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Your search matched 212 Projects
Jul 2017 - Jun 2025
Industry/University Consortium in Hypoid and Bevel Gear Mesh and Dynamics sponsored by University of Cincinnati
  Industry/University Research Consortium in Hypoid and Bevel Gear Mesh and Dynamics
Nov 2019 - Oct 2024
Project Match Made in Schools (MMS): Special Educators and Social Workers Enhancing Services for Students with Disabilities and High-Intensity Needs sponsored by Department of Education
The purpose is to produce scholars with interdisciplinary training in special education and social work.
The project will produce 46 scholars: 23 in special education and 23 in social work. The program will produce special education teachers who can connect students and families with necessary social work services and produce social workers who can provide evidence-based instruction to students and families. The project's goals include recruiting and retaining high-quality master's students; building capacity and systems for sustainability; providing high-quality collaborative field experiences and coursework; and evaluating the project's impact on scholars' ability to demonstrate project competencies.
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Aug 2018 - Jul 2023
Mechanisms of host protection during infection via the mitochondrial unfolded protein response (NIH R35 application) sponsored by National Institutes of Health (NIH)
The rise of antibiotic resistant pathogens in the clinic is undeniably a recognized medical concern since it is the cause of enormous human and economic loss worldwide.
Of further alarm is the lack of new therapeutics to combat these harmful and potentially deadly infections. Accordingly, it is critical that we generate novel approaches to address this growing problem. The development of reagents that enhance host immunity may be an effective alternative strategy to promote host resistance to infection by reducing pathogen numbers. In addition, identifying mechanisms that can support host tolerance to withstand the damage inflicted by harmful microbes and the inflammatory response is equally as vital.   Mitochondria have multiple essential cellular functions including a recognized role in mediating the immune response. The mitochondrial unfolded protein response (UPRmt), a stress-activated pathway that recovers mitochondrial function, also participates in host defense against infection through the regulation of innate immunity. Further investigation into the regulation and therapeutic potential of the UPRmt is therefore warranted considering its dual roles in preserving mitochondrial homeostasis and inducing anti-microbial defense. The current proposal will harness the power of Caenorhabditis elegans genetics to explore the role and regulation of the UPRmt in the context of pathogen infection to uncover novel means of manipulating its protective potential. Moreover, we will build on our current understanding by evaluating the potential role of the mammalian UPRmt in promoting host survival during infection. Consequently, we foresee many innovative concepts stemming from this research proposal.
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Jul 2018 - Jun 2023
Loss of Numb in Muscle Dysfunction in Aging sponsored by Bronx Veterans Medical Research Foundation, Inc.
Drs. Brotto and Cardozo have now a very solid collaboration having generated together the preliminary data for this proposal and having presented at meetings and published one abstract together.
Their first manuscript together will be published soon. Dr. Brotto will closely work with Dr. Cardozo in all the design, planning, and interpretation of all experiments requiring his expertise, particularly muscle and cell based experiments requiring his expertise. He will also advise Dr. Cardozo on other aspects of the proposal as needed and assist with interpretation of data and writing of manuscripts. They also plan to meet yearly at the ASBMR meeting and potentially one more time either through Lab visits or at the Experimental Biology or Biophysical Meeting.   
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Apr 2019 - Mar 2023
Evolution of effector caspase conformational landscapes sponsored by National Institutes of Health (NIH)
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Our primary goal in this proposal is to examine the evolution of the caspase family of proteases, which cells use for developmental processes and for cell death.
