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Humble Elementary/Humble ISD

Artistic fee subsidy for Creativity Shell to provide arts instruction at Humble Elementary in Humble, 09/01/23 - 12/15/23.

Society for Indo-American Arts

Artistic fee subsidy for Riyaaz Qawwali to perform at MATCHBOX4 in Houston, 11/24/23 - 11/24/23.

NEI - National Eye Institute

ABSTRACT Saccadic suppression, the attenuation of visual perception around the time of a saccade, is likely to be mediated by mechanisms at multiple stages of the visual system. Likely contributors include ocular mechanics, retinal processing, gating at the synapse between retinal ganglion cells and neurons in the lateral geniculate nucleus (LGN), and cortical mechanisms. How much each of these mechanisms contributes is unknown and has been challenging to estimate experimentally. This is because the psychophysical phenomenon of saccadic suppression is produced by their serial concatenation, and only rarely have they been studied in the same experimental preparation. The proposed research will fill this gap in knowledge by examining ocular and thalamic contributions to saccadic suppression in individual animal subjects. A key technical advance enabling this work is the ability to simultaneously record from identified retinal ganglion cell axons and their postsynaptic targets in the LGN using high- density silicon probes. This technical advance allows us to characterize the light responses of neurons at two key stages of the visual system, as well as the transfer function that links them, in animals making saccades. A further advance is the use of state-of-the-art models of retinal processing that can be fit directly to the data. We will leverage this new platform to determine how much signal attenuation occurs in the eye and how much occurs in the LGN. The proposed experiments bring the rigor of work in ex vivo retinas to the awake behaving primate, which will extend our understanding of the principles that give rise to perception and its disorders. Such an understanding promises to provide the means to promote recovery of visual function following trauma or neurological disease.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Early initiation of antiretroviral therapy (ART) after perinatal HIV infection is critical to reduce morbidity and mortality, while also limiting seeding of the HIV reservoir. However, while infants develop broad neutralizing antibodies in the absence of ART, early initiation of ART blunts the HIV-specific humoral immune responses in children. We have found that children enrolled in the Thai HIV-NAT209 cohort had limited development of HIV- specific IgG antibodies but, intriguingly, had increasing levels of HIV-specific IgM antibodies through the first three years of suppressive ART. This cohort provides a unique opportunity to study the early HIV-specific humoral response through characterization of IgM antibodies and germline-like IgM+ non-class-switched memory B cells. Through additional analysis of samples from children who experienced a period of viremia after ART initiation and developed HIV-specific IgG responses, we can characterize the differentiation of the humoral immune response after further antigen exposure. It has been shown that adults who initiated ART during acute HIV infection and later experienced a period of viremia developed neutralizing antibodies, and we hypothesize that children will similarly develop neutralizing antibodies after viral non-suppression. Further, we hypothesize that children will have distinct HIV-specific humoral immune characteristics compared to adults who initiated ART in acute HIV infection, including higher frequencies of HIV-specific non-class-switched memory B cells, shorter heavy chain complementarity-determining region 3 (HCDR3) lengths and lower levels of somatic hypermutation in the HIV-specific B cell receptor repertoire, and neutralizing antibodies with broader epitope targeting. To address this hypothesis, we will: (1) determine the magnitude, neutralization capacity, and epitope targeting of HIV-specific IgM and IgG antibodies and (2) determine the B cell receptor repertoire and transcriptome of HIV- specific B cells in children and adults who initiated early ART and either remained suppressed or experienced a period of viremia after ART initiation. Data from these studies will provide important information about the IgM+ HIV-specific humoral responses that persist in early treated children and their development of neutralizing antibody responses after antigen re-exposure, and will help to inform the development of pediatric targeted HIV vaccines to promote development of broadly neutralizing antibodies.

