Calcium Ions Regulate K+ Uptake into Brain Mitochondria: The Evidence for a Novel Potassium Channel

The mitochondrial response to changes of cytosolic calcium concentration has a strong impact on neuronal cell metabolism and viability. We observed that Ca²⁺ additions to isolated rat brain mitochondria induced in potassium ion containing media a mitochondrial membrane potential depolarization and an accompanying increase of mitochondrial respiration. These Ca²⁺ effects can be blocked by iberiotoxin and charybdotoxin, well known inhibitors of large conductance potassium channel (BK_Ca channel). Furthermore, NS1619 – a BK_Ca channel opener – induced potassium ion–specific effects on brain mitochondria similar to those induced by Ca²⁺. These findings suggest the presence of a calcium-activated, large conductance potassium channel (sensitive to charybdotoxin and NS1619), which was confirmed by reconstitution of the mitochondrial inner membrane into planar lipid bilayers. The conductance of the reconstituted channel was 265 pS under gradient (50/450 mM KCl) conditions. Its reversal potential was equal to 50 mV, which proved that the examined channel was cation-selective. We also observed immunoreactivity of anti-β₄ subunit (of the BK_Ca channel) antibodies with ~26 kDa proteins of rat brain mitochondria. Immunohistochemical analysis confirmed the predominant occurrence of β₄ subunit in neuronal mitochondria. We hypothesize that the mitochondrial BK_Ca channel represents a calcium sensor, which can contribute to neuronal signal transduction and survival.     

不同角度内模填充衣架型机头的数值模拟

利用Polyflow软件对填充了不同角度内模的衣架型机头流道进行了模拟。研究了不同内模夹角对流道压力分布、出口压力、出口速度以及流道内流体停留时间的影响。结果表明:不同角度内模填充机头流道后,流道压力分布、出口压力和出口速度无明显改变;流道内物料主要停留在歧管端部;通过改变内模夹角,可以改变物料最大停留时间及停留面积,内模夹角为40°时,流道内最大停留时间短,物料停留少。     

阻坝扩张式复合机头结构参数对短纤维补强橡胶复合材料性能的影响

研究阻坝扩张式复合机头的结构参数包括扩张比、扩张角、阻坝间隙、定型流道段长度、收敛角和过渡流道段长度对短纤维补强橡胶复合材料性能的影响。结果表明:当扩张比为5、扩张角为150°、阻坝间隙为4 mm、定型流道段长度为50 mm、收敛角为120°、过渡流道段长度为30 mm时,短纤维补强橡胶复合材料的综合物理性能较好,且各向异性明显。     

Ionic mass transfer in open channel flow

An analysis of open-conduit electrolytic cells is presented via open channel theory and the concept of an interaction parameter related to free and forced convection effects.     

Diffusion pathways of benzene, toluene and p-xylene in MFI

The diffusion of alkyl-substituted aromatic molecules in H-ZSM-5 was investigated by means of the frequency response method decoupling particle size effects and intracrystalline diffusion. For zeolite crystals above 5 μm average diameter, the transport in the zeolite pores exerts a significant effect on the overall transport causing anisotropic diffusion as the aspect ratio of the aromatic molecules increases. Diffusion of benzene is nearly isotropic, while p-xylene shows marked differences between the diffusive processes in the straight and sinusoidal channel system of ZSM-5. The isotropic diffusion of benzene is rationalized on the basis of its ability to reorient between the two channel systems without major hindrances. For p-xylene, switching between the channels is only possible by energetically unfavorable rotational motions leading to a low probability for changing between both channel systems.     

Pharmacologically Targeting the Fibroblast Growth Factor 14 Interaction Site on the Voltage-Gated Na+ Channel 1.6 Enables Isoform-Selective Modulation

