THE ARTS, INC.

CNSTR/RHAB

SPRINGVILLE CENTER FOR THE ARTS, INC.

CNSTR/RHAB

RBC Foundation

RBC Foundation invests $100M annually in communities across Canada supporting youth employment, water stewardship, arts, and community well-being.

NIDA - National Institute on Drug Abuse

ABSTRACT Systems neuroscience is acquiring exponentially more neural activity data in vivo and is employing richer stimuli to study ethologically relevant behaviors. Models of neural dynamics in low-dimensional spaces (‘neural manifolds’) are increasingly state-of-the-art for describing the underlying neurobiological mechanisms to encode rich stimuli and evoke behavior. However, causally testing these theories remains challenging, as it requires dynamic manipulation of activity across neurons and time, conditioned on the individual brain, task, or environment. Here, we propose to build new machine learning methods to construct low-dimensional neural manifolds shaped by external stimuli in real time, and design perturbations of neural dynamics on these manifolds to directly test hypotheses of neural circuit function. We will broadly learn how external stimuli drive ongoing neural dynamics and which neuronal stimulations optimally align with these latent vectors. Our real-time approach will also enable us to consider multiple competing models in parallel and choose stimulations to differentiate between them, causally testing competing hypotheses of neural manifold landscapes. We will validate our models in vivo in the larval zebrafish using high-dimensional visual stimuli concurrently with holographic optogenetic photostimulation. In Aim 1, we will develop real-time dimensionality reduction algorithms to construct neural manifolds shaped by external stimulus information. In Aim 2, we will design probabilistic models for predicting the effects of neural stimulations on latent neural dynamics. In Aim 3, we will develop a method for jointly optimizing external stimuli and direct neural stimulation patterns to shape ongoing neural dynamics in real time. Successful completion of this project will result in generalizable machine learning methods that can automatically learn stimulus-shaped neural dynamics and optimize neural stimulations to drive dynamics on the manifold. These tools will be widely available and broadly useful to many neuroscientists.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

ABSTRACT Neurological studies greatly benefit from functional brain imaging to investigate brain activity and understand the underlying mechanisms of healthy and disordered behavior. Studying non-human primates (NHP) stands at the forefront of neurological research, offering unparalleled insights into complex brain activities and advanced cognitive and behavioral processes. Utilizing optical or ultrasound technologies, researchers have developed various brain imaging methods that are versatile for studying a range of awake and behaving applications. However, these tools have been restricted to only small animal models. Recently, photoacoustic tomography (PAT) has emerged as a promising non-invasive, label-free technique capable of mapping deep brain hemodynamic functions by acoustically probing the brain’s optical contrast. Yet, the efficacy of traditional photoacoustic imaging is compromised by the strong acoustic aberration induced by the NHP’s dense, curved, and thick skull. Furthermore, current PAT systems are ill-suited for awake NHP imaging, due to their unwieldy size and complex operation. In this proposal, we will transcend these limitations by developing a four-dimensional smart epidermal photoacoustic tomography (4D-SEPAT) technology, allowing for real-time, longitudinal, functional brain imaging in behaving NHPs. The proposed 4D-SEPAT technology will leverage state-of-the-art epidermal electronics, which combines soft ultrasound transducer array and high-precision shape mapping. Most importantly, the soft ultrasound transducer array, with integrated shape sensor and high-power laser source, can closely adapt to the contour of the NHP head, effectively mitigating the skull’s aberration effect. Powered by fast 3D image reconstruction, 4D-SEPAT will enable real-time transcranial brain imaging while maintaining its high sensitivity to hemodynamic functions. With full conformability to the head, 4D-SEPAT is insensitive to motion artifacts, can be longitudinally applied to behaving NHPs, and allow for deep-brain analysis of sensory and cognition. To achieve this objective, we will pursue the design, development, and validation of the proposed 4D- SEPAT system in Aim 1 and Aim 2, and demonstrate its imaging performance in awake rhesus macaques during visual-oculomotor behavior in Aim 3. Success of this 4D-SEPAT technology has the potential to revolutionize the way the brain is studied, diagnosed, and treated, by providing non-invasive, longitudinal, real-time mapping of deep brain functions.

