An Autophagy-Disrupting Small Molecule Promotes Cancer Cell Death via Caspase Activation

A novel autophagy inhibitor, autophazole (Atz), which promoted cancer cell death via caspase activation, is described. This compound was identified from cell-based high-content screening of an imidazole library. The results showed that Atz was internalized into lysosomes of cells where it induced lysosomal membrane permeabilization (LMP). This process generated nonfunctional autolysosomes, thereby inhibiting autophagy. In addition, Atz was found to promote LMP-mediated apoptosis. Specifically, LMP induced by Atz caused release of cathepsins from lysosomes into the cytosol. Cathepsins in the cytosol cleaved Bid to generate tBid, which subsequently activated Bax to induce mitochondrial outer membrane permeabilization (MOMP). This event led to cancer cell death via caspase activation. Overall, the findings suggest that Atz will serve as a new chemical probe in efforts aimed at gaining a better understanding of the autophagic process.     

铝合金ADC12Z高压铸造过程中铸件与铸型间界面热交换系数的研究

通过采集高压铸造过程中铸型内部温度的变化曲线,采用热传导反算法,求解了以铝合金ADC12Z为铸件材料的铸件-铸型界面换热系数,分析了该界面换热系数随铸件厚度的变化规律.计算及分析结果表明:在压铸过程中,铸件-铸型界面换热系数迅速升至最大值,随后下降,凝固结束后趋于稳定.铸件厚度增大不仅提高了换热系数,而且对换热系数的变化趋势也有很大影响.同时,不同厚度的铸件,其固相率和冷却速率的变化规律也有较大区别.     

Analysis on the thermal and electrical characteristics of impregnating materials for the bifilar winding-type superconducting fault current limiter

The resistive type high temperature superconducting fault current limiter (HTSFCL) limits the fault current with the resistance that generated by fault current. The generated resistance by fault current makes large pulse power which makes the operation of HTSFCL unstable. So, the cryogenic cooling system of the resistive type HTSFCL must diffuse and eliminate the pulse energy very quickly. Although the best way is to make wide direct contact area between HTS winding and coolant as much as possible, HTS winding also need the impregnation layer which fixes and protects it from electromagnetic force. This paper deals with thermal conductivity and dielectric strength of some epoxy compounds for the impregnation of high temperature superconducting (HTS) winding at 77 K. The measured data can be used in the optimal design of impregnation for HTS winding. Aluminar filling increased the thermal conductivity of epoxy compounds. Hardener also affected the thermal conductivity and the dielectric strength of epoxy compounds.     

Low molecular weight β-glucan stimulates doxorubicin-induced suppression of immune functions in mice

The aim of this study was to evaluate the protective effect of low molecular weight β-glucan (LMG) against doxorubicin (DOX)-induced immune suppression of tumor-bearing mice. The tumor size and spleen cell functions such as spleen cell proliferation, cytokine production (interferon-γ and interleukin-2), and the population of CD4⁺ and CD8⁺ T cells were estimated. In the tumorbearing mice, the tumor size was significantly (p<0.05) decreased by DOX treatment. However, there was no significant difference between mice treated with high molecular weight β-glucan (HMG) and mice treated with LMG. Spleen cell proliferation and cytokine production were significantly (p<0.05) decreased in only DOX treated group, but increased in all β-glucan treated groups with DOX. Moreover, the populations of CD4⁺ and CD8⁺ T cells were also increased in the LMG-treated group. It appears that LMG effectively reduces the DOX-induced immune toxicity through activation of immune cells such as splenocytes.     

Molybdenum carbide embedded in carbon nanofiber as a 3D flexible anode with superior stability and high-rate performance for Li-ion batteries

The fabrication process and material design of flexible lithium-ion batteries (LIBs) are essential in flexible portable devices. In particular, the carbon nanofiber (CNF)-based active anodes with flexibility synthesized using an electrospinning technique showed fairly stable cycling performance in the LIBs. In this study, we synthesized the molybdenum carbide (MoC) embedded in CNFs as an anode for LIBs (MoC/CNF) using an electrospinning technique with amorphous Mo precursor and polyacrylonitrile as the molybdenum and carbon sources, respectively, and using a heating process under an N₂ atmosphere. The as-prepared flexible MoC/CNF showed a 3D porous structure consisting of crystalline MoC and amorphous CNF. MoC/CNF, directly utilized as an active electrode without binder, conductor, or current collector, exhibited superior LIB performance, i.e. high capacity, cyclability, and high-rate properties. In particular, at a considerably high charge/discharge rate of 10?A?g^?1, the specific capacity of MoC/CNF (109?mAh?g^?1) was significantly higher than that of pure CNF electrode (3?mAh?g^?1).     

