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gen_de3ad9c302d6e061e66e6760df5f7254 | Training in Pharmacological Sciences | NIH | VANDERBILT UNIVERSITY | 5T32GM149363-02 | Project Summary/Abstract: The long-term goal of this training program is to develop members of a diverse workforce with rigorous training in an area of biomedical science and to foster a deep understanding of the principles of pharmacology to create scientists who will be well positioned to participate in the process of moving basic science discoveries to much needed therapies. This training will be accomplished in an interdisciplinary and inclusive environment that brings together trainees from multiple institutions who represent a broad range of scientific interests and a shared desire to understand the principles that underlie the development of safe and effective therapies. A cohort of 3 trainees will be appointed for the second and third year of their graduate training, a stage in their training where pharmacology-specific training is best delivered and solidified. We aim to train scientists equipped with the principles of the discipline of pharmacology who are uniquely prepared to identify and solve research questions in the biomedical sciences. Mastery of the principles of pharmacology will allow trainees to serve as leaders in transitioning discoveries into therapies. To this end we have developed a predoctoral training program that will: provide each trainee with the foundational tenants of the discipline of pharmacology such as receptor theory, drug metabolism, and pharmacokinetics; develop the professional skills necessary for success; support individual research mentoring that provides directed research in an area of biomedical science of interest to the trainee alongside discipline-specific training; and evaluate the attainment of individual trainee and program goals. Timely and actionable feedback on the progress of trainees is provided by a competency-based assessment plan developed in collaboration with a select group of like-minded predoctoral training programs. All facets of the proposed program are supported by a comprehensive evaluation plan designed to both assure the development of individual trainees and provide feedback to improve the overall training program. These experiences are supplemented to build competence in research ethics, scientific rigor, presentation of scientific data, and assessment of data. We convey to trainees the expectation and the tools to pursue life-long learning as an essential component for success. Professionalism will be intentionally addressed to impart skills in areas such as communication, teamwork, mentoring, and self-assessment in order to aid in the development of resilience, integrity, and leadership. These program aims are supported by longstanding strengths that include the history of collaboration amongst the partner institutions, the past success of trainees, and a dynamic, intellectually diverse research environment that supports pharmacological investigation. Our goal is to produce trainees who will become leaders in careers found in academic and industrial research, government and regulatory affairs, and education. Project Narrative Funds provide for students to receive training in the discipline of Pharmacology. Training includes both coursework and mentored research. Scientists trained in this area perform important jobs in drug development in universities and industries, product safety, and regulatory affairs. | Training, Institutional | 2institutional_funding
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gen_6107a38dc0bc4b789417340faceb688e | Polyamine Dysregulation in the Gastric Epithelium during Helicobacter pylori Infection and its Impact on Gastric Carcinogenesis | NIH | VANDERBILT UNIVERSITY | 5F31CA278330-02 | PROJECT SUMMARY Helicobacter pylori colonizes the stomach of about 50% of the world’s population and is the strongest known risk factor for developing gastric cancer, the fourth most common cause of cancer related deaths. Failure of the host response to control the infection leads to persistent inflammation, which initiates disease progression from chronic gastritis through a histological “Correa Cascade” that results in gastric carcinoma in 1-3% of all those infected. Due to antibiotic resistance, and the fact that antibiotic treatment may not be effective in reducing cancer risk once precancerous lesions are present, we need to develop new therapeutic strategies to limit progression to dysplasia and carcinoma. Our lab investigates the role of the polyamines, putrescine, spermidine, and spermine in gastric inflammation and carcinogenesis. Putrescine is sequentially converted to spermidine and spermine, which is back-converted to spermidine by spermine oxidase (SMOX). We have shown that SMOX expression is elevated in human and mouse gastric tissues infected with H. pylori. Furthermore, infected C57BL/6 Smox–/– mice exhibit depleted spermidine levels, and a decrease in gastritis and carcinogenic signaling compared to wild-type mice. Using FVB/N INS-GAS mice prone to developing gastric dysplasia and intramucosal carcinoma with H. pylori infection, we have seen that Smox–/– mice infected with H. pylori exhibit a significant reduction in gastric intramucosal carcinoma and extent of dysplasia. Spermine catabolism by SMOX generates 3-aminopropanol, which can spontaneously form acrolein, a reactive electrophilic aldehyde that has the potential to damage DNA and proteins. Our preliminary findings demonstrate that acrolein is produced in gastric tissues of H. pylori-infected FVB/N INS-GAS mice and is significantly reduced in Smox–/– FVB/N INS-GAS mice. Additionally, spermidine is an essential substrate for the synthesis of hypusine, a unique amino acid that is only found in the protein eukaryotic translation initiation factor 5A (EIF5A) by the action of the enzyme deoxyhypusine synthase (DHPS). Our recent work with human gastric organoids has revealed induction of hypusinated EIF5A levels with H. pylori infection, which was ablated with the chemical inhibitor of the pathway. Proteomic analysis on these organoids implicated hypusination as a critical pathway for oncogenesis. Taken together, we hypothesize that polyamine dysregulation due to SMOX activity in H. pylori-infected gastric epithelial cells leads to the generation of spermidine and acrolein, and upregulation of the hypusination pathway resulting in increased risk for gastric cancer development. Our specific aims are to determine: 1) the role of SMOX activity in gastric carcinogenesis, including effects of spermidine, spermine and acrolein in FVB/N INS-GAS mice. 2) if spermidine generated by SMOX contributes to gastric cancer development through hypusination using studies in human gastric organoids and mice with an epithelial-specific deletion of Dhps. This proposal seeks to elucidate the mechanisms by which SMOX induces gastric disease progression, thus identifying novel pathways to be targeted for therapeutic benefit, while providing the ideal training for my future career as a principal investigator. PROJECT NARRATIVE Helicobacter pylori infects half of the world’s population and is the strongest known risk factor for gastric cancer; however, traditional treatment with antibiotics is often ineffective, especially once precancerous lesions are present. We have previously shown that polyamines are involved in gastric inflammation and carcinogenesis, and our data indicate that the enzyme spermidine oxidase (SMOX) regulates key pathways involved in the progression to cancer. This project will investigate the mechanisms by which SMOX contributes to gastric carcinogenesis by examining its metabolic products, spermidine and the toxic metabolite acrolein, and the enhancement of a pathway involved in translation, hypusination, all of which could contribute to carcinogenetic signaling, with the ultimate goal of discovering novel pathways to be therapeutically targeted. | Training, Individual | 6project_grants_public
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gen_63df496c2ef14d885f9e454285bca639 | Resource Development Core | NIH | UNIVERSITY OF ALABAMA AT BIRMINGHAM | 1U54DK137307-01 | Innovations to mitigate the global burden of acute kidney injury (AKI) require catalyzers that network investigators and provide them with resources that facilitate discovery, translation and implementation science to impact bedside care, improve policy and dismantle health inequalities. The overarching objective of the Resource Development Core is to incubate novel and strategic approaches to continuously support AKI research across a diverse universe of investigators in the O'Brien Kidney Consortium. This Core will provide a dynamic resource and platform to develop, test and refine innovations that could accelerate pre-clinical and clinical research and then can be offered as part of the Biomedical Resource Cores. The initial focus of this Core will be centered in advanced and quantitative AKI biological characterization and big data analyses. In the pre-clinical area, novel analytical approaches in metabolomics and molecular and functional in vivo imaging will be incubated to probe unique biological characteristics of disease development. In the clinical area, tools for multi-institutional Electronic Health Record (EHR) data management and harmonization and a novel federated learning platform to evaluate Artificial Intelligence (AI)-based tools will be developed. These development areas will be frequently evaluated to assure that the selected tools to be refined or developed are relevant to patients and investigators, and use the most advanced technologies to maintain high standards of validation, reproducibility and transferability tailoring the growing investigator's needs with a pathway to be offered in the Biomedical Cores in the future. To continue to drive innovations in AKI research, the following Specific Aims are proposed. In Aim 1, we will develop an incubator for novel technologies to support pre-clinical research in AKI. Specifically, in Aim 1A, we will develop tools for the examination of the disturbed distribution of small molecules and peptides in AKI. We will develop novel microfluidic methods aimed at high resolution molecular cartography in kidney tissue. In Aim 1B, we will develop molecular and functional kidney-specific imaging and image-analysis approaches in pre-clinical animal models of AKI. Probing for longitudinal evaluations of tissue- scale biological changes with translational positron emission tomography (PET) and magnetic resonance imaging (MRI) will elucidate key molecular, functional, and anatomical alterations during AKI development and in response to novel therapeutics. In Aim 2, we will develop an incubator for digital workspace technologies to support EHR data analyses in AKI. This will include enhancements in existing collaborative digital workspaces to support EHR data management and harmonization (Aim 2A) and the development of a novel federated multi- task learning platform to evaluate AI-based tools (Aim 2B). These aims are forward-thinking to enable novel methodologies to better understand the pathobiology and heterogeneity of AKI. Project Narrative As per the RFA, not needed for individual components. | Research Centers | 2institutional_funding
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gen_c8399bffa4c34295571724788ed5098e | Translational Pathology Core | NIH | UNIVERSITY OF MICHIGAN AT ANN ARBOR | 1P50CA269022-01A1 | PROJECT SUMMARY-ABSTRACT (Translational Pathology Core) The overarching mission of the Translational Pathology Core is to collect human tissues associated with clinical information and distribute to SPORE investigators to facilitate translational research. The Translational Pathology Core will be housed and administered within the Department of Pathology to ensure uncompromised patient care, optimal use of limited tissue resources, and patient confidentiality. The specific goals of the core include: (1) Uncompromised patient care and proper surgical pathology diagnosis. All tissues will be collected under IRB-approved protocols. (2) Prospective procurement of appropriate brain, breast, pancreas and other future tissues as dictated by the needs of the SPORE projects. The core will work closely with and enhance the existing Tissue Procurement Service of the Tissue and Molecular Pathology Shared Resource of the University of Michigan Rogel Cancer Center. Dr. Thomas Giordano has been a director of this shared resource continuously since 1996. (3) Expert pathology review of human tissues from surgical pathology specimens. Dr. Sriram Venneti, a neuropathologist and accomplished glioma investigator, will review all brain tissues, Dr. Jiaqi Shi, a GI pathologist with special expertise in pancreas cancer, will review all pancreas tissues, and Dr. Thomas Giordano, a surgical pathologist with decades of experience in breast pathology, will review all breast tissues. As needed, other expert pathologists from the Department of Pathology will be recruited to support the core. (4) Tissue-based gene expression and biomarker validation studies, such as immunohistochemistry, as indicated by the needs of the SPORE projects. Dr. Dafydd Thomas, an expert in tissue-based investigation, will lead these efforts. Collectively, the services of the Translational Pathology Core will support the projects by facilitating translational research and also enhance the resources of other NCI-supported networks. | Research Centers | 6project_grants_public
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gen_f9f57c6ce6c7c81873bc955f74df451e | Biosynthesis of Several Oxyvinylglycine Nonproteinogenic Amino Acids Bearing Unusual Alkoxyamine Bonds | NIH | UNIV OF NORTH CAROLINA CHAPEL HILL | 1F32GM151822-01 | Project Summary Natural products serve crucial roles in the pharmaceutical industry as drugs or leads for drug compounds. Generated through secondary metabolism, these molecules impact the virulence, symbiosis, and survival of microorganisms. The nonproteinogenic oxyvinylglycine amino acids are an interesting class of secondary metabolites characterized by the presence of a vinyl oxygen moiety. Members of this class, such as 4-(2’- aminoethoxy)vinylglycine (AVG), are known to arrest germination in plants by inhibiting the pyridoxal 5’- phosphate (PLP)-dependent enzyme 1-aminocyclopropane-1-carboxylate (ACC) synthase.2 While the biosynthesis of vinyl ether-bearing oxyvinylglycine nonproteinogenic amino acids including AVG has been explored, the formation of other members of the family with alternative functional groups remains undetermined. 4-Formylaminooxyvinylglycine (FVG), an oxyvinylglycine containing an N–O bond, was reported to have duel herbicidal and bactericidal activity.3,4 The gvg biosynthetic gene cluster in Pseudomonas fluorescens strain WH6 is responsible for the biosynthesis of FVG and the related compounds guanidinooxyvinylglycine (GOVG) and aminooxyvinylglycine (AOVG) though the exact biosynthetic mechanism remains unclear.5,6 In this proposal I will determine the biosynthetic pathways responsible for the formation of FVG, GOVG, and AOVG. I will use a combination of feeding experiments and in vitro biochemical assays to determine the substrate and product of each enzyme along the biosynthetic pathway of these three nonproteinogenic amino acids. The vinyl alkoxyamine is unusual in amino acids, therefore I will characterize the enzyme responsible for N–O bond construction and determine its chemical mechanism. These studies will facilitate the bioinformatic discovery of similar oxyvinylglycine nonproteinogenic amino acids. Moreover, characterization of the iron-dependent enzyme responsible for N–O bond formation will facilitate its use in a synthetic context to expand the repertoire of oxidative biocatalysts. PROJECT NARRATIVE Natural products are an invaluable source of and inspiration for pharmaceuticals and agrochemicals. This project proposes to study the biosynthetic pathways of bioactive nonproteinogenic amino acid secondary metabolites that contain unusual vinyl N–O bonds. Understanding the synthesis of these small molecules and the biochemical mechanisms underlying their formation will enable our search for similar bioactive compounds and expand the toolbox of biocatalytic oxidative enzymes. | Training, Individual | 6project_grants_public
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gen_13581869b3d73cdc4dda195fd0fdefb1 | A simulation platform to predict dose and therapeutic window of immunocytokines | NIH | APPLIED BIOMATH, LLC | 1R44AI177133-01 | Project Summary/Abstract Immunocytokines (ICs) are fusion proteins of an engineered cytokine conjugated to an antibody. These novel molecules are the next generation of cytokine-based immunotherapies with potential applications in a diverse range of diseases such as rheumatoid arthritis (RA), psoriasis, and cancer. ICs are designed to selectively target diseased tissue or specific immune cells with minimal systemic immune activation that typically leads to dose-limiting toxicity in recombinant cytokine therapy. However, it is challenging to design a molecule with high target specificity, predict its pharmacokinetics and identify doses that achieve high efficacy but low toxicity, i.e. the therapeutic window. We are proposing to develop a simulation platform for IC screening that will computationally predict dose and therapeutic window of novel ICs under development. The platform will implement a quantitative systems pharmacology (QSP) model that mechanistically describes the binding of an IC to target and off-target cells and links cytokine receptor occupancy to cellular activation and expansion dynamics. The model will predict in vivo pharmacokinetics (PK) and pharmacodynamics (PD) for an input dose and dosing regimen of a proposed IC. Simulations will report readouts such as cell counts and soluble cytokine levels that are clinically observable biomarkers of efficacy and toxicity. The model will be general enough to simulate pro- and anti-inflammatory ICs. A modular design will allow us to add new cell types and cytokines/receptors as needed to adequately model the crosstalk between the inflammatory and regulatory arms of the immune response. In Phase I of this Fast Track proposal, we will demonstrate the technical feasibility of developing a single mechanistic QSP model structure that captures drug dose- dependent expansion and contraction of four unique IC molecules. By fitting preclinical and clinical data for each molecule, we will establish a robust translational strategy for human dose prediction. In Phase II the platform model will be integrated with and made accessible through Applied BioMath’s Assess™ browser-based interface. With this setup, users can interactively explore the IC design space and use simulations to understand the impact of varying dose, dosing interval, target affinities, cytokine potency and drug half-life on clinical PK/PD. We expect that this interactive tool will foster effective communication within multidisciplinary drug development teams, and help them rationally identify optimal molecular characteristics and dosing strategies for novel ICs. The platform will also allow virtual patient cohort simulations to guide selection criteria for clinical trials. There are currently no effective tools to screen candidate molecules in the IC space. Our proposed computational platform to predict the optimal dose and therapeutic window of novel ICs will accelerate the lengthy and expensive lead candidate selection process, and thus lower the cost of IC development, facilitate clinical trial design, reduce late stage attrition and bring new drugs to the market faster to benefit patient healthcare. Project Narrative Immunocytokines (IC) are a promising class of cytokine-based therapeutics with high efficacy, but achieving an adequate therapeutic window is complicated by potentially high risk of toxicity due to off-target effects. The proposed project will develop a simulation platform to facilitate the prediction of optimal dose, therapeutic window and best dosing strategy for a more efficacious and safer treatment for patients. This simulation platform will help optimize the next generation of ICs developed to treat diseases such as rheumatoid arthritis and cancer by addressing key questions in IC drug development. | SBIR/STTR | 0business_rnd_innovation
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gen_d0089c2894fe005d030390fef08a30a0 | Ethics Core (FABRIC) | NIH | YALE UNIVERSITY | 5U54HG012510-04 | Bridge2AI: a FAIR AI BRIDGE Center (FABRIC) Ethics Core Summary The use of artificial intelligence (AI), and particularly machine learning (ML), in healthcare opens up many opportunities to improve healthcare and biomedical research. However, AI/ML also raise important issues that implicate ethics and trust, including defining parameters for consent and re-use of personal data, protecting privacy, ensuring transparency and engagement with stakeholders about this research, and developing and deploying tools that are useful and valid for all people. Without an ethically robust set of principles and practices that are generalizable and reusable in a wide range of biomedical environments, AI/ML could violate personal rights, widen the gap between fairness and equality, and fan the flames of mistrust, as exemplified by recent work showing how racial bias can influence clinical decision algorithms. Our vision for the FAIR AI Bridge Center - Ethics Core (FABRIC-Ethics) is to ensure that AI/ML is developed and applied in an ethical and trustworthy manner. FABRIC-Ethics will support the Bridge2AI program to become sustainable by making it more ethical and trustworthy by the end of the four-year project period. To realize this vision, we will use an iterative and reflective four-step cycle: 1) Scaffold, 2) Assess, 3) Facilitate and 4) Evaluate and educate, or SAFE, to provide a platform for convening, analyzing and curating, public relations and original research in a multidisciplinary manner. We will work with the Bridge2AI program to formulate ethical and trustworthy principles for AI/ML (ETAI) to address existing and future practices in biomedical AI research and applications. These include the collection and management of data, the development and deployment of AI/ML technologies and AI/ML applications. In close collaboration with the Bridge2AI program and its Data Generation Projects (DGPs), we will conduct a closed- and open-ended survey, discuss priorities and experiences with Bridge2AI DGPs, and develop an open, curated catalog of relevant literature. These efforts will run in parallel with multiple mechanisms for building a learning ETAI community, convening Bridge2AI data generation projects to distill best practices, and organizing studio sessions to support contact with the other core areas of the Bridge2AI Center and the broader community. Our core will further develop a digital health checklist and framework that prepares Bridge2AI DGPs to evaluate: 1) access and usability, 2) risks and benefits, 3) privacy and 4) data management. We will work with the Bridge2AI DGPs to share knowledge about ETAI, inform the development of principles and best practices, and to set up conferences for sustainable development of ETAI culture beyond Bridge2AI. The team assembled for the core has expertise in a wide range of areas, including bioethics, digital health research ethics, law, public policy, AI/ML, data protection, informatics, medicine, human- centered design, implementation science, and community engagement. To ensure success, FABRIC-Ethics will be led by four PIs with a proven track record in multidisciplinary approaches to the study of ethical issues in technology, center management, and core support. | Research Centers | 6project_grants_public
