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Town of Delmar

Sewer System Study

City of Toledo

SF Mainline Replacement & Collection System Improv

Groton

Shennecossett Golf Course HVAC System Upgrade

Shield Crest Water Company

Shield Crest WaterCo WaterSystem Feasibility Study

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary/Abstract Proteoforms are molecular forms of proteins in cells and tissues containing site-specific sequence variations and post-translational modifications. Proteoforms effectively describe cell phenotypes and provide important implications in disease mechanisms. Recent studies in immunobiology and disease pathology have emphasized intact proteoform characterization without enzymatic digestion in bottom-up approaches. Current mass-spectrometry-based top-down proteomics technologies fall short in capturing the complex proteome in small biological samples such as single cells. This proposal generates a suite of novel technologies for high-throughput omics- scale single cell proteoform profiling using innovative instrumentation, bioinformatics and high- throughput strategies. I will use human kidney cells as a model biological system in this proposal, and the approaches are generalizable to different cell types. I have recently developed a technology employing localized proteoform sampling coupled to single-molecule mass spectrometry to directly image and identify intact proteoforms in tissue sections (Su et al., 2022, Sci. Adv.). In Aim 1, I will expand the proteome detection and identification capabilities in this technology using innovative instrumentation, sampling and data acquisition algorithms. Together these will curate a knowledgebase serving as a proteoform library for kidney single cell proteoform profiling. In Aim 2, I will develop a novel platform leveraged for profiling of single cells dissociated from human kidney biopsies. I will develop a single cell preparation protocol for maximizing proteoform detection in kidney parenchymal and immune cells. I will also develop a bioinformatics approach tailored for proteoform identification in single cell datatype and discover proteoform signatures that differentiate cell types. In Aim 3, I will address the limitation in rare cell profiling by developing a series of high-throughput strategies including high-speed sampling and microarray cell patterning. These new technologies will unravel proteoform landscapes and signatures in rare kidney-resident innate immune cells (e.g., macrophages and dendritic cells) for the discovery of new cell populations that can be used as therapeutic targets and diagnostic tools for inflammatory diseases. My mentoring team consists of Dr. Neil Kelleher (mentor), a world-renowned protein biochemist, and Dr. Satish Nadig (co-mentor), a leading expert in kidney immunobiology. The proposed research is a substantial technological advancement in single-cell proteomics and sets a solid foundation for the pursuit of my independent career. The proposed research also well aligns with my long term research interest in developing enabling analytical technologies for biomedical science community with a special interest in the human innate immune system.

NIDA - National Institute on Drug Abuse

Neurogenomic studies by the SCORCH (Single Cell Opioid Response in the Context of HIV) consortium strongly suggest that brains of individuals living with HIV in the context of opioid or (polys)substance use disorder (OUD/SUD) comorbidity harbor a molecular environment permissive for HIV viral replication and risk for cytotoxic damage. This conclusion also applied to donors who showed systemic, antiretroviral drug- mediated suppression of the virus. There was a stepwise progression of transcriptomic dysregulation in OUD+HIV+ brain, culminating in widespread neuronal pathology and pronounced inflammatory signatures in microglia from individuals with poor viral suppression. The goals of the current project are two-fold. First, we aim for single molecule validation of SCORCH single cell results, by analyzing~12-20kb single molecule fiber- seq libraries from cingulate cortex of SCORCH brains carefully annotated for OUD/SUD and systemic (HIV) suppression status. We will embark on single fiber-level multiomic profiling with differential analyses to uncover effects of HIV infection on nucleosome phasing, positioning and offset at transcription start sites, together with endogenous m5CpG methylation and transcription factor footprints. Integrating single cell (RNA+ATAC-seq) data already generated from the same set of SCORCH brain cohort, with our new single molecule multiomic fiber-seq mappings is expected to provide unprecedented neurogenomic insights into the HIV and substance-exposed brain. Second, we aim for additional functional validation of SCORCH data, by employing HIV-induced lineage tracing (HILT) in human induced pluripotent stem cell (hiPSC)-derived Neuron-Astrocyte-Microglia (hiPSC N-A-Mg) tricultures, in conjunction with CRISPRi for multiplexed microglial promoter repression focused on genes that are both (i) dysregulated in SCORCH SUD+ postmortem brain and (ii) implicated in HIV expression or replication. We will assess viral integration frequency, numbers and proportions of infected microglia, and compare transcriptomes and chromatin of infected/integrated HIV+ microglia with those from exposed bystander cells. This project is a first step to validate SCORCH genomic discoveries on the single molecule level, followed by the design of novel therapeutic tools targeting opioid/substance-dysregulated genes that could foster HIV infection and spread in the brain.