NIAID - National Institute of Allergy and Infectious Diseases

Vaccines are the most successful prophylactic measure against pathogens, and their protective capacity depends on the formation of long-lived immunological memory, e.g. memory T lymphocytes (TMEM). Coordination between B and T lymphocytes is required against intracellular pathogens to neutralize pathogens and eradicate infected cells, respectively, as recently highlighted with COVID19 vaccine responses. Individuals living with chronic infections were shown to exhibit inferior responses to subsequent infections and vaccination. Studies in animal models suggested the cause to be the inferior recall responses by the TMEM generated to acute stimuli in hosts with preexisting chronic infection (hereafter termed inflm-TMEM). However, epigenetic imprints of persistent inflammation on inflm-TMEM have not been examined, and interventions to restore efficient protective recall responses by inflm-TMEM are understudied. Previous studies and our preliminary data demonstrated arrested development of inflm-TMEM, especially the central memory subset (TCM). Previous transcriptional profiling and our chromatin-accessibility profiling revealed skewed transcriptional and epigenetic landscapes of antigen-specific inflm-TMEM compared to bona fide TMEM, with enrichment of signatures associated with inflammatory mediators including type I interferon (IFN-I) and interleukin-6 (IL-6), which signal downstream janus kinase 1/2 (JAK1/2). We hypothesize that JAK1/2 inhibition would recover normal TMEM differentiation in hosts with preexisting chronic infection. To investigate this, we will use the same mouse model utilized for our preliminary studies to examine the differentiation of antigen-specific T cells responding to acute infection in the presence of preexisting chronic infection with or without JAK1/2 inhibition (JAKi) treatment. We will dissect the profiles of inflm-TMEM using high- dimensional flowcytometry and combined scRNAseq/scATACseq (MultiOme) profiling. More importantly, we will investigate the functional impact of JAKi-treatment on enhanced pathogen clearance and protection upon rechallenge. Our team has expertise in immunology, mouse models, and MultiOme profiling tools. This puts us in a unique position to address our main objectives which are: (1) to examine the capacity of FDA-approved interventions (JAKi) to recover generation of efficient TMEM in hosts with preexisting chronic infection, and (2) to gain insights into the molecular mechanisms underlying the skewed differentiation of inflm-TMEM., and aspects recovered by JAKi treatment. These studies push the envelope of innovation where we will employ combined state-of-the-art high-dimension flowcytometry, functional assays, and MultiOme profiling, to decipher specific mechanisms associated with lower recall capacity of inflm-TMEM that is understudied to date. We will validate novel therapeutic approaches using FDA-approved medication(s) for enhancing TMEM formation in hosts with preexisting chronic infection. This is of high relevance for enhancing vaccine efficiency in people living with chronic viral infection, and can be extended to benefit other populations living with chronic diseases with underlying inflammation. Summary