Voltage-gated Na⁺ (Na_v) channels are the primary molecular determinant of the action potential. Among the nine isoforms of the Na_v channel α subunit that have been described (Na_v1.1-Na_v1.9), Na_v1.1, Na_v1.2, and Na_v1.6 are the primary isoforms expressed in the central nervous system (CNS). Crucially, these three CNS Na_v channel isoforms display differential expression across neuronal cell types and diverge with respect to their subcellular distributions. Considering these differences in terms of their localization, the CNS Na_v channel isoforms could represent promising targets for the development of targeted neuromodulators. However, current therapeutics that target Na_v channels lack selectivity, which results in deleterious side effects due to modulation of off-target Na_v channel isoforms. Among the structural components of the Na_v channel α subunit that could be pharmacologically targeted to achieve isoform selectivity, the C-terminal domains (CTD) of Na_v channels represent promising candidates on account of displaying appreciable amino acid sequence divergence that enables functionally unique protein–protein interactions (PPIs) with Na_v channel auxiliary proteins. In medium spiny neurons (MSNs) of the nucleus accumbens (NAc), a critical brain region of the mesocorticolimbic circuit, the PPI between the CTD of the Na_v1.6 channel and its auxiliary protein fibroblast growth factor 14 (FGF14) is central to the generation of electrical outputs, underscoring its potential value as a site for targeted neuromodulation. Focusing on this PPI, we previously developed a peptidomimetic derived from residues of FGF14 that have an interaction site on the CTD of the Na_v1.6 channel. In this work, we show that whereas the compound displays dose-dependent effects on the activity of Na_v1.6 channels in heterologous cells, the compound does not affect Na_v1.1 or Na_v1.2 channels at comparable concentrations. In addition, we show that the compound correspondingly modulates the action potential discharge and the transient Na+ of MSNs of the NAc. Overall, these results demonstrate that pharmacologically targeting the FGF14 interaction site on the CTD of the Na_v1.6 channel is a strategy to achieve isoform-selective modulation, and, more broadly, that sites on the CTDs of Na_v channels interacted with by auxiliary proteins could represent candidates for the development of targeted therapeutics.     

Analytical Study of Effect of Channel Doping on Threshold Voltage of Metal Gate High-k SiGe MOSFET

The paper reports the analytical model for the analysis of the effects of channel doping on the threshold voltage. A silicon germanium p-MOSFET with high-k dielectric material along with a metal gate is used for the analysis. The presented model considers the short channel effects, junction depth, doping of the layers and metal gate work function. Results are validated with the 22 nm device geometry. The MOSFET with reduced channel doping reflects the corresponding reduction in the threshold voltage. The model can effectively analyze the SiGe p-MOSFET for device designing in the nanometer regime.     

Effect of drainage channel dimensions on the performance of wave-plate mist eliminators

We investigated the effects of drainage channel dimensions on droplet removal efficiency and pressure drop of the gas droplet flow in a wave-plate mist eliminator. Droplet dispersion in turbulent gas flows is numerically simulated using eddy interaction model (EIM) and Eulerian-Lagrangian method. Reynolds stress transport model (RSTM) with enhanced wall treatment and shear stress transport (SST) k-ω model are used for simulating the turbulent airflow. Comparison between the numerical simulations and available experimental data shows that eddy lifetime constant (C _L ) can affect the results significantly, and by selecting suitable values of the eddy lifetime constant, both turbulence models give reasonable predictions of droplet removal efficiency. Simulations of gas droplet flow in the eliminators with various drainage channel dimensions show that the drainage channel length (L _DC ) has a greater effect on droplet removal efficiency than the drainage channel width (W _DC ).     

Effects of flow channel geometry on cell performance for PEM fuel cells with parallel and interdigitated flow fields

A 3D numerical model was developed to explore the effects of the cathode flow channel configuration on the local transport phenomena and cell performance for parallel and interdigitated flow fields in proton exchange membrane (PEM) fuel cells. The effect of liquid water formation on the reactant transport is taken into account in the model. For operating voltages greater than 0.7 V, the electrochemical reaction rates are low with a small amount of oxygen consumption and liquid water production, and all cell designs provide sufficient oxygen for the electrochemical reactions. Thus, the flow channel aspect ratio and the flow channel cross-sectional area have little effect on the cell performance. For operating voltages lower than 0.7 V, as the operating voltage decreases the electrochemical reaction rates gradually increase with a large amount of oxygen consumption and liquid water production, so the cell performance is strongly dependent on the flow field design. For the parallel flow field design, lower flow channel aspect ratios and flow channel cross-sectional area areas improve liquid water removal, thus, decreasing both improves cell performance. However, the interdigitated design has an optimal aspect ratio of 1.00 and an optimal cross-sectional area of 1.000 mm × 1.000 mm.     

陶瓷膜通道相互作用的实验分析及CFD优化

提出陶瓷膜过滤时,通道之间存在3种效应关系（壁厚效应、干扰效应、遮挡效应）,并用实验进行了验证。对于多通道陶瓷膜构型的设计,要考虑3种效应。膜孔径小于200 nm的陶瓷膜,可以增大其通道的排布密度,通过提高装填密度可以提高单位体积的处理量;膜孔径大于500 nm的陶瓷膜,中间的通道对通量几乎没有贡献,提高装填密度意义不大。固定膜元件的外径,选取通道直径a_c和壁厚a_w,并设定两参数的比值为α,采用计算流体力学（CFD）软件进行模拟计算,获得了通量与处理量随孔径与α值的变化关系。     