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

ABSTRACT Sub-Saharan Africa's (SSA) 400 million adolescent girls and young women (AGYW, age 15-24) face disproportionate rates of HIV acquisition and suboptimal HIV care engagement. Despite the widespread availability of oral PrEP at public health facilities, uptake is impeded by low awareness, socio-cultural and access barriers, provider bias, and user dissatisfaction. Moreover, among PrEP-aware AGYW, uptake and continuation of PrEP is low due to side effects, fear of being seen with medicines, and low adherence support, undermining PrEP's preventative effects and leaving AGYW in need of critical HIV prevention. Our team and others have demonstrated that AGYW are interested in PrEP, especially newer modalities such as injectables, and that they prefer to seek HIV care at locations that foster privacy, are convenient, and are girl-friendly. Given the growing recognition that pharmacies, staffed by health workers who can be trained to provide expanded services, outnumber health facilities, can promote beneficial health behaviors, bridge gaps in health services, and mitigate health workforce shortages, we aim to expand this body of research to conduct an implementation science study on potential implementation models of pharmacy-based PrEP provision and adherence support for AGYW. In Uganda, the Community Retail Private Pharmacy Drug Distribution Point (CRPDDP) already provides pharmacy-based anti-retroviral therapy (ART) to over 48,000 clients across 160+ pharmacies (and increasing). Given the Uganda Ministry of Health's interest to expand this pharmacy-based differentiated service delivery model for increased reach and extended prevention offerings, we propose a mixed-methods study to garner foundational evidence to evaluate how this cadre of pharmacies already providing ART refills to PLHIV can include PrEP services generally and specifically tailored to AGYW. We hypothesize that these pharmacies can be well-equipped to reach AGYW with PrEP, given the critical role they already play in the community providing expanded care. As such, we propose to conduct formative research among CRPDDP pharmacies and their AGYW clients to advance implementation of pharmacy-based PrEP and adherence support. Guided by participatory processes of human-centered design, including in-depth interviews with AGYW who are potential PrEP users, pharmacists, and focus groups with pharmacy and youth advisory boards and MOH stakeholders, we will conduct formative research to understand barriers, facilitators, and desires for pharmacy-based PrEP to inform a discrete choice experiment (DCE) (Aim 1). We will then evaluate a series of implementation science outcomes—willingness, acceptability, feasibility, and readiness—among CRPDDP pharmacists (n=~160) (Aim 2), and conduct parallel DCE surveys among CRPDDP pharmacists and their AGYW clients (n=300) to evaluate preferences for pharmacy-based PrEP implementation models (Aim 3). By the end of the study, we will understand how a potentially ready platform of pharmacies can be expanded to provide PrEP care to a key population, and will have identified potential implementation gaps from user, provider, and policy perspectives .

Philadelphia Cultural Fund

The Philadelphia Cultural Fund provides general operating support to Philadelphia-based nonprofit arts and cultural organizations, with a focus on organizations that enrich the cultural life of Philadelphia's communities.

Dr. Jose Rizal Park Restoration Project

Philippines Lantern Holiday Festival will be held on Saturday, December 14, 2019 from 1:00 PM to 9:00 PM at the Dr. Jose Rizal Park, located at 1007 12th Ave S Seattle WA 98144. The event will promote and preserve the Philippine holiday tradition by showcasing and sharing traditional lanterns, treats, arts, and culture.

Friends of Phinney Ave N Street Painting

This project is to create intersection paintings and street art along our block on Phinney Ave N from 90th to 92nd street. This will provide an opportunity for the community to come together to give design input, paint, and play along the street, and increase visual appeal and interest for the many neighbors who walk along our street. We also hope this will create a safe playing environment for the children along the street and in the neighborhood by increasing neighbor and vehicle awareness through visual interest. We plan to include a mural in each intersection and a larger image mid-block, with stencils for small images that people can add to the design in their preferred locations and colors. This provides an additional opportunity for community engagement and support, allowing access to creating the art regardless of age and painting experience. A local parent and teacher will create our design, and the neighborhood will come together to prepare, paint, and enjoy the art.