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary/Abstract Current state-of-the-art immunosuppressive strategies have significantly improved short-term graft survival rates, but they have failed to promote immunoregulation and improve long-term graft outcome. Although much research has been performed on CD4+ T cells in the process of rejection, B cells are well-established to be of great significance in alloimmunity. B cells function as antigen presenting cells to promote alloreactive T cell activation, they interact with activated T cell subsets and they differentiate into alloantibody producing plasma cells that elicit humoral rejection which rapidly accelerates graft failure. Nevertheless, distinct but rare subsets of B cells have also been identified to promote immunoregulation, and these regulatory B cells are postulated to have critical protective functions following human solid organ transplantation. In recently published studies, we observed that a regulatory receptor called Neuropilin-2 (NRP2) is expressed on distinct subsets of human and mouse B cells. In preliminary studies, we find that NRP2-expressing B cells have phenotypic features of B regulatory cells, and further that they have potential to suppress CD4+ T effector cell activation responses. In this R21 proposal, we plan to examine this possibility by profiling NRP2-expressing B cells and assessing their function to suppress alloimmune effector T cell activation. Furthermore, we will examine the effects of the NRP2 ligand Semaphorin3F (Sema3F) by profiling responsive genes in NRP2-expressing human and mouse B cells. The overall objective of this proposal is to evaluate whether Sema3F-NRP2 interactions promote immunoregulatory function in B cells. We will test the hypothesis that Semaphorin-induced signaling within NRP2-expressing B cells results in their differentiation into regulatory subsets that suppress CD4+ T effector cell activation following transplantation. We propose two specific aims in which we will: 1) profile NRP2 expression on subpopulations of human and mouse B cells to identify its function in B regulatory cell activity in vitro, and 2), determine whether NRP2-expressing B cells are of functional significance in the prevention of rejection and/or in long-term graft survival. Collectively, the proposed studies address a clinically relevant problem and our approach provides for cohesiveness to translate in vitro findings using human cells into relevant murine transplant models in vivo.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Although HIV-1 infection can be controlled through long-term treatment with anti-retroviral therapy (ART), a true cure has been elusive. Reservoir cells persist over time and support latent HIV-1 reactivation upon therapy cessation, yet little is known about the underlying molecular mechanisms. Our lab has recently identified previously unknown facets in the HIV-1 transcriptional program that we will explore in this proposal to help fill this knowledge gap, and may offer key insights into HIV-1 biology as well as cure strategies. The major goal of this grant application is to understand the role of transcription factors (TFs) in reservoir cells and Tat in first igniting and then sustaining the HIV-1 transcription reactivation program. We will accomplish this goal by leveraging genetic and genomic approaches to explore HIV-1 transcription at high-resolution in several immortalized cell models of latency and then cross-validate the data in samples from HIV-1 infected participants. Our recent studies have revealed that HIV-1 transcription reactivation proceeds through a previously unknown two-step mechanism: first ignited by transcription initiation through de novo Pol II recruitment (host phase) and later sustained by synchronization of pause release with re-initiation (viral phase). These two steps are the major transcriptional bottlenecks in the HIV-1 transcriptional program for a functional cure. Overcoming these bottlenecks guarantees a transcriptional switch that facilitates efficient latency reactivation. We will focus on defining the molecular mechanisms supporting HIV-1 transcription reactivation throughout the multi-phase HIV-1 transcription program. Specifically, we will explore the unifying central hypothesis that the composition and density of TFs at the proviral genome dictates the initial wave of HIV-1 transcription reactivation directly influencing Tat function and reactivation potential. We will examine the roles of the integration site, ligands stimulating reservoir cells and the interplay between TFs and chromatin accessibility. These goals are reflected in two Specific Aims: to define the relevance of TFs in reservoir cells that initiate and sustain HIV-1 reactivation (Aim 1), and to explore the interplay between TFs and chromatin accessibility during the transcriptional switch that facilitates efficient latency reactivation (Aim 2). If successful, this project will yield a better understanding of the molecular mechanisms by which TFs in reservoir cells and Tat converge to promote efficient HIV-1 transcription and latency reactivation, collectively having a sustained impact in the field. In keeping with NIAID’s mission of ending the HIV-1 epidemic, our long-term objective is to force the basic discoveries to devise alternative cure strategies. Thus, the fundamental knowledge to be gained could be used in future studies beyond the scope of this study, to exploit the transcriptional bottlenecks for functional cure approaches.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY/ABSTRACT Our lab aims to understand the fundamental mechanisms of mitochondrial gene regulation to advance our understanding of metabolic adaptation and mitochondrial-associated diseases. Over the next five years, we will develop and apply cutting-edge sequencing technologies to reveal how cells regulate their energy production through mitochondrial DNA (mtDNA) packaging, expression, and replication. Mitochondria generate ATP through oxidative phosphorylation (OXPHOS) and contain their own genome, which encodes 13 core OXPHOS subunits, exists in hundreds to thousands of copies per cell, and is packaged into “nuceloids” by TFAM. The high ploidy of mtDNA has posed challenges to previous functional genomics techniques that rely on Illumina short- read sequencing, as population averaging effects obscure any relevant information. We previously developed mtFiber-seq, an approach that measures mtDNA accessibility at single-genome resolution. We discovered that most nucleoids are inaccessible but can change state during OXPHOS dysfunction or cellular generation. Many questions remain regarding how mitochondrial gene expression is regulated in response to perturbations to rewire metabolism and maintain homeostasis. The high ploidy of mtDNA allows for mechanisms unique from those in the nucleus. Using a variety of perturbations and systems, we will determine how gene expression is regulated on both short and long time scales. TFAM acts as both a repressor and activator through poorly understood mechanisms. We showed that varying TFAM levels can shift the active nucleoid population and developed an in vitro version of mtFiber-seq with reconstituted nucleoids which allowed us to understand new binding properties of TFAM and recapitulated cell culture observations. How TFAM behavior is regulated and how nucleoids shift between inactive and active states is not understood. This is likely done through TFAM post- translational modifications, but these modified PTMs remain understudied. We expect to clarify how these changes change the propensity of TFAM to repress and activate transcription and replication. We are developing an expanded mtFiber-seq approach that will allow us to simultaneously map DNA accessibility and the positions of specifically modified TFAM on single genomes. There are also many outstanding questions regarding mtDNA replication, and this process is critical for maintaining a healthy population of mtDNA. The signals controlling replication are not understood. Using mtFiber-seq with metabolic labeling, we will study differences in replicating and non-replicating populations to understand how these signals control replication and copy number. Overall, we seek to better understand the mechanisms of nucleoid regulation, and mitochondrial gene expression more broadly, by applying state-of-the-art technologies that are allowing for previously impossible levels of resolution. This work will provide fundamental insights into how cells maintain energy homeostasis and adapt to changing metabolic demands, with implications for understanding mitochondrial diseases and developing therapeutic strategies.

