2,144 research outputs found
Right Focal Boundary Value Problems for Difference Equations
An application is made of a new Avery et al. fixed point theorem of compression and expansion functional type in the spirit of the original fixed point work of Leggett and Williams, to obtain positive solutions of the second order right focal discrete boundary value problem. In the application of the fixed point theorem, neither the entire lower nor entire upper boundary is required to be mapped inward or outward. A nontrivial example is also Provided
Three point boundary value problems for ordinary differential equations, uniqueness implies existence
We consider a family of three point n − 2, 1, 1 conjugate boundary value problems for nth order nonlinear ordinary differential equations and obtain conditions in terms of uniqueness of solutions imply existence of solutions. A standard hypothesis that has proved effective in uniqueness implies existence type results is to assume uniqueness of solutions of a large family of n−point boundary value problems. Here, we replace that standard hypothesis with one in which we assume uniqueness of solutions of large families of two and three point boundary value problems. We then close the paper with verifiable conditions on the nonlinear term that in fact imply global uniqueness of solutions of the large family of three point boundary value problems
A Targeted<em> in Vivo</em> SILAC Approach for Quantification of Drug Metabolism Enzymes:Regulation by the Constitutive Androstane Receptor
The modulation of drug metabolism enzyme (DME) expression by therapeutic agents is a central mechanism of drug-drug interaction and should be assessed as early as possible in preclinical drug development. Direct measurement of DME levels is typically achieved by Western blotting, qPCR, or microarray, but these techniques have their limitations; antibody cross-reactivity among highly homologous subfamilies creates ambiguity, while discordance between mRNA and protein expression undermines observations. The aim of this study was to design a simple targeted workflow by combining in vivo SILAC and label-free proteomics approaches for quantification of DMEs in mouse liver, facilitating a rapid and comprehensive evaluation of metabolic potential at the protein level. A total of 197 peptides, representing 51 Phase I and Phase II DMEs, were quantified by LC-MS/MS using targeted high resolution single ion monitoring (tHR/SIM) with a defined mass-to-charge and retention time window for each peptide. In a constitutive androstane receptor (Car) activated mouse model, comparison of tHR/SIM-in vivo SILAC with Western blotting for analysis of the expression of cytochromes P450 was favorable, with agreement in fold-change values between methods. The tHR/SIM-in vivo SILAC approach therefore permits the robust analysis of multiple DME in a single protein sample, with clear utility for the assessment of the drug-drug interaction potential of candidate therapeutic compounds. </p
Identification of novel pathways of osimertinib disposition and potential implications for the outcome of lung cancer therapy
Prospects for Nonlinear Laser Diagnostics in the Jet Noise Laboratory
Two experiments were conducted to test whether optical methods, which rely on laser beam coherence, would be viable for off-body flow measurement in high-density, compressible-flow wind tunnels. These tests measured the effects of large, unsteady density gradients on laser diagnostics like laser-induced thermal acoustics (LITA). The first test was performed in the Low Speed Aeroacoustics Wind Tunnel (LSAWT) of NASA Langley Research Center's Jet Noise Laboratory (JNL). This flow facility consists of a dual-stream jet engine simulator (with electric heat and propane burners) exhausting into a simulated flight stream, reaching Mach numbers up to 0.32. A laser beam transited the LSAWT flow field and was imaged with a high-speed gated camera to measure beam steering and transverse mode distortion. A second, independent test was performed on a smaller laboratory jet (Mach number < 1.2 and mass flow rate < 0.1 kg/sec). In this test, time-averaged LITA velocimetry and thermometry were performed at the jet exit plane, where the effect of unsteady density gradients is observed on the LITA signal. Both experiments show that LITA (and other diagnostics relying on beam overlap or coherence) faces significant hurdles in the high-density, compressible, and turbulent flow environments similar to those of the JNL
Mechanical design and development of TES bolometer detector arrays for the Advanced ACTPol experiment
The next generation Advanced ACTPol (AdvACT) experiment is currently underway
and will consist of four Transition Edge Sensor (TES) bolometer arrays, with
three operating together, totaling ~5800 detectors on the sky. Building on
experience gained with the ACTPol detector arrays, AdvACT will utilize various
new technologies, including 150mm detector wafers equipped with multichroic
pixels, allowing for a more densely packed focal plane. Each set of detectors
includes a feedhorn array of stacked silicon wafers which form a spline profile
leading to each pixel. This is then followed by a waveguide interface plate,
detector wafer, back short cavity plate, and backshort cap. Each array is
housed in a custom designed structure manufactured from high purity copper and
then gold plated. In addition to the detector array assembly, the array package
also encloses cryogenic readout electronics. We present the full mechanical
design of the AdvACT high frequency (HF) detector array package along with a
detailed look at the detector array stack assemblies. This experiment will also
make use of extensive hardware and software previously developed for ACT, which
will be modified to incorporate the new AdvACT instruments. Therefore, we
discuss the integration of all AdvACT arrays with pre-existing ACTPol
infrastructure.Comment: 9 pages, 5 figures, SPIE Astronomical Telescopes and Instrumentation
conference proceeding
Novel Pathways Of Ponatinib Disposition Catalysed By CYP1A1 Involving Generation Of Potentially Toxic Metabolites
Stop Atherosclerosis in Native Diabetics Study (SANDS): Baseline Characteristics of the Randomized Cohort
Objectives: To present baseline characteristics of American Indians in the Stop Atherosclerosis in Native Diabetics Study (SANDS) and compare them with population-based data from American Indians and other ethnic groups. Design: 499 people with type 2 diabetes ≥ age 40, without known CVD, were recruited for a randomized 3-year trial to evaluate treatment targets for LDL-C (70 vs. 100 mg/dL) and systolic blood pressure (BP) (115 vs. 130 mmHg). Baseline evaluations included physical exam, collection of blood and urine samples, and carotid ultrasound and echocardiographic measures. Results: Mean age was 56 years; 66% were female. Average BMI was 33 kg/m2. Average duration of both hypertension and diabetes was 10 years, average A1c was 8.0 %, and mean LDL-C was 104 mg/dL. Participants in the conventional treatment group had slightly higher systolic BPs than participants in the aggressive treatment group (133 mm Hg vs. 128 mm Hg, p \u3c 0.002). Compared with the population-based cohorts of the Strong Heart Study (SHS), NHANES, and the TRIAD registry, SANDS participants had similar values for lipids, BP, and CRP, as well as degree of obesity, smoking rates, and renal function as indicated by estimated glomerular filtration rate. Conclusions: The baseline characteristics of the SANDS cohort are similar to those of a population-based sample of American Indian diabetic men and women and closely resemble diabetic men and women of other ethnic groups. Results from this study can be used to identify appropriate targets for LDL-C and BP lowering in diabetic American Indians and diabetic patients in other ethnic groups
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