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Josephine Community Libraries, Inc.

The Expanding Opportunities Program seeks to meet the needs of Josephine County citizens looking to develop their prospects and improve their lives in the areas of education, employability, and entrepreneurship; specifically by partnering with local organizations and providing training on the resources and technology available through the library system.

Josephine Community Libraries, Inc.

Josephine County has lower rates of high school and college graduates and higher rates of unemployment than the rest of the state. Business enterprises can use more support to succeed, grow, and hire more employees. The Expanding Opportunities Program seeks to meet the needs of Josephine County citizens looking to develop their prospects and improve their lives in the areas of education, employability, and entrepreneurship; specifically by partnering with local service providers and delivering information literacy training workshops on the resources and technology available through the library system. Year one of the program emphasizes program setup, needs assessment, and connection with partnering organizations. Year two will focus, refine, and grow the program offerings to meet the information literacy needs of the target audience.

Con-Vey/Keystone, Inc.

Expansion of company which engineers and manufactures material handling equipment for the wood products industry, including automation solutions and robotics systems integration.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT: Our goal is to understand why measles virus (MeV) is the most contagious human virus. MeV is a worldwide leading cause of vaccine-preventable deaths. Understanding what sets its mechanism of transmission apart from other viruses is important. Humans are the only natural reservoir for MeV. Thus, a critical challenge for MeV study is identification of representative model systems. Well-differentiated primary cultures of airways epithelial cells from human donors (HAE) provide a physiological relevant model of human airways. In HAE, direct cell-to-cell spread of MeV results in well-defined foci termed infectious centers that ultimately dislodge from the epithelial layer en masse. Of the many respiratory viruses screened to date, only MeV results in infectious center formation in HAE. We hypothesize that infectious center formation, release, and environmental contamination are vital steps for efficient host-to-host spread of MeV. In Aim 1, we address fundamental questions about the formation of infectious centers. We hypothesize that MeV targets mitochondria and induces mitophagy. Release of mitochondrial DNA into the cytoplasm is detected by the DNA sensing molecule cGAS which initiates a cascade that stimulates antiviral genes. Next, we ask where intracellular assembly of MeV occur in HAE. Again, preliminary data suggest that mitochondria may play an important role in this process. This model will challenge the currently accepted paradigm of how MeV replicates in airway epithelial cells. In Aim 2, we demonstrate that infectious center formation can be approximated by expression of only 2 MeV proteins: Fusion (F) and Hemagglutinin (H). We use replication deficient adenoviral vectors for delivery. Modular expression of adenoviral expressed viral proteins allows numerous advantages including: 1) rapid generation of recombinant expression vectors; 2) low risk that genetic manipulations of transgenes will impact vector titer; and 3) many combinations of viral protein comparisons are possible. This novel tool will allow for the substitution of proteins with known mutations that will alter complex formation; as well as, substitution of orthologous proteins from other viruses, such as respiratory syncytial virus, Nipah virus, and Sendai virus. In Aim 3 we determine how long aerosolized MeV remains viable under common environmental conditions. Dislodged infectious centers could protect the virus from desiccation and prolong the infectious period. We develop tools to aerosolize cell-associated or cell-free MeV. Subsequently, the infectivity will be compared following exposure to environmental conditions, (e.g., desiccation or temperature). Defining the stability of MeV across different environmental conditions could inform policy to reduce transmission. In summary, fundamental biological questions remain about the highly contagious MeV. Within airway epithelial cells, MeV undergoes its final amplification and prepares itself for spread to the next host. This final step is likely key to the contagious nature of MeV.

