Three-dimensional simulation of long-wavelength free-electron lasers with helical wiggler and ion-channel guiding

A three-dimensional simulation of a steady-state amplifier model of a long-wavelength free-electron laser （FEL） with realizable helical wiggler and ion-channel guiding is presented. The set of coupled nonlinear differential equations for electron orbits and fields of TE 11 mode in a cylindrical waveguide are solved numerically by the Runge–Kutta algorithm with averages calculated by the Gaussian quadrature technique. Self-fields and space-charge effects are neglected, and the electron beam is assumed to be cold and slippage is ignored. The parameters correspond to the Compton regime. Evolution of the radiation power and growth rate along the wiggler is studied. Ion-channel density is chosen to obtain optimum efficiency. Simulations are preformed for the FEL operating in the neighborhood of 35 GHz and 16.5 GHz for the electron beam energies of 250 keV and 400 keV, respectively. The result of the saturated efficiency was found to be in good agreement with the simple estimation based on the phase-trapping model.

Gain calculation of a free-electron laser operating with a non-uniform ion-channel guide

Amplification of an electromagnetic wave by a free electron laser （FEL） with a helical wiggler and an ion channel with a periodically varying ion density is examined. The relativistic equation of motion for a single electron in the combined wiggler and the periodic ionbchannel fields is solved and the classes of possible trajectories in this configuration are discussed. The gain equation for the FEL in the low-gain-per-pass lirnit is obtained by adding the effect of the periodic ion channel. Numerical calculation is employed to analyse the gain induced by the effects of the non-uniform ion density. The variation of gain with ion-channel density is demonstrated. It is shown that there is a gain enhancement for group I orbits in the presence of a non-uniform ion-channel but not in a uniform one. It is also shown that periodic ion-channel guiding is used to reach the maximum peak gain in a low ion-channel frequency （low ion density）.

Anti-proliferative and anti-angiogenic activities of ion-channel modulators:In-ovo,in-vitro and in-vivo study

Objective:Angiogenesis is the development of new blood vessels.The ion channels on endothelium play a vital action in cell proliferation and so in the related angiogenesis.We aimed to investigate the anti-angiogenic effects of Mefloquine(Cl-channel blocker) and4-Aminopyridine(K+ channel blocker).Methods:The anti-angiogenic activities of Mefloquine and 4-Aminopyridine(4-AP)were investigated by in-vivo(sponge implantation method),in-vitro(aortic ring assay)and in-ovo(CAM,Chick Chorioallantoic membrane) methods.The standard antiangiogenic drug used was Bevacizumab.Results:In the CAM assay,both the ion channel blockers exhibited noticeable antiangiogenic activity at the concentrations of 10-5M and 10-4M where they significantly exhibited ant proliferative activity by inhibiting the new blood vessel formation.For the further confirmation anti-angiogenic activity was evaluated in vitro and in vivo.In Rat aortic ring assay reduction in the area of sprouts were observed with 40 m M of 4-AP and7 m M of Mefloquine.A significant reduction in weight of sponges,number of blood vessels formed and hemoglobin content were observed at 4.2 mg/kg of 4-AP and 20 mg/kg and 30 mg/kg of Mefloquine.Conclusions:These scientific findings indicate the use of Mefloquine and 4-Aminopyridine in pathological situations involving excessive angiogenesis.Negative regulation of cell volume,cell migration and proliferation of blood vessels may be the underlying molecular mechanisms.

Safety-Critical System Reliability Modeling and Their Analyses in Terms of Effects of Component Failure Modes

New models of safety-critical systems are built here. In these systems, when components fail, different defect states have different effects, hence need different ways to measure. In the models, there are two kinds of failure modes of the components： one could be called failed-safe, and the other may be named failed- dangerous In practice, the so-called failed-dangerous components may lead a system to peril. However, failed-safe components will not. Reliability and safety issues are analyzed using Ion-Channel modeling theory to get count of repairs and time duration before the system becomes dangerous. In the closing section a numerical example is presented to illustrate the results obtained in the paper.

Dispersion relation and growth rate for a corrugated channel free-electron laser with a helical wiggler pump

The effects of corrugated ion channels on electron trajectories and spatial growth rate for a free-electron laser with a one-dimensional helical wiggler have been investigated. Analysis of the steady-state electron trajectories is performed by solving the equations of motion. Our results show that the presence of a corrugated channel shifts the resonance frequency to smaller values of ion channel frequency. The sixth-order dispersion equation describing the coupling between the electrostatic beam mode and the electromagnetic mode has also been derived. The dispersion relation characteristic is analyzed in detail by numerical solution. Results show that the growth rate of instability in the presence of corrugated ion channels can be greatly enhanced relative to the case of an uniform ion channel.

