DMSO Chemically Alters Cell Membranes to Slow Exocytosis and Increase the Fraction of Partial Transmitter Released

Dimethyl sulfoxide (DMSO) is frequently used as a solvent in biological studies and as a vehicle for drug therapy; but the side effects of DMSO, especially on the cell environment, are not well understood, and controls with DMSO are not neutral at higher concentrations. Herein, electrochemical measurement techniques are applied to show that DMSO increases exocytotic neurotransmitter release, while leaving vesicular contents unchanged. In addition, the kinetics of release from DMSO‐treated cells are faster than that of untreated ones. The results suggest that DMSO has a significant influence on the chemistry of the cell membrane, leading to alteration of exocytosis. A speculative chemical mechanism of the effect on the fusion pore during exocytosis is presented.     

Regioselective synthesis of new 5-methyl-5H-pyrimido[4′,5′:4,5][1,3]thiazino [3,2-a]perimidines

A convenient and efficient regioselective synthesis of new pyrimido[4′,5′:4,5] [1,3]thiazino[3,2-a]perimidines is described through intermolecular heterocyclization of 2,4-dichloro-5-(chloromethyl)-6-methylpyrimidine and 1H-perimidine-2(3H)-thione in short reaction times under mild conditions.     

Elimination of mercury by adsorption onto activated carbon prepared from the biomass material

Following the previous work (Kaghazchi et al., 2010 [11]), dealing with applying a combination of two kinds of agricultural wastes to produce a new adsorbent, this study is dedicated to investigate the details of mercury adsorption process from aquatic medium by this adsorbent. So the Mix-ZC activated carbon (the sample prepared by chemical activation of a mixture of pistachio-nut shells and licorice residues impregnated with zinc chloride) was selected for doing a series of batch adsorption experiments on it. Equilibrium isotherms, such as Freundlich, Langmuir, Dubinin–Redushkevich and Temkin have been tested. Kinetic studies based on Lagergren first-order, pseudo-second-order rate expressions and intra-particle diffusion studies have been done. The mechanisms of mercury adsorption onto this adsorbent under the operating conditions were also studied.     

Investigation of the Effect of Tungsten Substitution on Microstructure and Abrasive Wear Performance of In Situ VC-Reinforced High-Manganese Austenitic Steel Matrix Composite

Particulate VC-reinforced high-manganese austenitic steel matrix composites with different vanadium and tungsten contents were synthesized by conventional alloying and casting route. Microstructural characterizations showed that the composites processed by in situ precipitation of the reinforcements were composed of V₈C₇ particulates distributed in an austenitic matrix. It was observed that addition of tungsten to austenite increases work-hardening rate of subsurface layer during pin-on disk wear test. The maximum abrasive wear resistance was achieved at tungsten content equal to 2 wt pct. However, excessive addition of tungsten promoted the formation of W₃C phase and reduced the abrasive wear resistance because of decrease in distribution homogeneity and volume fraction of the reinforcing VC particles.     

A review of surface engineering issues critical to wind turbine performance

Wind turbine performance can be significantly reduced when the surface integrity of the turbine blades is compromised. Many frontier high-energy regions that are sought for wind farm development including Nordic, warm-humid, and desert-like environments often provide conditions detrimental to the surface of the turbine blade. In Nordic climates ice can form on the blades and the turbine structure itself through a variety of mechanisms. Initial ice adhesion may slightly modify the original aerodynamic profile of the blade; continued ice accretion can drastically affect the structural loading of the entire rotor leading to potentially dangerous situations. In warmer climates, a humid wind is desirable for its increased density; however, it can come at a price when the region supports large populations of insects. Insect collisions with the blades can foul blade surfaces leading to a marked increase in skin drag, reducing power production by as much as 50%. Finally, in more arid regions where there is no threat from ice or insects, high winds can carry soil particles eroded from the ground (abrasive particles). Particulate-laden winds effectively sand-blast the blade surfaces, and disrupt the original skin profile of the blade, again reducing its aerodynamic efficiency. While these problems are challenging, some mitigative measures presently exist and are discussed in the paper. Though, many of the current solutions to ice or insect fouling actually siphon power from the turbine itself to operate, or require that the turbine be stopped, in either case, profitability is diminished. Our survey of this topic in the course of our research suggests that a desirable solution may be a single surface engineered coating that reduces the incidence of ice adhesion, insect fouling, and protects the blade surface from erosive deterioration. Research directions that may lead to such a development are discussed herein.     

