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Groton

Community Center Athletic Field Irrigation System and Field Reconstruction

Treasury Department

The U.S. Department of the Treasury, as part of a continuing effort to reduce paperwork and respondent burden, invites the general public and Federal and State agencies to take this opportunity to comment on proposed and/or continuing information collections, as required by the Paperwork Reduction Act (PRA) of 1995, 44 U.S.C. 3506(c)(2)(A). Currently, the Community Development Financial Institutions (CDFI) Fund, Department of the Treasury, is soliciting comments concerning the Opportunity Zone (OZ) Nomination Tool. The OZ Nomination Tool contains online forms submitted through the CDFI Fund's Awards Management Information System (AMIS).

Waldport Public Library

We expect the benefits of the grant project's additions to our STEM programs and services to bring up mathematical proficiency scores of current and future south Lincoln County youth, and foster a community of math-mindedness, making success in STEM programs and work attainable through confident skills. Augmenting the current programs in place at the local schools will lead to more time available for math for more students in all walks of life, particularly those who are underserved or homeless in south Lincoln County and need a safe place to be after normal school hours.

Arboretum Foundation

The Arboretum Foundation will install an environmentally-friendly composting toilet system in the area adjacent to the Pacific Connections Gardens in the Washington Park Arboretum located at 2300 Arboretum Drive East. A prefabricated, composting toilet system will alleviate the lack of facilities, reduce water waste, and promote sustainable practices in outdoor recreation and education. The composting toilet is a low-impact, environmentally responsible solution which also provides a gender neutral option for the park. This project will be completed by March 31, 2020.

NIAID - National Institute of Allergy and Infectious Diseases

Summary. The prevalence of antibiotic resistant (AR) bacterial infections continues to grow. Although the development of novel antimicrobial compounds is one approach to combat AR infections, phage therapy or using lytic phage to treat bacterial infections, offers another solution that has many attractive benefits, including the specificity of infection, leaving the healthy microbiome intact, low toxicity, and the diversity of phages available. However, before phage therapy can be widely used in the clinic, one of the significant challenges that must be addressed is the selection of which phage to use for a given bacterial pathogen. Phage infection specificity is complicated by the fact that bacteria encode a diverse array of phage defense systems that block phage infection, typically expressed by horizontally transferrable DNA elements. The bacterial pathogen must also encode and express the phage receptor and any bacterial host factors that the phage requires for successful replication and phage production. Currently, bacterial pathogens are manually screened against large phage biobanks to select phage cocktails that can provide effective in vivo killing. Although this has been effective, such an approach is costly and, more importantly, time-intensive, and it will be challenging to scale up as phage therapy becomes more widely used. The field, therefore, needs rapid and cost-effective approaches to identify effective phages for any bacterial pathogen, given the genome sequence of the bacteria and phages. The MPIs of this proposal, Ravi and Waters, will use their diverse expertise in bacterial pathogenesis, phage biology and defense, AR, microbial genomics, and computational biology, to develop an ML-based prediction model that can identify effective phage and phage resistance-associated molecular features for any given E. coli strain. Another critical outcome of this work will be the gold-standard data set generated in Aim 1 that will define the successful infection of 69 dsDNA E. coli phage in the well-characterized BASEL phage collection with ~600 sequenced pathogenic and non-pathogen E. coli strains generating ~42,000 unique data points. Aim 2 will first define all known phage defense, AR, and virulence elements in this collection of E. coli and merge these annotated features with the phage host infection phenotypes generated in Aim 1 using (un)supervised ML-based approaches (e.g., logistic regression, random forest) to generate models that can predict effective phage infections of any given E. coli host, along with the underlying molecular features (genes, proteins, domains) culminating in resistance/susceptibility. This model will be validated with 50 new E. coli strains. Successful completion of this proposal will generate a clinically useful predictive model for E. coli and lay the framework for generating such predictive models for phage therapies against other bacterial pathogens. Moreover, the model will lead to the discovery of novel phage defense elements and bacterial factors that impact phage infection, and a deeper understanding of how bacterial pathogens evolve resistance to phage infection, knowledge, which can be used to effectively tailor phage therapy to prevent widespread emergence of resistance.

iTouch Biometrics LLC

Information Technology Broadcasting and Telecommunications

Sound Child Care Solutions

Set up a mobile computer lab equipped with Internet access to increase tech literacy for low-income child care providers so they can register and participate in Early Achievers, the Quality Rating Improvement System.