Nanoscale interactions between the nicotinic acetylcholine receptor and cholesterol

Cholesterol is a major lipid in biological membranes.It not only plays a structural role but also modulates a wide range of functional properties of neurotransmitter and hormone receptors and ion channels.The membraneembedded segments of the paradigm neurotransmitter receptor for acetylcholine(nAChR)contain linear sequences of amino acids with the capacity to recognize cholesterol.These cholesterol consensus domains have been designated as“CARC”and its mirror sequence“CRAC”.CARC preferentially occurs in the exoplasmic-facing membrane leaflet,and CRAC,in the cytoplasmic-facing hemilayer.Both motifs are highly conserved among ion-channel and neurotransmitter receptor proteins in vertebrate nervous systems,where they recognize cholesterol,and in prokaryotic homologues in bacteria,where they recognize hopanoids.This phylogenetically conserved trait is an indication that the hopanoids in some bacteria and cholesterol in eukaryotes subserve analogous functions,probably contributing to the stability of membrane-embedded protein domains.Structural studies from our laboratory using superresolution optical microscopy(“nanoscopy”)have disclosed other interrelated functional and structural properties exerted by cholesterol on the nAChR.The neutral lipid content at the cell surface influences both the macromolecular organization of the receptor and its translational mobility(diffusion)in the plane of the membrane.

Electron acceleration in the inverse free electron laser with a helical wiggler by axial magnetic field and ion-channel guiding

Electron acceleration in the inverse free electron laser （IFEL） with a helical wiggler in the presence of ion-channel guiding and axial magnetic field is investigated in this article. The effects of tapering wiggler amplitude and axial magnetic field are calculated for the electron acceleration. In free electron lasers, electron beams lose energy through radiation while in IFEL electron beams gain energy from the laser. The equation of electron motion and the equation of energy exchange between a single electron and electromagnetic waves are derived and then solved numerically using the fourth order Runge-Kutta method. The tapering effects of a wiggler magnetic field on electron acceleration are investigated and the results show that the electron acceleration increases in the case of a tapered wiggler magnetic field with a proper taper constant.

Exercise and Ion-Channel Remodeling in Vascular Smooth Muscle During Hypertension:Therapeutic Implications

Myogenic contraction of vascular smooth muscle cells(VSMCs)in resistance arteries and arterioles plays a critical role in regulating peripheral resistance.Ion channels expressed in VSMCs control ion influx or efflux from the plasma membrane and endoplasmic reticulum to regulate membrane potential,which contributes to the regulation of vascular tone.With the depolarization of VSMC membranes,an elevation of intracellular calcium ion(Ca^(2+))concentration is mediated by voltage-gated Ca^(2+)channels and can trigger a vasoconstrictive response.In addition,potassium ion(K^(+))efflux through K^(+)channels can hyperpolarize VSMCs,resulting in vasodilation.However,in the pathophysiological progression of diseases such as hypertension,VSMCs undergo a wide range of pathological changes,among them is"electrical remodeling",which refers to changes in ion channels.Under physiological or pathological conditions,exercise has a profound impact on the human body,and ion channels are an essential target of the beneficial adaptive responses.This review provides insight on the physi-ological function of ion channels in VSMCs,including Cav1.2 channels,voltage-gated K^(+)channels,large-conductance Ca^(2+)-activated K^(+)channels,and inward-rectifier K^(+)channels,and the changes of these ion channels during hypertension.Focus is given to the effects of exercise on these ion channels and its implications in disease treatment.

Reconstruction of biomimetic ionic channels within covalent organic frameworks for ultrafast and selective uranyl capture