Effects of Energy Relaxation via Quantum Coupling Among Three-Dimensional Motion on the Tunneling Current of Graphene Field-Effect Transistors

We report theoretical study of the effects of energy relaxation on the tunneling current through the oxide layer of a two-dimensional graphene field-effect transistor. In the channel, when three-dimensional electron thermal motion is considered in the Schrödinger equation, the gate leakage current at a given oxide field largely increases with the channel electric field, electron mobility, and energy relaxation time of electrons. Such an increase can be especially significant when the channel electric field is larger than 1 kV/cm. Numerical calculations show that the relative increment of the tunneling current through the gate oxide will decrease with increasing the thickness of oxide layer when the oxide is a few nanometers thick. This highlights that energy relaxation effect needs to be considered in modeling graphene transistors.     

Effect of varying incidental angles of a wire-rod insert on the performance of tubular ultrafiltration membranes

Increasing the fluid velocity in cross-flow membrane ultrafilter has two conflicting effects: one, the decrease in concentration polarization resistance, which is good for ultrafiltration; while the other, the decrease in average transmembrane pressure is bad for performance. Along the flow channel of a cross-flow membrane ultrafiltration, concentration polarization increases while transmembrane pressure decreases. Therefore, proper adjustment of the convection strength along the flow channel might effectively suppress the undesirable concentration polarization resistance while still preserving effective transmembrane pressure, and thereby lead to improved permeate recoveries. The effect of hydraulic behavior on membrane ultrafiltration in a tubular module inserted concentrically with a steel rod wrapped by a wire spiral with a wire angle varied at a uniform rate along the flow channel was investigated, and the appropriate manner of wire-angle variation along the tube discussed. It was concluded that for the modules of fixed average wire-spiral angle, the best manner of wire-angle variation is such that the wire angle should increase gradually from 0° along the flow channel.     

CFD analysis of microchannel emulsification: Droplet generation process and size effect of asymmetric straight flow-through microchannels

Asymmetric straight flow-through microchannel (MC) arrays are high-performance MC emulsification devices for stable mass production of uniform droplets. This paper presents computational fluid dynamics (CFD) simulation and analysis of the generation of soybean oil-in-water emulsion droplets via asymmetric straight flow-through MCs, each consisting of a microslot and a narrow MC. We also used CFD to investigate the effects of the channel size and the flow of the dispersed phase on MC emulsification using asymmetric straight flow-through MCs with a characteristic channel size of 5–400 μm. The overall shape of an oil–water interface and the time scale during droplet generation via a control asymmetric straight flow-through MC were appropriately simulated. Better insight was obtained on the flow profile of the two phases and the internal pressure balance of the dispersed phase during droplet generation. Comparison of the CFD and experiment results also provided insight into dynamic interfacial tension during droplet generation. Successful droplet generation was observed below a critical dispersed-phase velocity. In this case, the resultant droplet size was proportional to the channel size and was not sensitive to the dispersed-phase velocity applied. The maximum droplet generation rate per channel was inversely proportional to the channel size, unless the buoyancy force did not promote droplet detachment. The maximum droplet productivity per unit area of an asymmetric straight flow-through MC array was estimated to be constant, regardless of channel size.     

A Novel Technique to Investigate the Impact of Temperature and Process Parameters on Electrostatic and Analog/RF Performance of Channel Modulated Junctionless Gate-all-around (CM-JL-GAA) MOSFET

Silicon - The channel modulated junctionless gate all around (CM-JL-GAA) MOSFET improves the SCE’s with high graded doping of the channel region. Temperature effects on electrostatic and...     

Controlled atmosphere electron microscopy studies of graphite gasification—3. The catalytic influence of molybdenum and molybdenum trioxide

CAEM has been used to investigate the behaviour of Mo and MoO₃ as catalysts in the graphite-oxygen reaction. Both pitting and channelling activity were observed. The effects of temperature and particle size on channel propagation rates have been quantitatively evaluated. Intercalation of MoO₃ is suggested as playing a role in the exfoliation of graphite sheets. Difficulties in the interpretation of anisotropy effects are discussed.     

The flow properties of fluidized solids

Experimental measurements of the non-Newtonian flow properties of a 200-μm-diam. sand fluidized at 1.5 – 3 U_mf in open channel flow are reported.Asymmetry in the velocity profile was found to change with change in the experimental conditions, but it is thought primarily to be a consequence of air maldistribution which is partly generated by the bed flow in the experimental rig.There was evidence of varying degrees of drag across the distributor, from conditions of slip giving rise to a semi-plug flow profile at higher fluidizing velocities and bed flow rates, to conditions where the drag exacted across the distributor at lower solids flow rates exceeds that at the vertical channel walls.Bed flow properties deteriorate as the bed depth increases. This is a consequence of the deleterious effect of bubble growth within the bed.Reasonable agreement was obtained between velocity profiles predicted following Wheeler and Wissler and those measured under conditions where the drag across the distributor and the vertical channel walls was of similar magnitude. Some estimate was made of the relative effects of power law index, channel aspect ratio and slip on the solids flow.     

