Gating Parameters Research Articles

A Method for Effective Work Function Monitoring

The effective work function (EWF) is a critical gate parameter dependent on metal, dielectric, and interaction between them. As such, it requires stringent control, both in R&D stage and in manufacturing of advanced MOSFET’s. In this work we present non-contact charge-based EWF monitoring that brings advantages of cost-effectiveness and fast data feedback. The method extends our micro corona-Kelvin testing of dielectrics and interfaces in scribe-line boxes to EWF suitable configuration with a thin metal layer on a top of a dielectric. Two key elements are used in the present method: 1) corona charge deposition on metal surface and 2) surface voltage measurement by Kelvin force microscopy. In a dynamic version of the flatband voltage determination, the surface voltage decay after corona charging is measured under modulated light conditions enabling parameter free extraction of VFB. Results for n- and p-type metals show sensitivity of VFBto EWF and agreement with results at end of the line CV measurements. The micro corona-Kelvin method allows quantification of two more work function sensitive parameters: the silicon surface barrier, Vsb, and the tunneling barrier related to the band offset at the metal / high-k dielectric interface. Results for n- and p-type metals correlate with the expected behavior. Measurement of the silicon surface barrier, Vsb, can be especially attractive since it can be done on a blanket wafer with a thin metal layer over the high-k dielectric, providing means for high resolution mapping. The third EWF sensitive parameter is obtained from the analysis of the tunneling current across the dielectric under negative bias condition, i.e. tunneling of electrons from the metal gate through the dielectric. Measured shifts of the tunneling barrier were consistent with EWF.

Silica-Kaolin Mix Effect on Evaporative Pattern Castings Surface Roughness

Abstract The influence of the refractory coating which is a mixture of silica flour and kaolin on the surface roughness of the plate castings produced using evaporative patterns had been considered in this work. The kaolin was used as a binder and ratio method was employed to form basis for the factorial design of experiment which led to nine runs of experiments. Methyl alcohol at 99% concentration was used as the carrier for the transfer of the coating to the surface of the patterns. Pouring temperature was observed as a process parameter alongside the mix ratios of the coating. Attempts were made to characterize the refractory coating by using two methods; differential thermal analysis (DTA) and X-ray diffraction. Attempt was also made to characterize the casting material. Gating system design was done for the plate casting to determine the correct proportions of the gating parameters in order to construct the gating system properly to avoid turbulence during pouring of liquid metal. A digital profilometer was used to take the measurements of the surface roughness. It was observed that the mix ratio 90% silica flour-10% kaolin produced the lowest value of the surface roughness of the plate castings and had the lowest material loss in the DTA test. The pouring temperature of 650°C produced best casting.

Superfluid transport dynamics in a capacitive atomtronic circuit

We simulate transport in an atomtronic circuit of a Bose-Einstein condensate that flows from a source region into a drain through a gate channel. The time-dependent Gross-Pitaevskii equation (GPE) solution matches the data of a recent experiment. The atomtronic circuit is found to be similar to a variable-resistance RLC circuit, which is critically damped at early times and shows LC oscillations later. The GPE also predicts atom loss from the drain. Studies of the dependence of condensate transport upon gate parameters suggest the utility of the GPE for investigation of atomtronic circuits.

Effects of Temperature on Heteromeric Kv11.1a/1b and Kv11.3 Channels

Kv11.1 channels are crucial in cardiac physiology, and there is increasing evidence of physiological roles of different Kv11 channels outside the heart. The HERG (human Kv11.1a) channel has previously been shown to carry substantially more current at elevated temperatures, and we have now comparably investigated the temperature dependence of neuronal Kv11.3 channels and the more ubiquitous heteromeric Kv11.1a/1b channels. Transiently expressed rat Kv11 channels were studied at 21°C, 30°C, and 35°C. At near-physiological temperature, the maximal sustained outward current density was almost three times the mean value obtained at room temperature for Kv11.1a/1b, and increased by ∼150% for Kv11.3. For both channels, reduced inactivation contributed to the current increase at higher temperature. Elevated temperature moved Kv11.1a/1b isochronal activation curves to more negative potentials, but shifted the potential of half-maximal Kv11.3 channel activation to more depolarized values and reduced its voltage sensitivity. Thus, increased temperature stabilized the open state over the closed state of Kv11.1a/1b channels and exerted the opposite effect on Kv11.3 channel activation. Both Kv11 channels exhibited an overall high temperature sensitivity of most gating parameters, with remarkably high Q10 factors of ∼5 for the rate of Kv11.1a/1b activation. The Q10 factors for Kv11.3 gating were more uniform, but still higher for activation than for inactivation kinetics. The results demonstrate that characteristic differences between Kv11.1a/1b and Kv11.3 determined at room temperature do not necessarily apply to physiological conditions. The data provided here can aid in the design of models that will enhance our understanding of the role of Kv11 currents in excitable cells.