The efficient extraction of uranium,as the primary component of nuclear energy,holds significant implications.Drawing inspiration from the charge interaction observed in biological ion channels,we encapsulated negatively charged polystyrene sulfonate(PSS)or sodium polystyrene carboxylate(PVBA)into the nanochannels of amidoxime functionalized covalent organic framework(COF-AO)in-situ to alter the cavity environment of COF-AO.The synthesized COF-AO-PSS and COF-AO-PVBA are used for ultra-fast and highly selective uranium recovery.The negatively charged PSS/PVBA was confined in the COF-AO channel providing the driving force for uranium transport and blocking other ions,thus creating a highly selective“uranium highway”.Additionally,introducing sulfonate groups or carboxyl groups into COF-AO offers supplementary coordination environments and weak interactions with uranium.Due to charge-assisted migration and various interaction mechanisms,both COF-AO-PSS and COF-AO-PVBA exhibit faster adsorption kinetics and higher selectivity compared to COF-AO alone.Their adsorption capacities are 3.8 times and 2.4 times that of COF-AO alone respectively which highlights the necessity for constructing biomimetic ion channels in uranium adsorption processes.This work presents a bionic adsorbent based on covalent organic frameworks(COFs)for the first time,overcoming environmental and equipment limitations associated with traditional photocatalysis and electrocatalysis methods for uranium capture,opening up new avenues for designing multifunctional materials that mimic biological systems.

Recent development in NMDA receptors

Purpose To identify the structure and the function of NMDA receptors, to understand the modulatory mechanism of some endogenous and exogenous compounds on NMDA receptors, and to provide theoretical basis for developing new drugs that modulate NMDA receptors Data sources A total of 24 originally identified articles were selected Study selection A total of 24 articles were selected from several hundred original articles or reviews. The content of selected articles are in accordance with our purpose and the authors are authorized scientists in the study on NMDA receptors.Data extraction After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria and our experience in the research of NMDA receptors.Results NMDA receptor contains at least five subunits. They were designated as the NR1 (ζ1), NR2A (ε1), NR2B (ε2), NR2C (ε3), and NR2D (ε4). A unique feature of NMDA receptor is the requirement for both glutamate and the co agnist glycine for the efficient gating. NMDA receptor is modulated by a number of endogenous and exogenous compounds. Mg 2+ not only blocks the NMDA channel in a voltage dependent manner but also potentiates NMDA induced responses at positive membrane potentials. Na +, K + and Ca 2+ not only pass through the NMDA receptor channel but also modulate the activity of NMDA receptors. Zn 2+ blocks the NMDA current in a noncompetitive and a voltage independent manner. It has been demonstrated that polyamines do not directly activate NMDA receptors, but instead act to potentiate or inhibit glutamate mediated responses. The activity of NMDA receptors is also strikingly sensitive to the changes in H + concentration, and partially inhibited by the ambient concentration of H + under physiological conditions.Conclusions NMDA receptors are glutamate regulated by ion channels that are permeable to Ca 2+ , Na +, K + and are sensitive to voltage dependent Mg 2+ block This channel complex contributes to excitatory synaptic transmission at sites throughout the brain and the spinal cord,and is modulated by a number of endogenous and exogenous compounds NMDA receptors play a key role in wide range of physiologic and pathologic processes Five NMDA receptor subunits have now been characterized in both rat and mouse brain

Vanilloid agonist-mediated activation of TRPV1 channels requires coordinated movement of the S1–S4 bundle rather than a quiescent state

Transient receptor potential vanilloid 1(TRPV1)channel plays an important role in a wide range of physiological and pathological processes,and a comprehensive understanding of TRPV1 gating will create opportunities for therapeutic intervention.Recent incredible advances in cryo-electron microscopy(cryo-EM)have yielded high-resolution structures of all TRPV subtypes(TRPV1-6)and all of them share highly conserved six transmembrane(TM)domains(S1-S6).As revealed by the open structures of TRPV1 in the presence of a bound vanilloid agonist(capsaicin or resiniferatoxin),TM helices S1 to S4 form a bundle that remains quiescent during channel activation,highlighting differences in the gating mechanism of TRPV1 and voltage-gated ion channels.Here,however,we argue that the structural dynamics rather than quiescence of S1-S4 domains is necessary for capsaicin-mediated activation of TRPV1.Using fluorescent unnatural amino acid(flUAA)incorporation and voltage-clamp fluorometry(VCF)analysis,we directly observed allostery of the S1-S4 bundle upon capsaicin binding.Covalent occupation of VCF-identified sites,single-channel recording,cell apoptosis analysis,and exploration of the role of PSFL828,a novel non-vanilloid agonist we identified,have collectively confirmed the essential role of this coordinated S1-S4 motility in capsaicin-mediated activation of TRPV1.This study concludes that,in contrast to cryo-EM structural studies,vanilloid agonists are also required for S1-S4 movement during TRPV1 activation.Redefining the gating process of vanilloid agonists and the discovery of new non-vanilloid agonists will allow the evaluation of new strategies aimed at the development of TRPV1 modulators.