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gen_66ad22898cb557cbfb362c34c79210ce | Thick and Thin Filament Dysfunction in Obese Heart Failure with Preserved Ejection Fraction | NIH | JOHNS HOPKINS UNIVERSITY | 1F31HL168850-01 | PROJECT SUMMARY Heart Failure with Preserved Ejection (HFpEF) is one of the largest unmet needs of all cardiovascular disease. Although it now is the most common form of heart failure, to date, it has little to no specific effective therapy. An obesity pandemic has now changed its phenotype, with obesity and metabolic syndrome now significant drivers of the disease. We recently reported that an obese-HFpEF phenotype exhibits striking depression of right ventricular myocyte tension generation at higher (contraction-related) levels of calcium. Critically, the mechanism by which this occurs is unknown. Myocyte tension is regulated by both the thick filament, consisting of myosin, and the thin filament, consisting of actin, tropomyosin, and cardiac troponins. In the thick filament, approximately half of all myosin heads are in a conformation known as the super-relaxed (SRX) state, and the proportion of myosin in this state is an important regulator of tension. The thin filament regulates tension by altering calcium sensitivity, and one regulator is phosphorylation of cardiac troponin I (cTnI). In exciting new preliminary data, I find that thick filament structure and phosphorylation of myofilament proteins are altered in obese-HFpEF. This proposal derives from these data and aims to elucidate how obesity alters the thick and thin filament in human HFpEF. In Aim 1, I will test the hypothesis that structural inactivation of the thick filament in obese-HFpEF results from an excess of SRX myosin. To assess thick filament structure, I use small angle x-ray diffraction, a technique that leverages the ordered structure of cardiac muscle to quantify distances between sarcomere proteins. This technique is performed at the synchrotron at Argonne National Laboratory, one of few locations globally that can perform the assay, and this proposal describes the first application of this technique to endomyocardial biopsies from human HFpEF patients. While informative, X-ray diffraction on its own cannot prove the presence of excess SRX myosin. For this, I will measure the myosin ATP turnover from single cardiomyocytes from HFpEF patients. I will then explore whether obesity is a driver of excess SRX myosin by measuring both assays in HFpEF patients with both obesity and hypertension/hypertrophy. In Aim 2, I explore the mechanism underlying how hyperphosphorylation alters calcium activated tension. My preliminary data finds that the exposure to enzymatically active protein phosphatase 2A (PP2A) partially reverses the deficit observed in calcium activated tension in obese HFpEF, but the mechanism is unknown. I will test if this is from thick filament activation by measuring x-ray diffraction patterns and myosin ATP turnover after PP2A exposure. I also test if this results from thin filament hyperphosphorylation, specifically at cTnI, in HFpEF. We have identified a novel threonine 181 residue of cTnI to be hyperphosphorylated in HFpEF, but its function is unknown. Phospho-null/mimetic transgenic cTnI Thr181 will be swapped into skinned myocytes from HFpEF patients, and myocyte tension measured. These studies will advance our understanding of the thick and thin filament in HFpEF and could pave the way for new therapies with small molecule sarcomere enhancers that target these mechanisms. PROJECT NARRATIVE Recently, we have demonstrated that patients with heart failure and preserved ejection fraction (HFpEF) with comorbid obesity have striking depression of right ventricular myocyte calcium activated force, with force negatively correlating with BMI. This finding has clinical implications, suggesting that the selective use of small molecule sarcomere enhancers might benefit patients with obese HFpEF. In this proposal, I aim to elucidate the mechanism of obesity mediated myocyte dysfunction, specifically exploring the impact of obesity on both the thick and thin filament in HFpEF. | Training, Individual | 6project_grants_public
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gen_fb6fa03ac62589b5300ba2262dd895c0 | Multiplexed analysis of secreted proteins from single-cells using high dynamic range nanovials | NIH | PARTILLION BIOSCIENCE CORPORATION | 1R43AI179363-01 | ABSTRACT Cellular secretions make up a significant portion of the proteome, playing a crucial role in governing a range of bodily functions – in particular immunity. Despite their significance, the study at cellular secretions at the single- cell level has been limited due to a lack of accessible technologies. An ideal assay would have single-cell resolution, measure several secreted products, and allow for recovery of cells for further downstream study. No one assay fulfills all of these requirements. The lack of methodologies to identify and interrogate cells which display high levels of secretory capacity has effectively stalled research into these potentially highly potent cells for cell therapies. The most common technique to characterize cell secretion at the single-cell level is the decades old ELISpot technology, however, this technology is limited in the number of secretions that can be measured and cells cannot be sorted based on the results of the assay. Thus, there is a critical need to develop accessible technologies which offer the capability to functionally screen and recover cells in a highly multiplexed secretion format. To address this gap, we will engineer nanovials, cavity-containing hydrogel particles, to create a robust 5-plex assay format capable of measuring five secreted cytokines from single cells, supporting several different workflows such as rare polyfunctional T cell sorting, or other immune cell screening by function. In the first aim of this project, we will develop nanovial formulations compatible with a 5-plex secretion assay by increasing the number of binding sites for secretion capture. We will also identify suitable antibody pairs and modification stoichiometry for IFN-gamma, TNF-alpha, GM-CSF, IL-2, and Granzyme B. In the second aim we will validate the nanovial single-cell assays by comparing the single-cell secretions of HLA-matched PBMCs activated by peptide presentation using both ELISpot and the developed nanovial assays. Successful completion of our aims will address critical gaps in traditional secretion-based profiling of single cells such as ELISpot or intracellular cytokine staining. This multiplexed assay will enable researchers to discriminate and recover highly functional cells which will spur innovation in both fundamental research and therapeutic development. NARRATIVE Cell secretions play a crucial role in many bodily functions, but there are currently no tools available that can measure multiple secretions from single cells and allow the cells to be recovered for further study. This project aims to develop accessible technologies that can measure the secretions of individual cells in a highly multiplexed format, which could lead to a better understanding of how cells function and potentially lead to the development of new cell therapies. | SBIR/STTR | 0business_rnd_innovation
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gen_58ed133c5022779e30eb49f666f6c9c2 | Cancer-associated fibroblasts promote thyroid cancer malignancy through Wnt signaling | NIH | VANDERBILT UNIVERSITY | 5F30CA281125-02 | PROJECT SUMMARY Many aggressive cancers have a robust tumor microenvironment composed of heterogenous stromal and immune cells. Although the advent of immune checkpoint inhibitors has shifted therapeutic targets of cancer research to include tumor-cell extrinsic targets, the therapeutic potential of targeting the tumor stroma remains underexploited. Recently, cancer-associated fibroblasts (CAFs) have been implicated as drivers of disease progression. From preliminary attempts to harness the therapeutic potential of targeting CAFs, it has become clear that targeting CAFs as a bulk population of cells will not be sufficient. As such, there have been efforts in breast and pancreatic cancer to define the heterogeneity of CAFs. These efforts have yielded diverse subtypes commonly described by two overarching groups: myofibroblast CAFs (myCAFs) and inflammatory CAFs (iCAFs). In pancreatic cancer, myCAFs are observed to be tumor-adjacent and iCAFs are more distant from tumor cells. While defining subtypes of CAFs is a necessary first step, the development of novel therapeutic approaches will likely require the identification of specific functions of CAF subtypes. To this end, Wnt2 has been identified as upregulated in CAFs from pancreatic, breast, and colorectal cancer, yet the role of CAF-driven Wnt signaling on tumor progression remains largely unknown. Anaplastic thyroid carcinoma (ATC) is a lethal disease (~3-5 month median survival) with an abundant tumor stroma and no efficacious treatment options. The composition of the tumor stroma in ATC has been largely unexplored. My preliminary work identifies a prominent fibroblast population in ATC that expresses WNT2. As ATC is known to have upregulated Wnt signaling relative to other thyroid neoplasms, this provides a unique opportunity to study the dynamics of CAF-driven Wnt signaling. The goal of this proposal is to define the CAF subtypes present in thyroid carcinoma and determine the functional role of CAF-derived Wnt2 on tumor growth. I hypothesize that distinct CAF populations promote tumor growth and invasion in thyroid carcinoma through Wnt signaling and have unique spatial relationships. To test my hypothesis, I will perform experiments in ATC models and papillary thyroid carcinoma (PTC) models. PTC is a predominantly indolent thyroid carcinoma that can transform to ATC in vivo, making it ideal for examining the ability of CAFs to promote disease progression. In aim 1, I will elucidate subtypes of CAFs present in ATC and PTC and probe Wnt ligand-receptor interactions. Further, I will determine spatial resolution of myCAF and iCAF fibroblast populations in thyroid carcinoma. In aim 2, I will utilize >40 primary patient thyroid carcinoma CAF cultures that our lab has collected to demonstrate the role of CAF-derived Wnt2 signaling both paracrine on PTC and ATC tumor cells and autocrine to shape the phenotype of CAFs. In completing these studies, I will for the first time define the heterogeneity of CAFs in thyroid carcinoma and characterize a potential novel therapeutic target applicable to CAFs in multiple cancer types. PROJECT NARRATIVE Cancer-associated fibroblasts (CAFs) are a heterogeneous stromal cell population that influence disease course and treatment responses in aggressive cancers. Anaplastic thyroid carcinoma has a substantial stromal component, yet the composition of the stroma and its role in promoting malignancy remain unclear. In this proposal, I will elucidate the subtypes of CAFs in thyroid carcinoma and investigate the tumor-promoting effects of CAF-driven Wnt signaling, providing a novel therapeutic target for a disease with an urgent need for new treatment options. | Training, Individual | 6project_grants_public
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gen_26086d5ac8bee1ef3702828109e2777b | Development of ultra-efficient antibodies for single cell mapping applications | NIH | EPICYPHER, INC. | 1R44AI174357-01 | PROJECT SUMMARY Histone post-translational modifications (PTMs) are some of the most widely studied epigenomic factors, and alterations in histone PTM abundance / distribution have been implicated in numerous disease etiologies. Epigenomic mapping of histone PTMs in limited cell populations or single cells (SCs) would provide the opportunity to study the epigenetic landscape of rare and heterogenous cell populations and be highly enabling for drug discovery research. The recent development of the antibody-mediated genomic mapping approach CUT&Tag (Cleavage Under Targets and Tagmentation) permits the study of select, abundant histone PTMs using very few cells and even SCs. Despite this progress, ultra-low input and SC CUT&Tag assays still present a unique challenge, and have not yet been successfully applied to many challenging targets, such as less abundant histone PTMs. Indeed, to maximize data yield per cell, ultra-low input and SC CUT&Tag assays require antibodies to exhibit high on-target epitope binding with minimal off-target binding, which most commercial antibodies do not offer. We envision a new class of “SC-grade” antibodies that deliver ultra-efficient histone PTM binding for dramatically increased CUT&Tag assay sensitivity, improving reliability and providing access to new targets that are currently intractable. Here, EpiCypher will leverage a novel antibody development pipeline to generate ultra-efficient, “SC-grade” antibodies to unlock the potential of genomic mapping technology for next- generation ultra-low input / SC applications. Unlike traditional antibody development pipelines that use histone peptides for screening, a central innovation of our strategy is the implementation of recombinant modified designer nucleosome technology during antibody development. In Phase I equivalent studies, we used our novel approach to select and validate ultra-efficient antibodies for two key histone PTM targets (H3K4me1 and H3K4me3), generating antibodies that exhibit a >5-10x increase in nucleosome capture efficiency vs. current best-in-class antibodies. Importantly, these ultra-efficient antibodies generated significantly greater signal-to- noise in genomic mapping assays that employ low cell inputs, demonstrating strong proof-of-concept for our approach. In Phase II, we will leverage this validated antibody development pipeline to develop a suite of ultra- efficient antibodies and use these reagents to develop low input and SC CUT&Tag assays for breakthrough immunology research. Toward this goal, we will first develop and screen antibodies for high-value histone PTM targets (Aim 1). We will then scale up production and rigorously validate antibody lots in CUT&Tag assays using both low input and SC workflows (Aim 2). Finally, we will test the application of our next-generation ultra-efficient antibodies to enable cutting-edge immunological research and provide our antibodies and validated protocols to leading epigenetics laboratories for beta testing (Aim 3). This research project will result in the development of a new class of histone PTM antibodies that will be used to increase the utility of CUT&Tag assays for breakthrough chromatin research and drug discovery. PROJECT NARRATIVE Histone post-translational modifications (PTMs) are some of the most widely studied epigenomic factors, and alterations in histone PTM abundance and distribution have been implicated in numerous disease etiologies. However, efforts to map histone PTMs in limited samples and single cells, such as rare primary immune cells and clinical samples, have been hindered by the lack of high-quality antibodies. To meet this need, EpiCypher is developing a novel antibody development pipeline to create ultra-efficiency antibodies that enable low and single cell genomic mapping assays. | SBIR/STTR | 0business_rnd_innovation
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gen_3d54979d3e8ef83289cea97b69251448 | Tumor Monorail Device for Serial Glioblastoma Biopsy | NIH | EXVADE BIOSCIENCE, INC. | 1R44CA285039-01 | Project Summary/Abstract Glioblastoma (GBM) is one of the most common and deadliest form of malignant brain tumors, with median patient survival of 12-15 months and five-year survival of less than 5%. The current standard of therapy for GBM comprises surgical resection then radiation and chemotherapy. However, due to the heterogeneity and invasive nature of GBM tumor cells there is a high rate (~80%) of tumor recurrence, leading to dismal survival rates that have not changed significantly in over 50 years. One of the primary hurdles to improving these out- comes is the lack of reliable and accurate means to monitor tumor progression and treatment response. The current standard methods of tumor monitoring, direct tissue biopsy and external imaging, are not able to safely provide accurate, focal, longitudinal information about the tumor progression and treatment response that would allow clinicians to modify treatment regimen to improve survival outcomes. Here we propose the Tumor Monorail as a platform that allows direct, serial access to tumor material, providing critical information about tumors in real time that will help clinicians improve active treatment management and patient survival. The Tumor Monorail is a Breakthrough Designated device and has been the subject of multiple FDA pre-sub- mission meetings and extensive verification and biocompatibility testing. By leveraging design and material se- lections with a long history of safe clinical use, the Tumor Monorail can safely provide access to this typically inaccessible tumor in an outpatient setting. This will provide clinicians with an unprecedented amount of infor- mation about tumor genetics and treatment response in real time that is critically important to improving out- comes for the treatment of GBM. The potential impact of this paradigm shifting diagnostic tool is wide ranging, including enhancing the efficacy of current standard of care and novel treatment regimens, increasing clinical trial efficiency by accelerating patient placement and data collection, removing uncertainty about treatment effi- cacy and tumor progression inherent in imaging, and more. The aims of this proposal are focused on optimization and clinical translation of the Tumor Monorail as a plat- form for longitudinal GBM sampling. In the Phase 1 portion of the proposal we will first optimize the sampling ability and cellular migration in the device and perform multiple pre-clinical verification tests that will improve usability and ease regulatory approval. In the Phase II portion we will validate the device efficacy in concert with standard of care treatment in a rodent model and perform more FDA requested pre-clinical testing that will confirm long term explantability, clinical usability, and preparation of the device for rapid clinical translation. These activities will ensure that the Tumor Monorail is well positioned for submission of an Investigational De- vice Exemption (IDE), clinical translation, and rapid adoption to provide a new treatment path for GBM focused on active disease management and individually targeted, responsive treatment that would allow clinicians to tailor interventions in real time, increasing patient outcomes that have been stagnant for decades. Project Narrative Glioblastoma Multiforme (GBM) is a highly aggressive form of brain cancer with a fatality rate close to 100% despite aggressive therapies, primarily because the invasive nature and inaccessibility of the tumors makes recurrence after treatment very common and treatment efficacy hard to assess. We have developed a system that can provide serial direct tissue biopsy of the tumor, allowing for collection of data about the tumor genetic profile and treatment efficacy that will allow clinicians to make more informed decisions about treatment course and accelerate entrance into suitable clinical trials. This information will empower clinicians by giving them access to an unprecedented level of information about tumor response to treatment in real time, allowing them to enhance the effectiveness of current treatments, increase the efficiency of clinical trials, and finally improve GBM outcomes that have not changed in decades. | SBIR/STTR | 0business_rnd_innovation
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gen_ba76733fcaf394b4ddaad0330ab9e79c | Impact of interferon λ signaling on lung macrophage function and type 17 immunity during bacterial super-infection following influenza | NIH | UNIVERSITY OF PITTSBURGH AT PITTSBURGH | 1F31HL164031-01A1 | Abstract Lung diseases and syndromes caused by respiratory pathogens represent a leading cause of death worldwide. Each year, influenza infections result in a significant number of fatalities, a majority of which are complicated by secondary bacterial super-infection. Primary influenza infection has been shown to increase susceptibility to secondary methicillin-resistant Staphylococcus aureus (MRSA) infection by altering the pulmonary host immune response and damaging the lung epithelial barrier, leading to increased morbidity and mortality. Macrophages, both lung-resident and those recruited to the lung, are important in super-infection resolution as they engulf, degrade, and present bacterial antigen to adaptive immune cells, ultimately leading to activation of type 17 cells, which promote pathogen clearance. While the role of interferon-(IFN)α/β during super-infection has been well characterized, type III IFNs have not been as extensively studied within the context of the lung. Data shows that IFNα/β are involved in type 17 attenuation after primary influenza infection, which may indicate that IFNλ exhibits similar inhibitory functions due to overlapping signaling pathways, although the potential for unique functions on lung cells is unresolved. Our lab has preliminary data suggesting that administration of exogenous IFNλ during super-infection reduces bacterial uptake by neutrophils and monocyte-derived cells, but the specific cell subsets impacted are unknown. I hypothesize that lung-resident macrophages are sensitive to IFNλ and that IFNλ signaling impairs phagocytosis and the type 17 immune response during super-infection. In the proposed studies, I will determine which myeloid subsets express the IFNλ receptor (IFNLR1) and identify how intact or disrupted IFNλ signaling broadly impacts lung injury and resolution after infection. More specifically, these experiments will determine how IFNλ impacts MRSA uptake and the initiation of a type 17 immune response during super- infection. IFNλ administration has been considered for therapeutic potential, and the outcomes of this proposal will shed light on potential caveats to the use of IFNλ as a possible treatment method during super-infection. Further, demonstration of the effects of IFNλ on myeloid cells will potentially be applicable to several other settings where an antiviral interferon response is observed. Project Narrative A severe complication of influenza infection is secondary Staphylococcus aureus, and previous data has shown that type I interferons produced during influenza infection result in a defective bacterial immune response. Type III interferons are a more recently discovered family of interferons that share signaling pathways with type I interferons. This project will determine the role of type III interferons in impairment of the immune response against secondary bacterial infection by decreasing lung macrophage function and subsequent type 17 immune induction. | Training, Individual | 1fellowships_scholarships
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gen_ffa030e4e4811d90f67565456b661350 | Einstein-Montefiore Clinical and Translational Science Award Hub | NIH | ALBERT EINSTEIN COLLEGE OF MEDICINE | 5UM1TR004400-02 | The Harold and Muriel Block Institute for Clinical and Translational Research (ICTR) at the Albert Einstein College of Medicine and Montefiore Medical Center serves as the home of our CTSA program. The vision of the ICTR is to improve the health of the Bronx, and other communities that disproportionately and unjustly suffer from poor heath and premature death, by accelerating the translation of biomedical discoveries into effective and sustainable disease prevention and treatment strategies. Created in 2007, the ICTR has transformed clinical and translational research (CTR) throughout Einstein and Montefiore by creating a robust research environment; re- engineering CTR processes; integrating research and healthcare; and developing strong community relationships. The ICTR theme of “Building Bridges in the Bronx and Beyond” underscores the importance of bridging gaps between our researchers, health system leaders, clinicians, patients, communities, and CTSA partners to advance translational science and health equity. The specific aims of the ICTR are to: (1) Catalyze innovations that will enhance the efficiency and effectiveness of translational research. We will support and fund studies with high potential to overcome major CTR roadblocks and health inequities; create methodological and informatics translational science innovations; improve CTR operations, and enhance dissemination and implementation strategies. (2) Engage communities, patients, and other partners early and throughout the translational process. Our new Community and Stakeholder Engagement Research module will transform our learning health system into a “learning health research community”; promote active and continuous bidirectional communication with communities, patients and other partners; facilitate research to identify and mitigate social determinants of health, and enhance uptake of evidence-based programs by target populations. (3) Develop and implement state-of-the-art clinical research and informatics resources and services to improve the rigor, safety, efficiency, effectiveness, and generalizability of CTR. (4) Train, develop, and maintain a skilled, multidisciplinary, and diverse translational workforce to support and lead high quality research with new training and pathway programs to ensure members of historically excluded groups engage in CTR and become research leaders. (5) Partner with other CTSA hubs and the CTSA consortium to accelerate CTR and rapidly respond to urgent public health needs. Our aims are aligned with the new CTSA program goals and will enable the ICTR to maximally contribute to the collective efforts of the national collaborative CTSA consortium to deliver more treatments to more patients more quickly in the Bronx and beyond. The Harold and Muriel Block Institute for Clinical and Translational Research (ICTR), a partnership between the Albert Einstein College of Medicine and Montefiore Medical Center, aims to create a robust and collaborative research enterprise that is committed to advancing clinical and translational science and promoting health equity. The ICTR will catalyze innovations to overcome research roadblocks across the translational spectrum, and will create and maintain a skilled and diverse research workforce, to accelerate the process of turning discoveries in the laboratory, clinic, and community, into health benefits for all. | Non-SBIR/STTR | 2institutional_funding