Longy School of Music

Sistema Side by Side

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY: SKIN-TARGETED METAL-ORGANIC FRAMEWORK-BASED SUBUNIT VACCINES Driven by their affordability, manufacturability, and safety benefits over traditional vaccines, subunit antigens are an important component of modern vaccinology. However, they exhibit poor immunogenicity and efficacy, and thus, new and rational strategies are required to improve their immunogenicity and efficacy. We propose a novel skin immunization platform (SIP) to address the limitations of vaccine development with subunit antigens. Our innovative and globally deployable SIP leverages emerging vaccine technologies, including (1) metal-organic framework (MOF) nanovaccine constructs; (2) a clinically de-risked adjuvant, and (3) needle-free, thermostable, and self-applied microneedle arrays (MNAs), as well as highly immunoresponsive skin niche for the development of effective and accessible subunit vaccines. The central hypothesis of our project is that in situ harnessing of the immunologically rich milieu of skin with our SIP in a spatially and temporally controlled manner will drive the generation of robust, durable antigen-specific humoral and cellular responses in a well-tolerated manner. Our SIP is engineered in the form of rapidly separable MNAs (rsMNAs) that consist of high-quality obelisk-shaped microneedles comprising dissolving polymer matrix tips loaded with MOF vaccine constructs and non-dissolvable stems with filleted bases attached to the backing layer. Unlike traditional MNAs that require relatively longer wear times (minutes), our rsMNA design, which is enabled by the unique ability of biodegradable MOFs in protecting vaccine components against denaturing organic solvents needed to form non-dissolvable stems of microneedles, facilitates the implantation of MOF vaccines into the skin in less than 10 s via shear force. Our SIP offers the superior vaccine delivery and immunogenicity characteristics compared to needle-and-syringe (N&S) vaccines and conventional MNA-based vaccines. As such, our SIP unlocks the true potential of the skin immune system for improved cutaneous vaccination strategies with subunit antigens. Ultimately, this project will yield a rapidly translatable SIP that will provide unparalleled flexibility and efficacy for vaccination with subunit antigens, which is unattainable with the state-of-the-art immunization platforms.

Environmental Conservation

Small, Underserved and Disadvantaged Water System WIIN Grant - 2024 Rollover

East Side Elementary School

Purchase 7 TeqRetrofit Kits, (1) Smart USB Audio System, (1) Smart Board move, (1) "77" Smart Board Teq Ultra Short Throw Projector with rail System, Audio & Cover, (4) Teq Professional Development hours for participants, (10) 1-hr service calls. Purchase and install an electronic message board in lobby.

Smilow Rainier Vista Clubhouse & Teen Center

Replace aging computers with 28 up-to-date computers in the Club's two technology labs for youth and teens. Provide more hands-on academic and a Science, Technology, Engineering and Math (STEM)-based education programs to youth.

NSF

This project will contribute to the national need for well-educated scientists, mathematicians, engineers, and technicians by supporting the retention and graduation of high-achieving, low-income students with demonstrated financial need at Arkansas Tech University. A total of 40 scholars pursuing Bachelor of Science in Computer Science, Cybersecurity, Mathematics, Physics, Engineering Physics, Computer Engineering, Electrical Engineering, and Mechanical Engineering will receive scholarships averaging $7,000 for up to five years. Scholars will receive faculty mentoring and the project will build strong scholar cohorts through a living learning community, social and networking opportunities, and events that promote family and community involvement. Additional activities for scholars include research internships, micro-internships, and career shadowing. The overall goal of this Track 1 Scholarships in STEM project is to increase STEM degree completion of academically talented, low-income undergraduates with demonstrated financial need. There is a significant national need to grow the STEM workforce and nurture key talent that will ensure economic competitiveness and provide domestic leadership across critical sectors. This project directly speaks to this need by supporting STEM student success, which will strengthen the workforce in artificial intelligence, advanced materials and manufacturing, cybersecurity, and other key areas of need. The project will be assessed by an experienced evaluator that will offer insights into the program's strengths and weaknesses to demonstrate its efficiency and impact on participating scholars, and the data generated will contribute to the knowledge base regarding effective strategies to support talented, low-income students in STEM. This project is funded by NSF’s Scholarships in Science, Technology, Engineering, and Mathematics program, which seeks to increase the number of academically talented, low-income students with demonstrated financial need who earn degrees in STEM fields. It also aims to improve the education of future STEM workers, and to generate knowledge about academic success, retention, transfer, graduation, and academic/career pathways of low-income students. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

South Carolina Technical College System / ReadySC

ReadySC provides customized workforce training grants to new and expanding businesses in South Carolina, funding employee training programs developed in partnership with the state's technical college system to build a skilled workforce.

