Search

We present a simple and effective method for evaluating double-and single-layer potentials for Laplace's equation in three dimensions close to the boundary. The close evaluation of these layer potentials is challenging because they are nearly singular integrals. The method we propose is based on writing these layer potentials in spherical coordinates where the point at which their kernels are peaked maps to the north pole. An N-point Gauss-Legendre quadrature rule is used for integration with respect to the the polar angle rather than the cosine of the polar angle. A 2N-point periodic trapezoid rule is used to compute the integral with respect to the azimuthal angle which acts as a natural and effective averaging operation in this coordinate system. The numerical method resulting from combining these two quadrature rules in this rotated coordinate system yields results that are consistent with asymptotic behaviors of the double- and single-layer potentials at close evaluation distances. In particular, we show that the error in computing the double-layer potential, after applying a subtraction method, is quadratic with respect to the evaluation distance from the boundary, and the error is linear for the single-layer potential. We improve upon the single-layer potential by introducing an alternate approximation based on a perturbation expansion and obtain an error that is quadratic with respect to the evaluation distance from the boundary., Comment: 21 pages, 15 figures

Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biolo, QC 20200910

BACKGROUND: The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. OBJECTIVES: The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. MATERIAL AND METHODS: The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. RESULTS: All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). CONCLUSIONS: Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient com

BACKGROUND: The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. OBJECTIVES: The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. MATERIAL AND METHODS: The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. RESULTS: All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). CONCLUSIONS: Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient com

We briefly address Landauer's Principle and some related issues in thermal demons. We show that an error-free Turing computer works in the zero-entropy limit, which proves Landauer's derivation incorrect. To have a physical logic gate, memory or information-engine, a few essential components necessary for the operation of these devices are often neglected, such as various aspects of control, damping and the fluctuation-dissipation theorem. We also point out that bit erasure is typically not needed or used for the functioning of computers or engines (except for secure erasure).

BACKGROUND: Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This report presents for the first time the study design, and characteristics of the recruited subjects.METHODS: Patients with a range of asthma severity and healthy non-atopic controls were enrolled. The asthmatic subjects were followed for 12 months. Assessments included history, patient questionnaires, spirometry, airway hyper-responsiveness to methacholine, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum, blood, and bronchoscopy samples. All subjects underwent sputum induction and 30 subjects/cohort had bronchoscopy.RESULTS: Mild (n = 52), moderate (n = 55), severe (n = 51) asthma cohorts and 30 healthy controls were enrolled from North America and Western Europe. Airflow obstruction, bronchodilator response and airways hyperresponsiveness increased with asthma severity, and severe asthma subjects had reduced forced vital capacity. Asthma control questionnaire-7 (ACQ7) scores worsened with asthma severity. In the asthmatics, mean values for all clinical and biomarker characteristics were stable over 12 months although individual variability was evident. FENO and blood eosinophils did not differ by asthma severity. Induced sputum eosinophils but not neutrophils were lower in mild compared to the moderate and severe asthma cohorts.CONCLUSIONS: The ADEPT study successfully enrolled asthmatics across a spectrum of severity and non-atopic controls. Clinical characteristics were related to asthma severity and in general asthma characteristics e.g. lung function, were stable over 12 months. Use of the ADEPT data should prove useful in defining biological phenotypes to facilitate personalized therapeutic approaches.

The interaction between wind waves and sediment movement at shores is a complex process, and its understanding is important. An accurate wave forecasting can result in better estimates of sediment movement along beaches. In addition, it will provide opportunities for improved planning and taking appropriate safety measures against the extreme events. A number of numerical models for wind-wave prediction are available which use inherent physics for wind-wave evolution. These models perform better for deep water predictions but still lack full understanding of balance of sources terms in finite water depth. An enhanced understanding of these terms will result in better estimation of sediment transport on beaches. The present study provides increased insight into the variation of two important source terms; non-linear wave-wave interactions and bottom friction which have significant effect on sediment transport. The non-linear wave-wave interactions have positive and negative signature and is the least understood term in wind-wave evolution. The bottom friction is always negative and withdraws energy from the spectrum. Thus, this study has provided better understanding of these two terms, and shows that together these affect the development of peak of the spectrum and hence wave energy. Consequently, because of their importance it will affect sediment balance at the shore.

The micromechanical behaviour of various thermoplastics based nanocomposites was investigated with the aid of the microindentation technique. The materials studied were microphase separated styrene-butadiene block copolymer systems and several thermoplastics reinforced with nano-sized fillers having variable dimensionality. It was found that the microhardness behaviour of the nanocomposites studied was strongly influenced by the dimensionalities of the filler. Due to large surface to volume-ratio one- and two-dimensional fillers exhibit a far better reinforcing behaviour than the three dimensional ones. In case of nanostructured block copolymers, the microhardness is not determined by the total polystyrene (PS)/ polybutadiene (PB) composition alone but diminishes gradually in presence of freely standing dangling polybutadiene chains even if the morphology of the systems remains unaltered. Copyright © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

In this Phase I SBIR program, Foster-Miller demonstrated the feasibility of an innovative joining technique for two-dimensional carbon/carbon (C/C) composite materials using active braze alloys. Traditionally, brazing of C/C composites required use of high- temperature vacuum furnaces. Vacuum brazing required expensive capital equipment with a limited working area and brazing cycles on the order of several hours to more than a day. The Foster-Miller technique utilized a controlled atmosphere induction brazing to reduce the brazing times to minutes and increased the interlaminar strengths by using of the proprietary Foster-Miller z-pin reinforcement technique. The use of the out-of-furnace brazing concept combined with z-direction reinforcements showed strengths of up to 1550 psi compared to the vacuum furnace braze joint strengths of 1153 psi. The constituents of the purging gases as well as proprietary solid oxygen getters were adjusted to eliminate all oxygen while brazing, thus minimizing problems associated with oxidation. This program analyzed the advantages of the oxygen getters in addition to the effect of braze layer thicknesses on strengths of the brazed C/C joints. The follow-on Phase II program will focus on transitioning the brazing technology to aerospace and terrestrial thermal management and structural applications of C/C composites.