NIA - National Institute on Aging

SUMMARY Alzheimer’s disease (AD), the most common form of dementia, is a looming crisis that imposes huge healthcare, economic and social burden in the US. AD progression is associated with neurodegeneration while the pathogenetic mechanisms underlying neuronal death and dysfunction remain unclear. This neurodegenerative process involves complex interactions of AD hallmarks β-amyloid (Aβ) and tau with the localized inflammation contributed by glial cells. But little is known about how the cells near AD hallmarks regulate themselves and respond to the microenvironment. Recently, chromatin accessibility has been recognized as a dynamic central regulator of transcription since chromatin remodeling enables access of cis-regulatory elements, while closed chromatin regions impair the accessibility of promoters and enhances. AD-associated chromatin signatures show brain region and cell-type specificity, implicating noncoding regulatory regions within AD genetic risk loci that participate in a variety of biological pathways as well as changes in TF regulation. Another layer of cell regulation is through signaling transduction and activation of transcription factors at the protein level. The outcomes of epigenetic regulation should be better described by protein measurements since proteins predominantly represent cell identity, drug target, clinical biomarkers, signaling networks, transcriptional factors, functional readouts of proliferation, cell cycle status, metabolism regulation and apoptosis makers. However, these two layers of regulatory machinery have not been integrated before for spatially distributed heterogeneous tissue cells. The current single-cell omics tools often lack spatial information, and the spatial omics tools frequently lack single-cell resolution. Integration of single-cell spatial proteomics is particularly difficult as most state of the art can only detect a few proteins. Based on our multiplex in situ tagging (MIST) microchip technique, we have successfully measured hundreds of critical proteins in cell identification, signaling transduction and transcription from single brain cells. This technique is also compatible with chromatin accessibility assays. With that, we propose to (1) Sequentially measure functional proteome and epigenome by MIST-seq with high accuracy and spatial resolution; (2) Determine molecular signatures and regulation of cells near amyloid plaques in the early AD stages. Through the unique single-cell spatial omics technology, we will not only uncover the regulatory landscape of damaged neurons in AD onset and progression, but also reveal the contribution of the inflammatory microenvironment near Aβ plaques. The success of this project will advance our understanding of neuronal loss in the early stages of AD, assist identification of drug targets and biomarkers, and uncover the complex relationship between inflammation and neurodegeneration.

