Developing an Irreversible Inhibitor of Human DDAH‐1, an Enzyme Upregulated in Melanoma

Inhibitors of the human enzyme dimethylarginine dimethylaminohydrolase‐1 (DDAH‐1) can raise endogenous levels of asymmetric dimethylarginine (ADMA) and lead to a subsequent inhibition of nitric oxide synthesis. In this study, N⁵‐(1‐imino‐2‐chloroethyl)‐L ‐ornithine (Cl‐NIO) is shown to be a potent time‐ and concentration‐dependent inhibitor of purified human DDAH‐1 (K_I=1.3±0.6 μM ; k_inact=0.34±0.07 min^?1), with >500‐fold selectivity against two arginine‐handling enzymes in the same pathway. An activity probe is used to measure the “in cell” IC₅₀ value (6.6±0.2 μM ) for Cl‐NIO inhibition of DDAH‐1 artificially expressed within cultured HEK293T cells. A screen of diverse melanoma cell lines reveals that a striking 50/64 (78 %) of melanoma lines tested showed increased levels of DDAH‐1 relative to normal melanocyte control lines. Treatment of the melanoma A375 cell line with Cl‐NIO shows a subsequent decrease in cellular nitric oxide production. Cl‐NIO is a promising tool for the study of methylarginine‐mediated nitric oxide control and a potential therapeutic lead compound for other indications with elevated nitric oxide production, such as septic shock and idiopathic pulmonary fibrosis.     

Effect of colloidal silica on the mechanical properties of fiber–cement reinforced with cellulosic fibers

The effect of colloidal silica on the hydration reaction of the Portland cement system and its effect on the resulting mechanical properties are not completely understood. Silica nanoparticles can affect the behavior and performance of fiber–cement, such as the calcium–silicate–hydrate gel of the matrix and the fiber–matrix interface bonding. The main objective of this study is to evaluate the effects of various contents of colloidal silica (0, 1.5, 3, 5, and 10 % w/w) on the microstructure and mechanical performance of cement composites reinforced with cellulosic pulp. Fiber–cement composites with unbleached eucalyptus Kraft pulp as the micro-fiber reinforcement were produced by the slurry dewatering technique followed by pressing. The average values of the modulus of rupture of the fiber–cement decreased with increasing colloidal silica content. However, the pullout of the fibers increased significantly in the fiber–cement composites with additions between 3 and 10 % w/w of colloidal silica suspension, as indicated in the scanning electron microscopy images and by the improvement in the energy of fracture values.     

A physical perspective of the element‐based finite volume method and FEM‐Galerkin methods within the framework of the space of finite elements

The literature shows an increasing number of works focused on investigating the behaviour of methods that uses concepts of control volumes in the solution of structural problems. In recent years, new approaches using unstructured meshes have been proposed, most of which addressing new applications and, to a lesser extent, the underling physical perspective. This paper presents a unified approach to the element‐based finite volume method and FEM‐Galerkin within the framework of the finite element space. Numerical examples highlight some accuracy issues associated with the element‐based finite volume method developed in this work. Copyright © 2014 John Wiley & Sons, Ltd.     

Preparing of pellets by extrusion/spheronization using different types of equipment and process conditions

Introduction: The focus of this work was to produce matrix pellets made by extrusion/ spheronization using two types of equipment. The aim was to accomplish the laboratory-scale I process that has been already optimized and accepted with another type of equipment (laboratory-scale II).

Methods: A matrix pellet formulation consisting of MCC, Eudragit NE 30D and diclofenac sodium was used in the two types of equipment. Physico-chemical parameters and the dissolution profiles of the pellets in phosphate buffer pH 6.8 were compared.

Results: Pellets from both processes were similar in shape and tensile strength. They differed in particle size and dissolution profile. This may be contributed to different spheronization conditions.     

The Vortex Path Model Analysis of the Field Angle Dependence of the Critical Current Density in Nanocomposite YBa2Cu3 O 7−x – BaZrO3 Films Obtained by Low Fluorine Chemical Solution Deposition

In the present paper, we analyze the role of in situ grown BaZrO₃ (BZO) inclusions in YBa₂Cu₃O_7?x (YBCO) thin films prepared by chemical solution deposition using a low fluorine coating solution, on the field angle dependence of the critical current density, J _c (??), data using the vortex path model. In order to form a coherent picture on the BZO doping influence on the pinning properties of the YBCO matrix, detailed structural analyses performed by X-ray diffraction techniques and microstructural evaluation by transmission electron microscopy are also presented. The evaluation of different contributions to the overall, J _c , permitted us to prove the effectiveness of the BZO inclusions acting as isotropic pinning centers, reflected in a uniform component of high relative value with respect to other components. For the studied 10 mol % BZO doping concentration, a threefold increase in the critical current density, J _c , of the YBCO host is measured, in self-field at 77 K, corresponding to a value of J _c =2.9MA/cm², whereas a factor 10 is measured at 1 T (J _c =0.35 MA/cm²).     

Probabilistic cumulative damage model to estimate fatigue life

This paper introduces a numerical model to estimate fatigue life under step‐stress conditions, using the Weibull and lognormal distributions. The maximum likelihood method was used to estimate the free parameters of the distributions. The model was fitted to an experimental data on fatigue life in the specimens of steel SAE 8620, by using evolutionary computation to optimize the likelihood function. Results are reported on the values of the parameters and their confidence interval. Also, a validation of the model is discussed using analysis of residuals.     

Demonstration of the environmental and demand-side management benefits of grid-connected photovoltaic power systems

This study investigated the pollutant emission reduction and demand-side management potential of 16 photovoltaic (PV) systems installed across the US during 1993 and 1994. The US Environmental Protection Agency (EPA) and 11 electric power companies sponsored the project. This article presents results of analyses of each PV system's ability to offset power plant emissions of sulfur dioxide (SO₂), nitrogen oxides (NO_x), carbon dioxide (CO₂) and particulates and to provide power during peak demand hours for the individual host buildings and peak load hours for the utility. The analyses indicate a very broad range in the systems' abilities to offset pollutant emissions, due to variation in the solar resource available and the emission rates of the participating utilities' load following generation plants. Each system's ability to reduce building peak demand was dependent on the correlation of that load to the available solar resource. Most systems operated in excess of 50% of their capacity during building peak load hours in the summer months, but well below that level during winter peak hours. Similarly, many systems operated above 50% of their capacity during utility peak load hours in the summer months, but at a very low level during winter peak hours.     

An approximate model for sizing and costing a solar thermal collector-central receiver system

An approximate generalized theoretical model is presented for the geometry and energy transfer of a solar thermal collector-central receiver system. Equations permit sizing the receiver, tower, and heliostat field. Cost functions correlate data from Department of Energy studies. Based on a set of assumed conditions, simplified, optimized sizing equations yield the minimum capital cost. The costs of the tower and central receiver will change with plant and equipment cost indices, while heliostat costs are expected to diminish as annual production increases. The heliostat cost is the major cost component even at lowest projected unit cost; therefore optimization tends toward minimum heliostat area. The model permits order-of-magnitude cost estimates to be made very quickly, compared to detailed simulation.