South Dakota Department of Environment and Natural Resources (DENR)

The Consolidated Water Facilities Construction Program provides grants and loans to South Dakota communities for drinking water and wastewater system improvements, ensuring safe and reliable water infrastructure across the state.

South Dakota Department of Environment and Natural Resources (DENR)

Solid Waste Management grants support South Dakota communities in developing and improving solid waste management systems including recycling programs, landfill improvements, and waste reduction initiatives.

The New 42nd Street, Inc.

Convert their Studios for rehearsal space to performance space allowing NYC nonprofits to use the space for a wide range of public presentations, rehearsals, workshops, showcases and events. There will be upgrades to to the audio and lighting systems, mo

NIDCD - National Institute on Deafness and Other Communication Disorders

PROJECT SUMMARY Balance disorders are common and devastating – it is estimated that one third of US adults over the age of 40 (69 million) have vestibular dysfunction. A major underlying cause of vestibular dysfunction is damage to hair cells in the vestibular organs of the inner ear. Unfortunately in mammals including humans the consequences of this damage are irreversible. The zebrafish has emerged as a model system for studying vestibular function, with its small size and optical clarity advantages for studying hair cells in vivo. Moreover within the zebrafish inner ear, hair cells are able to fully regenerate after damage. Within vestibular organs hair cells are organized into distinct central and peripheral regions with functional and molecular identities highly conserved across species. We propose experiments to study how these spatial identities are initially established within the zebrafish ear. We will determine how hair cells are added during development, and how they undergo phenotypic switching, changing spatial identity during organ growth. We will test how spatial identity regulates regional differences in mitochondrial activity. We will test whether retinoic acid signaling plays a conserved role in zonal patterning. We will test whether transcription factors enriched in zonal expression underlie gene regulatory networks establishing spatial patterning. Together these studies will provide a comprehensive picture for how this core conserved feature of vestibular function is established.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Type 1 diabetes is an autoimmune disease where the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. Our research has discovered unique hybrid molecules, called Hybrid Insulin Peptides (HIPs), that form in beta cells when fragments of insulin fuse with other protein fragments. Various HIPs contributing to disease in humans and mice are generated by an enzyme called Cathepsin D and serve as key targets for the immune system’s attack on beta cells. Interestingly, while HIPs are consistently detectable in laboratory mice used to study diabetes, they are harder to detect in human tissue samples even when analyzing larger amounts. We discovered this difference stems from how HIPs are made: the human version of Cathepsin D requires more acidic conditions to function compared to the mouse version. This could explain why human and mouse diabetes look different under the microscope - mice show widespread inflammation throughout the pancreas, while humans show more localized damage. To better understand how HIPs form in human disease, we propose to create a new mouse model where we replace the mouse version of Cathepsin D with the human version. We expect these “humanized” mice will form HIPs less readily, similar to humans. This model will help us understand how environmental factors influence HIP formation and disease development, potentially identifying new ways to prevent or treat type 1 diabetes. This research could reveal important insights into why type 1 diabetes develops and how environmental factors might influence disease progression through their effects on HIP formation, potentially leading to more effective prevention strategies.

NIAID - National Institute of Allergy and Infectious Diseases

SUMMARY Type I interferon (IFN) is the first line of defense in innate antiviral immunity, orchestrating transcriptional and metabolic responses that restrict viral replication. While IFN signaling is known to modulate sterol and glycerolipid pathways, its impact on sphingolipids (SPLs)—a class of bioactive lipids involved in immune signaling and cell stress responses—remains poorly understood. Mounting evidence suggests that infections by RNA viruses, including flaviviruses and coronaviruses, induce the accumulation of ceramide (Cer), but whether this promotes viral replication or enhances antiviral defenses is unclear. Our preliminary studies show that Zika virus (ZIKV) triggers overall changes in SPL composition and relies on Cer biosynthesis for successful infection. However, other studies implicate Cer in restricting viral replication and promoting cell survival, raising the possibility that these lipids are upregulated by the host response rather than the virus. The central goal of this proposal is to uncover how type I IFN affects SPL metabolism and to determine whether these lipids, in turn, control the IFN response and infection outcomes. We hypothesize that SPLs, particularly Cer, play a dual role in infection and immunity. Viruses may induce Cer to suppress innate immune responses, including IFN production, as suggested by the known roles of Cer in modulating host signaling pathways. However, we also propose that IFN itself alters SPL metabolism, as it does with other lipid classes, and that these IFN-induced lipid changes may contribute to antiviral defense. To disentangle these possibilities, we will use a combination of untargeted lipidomics, innovative SPL probes, CRISPR gene editing, and organelle-targeted lipid perturbation to systematically determine the causes and consequences of SPL dysregulation in infection. Aim 1 will define how IFN-β alters SPL content and distribution in infected and uninfected cells. In doing so, we will generate the first comprehensive map of IFN-driven changes in the cellular lipidome—including SPLs—across multiple cell types, providing a foundational resource for the broader virology and immunometabolism communities. Aim 2 will determine whether Cer regulates IFN-β signaling and antiviral defense, and whether the subcellular location of Cer influences its role as a pro- or anti-viral signal. Together, these studies will determine how IFN shapes and is shaped by SPLs, providing fundamental insight into the role of these lipids in the earliest steps of antiviral innate immunity.

