A5078071300- NMR spectroscopy and applications
- Advanced NMR Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Advanced MRI Techniques and Applications
- Photoacoustic and Ultrasonic Imaging
- Spectroscopy Techniques in Biomedical and Chemical Research
- Protein purification and stability
- Optical Imaging and Spectroscopy Techniques
- Membrane-based Ion Separation Techniques
- Pancreatic function and diabetes
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Fuel Cells and Related Materials
- Metabolism, Diabetes, and Cancer
- Electron Spin Resonance Studies
- Glutathione Transferases and Polymorphisms
- Enzyme-mediated dye degradation
- Synthesis and Catalytic Reactions
- Microbial Inactivation Methods
- Gyrotron and Vacuum Electronics Research
- Advanced Battery Technologies Research
- Drug-Induced Hepatotoxicity and Protection
- Sphingolipid Metabolism and Signaling
- Atherosclerosis and Cardiovascular Diseases
Eli Lilly (United States)
2004-2022
Michigan Technological University
1986-2020
Montreal Heart Institute
2015
Virginia Department of Environmental Quality
2015
Merck & Co., Inc., Rahway, NJ, USA (United States)
2007-2012
Purdue University West Lafayette
2007
University of Massachusetts Chan Medical School
2004
City University of Seattle
1989
University of Maryland, Baltimore
1989
Johns Hopkins University
1989
The increased interest in using monoclonal antibodies (mAbs) as a platform for biopharmaceuticals has led to the need new analytical techniques that can precisely assess physicochemical properties of these large and very complex drugs purpose correctly identifying quality attributes (QA). One QA, higher order structure (HOS), is unique essential establishing consistency biopharmaceutical manufacturing, detecting process-related variations from manufacturing changes comparability between...
As the number of therapeutic proteins produced by mammalian cell cultures in pharmaceutical industry continues to increase, need improve productivity and ensure consistent product quality during process development activities becomes more significant. Rational medium design is known culture performance, but an understanding nutrient consumption metabolite accumulation within required. To this end, we have developed a technique for using 1D (1)H NMR quantitate nonprotein feed components...
Fermentanomics, or a global understanding of culture state on the molecular level empowered by advanced techniques like NMR, was employed to show that model hybridoma supplied with glutamine and glucose depletes aspartate, cysteine, methionine, tryptophan, tyrosine during antibody production. Supplementation these amino acids prevents depletion improves performance. Furthermore, no significant changes were observed in distribution glycans attached IgG3 cultures supplemented specific acids,...
Ultra-rapid insulin formulations control postprandial hyperglycemia; however, inadequate understanding of injection site absorption mechanisms is limiting further advancement. We used photoacoustic imaging to investigate the dynamics dye-labeled lispro in Humalog® and Lyumjev® using murine ear cutaneous model correlated it with results from unlabeled pig subcutaneous model.We employed dual-wavelength optical-resolution microscopy study diffusion near-infrared Humalog Lyumjev mouse ears....
The pharmacokinetics and metabolism of anacetrapib (MK-0859), a novel cholesteryl ester transfer protein inhibitor, were examined in rats rhesus monkeys. Anacetrapib exhibited low clearance both species moderate oral bioavailability ∼38% ∼13% area under the plasma concentration-time curve increased less than dose-proportional manner over an dose range 1 to 500 mg/kg. After administration [<sup>14</sup>C]anacetrapib at 10 mg/kg, ∼80 90% radioactive was recovered 48 h postdose from monkeys,...
In our previously published work, we reported rapid polysorbate 80 (PS80) oxidation in a histidine buffer after brief exposure to stainless steel and the ability of citrate EDTA prevent this oxidation. The focus current study was mechanistically understand PS80 by studying impacts temperature, light, role EDTA. Additionally, studied three different systems: histidine, citrate, phosphate. When PS80-containing buffers glass containers were exposed elevated temperature 50°C, no observed either...
In high-throughput scenarios, a large number of similar NMR spectra from single study need to be analyzed. The complexity the data required use spectral databases characterize resonances interest and extract quantitative information. recently reported CRAFT (Complete Reduction Amplitude Frequency Table) technique, based on Bayesian analysis approach, converts time-domain FID frequency-amplitude table in robust, automated, time-efficient fashion. We report application technique extraction...
[(3<i>R</i>)-4-(4-Chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopentaindol-3-yl]acetic acid (MK-0524) is a potent orally active human prostaglandin D<sub>2</sub> receptor 1 antagonist that currently under development for the prevention of niacin-induced flushing. The metabolism and excretion [<sup>14</sup>C]MK-0524 in humans were investigated six healthy volunteers following single p.o. dose 40 mg (202 μCi). was absorbed rapidly, with plasma <i>C</i><sub>max</sub> achieved...
A structure-activity relationship study of the imidazolyl-β-tetrahydrocarboline series identified MK-4256 as a potent, selective SSTR3 antagonist, which demonstrated superior efficacy in mouse oGTT model. reduced glucose excursion dose-dependent fashion with maximal achieved at doses low 0.03 mg/kg po. As compared glipizide, showed minimal hypoglycemia risk mice.