Exploration of Inter-Die Bulk Fin-Typed Field Effect Transistor Process Variation for Reduction of Device Variability.

This work first reports a novel exploration technique to systematically prioritize key fabrication in-line process parameters of 16-nm high-k metal gate (HKMG) bulk FinFET to reduce device's die-to-die variation. To extract hidden correlations and reduce decision variables among the complex in-line process parameters, a data mining technique is employed to highlight and group associated parameters. To correlate the measured data with the distribution of physical dimension of devices for all in-line processes, a sensitivity analysis is then performed. Because the variability of current process deeply affects the next process, so the sequence of fabrication process is further added into the analyzing procedure to increase the searching efficiency. The source of variation of the initial process can be monitored and traced by the proposed methodology. The result of this study indicates that the gate spacer is a key process factor and will determine the uniformity of process including, such as the source-and-drain proximity, and the depth, lateral offset and overlap of sequential doping implants. The ranked key in-line process parameters can be used to optimize process and minimize the device variability of 16-nm HKMG bulk FinFET devices.

Few-photon scattering in dispersive waveguides with multiple qubits.

We extend the Krylov-subspace-based time-dependent numerical simulation technique for a qubit interacting with photons in a waveguide to the multiple qubit case. We analyze photon scattering from two qubits and derive expressions for the bound states in the continuum (BICs). We show how the BIC can be excited. We use the BIC in a recent Pauli-Z gate proposal involving decoherence free subspaces and obtain the gate fidelity as a function of the gate parameters. The techniques presented in this Letter are useful for investigating the time evolution of quantum gates and other many-body systems with multiple quenches in the Hamiltonian.

Reconstruction of Cell Surface Densities of Ion Pumps, Exchangers, and Channels from mRNA Expression, Conductance Kinetics, Whole-Cell Calcium, and Current-Clamp Voltage Recordings, with an Application to Human Uterine Smooth Muscle Cells.

Uterine smooth muscle cells remain quiescent throughout most of gestation, only generating spontaneous action potentials immediately prior to, and during, labor. This study presents a method that combines transcriptomics with biophysical recordings to characterise the conductance repertoire of these cells, the ‘conductance repertoire’ being the total complement of ion channels and transporters expressed by an electrically active cell. Transcriptomic analysis provides a set of potential electrogenic entities, of which the conductance repertoire is a subset. Each entity within the conductance repertoire was modeled independently and its gating parameter values were fixed using the available biophysical data. The only remaining free parameters were the surface densities for each entity. We characterise the space of combinations of surface densities (density vectors) consistent with experimentally observed membrane potential and calcium waveforms. This yields insights on the functional redundancy of the system as well as its behavioral versatility. Our approach couples high-throughput transcriptomic data with physiological behaviors in health and disease, and provides a formal method to link genotype to phenotype in excitable systems. We accurately predict current densities and chart functional redundancy. For example, we find that to evoke the observed voltage waveform, the BK channel is functionally redundant whereas hERG is essential. Furthermore, our analysis suggests that activation of calcium-activated chloride conductances by intracellular calcium release is the key factor underlying spontaneous depolarisations.

Ion Channel Based Bio-Synthetic Modulator for Diffusive Molecular Communication.