We utilize evolutionary, biochemical, and structural approaches to determine when neofunctionalization occurred in the caspase clusters, how the allosteric sites affect conformational selection or communication networks with the active sites, and how cells utilize these features to fine-tune enzyme activity. Caspase enzymes are cysteinyl proteases that are critical to apoptosis, or programmed cell death, and may have evolved in metazoans from ancestral functions used in immune responses. The human caspase family contains eleven enzymes, and all caspases cleave substrates following aspartate residues (P1), while specificity is determined primarily by the fourth amino acid in the substrate recognition sequence (P4). In addition to their roles in apoptosis, the effector caspases-3, -6, and -7 are important enzymes in developmental processes when enzyme levels are held below the threshold required for cell death. The caspase family is an excellent model to study functional diversity because key features of substrate specificity and allosteric regulation are retained through hundreds of millions of years of evolution, while other regulatory features are modern and cluster-specific. In order to examine allosteric regulation of caspases, we developed a database for phylogenetic analysis of the caspase family, and we analyzed the caspase-3,6,7 cluster of effector caspases to annotate each residue in the enzyme and to reconstruct ancestral caspases. We developed tools for genomic and structural analyses, and phage-display substrate libraries, allowing for a comprehensive characterization of caspases. From our analysis of modern and ancestral caspases, we will determine how enzyme specificity evolved in the caspase-3,6,7 cluster, and we propose an evolutionary pathway for redesigning enzyme specificity. We will also examine recently evolved motifs in the pro-domain of mammals to determine how an allosteric site utilizes the new motifs to assist in dimer assembly, and we will examine a common phosphorylation network that also provides individualized regulation. We will examine the expansion of the conformational landscape in the caspase-6 cluster that resulted in a new inactive state, which provides additional regulation during neuron development. Understanding how cells fine-tune caspase activity is important physiologically because the dysregulation of caspases is a common mechanism observed in a number of disease states, from heart disease, to diabetes, arthritis, Alzheimer’s and cancer, in which either too much or too little caspase activity leads to disease progression.
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Apr 2018 - Mar 2023
Estrogen and Zoster Associated Orofacial Pain sponsored by Texas A&M University System (TAMU)
Pain is a common complication of herpes zoster (HZ) infection which results from reactivation of a latent varicella zoster virus (VZV).
Importantly, about 80% of trigeminal ganglia are infected with VZV and womenreport pain due to HZ up to 3 times more often than men but the reason for sex this difference is unknown. To address the mechanism for this sex difference a screen of over 30,000 genes in five brain regionsindicated that glutamate decarboxylase 2 GAD2, and vesicular GABA transporter (VGAT) were elevated in the thalamus of proestrus, high 17 ?-estradiol (E2) versus diestrus rats (low E2). Using a rat model fororofacial VZV associated hypersensitivity ovariectomized (OVX) female rats had greater VZV associated hypersensitivity than male rats and blockade of E2 production in males by aromatase antagonist letrozoleincreased VZV associated hypersensitivity. Moreover, reducing VGAT in the thalamus increased hypersensitivity. Based on these preliminary studies it was hypothesized that E2 reduces orofacial zosterassociated hypersensitivity through increasing VGAT or GAD2 expression. To test this we propose the following three specific aims. Aim #1 will characterize thalamic inhibitory pathways that control VZVassociated orofacial hypersensitivity. Our working hypothesis is that GABA expressing inter-neurons in the reticular thalamic nuclei (Rt) or zona incerta (ZI) inhibit activity in the posterior thalamic nuclei (Po) orventroposteriormedial thalamic nucleus (VPM) to reduce VZV associated orofacial hypersensitivity. To test this hypothesis first, VZV associated hypersensitivity and neuronal activity in the Po and VPM will bemeasured after inhibiting or stimulating these interneurons. Second, hypersensitivity and activity will be determined after modulating VGAT and GAD2 expression in these interneurons. Aim #2 will determine therole of sex steroids on VZV associated orofacial hypersensitivity and cellular activity in both males and females. Our working hypothesis is that elevated E2 increases expression of VGAT and GAD2 in thethalamus to modulate neuronal activity and reduce VZV associated hypersensitivity in both female and male rats. Hypersensitivity and neuronal activity will be measured after E2 is administered to OVX rats and after E2 and aromatase inhibitors are administered to male rats. Aim #3 will characterize the mechanism by which sex steroids modulate VGAT and GAD2 expression in the lateral thalamic region of males and females. Our working hypothesis is that E2 binds estrogen receptor (ER?) to increase expression of VGAT and GAD2 in the lateral thalamus. We expect to show 1) that GABA inter-neurons of the ZI or Rt inhibit orofacial pain responses, 2) that elevated E2 increases VGAT and GAD2 in males and females through a ER? dependent mechanism and 3) that these genes are responsible, in part, for the decrease in hypersensitivity observed in males. Upon completion of these studies a novel mechanism by which E2 affects orofacial hypersensitivity will be identified providing new targets for treating people suffering from HZ associated pain.
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Sep 2019 - Feb 2023
Immunomodulating Ruthenium Metal Complexes for Melanoma Photodynamic Therapy sponsored by National Cancer Institute (NCI)
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This proposal seeks to develop a novel class of ruthenium (Ru) compounds that can be activated with light to eliminate primary tumors, inhibit disseminated disease, and prevent recurrence.