CDC42-IQGAP Interactions Scrutinized: New Insights into the Binding Properties of the GAP-Related Domain

The IQ motif-containing GTPase-activating protein (IQGAP) family composes of three highly-related and evolutionarily conserved paralogs (IQGAP1, IQGAP2 and IQGAP3), which fine tune as scaffolding proteins numerous fundamental cellular processes. IQGAP1 is described as an effector of CDC42, although its effector function yet re-mains unclear. Biophysical, biochemical and molecular dynamic simulation studies have proposed that IQGAP RASGAP-related domains (GRDs) bind to the switch regions and the insert helix of CDC42 in a GTP-dependent manner. Our kinetic and equilibrium studies have shown that IQGAP1 GRD binds, in contrast to its C-terminal 794 amino acids (called C794), CDC42 in a nucleotide-independent manner indicating a binding outside the switch regions. To resolve this discrepancy and move beyond the one-sided view of GRD, we carried out affinity measurements and a systematic mutational analysis of the interfacing residues between GRD and CDC42 based on the crystal structure of the IQGAP2 GRD-CDC42^Q61L GTP complex. We determined a 100-fold lower affinity of the GRD1 of IQGAP1 and of GRD2 of IQGAP2 for CDC42 mGppNHp in comparison to C794/C795 proteins. Moreover, partial and major mutation of CDC42 switch regions substantially affected C794/C795 binding but only a little GRD1 and remarkably not at all the GRD2 binding. However, we clearly showed that GRD2 contributes to the overall affinity of C795 by using a 11 amino acid mutated GRD variant. Furthermore, the GRD1 binding to the CDC42 was abolished using specific point mutations within the insert helix of CDC42 clearly supporting the notion that CDC42 binding site(s) of IQGAP GRD lies outside the switch regions among others in the insert helix. Collectively, this study provides further evidence for a mechanistic framework model that is based on a multi-step binding process, in which IQGAP GRD might act as a ‘scaffolding domain’ by binding CDC42 irrespective of its nucleotide-bound forms, followed by other IQGAP domains downstream of GRD that act as an effector domain and is in charge for a GTP-dependent interaction with CDC42.     

p53 Family in Resistance to Targeted Therapy of Melanoma

Metastatic melanoma is one of the most aggressive tumors, with frequent mutations affecting components of the MAPK pathway, mainly protein kinase BRAF. Despite promising initial response to BRAF inhibitors, melanoma progresses due to development of resistance. In addition to frequent reactivation of MAPK or activation of PI3K/AKT signaling pathways, recently, the p53 pathway has been shown to contribute to acquired resistance to targeted MAPK inhibitor therapy. Canonical tumor suppressor p53 is inactivated in melanoma by diverse mechanisms. The TP53 gene and two other family members, TP63 and TP73, encode numerous protein isoforms that exhibit diverse functions during tumorigenesis. The p53 family isoforms can be produced by usage of alternative promoters and/or splicing on the C- and N-terminus. Various p53 family isoforms are expressed in melanoma cell lines and tumor samples, and several of them have already shown to have specific functions in melanoma, affecting proliferation, survival, metastatic potential, invasion, migration, and response to therapy. Of special interest are p53 family isoforms with increased expression and direct involvement in acquired resistance to MAPK inhibitors in melanoma cells, implying that modulating their expression or targeting their functional pathways could be a potential therapeutic strategy to overcome resistance to MAPK inhibitors in melanoma.     

A 110–140 GHz Millimeter-Wave VCO Using Varactor and Bulk Effective Technique in 65 nm CMOS Process

In this paper, an enhanced voltage controlled oscillator (VCO) at center frequency 125 GHz with tuning rang of 24% is presented. The proposed idea is based on the tuning capacitance using MOS varactor. The structure is consisted of applying an MOS varactor capacitor to the drain and bulk (in parallel) of NMOS transistor in 65 nm CMOS standard technology. The obtained output of the proposed VCO at 2nd harmonic is tunable at 110–140 GHz frequency with applying?±?1.2 input tuning voltage. Simulation results of the proposed circuit are obtained after extracting post layout (with total chip size of 0.07 mm²) and confirm theoretical results. Compared to the resent designs, the obtained results indicate that the proposed circuit has high tuning range, low die area and a good figure of merit @ 1.2 power supply voltage.