NIDCR - National Institute of Dental and Craniofacial Research

PROJECT SUMMARY/ABSTRACT Temporomandibular joint (TMJ) osteoarthritis (OA) is characterized by chronic inflammation, resulting in cartilage degradation and subchondral bone erosion, leading to jaw pain and a compromised quality of life. With no effective treatment currently available, there is a pressing need for new clinical approaches to the problem. Our innovative approach, which could potentially prevent the progression of TMJ-OA to more advanced stages, has the potential to reduce the need for complex and costly surgical procedures. Photocrosslinking tissue proteins (i.e., collagen) is a straightforward and clinically advantageous procedure. It involves applying an aqueous Rose Bengal (RB) solution to the tissue and exposure to green light. Protein crosslinking has been investigated for wound closure, anastomosis, nerve repair, and enhanced wound healing in many tissues. It has also been shown to reduce inflammatory responses in treated tissues, hence the term photochemical tissue passivation (PTP). Published data from our group shows that the network formed by extracellular protein crosslinking prevents inflammatory markers from infiltrating the treatment site. We also showed in rodent knee and shoulder models of fibrosis and post-traumatic arthritis that PTP reduces inflammation in the joint capsule. PTP was initially applied in other tissues by Dr. Redmond’s group. Only after collaborations with Dr. Guastaldi the leap was made to TMJ and this proposal. Dr. Redmond is a pioneer of photocrosslinking therapeutics, and Dr. Guastaldi has extensive experience with animal models, TMJ disease, and regeneration. We believe this innovative approach is only possible due to this partnership's unique combination of expertise. In addition, utilizing state-of-the-art optical diagnostic imaging techniques via Dr. Redmond’s and Dr. Guastaldi’s collaborators at the Wellman Center for Photomedicine (MGH) is another powerful and innovative step in assessing TMJ disease progression and therapeutic efficacy. Polarization- sensitive optical coherence tomography (PS-OCT) is an optical technique that has recently demonstrated the ability to measure cartilage fiber structure and orientation. Dr. Vakoc is a leader in the field of PS-OCT, and his lab is well-equipped to conduct rapid volumetric PS-OCT imaging. We propose to apply to the TMJ for the first time. The overall goal is to explore the potential of PTP to reduce inflammation and prevent the progression of TMJ-OA. A well-established rat model of TMJ-OA will be used to achieve this goal. We hypothesize that PTP of the TMJ capsule offers a promising, minimally invasive approach to halting TMJ-OA progression by reducing inflammation within the TMJ. The following specific aims will address the hypothesis: SA1) To assess the effect of PTP on the whole TMJ structure. PS-OCT imaging, micro-CT, histology, and pain assessment will assess the impact of PTP on the whole TMJ structure. SA2) To assess the efficacy of PTP to reduce TMJ-OA-related inflammation. Whole TMJ specimens tissues will undergo quantitative (Q-PCR) and qualitative (IHC staining) assessment for the presence of inflammatory markers.

Pillars Fund

Invests in Muslim Americans leading social change. Funds arts, media, policy, civic engagement, and narrative change programs.

Pittsburgh Foundation

The Pittsburgh Foundation provides community grants to nonprofits in Allegheny County working in areas including human services, education, arts and culture, environment, and economic development.

Belltown United

Belltown United will bring people together in a community-driven creative placemaking experience that will result in a collection of public street, traffic box, and sidewalk installations of relevant and engaging imagery and prose, with online (web-based) support to be sure it remains available to the community. The installation will contain visual art that identifies the distinct character of the Belltown neighborhood, from a collective understanding of the community's experiences and Belltown's history and cultural significance. The digital component will be integrated with the art to provides a storytelling experience for the pedestrian, linking them to the past, present, and future of Belltown. This project will be completed by August 31, 2023.

NIMH - National Institute of Mental Health

The Contractor, Guild Associates, Inc., aims to develop an electrochemical aptamer-based sensor device for simple, rapid, and low-cost detection and quantification of antiretroviral therapy (ART) drugs in urine and blood samples at the point-of-care (POC).