NINDS - National Institute of Neurological Disorders and Stroke

Abstract Cholinergic brain activity plays a crucial role in regulating sleep, particularly Rapid Eye Movement (REM) sleep, as demonstrated in animal studies. How these findings translate to humans remains insufficiently explored. Understanding the neurobiology of sleep in humans is critical, as sleep dysregulation is closely linked to neurodegeneration, making sleep a promising therapeutic target. REM sleep behavior disorder (RBD), an early sign of Parkinson’s disease (PD) and Dementia with Lewy Bodies—collectively known as Lewy Body Disorders (LBD) —often appears decades before diagnosis, where it is referred to as isolated RBD. Cholinergic changes also emerge early in LBD, possibly starting in isolated RBD phase. These changes extend beyond the typical decline in cholinergic activity and can include compensatory mechanisms, such as increased activity of the vesicular acetylcholine transporter. We hypothesize that changes in cholinergic neurotransmission, whether increases or decreases, can affect the tonic and phasic availability of acetylcholine. Changes in tonic and phasic availability of acetylcholine, in turn, may disrupt the sleep-wake cycle, leading to REM sleep disturbances such as RBD among others. Our preliminary findings in patients with PD support this hypothesis. We observed cholinergic changes using the selective brain PET radiotracer [18F]-FEOBV, which binds to the vesicular acetylcholine transporter, and self-reported measures of RBD symptoms and excessive daytime sleepiness. Wearable at-home sleep recording devices, such as the Sleep Profiler™, provide a patient-friendly method for quantifying sleep architecture and its alterations with performance comparable to traditional in-lab polysomnography. These technologies enable more ecological investigations of sleep biomarkers. The main aim of this study is to investigate the relationship between cholinergic brain changes and sleep, moving beyond qualitative, questionnaire-based measures in patients with PD (K99) and isolated RBD (R00). We will do that by using advanced imaging techniques ([18F]-FEOBV PET) and wearable sleep recording devices (Sleep Profiler™). During the K99 phase, we will focus on patients with PD, examining the association between cholinergic changes and REM (Aim 1) and non-REM sleep alterations (Aim 2). Building on the skills acquired during the K99 (sleep recording analyses and neurobiology of sleep), I will transition to the independent R00 phase to investigate cholinergic changes in a newly recruited cohort of patients with isolated RBD. I will explore how these changes relate to sleep architecture and clinical progression (one-year follow-up). This research can provide valuable insights into how the cholinergic system contributes to sleep disturbances, potentially paving the way for novel cholinergic modulation treatments that target sleep to protect brain health in isolated RBD and LBD. It may also validate the use of wearable sleep devices for at-home monitoring of cholinergic system changes. The findings in this study will inform the design of future research on molecular mechanisms linked to sleep disturbances and neurodegeneration.

NIAID - National Institute of Allergy and Infectious Diseases

Infectious diseases caused by bacterial pathogens remain a major threat to human health. A wealth of studies have established the importance of host-pathogen interactions. However, the transition of environmental strains to become commensals or pathogens remains largely underexplored. In part, this is because the evolutionary forces that facilitate the transition of a strain from the environment to one that could establish an early stage infection are complex. Importantly, common features mark the transition: Strains must initially infect patients before causing disease. In a healthy individual, the innate immune system presents a sophisticated and multi-layered set of barriers to the establishment of infections such as bacteremias. Overcoming the multifaceted and robust barriers of the innate immune system requires a potential pathogen to adapt to these challenges. While there are many excellent studies on individual host-pathogen interactions, there is less consensus on how specific attributes of the innate immune response are integrated to eliminate specific strains and how a compromised innate immune system might shape the adaptive evolutionary landscape to allow for pathogen emergence. To investigate microbial emergence and adaptation, we are taking a high-throughput approach to the interactions of environmental bacteria with an in vitro model innate immune system that is comprised of the humoral and cellular components. Utilizing a unified experimental framework with a model innate immune system, we aim to identify how the humoral and cellular components of the innate immune response eliminate diverse environmental microbes (Aim 1) and how these microbes adapt in response (Aim 2). This combined approach, leveraging microfluidics, in vitro experimental evolution, and genomic/phenotypic characterization, will identify traits required for the environmental-to-pathogen/commensal transition and how a compromised innate immune system might shape their evolution. This knowledge can be harnessed for pre-emergent pathogen biosurveillance, improved early diagnostics, and potentially, the development of immunomodulatory therapies.