It is hypothesized that light- responsive prodrugs with these capabilities will be of use in the development of photodynamic therapy (PDT) for treating melanoma. PDT is an underutilized, niche cancer treatment modality that combines light and a photosensitizer (PS) to create cytotoxic singlet oxygen for destroying tumors and tumor vasculature. Although commonly thought of as a local treatment, PDT has been known to stimulate anti-tumor immunity, which is crucial for controlling metastatic disease and subsequent tumor regrowth. PDT relies heavily on the presence of oxygen to exert its antitumor effects, and the PSs approved for PDT are generally organic compounds that are activated with red light. In order for PDT to be maximally effective toward melanoma, it would be advantageous to develop PSs that can function well in hypoxic tissue with wavelengths of light that are least attenuated by the melanin in pigmented melanomas (650-850 nm). If such agents could be incorporated into regimens that stimulate antitumor immunity, PDT might offer new treatment options for highly recurrent cancers such as melanoma, where chemotherapy and radiotherapy do not work. We previously developed very potent metal-based PSs that combine Ru and ?-expansive ligands to yield systems that create cytotoxic reactive oxygen species even at low oxygen tension due to their long excited state lifetimes and large bimolecular quenching rates. Separately, we developed osmium (Os)-based PSs that absorb light at wavelengths longer than 800 nm and can generate a modest PDT effect with this low-energy light even in hypoxic tissue. This proposal will combine the best features of the Ru (potency) and Os (activation >800 nm) PSs to yield new Ru metal complexes that are designed to elicit a strong PDT effect with near-infrared light in hypoxic tissue using increasingly more sophisticated melanoma models. Coordination chemistry will be used to generate a library of modular 3D compounds that can be subsequently modified to produce structurally diverse families. The photophysical and photochemical properties of these new compounds will be fully explored, and they will be assessed for their diagnostic potential and PDT effects using 2D cell and 3D tumor spheroid melanoma models. Promising candidates will be selected for MTD determination and PDT studies in two mouse melanoma models. PSs that are PDT-active and nontoxic to mice will be probed for their abilities to induce antitumor immunity through tumor rechallenge experiments. Finally, the immunological aspects of favorable PDT responses in mice will be investigated using both in vitro and in vivo techniques, and the PDT regimen will be explored and optimized for maximizing both local tumor control and stimulating antitumor immunity. This project will introduce novel PSs for melanoma PDT and will expand fundamental knowledge of metal complex chemistry, photophysics, and therapeutic properties.
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Dec 2018 - Dec 2022
PIRE: Sustainable Communities & Gold Supply Chains: Integrating Responsible Engineering & Local Knowledge (Smits Transfer from CSM) sponsored by Colorado School of Mines
Project Summary: Artisanal and small-scale gold mining (ASGM) is widespread in mineral rich developing countries and is credited with producing about 20-30% of all the extracted gold in the world used in jewelry, finances, electronics, aerospace, and medicine [1].
Colombia and Peru are among the top four biggest exporters of gold to the US [2], with 20 to 30% of that gold being produced through ASGM [3]. About 400,000 people in both countries work in ASGM [3], [4], providing rural communities with employment, a source of identity and cultural belonging, and increased participation in schooling and other business activities [5], [6]. As the Peace Accords between the leftist guerrillas and Colombian government take effect, many more thousands of people are expected to move into the conflict-free countryside and engage in ASGM. However, ASGM poses significant health and environmental hazards at local and global levels. In the Amazon Basin, one of the world’s most bio-diverse ecosystems, ASGM results in large-scale deforestation, air and water contamination, and human health risks, especially from the mercury used by miners to process the ore [7]. Governments, industries, and development agencies currently struggle with regulating and minimizing the negative impacts of ASGM while also supporting rural livelihoods. Few efforts to develop more sustainable ASGM technologies and practices have achieved longevity [8]–[10], mainly because they were developed for miners rather than with miners and affected communities. Therefore, ASGM continues to be one of the largest contributors to deforestation and atmospheric mercury pollution in the world, resulting in widespread land, sediment, water and air quality harms for rural and indigenous communities. The goal of this research is to reverse this trend. Most current interventions treat technology as a panacea for solving ASGM’s many problems [11]–[14]. These do not consider the full socio-economic and ecological context of why and how people choose to mine, nor do they integrate the knowledge miners and communities already possess about hazards and mitigation strategies and their own desires for sustainable livelihoods into proposed solutions. The proposed project breaks new ground by developing an integrated, community-centered approach to discovering how the social, environmental and technical dimensions of ASGM production systems influence one another, in order to ultimately design, implement, evaluate and ensure the long-term sustainability of ASGM practices and technologies. For the first time, US researchers and engineering students will work with Colombian and Peruvian faculty, students, miners and communities to develop socio-technical innovations, i.e., ensembles of people, organizations, and technologies that develop, nurture and constantly improve methods and practices for cleaner, safer, more economically attractive and more sustainable ASGM.   