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gen_f81a1428a2e9554d25a7773fa27d01c1 | Southwest Center on Resilience for Climate Change and Health (SCORCH) | NIH | UNIVERSITY OF ARIZONA | 1P20ES036112-01 | PROJECT ABSTRACT – Component: Overall Arid lands are home to one in three people, totaling a population of more than 2 billion spanning the globe. Arid land communities are facing multiple climate change-exacerbated threats impacting health including extreme heat events, wildfires, dust storms, biodiversity loss, emerging pathogens, poor air quality, and drought. The Southwest Center on Resilience for Climate Change and Health (SCORCH) brings together transdisciplinary research groups to conduct team-science projects addressing the health needs of arid lands communities adapting to climate change. The Center's overarching mission is to improve health equity across the lifespan by enhancing community partnerships and supporting adaptation efforts by Indigenous, Latinx, low-resource urban, and rural communities in the Southwestern United States and globally. Based at the University of Arizona (UArizona), home of internationally recognized climate science and adaptation researchers and Centers, SCORCH will serve as a foundation for expanding UArizona campus initiatives aiming to increase health research at the intersection of climate change science. The three-year planning phase will be used to identify researchers whose expertise align with climate change and health across UArizona and the region, build transdisciplinary teams, identify priority research areas for community adaptation planning, and implement two research projects to develop our initial Research Focus Group (RFG) themes. Our initial three RFGs build on the expertise of the current SCORCH team members and are purposefully broad to encompass evolving research priorities. These three themes include: 1) Health impacts of extreme weather events; 2) Forecasting and early warning of climate change health outcomes; and 3) Adaptive responses in the built environment. Research Project 1 aligns with RFG 2 and 3, to develop an assessment tool that can predict potential health outcomes of greenspace designs. Research Project 2 aligns with RFG 1 to examine the role of maternal exposure to extreme heat and long-term child health outcomes. Through community engaged activities founded on respect and trust, led by the Community Engagement Core, and novel data visualization services, led by the Integrated Data Visualization Core, we will deepen existing and develop new partnerships with academic and community entities with diverse lived experiences and knowledge frameworks. The geographic location of SCORCH in the Southwestern United States provides unique research opportunities to support adaptation and resilience efforts of Indigenous, Latinx, low-resource urban, and rural communities in the region as well as addressing the unique circumstances found in borderland areas. The potential international reach of SCORCH enables high-impact climate change and health initiatives that will translate globally. PROJECT NARRATIVE – Component: Overall The Southwest Center for Resilience in Climate Change and Health (SCORCH) will bring together transdisciplinary research groups to conduct solutions-oriented team-science projects responsive to the human health needs of Arid Lands communities adapting to climate change. The Center’s overarching mission is to improve health equity across the lifespan by enhancing existing community partnerships and supporting adaptation efforts by Indigenous, Latinx, low resource urban and rural communities in the southwestern United States and globally. Research will span several areas including: Research Focus Groups; 1) Health effects of extreme weather events, 2) Forecasting and Early Warning, and 3) Adaptive Responses to the Built Environment. | Research Centers | 6project_grants_public
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gen_a475163d8f71bcc387196ffc232a4e2a | Molecular MR-PET to characterize malignant transformation and identify therapeutic vulnerabilities in human IDH-mutant gliomas | NIH | UNIVERSITY OF CALIFORNIA LOS ANGELES | 1F30CA284809-01 | PROJECT SUMMARY/ABSTRACT The World Health Organization (WHO) classification of gliomas has been steadily shifting from a histological classification towards a molecular classification. For example, isocitrate dehydrogenase (IDH) mutational status is a critical feature of the recent 2021 WHO classification. Compared to IDH-wild-type (IDH-wt) gliomas, IDH- mutant (IDH-m) gliomas have distinct clinical characteristics such as accounting for most low-grade gliomas (LGGs; grade 2), having better prognosis, growing slower, and affecting a younger patient population compared to IDH-wt gliomas. However, all WHO grade 2 IDHm gliomas are expected to eventually become malignant higher-grade (WHO grades 3-4) gliomas in a process known as malignant transformation. Upon malignant transformation, patients with IDHm gliomas have a significantly worse prognosis. Thus, early, non-invasive imaging biomarkers of IDHm glioma malignant transformation may allow for earlier identification of treatment failure and appropriate therapeutic interventions. Magnetic resonance imaging (MRI) is critical for the management of patients with IDHm gliomas. Currently, identification of malignant transformation in patients with IDHm gliomas involves the emergence of contrast- enhancing areas on T1-post-contrast MRI in previously non-enhancing grade 2 gliomas. However, advanced MRI biomarkers sensitive to acidity, perfusion, and cellular density may provide earlier identification of the tumor microenvironment changes associated with malignant transformation and earlier identification of treatment failure. Furthermore, combining our lab’s pH-sensitive MRI with metabolic positron emission tomography (PET) imaging may yield deeper insights into the tumor microenvironment, particularly for metabolic shifts associated with malignant transformation and new IDH inhibitor targeted therapies that inhibit the mutant IDH enzyme. As a result, this proposal seeks to identify molecular MR-PET biomarkers associated with malignant transformation and successful IDH inhibition of IDHm gliomas. In Specific Aim 1, we will establish a sequential order of advanced MRI biomarkers in IDHm gliomas undergoing malignant transformation using pH-sensitive, perfusion, diffusion, and anatomical MRI and then validate MR-PET biomarkers of IDHm gliomas with histopathological markers from targeted surgical biopsies. In Specific Aim 2, we will utilize pH-sensitive MRI and PET to evaluate metabolic perturbations in IDHm gliomas following successful IDH inhibitor therapy. The proposed studies may improve IDHm glioma management by establishing imaging biomarkers of malignant transformation and successful IDH inhibitor treatment response. PROJECT NARRATIVE Isocitrate dehydrogenase (IDH)-mutant gliomas have distinct metabolic characteristics and therapeutic vulnerabilities. However, advanced imaging biomarkers of IDH-mutant glioma remain limited for malignant transformation and new IDH inhibition therapy. Our proposed studies will utilize molecular MR-PET imaging to identify imaging biomarkers that could improve the clinical management of IDH-mutant gliomas. | Training, Individual | 6project_grants_public
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gen_1c5e0423159384e7b7966fbc83f8c98b | ADDITIVE MANUFACTURING OF PDMS MICROFLUIDICS | NIH | PHASE, INC. | 2R44TR003968-02 | Development of new therapeutics often fails in human clinical trials due to the biological differences between humans and animal models and the inability of current in vitro models to accurately recapitulate the in vivo state. As such, in vitro microfluidic (MF) models have seen significant growth and become a key tool for understanding biological systems, and for testing and development of new therapeutics. Innovation in microfluidics, however, is limited by materials and manufacturing challenges associated with conventional processes such as soft lithography, injection molding, and mechanical milling. Additive manufacturing (AM), also referred to as 3D printing, has been heralded as the solution to these manufacturing challenges and AM additionally offers broad design freedom not accessible via conventional manufacturing. However, AM faces a critical hurdle: the limited ability to 3D print conventional (thermally-curable) polydimethylsiloxane (PDMS), the most widely established R&D microfluidic material. Despite the potential manufacturing and design benefits, AM has not been broadly adopted for MF production due in large part to the potential material risks. Of the commercially available AM processes and those being researched, none offer a clear path to commercial 3D printing of conventional PDMS MF devices. Our hypothesis is: combining the knowledge-base and familiarity of conventional PDMS with our 3D PDMS process will fundamentally change the way microfluidics are fabricated and unlock the design freedom of additive manufacturing for the MF community, which will lead to significant advancements of in vitro MF models. Building upon our successful Phase I effort — during which we demonstrated the ability of our patent-pending 3D PDMS process to 3D print MF devices from conventional PDMS — this Phase II effort focuses on developing a pilot-scale commercial 3D PDMS system and using the 3D PDMS process to fabricate cutting edge in vitro blood-brain-barrier models for testing by our collaborators at Virginia Tech. They recently developed a MF BBB model containing a nanofiber basement membrane mimic which demonstrates a superior ability to recapitulate the in vivo BBB architecture. In Phase II, the team will optimize the architecture of the nanomembranes and then design and demonstrate a commercially producible 3D PDMS MF nanomembrane BBB model with integrated electrodes. We will also collaborate with the Nadkarni group at Harvard MGH to characterize the PDMS curing kinetics in 3D PDMS printing using laser speckle rheology. Aim 1: Operational Pilot-Scale 3D PDMS System. The objective of this aim is to design and a build pilot-scale 3D PDMS system. Milestone 1A: 3D PDMS Simulation & Model Accurately Predict Curing within +/-10%; Milestone 1A: 3D PDMS Simulation Model Accurately Predicts Curing within +/-10%; Milestone 1B: 3D PDMS unit achieves 200 mm3/hr build rate for MF device. Aim 2: 3D Printed Nanofiber Blood-Brain-Barrier Model. The objective of this aim is to 3D print a highly reproducible BBB model which incorporates a nanofiber membrane and integrated TEER electrodes. Milestone 2A: Transport master curves for nanofiber membranes developed; Milestone 2B: Optimized nanofiber BBB model demonstrated by a 20% increase in TEER values for a co- culture sample as compared to a monoculture sample. Project Summary/Abstract Narrative Microfluidics (MF) are the test tubes of the digital age and play a vital role in drug discovery, biotechnology, lab- and organs-on-a-chip, personalized point-of-care diagnostics and treatment, disease research, and more. Phase, Inc. is developing a new 3D printing technology to create PDMS microfluidics that believe will fundamentally change the way PDMS microfluidics are fabricated and unlock the design freedom of additive manufacturing for the MF community, which will lead to significant advancements of in vitro MF models. This new 3D printing technology will allow researchers to quickly design and create microfluidic devices in a matter of hours – as opposed the weeks it now takes. This will enable researchers to more quickly test drugs to treat illness and decrease the time needed for new medicines to reach the market and, in turn, patients. Narrative | SBIR/STTR | 0business_rnd_innovation
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gen_9095655c8f382e87af126ecc5e067777 | Senescent hepatocytes mediate reprogramming of immune cells in acute liver failure | NIH | UNIVERSITY OF KANSAS MEDICAL CENTER | 5F31DK134197-02 | PROJECT SUMMARY Acute liver failure (ALF) is characterized by coagulopathy, hepatic encephalopathy, jaundice and multi-organ failure. Fifty percent of all ALF cases in the United States and UK are due to acetaminophen (APAP) overdose. Supraphysiological doses of APAP overwhelm safe detoxification pathways in the liver leading to excessive bioactivation of APAP by Cyp2e1 into the highly reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI). This initiates a cascade of intracellular events driving hepatocyte death. An extensive body of work has elucidated the molecular mechanisms of hepatocyte necrosis during APAP overdose, but detailed mechanisms involved in the development of ALF have been largely unexplored. The innate immune response after liver injury plays a critical role in liver recovery in the human relevant mouse model of APAP overdose. However, immune cell dysfunction has been implicated in the development of ALF. Though crosstalk between stressed hepatocytes and immune cells actively supports liver recovery, persistent and prolonged hepatocyte stress may alter this communication network, resulting in immune cell reprogramming towards detrimental phenotypes which facilitate ALF. Excessive cell stress can elicit temporary or permanent cell cycle arrest, a cell fate decision called senescence. Some cells acquire a senescent associated secretory phenotype (SASP) which can elicit pleotropic effects on nearby cells and the tissue microenvironment. Our preliminary data demonstrate that Klf6 and p21 induce hepatocyte senescence after a severe APAP overdose and that these hepatocytes have an active SASP, enriched in the cytokine Cxcl14 which persists in circulation. These key findings lead us to hypothesize that upon severe APAP-induced liver injury, prolonged hepatocyte senescence results in a sustained secretome exposure enriched in Cxcl14 causing immune cell reprogramming impeding tissue repair and injury resolution. This hypothesis will be tested by pursuit of two specific aims. Experiments in Aim 1 are designed to evaluate how Klf6 induces p21 and Cxcl14 and the influence of in vivo silencing of Klf6 on APAP-induced senescence and liver recovery after injury. Aim 2 will use single-cell RNA sequencing in combination with wet-lab approaches to define how the critical SASP component Cxcl14 alters the global communication network between senescent hepatocytes and immune cells after a severe APAP overdose. Collectively, these data will define the molecular mechanisms responsible for sustained induction of hepatocyte senescence, its relationship to the induction of a senescent associated secretory phenotype, and the signaling interactions between senescent hepatocytes and the innate immune response. This proposed work will provide valuable insights into why ALF develops after severe APAP overdose and will assist in addressing this unmet clinical need. PROJECT NARRATIVE Acute liver failure (ALF) is associated with a dysfunctional immune response, but the reason for this is unclear. My proposal will investigate if senescent hepatocytes reprogram infiltrating immune cells interfering with their capacity to promote liver regeneration after injury. This work will elucidate the role of hepatocyte senescence in influencing the liver microenvironment to facilitate ALF and will support the identification of novel therapeutic approaches to address this unmet clinical need. | Training, Individual | 6project_grants_public
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gen_99f597ab514511cac67f319c5dfa68af | NIAID Division of AIDS (DAIDS) Chemotherapeutic Agents Repository | NIH | FISHER BIOSERVICES, INC. | 75N93021D00012-0-759302400001-1 | Not available | R and D Contracts | 0business_rnd_innovation
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gen_adbc44fe348d8e63998d31885f1bd98a | i-AKC: Integrated AIRR Knowledge Commons | NIH | UT SOUTHWESTERN MEDICAL CENTER | 5U24AI177622-02 | PROJECT SUMMARY/ABSTRACT: Immune receptors of the adaptive immune system (antibody/B-cell or T-cell receptors, or AIRR data) are designed to recognize and remove pathogens, and also recognize and preserve self-molecules. Therefore, these receptors have to be highly variable; it has been estimated that the number of possible human B-cell receptors approaches 1013. In addition to the diversity of these receptor sequences, the genes that underlie the production of these receptor molecules are highly diverse and complicated, and the data describing how these receptors bind to antigens (such as influenza) are also highly complex. Repositories to curate, analyze, and share these data are necessary to characterize B/T cell function in disease, as well as facilitate the discovery of new vaccine leads and therapeutic monoclonal antibodies to suppress autoimmune disease and cancer. Such data repositories are available, but they tend to focus on only one aspect of the data. Given that these repositories typically have been developed independently, the primary data and associated metadata (age, demography, sex, etc.) of the samples are stored in non-compatible forms, and in addition, the enormous size and complexity of the data make data sharing and integrated analyses extremely challenging. The goal of the proposed research is to establish the integrated AIRR Knowledge Commons (i-AKC), a novel knowledgebase that will allow seamless access, exploration, analysis, querying, and downloading of these various data types from a single point of entry. Our approach will be based on the very successful AIRR Community initiative, a group of immunologists, bioinformaticians, and experts in ethics and data sharing who have worked together since 2015 to develop protocols and standards for analysis and data sharing tools. One of the outcomes of the AIRR Community is the AIRR Data Commons, a set of data repositories that store the immense immune receptor repertoires that underlie the adaptive immune response. The proposed research takes the next important step of integrating (1) the AIRR Data Commons with repositories of (2) antigen/receptor binding and (3) germline immune genes. Steps to producing the i-AKC are (1) develop a common data model and establish common data elements relying on existing ontologies and community standards, (2) integrate the data using innovative algorithms and automation tools and enrich it with new knowledge derived from algorithms operating on the integrated data, and (3) community building. Using the i-AKC, researchers will, for example, be able to discover receptor sequences based on metadata or sequence searches, seamlessly examine information on the germline genes underlying these receptor sequences or examine what is known about the binding targets of these receptors. This novel and innovative knowledgebase will facilitate data and knowledge exploration that would be prohibitively difficult using sets of “siloed” repositories and will greatly accelerate biomedical research in autoimmune disease, infectious disease, transplantation, and cancer and directly improve patient care. PROJECT NARRATIVE The adaptive immune response is shaped by a constellation of factors including genetics, immune preparedness, and antigen exposure that can protect us from or predispose or drive us to illness. While isolated data repositories exist that cover each of these factors, the proposed work will harmonize, integrate, and enhance those resources to enable a holistic understanding of adaptive immune responses. The systems-level analysis made possible by this knowledge integration will improve public health by accelerating the use of adaptive immune repertoire data to develop new therapeutics, diagnostics, and patient monitoring. | Other Research-Related | 7research_infrastructure
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gen_e95833b1c6f1cf20f2c55078aede28f4 | Elucidating the Host Metabolic Response to Consumption of Kombucha-associated Microorganisms | NIH | UNIV OF NORTH CAROLINA CHAPEL HILL | 1F31AT012138-01A1 | PROJECT SUMMARY Kombucha is a popular fermented tea that contains probiotics. This beverage has seen a surge in popularity in the United States since the turn of the century and is purported to have many health benefits. Some of these health claims have been cursorily examined, however, none have been rigorously tested and the mechanistic interactions between the microbial components of Kombucha and the host remains unexplored. I will elucidate the host metabolic response to consumption of Kombucha-associated microbes (K. microbes), thereby informing its use in complementary health approaches. The impact of individual probiotic microbes on human health is difficult to deconvolute as humans consume a complex diet, have trillions of gut microbes (including many unidentified species), and measuring host-microbe interactions is not feasible in human subjects. Therefore, animal model systems are essential to investigate the effects of consuming probiotics, including those in Kombucha, on host physiological processes. Caenorhabditis elegans is an excellent model system to explore how K. microbes modulate the host pathways that govern lipid homeostasis, because their microbiomes are easily manipulated through the food source provided and they are a well-established system to study metabolism and the aging process in vivo. I have established a standardized method to maintain C. elegans on a diet exclusively consisting of K. microbes that is consistent with the community found in the fermenting culture (confirmed through 16S rRNA sequencing). In preliminary investigations, I observed that populations of C. elegans exclusively consuming K. microbes, as compared to a control diet (E. coli, the standard laboratory food source), have altered expression of core lipid metabolism genes (e.g., beta-oxidation, fatty acid desaturation), decreased fat levels, and an increased median lifespan. Critically, the molecular mechanisms by which K. microbes alter host physiology is completely unknown. Therefore, I plan to use molecular and genetic approaches in C. elegans to systematically identify the molecular mechanisms that govern the host response to K. microbe consumption and elucidate the components of Kombucha that are necessary and sufficient to confer the observed metabolic and lifespan phenotypes. The proposed experiments will provide unprecedented insight into the mechanism by which K. microbe consumption reconfigures host metabolism. PROJECT NARRATIVE Kombucha, a fermented tea that contains probiotic microbes, has seen a surge in popularity in the United States since the turn of the century. Kombucha is purported to have many health benefits, however, none have been rigorously tested and the molecular relationship between the microbial components of Kombucha and the consumer remains unexplored. The impact of individual probiotic microbes on human health is difficult to deconvolute, therefore, I will use C. elegans as a model to elucidate the molecular mechanisms by which Kombucha-associated microbes may promote health and longevity. | Training, Individual | 1fellowships_scholarships
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gen_7d5be766c3e477103a3213c5c1b61a36 | Johns Hopkins Retinal Degenerations and Visual Electrophysiology Conference 2023. | NIH | JOHNS HOPKINS UNIVERSITY | 1R13EY035562-01 | Project Summary/Abstract This application seeks to support three biennial editions of the Johns Hopkins Retinal Degenerations and Visual Electrophysiology Conference. These meetings will continuously update early-stage investigators, trainees, clinicians, and scientists on the latest translational and clinical research on Inherited retinal diseases (IRDs). In addition, the conference will address multiple identified gaps in knowledge in interpreting visual function tests, including electrophysiology and microperimetry. The meetings will be held biannually in September in Baltimore, Maryland. The specific aims covered by this conference include 1) understanding the cellular and molecular basis of selected IRDs, 2) reviewing the recommendations from the Society of Clinical Electrophysiology of Vision (ISCEV) regarding visual neurophysiology testing, 3) reviewing the structural and functional outcome measures of IRDs, including those relevant to research subjects with ultra-low vision, 4) analyzing data and results from current treatments in development, especially those in Phase I, II, and III clinical trials and large animal studies, with an emphasis on retinal stem cells and gene therapy, and other treatment modalities, and 5) reviewing aspects relating to equitable access to clinical care and research for IRD patients, and ethical considerations unique to people with vision loss due to IRDs. The requested funds will support the attendance of trainees and early-career investigators, travel awards, and diversity awards to support women, under- represented minorities (URMs), and international participants, including those from developing countries. These meetings will be an ideal opportunity for trainees of diverse backgrounds, early-stage investigators, under- represented minorities, and international trainees to network and learn from leaders in the field of retinal degeneration. In addition, we hope this meeting will encourage multidisciplinary and international collaboration between clinicians and investigators to develop novel therapies and clinical trials end points. Project narrative Considering the current rapid development of novel treatments for inherited retinal diseases (IRDs), we propose to organize a scientific conference focusing primarily on translational and clinical IRD research, to complement other basic science conferences. The proposed conference will emphasize latest developments in cell therapy, gene therapy, genome editing, pharmacotherapy and nanomedicine, artificial intelligence for case detection and progression analysis, structural and functional IRD outcome measures, Phase I–III clinical trial data, ethics and equity, and surgical delivery in humans. We have prioritized avenues to promote the participation of trainees, women, and under-represented minorities while fostering international ideas exchange. | Other Research-Related | 6project_grants_public