NHLBI - National Heart Lung and Blood Institute

Abstract In Tanzania, over 1.5 million people are living with HIV (PLH). With improvements in access to effective ART, the number of PLH surviving into older age has increased substantially. Currently, 30% of PLH in Tanzania are aged 50 years and older, with this population expected to increase by 25% by 2040. Ageing PLH face a significant burden of cardiovascular disease (CVD) due to a combination of traditional risk factors, HIV associated inflammation, and immune dysfunction. Heart failure is one of the leading causes of cardiac disease in adults in Tanzania, with hypertension accounting for about half of all cases. Cardiac echocardiography is a valuable, non-invasive tool for detecting structural and functional abnormalities associated with heart failure, including left ventricular dysfunction, valvular disease, and diastolic impairment. However, access is limited in resource constrained settings like Tanzania and as a result diagnoses are often made very late. Point-of-care cardiac ultrasound (POCUS) offers a potentially scalable solution for cardiovascular screening in ageing PLH in HIV clinics and early detection of cardiac abnormalities that could lead to heart failure. This R21 exploratory/developmental grant proposes to assess the clinical utility, feasibility and impact of implementing AI-POCUS for early detection of cardiac dysfunction in aging PLH in Tanzania. 400 PLH equal to or greater than 50 years enrolled in the Tanzania HIV ageing longitudinal cohort study (THALCS), a multisite observational cohort study of ageing outcomes and quality of life, will undergo a focused AI-POCUS assessment using the Butterfly iQ3™ portable AI-driven ultrasound system, performed by trained non-specialist providers (HCP) at THALCS study sites. Specifically, we will (1) evaluate the utility of POCUS for identifying key markers of cardiac dysfunction (e.g., left ventricular hypertrophy, systolic/diastolic dysfunction, pericardial effusion) and need for cardiology referral; and (2) assess the feasibility and acceptability of AI-POCUS among healthcare providers and participants and the clinical impact of AI-POCUS on short term (12 month) participant outcomes. The proposed work also has direct relevance to the United States, where more than half of PLH in care are now aged 50 years and older and experience disproportionately high rates of hypertension, heart failure, and other cardiovascular complications. Findings from this study may inform scalable, task-shifted approaches for integrating AI-assisted cardiac screening into HIV primary care settings in the US, including federally qualified health centers and rural clinics with limited access to cardiology and echocardiography services. This project will generate critical pilot data to inform scalable strategies for CVD screening in aging PLWH and lay the groundwork for future trials of POCUS-guided interventions. Ultimately, it seeks to reduce cardiovascular morbidity and improve quality of life in a vulnerable and growing population.

NHLBI - National Heart Lung and Blood Institute

Abstract In Tanzania, over 1.5 million people are living with HIV (PLH). With improvements in access to effective ART, the number of PLH surviving into older age has increased substantially. Currently, 30% of PLH in Tanzania are aged 50 years and older, with this population expected to increase by 25% by 2040. Ageing PLH face a significant burden of cardiovascular disease (CVD) due to a combination of traditional risk factors, HIV associated inflammation, and immune dysfunction. Heart failure is one of the leading causes of cardiac disease in adults in Tanzania, with hypertension accounting for about half of all cases. Cardiac echocardiography is a valuable, non-invasive tool for detecting structural and functional abnormalities associated with heart failure, including left ventricular dysfunction, valvular disease, and diastolic impairment. However, access is limited in resource constrained settings like Tanzania and as a result diagnoses are often made very late. Point-of-care cardiac ultrasound (POCUS) offers a potentially scalable solution for cardiovascular screening in ageing PLH in HIV clinics and early detection of cardiac abnormalities that could lead to heart failure. This R21 exploratory/developmental grant proposes to assess the clinical utility, feasibility and impact of implementing AI-POCUS for early detection of cardiac dysfunction in aging PLH in Tanzania. 400 PLH equal to or greater than 50 years enrolled in the Tanzania HIV ageing longitudinal cohort study (THALCS), a multisite observational cohort study of ageing outcomes and quality of life, will undergo a focused AI-POCUS assessment using the Butterfly iQ3™ portable AI-driven ultrasound system, performed by trained non-specialist providers (HCP) at THALCS study sites. Specifically, we will (1) evaluate the utility of POCUS for identifying key markers of cardiac dysfunction (e.g., left ventricular hypertrophy, systolic/diastolic dysfunction, pericardial effusion) and need for cardiology referral; and (2) assess the feasibility and acceptability of AI-POCUS among healthcare providers and participants and the clinical impact of AI-POCUS on short term (12 month) participant outcomes. The proposed work also has direct relevance to the United States, where more than half of PLH in care are now aged 50 years and older and experience disproportionately high rates of hypertension, heart failure, and other cardiovascular complications. Findings from this study may inform scalable, task-shifted approaches for integrating AI-assisted cardiac screening into HIV primary care settings in the US, including federally qualified health centers and rural clinics with limited access to cardiology and echocardiography services. This project will generate critical pilot data to inform scalable strategies for CVD screening in aging PLWH and lay the groundwork for future trials of POCUS-guided interventions. Ultimately, it seeks to reduce cardiovascular morbidity and improve quality of life in a vulnerable and growing population.