CRISIS (Compensation of Refocusing Inefficiency with Synchronized Inversion Sweep) is a powerful technique for obtaining multiplicity-edited HSQC spectra without compromising sensitivity. However, the stringent requirement duration waveforms makes them unsuitable other functions, such as band selection or IMPRESS (IMProved REsolution using Symmetrically Shifted pulses). We report here modified CRISIS-gHSQC pulse sequence employing time-reversed 13C π/2 EBURP-2 pulses. This IC-bs-gHSQC...
1-{4-[(4-Phenyl-5-trifluoromethyl-2-thienyl)methoxy]benzyl}azetidine-3-carboxylic acid (MRL-A) is a potent sphingosine-1-phosphate-1 receptor agonist, with potential application as an immunosuppressant in organ transplantation or for the treatment of autoimmune diseases. When administered orally to rats, radiolabeled MRL-A was found undergo metabolism several reactive intermediates, and this study, we have investigated its protein modification vivo vitro. irreversibly modified liver kidney...
We report the lateral diffusion properties of 2,2'-di-O-decyl-3,3'-di-O-(eicosanyl)-bis-(rac-glycero)-1,1'-diphosphocholine (C20BAS) using pulsed-field gradient NMR (PFG-NMR) and fluorescence recovery after photobleaching (FRAP). C20BAS membranes display a melting transition at Tm = 15.7 °C, as determined by differential scanning calorimetry 31P chemical shift anisotropy. The coefficient C20BAS, PFG-NMR FRAP, 25 were DPFG-NMR 1.9 ± 0.6 × 10-8 cm2/s DFRAP 1.2 0.1 cm2/s, respectively. In...
This letter provides the first pharmacological proof of principle that sst3 receptor mediates glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. To enable these studies, we identified selective antagonist (1R,3R)-3-(5-phenyl-1H-imidazol-2-yl)-1-(tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-β-carboline (5a), with improved ion channel selectivity and mouse pharmacokinetic properties as compared to previously described tetrahydro-β-carboline imidazole antagonists. We...
Abstract NOTE: The first page of text has been automatically extracted and included below in lieu an abstract Engineering Education Alternative Energy This paper describes education research efforts alternative energy at Michigan Technological University (MTU). A particular emphasis will be placed on the multidisciplinary chemical engineering undergraduate students energy. Experiences can involve enrollment interdisciplinary design project, elective fuel cell course, a hydrogen...
We have investigated the prospect of identifying organic reaction products directly from separated thin-layer chromatography (TLC) spots with high-resolution magic-angle spinning (HRMAS) NMR. The concept is to use TLC for NMR analysis so that spectra can be obtained before worked up, but without having elute product stationary phase. Thus, spot scraped plate, transferred an HRMAS sample rotor, and suspended a deuterated solvent. Herein, we describe effects phase present during acquisition....
MRL-1, a cannabinoid receptor-1 inverse agonist, was member of lead candidate series for the treatment obesity. In rats, MRL-1 is eliminated mainly via metabolism, followed by excretion metabolites into bile. The major metabolite M1, glutathione conjugate isolated and characterized liquid chromatography/mass spectrometry NMR spectroscopic methods. data suggest that <i>t</i>-butylsulfonyl group at C-2 furopyridine displaced glutathionyl group. vitro experiments using rat monkey liver...
The concentration of macromolecules in solution is a crucial property many areas research, including the development and commercialization biological therapeutics. For proteins particular, none reported methods for measuring detect molecular that known priori; rather, they rely on ligand binding, degradation derivitization, or an intrinsic must be determined experimentally. purpose this report to describe (1) diffusion-filtered qNMR experiment (DF-qNMR) quantitating complex matrices (2)...
Abstract The DOSY analysis of dilute mixtures can be a challenge because high signal‐to‐noise ratio is required for the best results. sensitivity increase gained from new probe technologies (e.g. cold and nano probes) could enable one to acquire good spectra on sample amounts too low conventional probes. In this article, we investigated performance probes qualitative concentrated sample‐limited mixtures, compared results with those probe. We first measured fluid flow each All three exhibited...
The use of alternative energy technology for vehicle propulsion and auxiliary power is becoming more important. Work being performed at Michigan Technological University's Keweenaw Research Center on an Army Laboratory cooperative agreement to develop two unmanned ground vehicles military applications. A wide range technologies were investigated, hydrogen-powered proton exchange membrane fuel cells identified as the most appropriate source. This due some development commercialization which...
Abstract Objective Ultra-rapid insulin formulations control postprandial hyperglycemia; however, inadequate understanding of injection site absorption mechanisms is limiting further advancement. We used photoacoustic imaging to investigate the dynamics dye-labeled lispro in Humalog ® and Lyumjev using murine ear cutaneous model correlated it with results from unlabeled pig subcutaneous model. Methods employed dual-wavelength optical-resolution microscopy study diffusion near-infrared mouse...