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gen_b40741736f54095e4adca01b75ae4117 | Development of CA-IL-12 for Triple Negative Breast Cancer | NIH | CYTONUS THERAPEUTICS, INC. | 5R44CA250887-03 | Most cancer patients die as a result of metastatic disease and our inability to effectively deliver therapeutic drugs into the anatomical niches where cancer cells thrive. Thus, there is a major unmet need to develop therapeutic strategies that effectively target cancer cells in the local tumor microenvironment (TME) while minimizing peripheral toxicity. Cytonus Therapeutics and UCSD Moores Cancer Center has co-developed a highly innovative first-in-class drug transporter platform (CargocytesTM) that is a safe and effective means to deliver therapeutic drugs to treat primary and secondary tumors. Cargocytes possess several unique features that we leverage for precision delivery of cancer therapeutics to patients with metastatic disease. First, Cargocytes possess innate tumor trophic properties and are engineered with additional homing controls that allow for precise, predictable, and safe delivery of therapeutic cargo to the TME. Moreover, because they lack a rigid nucleus, they clear critical FDA barriers to safety due to their inability to transfer or inappropriately express genomic DNA. In addition, they are smaller and more malleable than nucleated carriers and better able to penetrate deep within tumor tissue and metastatic foci. Furthermore, they retain all biosynthetic machinery and can express biological cargo within the TME. While Cargocytes can deliver a wide range of therapeutic cargoes, they are ideally suited for locally delivering potent immune activating agents, such as IL-12, into the immunologically “cold” TME. Our phase I proof-of-concept work shows that Cargocytes precisely deliver IL-12 into the TME, deeply penetrating and interdigitating within metastatic foci when delivered intratumorally or systemically and resulting in a dramatic reduction in metastatic burden that can be measured within 24 hours. While this was demonstrated using Cargocytes that secrete IL-12 (CA-IL-12), we have since focused on development of Cargocytes for intravenous delivery, a more desirable administration route for clinical development and treatment of systemic metastatic disease. Therefore, Phase II work will evaluate the potential of intravenously administered Cargocytes to deliver secreted (CA-IL-12) or surface contained (CA-scIL-12) to breast cancers that have metastasized to lungs or liver. Our hypothesis is that Cargocytes will home to metastases, deliver IL-12 deep within disease foci, and break immune tolerance when used in combination with ICB. This will lead to i) local and systemic antitumor immunity, ii) a reduction in metastatic burden, iii) improved tumor-free and overall survival, and iv) durable antitumor immunity. Three specific aims are outlined to test this hypothesis. Aim 1 will determine the abilities of peripherally administered CA-scIL-12 and CA-IL-12 to locally deliver IL-12 to primary and secondary tumors and to reprogram innate and adaptive anti-tumor immune responses. Aim 2 will then evaluate the ability of our lead CA-IL-12 medicine selected in aim 1 (CA-IL-12L) in combination with PD-1 antibody in the adjuvant setting to effectively treat ICB refractory tumors and generate systemic antitumor and antimetastatic immunity. Aim 3 will test the therapeutic efficacy of CA-IL-12L and ICB in a robust preclinical model of spontaneous breast oncogenesis that preserves tumor heterogeneity. Narrative. Cancer is a systemic disease and conventional treatment strategies that are administered systemically, ultimately fail due to an inability to achieve antitumor efficacy at tolerable doses for the patient. Cytonus has developed a first-in-class, precision delivery platform, called CargocytesTM, that is a safe and effective means to target therapeutic drugs to primary and secondary tumors. In this phase II study, we will evaluate the therapeutic efficacy of systemically-delivered, locally-active, membrane-tethered or secreted IL-12 to induce durable systemic antitumor and antimetastatic immunity. | SBIR/STTR | 0business_rnd_innovation
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gen_f869befa43d0cb711400f04ce4581493 | Metabolism Core | NIH | WASHINGTON UNIVERSITY | 5U54DK137332-02 | Project Summary/Abstract: Metabolism Core The Metabolism Core (Meta-Core) is a Biomedical Resource Core within the Washington University Chronic Kidney Disease National Resource Center. Chronically injured kidneys have altered metabolism, and recent data suggests that these metabolic changes play a causative role in progressive decline in kidney function. The ability to interrogate metabolism is crucial to understanding chronic kidney disease pathophysiology, but there are a number of barriers for kidney researchers to do so. First, many investigators interested in chronic kidney disease do not have expertise in metabolism and metabolic assays. Second, many of these assays require expensive equipment not readily available to many labs. To address these issues, the Meta-Core faculty consisting of Leslie Gewin, M.D., Core Director, Brian Finck, Ph.D., Associate Core Director, Gary Patti, Ph.D., Core Collaborator, and Leah Shriver, Ph.D., Core Collaborator, will perform consultations with Meta- Core users to guide and design the best metabolic assay to answer the research question. Several assays will be available to the Meta-Core users to interrogate metabolism at the cellular or whole kidney level. These assays include Seahorse bioflux analyses with the use of primary cells or freshly isolated tubules ex vivo, both more representative of the highly oxidative proximal tubules than commercially available primary human tubule cells or conditionally immortalized tubule cells. We can measure oxidation of fatty acids or glucose/pyruvate in kidney tissue ex vivo using radioactive substrate oxidation assays. The 3H-palmitate assay, not often performed on kidney tissue, has advantages over the more commonly used 14C-palmitate assay as it detects complete oxidation of long chain fatty acids through the electron transport chain and is easier to perform (collect 3H2O rather than 14CO2). We can also refer users to the Nutrition Obesity Research Center’s high- resolution respirometer (Oroboros Oxygraph 2k) to detect respiration in isolated mitochondria. In addition, untargeted metabolomics and stable isotope tracer studies will be performed on primary cells in vitro and in vivo. The Meta-Core faculty are all committed to sharing validated protocols and methods with the O’Brien Consortium as well as larger scientific community. In addition, we will help train the kidney scientific community how to generate primary proximal tubule cells and tubules and use the Seahorse bioflux analysis in a way that yields consistent, reproducible results. In particular, the importance of validating cell number to use, post- analysis correction for number of cells, and proper concentrations of reagents will be emphasized. The Meta- Core will leverage the expertise and equipment of other Cores at Washington University to produce complementary services for a reduced rate. | Research Centers | 7research_infrastructure
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gen_5744875a40c6e2e7c5741c5cc1417f99 | Rocky Mountain REACH (RMT-REACH) | NIH | UNIVERSITY OF MONTANA | 5U01GM152530-02 | PROJECT SUMMARY/ABSTRACT The L.S. Skaggs Institute for Health Innovation (SIHI)-Research Evaluation and Commercialization Hub (SIHI- REACH) at the University of Montana (UM) will catalyze the emerging biomedical industry corridor in Montana and the surrounding states by establishing a hub to accelerate translation of academic discoveries into products that impact human health. Untapped opportunities exist in IDeA states to turn biomedical research discoveries into technologies that address unmet medical needs, disease burden, and health disparities for populations across the United States (US). We have partnered with 10 academic institutions across the IDeA states in the Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) region—including a community, a technological, and a tribal college—as well as the Washington Entrepreneurial-REACH (WE-REACH) at the University of Washington to gain invaluable guidance from their leadership team. Academic discovery is indispensable for ensuring a pipeline of research for novel diagnostics, devices, and therapies, yet sustainable infrastructure to support academic innovators in resource-limited regions has yet to be fully realized. Geographically remote regions have unique challenges in developing and promoting commercialization and entrepreneurship, including lack of infrastructure, less access to innovators and subject matters experts, and lower levels of funding. Gaps in resource allocation contribute to higher rates of mortality and disease burden, and health systems in these areas have traditionally been late to implement health innovation when compared to their metropolitan counterparts. In order for health innovation to reach clinical usefulness for all people, efforts are needed to ensure the inclusion of minority, geographically-isolated, and historically medically underserved populations at every stage of the biomedical research life cycle. We will accomplish our ultimate goals through the following aims: 1) Identify emerging biomedical discoveries with commercial viability in academic institutions within the four regional IDeA states supported by SIHI-REACH, emphasizing discoveries that address disease burden and health disparities for underserved communities; 2) Develop an innovative implementation system to enable access to gap funding, key subject matter experts in areas of product development, regulatory, reimbursement, legal, business development, and overall commercial strategy for academic researchers in resource-limited areas; 3) Provide funding and project management support for promising technologies and development teams to accelerate product definition studies; and 4) Elevate a WWAMI region-wide pro-entrepreneurial culture among academic investigators by engaging and mentoring biomedical innovators in rural and tribal institutions. With a strong leadership team providing diverse and complementary expertise and proven experience in entrepreneurial startups, SIHI-REACH will train the next generation of biomedical innovators in entrepreneurship and product development, positively impact the regional economy, and bring products that address health disparities to market. 1 PROJECT NARRATIVE The L.S. Skaggs Institute for Health Innovation (SIHI) Research Evaluation and Commercialization Hub (SIHI- REACH) at the University of Montana will accelerate translation of academic discoveries into products that impact human health in states that have largely not benefitted from investment in commercialization. We have partnered with 10 academic institutions in the Washington, Wyoming, Alaska, Montana, Idaho (WWAMI) region—including a community, a technological, and a tribal college—and are building upon the success of the Washington Entrepreneurial REACH (WE-REACH) at the University of Washington. Participating institutions and innovators will gain access to funding, training, and resources to guide the research and development of new medical products, ultimately fostering a pro-entrepreneurial culture across the region, creating new small businesses, and bringing products to market that address disease burden and health disparities. 1 | Non-SBIR/STTR | 6project_grants_public
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gen_b711f9c749a5a2394ee333feecc5f60b | San Diego State University Advancing Cancer Careers for ExceLlence (ACCEL) | NIH | SAN DIEGO STATE UNIVERSITY | 1R25CA285813-01 | PROJECT SUMMARY / ABSTRACT San Diego State University’s Advancing Cancer Careers for ExceLlence (ACCEL) Program, in partnership with University of California San Diego (UCSD) Moores Cancer Center, will provide 70 SDSU postdoctoral fellows and graduate students each year with a coordinated and innovative array of resources to support excellence, inclusion and transformation of the cancer research science force. ACCEL will leverage existing infrastructure and develop new programming to a) expand and strengthen the pipeline of underrepresented (UR) scholars pursuing cancer research; and b) broaden SDSU’s capacity to support and advance UR pre- and postdoctoral cancer research scholars. Three distinct and complimentary aims have been developed to meet these larger objectives. Led by a Training Champion (TC) team with diverse areas of expertise, the ACCEL program will a) implement mentoring activities and community-building engagement that reduce feelings of isolation and increase sense of belonging to increase doctoral student and postdoctoral scholar participation and retention in cancer research; b) provide structured support services including skills development courses for doctoral students and postdoctoral scholars to broaden advancement in cancer research and promote diversity in the scientific workforce; and c) build tailored and sustainable linkages for SDSU students and scholars to existing support and resources through the National Cancer Institute and other partners. While ACCEL program development and implementation will benefit greatly from strong integration with existing partners and programs including the UC San Diego Moores Cancer Center, SDSU-UCSD CREATE Cancer Partnership, and the NCI Center to Reduce Cancer Health Disparities (CRCHD) training navigation, ACCEL will also introduce innovative methodologies to address isolation and build community and belonging in tandem with skills building. PROJECT NARRATIVE San Diego State University’s Advancing Cancer Careers for ExceLlence (ACCEL) Program, in partnership with University of California San Diego (UCSD) Moores Cancer Center, will provide 70 SDSU postdoctoral fellows and graduate students each year with a coordinated and innovative array of resources to support excellence, inclusion and transformation of the cancer research science force. ACCEL will leverage existing infrastructure and develop new programming to a) expand and strengthen the pipeline of underrepresented (UR) scholars pursuing cancer research; and b) broaden SDSU’s capacity to support and advance UR pre- and postdoctoral cancer research scholars. | Other Research-Related | 6project_grants_public
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gen_5649e81278b9a9a3f17a7cfbb845e30f | Prognostic modeling of pediatric tracheostomy-associated respiratory tract infections | NIH | JOHNS HOPKINS UNIVERSITY | 1K23HL163331-01A1 | PROJECT SUMMARY: Each year over 4,000 children undergo tracheotomy and account for more than 20,000 hospitalizations annually most commonly due to acute tracheostomy-associated respiratory infections (TARI). These hospitalizations are most often due to Pseudomonas aeruginosa infection. Efforts to improve the care of children with tracheostomy are challenged by the limited body of evidence on how patient factors, features of P. aeruginosa itself, and the child's immune response impact the risk of recurrent infection. This proposal will address this critical knowledge gap by identifying and characterizing prognostic factors for frequent rehospitalization in children hospitalized for TARI. In this K23 Mentored Career Development Award, Dr. John Morrison will: 1) leverage existing data from a six-center prospective cohort study of children hospitalized for TARI to identify clinical factors associated with recurrent TARI hospitalization; 2) prospectively determine the association of pathogen-specific factors and features of the host immune response with frequency of recurrent TARI hospitalization, and 3) derive a novel prognostic model incorporating clinical and molecular factors to identify patients at increased risk for recurrent TARI hospitalization. Achieving these aims will facilitate Dr. Morrison's long-term goal of leading prognostically-stratified interventional studies aimed at improving outcomes for children with tracheostomy and others affected by frequent respiratory infections. The applicant has dedicated his career to improving the care for children with chronic respiratory failure and other medical complexity as a physician-scientist. He is an Assistant Professor of Pediatrics with the Johns Hopkins University (JHU) School of Medicine at Johns Hopkins All Children's Hospital (JHACH) who seeks a mentored career development award during which he will develop the advanced training, education, and experience to become an independently funded investigator in biomarker-informed prognostic models and risk- stratified clinical trials in children with tracheostomy. This proposal will provide Dr. Morrison with the support needed to advance his career by 1) acquiring knowledge on the development and application of prognostic modeling, 2) developing expertise in conducting biospecimen-based translational research, 3) preparing to conduct a prospective, multicenter study validating a prognostic model and examining therapeutic strategies, and 4) expanding his practical understanding of individual- and system-level factors contributing to recurrent admissions among children with tracheostomy. Dr. Morrison will be supported by the extensive resources of the Institutes for Clinical and Translational Research at JHACH and JHU and has assembled a strong team of mentors with expertise in biomarker discovery, biomarker-informed prognostic modeling, and risk-stratified clinical trials. He will also pursue coursework through the JHU Bloomberg School of Public Health in biostatistics, molecular epidemiology, and clinical trial conduct to complement his experience in the basic and clinical sciences and acquire the skills necessary to transition to independence. PROJECT NARRATIVE: Little is known regarding why children with tracheostomy experience recurrent respiratory infections despite receiving clinically appropriate antibiotic therapy. This proposal seeks to derive a novel prognostic model that incorporates clinical factors and mechanistically-based laboratory measures of pathogen antibiotic resistance and host immune response to identify children at greatest risk for recurrent tracheostomy-associated respiratory infections (TARIs). The findings of this work under a career development award will provide the basis for future risk-stratified interventional trials employing targeted therapies to reduce the frequency of TARI hospitalization among children with tracheostomy. | Other Research-Related | 1fellowships_scholarships
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gen_aa4c0a07a6263c6216b2147abf7dc802 | Allogeneic BAFF Ligand Based CAR T Cells as a Novel Therapy for B Cell Malignancies | NIH | LUMINARY THERAPEUTICS, INC. | 1R44CA278021-01A1 | ABSTRACT Since the first FDA approval of chimeric antigen receptor (CAR) T cell therapy in 2017, the use of engineered T cells expressing specific CARs to treat cancer has generated durable cures for many patients. Nevertheless, a significant subset of patients with B cell malignancies relapse following treatment due to lack of CAR T cell persistence and the ability of cancer cells to change with time and evade therapeutic interventions. Autologous T cell therapies also carry significant timeline and cost burdens, making widespread adoption difficult. In this application, we propose a novel allogeneic CAR T cell therapy aimed at improving outcomes for patients with mantle cell lymphoma (MCL) by overcoming deficiencies present in current generation CD19 targeted therapeutics. B cell activating factor (BAFF) provides critical survival signals to both normal and neoplastic B cells through a family of receptors (BAFF receptor, TACI, and BCMA) thus mitigating potential for antigen escape. BAFF and its receptors have remained underexplored in the context of B cell malignancies where strategies have relied overwhelmingly on pan B cell antigens such as CD19 and CD20. Since BAFF binds its receptors with moderate affinity, we believe this will increase the ability of these cells to form memory populations and engage in serial killing. We will leverage this ligand-based CAR design in an allogeneic gamma delta (γδ) T cell platform, as γδ T cells have been shown to have high replicative properties in vitro and do not mediate graft versus host disease in new hosts. We have produced preliminary data that confirms our ability to use the non- viral TcBuster DNA transposon system to generate T cells with BAFF-CAR expression. The overall objective of this proposal is to further develop and evaluate our γδ BAFF-CAR T cell therapy for the treatment of MCL in IND enabling studies. In doing so, our allogeneic BAFF-CAR T cell therapy supports an urgently needed shift in therapeutic development toward new tumor antigens that protect against antigen escape while reducing the manufacturing burden associated with cellular therapies through use of a readily available cell source. PROJECT NARRATIVE This proposal describes a novel allogeneic chimeric antigen receptor (CAR) T cell therapy that aims to improve outcomes for patients with mantle cell lymphoma. Our approach improves upon current immunotherapies by engineering T cells in a unique way to express a novel CAR against multiple underexplored targets in an allogenic platform. We expect immunotherapeutic delivery of these modified T cells will reduce disease recurrence by preventing antigen escape, improving persistence, and decreasing manufacturing burden. | SBIR/STTR | 0business_rnd_innovation
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gen_e213528b2b8f22779f941625892afd3f | HN0001448 - CITY OF LE HAVRE - IMPLEMENTATION OF AN INTERNET SERVICE OFFER FOR LEGAL ENTITIES | Kohesio | COMMUNE DE LE HAVRE | https://linkedopendata.eu/entity/Q3680636 | The City of Le Havre and the Le Havre Urban Community (CODAH) plan to create a common service offering on the Internet for professionals, and are submitting a joint application to the Digital Uses call for projects. The city of Le Havre is the spokesperson for the two communities; its "Modernization, Organization and Quality" department being the pilot of the project. The City of Le Havre (3,500 agents serving 183,000 inhabitants) and the CODAH (550 agents serving 243,000 inhabitants spread over 17 municipalities, including the city of Le Havre) wish to offer a catalog of online procedures for legal entities: companies, associations, trustees, traders and craftsmen... The objective is to simplify user journeys professionals and to facilitate the completion of procedures thanks in particular to 24-hour access, the possibility of managing procedures on a single account by several members of a professional entity, saving time in exchanging documents, files, and allowing monitoring of the progress of requests at any time... The target catalog includes various services such as subscription and payment for water, monitoring of water consumption, subscription and payment for parking, certificate requests planning, subsidies, equipment rental, road authorization, various payments and invoice tracking... In addition, access to this offer is provided on all types of terminals: smart phones, tablets and computers. The preliminary work already carried out is likely to define the precise scope of the project, organize it and evaluate its costs. The first step consisted of building the catalog of target offers for the City of Le Havre and the CODAH, and of identifying the simplification services bringing added value to these procedures on the Internet (e.g.: monitoring of a request, electronic transmission of files, consultation, etc.). This initial work resulted in the development of functional specifications for the e-services platform. In addition, and always in order to be able to calibrate the workload and develop a deployment schedule, the experimental development of a brick of the platform is currently underway (creation of an account for a company). On this basis, it will be possible, in September 2015, to evaluate the average development times per brick and to refine the deployment schedule. In September 2015, the detailed design and development stage of the service platform, and one of the priority approaches (water subscription) will begin. At present, the release of the first group of services is targeted for the second half of 2016. The FEDER subsidy is an opportunity to help with creation of an innovative product adapted as closely as possible to the expectations of user legal entities. In summary on the calendar, the work to define the scope and framing of the project extends from September 2014 to September 2015, followed by the design and development work of the platform and the first Water services from September 2015 to the second half of 2016. The project then extends until December 2020 for the creation of new approaches (such as parking, town planning, cemetery or cultural...). The objective is to make 25 procedures available online by the end of 2019. | Smarter Europe / Information and communication technology / e-Government services and applications (including e-Procurement, ICT measures supporting the reform of public administration, cyber-security, trust and privacy measures, e-Justice and e-Democracy) | 5out_of_scope
