We consider two treatment comparison in a clinical trial setup where the responses from one treatment are a priori known for a fixed number of individuals and patients are allocated in a groupsequential way for the other treatment using inverse sampling. We consider the odds ratio as the measure of treatment difference at the end of each group, where for the calculation of odds ratios we consider the full data on one treatment, which are a priori known, and the available data on the other treatment up to that point of time. We have calculated the optimal number of index subjects for inverse sampling and examine the effects of different type I and type II error spending functions on group sequential testing in this context. The methodology is illustrated by using a real data set. 相似文献
Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson’s disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson’s disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules. 相似文献
This article presents numerical simulations of the laminar flow of lubricating greases in a channel with rectangular cross section. Three greases with different consistencies (NLGI grades 00, 1, and 2) have been considered in three different configurations composed of a rectangular channel without restrictions, one rectangular step restriction, and one double-lip restriction. The driving pressure drop over the channel spans from 30 to 250 kPa. The grease rheology is described by the Herschel-Bulkley rheology model, and both the numerical code and rheology model have been validated with analytical solutions and flow measurements using micro-particle image velocimetry. 相似文献
Mathematical models for single electrode reversible heat and non-isothermal electromotive force (EMF) of a solid oxide fuel cell (SOFC) are developed. These models estimate the volumetric reversible heat generation and EMF of electrochemical reactions, within each electrode at local conditions of temperature and pressure, based on entropy change of half reactions. The resulting equations are thermodynamically consistent. They inherently obey the conservation of energy law as the electrochemical energy released added to the heat of reactions at each electrode equate the enthalpy change of the reacted species. The equations are implemented to model electrodes in a tubular micro- solid oxide fuel cell (TμSOFC). The thermodynamic consistency of the model is numerically confirmed as the enthalpy of the reactants equates the electric energy released by the cell plus the sum of electrode heats plus electrolyte Ohmic heat. The effect of thermal gradients on the cell's overall EMF is found to be negligible. The reversible and irreversible heat generation of each electrode are distinguished. Overall, the anode is found to be endothermic, and the cathode exothermic. 相似文献
1. Background
The use of engineering tools, design, research, and thinking to create environments and capabilities whereby individuals who are currently under-e... 相似文献
Guayule natural rubber (GNR) is an alternative resource of Hevea natural rubber (HNR) with 99.9% cis content in its 1,4-polyisoprene chemical backbone. In this study, compounds were formulated independently with four different reinforcing fillers such as carbon black (HAF), precipitated silica (VN3), fume silica (FUM) and nanofly ash (NFA) for the advancement of GNR based products. The cure characteristic, dynamic-mechanical performance and mechanical properties of GNR composite were studied with the reinforcing effect of different fillers on GNR. The cure characteristic results demonstrated that HAF and FUM silica filled compounds had more processing safety than VN3 and NFA filled compounds. Viscoelastic parameters of the vulcanizates were studied by dynamic mechanical analysis to estimate the glass transition characteristics and dynamic behavior. The higher storage modulus of FUM silica vulcanizate was an indication of superior filler reinforcing nature and improved rolling resistance than other filled systems. Additionally, HRTEM analysis also proved the better filler dispersion ability of FUM silica in GNR matrix. The mechanical properties were studied with a variation of each filler loading of 8, 16, and 32 phr in GNR vulcanizates. The tensile strength of each filled system increased with an increase of filler content from 8 to 32 phr. In comparison, FUM silica GNR vulcanizates exhibited better mechanical properties, therefore, it was considered as a better structure-performance composite than those of HAF, VN3 and NFA filled composites.
The three GxxxG repeating motifs from the C-terminal region of β-amyloid (Aβ) peptide play a significant role in regulating the aggregation kinetics of the peptide. Mutation of these glycine residues to leucine greatly accelerates the fibrillation process but generates a varied toxicity profile. Using an array of biophysical techniques, we demonstrated the uniqueness of the composite glycine residues in these structural repeats. We used solvent relaxation NMR spectroscopy to investigate the role played by the surrounding water molecules in determining the corresponding aggregation pathway. Notably, the conformational changes induced by Gly33 and Gly37 mutations result in significantly decreased toxicity in a neuronal cell line. Our results indicate that G33xxxG37 is the primary motif responsible for Aβ neurotoxicity, hence providing a direct structure–function correlation. Targeting this motif, therefore, can be a promising strategy to prevent neuronal cell death associated with Alzheimer's and other related diseases, such as type II diabetes and Parkinson's. 相似文献
This study optimized the ventilator and furniture location of a tenement unit in a low-income urban habitat to obtain maximum experiential indoor environmental quality (e-IEQ) over the breathing zone. Hypothetical interior layouts using a combination of the two design parameters of ventilator location and bed position were generated for optimizing the design layout. This layout could promote maximum indoor airflow and minimum indoor air temperature and contaminant concentration. In this study, an improved indoor environment is hypothesized to be attainable through improved natural ventilation and thermal performance in the occupied zones. A sequential methodology involving “parametric design modeling–computational simulation–multiobjective optimization–multicriteria decision making”-based framework was selected. Results exhibited that the currently designed tenement unit had a poor indoor environment, whereas the hypothesized iterated layout “optimized design layout, scenario 3 (ODL 3)” derived from the optimization and decision-making algorithm performed effectively in providing e-IEQ. An increase in experiential indoor air velocity by 0.2 m/s and a decrease in temperature by 2 °C were observed over the monitoring point in the ODL 3 considering the existing scenario. Therefore, this study can find a way toward the development of sustainable habitat design guidelines under upcoming slum redevelopment policies across the nation. 相似文献
The understanding of the flow characteristics and effect of gas-solid interactions in pneumatic risers is fundamental to investigate to ensure effective design cost-effective operation. Thus, to understand the effect of gas-solid interactions on the hydrodynamics of newly proposed conversing risers, this study mainly focused on predicting pressure drop in the dilute phase pneumatic conveying system. The experiments were conducted in a converging riser having a convergence angle of 0.2693°. Various solid particles such as sago, black mustard, and alumina have been considered to study the effect of particle sizes and density on the pressure drop. The experimental outcomes indicate that the total pressure drop increases with an increase in the solid density and gas mass flow rate. Moreover, smaller particle sizes are also increased the pressure drop. An empirical correlation is developed for the prediction of total pressure drop ΔPT in converging pneumatic riser via dimensional analysis. All dependent variables such as particle and air density, drag force, acceleration due to gravity, the mass flow rate of air and particle, the diameter of particle and converging riser, the height of converging riser were considered to develop the empirical correlation. The established relationship is tested, and experimental data have been fitted for its validation. The estimated relative error of less than 0.05 proved the significance of the developed correlation. Hence, it can be stated that the established relationship is useful in studying the effects of various parameters on the pressure drop across the length of the conversing riser. 相似文献