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Dec 2019 - Nov 2022
Collaborative Research: Epidermal gland evolution and the origins of structural and chemical signaling diversity sponsored by National Science Foundation (NSF)
This project will identify the pathways behind multiple events of convergent evolution of epidermal glands in lizards, while jointly exploring their function in chemical signaling and diversity across groups.
Combining transcriptomic tools, comparative phylogenetics, top-notch ultrastructural imaging, and spectrometry of chemical compounds, genetic and structural mechanisms behind chemical signaling will be elucidated and correlations between the evolution of chemo-signalers and environmental and ecological parameters will be traced. Surprisingly, the genetic machinery of epidermal glands remains completely unexplored, and their structural organization has been investigated only for a few taxonomic groups, although a growing number of studies have shown that chemical signaling is a critical component of squamate communication. The comparative analyses of South American, African, and North American lizard groups will ultimately allow us to elucidate the origins of multiple epidermal glands types and write a new page on the evolutionary history of chemical signaling.
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Oct 2019 - Sep 2022
SHF: Small: Collaborative Research: Fuzzing Cyber-Physical System Development Tool Chains with Deep Learning (DeepFuzz-CPS) sponsored by National Science Foundation (NSF)
Overview:Recent years have seen an increasing interest in automated validation of commercial safety-critical cyberphysicalsystem (CPS) development and simulation tool chains.
Existing work in this area is limited bytwo main factors, i.e., (1) the lack of a corpus of public CPS models and (2) inefficiencies of state-of-thearttesting schemes in finding critical tool-chain bugs. This project addresses both of these key problemsin CPS research.To address the first problem, the PIs are building the by-far largest curated corpus of publicly availableCPS models and other CPS artifacts. The corpus currently contains some 1,000 public Simulink models.Preliminary results analyzing this corpus both confirms and contradicts earlier findings that are based onsignificantly fewer models, suggesting the utility of the corpus for future research.To side-step the age-old problem of missing complete formal specifications of CPS tool chains, the PIswill instead design a novel scheme to infer the CPS language validity rules via deep learning fromexisting CPS models, leveraging the PI's model corpus. Sampling the deep learner will enable generatingadditional programs for the PI's existing differential CPS tool chain testing infrastructure. PIs willsupplement the deep learner's training set via the first systematic CPS model mutation scheme based onequivalence modulo inputs (EMI). Initial experiments have yielded four Simulink bugs that have beenconfirmed by MathWorks.Kewyords: Cyber-physical system (CPS); CPS model corpus; CPS language semantics; CPS tool-chainbugs; Simulink.Intellectual Merit:The state of CPS development environments and corresponding verification and validation approachesmirrors that of computer architecture before the introduction of the SPEC benchmarks or the state ofimage recognition and machine learning before the release of the ImageNet training set. Developing awell-maintained, open, and accepted corpus of CPS models is essential for evaluating differentapproaches in a scientific and objective manner, but unfortunately, no such corpus exists. Understandingthe complexity of CPS in terms of meaningful metrics is a mostly unaddressed question. While everyonewould agree most CPS are complex, possibly with on the orders of millions of lines of code on thesoftware side, how do we truly evaluate to what degree a given CPS or model thereof is complex?Interlinked with the lack of a public CPS model corpus is the lack of reliable formal semantics for widelyused CPS development tool chains and the fact that these tool chains contain bugs. This project addressesall of these issues with novel research directions.Broader Impacts:CPS and verification researchers will benefit from both the available corpus and the novel CPS bugfinding tools. The PIs have an established track record of mentoring underrepresented persons incomputer science, and will build upon this. The PIs will also integrate their efforts into the formalmethods, software engineering, and CPS communities.
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