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gen_05250a55266f355c98a73d758b446c27 | REBOND FEDER loan fund Lower Normandy | Kohesio | BPIFRANCE FINANCEMENT | https://linkedopendata.eu/entity/Q3673261 | COVID-19 is a major socio-economic shock and uncertainties about developments over the coming months are high. The economic and financial consequences generate financing failures due in particular to the systemic nature of the shock (stoppage of business activities, disruption of supply chains, inducing a surge in the volume of cash flow needs over a concentrated period and an uncertain duration even as the financing market, particularly banking, faces the financial and economic consequences of the crisis (increased market volatility, uncertain economic outlook, costs of risk and increased liquidity, etc.). failures compromise the survival of businesses and the objectives of competitiveness and economic growth pursued by the FEDER Operational Programs. The operation presented will mobilize FEDER within the framework of a “FEDER Rebound Loan Fund 2014-2020”, a financial tool to aid economic development, for the benefit of small and medium-sized businesses encountering a cash flow need linked to cyclical difficulty or a situation of temporary fragility linked in particular to the measures taken within the framework. of COVID 19. The fund will intervene in the form of a zero-interest loan - without guarantee requirements and over a period of 7 years, to support projects to strengthen the financial structure and mainly cash flow needs linked to the economic situation, the increase in the need for working capital. | Smarter Europe / Competitiveness of SMEs / Advanced support services for SMEs and groups of SMEs (including management, marketing and design services) | 0business_rnd_innovation
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gen_d1091f2ac00d4d62b8a4013fa39ebdc8 | HN0001356 - CC CAUX VALLÉE DE SEINE - DEVELOPMENT OF E-ADMINISTRATION: DEPLOYMENT OF ELECTRONIC DOCUMENT MANAGEMENT FOR THE ENTIRE CVS TERRITORY | Kohesio | CA CAUX SEINE AGGLO | https://linkedopendata.eu/entity/Q3680966 | E-administration is a vector for modernizing administration and simplifying access to public services for users, as prefigured in the NOTRe law. | Smarter Europe / Information and communication technology / e-Government services and applications (including e-Procurement, ICT measures supporting the reform of public administration, cyber-security, trust and privacy measures, e-Justice and e-Democracy) | 5out_of_scope
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gen_a33452fdd1c36c2c75bd9b15021688bd | FEDER - ISPA-E - REACT PROJECT | Kohesio | ISPA ENTREPRISES | https://linkedopendata.eu/entity/Q3680231 | The unique properties of plastics explain the extent of their use in food packaging. They are light, which ensures reduced transport costs and lower CO2 emissions. They are transparent and custom trainable, which offers unparalleled marketing opportunities. But above all, through their barrier effect, they protect foods from oxygen and water which can quickly alter their quality or even make them dangerous for consumption. The use of plastic in packaging has thus largely contributed to reducing food waste, to curbing health problems relating to the food trade and to fighting against famine and malnutrition. The packaging industry, a victim of its success, consumes nearly 40% of plastic materials, the majority of which is used for food packaging. In France, each year, more than a million tonnes of plastic materials are used and placed on the market for household and food packaging. Unfortunately, a large part of these plastics are only used for their initial function (e.g. ham trays) and are neither reused nor recycled. Thus, 44% of French plastic waste is incinerated, and 34% is buried in landfills. Only 22% are recycled, mainly PET bottles. The low recycling rate of these consumer products is linked to the fact that only plastics isolated from others are recyclable. For example, a few percent by mass of PP in a volume of PET makes it impossible to recycle the latter. This is why efficient sorting of household plastics is essential to ensure the value chain of these materials. However, the vast majority of plastic packaging consists of co-extruded or laminated multilayers using different types of resin, each providing one or more specific properties. Alongside recycling, a second alternative to the treatment of plastic waste is the use of biodegradable, or even compostable, packaging for short-life applications, in the concept of Circular Economy and with the opportunity to overcome the difficulty relating to the multi-material nature of packaging. multilayers.To date, there is no high-performance recyclable or compostable food packaging. It is therefore urgent, in the interests of sustainable development, to design eco-responsible food packaging materials that are recyclable or compostable, or even both at the same time. The Normandy region, with the strong presence of academic and industrial players covering the entire value chain concerned (formulation and compounding of new materials, implementation of manufactured products, recycling and/or composting), appears ideally placed to develop this new job-creating sector, while improving eco-design of products and sustainable management of raw materials. Current societal challenges, which are the scarcity of resources and the end-of-life management of materials, must indeed make the development of materials from renewable resources a priority research axis at the heart of territorial challenges for transitions and sustainable development. The REACT project brings together a packaging manufacturer (B+K), a technology supplier (Polytechs), three research laboratories (UniRouen PBS), UniLaSalle UTA and ISPA), a technical center (IPC) and a CRT (Praxens). The project will lead to the creation of 10 direct jobs at the end of the project and several dozen over the next 3/5 years. REACT will be a pilot project for the creation of a regional sector intended to be duplicated on a national/European scale. Duplicating the Normandy sector on a national scale could lead to a reduction in CO2 emissions of around 1.7 Mt per year. | Smarter Europe / Research and innovation / Research and innovation activities in private research centres including networking | 0business_rnd_innovation
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gen_48f9a15bb810a0503a8629dc3e20e585 | FEDER - IFPC - Cidricole Station Renovation | Kohesio | ORGPRO - INSTITUT FRANCAIS DES PRODUCTIONS CIDRICOLES | https://linkedopendata.eu/entity/Q3680250 | Built in 1987, the IFPC cider station initially accommodated 2 employees. A first extension was carried out around 1995. Today, the IFPC can accommodate up to 10 employees and trainees but the organization of the building and the agricultural sheds are no longer adapted to the needs of the activities and reception. After 30 years, renovations and upgrading are necessary. | Smarter Europe / Research and innovation / Research and innovation activities in private research centres including networking | 7research_infrastructure
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gen_13935d821d6d9f175ff042831c07895b | FEDER - UNICAEN (LABO GREYC) - ONE4YOU PROJECT | Kohesio | UNIVERSITE DE CAEN NORMANDIE | https://linkedopendata.eu/entity/Q3680141 | SOGET, leader of this project, is a world-class player in the development and implementation of multimodal one-stop shops. Its vision is to serve the fluidity of port operations, by organizing for the various public and private operators, intelligent, shared and instantaneous management of information relating to logistics chains. GREYC, ISEL and SOGET wish to join forces in order to respond to the major structural challenges of international flows: The logistics ecosystem is changing with flow operators who are constantly looking for productivity gains and fluidity of trade. Conversely, sovereign actors (customs authorities, port authorities and other administrations) seek to control and secure the flow of goods. To respond to these two movements which can oppose each other, multimodal port and airport one-stop shops must reinvent themselves and combine facilitation and security of trade. On the other hand, the one-stop shop market is experiencing unprecedented development. As part of the WTO BALI agreements, an agreement on trade facilitation was ratified and came into force on February 22, 2017. The latter aims to accelerate the movement, release and customs clearance of goods at borders. Its entry into force marks the start of a new phase of reforms intended to facilitate trade around the world and creates important momentum for trade and the multilateral trading system as a whole. At the same time, new technologies are emerging, such as artificial intelligence which opens up new fields of application in logistics. These systems are capable of learning, making decisions, automating tasks, and carrying out global flow monitoring tasks based on exchange histories. Innovation being the pillar of research and development of any software publisher, SOGET launched in 2014 the reflection of the e-maritime 2 project "Artificial Intelligence at the service of logistics which was included in the CPER 2014-2020 as a priority digital project in transport. The e-maritime 2 project is part of the dynamic of the trade facilitation agreement of the World Trade Organization, the massification of one-stop shops has across the world, and the emergence of national operators of vital importance. This new complex environment requires the contribution of artificial intelligence to the service of tomorrow's logistics in a context of globalization at the level of operators and sovereign authorities. Artificial intelligence will be the true digital revolution in the service of trade facilitation. The e-maritime 2 project will consist of the development of new information systems for management, control, targeting and monitoring of international supply chains based on artificial intelligence technologies, the digital intensities of the Internet of Things and cyber-security linked to the dematerialized power of the Cloud. Already, a prospective study has been carried out with a certain number of companies following an internal reflection between SOGET, GREYC and ISEL which made it possible to determine various concrete expectations complementary to the S)ONE one-stop shop. These new services are grouped under the title ONE4YOU and represent one of the first components of e-maritime2. ONE4YOU thus aims to determine the research and development roadmap to address the global market for port single windows. | Smarter Europe / Research and innovation / Research and innovation activities in public research centres and centres of competence including networking | 6project_grants_public
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gen_2f5ed02f02e253dff7389d0f725e8816 | FEDER - UNICAEN - Design, synthesis and biological evaluation of MT5-MMP inhibitors Investment | Kohesio | UNIVERSITE DE CAEN NORMANDIE | https://linkedopendata.eu/entity/Q3673587 | Not available | Smarter Europe / Research and innovation / Research and innovation activities in public research centres and centres of competence including networking | 6project_grants_public
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gen_f133808d9761ef7af34d89f0851e06e6 | FEDER FCT DEVELOPMENT OF MANAGEMENT PLANS FOR 6 COTEAUX DE SEINE-MARITIME 2020-2021 CEN NORMANDY | Kohesio | CONSERVATOIRE D ESPACES NATURELS DE NORMANDIE | https://linkedopendata.eu/entity/Q3681826 | The Normandy Seine Natural Spaces Conservatory (CenNS) is a 1901 law association which contributes to the preservation of the natural, landscape and geological heritage in the Upper Normandy territory by developing knowledge, protection, management and development actions for natural spaces and by supporting public environmental policies. It currently manages 85 natural spaces, representing approximately 1,331 ha including 713 ha of limestone hillsides, 293 ha of wetlands and 229 ha alluvial terraces. On each of the sites it manages, the CenNS bases its policy on the creation of an ecological management plan, based on an ecological and socio-economic diagnosis, the evaluation of the issues and the definition of long-term objectives broken down into medium-term objectives and operations. The production of these management plans is a usual practice of the Conservatory of Natural Spaces. It has become mandatory since September 11, 2014, the date of signature by the regional prefect and the president of the regional council of the decree approving the CenNS. The approval decision is taken on the basis of the presentation of an action plan including the obligation to produce a scientifically validated management plan for each site for which the conservatory is responsible (decree no. 2011-1251 of October 7 2011).Currently, of the 85 sites managed by the CenNS (excluding the 12 “bat roosts” sites which do not require a management document): - 26 sites have a management document in the department of Seine-Maritime (on 33 sites excluding sites at Chiroptères); - 35 sites have a management document in the department of Eure (on 40 sites excluding Chiroptera sites).Among the 6 sites concerned by this request, 4 have already been managed by the CenNS for several years: Belbeuf, under management, using funding from Natura 2000 contracts in particular; Croixdalle and Mesnil-Lieubray by farmers, via MAEs; and Mesnières-en-Bray through the organization of volunteer workcamps. However, due to lack of funding, these sites do not benefit from updated management documents allowing the evaluation of the management carried out and the efficient planning of actions to preserve these limestone hillsides. The other 2 sites (Neuf-Marché and Villy-sur-Yères) are sites newly approved by the municipalities concerned with the Conservatory. For these 2 sites, these are the first management documents. | Greener, carbon-free Europe / Environment protection and resource efficiency / Protection and enhancement of biodiversity, nature protection and green infrastructure | 5out_of_scope
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gen_92b673fd5c5f14733dc5859a283f50d7 | FEDER - PEG - AEROTEX PROJECT | Kohesio | P.E.G. | https://linkedopendata.eu/entity/Q3681979 | The Aérotex project aims to revolutionize the field of thermal insulation for the technical clothing and building insulation sectors by developing new environmentally friendly materials with high thermal insulation performance, light, thin and flexible. To achieve this objective, the partnership will combine innovative technologies, such as silica airgel and Fibroline dry impregnation technology, with the know-how of leading insulation players and the expertise of university laboratories in the Auvergne-Rhône-Alpes and Normandy regions. The Aérotex project consortium is made up of 6 partners: PEG, Balsan, Millet, Fibroline, Enersens and Cethil. PEG is positioning itself in the project as both an expert supplier of raw materials (Polyester fiber wadding) as well as an end-user for a highly strategic field, building insulation. Integrating a collaborative innovation project will allow them to access all the technological expertise (ecological impregnation technology and Airgel insulating material) and scientific expertise (Characterization and modeling of insulators by the Cethil laboratory) to make this development a success in the Normandy region. During the project, insulation materials will be developed by optimizing fiber wadding and innovative impregnation technology. The performance of the impregnated Airgel will be analyzed and optimized to achieve the desired performance. The development of the prototypes will be done with an important point which is the resistance of the Airgel during handling and washing. Ultimately, 3 prototypes will be developed: a sleeping bag, a technical jacket and insulation for the building. | Smarter Europe / Research and innovation / Research and innovation activities in private research centres including networking | 0business_rnd_innovation
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gen_a0b46adade9510aa92ca49e0d1e73ef2 | HN0004952 - LINEN SAINT MARTIN - OLCO: COMPOSITE LINEN OPTIMIZATION | Kohesio | LA LINIERE DE SAINT MARTIN | https://linkedopendata.eu/entity/Q3680953 | Aware of the potential of linen fiber due to its properties, LSM has developed, with the skills of Mr. VANFLETEREN François, new products for composite applications. Light, ecological and with a strength close to that of fiberglass, flax fiber - transformed into linen sail - can in fact be the subject of multiple applications (boat hulls, skis, tennis rackets, bicycle frames, etc.) and thus enjoys a growing reputation in different sectors of industry such as automobiles, aeronautics and leisure. Thus, these new markets constitute very strong development potential for flax fiber as reinforcing fiber. Consolidation and gaining market share in composites require R&D work, particularly to optimize the technical and mechanical properties of Linen ribbons. In the OLCO project, LSM, preparer of flax for composite, joins the AGRI'TERR laboratory of the Institut Polytechnique LaSalle Beauvais-Esitpa in partnership to jointly carry out this research program. | Smarter Europe / Research and innovation / Research and innovation infrastructure, processes, technology transfer and cooperation in enterprises focusing on the low carbon economy and on resilience to climate change | 0business_rnd_innovation
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gen_7fe784a840783423636d081be89c327f | FEDER - 6NAPSE - MIMME PROJECT | Kohesio | 6NAPSE | https://linkedopendata.eu/entity/Q3681475 | - The reliability of on-board systems is a major issue for manufacturers in different sectors such as aerospace, aeronautics, automobiles, railways - The testing conditions imposed by manufacturers are increasingly strict - The demand from large groups is oriented towards: - The need to carry out innovative tests in vibration, thermal, fluid mechanics and materials analysis - A single point of contact for carrying out their research and development tests - For their part, SMEs insist on the need to simplify protocols Controlling product reliability will require in the near future: - A multi-physics approach (materials, mechanics, thermal, electrical) - A close correlation between digital and experimental approach - Testing means adapted to new customer requirements | Smarter Europe / Research and innovation / Research and innovation processes in SMEs (including voucher schemes, process, design, service and social innovation) | 0business_rnd_innovation
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gen_d298284d54a8a86325c7ef5c7a5c1222 | HN0008608 - MUNICIPALITY OF BLANGY SUR BRESLE - THERMAL REHAB MAURICE FLECHELLE SPORTS ROOM | Kohesio | COMMUNE DE BLANGY SUR BRESLE | https://linkedopendata.eu/entity/Q3681182 | The M. Flscale sports hall was built in 1960. An extension of the room (ping-pong room and dojo) was built in 1980. The part built in 1960 is heated by air heaters on a water network and cast iron radiators in the locker rooms powered by two gas boilers dating from 1989. The extension built in 1980 is heated by electric air heaters. The locker room showers are powered by two electric water heaters. In 2014, the municipality carried out, with the help of the department of Seine-Maritime, an energy assessment of the municipal heritage, which identified the most energy-intensive buildings, including the M. Flèdre room. Always with the help of the Energy Council made available by the Department, the municipality carried out in 2015 a preliminary energy diagnosis of the Flèche room. In May 2016, with the aim of identifying possible solutions to save money. energy, the municipality entrusted the JBL INGENIERIE firm with carrying out a thermal study with the aim of choosing the solution best suited to the desired objectives. | Greener, carbon-free Europe / Low-carbon economy / Energy efficiency renovation of public infrastructure, demonstration projects and supporting measures | 5out_of_scope
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gen_1d5909c7f655498b0a313502acc4e4ee | FEDER - V@SY - PEPSY PROJECT | Kohesio | VISIO ACTIVITES SPORTIVES INTERACTIVES | https://linkedopendata.eu/entity/Q3673404 | The PEPSY V@SI project is part of the field of specialization “Innovations in Biomedical Sciences and Technologies but also in the field of “Digital & Society”, mobile services sub-field of the research and innovation strategy based on intelligent specialization (RIS3) of the Lower Normandy region. Thanks to the expertise provided by the 2 laboratories in the field of schizophrenia for one (ISTS, UMR 6301) and in the field of APA for the other (COMETE, U), this project aims to develop an Adapted Physical Activity (APA) offer for patients presenting a schizophrenic disorder, a chronic, frequent pathology (1%), causing disability (80% of patients), a high sedentary lifestyle and severe co-morbidities (obesity, diabetes, cardiac pathologies). APA has already shown its effectiveness in reducing co-morbidities, social adaptation and quality of life in the general population. The major innovation of the program lies in the development of a complete offer covering the entire value chain: medical prescription, construction and individualized implementation of remote support (tele-support) through Adapted Physical Activity, deployment of an interactive technological platform integrating a video-conferencing system and a physiological data monitoring system (sensors). Tele-support developed by V@si is a promising and innovative way to facilitate patients' access to physical exercise. Indeed, physical capacities are lower in schizophrenic patients who are little motivated to go to traditional fitness centers. In parallel with this, the main objective of BodyCap within this research program is to provide and/or develop innovative solutions for monitoring heart rate and activity responding to all the constraints inherent in monitoring the target populations of this type of program; namely: - reliable and precise measurement of these parameters, - monitoring and feedback of information in real time, via a dedicated platform, - post-processing allowing, if necessary, to highlight the variability of the heart rate, - level of performance ensuring good acceptability on the part of the user: o confidentiality of data, o lifespan, o storage capacity, o transmission distance, o speed of data unloading. - Preserve user comfort: o miniaturization of the device, o optimization of the design and materials used. The ob'do Contact Agile company is participating in the project by focusing on the integration of the video-conferencing and physiological data monitoring system used by participants during remote coaching sessions. We will call this system the V@siBox. The action of ob'do Contact Agile is initially to set up prototypes of the V@siBox at the start of the project in order to start the research program. The V@si Box will have the function of connecting commercial sensors (example: BodyCap and ZephyrMonitoring). Secondly, ob'do Contact Agile will offer an industrializable version of the V@siBox thanks to feedback from the field. The ob'do Contact Agile team will be heavily involved in the first part of the program by creating prototypes. Its activity will continue with the maintenance and improvement of V@siBoxes and the preparation of their industrialization. | Smarter Europe / Research and innovation / Research and innovation processes in SMEs (including voucher schemes, process, design, service and social innovation) | 0business_rnd_innovation
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gen_513b44c289829e04e98a259d2f6ad47a | FEDER - UNIROUEN (LMSM) - Production of Actives and Cosmetic Products Modulating the Hair MICrobiota (MICCA) | Kohesio | UNIVERSITE DE ROUEN-NORMANDIE | https://linkedopendata.eu/entity/Q3681808 | The MICCA project aims to develop a hair cosmetic product acting on the communication between the cells of the hair follicle and the microbiota, through the use of raw materials of natural or peptide origin. This project is led by the LMSM (EA4312 of the University of Rouen Normandy) and the companies SEDERMA, SISLEY and GENOSKIN (PME). Activities of the consortium members: • SISLEY specializes in the creation and manufacturing of cosmetic products (skincare, makeup, hair and perfumes). • GENOSKIN provides a unique platform of ex vivo models of human skin to validate the development of cosmetic active ingredients, chemicals, drugs, or administered medical devices.•SEDERMA designs, produces, analyzes and markets cosmetic raw materials.•LMSM works to study the role of communication and environmental and host factors on bacterial adaptation and virulence. | Smarter Europe / Research and innovation / Technology transfer and university-enterprise cooperation primarily benefiting SMEs | 6project_grants_public
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gen_9e0e73c1a8b9c3da11abbb7a4c0abb90 | FEDER - ENERGY RENOVATION BBC 82 HOUSING RUE DES ROSIERS/RESIDENCE SAINT MARTIN CAEN | Kohesio | INOLYA | https://linkedopendata.eu/entity/Q3680182 | As part of its PSP INOLYA gave priority to this building located in the city center and whose profile of buildings was noted in value to be restored | Greener, carbon-free Europe / Low-carbon economy / Energy efficiency renovation of existing housing stock, demonstration projects and supporting measures | 5out_of_scope
