The Photosensitising Clinical Agent Verteporfin Is an Inhibitor of SPAK and OSR1 Kinases

STE20/SPS1‐related proline/alanine‐rich kinase (SPAK) and oxidative‐stress‐responsive kinase 1 (OSR1) are two serine/threonine protein kinases that play key roles in regulating ion homeostasis. Various SPAK and OSR1 mouse models exhibited reduced blood pressure. Herein, the discovery of verteporfin, a photosensitising agent used in photodynamic therapy, as a potent inhibitor of SPAK and OSR1 kinases is reported. It is shown that verteporfin binds the kinase domains of SPAK and OSR1 and inhibits their catalytic activity in an adenosine triphosphate (ATP)‐independent manner. In cells, verteporfin was able to suppress the phosphorylation of the ion co‐transporter NKCC1; a downstream physiological substrate of SPAK and OSR1 kinases. Kinase panel screening indicated that verteporfin inhibited a further eight protein kinases more potently than that of SPAK and OSR1. Although verteporfin has largely been studied as a modifier of the Hippo signalling pathway, this work indicates that the WNK‐SPAK/OSR1 signalling cascade is also a target of this clinical agent. This finding could explain the fluctuation in blood pressure noted in patients and animals treated with this drug.     

Effect of the Inclination of Baffles on the Power Consumption and Fluid Flows in a Vessel Stirred by a Rushton Turbine

The role of baffles in mechanically stirred tanks is to promote the stability of power drawn by the impeller and to avoid the fluid swirling, thus enhancing mixing. The present paper numerically investigates the baffles effects in a vessel stirred by a Rushton turbine. The geometric factor of interest is the baffle inclination which is varying between 25°, 32.5°, 45°, 70° and 90° at different impeller rotational speeds. The impeller rotational direction has also been varied. The vortex size and power consumption were evaluated for each geometrical configuration. It was found that the best configuration is the baffle inclination by α = 70° at a negative angular velocity.     

A statistical trust system in wireless mesh networks

Most trust and reputation solutions in wireless mesh networks (WMNs) rely on the intrusion detection system (IDS) Watchdog. Nevertheless, Watchdog does not consider packet loss on wireless links and may generate false positives. Consequently, a node that suffers from packet loss on one of its links may be accused wrongly, by Watchdog, of misbehaving. To deal with this issue, we propose in this paper a novel trust system which considers packet loss of links. Our trust system is based on a statistical detection method (SDM) implemented on each node of the network. Firstly, the SDM, via CUSUM test, analyzes the behavior of the packets loss in order to detect a dropping attack. Secondly, the SDM, through the Kolmogorov-Smirnov test, compares the behavior of the total packets loss with that of the control packets in order to identify the attack type. Our system allows every WMN’s node to assign to each of its neighbors, a trust value which reflects its real behavior. We have validated the proposed SDM method via extensive simulations on ns2 and have compared our trust system with an existing solution. The results display that our SDM solution offers better performance.     

An error calculation method for finite element analysis in large displacements

This article describes an error measurement and mesh optimization method for finite elements in non-linear geometry problems. The error calculation is adapted from a method developed by Ladeveze, based on constructing a local statically admissible stress field. The particular difficulty in non-linear geometry lies in choosing a configuration on which the fields is defined. We propose here the lagrangian or reference configuration. The error is then defined as the value in elastic energy of the difference between the two stresses. The optimization used is the type h version. © 1997 John Wiley & Sons, Ltd.     

Nonlinear analysis and reliability of metallic truss structures

The present study goes into the search for the safety domain of civil engineering structures. The objective is to show how a reliability-evaluation brought by a mechanical sizing can be obtained. For that purpose, it is necessary to have a mechanical model and a reliability model representing correctly the behavior of this type of structure.It is a question on one hand, to propose a formulation for the nonlinear calculation (mechanical nonlinearity) of the spatial structures in trusses, and on the other hand, to propose or to adapt a formulation and a modeling of the reliability. The principle of Hasofer-Lind can be applied, in first approach, for the reliability index estimation, scenarios and the probability of failure.The made check concerned metallic in truss structures. Finally, some structures are calculated using the method adapted by Hasofer-Lind to validate the probability approach of the reliability analysis.     

Non linear modeling of three-dimensional reinforced and fiber concrete structures

Under the effect of the ascending loading, the behavior of reinforced concrete structures is rather non linear. Research in industry and science aims to extend forward the use of non-linear calculation of fiber concrete for structural parts such as columns, veils and pious, as the fiber concrete is more ductile behavior then the classical concrete behavior. The formulation of the element has been established for modeling the nonlinear behavior of elastic structures in three dimensions, based on the displacement method. For the behavior of concrete and fiber concrete compressive and tensile strength (stress-strain) the uniaxial formulation is used. For steel bi-linear relationship is used. The approach is based on the discretization of the cross section trapezoidal tables. Forming the stiffness matrix of the section, the integral of the surface is calculated as the sum of the integrals on each of the cutting trapezoids. To integrate on the trapeze we have adopted the type of Simpson integration scheme.     