Intergenerational Innovations

Improve access to basic technology skills for seniors via middle and high school student teachers

NIA - National Institute on Aging

PROJECT SUMMARY There are now anti-amyloid therapies available to slow the clinical progression of Alzheimer’s disease (AD). These therapies come with the risk of negative side-effects including amyloid related imaging abnormalities (ARIA). Little is known about acute and long-term cognitive consequences of ARIA events given the expense and staff / patient burden associated with the imaging scans that are currently used to detect ARIA. Neuropsychological tests are frequently leveraged to provide an assessment of neurological integrity at very low cost. Nevertheless, because it is unknown precisely when an ARIA event may occur, cognitive testing would need to be relatively frequent, producing substantial burden on patients and clinical staff. The Cognitive Monitoring during Treatment for Alzheimer disease (CoMTAD) study aims to address these difficulties by developing and validating a cognitive safety monitoring system to detect adverse side effects of anti-amyloid therapy. We will administer an extremely brief, but well-validated, digital cognitive assessment using the Ambulatory Research in Cognition (ARC) smartphone platform, up to three times per week for approximately thirty weeks. Patients will be classified as having ARIA or not based on imaging findings. We will utilize changepoint models to evaluate if there are acute or long-term changes in cognition associated with incidence of ARIA. Cognitive consequences of ARIA may not manifest as a sudden drop in performance but rather a more subtle change in variability in cognitive scores across days. The high-frequency (3 times per week) assessment strategy of CoMTAD will afford the ability to examine these additional metrics. The ARC platform is uniquely suited for this purpose as it has already been extensively validated in a healthy older adult and symptomatic AD population. The ARC tasks have been specifically designed to be sensitive to cognitive change in this population and are well-tolerated by the majority of participants. Moreover, because ARC is administered remotely, it can be deployed at scale to patients regardless of their proximity to a major medical center. The ultimate goal of the study will be to provide easy to obtain, cost effective, cognitive safety monitoring information to medical providers so they can determine if a patient is experiencing an adverse neurological episode prior to an expensive and relatively burdensome MRI scan. Given the lack of cerebrospinal fluid or blood-based biomarkers of ARIA, we consider the CoMTAD study to provide an essential tool for physicians to track cognitive health of patients undergoing these novel therapies. This goal will be furthered by our secondary in-lab sleep restriction study. A group of volunteers will undergo 24-hours of sleep restriction to track how performance on ARC declines with increasing sleep deprivation. This will provide benchmarks for physicians to determine if declines in performance are clinically important.

Youth Ministries for Peace and Justice, Inc. (YMPJ)

Development of education , recreation and community outreach programs to promote use of the new Concrete Plant Park on the Bronx River, along with installation of water contamination warning systems.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT ABSTRACT Extreme heat exposure in the US caused over 120,000 heat-related emergency room visits in 2024; heat stroke leads to organ damage, including acute kidney injury, and even death. The health effects of recurrent, asymptomatic hyperthermia, however, remain unknown. Kidney disease disproportionately affects working-age persons living in hot regions of the world, including California’s Central Valley and Texas’ Rio Grande Valley and repetitive heat stress is posited to be the cause. If heat exposure is linked to kidney injury, a broad swath of heat-exposed workers—outdoor workers (farm workers, construction workers, and firefighters) and indoor industrial workers (warehouse workers, shipyard welders, and food truck operators)—are at risk. Since several individual-level factors contribute to heat stress—e.g., age, comorbidities, physical fitness, and acclimatization, heat stress itself can be challenging to quantify, particularly in large population studies. Consequently, systematic investigations on the causal effects of heat stress, and of mitigation strategies have also lagged. In this study, we propose two aims. In aim one, we will develop measures of heat stress using non-invasive proxies. In controlled climactic chambers experiments, we will conduct high frequency physiologic monitoring and biosampling during exercise in persons of working age (30-50 years) with varied temperature conditions. We plan to agnostically identify markers that correlate with changes in core temperature and kidney injury. In aim two, using a case-cross over randomized control trial design at the work site, we will implement and assess two active cooling interventions in 72 workers, accounting for individual response to heat and underlying comorbidities. Over sequential weeks, we will measure rate of core temperature change (primary outcome) and changes in kidney injury markers and worker acceptability (secondary outcomes). Testing and quantifying the effects of active cooling interventions on kidney injury markers not only helps to build the case for investment in a specific cooling technology, it will also provide supporting or refuting causal evidence for the link between heat stress and kidney injury. In future work, we can 1) apply a non-invasive heat stress marker in broader population-based studies on the health effects of heat, and 2) assess the cost-effectiveness of heat mitigation strategies and specifically their impact on worker productivity and satisfaction.

Aeon Nexus Corporation

Engineering and Research and Technology Based Services

TRANSYSTEMS CORPORATION

Engineering and Research and Technology Based Services

Port of Tillamook Bay

Construction of improvements and purchase/installation of equipment required to establish the FAA-approved test range for unmanned aerial systems.

Confederated Tribes of the Warm Springs Reservation

Construction of improvements required to establish the FAA-approved test range for unmanned aerial systems.