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gen_3f2df6d11abdff757bb7176343455b3f | FLERS - ITI - FEDER digital pass | Kohesio | FLERS AGGLO | https://linkedopendata.eu/entity/Q3673372 | The Pays de Flers Agglomeration community is leading a reflection on digital technology aimed at improving the quality of life of its citizens and taking advantage of the tourist attractiveness of the Flérien territory. The CAPF wishes to launch in September 2016 a digital pass constituting a digital platform of services oriented to leisure / commerce / tourism for the population. It will offer a directory with geolocation of businesses, tourist and cultural and leisure sites. It will offer discounts but also the possibility of receiving good deals and promotional offers. It will also make it possible to promote the territory with presentation sheets of tourist places. This Pass would take the form of a map and/or a mobile application for smartphones, tablets (iOS, Android Windows 10 Mobile) both using NFC and/or QR Code technologies in connected or disconnected mode (pre-download of the application), integrating all the partners and services offered in the area (geolocation, promotional sheet, NFC technology, QR Code) Creation of a web portal specific to this operation. A link will be made with the projects that will be developed in the area in terms of virtual reality. Estimated project cost 75,000 including 40,000 for digital solution supplies and 30,000 equipment The CAPF and its living area benefit from a favorable geo-tourist situation. Thus, the CAPF has a significant customer potential with more than 160,000 inhabitants within 30 minutes and 346,000 within 45 minutes. There are initiatives aimed at promoting access to shops and leisure sites: UCIA gift vouchers, Kart'A+ but these supports are not accessible to the greatest number of people, are not complementary and are in paper format. | Smarter Europe / Information and communication technology / e-Government services and applications (including e-Procurement, ICT measures supporting the reform of public administration, cyber-security, trust and privacy measures, e-Justice and e-Democracy) | 5out_of_scope
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gen_8f3b1f51cc12256c9de2fc5c5d8e6379 | FEDER - NXP - PF CNES PROJECT | Kohesio | NXP SEMICONDUCTORS FRANCE | https://linkedopendata.eu/entity/Q3680132 | Treating differently is a public health imperative in a context of population aging, medical desertification and increased patient demands. It is also an economic imperative which particularly affects France, whose health expenditure is today growing more strongly than GDP. The French health system, which was built on acute medicine and around the hospital, will have to reorient itself towards the management of a care pathway within which the hospital will certainly be an important step, but which will have to be more part of a collaboration with actors outside the hospital. In this logic, e-health has its place and holds promise for facing challenges and preserving the fundamentals of the health system while increasing its added value for professionals and patients alike. The development of digital solutions will make it possible to place the patient at the center of the care ecosystem with a set of medical and paramedical professionals gravitating around them. Building on this observation, NXP, an internationally renowned manufacturer in the IOT and secure transactions market, ELITT expert in the interoperability and security of card payment data, Pertimm, an SME with 20 years of experience in artificial intelligence and GREYC, a laboratory whose research work in algorithms and biometrics, have joined forces to develop an e-health digital trust platform (PF CNES) in the Caen area. This large-scale industrial project is awaited by regional economic players in the world of health, as well as organizations working to bring together the e-health sector in Normandy. This PF CNES platform is intended to be collaborative and unifying, in order to facilitate the rapid and sustainable adoption of e-health products and services. It aims to: Promote Innovation on an industrial scale by providing partners with industrial technological building blocks and support in certification processes and relations with regulatory authorities; Guarantee a level of Security and Integrity of health data in accordance with the requirements of health regulatory authorities; Facilitate the experimentation and deployment of products and services at the national and international level thanks to their interoperability. The challenge of this platform is certainly economic, but above all it is about bringing about societal innovation. Indeed, digital technologies represent a real opportunity to improve the quality of care for the patient and to improve the daily lives of professionals thanks to the organizational changes they allow. The economic challenge is to improve the efficiency of the health system and health spending and to create an e-health industrial sector which respects the standards/requirements of the regulatory authorities (security, interoperability, integrity), which innovates and which trains. | Smarter Europe / Research and innovation / Technology transfer and university-enterprise cooperation primarily benefiting SMEs | 0business_rnd_innovation
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gen_cc4cf182d3c914f73092d15d4dd5a225 | FEDER - URN - MOTHER OF PEARL - SPRINGBOARD | Kohesio | UNIVERSITE DE ROUEN-NORMANDIE | https://linkedopendata.eu/entity/Q3681630 | Currently, and more particularly in the pharmaceutical field, many substances discovered or in development are composed of chiral molecules. They can therefore exist in the form of two isomers with identical physicochemical properties but with different, or even opposing, biological activities and often only one of the two enantiomers has the required therapeutic activity. The development of processes allowing access to pure enantiomers (chiral resolution processes) therefore constitutes a major economic and scientific challenge. The SMS laboratory has extensive experience in the development of chiral resolution methods by crystallization (Pasteurian resolution, preferential crystallization, deracemization, preferential enrichment). It benefits from significant recognition from the scientific and industrial community in this field which results in different types of partnerships (university collaborations, research contracts, CIFRE Theses, patent filings, ANR, etc.). It is also thanks to this experience that the SMS laboratory is one of the beneficiary partners of the European ITN Marie-Curie CoRe project, (Continuous Resolution and Deracemization of Chiral Compounds by Crystallization) which started in October 2016 and will end in October 2020. The research carried out as part of the CoRe project has made it possible to highlight the need for the development of optimized processes of increased understanding and control. of the very first step of the crystallization process: nucleation. The idea that the theme of the nucleation of chiral phases should be the subject of a European request for a new ITN which would thus follow up on the research carried out within the framework of the CoRe project is now a consensus among our European partners. It is in this context that the SMS laboratory wishes to benefit from the support of the Normandy region. (see the description of the attached file) | Smarter Europe / Research and innovation / Research and innovation infrastructure (public) | 6project_grants_public
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gen_1bdc1e56339cd6118eaf0c86bf91c000 | FEDER - LA ROSERAIE EHPAD - WOOD BOILER CREATION | Kohesio | EHPAD LA ROSERAIE | https://linkedopendata.eu/entity/Q3673495 | During the work planned for the extension of its premises and the compliance for accessibility for people with reduced mobility, the EHPAD also integrated the construction of a wood boiler room, to ensure the site's energy production base (heating and domestic hot water), replacing the existing oil boiler room. Indeed, this new equipment is a strong sign showing the importance given to the energy theme within the territory in which the EHPAD is located and participates in this respect: awareness of greenhouse gas ("GHG") emissions in the territory, Control of energy consumption and energy savings, Development of renewable energies Finally, the establishment will participate in rural economic development by sourcing from local suppliers who are themselves committed to a quality and environmental approach, the wood coming from the sustainable maintenance of hedgerows, and/or from local wooded resources (20 km from the user). | Greener, carbon-free Europe / Low-carbon economy / Renewable energy: biomass | 5out_of_scope
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gen_c40c9256cad88d41093ddfb1137df7fd | FED INV FCT 17P04653 - DEPARTMENT 76 - IMPLEMENTATION OF NOMAD TOOLS IN THE CONTEXT OF MEDICO-SOC EVALUATIONS IN DOM FOLLOWING REQUEST FROM PCH OR APA | Kohesio | DEPARTEMENT DE LA SEINE MARITIME | https://linkedopendata.eu/entity/Q3680768 | The Personalized Autonomy Assistance (APA) benefit was created by the legislator to keep elderly people in their homes as much as possible (age 60). According to the same principle, the Disability Compensation Benefit (PCH) aims to improve the lives of disabled people as best as possible in their everyday lives. The management of the APA system for people residing in Seine Maritime is the responsibility of the departmental community, namely from receipt of the request to the decision, monitoring and payment. Management of the PCH system is the responsibility of the MDPH76 for its Instruction part and the local authority for payment and monitoring. In addition the compulsory administrative documents (proof of address, identity, income) and the compulsory medical documents (medical certificates), the PAPA and PCI-1 instruction procedures provide for a medico-social assessment at the person's home. The project aims to provide social workers with a mobile workstation (tablet) equipped with IT tools and utilities, in particular a forms system allowing the collection of data essential to the continuation of the procedure for examining the request. The solution must therefore allow: Before the trip to make an appointment in the GASPER application see glossary After confirmation of the appointment, to select the files of the people that the social worker will visit; that this selection pre-initializes the "electronic files" of the people During the visit, to complete the form (in creation or modification) following the "natural" course of the interview, which is not necessarily that of the form. Returning to the office the system resynchronizes the data of the form with the software automatically. This avoids paper exchanges between social workers and secretariat, and especially the re-entries and the delays which result from this. The Tablet which will be available to social workers must contain: o The forms which must be interactive with the IS (GENESiS). To do this, it will be a PDF document with fields potentially pre-initialized by the system and completed during the interview. The APA evaluation guide: Internal document designed by the Autonomy Department to identify the data essential for evaluating the degree of dependence. The GEVA form cf glossary (for the MDPII): Document whose form is imposed by the CNSA cf glossary but for which an "internal" form4 could be designed for improve readability and focus on data useful to the MDPI-I 76, • User guides for these forms, specifying in particular the semantics and nomenclatures • A summary sheet per on-board file, for consultation of essential datao A certain number of reference data, for consultation, constituting “bibles” or “directories”: - List of service providers and agents by M'AS AS see glossary - Single partner database - Capacity rating guide (GIR) • A "toolbox" allowing for example: To apply a spelling checker to the areas entered in the form To calculate the degree of dependency (GIR) see glossary To develop and calculate an assistance plan (Therefore being able to tell the person the amount of assistance to which they are entitled) - A GPS allowing the Social Worker to go to the person's home as quickly as possible. A scanner for scanning any documents provided by the person | Smarter Europe / Information and communication technology / e-Government services and applications (including e-Procurement, ICT measures supporting the reform of public administration, cyber-security, trust and privacy measures, e-Justice and e-Democracy) | 5out_of_scope
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gen_c015356060ae0efa29abf8257b0973bd | FEDER - ESIGELEC - ANDECE - INVEST/FONCT | Kohesio | ESIGELEC | https://linkedopendata.eu/entity/Q3680972 | In recent years, the growing penetration of the electrical energy vector in a large number of products and industrial sectors through the multiplication of electrical devices (machines-converters-storage) leads to complex systems with restrictive requirements in terms of operational safety and availability and which can be very critical for certain applications. For example, the automotive sector saw the implementation of the ISO 26262:2011 standard in 2011, which would guarantee the functional safety of a system embedded in the vehicle. Likewise, the ED-12C and DO-178C standards concern the analysis of safety for avionics. It should be noted that this expansion of the electrification of machines and objects in different sectors of human activity has been accompanied by a dazzling increase in the production of electrical machines and static converters throughout the world. This new situation accentuates the need for systems (devices and components) for the conversion and transformation of energy which, while not being totally immune, have qualities of intrinsic availability despite the occurrence of a fault. Thus, these increasingly strong requirements for availability and safety of systems, imply new requirements in the research effort on the methods and methodology of diagnosis/prognosis of electrical devices accompanied by a review of their design in order to structurally integrate availability through their capacity to be tolerant of certain defects. Indeed, diagnosis consists of detecting, locating and identifying faults allowing supervision systems to act effectively by applying one of fault tolerance scenarios, namely accommodation, reconfiguration or restructuring depending on the degree of severity of the fault. The prognosis for its part predicts the future operating state of the equipment concerned which is the subject of an international standard (ISO, 2004). Thus, prognosis is considered a key process in maintenance strategies. It is in this context that GREAH and IRSEEM combine their forces by constituting a multidisciplinary project team capable of dealing with many of the multiple aspects of the issue of safety and availability of electrical energy conversion and transformation devices. | Smarter Europe / Research and innovation / Research and innovation activities in public research centres and centres of competence including networking | 6project_grants_public
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gen_2eb11e65a20f8c0fad290e6eba316c06 | HN0009643 - COMMUNE OF FONTENAY - SCHOOL COMPLEX REHABILITATION AND CONSTRUCTION EXTENSION SCHOOL RESTAURANT AND DAYCARE | Kohesio | COMMUNE DE FONTENAY | https://linkedopendata.eu/entity/Q3681168 | The Fontenay school was built in 1978 and was extended in 1983. The school complex currently includes 5 primary and nursery classes, a school restaurant serving 100 meals in two courses and an after-school daycare. As part of its development, the town plans to increase its population from 1,056 inhabitants (INSEE data) to 1,700 inhabitants over a period of 6 to 8 years with the development in progress of a ZAC on the municipal territory. The current premises are old and no longer meet the needs of the municipality, taking into account the probable increase in staff numbers, the energy performance of the building and the comfort of users, accessibility for people with reduced mobility. | Greener, carbon-free Europe / Low-carbon economy / Energy efficiency renovation of public infrastructure, demonstration projects and supporting measures | 5out_of_scope
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gen_bf2b5d677926bb5dbdf16ab9b07128b4 | 2020 - Purchases of masks (FEDER BN) - NORMANDY REGION | Kohesio | RÉGION NORMANDIE | https://linkedopendata.eu/entity/Q3680420 | Not available | Smarter Europe / Competitiveness of SMEs / Advanced support services for SMEs and groups of SMEs (including management, marketing and design services) | 5out_of_scope
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gen_85965ccbc1f028f267b73c44da88ffb6 | Implementation of the Ornais phase 1 digital plan - FEDER request | Kohesio | DEPARTEMENT DE L ORNE | https://linkedopendata.eu/entity/Q3673366 | This project is carried out by the Department of Orne. The public actions included in the Ornais Digital Plan (PNO) aim to achieve a homogeneous treatment of the Orne territory allowing in the long term a generalized THD service to the department via the action of the Department, in addition to the operations carried out by private operators on the perimeter of the approved municipalities. The Department of Orne validated the PNO on March 22, 2013. The implementation of the first stage of the first phase, in the form of contracts works, was voted on September 27 and October 25, 2013. These first works contracts relate to the optical service of strategic sites. The work is carried out under project management and departmental project management. The municipalities or EPCI will be asked to provide financial participation. The action of the Department of Orne is concentrated only outside areas of private initiative, and in a search for maximum use of existing infrastructure, in order not to duplicate private networks. FttO The Department has chosen to connect by optical fiber the 33 ZA and 22 priority strategic public sites ineligible for an Orange FttO wholesale offer (CE2O type) on August 1 2014. The estimated total cost of connecting these 55 sites is 6.7 M excluding VAT.FttH The Department has chosen to deploy, in phase 1, the plates of the communities of communes (Cdc) of the Pays d'Argentan (former perimeter) and the Pays de L'Aigle and de la Marche, (in its 2013 administrative perimeter), because they meet the following criteria: - Plates complementary to private initiative; - Clear administrative division (EPCI of the 3rd and 4th commune of Orne); - Cost per catch among the lowest in Orne (around 700 for the Cdc of the Pays d'Argentan and 1,300 for the Cdc of the Pays de L'Aigle and de la Marche); - Plates of approximately 10,000 shots. The Pays d'Argentan Cdc brings together 9,909 outlets spread over 12 municipalities, including 8,000 in Argentan. The Cdc des Pays de L'Aigle et de la Marche brings together 12,456 outlets spread over 25 municipalities, including 5,300 in L'Aigle. The total estimated cost for these 2 public FttH plates is 23.4 M excluding tax, excluding final connection. The Department of Orne will be able to develop the FttH plates selected, depending on the appetite of Orne communities for an FttH deployment, as well as depending on the results of engineering studies. In the 2nd phase of the project, public FttH deployments will continue to achieve population coverage of 75% by 2030. | Smarter Europe / Information and communication technology / ICT: Very high-speed broadband network (access/local loop; >/= 100 Mbps) | 7research_infrastructure
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gen_24c29880db30a84233e4db7773b801a9 | OPH MANCHE HABITAT RENOVATION 96 LOG RESIDENCE “LE PETIT HAMEL” IN VALOGNES | Kohesio | OPHLM MANCHE HABITAT | https://linkedopendata.eu/entity/Q3673441 | Not available | Greener, carbon-free Europe / Low-carbon economy / Energy efficiency renovation of existing housing stock, demonstration projects and supporting measures | 5out_of_scope
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gen_56e12d121ba66b53b7fb9a3ed030065d | FEDER - UNICAEN - CPER INNOVONS - INNOVARET translational research - fct | Kohesio | UNIVERSITE DE CAEN NORMANDIE | https://linkedopendata.eu/entity/Q3673557 | Cerebral, cancer and cardiovascular pathologies represent the leading causes of mortality in all developed countries. They cause physical and cognitive disabilities and more or less severe disabilities that directly impact the quality of life of patients and their loved ones. The aging of the population in developed countries makes the burden of these pathologies increasingly heavy on public health. Improving the care of people suffering from these conditions depends directly on the emergence and diffusion of biomedical innovations from screening to treatment. The interest of these innovations can only be scientifically demonstrated by the implementation of rigorous experimental and/or clinical research protocols. The real impact of recent pre-clinical and clinical innovations on improving patient care in real life is very poorly understood and their impact on the organization of care is poorly evaluated. The rare studies conducted in the general population show how the practice of care and the integration of innovations often escape biomedical logic and depend on social, economic or geographical determinants. The development of supportive care, ambulatory care, therapeutic education as well as the establishment of a care network and the growing involvement of patients in their care have revealed and reinforced the close links between the occurrence and evolution of illnesses and the environment of individuals in its family, social, economic and geographical. Psychological and sociological approaches, facilitated by the growing involvement of user committees, have highlighted the need to take into consideration, around the role of the "carer", the patient's family environment to optimize their care. Geographic and sociological approaches have shown how taking into account the characteristics of the place of residence and the socio-economic environment of patients is a major criterion in the successful development of ambulatory medicine and care networks. Recent examples of health planning, the cancer plan, the Alzheimer's plan show how an integrative approach to the evaluation of innovations, from proof of concept to the measurement of efficiency, is essential to the optimization of care practices, the good management of financial resources in an ever more constrained context and the guarantee of social equity. On the North Caen plateau there is recognized expertise in the fields of neuroscience and oncology through international level research teams, approved by major national organizations (CNRS, INSERM, CEA), supported by cutting-edge regional infrastructures (CYCERON - IBISA platform in in vivo imaging -, CURB - IBISA platform in research on strokes (ESRP) -, SFR ICORE technical platforms), on remarkable coverage of the territory by morbidity registers; all in close relations with health centers (Caen University Hospital and Center François Baclesse). Innov@ReT is part of the more global INNOVONS project which will allow the consolidation of a coherent whole promoting pre-clinical and clinical investigations in the field of screening and functional explorations in neurology, oncology and cardiology. Innov@ReT focuses on the translational aspect of research ranging from cell biology to imaging in humans. This new tool will benefit existing and future EPST structures and the University's reception teams. In addition to providing these research units with the tools for their development and their interface with the clinic, it would be the place for common methodological developments. | Smarter Europe / Research and innovation / Research and innovation activities in public research centres and centres of competence including networking | 6project_grants_public
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gen_08b2f3c727ce3158f4d974ce95eba28d | FEDER - UNICAEN (EVA LAB) - ALGOEVA PROJECT | Kohesio | UNIVERSITE DE CAEN NORMANDIE | https://linkedopendata.eu/entity/Q3680074 | Over the past fifteen years, it has been established that anthropogenic activities combined with natural climatic factors lead to an acceleration of changes in agricultural crop conditions. As a result of these disturbances, plants undergo higher intensity abiotic stress. However, abiotic stresses (extreme temperatures, high salinity, drought, flooding, excess heavy metals, oxidative stress) are the leading cause of loss of agricultural production yields worldwide. In a global context where the challenge of tomorrow is to produce enough to feed an exponential world population, it is a question of innovating in techniques and products intended for agriculture while regulating and legislating effectively to ensure healthy and sustainable development of agricultural production throughout the world. The use of biostimulants is one of the innovative methods allowing sustainable production by limiting the supply of inputs (fertilizers, phytosanitary products). By definition, biostimulants are organic compounds that improve the growth and development of plants. Companies developing in this field need to have precise and rapid tools (bioassays) to test new molecules or extracts and understand their mechanisms of action to guarantee their effectiveness for producers while meeting the requirements of legislators. At the European level, a special council made up of biostimulant producers (EBIC) was created in 2011 to respond to this demand at the legislative and commercial level. Several companies producing algae extracts, including ALGAIA, collaborate within the EBIC on analytical and formulation aspects. Indeed, algae have been used for several generations to improve the performance and quality of plants. Among the molecules isolated from distinct algae sources, some (polysaccharides, mannitol, hormones, antioxidant compounds, etc.) have biostimulating properties. Algae also represent a source of molecules (dextran sulfate, heparin, sulfoevernan, fucoidans, etc.) with antiviral and antibacterial activities. Viral and bacterial infections constitute a major health risk for equines and cause significant economic losses for the equine industry. Thus, the Equine Viral Arteritis (AVE) virus persists in 30 to 70% of infected stallions in the accessory glands of the reproductive system. The virus is excreted in semen. These excretory standards constitute the reservoir of the virus, but no specific treatment allowing the elimination of the virus is currently available. Likewise, no effective vaccine or treatment is available to combat the Equine Infectious Anemia (EIA) retrovirus, which remains a major health concern since infected horses must be euthanized. In the equine industry, bacterial infections are frequent and serious, particularly in young animals. Depending on the age class, they are responsible for 20 to 50% of mortality cases in Normandy equines. In recent years, the intensive use of antibiotics has led to a sharp increase in resistant bacterial populations, with consequences both economic (costly treatments) and public health (possible transmission of multi-resistant strains from animals to humans). Resistance has already been described in certain pathogenic or commensal bacteria in horses such as enterobacteria, enterococci and staphylococci. Certain bacteria could ultimately become resistant to all molecules in the veterinary therapeutic arsenal. This prospect is all the more worrying as innovation in antibiotic molecules is now very limited, hence the need to develop alternative treatments. | Smarter Europe / Research and innovation / Research and innovation activities in public research centres and centres of competence including networking | 6project_grants_public