NINDS - National Institute of Neurological Disorders and Stroke

Abstract: Multiple Sclerosis (MS) is an extremely debilitating autoimmune disorder characterized by the destruction of myelin that remains incurable. MS impacts more than 1 million American lives, and its prevalence has almost doubled in the last 10 years. Despite the rapid increase in cases, the etiology of MS is poorly understood and is loosely defined as a combination of environmental and genetic risk factors. There is a critical need to further explore the reasons behind MS onset. Gastrointestinal symptoms are prevalent in two-thirds of MS patients, suggesting a potential link between the gut and disease pathology. Notably, a third of MS patients exhibited gastrointestinal symptoms before an MS diagnosis, hinting at a potential role of the gut in disease etiology. Enteric glial cells (EGCs), crucial components of the enteric nervous system governing autonomous digestive tract function, are widely distributed throughout the gastrointestinal (GI) tract. EGCs express myelin proteins observed in the Central Nervous System, and some of these proteins, including Proteolipid protein 1, are known to be targeted in MS patients. EGCs are fully equipped to respond to inflammatory cues and express immune receptors, cytokines, and antigen presentation machinery. Given this, it is compelling to speculate that the initial encounter of self-antigen to activate myelin- specific T cells could be driven by EGC derived myelin antigens in the gut—a highly dynamic environment prone to inflammation and rich in neuroimmune interactions. Our long-term goal is to shed light on the contribution of EGCs to MS initiation. The foundation of this proposal is formed by our data showing that EGCs express myelin transcripts, can perform antigen presentation, are activated in an animal model of MS, and the use of a new model to selectively ablate them. Our central hypothesis is that the destruction of EGCs in an inflammatory setting constitutes a pivotal event in MS onset by priming autoreactive T cells against EGC-derived myelin antigens in the gut-associated lymphoid tissue. We plan to test this hypothesis using experimental autoimmune encephalomyelitis (EAE). This hypothesis will be addressed by pursuing two specific aims: 1) Determine the impact of EGCs ablation on the peripheral immune response, and 2) Determine the impact of EGCs ablation on EAE initiation and progression. Our approach is innovative because it will utilize novel mouse strains to manipulate EGCs and test the role of EGCs in MS onset. The proposed research is significant because it will improve our knowledge about the function of EGCs in pathological conditions. The insights gained from our studies could lead to fundamental advances in preventing MS.