Elastic properties of perovskite-type hydride NaMgH3 for hydrogen storage

Mechanical properties of NaMgH₃ were investigated using the norm-conserving pseudopotentials and plane waves (PP–PW) within the general gradient approximation (GGA) in the frame of density functional theory (DFT). The elastic constants of NaMgH₃ were calculated for the first time. The NaMgH₃ compound is found to be mechanically stable at ambient pressure. The linear bulk modulus and the bulk modulus along crystallographic axes of single crystals have been derived using elastic constants. The calculated linear bulk moduli are found to be in good agreement with the theoretical value reported in the literature. Shear and Young's moduli as well as Poisson's ratio for ideal polycrystalline NaMgH₃ are also calculated. According to the obtained results, NaMgH₃ can be classified as brittle material. The shear anisotropic factors and the elastic anisotropy are also discussed. A Debye temperature of 648 K was also determined using theoretical elastic constants.     

Finished surface morphology,microstructure and magnetic properties of selective laser melted Fe-50wt% Ni permalloy

This work focuses on the structure and magnetic properties of Fe-50wt% Ni permalloy manufactured from the pre-alloyed powder by selective laser melting (SLM). The selective laser melted (SLMed) alloys were characterized by a 3D profilometer,optical microscope, scanning electron microscope, X-ray diffraction, etc. The effects of the volume energy density of laser(LVED) on structure, and magnetic properties with coercivity ( H _c ), remanence ( B _r ), and power losses ( P     

MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets

This study was carried out to quantitate the expression levels of microRNA-17, -19a, -34a, -155, and -210 (miRs) expressed in nine clear cell renal cell carcinoma (ccRCC) and one chromophobe renal cell carcinoma cell line with and without sarcomatoid differentiation, and in six primary kidney tumors with matching normal kidney tissues. The data in the five non-sarcomatoid ccRCC cell lines—RC2, CAKI-1, 786-0, RCC4, and RCC4/VHL—and in the four ccRCC with sarcomatoid differentiation—RCJ41T1, RCJ41T2, RCJ41M, and UOK-127—indicated that miR-17 and -19a were expressed at lower levels relative to miR-34a, -155, and -210. Compared with RPTEC normal epithelial cells, miR-34a, miR-155, and miR-210 were expressed at higher levels, independent of the sarcomatoid differentiation status and hypoxia-inducible factors 1α and 2α (HIFs) isoform expression. In the one chromophobe renal cell carcinoma cell line, namely, UOK-276 with sarcomatoid differentiation, and expressing tumor suppressor gene TP53, miR-34a, which is a tumor suppressor gene, was expressed at higher levels than miR-210, -155, -17, and -19a. The pilot results generated in six tumor biopsies with matching normal kidney tissues indicated that while the expression of miR-17 and -19a were similar to the normal tissue expression profile, miR-210, -155, -and 34a were expressed at a higher level. To confirm that differences in the expression levels of the five miRs in the six tumor biopsies were statistically significant, the acquisition of a larger sample size is required. Data previously generated in ccRCC cell lines demonstrating that miR-210, miR-155, and HIFs are druggable targets using a defined dose and schedule of selenium-containing molecules support the concept that simultaneous and concurrent downregulation of miR-210, miR-155, and HIFs, which regulate target genes associated with increased tumor angiogenesis and drug resistance, may offer the potential for the development of a novel mechanism-based strategy for the treatment of patients with advanced ccRCC.     

Effect of structure on the glass transition temperatures of linear and crosslinked poly(isobornylacrylate-co-isobutylacrylate)

A series of linear acrylic copolymers based on Isobornyl acrylate (IBOA) and isobutyl acrylate (IsoBA) were elaborated by radical photopolymerization. In addition, several photochemically crosslinked poly(IBOA-co-IsoBA) were prepared by introducing small amounts of 1,6-hexanedioldiacrylate as crosslinking agent. The evolution of the glass transition temperature was determined experimentally by differential scanning calorimetry as a function of composition for both linear and crosslinked poly(IBOA-co-IsoBA), yielding T_g values ranging from (~249) to (~315 K). Theoretical modeling was performed applying Fox, Gordon-Taylor and Couchman-Karasz models by simple calculations using experimental data, leading to only fair agreement between theoretical and experimental values, or by applying fitting procedures involving one or two adjustable parameters. Likewise, the Kwei model, known to take into account hydrogen bonding interactions between monomers, could not describe well the evolution of T_g, indicating the existence of other factors influencing T_g. Finally, a thermodynamic approach based on entropy considerations allowed to attribute an explanation of the evolution of T_g.