Genistein Inhibits Osteoclastic Differentiation of RAW 264.7 Cells via Regulation of ROS Production and Scavenging

Genistein, a phytoestrogen, has been demonstrated to have a bone-sparing and antiresorptive effect. Genistein can inhibit the osteoclast formation of receptor activator of nuclear factor-κB ligand (RANKL)-induced RAW 264.7 cells by preventing the translocation of nuclear factor-κB (NF-κB), a redox-sensitive factor, to the nucleus. Therefore, the suppressive effect of genistein on the reactive oxygen species (ROS) level during osteoclast differentiation and the mechanism associated with the control of ROS levels by genistein were investigated. The cellular antioxidant capacity and inhibitory effect of genistein were confirmed. The translation and activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1), as well as the disruption of the mitochondrial electron transport chain system were obviously suppressed by genistein in a dose-dependent manner. The induction of phase II antioxidant enzymes, such as superoxide dismutase 1 (SOD1) and heme oxygenase-1 (HO-1), was enhanced by genistein. In addition, the translational induction of nuclear factor erythroid 2-related factor 2 (Nrf2) was notably increased by genistein. These results provide that the inhibitory effects of genistein on RANKL-stimulated osteoclast differentiation is likely to be attributed to the control of ROS generation through suppressing the translation and activation of Nox1 and the disruption of the mitochondrial electron transport chain system, as well as ROS scavenging through the Nrf2-mediated induction of phase II antioxidant enzymes, such as SOD1 and HO-1.     

Cell Signal Distribution and Imprint Reliability in FeRAM with Hybrid Bit Line Architecture

We have investigated the cell signal distributions of ferroelectric random access memories (FeRAMs) using newly developed design scheme, hybrid bit line architecture and their reliability against imprint degradation. Since FeRAMs have relatively large signal distributions due to nonuniform ferroelectric storage capacitors, cell signal interference between neighboring bit lines severely degrades the sensing signal margin. In order to remove the cross-talk noise, hybrid bit line architecture is developed, which is a combination of the conventional folded and open bit line schemes. The lifetime against imprint degradation of FeRAM devices is also increased using hybrid bit line architecture.     

Virtual X-ray imaging techniques in an immersive casting simulation environment

A computer code was developed to simulate radiograph of complex casting products in a CAVE^TM-like environment. The simulation is based on the deterministic algorithms and ray tracing techniques. The aim of this study is to examine CAD/CAE/CAM models at the design stage, to optimize the design and inspect predicted defective regions with fast speed, good accuracy and small numerical expense. The present work discusses the algorithms for the radiography simulation of CAD/CAM model and proposes algorithmic solutions adapted from ray-box intersection algorithm and octree data structure specifically for radiographic simulation of CAE model. The stereoscopic visualization of full-size of product in the immersive casting simulation environment as well as the virtual X-ray images of castings provides an effective tool for design and evaluation of foundry processes by engineers and metallurgists.     

Hot rolling simulations of austenitic stainless steel

The dynamic, static and metadynamic recrystallization behavior of austenitic stainless steel during hot rolling was analyzed. In this approach, each of those recrystallization behaviors is described by appropriate kinetics equations. The critical strain for dynamic recrystallization was determined so that a distinction could be made between static and metadynamic recrystallization; then the amounts of strain accumulation compared with the critical strain each pass. The effects of grain size on the fraction recrystallized and of the latter on the flow stress were evaluated for each type recrystallization behavior. In this way, the dependence of the mean flow stress (MFS) on temperature could be analyzed in terms of the extent and nature of the prior or concurrent recrystallization mechanisms. Finally, an example is given of an industrial process in which DRX/MDRX can play an important role. More grain refinement can be achieved by increasing the strain rate, decreasing the interruption time and lowering the temperature of deformation.     

Grain Boundary Conformed Volumetric Mesh Generation from a Three-Dimensional Voxellated Polycrystalline Microstructure

We present a new comprehensive scheme for generating grain boundary conformed, volumetric mesh elements from a three-dimensional voxellated polycrystalline microstructure. From the voxellated image of a polycrystalline microstructure obtained from the Monte Carlo Potts model in the context of isotropic normal grain growth simulation, its grain boundary network is approximated as a curvature-maintained conformal triangular surface mesh using a set of in-house codes. In order to improve the surface mesh quality and to adjust mesh resolution, various re-meshing techniques in a commercial software are applied to the approximated grain boundary mesh. It is found that the aspect ratio, the minimum angle and the Jacobian value of the re-meshed surface triangular mesh are successfully improved. Using such an enhanced surface mesh, conformal volumetric tetrahedral elements of the polycrystalline microstructure are created using a commercial software, again. The resultant mesh seamlessly retains the short- and long-range curvature of grain boundaries and junctions as well as the realistic morphology of the grains inside the polycrystal. It is noted that the proposed scheme is the first to successfully generate three-dimensional mesh elements for polycrystals with high enough quality to be used for the microstructure-based finite element analysis, while the realistic characteristics of grain boundaries and grains are maintained from the corresponding voxellated microstructure image.