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gen_28b716fe2f67f1d85c52613b11e62c53 | Develop the skills of employees and new hires with low qualification levels through qualifying training actions - 2018 | Kohesio | DOCKERS DE NORMANDIE | https://linkedopendata.eu/entity/Q3701413 | Our project consists of qualifying training actions (CQP, CACES, driving license, etc.), internal and external to the company for present employees and for new hires of the year. This 2018 plan completes and extends our 2017 plan. The company DOCKERS DE NORMANDIE has an internal training center registered with the DRTEFP, approved as a CACES R 389 category 3, 4 and 6 testing center in accordance with the CNAMTS standard (annual control audit by VERITAS). It has been listed since 2017 on DATADOCK, which constitutes the reference base for training organizations meeting the "quality" criteria of training organizations established by decree 2015-790 of June 30, 2015. Staff of the DOCKERS DE NORMANDIE internal training center: * 1 manager of the training center * 1 manager of internal training, skills and professions * 8 full-time internal trainers in training activities * 1 occasional internal trainer, i.e. compared to 2017, an addition of 2 internal trainers (+25%) due to the increase in the 2018 training plan (doubled in costs and hours of training provided). Actions from the 2018 training plan (see the attached "action sheets" for details) proposed to the FSE: * **Internal actions** (actions carried out by the company's internal training center with rental machines) 1. Initial CQP "docker worker" training + seizure/security training + "experienced" confirmation (hiring path): 140 hours of training - 16 participants 2. Typical machine driver TUG fifth wheel tractor with CQP: 42 hours - 18 participants 3. Rider type machine drivers (handling containers on the terminal) with CQP: 154 hours - 35 participants 4. Rider driver retraining with renewal of qualification: 21 hours - 40 participants 5. Dock gantry operators (ship loading/unloading crane): 105 hours - 12 participants 6. Retraining platform gantry operator with renewal of qualification: 35 hours - 14 participants 7. CACES 4 R 389 with specialization on specific machine with CQP: 49 hours - 4 participants 8. CACES 3 R 389 with CQP: 35 hours - 20 participants 9. CACES 6 R 389: 21 hours - 12 participants * **External actions** (actions carried out by training organizations outside the company) 1. CACES 10 R 372: 28 hours - 12 participants 2. CACES 3B-PEMP R 386: 21 hours - 8 participants 3. C + CE + FIMO permit course: 350 hours - 4 participants In total a forecast of 195 participants for 14,028 hours of training. | Social Europe / Sustainable and quality employment / Adaptation of workers, enterprises and entrepreneurs to change | 5out_of_scope
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gen_ff5f76bc76dbdb7af263829aebc5ee81 | FED INV-15E00116-PAE-APPLI METIERS D ART | Kohesio | ASS PAYS D'AUGE EXPANSION CCI DU PAYS D'AUGE | https://linkedopendata.eu/entity/Q3673287 | Since 2010, Pays d'Auge Expansion has organized events featuring the artistic professions of Pays d'Auge, in particular Open-discover the artistic professions at the Château de Canon, in order to allow school and family audiences to discover these professions more closely. In this context, educational tools have been developed. In 2012, a meeting with Ariane Le Carpentier, Cultural Development Advisor at the DRAC of Basse-Normandie, made us aware of the problem of digital tools and their contribution to a new approach to culture and heritage. Drawing on its experience and the help of technical advisors, Pays d'Auge Expansion launched the project to create a fun digital application to promote artistic crafts. | Smarter Europe / Information and communication technology / e-Inclusion, e-Accessibility, e-Learning and e-Education services and applications, digital literacy | 5out_of_scope
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gen_f997b7b8403531e5fac631765f74fb51 | FEDER FCT GMN PRA CHIROPTERES DE NORMANDIE 2021 | Kohesio | ASS GROUPE MAMMALOGIQUE NORMAND | https://linkedopendata.eu/entity/Q3681854 | The 3rd National Action Plan for Bats 2016-2025 and its Norman version (Regional Bat Action Plan 2017-2025) aim to restore and then maintain the populations of the most threatened bat species. In Normandy, a network of actors has been strongly mobilized since 2009 and the interregional version of the 2nd PNA led by the Norman Mammalogical Group (Interregional Chiroptera Action Plan 2009-2013). | Greener, carbon-free Europe / Environment protection and resource efficiency / Protection and enhancement of biodiversity, nature protection and green infrastructure | 6project_grants_public
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gen_534d748190232136bc4539583e65f47c | FEDER - ESPRIMED - EM.SIM.BASICS PROJECT | Kohesio | ESPRIMED | https://linkedopendata.eu/entity/Q3673410 | Interventional radiology (IR) consists of using imaging, particularly X-rays, to guide devices in the human body for diagnostic or therapeutic purposes. The rate of increase in interventional procedures is of the order of 10 to 20% per year and this discipline is a major focus of the new 2014-2020 Cancer Plan. For example, the CAEN University Hospital carried out 2,023 IR procedures related to oncology in 2013. Due to the duration and complexity of the procedures, the radiation doses delivered to patients and received by practitioners can be very high. IR is definitely the practice to which the institutions responsible for preventing ionizing risks are paying the most attention today. The Nuclear Safety Authority is thus maintaining IR as an inspection priority for the coming years and the High Authority for Health (HAS) published in May 2014 a guide intended to support health professionals in the prevention of deterministic risk in IR. Prevention of radiological risk and the application of the principle of dose optimization mainly depend on the level of training and qualification of the healthcare teams. However, according to articles R.4451-47 and 50 of the labor code, any worker likely to work in a supervised or controlled zone must benefit from training in the radiation protection of the patient (renewed every 10 years) and training in the radiation protection of the worker (renewed every 3 years). This training obligation falls on the employer. Most often, the main obstacles to training mentioned by healthcare structures are the cost, the lack of time of healthcare staff but also the lack of attractiveness of theoretical lessons. The development of simulation for the initial and continuing training of health professionals stands out as an essential innovation which allows one to immerse oneself in reality, to mobilize one's knowledge without taking any risk for the patient and for oneself. This mode of simulation training is supported by the HAS. The objective of the project is therefore to create “serious game” type training software in which the learner will be placed at the center of the action in a very realistic 3D virtual environment reconstituting an IR or operating theater room. In this environment, the learner will be able to choose their operating protocol, their individual and collective protective equipment, freely place the patient and the position of their team in the room in order to identify the right gestures, good radioprotection practices, by illustrating in an interactive and visual manner the influence of their gesture on the dose they receive and on the dose delivered to the patient's skin. The project brings together 4 partners with complementary expertise, essential for the development of a digital training tool for radiation protection in a medical environment: OREKA INGENIERIE, CHU CAEN, esprimed and CEA/INSTN. | Smarter Europe / Research and innovation / Research and innovation activities in private research centres including networking | 6project_grants_public
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gen_32a525737d53bcfb30016b8a6c5b69f5 | FEDER - SEML Innovation Development Bio Materials - Compoline 2 Project | Kohesio | SEML INNOVATION DEVELOPPEMENT BIO MATERIAUX | https://linkedopendata.eu/entity/Q3673436 | Conventional wood panels are produced from wood flour or wood fibers bonded with a thermosetting resin, which is accused of emitting volatile organic compounds (VOCs) such as formaldehyde. These formaldehyde emissions are, today, heavily regulated by various European directives. Waste from the manufacturing and machining of MDF panels as well as that from the end of the life of furniture is not currently recycled and is either sent to landfill or crushed and put into a steam boiler. The woodworking profession is concerned about this and is looking for more environmentally friendly solutions. To remain competitive and face competition from countries with low labor costs, furniture and interior design companies must be innovative and respond to the needs of the market which requires greater customization of products and constant evolution of design. The Compo'line project financially supported by Europe through the objectives of axis 1 of the ERDF "develop the regional innovation potential" of measure 1.2 “making research a priority instrument for the competitiveness of the Lower Normandy economy” and sub-measure 12.2. "supporting partnership research projects between research centers and companies, presenting opportunities in terms of market" by the, the State (DIRECCTE) and the Lower Normandy Region over the years 2010 to 2013, made it possible to develop a 100% bio-sourced thermoformable hybrid wood for furniture and interior design whose commercial name is Selun®. For the wood sector, the project aims upstream to recycle waste from the wood industry in high value-added applications and downstream to modernize furniture manufacturing processes to adapt them to the requirements of the current market and make them more competitive. It aims to innovate in terms of design in order to offer a new furniture offering. Finally, it allows the wood industry to offer recyclable furniture and interior fittings. The arrival on the market of Selun® should make it possible to give new impetus to the regional wood industry, hard hit by company relocations and the consequences of the 1999 storm. This project has been supported since the beginning by the PROFESSIONBOIS association (Interprofessional Association Forêt Bois de Basse Normandie) which brings together the different players in the wood industry. lower-Norman (foresters, sawyers, cabinetmakers, architects), CODIFAB (professional committee for the development of the French furniture and wood industries) and VIA (Valorization of Innovation in Furniture, whose mission is to promote creation and innovation in the sector of furnishing the domestic, professional or urban living environment). The Architect@work trade show in October 2013 where the Selun® was presented for the first time to professionals (architects, specifiers, major accounts) and the numerous contacts such as Beneteau, Bouygues have made it possible to verify the excellent reception of the material which foreshadows a very good entry into the luxury and boating construction materials (2nd work) market. An in-depth European and global market study combined with a business plan are essential for the development of an industrial and commercial development strategy for Selun® as well as its production method and logistics. | Smarter Europe / Research and innovation / Research and innovation activities in private research centres including networking | 0business_rnd_innovation
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gen_a76bd70c6397f5f95659e3230275f5a6 | FEDER - INV - CEN NORMANDY SEINE - REGIONAL WETLAND MANAGEMENT WORKS 2019-2021 | Kohesio | CONSERVATOIRE D ESPACES NATURELS DE NORMANDIE | https://linkedopendata.eu/entity/Q3681344 | Wetlands constitute remarkable natural habitats in Normandy. They are home to almost 40% of the bird species recorded in the region, but also 100% of amphibians and 100% of odonata. The flora, linked to these environments, is extremely rich. These environments are major reservoirs of biodiversity in Normandy and more generally in France. These environments have seen their surface area reduced considerably, more than 70% in around fifty years. The fauna and flora diversity of these humid biotopes is, in fact, seriously threatened. In addition, wet herbaceous areas have a natural tendency to gradually become wooded, which adds to the threat to many species linked to megaphorbias, wet meadows and reed beds. The wetlands of Croisy sur Andelle, Elbeuf sur Andelle and Mesnil Lieubray are home to the last reed beds in this valley. These environments are key to creating a vital ecological corridor for many avifaunal species. They are considered predominant as migratory axes in the Regional Ecological Coherence Scheme of the Normandy region. The CenNS has control of the use or land of wetlands in former Upper Normandy for which it ensures ecological management with the aim of preserving habitats, flora and fauna. Management documents on these 8 wetlands have been produced. These documents set out the different actions to be planned to achieve the objectives of conserving the biological integrity of each site managed by the Conservatory of Natural Spaces of Upper Normandy. Thus the Conservatory of Natural Spaces of Upper Normandy has set up a campaign in 2019 and 2020 of different ecological management operations on 8 wetlands over which it has use or land control. These operations will consist, mainly, of carrying out vegetation mowing actions in order to combat spontaneous afforestation, limit eutrophication and limit the development of invasive exotic species. In addition, actions will make it possible to establish or carry out extensive grazing in certain wetlands. Deforestation operations will also be carried out in very specific sectors of certain wetlands. Finally, several ponds will be dug in order to encourage the reception of Amphibians and Odonates. Several operations such as mowing and digging of ponds will be carried out under subcontracting. the cutting operations (deforestation and maintenance of tadpoles will be carried out by the technical team of the Normandy Seine Natural Space Conservatory. This is made up of six natural space management technicians and a technical manager. They have suitable equipment to carry out this type of restoration work (brush cutters, chainsaws, etc.). | Greener, carbon-free Europe / Environment protection and resource efficiency / Protection and enhancement of biodiversity, nature protection and green infrastructure | 5out_of_scope
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gen_78749e0b8556a3f6134aef66694e0bed | HN0005687 - HABITAT 76 - REHABILITAT° ENERGETIQ BBC FROM 143 TO 124 SOCIAL RENTAL HOUSING 11 TO 19 BD W CHURCHILL IN LE HAVRE | Kohesio | Office Public de l'Habitat du Département de la Seine Maritime | https://linkedopendata.eu/entity/Q3681192 | The Office owns a set of 143 housing units located at 11 to 19 Bld W. Churchill on the immediate outskirts of the city center of the commune of Le Havre. It has decided to initiate a major rehabilitation program for this site, with a strong energy dimension with an equivalent level of performance "low energy consumption building BBC 2009 renovation". Elevators will be integrated, the common areas taken over and the housing units will be enlarged, reducing their number to 123. | Greener, carbon-free Europe / Low-carbon economy / Energy efficiency renovation of existing housing stock, demonstration projects and supporting measures | 5out_of_scope
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gen_f863cae0e2719df4cc90a3eb103a0be9 | HN0002219 - SILOGE - THERMAL REHABILITATION WORK ON 235 COLLECTIVE RENTAL HOUSING IN LERY | Kohesio | SOC IMMOB LOGEMENT DE L'EURE SA HLM | https://linkedopendata.eu/entity/Q3680800 | Located in the commune of LERY and bordering the town of VAL DE REUIL, the Quartier des Sentiers is made up of 20 buildings ranging from R+3 to R+5, bringing together 235 collective housing units built between the years 1975 and 1980, totaling a living area of 15,746 m2. These housing units are equipped with individual gas boilers ensuring heating and the production of domestic hot water. The ventilation of the housing units is ensured by self-adjusting Gas Controlled Mechanical Ventilation. Ventilation installations are located on terraces and in attics. The extractors are in good condition but their performance is average compared to current technologies. The BAZ type vents for connecting the boiler in the kitchen are in average condition. Part of the facades (wooden panels) are covered with wood in poor condition, the other part of the woodwork panels are covered with sheet metal in average condition. We can see thermal bridges on the facades/intermediate floors. The original radiators are aging, the thermostatic valves are in average condition and of average performance. | Greener, carbon-free Europe / Low-carbon economy / Energy efficiency renovation of existing housing stock, demonstration projects and supporting measures | 5out_of_scope
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gen_94b552dc480c310c8efbee3b685155fe | FEDER - UNICAEN (LCMT LAB) - FOVETH PROJECT | Kohesio | UNIVERSITE DE CAEN NORMANDIE | https://linkedopendata.eu/entity/Q3680127 | The research project “FOrmulation and development of a Thermogravable VErnis (FOVETH), carried out by the company Mulann Industries and the LCMT laboratory, is a collaborative project aimed at formulating innovative polymer coatings for lacquers. Lacquers are aluminum discs covered with a polymer varnish, used for the manufacture of molds or “stampers” intended to press vinyl records. These lacquers are engraved from a sound recording, then undergo an electroforming (or electroplating) step to obtain a “master” or “original” which will then allow the manufacture of “positives” then “stampers”. The lacquer market (200 to 250,000 pieces per year) is shared on a global scale between two manufacturers: Transco in the USA and MDC in Japan. The FOVETH project should enable the Mulann company, an SME located in Avranches (40 people, €5.5 million turnover) and specialized in the design, manufacturing and distribution of magnetic tapes (analog audio and bank cards), to become the only producer of lacquers in Europe. Taking advantage of the rebound in the vinyl industry since 2017 and the dynamism of the European pressing market (75% of the global market, including the leaders GZ records, MPO, Optimal Media and Record Industries), the capture of 30% of the market for a turnover of 1 to 1.5 M€/year is envisaged based on the need to secure lacquer supplies from European manufacturers and the development of competitive and innovative products. The formulas used to produce lacquer varnishes were developed in the 1950s during the emergence of the vinyl record market. These varnishes are nitrocellulose resins, the use of which was very widespread at the time due to their rigidity and the ease of their implementation (by simple evaporation of solvent). The final properties of the coating are adjusted using solvents or various additives which may be plasticizers, polymers or mineral fillers. Due to the slowdown in the market at the end of the twentieth century, caused by the appearance of new digital media, there is very little recent research devoted to the formulation of this type of varnish. Societal concerns linked to the flammability of solvents used to apply nitrocellulose varnishes (acetates) have led to their substitution in certain applications (furniture), but they remain widely used, particularly in cosmetics (nail varnish). The durability of nitrocellulose varnishes remains limited (UV resistance, sensitivity to humidity) compared to “modern varnishes developed on a polyurethane base for example. In addition, their implementation by solvent evaporation involves application constraints. For example, the time required for drying varnishes (several months) does not allow lacquer producers to be able to respond to urgent demand without maintaining a large stock. In conclusion, there are therefore multiple potential avenues for formulating an innovative and competitive lacquer varnish in a market that has been neglected for several decades. The need to secure the supply of European vinyl manufacturers, the low competition on an international scale, the opportunity to develop innovative and modern formulas, and the adequacy of the skills of the Mulann company and the LCMT laboratory justify the establishment of this research project. | Smarter Europe / Research and innovation / Research and innovation infrastructure (public) | 6project_grants_public
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gen_501464355393726da7e58ce2142d70ca | FED FCT 16E00132 GCS TSBN SI Coordination Secure data sharing and exchange services | Kohesio | GROUPEMENT DE COOPERATION SANITAIRE NORMANDE SANTE | https://linkedopendata.eu/entity/Q3673473 | In 2013, the release of several reports and strategic roadmaps (Pacte Territoire Santé, Cordier Report, National Health Strategy) highlighted the need to decompartmentalize the French health system to enable it to respond to the challenges linked to: - the aging of the French population; - medical desertification, which generates strong territorial inequalities in terms of access to care; - the strong growth in the number of patients suffering from chronic diseases. Faced with these new challenges and the emergence of these new professional practices, e-health constitutes a major lever of transformation. Indeed, information and communication technologies (ICT) applied to health constitute a structuring technological base essential for organizations based on a logic of openness, communication and sharing. The ambulatory component of the SROS determines the regional strategy for organizing ambulatory care by defining action priorities in terms of structuring the provision of primary care. The two major challenges are: maintaining access to local care and decompartmentalizing care. By providing coordination teams and partner health professionals with a professional tool for patient care (diagnosis, PPS creation, needs assessment, advice, expertise), the project aims to provide support for the coordination of professionals serving the decompartmentalization of the patient journey, facilitating collaborative and multi-professional care. | Smarter Europe / Information and communication technology / ICT solutions addressing the healthy active ageing challenge and e-Health services and applications (including e-Care and ambient assisted living) | 6project_grants_public