Structure‐Based Virtual Screening and Electrophysiological Evaluation of New Chemotypes of Kv1.5 Channel Blockers

Atrial fibrillation (AF) is the most prevalent nonfatal cardiac rhythm disorder associated with an increased risk of heart failure and stroke. Considering the ventricular side effects induced by anti‐arrhythmic agents in current use, K_v1.5 channel blockers have attracted a great deal of deliberation owing to their selective actions on atrial electrophysiology. Herein we report new chemotypes of K_v1.5 channel blockers that were identified through a combination of structure‐based virtual screening and in silico druglike property prediction including six scoring functions, as well as electrophysiological evaluation. Among them, five of the 18 compounds exhibited >50 % blockade ratio at 10 μM , and have structural features different from conventional K_v1.5 channel blockers. These novel scaffolds could serve as hits for further optimization and SAR studies for the discovery of selective agents to treat AF.     

Effects of anode orientation and flow channel design on performance of refuelable zinc-air fuel cells

The effects of anode orientation (whether an anode is located above or under a cathode) and flow channel design (parallel or serpentine flow channel) on the performance of refuelable zinc-air fuel cells (RZAFC) continuously fed with KOH electrolyte were investigated. The performance test was conducted at different electrolyte flow rates of 2, 4, and 6 ml h^?1. A polarization test of the cell was conducted at the initial stage of operation, followed by a long-term current discharge test in potentiostatic mode. The spent zinc powders were characterized by a scanning electron microscope and X-ray diffraction. The experimental results revealed that the anode-bottom orientation in the cell performed much better than the anode-top orientation with 11.4 times higher zinc utilization. The performance reduction of the anode-top orientation cell was caused by the cathode overpotential, due to the flooding of the cathode by water crossover from the anode, which was induced by the gravity force. For the flow channel design effects, there was an optimum electrolyte flow rate, to yield a maximum current discharge capacity, of 4 ml h^?1 in this study. At this optimum flow rate, the total charge per gram of zinc delivered from the anode serpentine cell was 1.75 times higher than that from the anode-parallel one.     

Ketamine Produces a Long-Lasting Enhancement of CA1 Neuron Excitability

Ketamine is a clinical anesthetic and antidepressant. Although ketamine is a known NMDA receptor antagonist, the mechanisms contributing to antidepression are unclear. This present study examined the loci and duration of ketamine’s actions, and the involvement of NMDA receptors. Local field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant and anesthetic concentrations. Effects of NMDA receptor antagonists APV and MK-801, GABA receptor antagonist bicuculline, and a potassium channel blocker TEA were also studied. Ketamine decreased population spike amplitudes during application, but a long-lasting increase in amplitudes was seen during washout. Bicuculline reversed the acute effects of ketamine, but the washout increase was not altered. This long-term increase was statistically significant, sustained for >2 h, and involved postsynaptic mechanisms. A similar effect was produced by MK-801, but was only partially evident with APV, demonstrating the importance of the NMDA receptor ion channel block. TEA also produced a lasting excitability increase, indicating a possible involvement of potassium channel block. This is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anesthesia, while increased excitatory transmission contributes to its antidepressant effects.     

Crosswise ridge micromixers with split and recombination helical flows

This study presents a novel crosswise ridge micromixer (CRM) with a series of microstructures placed on the top and bottom floors of channels. Passive micromixers fabricated by Micro Electro-Mechanical Systems (MEMS) technologies with slanted ridges are investigated. Numerical simulations and experimental investigations are undertaken to determine the effects of various microstructure patterns on mixing efficiency with Reynolds numbers (Re) of 0.05–50. The confocal images at the cross-sections along the channel with ridges on both the channel top and bottom are first investigated in our study. A significant amount of split and recombination (SAR) helical flows is produced by the slanted ridges embedded on the two floors of the channels. The effects of non-dimensional parameters, such as the Re, as well as geometrical parameters on mixing performance are presented in terms of the mixing index. When the Re exceeds 1, the mixing index of the micromixer with slanted ridges increases as the Re increases further. Simulation results are presented and compared with experimental data. The trends of the experimental results and numerical data are very similar. Finally, various numbers of slanted ridges in the same orientation in one channel cycle are investigated to determine mixing performance in microchannels. The mixing performance achieves an optimum value in case where the number of ridges per cycle is equal to 8.