Belltown United

Belltown United, an all-volunteer community non-profit, passionately advocates for improvements in Belltown. Our sustained efforts at the Portal Park site have gained momentum bringing public art, outdoor programs, and public interest to the space. This momentum has rallied increasing support for transforming Portal Park into a vibrant community open/green space. Now at a critical juncture, Belltown United must balance patience with proactive engagement. The optimal solution, both for the community and from a political standpoint, is to keep activating Portal Park and involving our community in all aspects of advocacy, activation, and design. These efforts ensure our collective vision for a future park will become an admired feature of Belltown's landscape and community well-being. This year we propose two initiatives that build on our success from last year: a community engagement and public access initiative and a series of onsite public art activation(s).

NIDCR - National Institute of Dental and Craniofacial Research

PROJECT SUMMARY The Portland Oral Health Research Training (PORT) Program at the Oregon Health & Science University (OHSU) School of Dentistry develops the next generation of oral health researchers. PORT leverages OHSU’s strong record of mentoring and training, rigorous scientific research, and newly renovated state-of-the-art laboratory and education facilities. The program builds on the School’s strengths in microbial sciences, biomaterials/tissue engineering, regenerative medicine, and clinical and translational research, supported by major NIH funding, including two R35 awards to mid-career faculty. PORT is closely integrated with OHSU’s campus-wide research ecosystem, which includes multiple NIH training programs and partnerships with Portland State University and Oregon State University, providing access to a robust pool of research-experienced students. PORT is facilitated by an institutionally supported prematriculation summer research program for incoming D.M.D. students that creates an early research exposure and provides continuity into advanced predoctoral and postdoctoral T32 training after matriculation/eligibility. The program’s four complementary tracks include: (I) D.M.D. summer research with post-matriculation continuation; (II) D.M.D./Ph.D.; (III) Ph.D. predoctoral training; and (IV) postdoctoral training, including a sub-track with a Master of Science in Clinical & Translational Research. We are requesting five (5) slots for Track I each summer; one (1) slot in Year 1 and two (2) slots in Years 2-5 for the Track II DMD/PhD training program; three (3) slots for the Track III predoctoral training, and four (4) slots for Track IV postdoctoral training. We anticipate that trainees will participate in Track I for eight (8) weeks, Track II for up to five (5) years, or Tracks III or IV for approximately 2-3 years. The goal is that each trainee in Tracks II-IV will apply for and receive individual funding toward the end of their tenure. Training experience emphasizes rigorous scientific reasoning and reproducibility, Responsible Conduct of Research, quantitative and computational methods, and effective scientific communication. Structured activities include seminars, workshops in grant writing, leadership, team science, and presentation skills, and formal mentor training for faculty. Trainees engage in institutional scholarly events such as the Dean’s Seminar Series and OHSU Research Week, develop Individual Development Plans with near-peer and alumni mentoring, and may pursue short, mentored externships to explore research careers across academia, industry, and government/regulatory enterprise. Program evaluation tracks skills acquisition, research outputs, time to degree or next stage, and career destinations, with aggregate training and career outcomes publicly posted on an OHSU webpage. By providing a rigorous, interdisciplinary, and professionally structured training environment, PORT will accelerate the transition of motivated dental, dual-degree, predoctoral, and postdoctoral trainees into productive research and related careers and advance the NIH mission to improve health through discovery.