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gen_818164438f68afd1dd0f95052a1055e8 | HN0004284 - CREFOR EMPLOYMENT TRAINING RESOURCE CENTER - PROFESSIONALIZATION OF REGIONAL ACTORS IN GUIDANCE AND LIFE-LONG TRAINING IN THE FRAMEWORK OF THE SPRO | Kohesio | CREFOR DE HAUTE-NORMANDIE | https://linkedopendata.eu/entity/Q3681101 | The law of March 5, 2014 and the implementation of the new measures it introduces, in particular the Regional Public Guidance Service, aim to make guidance services and places more operational, more efficient and more identifiable, for greater quality of guidance for the public. This new context sheds strong light on the challenges of the professionalization of actors and the need to support them in their practices, in the evolution of their skills and in the construction of new benchmarks. At the same time, the merger of Upper and Lower Normandy into a single large Normandy region on January 1, 2016 effectively poses a new territorial framework of intervention for all guidance actors, thus making the need to work on the harmonization of practices even more essential. throughout Normandy. For several years, Crefor has been implementing a professionalization action program aimed at those involved in guidance, training, integration and employment. Some of these actions should enable guidance operators to consolidate and broaden their skills and to be able to exchange with each other about their practices and experiences. The actions that Crefor proposes involve working on both the “expertise” and the positions of professionals, by crossing the different networks: local missions, employment center, assessment centers, employment cap, etc. | Social Europe / Educational and vocational training / Improving the labour market relevance of education and training systems, facilitating the transition from education to work, and strengthening vocational education and training systems and their quality, including through mechanisms for skills anticipation, adaptation of curricula and the establishment and development of work-based learning systems, including dual learning systems and apprenticesh | 5out_of_scope
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gen_116cbb462b3b958a739b833d28ace1a5 | 18E03435 - CH INTERCOMMUNAL EURE SEINE - DIGITAL PATIENT JOURNEY IN AN EMERGENCY DEPARTMENT | Kohesio | CENTRE HOSPITALIER INTERCOMMUNAL EURE SEINE | https://linkedopendata.eu/entity/Q3681357 | The CH Eure Seine is part of a development and innovation approach, supported by the Normandy Evreux-Vernon Center for Innovation, Clinical Research and Education (CIRCE-NEV). This structure aims to attract practitioners and students to the Hospital Center and the health region by offering them the means to structure and participate in clinical research projects, to engage in the development and deployment of innovative solutions. This diversification of activity makes it possible, while strengthening attractiveness, to fight against medical desertification in the region. With this in mind, the system is open to members of the GHT, private medicine and primary care stakeholders. Above all, this must allow patients in our healthcare region to access research protocols and the most innovative therapies and care techniques. Indeed, recent technological progress, awareness of the issues, as evidenced by the Villani report, and regional dynamism in the field of e-health have led CIRCE-NEV to integrate a digital axis. The conventional partnerships put in place with local authorities, the University of Rouen, the INSA of Rouen and the URML allow this center to respond to the needs of caregivers and the local population while positioning, through its innovative nature, the territory as a precursor in the domain. The actions are divided into 3 axes: teaching, communication, and “pilot digital emergencies”, an innovative global project making it possible to address themes of development of digital tools, exploitation of data, research while being strongly anchored with the socio-economic fabric and the real needs of caregivers and patients. The latter will be able, if they wish, to benefit from digital support for admission to post-emergency follow-up. Particular attention will be paid to supporting the patient throughout their journey. Thus work will be carried out on the ergonomics of the solutions proposed in order to reach the widest population while taking into account particularities and disabilities. The tools will be part of the national e-health strategy by allowing links with the DMP. The emergency department constitutes an interface between hospital care and the ambulatory health network. It also represents an area of tension: with 92,000 passages per year, improving operation with constant human resources represents a real challenge. EMERGENC-e aims to respond to these issues while working to improve patient care. Thus, each step of the journey will be evaluated to measure the quality of the response to these different objectives. Its reproducible nature will make its deployment possible in other services and across the GHT and then in other establishments interested in the solution. Obtaining a significant volume of data will make it possible to address various research issues, whether in terms of improving the quality of care, modeling patient behavior, or controlling health costs. This project will involve strong interdisciplinarity since joint work will have to be carried out with academic mathematics and computer science laboratories. It will have an impact with the training of young graduates who will evolve in an atypical environment by approaching patient care from a new angle at the cutting edge of digital technology. Finally, interactions with the socio-economic fabric will be favored via access to the living-lab, and the entanglement of the device in the digital space of the agglomeration, and inclusion in a global strategy to take into account disabilities in the territory. | Smarter Europe / Information and communication technology / e-Government services and applications (including e-Procurement, ICT measures supporting the reform of public administration, cyber-security, trust and privacy measures, e-Justice and e-Democracy) | 6project_grants_public
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gen_0db0687c87b6bb3c75f00f3fb8237716 | FEDER - FCT - REG PROGRAM OF ACTIONS IN FAVOR OF MARES 2019 - CEN NORMANDY SEINE | Kohesio | CONSERVATOIRE D ESPACES NATURELS DE NORMANDIE | https://linkedopendata.eu/entity/Q3681353 | Ponds once had many practical uses to meet human needs: domestic uses (water reserve, fish tank for food, laundry), agricultural uses (watering trough for animals, retting of flax and hemp), artisanal uses (basketry) but also for leisure activities (swimming, fishing, etc.). The evolution of agricultural practices (consolidation, drainage, intensification) and the arrival of drinking water in homes have led to a gradual abandonment of ponds and many of them were filled in or filled in naturally. Since 1950, between 30 and 50% of ponds have disappeared in France. The remaining ponds are mostly abandoned. In Normandy, it is estimated that 40% of ponds are threatened in the short term. Today, ponds are once again recognized as special environments with multiple interests. From an ecological point of view, they constitute real reservoirs of biodiversity in which numerous animal and plant species linked to the presence of water can develop and reproduce. As such, ponds constitute a formidable educational tool for educating schoolchildren and the general public about the protection of nature. These environments also constitute an essential link in the blue network, particularly in plateau areas where they are often the only constituent element of this network. Ponds also play a hydraulic role in the regulation and storage of runoff water. They also contribute to water purification and the preservation of hydrosystems through the trapping of sediments, pollutants (pesticides, nitrates, etc.) and their degradation through microbial processes. They have an interest in livestock breeding since they are also used to water livestock in grazed meadows. Furthermore, these environments constitute a strong element of landscape diversification, particularly in areas of intensive agriculture, and a space of relaxation and discovery for the public. Awareness of the need to protect these environments has emerged among several Norman stakeholders (intercommunities, local associations, watershed unions) for several years. Numerous actions in favor of ponds are thus emerging, but in a more or less concerted manner and with objectives specific to each structure and which sometimes do not necessarily go in the direction of improving the ecological quality of ponds. Conversely, other territories do not benefit from restoration and protection actions in favor of these environments. The need to coordinate actions, to mobilize all stakeholders in the territory, to improve consideration of the biodiversity of ponds but also to educate the general public and schools required the development and implementation of a regional plan: the Regional Action Program in favor of Normandy ponds. This program, the challenge of which is to halt the process of degradation and disappearance of ponds in the region was initiated and is supported by the Conservatories of Natural Spaces of Normandy. This request for financial assistance only concerns the Conservatory of Natural Spaces Normandy Seine for the regional animation of the PRAM and its variation on the territory in the departments of Eure and Seine-Maritime. On the other hand, the project described in this technical report (lines of work, objectives and operations) is the result of concerted work common to both Conservatories of natural spaces to be available across Normandy. For territorialized actions, each Conservatory is responsible for implementing them in its territory of competence. For actions across Normandy, the Conservatories work together in complete coherence and complementarity. | Greener, carbon-free Europe / Environment protection and resource efficiency / Protection and enhancement of biodiversity, nature protection and green infrastructure | 5out_of_scope
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gen_9847bcca8b4aeabfefaa6b28be8026b5 | FEDER - UNICAEN - SCHISM - SPRINGBOARD | Kohesio | UNIVERSITE DE CAEN NORMANDIE | https://linkedopendata.eu/entity/Q3680427 | Early research on machine learning (ML) and data mining (DM) tried to fully automate knowledge discovery processes, and reduce human intervention. For good reasons: we have trouble dealing with large amounts of (high-dimensional) data, a tendency to see patterns everywhere, and technical progress has always relieved us of time-consuming tasks. This also motivates current work on automatic parameter tuning [26]. While this can work well in supervised settings where the label to predict gives feedback and a well-working black box model might be all that is needed, this consensus is increasingly being questioned in DM today. users’ assumptions [1], are relatively recent. Also recent is research on interactive data mining methods, which allow the user to give feedback during the mining process – not just before and after – to change exploration strategies, narrow or widen search spaces etc. [3]. The reasons for this shift have been multifold:1. In unsupervised settings such as clustering and pattern mining, labels are by definition absent and automation based on label-information therefore impossible. Yet even in many real-life “supervised” problem settings, a large proportion of data might be unlabeled, and existing labels might be unreliable, so that a user finds herself at best in a semi-supervised setting.2. In an unsupervised or semi-supervised setting, it is almost impossible for users to a priori specify their assumptions, expectations, and goals. If they manage, translating them into, somewhat limited, available constraint languages is difficult. The current framework, where users set parameters before mining, and sift through and interpret output after, wastes time (and money), and is counterintuitive to how we process information. What users can do, however, is react to (partial) results and indicate whether those agree with their intuition, appear interesting etc.3. Often, experts need to understand why algorithms produce the results they do, because large amounts of money or resources are in play, e.g. in drug development or infrastructure deployment, or even lives at stake, e.g. in medicine, disaster preparedness, or military settings. Or they want to understand them because unsupervised DM serves as a hypothesis generator: observing the results of a pattern mining operation or a produced clustering can trigger new insights and inform new research directions - the final step in the “knowledge discovery” process. In the context of SCHISM, we think this process starting from a chemoinformatics setting. Chemoinformatics deals with the description of molecular entities, and both pattern mining and clustering have been used to derive new knowledge: a) Pattern mining, to identify promising substructures for drug development, or shared subpatterns of toxic compounds [19, 13] b) Clustering to identify and select representatives of molecular libraries for virtual or experimental screening, to design novel diverse or focused libraries, and compare libraries from various providers [11], and more generally to actively investigate structural similarity. chemogenomic analysis to pre-clinical studies, cluster-analysis can be used:¿ to get the level of diversity of a molecular dataset,¿ to find molecular structures that share a given structural scaffold,¿ to get a first view of structure-activity relationship by a comparison of chemicals in each cluster,¿ to decide which compounds to prioritize in an acquisition decision, ¿ to guide a lead selection. See application file | Smarter Europe / Research and innovation / Research and innovation activities in public research centres and centres of competence including networking | 6project_grants_public
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gen_7a5788706e859d81bf429615bc216e44 | FEDER - ANALYZES AND SURFACE - CLIP FAM PROJECT | Kohesio | ANALYSES ET SURFACE | https://linkedopendata.eu/entity/Q3681429 | Metal Additive Manufacturing is identified as a key technology because it has two major advantages: - Production of parts with complex shapes - Possibility of producing very small flexible series It is estimated that the market grows by 20% each year and it is essential that France remains in the competition with this technology. Many projects relate to Additive Manufacturing whether on: - Design, digital - Characterization and performance of parts - Implementation of this technology and new processes With large centers of skills (IRT Jules Vernes, CETIM, Mines). Normandy has strong skills around: - The development of powders (Metal Value to come) - Studies and modeling on the powder, from the finished product to its optimization in situ or post-manufacturing: structure / properties relationship (GPM, CNRT Materials, Analysis and Surfaces, CEVAA, ArianeGroup) - Implementation - Industry (Volum-e / ArianeGroup)A structuring of additive manufacturing players in Normandy is underway (supported by the NAE RTI roadmap) | Smarter Europe / Research and innovation / Research and innovation infrastructure, processes, technology transfer and cooperation in enterprises focusing on the low carbon economy and on resilience to climate change | 3networking_collaborative
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gen_462a243850877703aba484d694371398 | 2019 - Support for artisans and traders in the use of digital technology | Kohesio | COMMUNAUTE DE COMMUNES DE VILLEDIEU INTERCOM | https://linkedopendata.eu/entity/Q3680195 | The Normandy Region set up an FEDER (European Regional Development Fund) system in April 2018 which is aimed at EPCIs with an approach to raising digital awareness among artisans/traders. This system falls under measures 1.4 of the Orne/Manche/Calvados Operational Program. The digital transition of craftsmen-traders is a major issue for the Region, both to respond to its economic development strategy and to ensure the sustainability of crafts. and local businesses which largely contribute to social ties in the region's towns and medium-sized towns. To this end, the Region wishes to strengthen the EPCIRégion duo to support artisan-retailers in their digital transformation. Indeed, the benefits of digital tools and services for these players are major in terms of productivity and efficiency: time saving, cost reduction, simplification of management, optimization of organization, improvement of the quality of products and services, visibility to the public. This aid, awarded in the form of a grant, aims to support EPCIs in awareness-raising and support actions for artisan-traders for the appropriation of digital tools in their professional practices: - Global and individual diagnosis of the use of digital tools and services by artisans/traders - Conducting awareness-raising workshops/sharing digital experiences - Individual or collective support These actions can be carried out by EPCI staff and/or by external service providers. The amount of FEDER aid amounts to 50% of expenses and the amount of the grant granted cannot be less than €20,000 (i.e. a minimum amount of eligible expenses of €40,000). The maximum rate of public aid received on the project cannot exceed 80%. It appears today that Villedieu Intercom has initiated this type of approach with craftsmen and traders. As a result, Villedieu Intercom is approaching the Normandy Region as part of this system. | Smarter Europe / Competitiveness of SMEs / Advanced support services for SMEs and groups of SMEs (including management, marketing and design services) | 0business_rnd_innovation
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gen_89c4eff769d95004b1696d42c3106376 | HN0002488 - HABITAT 76 - ENERGY REHABILITATION OF THE CITY GATES IN MAROMME | Kohesio | Office Public de l'Habitat du Département de la Seine Maritime | https://linkedopendata.eu/entity/Q3680688 | Habitat 76 attaches the greatest importance to controlling rental charges. In this regard, the Office has classified its assets into two categories, depending on the situation of the residences in relation to a threshold of rental heating charges borne by the tenants. Below this threshold, residences will be subject to treatment relating only to the operation of existing thermal installations. Beyond this threshold, residences, in addition to taking operation into account, will benefit from work to improve energy performance. For this, the Office has opted for Energy Performance Contracts (EPC) which combine works, supplies and services, with at least an energy service company, one or more building companies, an engineer and an architect. The three dimensions to be highlighted in this project are the energy performance work for controlling costs. rental properties, the choice of energy sources to limit the use of fuel oil and propane and use renewable energies where appropriate, and the notion of performance guarantee, essential to ensure the level of tenants' charges | Greener, carbon-free Europe / Low-carbon economy / Energy efficiency renovation of existing housing stock, demonstration projects and supporting measures | 5out_of_scope
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gen_f8ceec1604dcd79ec8ff544b64ba196d | FEDER 2020 - Luminopolis - Uncover the mysteries of energy in Normandy | Kohesio | SCIENCE ACTION HAUTE-NORMANDIE | https://linkedopendata.eu/entity/Q3681678 | Part of a territorial development movement, the Atrium's programming evolves each year according to an editorial choice. In 2019, a major exhibition “Journey to Mars” inaugurated this first year with more than 17,000 visitors. In 2020, it is a focus on a new theme: Energy, a project co-constructed with Normandie Energies, the Normandy energy mix sector. A true regional showcase to promote regional industrial sectors of excellence, the Atrium will offer around the scientific and societal dimensions of Energy, a major exhibition of scientific culture with the richness of Normandy's industrial fabric at its heart in order to present innovative know-how and the resulting professions from the sector which has more than 200 players. | Smarter Europe / Research and innovation / Research and innovation infrastructure (public) | 5out_of_scope
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gen_5066f1cbfb9f5058a3bdfd18bbe207c4 | FEDER - DEDIENNE MULTIPLASTURGY GROUP - PROJET THESIS | Kohesio | DEDIENNE MULTIPLASTURGY GOUP | https://linkedopendata.eu/entity/Q3680515 | The aeronautics sector is constantly looking for solutions to improve performance and limit fuel consumption. In this sense, a technological breakthrough in terms of energy architecture is currently being studied. The objective is to eliminate the drawing of high temperature and high pressure air from the engines and to replace it with the generation of electrical energy. This change in architecture aims to improve the overall energy balance of the aircraft. This change in architecture involves reviewing certain aircraft systems which currently operate using high temperature and high pressure air. | Smarter Europe / Research and innovation / Research and innovation infrastructure, processes, technology transfer and cooperation in enterprises focusing on the low carbon economy and on resilience to climate change | 0business_rnd_innovation
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gen_18d989059176c18abbe9b5b58986a284 | CREACOOP 14 - Plan d'actions 2019 - FEDER | Kohesio | CREA COOP 14 | https://linkedopendata.eu/entity/Q3680208 | Support for project leaders aiming to create their own job. | Smarter Europe / Competitiveness of SMEs / Advanced support services for SMEs and groups of SMEs (including management, marketing and design services) | 0business_rnd_innovation
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gen_38699d252574419329ddde1381ed96ae | Support for the implementation of Real Estate Master Plans for medium-sized towns in Normandy | Kohesio | AGENCE DE L ENVIRONNEMENT ET DE LA MAITRISE DE L ENERGIE | https://linkedopendata.eu/entity/Q3680559 | Not available | Greener, carbon-free Europe / Low-carbon economy / Energy efficiency renovation of public infrastructure, demonstration projects and supporting measures | 5out_of_scope
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gen_815af83d8f863efb0fdcc625743f3bff | Auto-Cove 2.0; Greening Europe with support of Clean-tech-vehicle education | European Commission (EC) | JAKOB-PREH-SCHULE STAATLICHE BERUFSSCHULE BAD NEUSTADT AD SAALE;TARTU LINNAVALITSUS;TECHNISCHE HOCHSCHULE WUERZBURG-SCHWEINFURT;Estonian University of Life Sciences;VOLVO CAR FINLAND OY AB;Kaunas University of Applied Engineering Sciences;VENTSPILS TEHNIKUMS;Teknologian tutkimuskeskus VTT Oy;SOCIETE D'ENSEIGNEMENT PROFESSIONNEL DU RHONE;KAUNO TECHNOLOGIJU MOKYMO CENTRAS;BILIA OY AB;ELECTUDE INTERNATIONAL BV;STICHTING REGIONAAL ONDERWIJS CENTRUM NOORDOOST-BRABANT;ESPOON SEUDUN KOULUTUSKUNTAYHTYMA OMNIA;PREH GMBH;TOYOTA BALTIC AKTSIASELTS | Not available | Unknown | 6project_grants_public
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gen_735b54f3ec7b01bb704160d10b2f4c7e | LEAarning analytics and AI for personaliseD lEaRning | European Commission (EC) | VIRTUALCARE, LDA;Πανεπιστήμιο Κρήτης – Τμήμα Βιολογίας;CENTRE FOR ADVANCEMENT OF RESEARCH AND DEVELOPMENT IN EDUCATIONAL TECHNOLOGY LTD-CARDET;EDEX - EDUCATIONAL EXCELLENCE CORPORATION LIMITED;Tallinn University;University of Pitesti | Not available | Unknown | 6project_grants_public
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gen_ca2a73721bfd733e78aef078dd06bd62 | Teaching History for Disabled Students through Digitilized Gamification Tools | European Commission (EC) | Stichting International Excellence Reserve;ZDRUZENIE INSTITUT ZA RAZVOJ NA ZAEDNICATA;State Higher Vocational School in Skierniewice;Avrasya Yenilikçi Toplum Derneği;Istituto d'Istruzione Superiore Mandralisca;SCOALA GIMNAZIALA SPECIALA PENTRU DEFICIENTI DE VEDERE | Not available | Unknown | 6project_grants_public
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gen_e739adfb6f827c0c7d2349c20829d37e | EMPATHY FOR CHILDREN | European Commission (EC) | Sukromna zakladna skola;European Center of Entrepreneurship Competence & Excellence;Infomedia Formazione;Institute for Research and Development “Utrip”;HLAVNE MESTO SLOVENSKEJ REPUBLIKY BRATISLAVA | Not available | Unknown | 5out_of_scope
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gen_fe2b81803c19fe9b2ed1d4ec3b255620 | Creative learning for boosting bio-economy within HEIs’ curricula | European Commission (EC) | University of Foggia;UNIVERSIDADE DE AVEIRO;Warsaw University of Life Sciences;EDEX - EDUCATIONAL EXCELLENCE CORPORATION LIMITED;Valuedo srl | Not available | Unknown | 6project_grants_public
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gen_4666bb7d834e3f619fd6aca4ccde2154 | Excellence in Esport Education | European Commission (EC) | Teknikum;Arna vidaregåande skule;Svenska Framtidsskolan i Helsingforsregionen Ab | Not available | Unknown | 6project_grants_public
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gen_8dfea1b1aeacb5bdcdcc793bbde4c607 | Non-archimedean methods in geometry and topology | Swiss National Science Foundation (SNSF) | Chair de géométrie arithmétique EPFL - SB - MATH - ARG | Not available | Unknown | 6project_grants_public
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gen_12f40cb526167fa300bce66cf1ca65ca | Managing a Just Transition to Net-Zero | Swiss National Science Foundation (SNSF) | College of Management;PASU Chair Odyssea Station 5 EPFL | Not available | Unknown | 6project_grants_public
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gen_b4b376aa202d92e632dab7afd4f4c20d | Hyper-Representations: Learning from Populations of Neural Networks | Swiss National Science Foundation (SNSF) | Chair in Artificial Intelligence & Machine Learning - School of Computer Science;University of St. Gallen | Not available | Unknown | 6project_grants_public
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gen_abec02e6588698e695fef37f0b79b367 | L'exécution forcée en Égypte ptolémaïque et romaine | Swiss National Science Foundation (SNSF) | Chair of Roman Law and the Law of Antiquity Faculty of Law University of Warsaw | Not available | Unknown | 6project_grants_public
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