GASVODA & ASSOCIATES INC

Distribution and Conditioning Systems and Equipment and Components

St Cousair Oregon Orchards, Inc.

St. Cousair began working with Business Oregon in October 2016 when they first visited Oregon to search for potential locations for a U.S. manufacturing facility. After several months of site selection and extensive due diligence, St. Cousair purchased a location in Newberg, Oregon, for their U.S. facility in late April 2017. The company has already invested $4,100,000 in both real estate and the purchase of Berry Noir Co-Packing. The company plans to invest an additional $6,000,000 during the next 18 months in equipment, extensive facility upgrades and new buildings, waste water system improvements, and operating capital. In addition to the capital investment outlined above, the company will utilize the $100,000 SRF request to assist with improvements and upgrades to their facility in 2017.

NINDS - National Institute of Neurological Disorders and Stroke

PROJECT SUMMARY Proper cerebellar function is important for many aspects of mental health, as evidenced by the wide range of neurological and neuropsychiatric disorders that have been associated with impaired neural processing in the cerebellum, from ataxia and dystonia to schizophrenia, autism and attention-deficit/hyperactivity disorder (ADHD). To understand how the cerebellum contributes to both motor control and cognitive functions it is necessary to define what kind of inputs it receives, particularly via the massive mossy fiber system, which carries the bulk of all sensory, motor and cognitive signals sent to the cerebellum from the rest of the brain. Furthermore, variations in brain state are likely to alter the information content of mossy fiber inputs and have a major impact on how well and reliably the cerebellum can perform its function. Unfortunately, conventional extracellular recording methods do not offer enough stability and often fail to distinguish signals of mossy fibers from other cell types in the cerebellar cortex. As a result, there is very limited knowledge about mossy fiber activity in cerebellar tasks, and no information at all about state-dependent modulation of mossy fiber responses or which mossy fiber states may be associated with enhanced cerebellar function. The experiments in this application take advantage of Neuropixels probes and a recent semi-supervised deep learning algorithm to overcome previous technical limitations and record for the first time from identified mossy fiber populations while mice perform a cerebellar-dependent eyeblink conditioning task. The analysis of mossy fiber activity, both before and during conditioning trials, is meant to achieve the following goals: (1) to provide new biological insight into the moment-to-moment variability of mossy fiber states, (2) to help define which mossy fiber states are associated with ‘faulty’ vs ‘reliable’ cerebellar function and, (3) to reveal how locomotion and non-invasive stimulation of the prefrontal cortex can be used to steer mossy fibers toward favorable states that are linked to improved performance of cerebellar-driven motor responses. Thus, the findings will have important implications for enhancing cerebellar function, both in health and disease, by developing new therapeutic interventions that can be used to promote beneficial mossy fiber states. Given the well-established role of the cerebellum in the control of movement, it is expected that the findings will impact patients with motor problems most directly. However, cerebellar dysfunction has also been associated with impairments in executive function, abstract reasoning, working memory, high-level language processing and attentional control. To the extent that the neural signature of ‘faulty’ and ‘reliable’ mossy fiber states is similar in regions of the cerebellum involved in these cognitive functions, the aims of this application and the implications for future treatments may apply to them as well.

Affiliated Steam & Hot Water

Distribution and Conditioning Systems and Equipment and Components

Kids and Paper

Kids and Paper has served children ages 5-12 with afterschool and summer program through homework help, SEL development through creative arts, healthy meals, and recreational activities at Magnuson Community Center, located at 7110 62nd Ave NE Seattle, WA. We are now looking to expand our educational impact by adding a new element to our program, specific STEM focused activities and tutoring that expose children to topics and hands-on learning. This will help students connect what they are learning with real-world applications. We will offer the new STEM program through the summer of 2023 and anticipate closing this project on September 30, 2023.