NCI - National Cancer Institute

ABSTRACT E-cigarette use (i.e., vaping) among young adults is common, and many report a strong desire to quit but difficulty in doing so. The retail environment is a key potential point of intervention whereby innovative regulations can be enacted to both encourage cessation efforts and provide support to young people seeking help with cessation. Interventions employed in the nicotine retail space may be particularly effective as they reach young people at a time when they are most susceptible to continued use (i.e., just prior to purchasing e-cigarettes or vaping products). In the current study, we propose to test two innovative policy interventions to support cessation efforts among young people using our state-of-the-art simulated vape shop experimental lab space (“The Puff Point”). The proposed policies under study include (a) availability of cessation products (nicotine replacement therapy; NRT), and (b) prominent display of cessation resources at the point of sale in the retail environment. Policies that increase access to and awareness of cessation products (e.g., NRT) and cessation resources (e.g., text-to- quit lines, cessation programs or apps) in the retail environment have the potential to positively impact cessation efforts and success in cessation among young adults. This study will utilize a sophisticated 2x2 factorial design to test the effect of both policy interventions on e-cigarette purchasing behaviors and cessation intentions. Aim 1 will assess the impact of inclusion of NRT for sale in the retail space; Aim 2 will assess the impact of prominent display of cessation support services at the point of sale; Aim 3 will assess the joint effect of both policies (i.e., the interactive effects of inclusion of NRT for sale and display of cessation literature). Participants (N=200) will include young adults (21-30 years) who report having used e-cigarettes 3 or more days per week and have purchased e-cigarettes from a vape shop at least once per month, over the last 6 months. After a remote zoom session to assess eligibility, participants will visit our simulated vape shop and make purchases under one of the four conditions. A subsample will participate in a brief qualitative interview following the purchasing task to assess perceptions of the intervention. All participants will complete both a pre-task and post-task survey to assess cessation intentions. Analyses will investigate the effect of each policy on purchases made (including number of products and total amount of nicotine in non-NRT products purchased) and cessation intentions (any intentions to quit, planned timeframe for cessation [e.g., within the next month, next 6 months, next year], and specific plans for support with cessation attempt [e.g., NRT, app). Secondary analyses will investigate changes in cessation intentions pre- to post-purchasing task and whether changes differ by experimental condition. This project addresses regulations that are easily scalable and could encourage cessation from vaping among young people. The point of sale is a key intervention point, and data are urgently needed to guide regulatory efforts to reduce nicotine use and support cessation efforts among young adults seeking to do so, to reduce the adverse public health consequences of vaping in this population.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY T cell memory is stored across heterogeneous subsets with diverse functions in both tissues and circulation. While most studies have focused on the pro-inflammatory and cytotoxic functions of memory T cells, regulatory T cells (Tregs) serve an equally important immunomodulatory role in memory responses, particularly in tissues. While specific roles for Tregs in establishing tolerance and promoting tissue homeostasis have been elucidated in mouse models, the role of human Tregs in healthy immune responses and protective immunity in vivo has been difficult to assess. Moreover, the identity and function of human Tregs in diverse tissues remains unknown. We have established an organ donor tissue resource for human immunology that has allowed us to profile antigen-specific T cells across human tissues. Through these efforts, we found that antigen-specific Tregs are substantially enriched among memory T cells that respond to antigens from multiple viruses, including SARS-CoV-2, influenza, and EBV, and are particularly enriched in lymph nodes, spleen and lungs compared to blood, bone marrow and other sites. In addition, we found that memory Tregs induce an activation program that is distinct from effector memory T cells (TEM) involving CCL17 as a novel Treg-derived cytokine not produced by TEM cells or any other T cell subset. Moreover, tissue memory Tregs exhibit clonal overlap with TEM cells within and between sites. These findings raise the possibility that memory Tregs are generated along with TEM during priming and that they share a common pre-cursor with TEM. In the proposed studies, we will pursue three aims: 1) Determine the role of antigen and tissue in memory Treg induction; 2) Define the clonal and migratory relationships (i.e. tissue distributions) between memory Treg and other memory subsets; 3) Elucidate the functional and spatial interactions of tissue Tregs with immune and structural cells in the lymph node. We will combine state-of-the-art technologies for single-cell and spatial profiling with our unique human tissue resource to elucidate mechanisms for the generation, function, and maintenance of memory Tregs in human tissues. The results from this study will be important for designing strategies to promote immunoregulation and tissue repair for protective immunity and can inform Treg-directed therapies for autoimmunity and transplantation.

