A5007378854- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Protein Structure and Dynamics
- Machine Learning in Bioinformatics
- Enzyme Structure and Function
- Maritime Ports and Logistics
- Transport and Economic Policies
- Estrogen and related hormone effects
- Urban and Freight Transport Logistics
- RNA and protein synthesis mechanisms
- Hepatitis C virus research
- Transport Systems and Technology
- Transportation Planning and Optimization
- Computational Drug Discovery Methods
- Fuzzy Logic and Control Systems
- Receptor Mechanisms and Signaling
- Biochemical and Molecular Research
- Monoclonal and Polyclonal Antibodies Research
- Neural Networks and Applications
- Reproductive tract infections research
- Rough Sets and Fuzzy Logic
- Bioinformatics and Genomic Networks
- Infrastructure Maintenance and Monitoring
- Oral microbiology and periodontitis research
- Pancreatic function and diabetes
Duke University
2012-2024
Duke University Hospital
2013-2024
Clinical Research Institute
2013-2024
Keio University
2024
Renishaw (United Kingdom)
2023
Hackensack University Medical Center
2023
Georgia State University
2013-2022
Brigham and Women's Hospital
2022
Renishaw (Ireland)
2022
Stanford University
1985-2021
We designed, synthesized, and identified UIC-94017 (TMC114), a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF) sulfonamide isostere which is extremely potent against laboratory HIV-1 strains primary clinical isolates (50% inhibitory concentration [IC(50)], approximately 0.003 micro M; IC(90), 0.009 M) with minimal cytotoxicity cytotoxic for CD4(+) MT-2 cells, 74 M). blocked the...
Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after surgery.In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated efficacy and safety of levosimendan patients with left ventricular ejection fraction 35% less who were undergoing surgery use cardiopulmonary bypass. Patients randomly assigned receive either intravenous (at dose 0.2 μg per kilogram body weight minute for 1 hour, followed by 0.1...
<h3>Importance</h3> Adoption of guideline-directed medical therapy for patients with heart failure is variable. Interventions to improve have failed consistently achieve target metrics, and limited data exist inform efforts quality care. <h3>Objective</h3> To evaluate the effect a hospital postdischarge improvement intervention compared usual care on outcomes <h3>Design, Setting, Participants</h3> This cluster randomized clinical trial was conducted at 161 US hospitals included 5647 (2675 vs...
The three-dimensional structure of human decorin, a secreted proteoglycan involved in the regulation collagen fibrillogenesis and cellular growth, has been modeled based on crystal porcine ribonuclease inhibitor. Both proteins contain leucine-rich repeats share 18% identical residues. This model decorin an arch shape with single glycosaminoglycan chain three N-linked oligosaccharides located same side molecule. Decorin was as binding to polar sequence type I found d band. inner concave...
Whether left ventricular hypertrophy (LVH) in obesity results from increased hemodynamic load or altered neurohormonal signaling remains controversial. Dysregulation of leptin, a neurohormone essential to energy homeostasis, is implicated the pathogenesis obesity. Because leptin has cardiovascular bioactivity, we hypothesized that disruption mediates development obesity-associated LVH.We measured (LV) wall thickness and LV mass with echocardiography mice lacking (ob/ob, n=15) functional...
Phase recovery from unphased data is the central problem in interpretation of crystal diffraction data. There are a number experimental methods for determining phases, and small molecules computational work very well. The developing robust large not yet solved. Most approaches variants Grechburg–Saxton algorithm [ Optik35, 237– 246 ( 1972)]; with sufficiently good initial phase estimates these converge, but general they fail stagnation similar to that seen image processing DaintyJ....
The rat liver glucocorticoid receptor was partially purified and used to immunize a BALB/c mouse whose splenic lymphocytes were fused with the nonsecreting myeloma cell line P3-AgX-653. fusion products selected in HAT (hypoxanthine, aminopterine, thymidine) medium stable antibody-producing clone designated BuGRl obtained from 1 of 81 positive wells. Immunological specificity for confirmed by sucrose density gradient analysis when sedimentation constant specifically labeled altered reaction...
