Thrombin activates protease-activated receptor-1 (PAR-1) by cleavage of the amino terminus to unmask a tethered ligand. Although peptide analogs can activate PAR-1, we show that functional responses mediated via PAR-1 differ between agonists. caused endothelial monolayer permeability and mobilized intracellular calcium with EC(50) values 0.1 1.7 nm, respectively. The opposite order activation was observed for agonist (SFLLRN-CONH(2) or TFLLRNKPDK) activation. addition inactivated thrombin...

The omega-3 polyunsaturated fatty acid docosahexaenoic (DHA) possesses potent anti-inflammatory properties and has shown therapeutic benefit in numerous inflammatory diseases. However, the molecular mechanisms of these are poorly understood. DHA is highly susceptible to peroxidation, which yields an array potentially bioactive lipid species. One class compounds cyclopentenone neuroprostanes (A(4)/J(4)-NPs), reactive similar structure prostaglandins. Here we show that a synthetic...

Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) found in marine fish oils are known to suppress inflammation associated with a wide variety of diseases. Eicosapentaenoic acid (EPA) is one the most abundant ω-3 oil, but mechanism(s) by which EPA exerts its beneficial effects unknown. Recent studies, however, have demonstrated that oxidized EPA, rather than native possesses anti-atherosclerotic, anti-inflammatory, and anti-proliferative effects. Very few studies date investigated oxidation...

Thrombospondin-1 (THBS1) is a large extracellular matrix glycoprotein that affects vasculature systems such as platelet activation, angiogenesis, and wound healing. Increases in THBS1 expression have been liked to disease states including tumor progression, atherosclerosis, arthritis. The present study focuses on the effects of thrombin activation G-protein-coupled, protease-activated receptor-1 (PAR-1) gene microvascular endothelium. Thrombin-induced changes were characterized by microarray...

Previously published studies have shown that cytochrome P450 (P450) enzyme systems can produce reactive oxygen species and suggest roles of P450s in oxidative stress. However, most the been done vitro, potential link between induction vivo damage has not rigorously explored with validated biomarkers. Male Sprague-Dawley rats were pretreated typical inducers (β-naphthoflavone, phenobarbital (PB), Aroclor 1254, isoniazid, pregnenolone 16α-carbonitrile, clofibrate) or general inhibitor...

Increased intake of fish oil rich in the omega-3 fatty acids eicosapentaenoic acid (EPA, C20:5 omega-3) and docosahexaenoic (DHA, C22:6 reduces incidence human disorders such as atherosclerotic cardiovascular disease. However, mechanisms that contribute to beneficial effects consumption are poorly understood. Mounting evidence suggests oxidation products EPA DHA may be responsible, at least part, for these benefits. Previously, we have defined free radical-induced arachidonic vitro vivo...

New technologies are required to combat the challenges faced with manufacturing commercial quantities of oligonucleotide drug substances which for treating large patient populations. Herein we report a convergent biocatalytic synthesis strategy an Alnylam model siRNA. The siRNA chemical structure includes several unnatural modifications and conjugations typical substances. Using Almac's 3-2-3-2 hybrid RNA ligase enzyme that sequentially ligates short fragments (blockmers), target was...

Ischemic preconditioning is a phenomenon in which low-level stressful stimuli upregulate endogenous defensive programs, resulting subsequent resistance to otherwise lethal injuries. We previously observed that signal transduction systems typically associated with neurodegeneration such as caspase activation are requisite events for the expression of tolerance and induction HSP70. In this work, we sought determine extent duration oxidative energetic dysfunction well role effector kinases on...

J. Neurochem. (2011) 119 , 604–616. Abstract Fatty acids such as eicosapentaenoic acid (EPA) have been shown to be beneficial for neurological function and human health. It is widely thought that oxidation products of EPA are responsible biological activity, although the specific peroxidation product(s) which exert these responses not yet identified. In this work we provide first evidence synthesized representative cyclopentenone IsoP, 15‐A 3t ‐IsoP, serves a potent inhibitor...

View Video Presentation: https://doi.org/10.2514/6.2023-0672.vid While several studies have explored the mild hybrid turbofan idea, there is currently a lack of parametric representation these types systems in conceptual literature. Parts hybridization problem been studied by other authors, and some integrated system attempted, but remains fully-integrated aircraft propulsion models modeling capabilities which can facilitate design space exploration. This paper extends, integrates,...

Electrified aircraft propulsion concepts have been proposed to meet aggressive future performance and environmental goals for the next generation of aircraft. However, electrified present a unique modeling simulation challenge as they introduce multiple energy sources system, providing various means thrust requirements, compared conventional gas turbine architectures where only fuel is available. Additionally, introduction an electric powertrain existing system enables flight modes exist...

Stroke is the leading cause of adult disability in U.S. and now recognized as a global epidemic. There are currently no FDA-approved drugs to block cell death that results from oxygen glucose deprivation. This void clinical medicine has sparked an intense interest understanding endogenous cellular protective pathways might be exploited for therapeutic development. The work highlighted here describes critical role between redox tone energetic stress signaling mediating mitophagy determining...

Soil aquifer treatment (SAT) is an established and sustainable wastewater approach for water reuse that has been gaining increased attention in various countries around the world. Increasing volumes of domestic escalating real estate prices urban areas emphasize urgent need to maximize efficiency by revisiting SAT setup. In this study, a novel was examined increase biodegradation rates improve quality topsoil effluent. Experiments with midscale, custom-made columns were carried out sand...

This paper presents a parametric modeling and integrated sizing approach for 50-passenger regional short takeoff landing propeller aircraft with parallel hybrid electric powertrain. In order to isolate the impact due powertrain hybridization component technologies, an advanced baseline model conventional is first established by infusing viable 2030 airframe engine technologies on based De Havilland DHC-7 aircraft. A parametric, physics-based true-parallel then developed which can operate in...

Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL DOI

This work demonstrates how a water and energy sustainable building's heating, ventilation, air conditioning (HVAC) system may be operated to maximize condensate production while upholding user thermal comfort consumption requirements. A physics-based HVAC model was presented validated against operating data from the Kendeda Building for Innovative Sustainable Design (KBISD), 3,437.4-m2 (37,000-ft2) academic building on Georgia Institute of Technology's Atlanta campus. sensitivity study power...

This paper documents the unique operations journey and an overview of accompanying model-based analysis award-winning Kendeda Building for Innovative Sustainable Design, designed to become most environmentally sustainable classroom lab building in Southeast US, addressing performance metrics including energy water use. As energy, primary goal was achieve Leadership Energy Environmental Design (LEED) Zero as well International Living Future Institute's (ILFI) Challenge (LBC) certifications,...