Ambani Foundation

Largest Indian private foundation; funds education, healthcare, rural transformation, and arts.

Dept of the Army -- Materiel Command

This solicitation invites applications (also referred to as proposals ) for basic research projects. The proposals must align with the research areas of interest to the DoW (which includes the USW(R&E) and the Agencies) and enhance the education of students in areas of STEM that align with the DoW research interests. Information about these areas of interest (including websites) is discussed below. The USW(R&E) Critical Technology Area descriptions are at https://www.cto.mil/wp-content/uploads/2025/11/CTA-One-Pager-Option-Nov2025.pdf. The critical technology priorities rely on innovation and workforce talent. The critical technology areas are: - Applied Artificial Intelligence (AAI) - Biomanufacturing (BIO) - Contested Logistics Technologies (LOG) - Quantum and Battlefield Information Dominance (Q-BID) - Scaled Directed Energy (SCADE) - Scaled Hypersonics (SHY) Basic research projects in research areas of interest to the Agencies are presented in their respective Broad Agency Announcements (BAAs), which are available as follows: Army Research Laboratory combined Broad Agency Announcement is available at: https://www.arl.army.mil/collaborate-with-us/opportunity/arl-baa/. This BAA may also be found on Grants.gov (https://www.grants.gov) by entering the BAA number, W911NF-23-S-0001, in the Search Grants keyword box. Office of Naval Research: https://www.onr.navy.mil/ Select Work With Us, then Funding Opportunities, and then BAAs, FOAs and Special Program Announcements to see the FY26 Long Range Broad Agency Announcement for Navy and Marine Corps Science and Technology, BAA N00014-23-S-B001. This BAA may also be found on Grants.gov (https://www.grants.gov) by entering the BAA number in the Search Grants keyword box. In addition to providing details about the Agencies research interests, the above documents include names and contact information of technical program managers. Principal Investigator and a Co-Principal Investigator (PI/Co-PI) are encouraged to peruse the research interests of each Agency and to contact the respective program managers to discuss mutual research interests. Applications with relevance to the interests of multiple Agencies may receive multiple reviews. Additional information and questions about the critical technology areas should be directed to Agency Contacts identified in Section II.G. of this NOFO. Other research areas that are not aligned with the (OUSW(R&E)/ASW(S&T) critical technology priorities listed in I.B.7 will be considered. The Agencies BAA listed above under I.B.6 provides other research areas of interest to the DoW. NOTE: Use the above-referenced Agency documents only to identify research areas of interest to the Agencies. Disregard instructions contained therein regarding application preparation, content, and submission requirements. Instead, follow the instructions in this NOFO. Projects proposed for funding under this NOFO must be for basic research. As defined by DoW, basic research is systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable facts without specific applications toward processes or products in mind. It includes all scientific study and experimentation directed toward increasing fundamental knowledge and understanding in those fields of the physical, engineering, life sciences, and information sciences related to long-term national security needs. Principal Investigator and a Co-Principal Investigator (PI/Co-PI) are encouraged to consider innovative approaches for their research projects with a view toward enhancing the ability of their institution to develop stronger science and engineering programs that will enable the institution to participate more competitively in a variety of defense research programs, attract and retain good students by exposing them to state-of-the-art research, and encourage them to pursue careers in STEM disciplines. Methods through which these goals can be achieved are varied. Factors such as research capabilities, facilities, and equipment are unique to each institution. Therefore, DoW will not prescribe the approach for a research project; instead, it expects applications to reflect the unique needs and capabilities of the applicant institution.