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY/ABSTRACT Chronic obstructive pulmonary disease (COPD) accounts for 6% of all deaths worldwide and is potentially preventable, with well-described but poorly elucidated childhood origins. Improved understanding of early life origins of COPD could lead to interventions to substantially reduce morbidity and mortality from COPD, particularly in high-risk populations. Dysanapsis refers to a mismatch between airway tree caliber and lung volume that arises early in life. Our research team recently identified that dysanapsis is: 1) prevalent among older adults, 2) is a major predictor of COPD risk – exceeding tobacco smoke and other established risk factors, and 3) is not fully explained by genetics. We also know that there are heterogenous structural presentations of dysanapsis. However, the early life origins of dysanapsis are poorly understood. This R01 study will leverage 8 longitudinal birth cohorts of children to examine the relationship between early- life exposures and events and both structural (imaging-confirmed) and functional (spirometry-assessed) dysanapsis throughout childhood and adolescence to identify modifiable risk factors and help reduce risk of COPD in future generations at risk. Building on our preliminary data showing that magnetic resonance imaging (MRI) is as accurate as computed tomography (CT) at identifying dysanapsis, we will integrate state-of-the-art lung MRI data with extensive early-life exposure and lung function data. Aim 1 will establish relationships between early life dysanapsis and childhood lung function trajectories, and their relationship to structural dysanapsis at late adolescence. Aim 2 will determine if individual-level factors, specifically obesity and viral infections, contribute to functional dysanapsis (spirometry-assessed) and distinct structural subtypes of dysanapsis (imaging-confirmed). Aim 3 will examine community-level factors and associations with functional dysanapsis (spirometry-assessed). This study aligns with NHLBI’s strategic objective to investigate factors accounting for health differences among populations. We will establish the early-life risk factors that contribute to airway-to-lung phenotypes and enhance our understanding of the utility of both imaging- and spirometry-based measures of dysanapsis. Moreover, our findings will inform targeted interventions in high-risk groups of children to reduce their subsequent risk of COPD.

NIEHS - National Institute of Environmental Health Sciences

Project Summary/Abstract: Autism spectrum disorder (ASD) is a growing public health concern, with rising prevalence and substantial economic and societal costs. Epidemiologic evidence links abnormal maternal thyroid function during pregnancy to increased risk of child ASD and other neurodevelopmental disorders. Lithium, widely used as a psychiatric medication for bipolar disorder and depression due to its mood-stabilizing effects, also presents concerns as an environmental exposure during pregnancy. Lithium inhibits thyroidal iodine uptake, is concentrated in the thyroid, and has known neurotoxic effects. Additionally, more than 56% of U.S. groundwater samples exceed the EPA’s health advisory level for lithium, and conventional water treatment processes do not remove it. Findings from prior case-control studies on the relationship between prenatal lithium exposure and ASD risk are limited by retrospective exposure assessment, emphasizing the need for direct measures of lithium exposure during pregnancy. Our central hypothesis is that higher prenatal lithium exposure increases the risk of maternal thyroid dysfunction, which in turn elevates the risk of child ASD. To our knowledge, no prior study has explored a pathway linking prenatal lithium exposure to ASD through thyroid dysfunction as a potential mechanism. To test our hypothesis, we plan to take advantage of two established ASD studies: (1) MARBLES (Markers of Autism Risk in Babies – Learning Early Signs), a prospective cohort of over 550 pregnant women who have a child with ASD and CHARGE (CHildhood Autism Risk from Genetics and Environment), a population-based, case-control study with over 2000 children and families enrolled. In this project, after selecting MARBLES pregnant women who provided urine samples during pregnancy and subsequently delivered a child with a final diagnosis, we will analyze their urine samples for lithium. Then, we will examine whether prenatal exposure to lithium is associated with child ASD. We will also examine the impact of prenatal lithium exposure on thyroid dysfunction. For CHARGE, we will reconstruct prenatal residential lithium exposure for 500 cases and 500 controls by integrating lithium levels of national databases with geocoded residential histories and drinking water source data, applying the same hypothesis tests as MARBLES. To explore the broader impact of exposure mixtures, we will apply state-of-the-art modeling strategies, and mediation analyses will be conducted to evaluate thyroid dysfunction as a potential mediator in the pathway from lithium exposure to ASD. This study is expected to (1) provide robust evidence of a causal pathway linking prenatal lithium exposure, thyroid dysfunction, and ASD etiology; (2) identify critical windows of exposure to lithium that contribute to thyroid dysfunction and/or ASD; and (3) elucidate the impact of exposure mixtures on thyroid dysfunction and ASD risk. By focusing on modifiable environmental factors, this research will inform intervention and prevention strategies to reduce lithium exposure and mitigate ASD risk, offering actionable insights for public health.