Abstract —Allopurinol, an inhibitor of xanthine oxidase, increases myofilament calcium responsiveness and blunts cycling in isolated cardiac muscle. We sought to extend these observations conscious dogs with without pacing-induced heart failure tested the prediction that allopurinol would have a positive inotropic effect increasing energy expenditure, thereby mechanical efficiency. In control (n=10), (200 mg IV) caused small effect; (dP/dt) max increased from 3103±162 3373±225 mm Hg/s...
We have used a monoclonal antibody to purify glucocorticoid-receptor complexes from WEHI-7 mouse thymoma cells.Molybdate-stabilized, nonactivated were found contain two distinct proteins which could be separated by polyacrylamide gel electrophoresis under denaturing and reducing conditions.One of the proteins, 100 kDa, was labeled when cytosol incubated with affinity ligand [3H]dexamethasone 21-mesylate.The second protein, 90 not labeled.Several lines evidence, including Western blot...
DNA polymorphisms in the glucokinase gene have recently been shown to be tightly linked early-onset non-insulin-dependent diabetes mellitus approximately 80% of French families with this form diabetes. We previously identified a nonsense mutation exon 7 one these and showed that it was likely cause glucose intolerance dominantly inherited disorder. Here we report isolation partial sequence human identification two missense mutations 7, Thr-228----Met Gly-261----Arg, cosegregate mellitus. To...
Inhibition of xanthine oxidase (XO) in failing hearts improves cardiac efficiency by an unknown mechanism. We hypothesized that this energetic effect is due to reduced oxidative stress and critically depends on nitric oxide synthase (NOS) activity, reflecting a balance between generation (NO) reactive oxygen species. In dogs with pacing-induced heart failure (HF), ascorbate (1000 mg) mimicked the beneficial effects allopurinol, increasing both contractility efficiency, suggesting antioxidant...
A study of the effects synthetic detergents and wetting agents on respiration glycolysis Gram-positive Gram-negative microorganisms has led to following conclusions. 1. All cationic studied are very effective inhibitors bacterial metabolism at 1:3000 concentration, several equally active 1:30,000. Few anionic inhibit as effectively compounds. 2. sensitive action detergents. On other hand, all included in our studies selectively microorganisms. 3. The inhibitory both types is influenced...
Although protein S -nitrosylation is increasingly recognized as mediating nitric oxide (NO) signaling, roles for denitrosylation in physiology remain unknown. Here, we show that -nitrosoglutathione reductase (GSNOR), an enzyme governs levels of by promoting denitrosylation, regulates both peripheral vascular tone and β-adrenergic agonist-stimulated cardiac contractility, previously ascribed exclusively to NO/cGMP. GSNOR-deficient mice exhibited reduced depressed inotropic responses were...
The structural and kinetic effects of amprenavir (APV), a clinical HIV protease (PR) inhibitor, were analyzed with wild‐type enzyme mutants single substitutions V32I, I50V, I54V, I54M, I84V L90M that are common in drug resistance. Crystal structures the APV complexes at resolutions 1.02–1.85 Å reveal changes due to mutations. Substitution larger side chains PR V32I , I54M resulted formation new hydrophobic contacts flap residues, residues 79 80, Asp25, respectively. Mutation smaller...
1. The bactericidal action of a number anionic and cationic synthetic detergents on four Gram-positive three Gram-negative bacteria has been investigated. 2. Cationic detergents, as group, were found to exhibit marked effects microorganisms somewhat less pronounced organisms. 3. germicidal only against the organisms, they considerably effective than compounds. Of most active one was an alkyl sulfate derived from branched-chain, secondary alcohol. 4. Correlations between inhibition bacterial...
1. Lecithin, cephalin, and sphingomyelin prevent the inhibition of bacterial metabolism which is caused by synthetic anionic cationic detergents. The phospholipids must be added either before or simultaneously with detergent. Addition after detergent without effect. Bacteria still exhibit this phenomenon they have been exposed to phospholipid thoroughly washed. 2. A similar action has demonstrated towards bactericidal compounds isolated Dubos Hoogerheide from soil bacteria. There very little...