Air Force Academy

<p>The USAFA invests in an active research program for three main reasons. First and foremost, research significantly enhances the cadet learning experience. Our research is done by, for and with cadets who work alongside fellow cadets and faculty mentors. Research provides cadets with rich independent learning opportunities as they tackle ill-defined problems and are challenged to apply their knowledge and abilities.</p><p><br></p><p>Second, our research program provides opportunities essential for faculty development. Research broadens and deepens the experience base of the faculty. This infuses current, relevant, state-of-the-art and cutting-edge applications and examples into the curriculum. This also helps our faculty remain current in their respective fields.</p><p><br></p><p>Third, at USAFA we strive to conduct research to enhance the ability of the Air Force to perform its mission. There are ongoing research projects spanning topics as diverse as super hypersonics, cyber security, spatial disorientation, athletic performance and homeland defense. This BAA offers a vehicle for research to be performed to satisfy these three objectives, while also meeting research needs of industry counterparts/serve a public purpose. USAFA’s partnerships with non-Government firms enables development in the public arena, stimulating the studies in the greater technical community. All awards issued against this BAA must serve to benefit the objectives identified above.</p>

Air Force Academy

The USAFA invests in an active research program for three main reasons. First and foremost, research significantly enhances the cadet learning experience. Our research is done by, for and with cadets who work alongside fellow cadets and faculty mentors. Research provides cadets with rich independent learning opportunities as they tackle ill-defined problems and are challenged to apply their knowledge and abilities.Second, our research program provides opportunities essential for faculty development. Research broadens and deepens the experience base of the faculty. This infuses current, relevant, state-of-the-art and cutting-edge applications and examples into the curriculum. This also helps our faculty remain current in their respective fields.Third, at USAFA we strive to conduct research to enhance the ability of the Air Force to perform its mission. There are ongoing research projects spanning topics as diverse as super hypersonics, cyber security, spatial disorientation, athletic performance and homeland defense. This BAA offers a vehicle for research to be performed to satisfy these three objectives, while also meeting research needs of industry counterparts/serve a public purpose. USAFA s partnerships with non-Government firms enables development in the public arena, stimulating the studies in the greater technical community. All awards issued against this BAA must serve to benefit the objectives identified above.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Despite remarkable advances in HIV cure science, emerging cure candidates will likely involve trade-offs (e.g., incomplete eradication, monitoring burdens) and must compete with increasingly convenient long-acting ART; without early implementation guidance, even efficacious products may see limited uptake, particularly among the ~30–40% of people with HIV (PWH) in the U.S. who are not durably suppressed. We propose REALISE, a multidisciplinary program to define plausible cure profiles, quantify end-user preferences, and project population-level impact to inform product design and policy before market entry. Aim 1 conducts qualitative interviews with ~30 researchers and developers to delineate credible 10–20-year cure and long-acting treatment scenarios (eradication vs functional control, safety, monitoring, durability), yielding bounded “target product profiles.” Aim 2 elicits patient-centered preferences through a two-stage study: formative interviews (n=60; ≥50% not virally suppressed) to identify salient attributes; best-worst scaling (n=360 across Missouri, Georgia, and San Francisco) to prioritize attributes; and a discrete choice experiment (n=360) to quantify trade-offs versus alternative therapies, with latent class analysis to identify preference segments and estimate potential reach. Aim 3 integrates preference-based uptake from Aim 2 with Aim 1 efficacy and cost inputs in a mathematical model to estimate health impact, QALYs, net QALYs, and incremental cost-effectiveness across heterogeneous populations and Ending the HIV Epidemic jurisdictions. Innovation lies in linking cure R&D horizons to end-user preferences and transmission-dynamic outcomes, an approach that anticipates real-world use rather