OD - NIH Office of the Director

ABSTRACT Protein aggregation is a shared pathology of Alzheimer’s disease and related dementias known as tauopathies. Because each disorder develops a unique combination of protein aggregate polymorphisms that may influence the course and severity of disease, elucidating the relationship between tau aggregate structure and biological activity has become a high priority in the field. Advances to date have been limited, however, by the lack of rigorously standardized aggregate preparations from tissues and cells which is the focus of many researchers at our university and beyond. Acquiring the proposed state-of-the-art high-performance liquid chromatography (HPLC) system is key component of our efforts to provide high quality protein aggregates associated with Alzheimer's Disease (AD) and Alzheimer's Disease Related Dementias (ADRD e.g. Tau to researchers at Mitchell Center for Neurodegenerative Diseases (MCND), the University of Texas and nationwide. These protein preparations will support research into the molecular basis of disease pathogenesis and catalyze efforts toward creating novel diagnostic and therapeutic strategies specifically tailored against protein aggregate polymorphs.

National Park Service

A. Project Goals 1. To advance and promote to use of research, science, and technology for conserving our nation s cultural heritage. B. Project Objectives 1. Create two videos for art conservators to expose the public to art conservation methods for recovering collections after a disaster. 2. Disseminate preservation technology information.

NIMH - National Institute of Mental Health

Project Summary The majority of Americans will experience a traumatic event during their lifetimes, but only a subset experience chronic negative psychiatric outcomes such as post-traumatic stress disorder (PTSD) and depression. Several cohort studies over the past 10 years have identified brain-based risk mechanisms early after trauma, which predict risk for chronic symptoms such as hyper-arousal, intrusive memories of the trauma, and negative affect. One of the most widely-replicated and theoretically-grounded such mechanisms involves early high amygdala responses to threat cues. Given the strength of current evidence, we propose that this is an actionable target for intervention early post-trauma, to prevent chronic impairing and distressing symptoms. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that can induce functional brain changes as potential intervention for neuropsychiatric disorders. Emerging findings along with our preliminary data suggest that the amygdala can be reached and dampened via stimulation of a functionally connected cortical prefrontal area. Here we propose that using TMS to dampen amygdala hyperreactivity will prevent a cascade of symptoms that could develop following trauma exposure. We propose to identify Emergency Department patients who have experienced a recent traumatic event (meets DSM-5 Criterion A), and who have high initial PTSD symptoms at 1 week post-trauma. In the R61 phase we will deliver a staged single-blind TMS intervention with a lead-in sham, followed by active treatments with increasing doses, measuring amygdala reactivity at each phase. R61 milestones involve: 1: Target engagement: Determination that active TMS versus sham decreases within-subject amygdala threat reactivity (decrease in reactivity to fearful faces). 2: Dose response: Determination that 4 vs 1 session of TMS decreases these same targets. 3: Safety and feasibility: Demonstrating feasibility of recruitment and retention (75% of participants are able to complete 75% of sessions), and no Serious Adverse Events (SAE) deemed related to the TMS intervention. If these are met, the R33 phase will involve a randomized double-blind sham-controlled trial, providing a double- blind replication of the immediate effects on the amygdala target and 1-month later, as well as longitudinal assessments of TMS effects on both PTSD and depression symptoms over 3 months post-trauma. The research environment at Emory University School of Medicine will provide excellent support for the successful completion of the proposed research, particularly with state-of-the-art neuroimaging facilities, a well-developed infrastructure for identifying participants at risk for chronic trauma-related symptoms through the Grady Trauma Project and Grady Healthcare System, and a strong community of experts in trauma and neuromodulation. If the hypotheses are confirmed, this study will lay the groundwork for future early intervention trials using non- invasive dampening of amygdala reactivity to prevent chronic trauma-related symptoms.