NIAID - National Institute of Allergy and Infectious Diseases

Methicillin-resistant Staphylococcus aureus (MRSA) strains are antibiotic resistant bacteria that are the leading cause of healthcare associated infections in the United States and around the world. While research has focused on the development of new and more powerful antibiotics, the strains keep evolving resulting in ‘super bugs’ that are difficult to eradicate. Therefore, a key knowledge gap is the lack of an efficient approach that can target these superbugs ubiquitously with minimal effects on host cells. CRISPR-based gene editing can be a promising approach to address this knowledge gap. However, translation of CRISPR therapeutics faces a tremendous challenge as current technology focuses mainly on vector-based approaches to constitutively express CRISPR components (Cas9 enzyme and the targeting single guide RNA (sgRNA)) in recipient cells. This approach is fraught with logistical challenges as well as severe side effects. These are major hurdles to clinical translation. The translatability of CRISPR therapeutics can improve tremendously if the rhCas9 enzyme and the sgRNA can be delivered directly as a ribonucleoprotein (RNP) complex. However, this has not been achieved in bacteria. This application is an ambitious effort to address both the knowledge gap as well as the translational hurdle to CRISPR-based antimicrobials. Utilizing our foundational knowledge gained by studying extracellular vesicles (EVs) for the past decade, we hypothesize that: Artificial vesicles (AVs), mimicking the bioactivity of natural EVs can be used to deliver antibacterial CRISPR RNP complex to MRSA strains without ectopic activity on mammalian cells. To test this hypothesis, we propose two specific aims. Aim 1 will engineer artificial vesicles capable of bacterial entry with specific focus on MRSA strains found predominantly in the USA and Aim 2 will develop CRISPR RNPs targeting the conserved regions of 16s rRNA gene to produce vesicles that are capable of bactericidal activity upon entry into MRSA. This aim will also study the effects (absence of) the vesicles in representative mammalian cells as well as evaluate the efficacy of the strategy in a systemic model of mouse MRSA infection. Overall, successful completion of these aims will establish a system for delivering CRISPR-based therapeutics for combating antibiotic resistance super bugs.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY/ABSTRACT Diabetic neuropathy (DN) is a painful and debilitating condition that affects 50% of people with diabetes. Despite its high prevalence, the precise biological mechanisms of DN are not known and no disease arresting treatment is currently available. An important barrier to effective natural history studies and interventional clinical trials in DN has been the paucity of non-invasive, clinically meaningful biomarkers. Blood concentrations of neurofilament light chain (NFL) have proved useful in select acquired and genetic nerve disorders, however, these have important limitations as biomarkers for DN. Our recent study examining plasma NFL concentrations in youth-onset type 2 diabetes demonstrated that NFL is elevated in people with diabetes both with and without neuropathy, likely owing to its release in response to axonal injury in both the central and the peripheral nervous system (PNS). The overall goal of the proposed studies is to define specific membrane-bound extracellular vesicle (EVs)-derived protein biomarkers of PNS origin for diabetic neuropathy (DN). The analysis of proteomic profiles in EVs has recently emerged as a strategy to identify tissue specific biomarkers in several central nervous system disorders, including Down syndrome, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. EVs are secreted by all cell types, however, they can be traced back to their cell of origin using their specific surface markers. We new technique derived propose to employ a broad proteomic approach to identify EV-derived biomarkers relevant to DN. Subsequently, we will translate our specific-cell type EV enrichment to evaluate whether inflammatory and neurotrophic markers can be detected in Schwann cell (SC)- EV cargo.Our overall hypothesis is that the use of these two unique technical approaches will allow for the identification of unique EV-derived protein signatures for DN. To address this hypothesis, we have developed two specific aims. In Aim 1, we will use the new Mag-Net technology to carry out a high- throughput proteomic analysis to define new EV-derived protein markers specific to DN. In Aim 2, we will interrogate the PNS using a targeted approach to examine the cargo of SC-derived EVs. We will use immunocapture techniques to target surface markers specific to SCs and examine the cargo of SC-derived EVs for inflammatory and neurotrophic markers in participants with DN, as compared to controls and two forms of genetic neuropathy. Our interdisciplinary team includes world renowned experts in diabetes, EV methodology, proteomic approaches, and neuropathy biomarker development, and is therefore in a unique position to successfully execute this work. The biomarkers use of combined argeted and untargeted approaches will maximize our ability to define new EV-derived for DN and lay the groundwork for more detailed, prospective studies. t