CLARITY PARTNERS LLC

Management and Business Professionals and Administrative Services-Management advisory services-Business and corporate management consultation services-Business intelligence consulting services

RaySecur, Inc

Defense and Law Enforcement and Security and Safety Equipment and Supplies

NIAID - National Institute of Allergy and Infectious Diseases

SUMMARY Staphylococcus aureus is a major human pathogen that is a common cause of hospital and community acquired pneumonia, both of which lead to significant morbidity and mortality. Increasing antibiotic resistance and prevalence of methicillin resistant strains is of critical concern. The long-term goal of our research is to better understand the host-pathogen interaction between S. aureus and the host innate immune system. It is hoped that an improved understanding of this interaction could lead to novel therapies targeting the bacterium or modulating the host to thwart this multidrug resistant pathogen. The objective of this proposal is to understand how type III IFN contributes to the pathogenesis of S. aureus infection. The rationale for this approach is that new targets are needed to either develop antibiotics/inhibitors or vaccines against S. aureus. Studies investigating type III IFN to-date are largely focused on viral infections where activation of signaling is important to control the infection. We have shown that type III IFN signaling contributes to the pathogenesis of acute S. aureus pneumonia. We have demonstrated alterations to the alveolar macrophage population can improve bacterial clearance by manipulating the pathways identified from our RNA-seq analysis. Investigation of both differential transcripts and proteins indicates changes to the epithelial barrier occur when type III IFN signaling is present. We also have data that shows that S. aureus strains can activate type I and III IFN signaling with variable intensity and independent of each pathway. Precise mechanisms for this involvement of type III IFN signaling are still lacking. This contribution is significant as it will provide a deeper understanding on how the type III IFN pathway influences the clearance of S. aureus from the airway. Completion of our objectives will be accomplished by pursuing two specific aims: 1) Determining the role of type III IFN in pathogenesis through studies on MID1 in alveolar macrophages, the role of IL-1β in immunopathology its effect in the airway barrier and 2) defining how S. aureus activates type III IFN, its comparison to type I IFN signaling and the utility in targeting this pathway. The innovation of this research is both conceptual and technical. The concept that the pathway is inhibitory to bacterial clearance through the epithelial response to type III IFN signaling is unique. We will examine both direct effects on airway epithelial cells as well as the effects IFN signaling has on professional phagocytes. It is also thought activation of type I&III IFN is linked, and we provide evidence this is not entirely the case. We will utilize techniques across multiple fields, microbiology, immunology, cell and molecular biology, utilizing a well-tested animal model of pneumonia, in vitro functional and primary cell culture assays and global approaches to understand the host response such as RNA-seq. At the conclusion of these studies, we will have expanded our knowledge on how an innate signaling pathway can impact negatively on acute bacterial infection in the airway, how this pathway can be activated and how it can coordinate multiple cells in response to its activation.

NIA - National Institute on Aging

ABSTRACT: The accumulation of waste and neurotoxic proteins, such as amyloid-β and tau, is a hallmark of aging and neurodegenerative disorders like Alzheimer’s disease. The glymphatic system plays a critical role in brain-waste clearance. It facilitates the perfusion of cerebrospinal fluid (CSF) into the brain, which interchanges with interstitial fluid to flush out harmful waste, nanoplastics, and neurotoxic proteins. Our recent findings indicate that conditions impeding CSF flow dynamics—such as craniosynostosis and normal aging—disrupt this clearance system, exacerbating amyloid plaque buildup. Importantly, we have also shown that pharmacological activation of Piezo1, a mechanosensitive ion channel, using Yoda1 agonist enhances CSF-mediated waste clearance in both craniosynostosis and aged wild-type mice. However, a major gap remains in our understanding of how waste clearance is regulated at the cellular level. This obscures the cellular mechanism(s) by which Piezo1 acts to control brain waste clearance. Key preliminary data suggest that mechanical forces exerted by CSF flow may activate Piezo1 in brain border macrophages (BBMs). These cells are essential for brain waste clearance as they degrade extracellular matrix (ECM) proteins along arterial basement membranes, enabling proper arterial motion to drive CSF flow. This proposal aims to determine whether Piezo1 functions in BBMs to control brain-waste clearance, leveraging our team’s expertise in mouse genetics, high-resolution multi-photon imaging, and computational modeling. Aim 1 uses a pharmacological approach to investigate whether Yoda1 enhances brain-CSF perfusion by acting on BBMs to help regulate ECM remodeling. Aim 2 uses genetic approaches to directly test whether Piezo1 is required in BBMs to maintain CSF hydrodynamics and waste clearance by facilitating ECM degradation and arterial motion. Aim 3 examines the impact of Piezo1 manipulation in BBMs on amyloid pathology in mouse models of Alzheimer’s disease, including assessing whether stimulating Piezo1 activation can enhance amyloid clearance. By defining the role of Piezo1 in CSF- driven waste clearance, this work will establish a mechanistic framework for preserving glymphatic function across the lifespan. Targeting Piezo1 in BBMs may represent a novel therapeutic strategy to counteract age- related and disease-associated declines in brain-waste clearance, addressing a critical unmet need in Alzheimer’s disease and related dementias. As such, we expect our findings will lay the groundwork for translational efforts to develop new therapies aimed at sustaining cognitive health in aging populations. Our approaches may also be leveraged in the future to investigate how environmental pollutants (e.g., nanoplastic accumulation) may affect waste clearance and BBM functions, leading to cognitive impairment.

FEEST

COO: Systems & Policy Change

Not This Time!

COO: Systems & Policy Change

Got Green

COO: Systems & Policy Change

ForFortyTwo

COO: Systems & Policy Change

Casa Latina

COO: Systems & Policy Change