than retrofitting after approval. Deliverables include ranked cure attributes for product optimization, uptake projections including among unsuppressed PWH, and jurisdiction-specific value assessments to guide public health investment. By aligning cure design with what patients will accept and systems can sustain, REALISE will accelerate effective deployment of future cure strategies and maximize their contribution to Ending the HIV Epidemic. In doing so, this study advances NIH's priorities by connecting implementation science with prevention, treatment, and cure research. Using a multidisciplinary strategy to refine and extend `target product profiles,' REALISE will ensure cure development reflects patient needs and accelerate translation into real-world benefit.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT ABSTRACT Human immunodeficiency virus-1 (HIV-1) can be controlled with antiretroviral therapy (ART), but a cure remains elusive due to the persistence of latently infected reservoirs. These reservoirs remain transcriptionally silent, allowing the virus to evade immune clearance and rebound when therapy is interrupted. One proposed strategy to eliminate the latent reservoir is the shock and kill approach, which utilizes latency-reversing agents (LRAs) to reactivate viral gene expression, thereby enabling clearance by cytotoxic CD8 T cells. However, HIV accessory proteins such as Nef and Vpu downregulate HLA-I on infected cells, preventing recognition by CD8 T cells even after reactivation. IL-15 is a particular LRA of interest, along with its superagonist N-803, that can expand effector lymphocytes and enhance their cytolytic activity; however, its ability to rescue HLA-I expression on HIV-infected cells remains uninvestigated. IL-15 signals through the JAK/STAT pathway, which is negatively regulated by the non-receptor tyrosine phosphatases PTPN1 and PTPN2. Small-molecule inhibitors of these phosphatases, including 3-Hydroxy-1,2,3- benzotriazin-4(3H)-one (HODHBt) and ABBV-CLS-484 (AC-484), enhance STAT signaling, promote viral reactivation, and increase HLA-I expression on infected CD4 T cells. Preliminary data demonstrate that IL-15 can restore HLA-I expression on HIV-infected cells, and this effect is enhanced with PTPN1/2 inhibition. However, viral strains belonging to subtypes AD and D exert resistance to IL-15-mediated HLA-I rescue on HIV-infected CD4 T cells, suggesting subtype-specific mechanisms. In Aim 1, I will test whether IL-15-mediated HLA-A, -B, and -C rescue is possible when CD4 T cells are infected with viral strains isolated from the latent reservoir of people with HIV across a variety of subtypes and then assess if rescue is associated with increased recognition and killing of infected cells by HIV-specific CD8 T cells. In Aim 2, I will dissect the mechanism by which viral strains belonging to subtypes AD and D promote resistance to IL-15 signaling and whether this is associated with the viral protein Nef, the protein responsible for HLA-I downregulation. By uncovering how the IL- 15/STAT/PTPN1/2 axis regulates HLA-I expression and CD8 T cell recognition of HIV-infected CD4 T cells, this project will inform the design of cure strategies that enhance immune clearance of latent reservoirs. Completion of these studies will also provide rigorous training in immunology, virology, and translational therapeutics to prepare me for a career as an independent HIV investigator.

South End Seattle Arts Center dba ReVision Arts

ReVision Arts wants to make accessible our Rainier Valley Neighborhood Art Grant Projects and ReVision Arts Annual Please Touch Tactile Exhibit. This will include: 1) Translation and Interpretation of Neighborhood Art Grant Projects as needed. Public sub grantee events will be April to Sept. To create an accessible projects meeting ADA, we need $$ for Sign Language Interpreters for sub grantee events in the Rainier Valley. 2) Orientation on April 4th a) Provision of Interpreters for sub grantee Orientation b) Presentation regarding access and event planning 3) ReVision Arts will bring Please Touch Tactile Art Exhibit to Rainier Valley to celebrate the ADA Anniversary 2023. Attendance is free and open to all. For above events: Subgrantees mother tongue may not be English, we will provide language interpretation as requested. We want to close caption digital presentations. Digital translation is not always accurate, we need an editor /proof reader.

Refugee Women's Alliance (ReWA)

Refugee Women's Alliance will host a community carnival on April 27, 2019 from 3 pm - 6 pm at 4008 Martin Luther King Jr. Wy S. The event will showcase the creative contributions of refugee and immigrant youth and will include performances, art, and food.