NIAID - National Institute of Allergy and Infectious Diseases

SUMMARY Current treatments for the suppression of allograft rejection have remained largely unchanged over the last several decades, relying on systemic calcineurin inhibition, anti-metabolites, and steroids. Although effective in curtailing alloimmune responses, these systemic therapies produce significant undesired off-target effects, which often lead to early organ loss and patient mortality. There is an urgent need for innovative strategies to mitigate these critical side effects, extend transplant survival, and improve organ recipient lifespans. Among nanotherapies, antibody-drug conjugates (ADCs), represent a cutting-edge technology that combines biologics with small molecules to target specific cells. ADCs have been successful in cancer, where they leverage antibody specificity to deliver cytotoxic drugs directly to target cells, achieving impressive tumor efficacy with reduced systemic toxicity compared to chemotherapy. However, their application to the field of organ transplantation has been hindered by the high immunogenicity of the Fc portion, poor tissue penetration, and the absence of tools to track cargo delivery to the target cells, essential for controlling immunosuppression. We hypothesize that Fab-fragment drug conjugates (FDCs), which lack the limitations of ADCs, can be utilized to selectively deliver immunosuppressive drugs both intracellularly to T cells (intra-FDCs) and locally to sites of allograft inflammation (local-FDCs), while maintaining low drug systemic levels of free drug. Our approach, supported by our preliminary results, introduces an innovative design for these nanotherapies, which enables precise monitoring of drug release both in vitro and in vitro, combining both therapeutic and diagnostic (theranostic) purposes. In Aim 1 we will design and optimize an FDCs-based platform for the targeted delivery of the calcineurin inhibitor Tacrolimus, and the anti-metabolite mycophenolic acid (MPA) directly into T cells (Intra-FDCs). In Aim 2 we will establish an FDCs-based strategy to locally release the corticoid methylprednisolone at inflamed allograft sites (local-FDCs). While both intra-FDCs and local-FDCs utilize Fab fragments, they rely on independent mechanisms of action and drug-release triggers. This independence ensures that each approach can be pursued separately. This R21 application will generate intra-FDCs and local-FDCs leveraging a fluorescent theranostic platform to enable real-time tracking of their delivery and activity. This approach, while technically challenging (high-risk), offers a potentially transformative solution to a critical unmet need in transplant immunosuppression and other contexts, such as autoimmune disease (high-reward). Successful outcomes will set a clear path forward for developing these FDC strategies for human use and will constitute the basis for applications to other funding mechanisms. 1

City of Prairie City

Faiman Wells Water System Connection

Pioneer Library System

Fall Institute

JUSTICE, DEPARTMENT OF.FEDERAL PRISON SYSTEM / BUREAU OF PRISONS.USP TERRE HAUTE

FCC Terre Haute HALAL FY26 QTR3

Elderberry-Nehalem Water System

Feasibility Study

Lincoln County Library District

Discover the most cost-effective, inclusive option for a shared ILS between libraries in Lincoln County in preparation for establishing a unified system for Lincoln County libraries that will provide excellent library services for Lincoln County Library District citizens.

City of Powers

Feasibility Study for Telemetry and Control System

Eastmont Water Company

Feasibility Study for Water System Improvements

Freeway Estates Community Orchard

FECO will add additional rainwater catchment from a small roof and install pumps to move water from the cisterns to elevated tanks that will serve the low-pressure gravity fed irrigation system. This will increase efficiency in watering the community orchard, enhance our water conservation efforts, and allow people of various physical abilities to assist with watering. This project will be completed by September 2018.

Research Foundation for Mental Hygiene

The Ticket to Work initiative is specifically designed to assist recipients of Supplemental Security Income (SSI) and Social Security Disability Insurance (SSDI) between the ages of 18-64 to either enter or return to the workforce. Services and supports can include benefits counseling, job development, job coaching, as well as an array of other employment related supports.

Governor's Office of Emergency Services

The purpose of the SL Program is to assist local governments, including school districts and special districts, and federally recognized tribes address cybersecurity risks and threats to information systems, and improve security of critical infrastructure and resilience of the services these entities provide to their communities.

Governor's Office of Emergency Services

The purpose of the SG Program is to assist agencies of the State of California address cybersecurity risks and threats to information systems, and improve security of critical infrastructure and resilience of the services these entities provide to their communities.

City of Monument

Final Design: Water System Compliance Project

DEPENDABLE FIRE EQUIPMENT

Building and Facility Construction and Maintenance Services

The Fashion Institute of Technology

Replace fire alarm system in all of its (5) academic buildings with a new state-of-the-art fully addressable fire alarm and detection system using microprocessor technology and graphics display.