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

Project Summary While antiretroviral therapy (ART) has drastically reduced mother-to-child HIV transmission, increasing evidence suggests that in utero ART exposure can disrupt fetal immune development and placental function—even in the absence of vertical infection. HIV-exposed uninfected (HEU) infants experience higher rates of preterm birth, growth restriction, and immune dysregulation, yet the mechanisms remain poorly understood. Addressing these gaps is critical for reducing long-term immune-mediated morbidity in this growing population. Our central hypothesis is that ART exposure reprograms immune signaling at the maternal-fetal interface (MFI), creating a pro-inflammatory environment that impairs immune tolerance and fetal immune maturation. In response to PAR- 25-362, we propose a multi-pronged investigation into how ART influences immune cell development, antigen presentation, and extracellular vesicle (EV)-mediated communication at the MFI. Our study will use cutting-edge immunopeptidomics, transcriptomics, and functional co-culture assays to define how ART disrupts key regulatory mechanisms at the placenta. This work will generate mechanistic insights into immune dysregulation in HEU infants and inform safer therapeutic strategies during pregnancy.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY Acute ischemic stroke (AIS) resulting from large vessel occlusion (LVO) is a primary cause of global morbidity and mortality. Mechanical thrombectomy (MT) is the current standard of care for LVO, and it is one of the most effective interventions in modern day medicine. This procedure involves catheter-based endovascular access to the intracranial vasculature for clot retrieval. The number of retrieval attempts required for successful recanalization is variable, influenced by clot characteristics, patient anatomy, and procedural technique. Clinical trials have established the efficacy of MT in AIS, with recent studies demonstrating a strong correlation between successful first-pass recanalization and favorable clinical outcomes. Despite the established population-level efficacy of mechanical thrombectomy (MT) in acute ischemic stroke (AIS), individual patient outcomes exhibit significant variability and prognostic uncertainty. The ability to more accurately predict MT outcomes for individual patients from clinical data would offer highly valuable guidance for clinical decision-making. Prior published works have utilized classic deterministic machine learning methods to generate singular expected outcome estimates, which do not adequately describe the broad distribution of potential outcomes. In this work, we propose to develop new probabilistic machine learning models, which directly infer outcome distributions, providing a more informative assessment of the anticipated prognosis in the setting of real-world clinical uncertainty. For this purpose, we leverage the NeuroVascular Quality Initiative – Quality Outcomes Database, which contains highly granular clinical, procedural, and outcomes data for over 10,000 MT procedures. In our first aim, we will develop multiple state-of-the-art probabilistic models to predict MT procedural success, MT first-pass success, and functional and neurological outcomes from the clinical data available in the NVQI-QOD. As part of this first aim, we will evaluate a new and extremely powerful probabilistic foundational model for Bayesian inference, and compare it to state-of-the-art tree-based probabilistic methods. In our second aim, we will utilize methods from Explainable AI (XAI) to identify the most important predictors of procedural success and clinical outcomes and then to also characterize their interactions. We anticipate that this work will provide valuable insight into the complex determinants of large vessel stroke outcomes and identify high-priority targets for future research.