In diffusion-based molecular communication (DMC), a transmitter nanomachine is responsible for signal modulation. Thereby, the transmitter has to be able to control the release of the signaling molecules employed for representing the transmitted information. In nature, an important class of control mechanisms for releasing molecules from cells utilizes ion channels which are pore-forming proteins across the cell membrane. The opening and closing of the ion channels is controlled by a gating parameter. In this paper, an ion channel based modulator for DMC is proposed which controls the rate of molecule release from the transmitter by modulating a gating parameter signal. Exploiting the capabilities of the proposed modulator, an on-off keying modulation technique is introduced and the corresponding average modulated signal, i.e., the average release rate of the molecules from the transmitter, is analyzed. However, since the modulated signal is random in nature, it may deviate from its average. Therefore, the concept of modulator noise is introduced and the statistics of the modulated signal are investigated. Finally, by assuming a simple transparent receiver, the performance of the proposed on-off keying modulation format is studied. The derived analytical expressions for the average modulated signal are confirmed with particle based simulations. Our numerical results reveal that performance estimates of DMC systems obtained based on the assumption of instantaneous molecule release at the transmitter may substantially deviate from the performance achieved with practical modulators.

Stochastic Model of Gap Junctions Exhibiting Rectification and Multiple Closed States of Slow Gates

Gap-junction (GJ) channels formed from connexin (Cx) proteins provide direct pathways for electrical and metabolic cell-cell communication. Earlier, we developed a stochastic 16-state model (S16SM) of voltage gating of the GJ channel containing two pairs of fast and slow gates, each operating between open (o) and closed (c) states. However, experimental data suggest that gates may in fact contain two or more closed states. We developed a model in which the slow gate operates according to a linear reaction scheme, o↔c1↔c2, where c1 and c2 are initial-closed and deep-closed states that both close the channel fully, whereas the fast gate operates between the open state and the closed state and exhibits a residual conductance. Thus, we developed a stochastic 36-state model (S36SM) of GJ channel gating that is sensitive to transjunctional voltage (Vj). To accelerate simulation and eliminate noise in simulated junctional conductance (gj) records, we transformed an S36SM into a Markov chain 36-state model (MC36SM) of GJ channel gating. This model provides an explanation for well-established experimental data, such as delayed gj recovery after Vj gating, hysteresis of gj-Vj dependence, and the low ratio of functional channels to the total number of GJ channels clustered in junctional plaques, and it has the potential to describe chemically mediated gating, which cannot be reflected using an S16SM. The MC36SM, when combined with global optimization algorithms, can be used for automated estimation of gating parameters including probabilities of c1↔c2 transitions from experimental gj-time and gj-Vj dependencies.

Parametric optimization and solidification analysis of grey cast pump adapter castings using DOE and CAE – a case study

Casting defects account great threat to a growing foundry, since it is directly related to the economy. In this work, grey cast pump adapter casting process in a foundry is optimized to produce quality castings using design of experiments (DOE) and Computer aided Engineering (CAE) approaches. Prominent parameters like clay percentage, moisture percentage and mould hardness are considered for performing DOE with three different levels of Box–Behnken Design. Experimental trials were conducted and number of defective components was measured. Results are evaluated using Design Expert Evaluation software to obtain optimal settings. Analysis of Variance test revealed contribution level of each parameter in the casting process. DOE is an efficient tool to optimize casting process that can produce quality castings. In addition, possible defects in castings are analysed using CAE technique (PROCAST simulation software). Simulation using PROCAST is carried out to investigate internal defects by carefully designing gating and feeding parameters in pump adapter castings. Bottom filling is encouraged in the mould cavity to control metal filling process. It can be inferred that DOE and CAE PROCAST simulation has enabled to achieve uniform cooling rate and directional solidification to produce defect free grey cast pump adapter castings.

Isopimaric Acid - A Promiscuous Ion Channel Modulator and a Potential Drug Candidate Against Atrial Fibrillation

Atrial fibrillation is a common cardiac arrhythmia in adulthood, and it is not well controlled by the present-day drugs. Previously, resin acids has been shown to open voltage-gated potassium channels and reduce cellular excitability in dorsal-root ganglion neurons. In this study we explored the effects of a resin acid, Isopimaric acid (IPA), on excitability in cardiomyocytes. Whole-cell patch-clamp recordings showed that 1-25 µmol/L IPA reduced the action potential frequency by up to 50 % in spontaneously beating mouse atrial HL-1 cells. The effect of IPA on six different voltage-gated ion channels were investigated; most voltage-dependent parameters of ion-channel gating were shifted in negative direction along the voltage axis, consistent with an hypothesis that a lipophilic and negatively charged compound binds to the lipid membrane close to the positively charged voltage sensor of the ion channels. The major finding was that IPA inactivated sodium channels and L- and T-type calcium channels more than it activated these channels. It also activated the rapid delayed rectifier potassium channel, the transient outward potassium channel, but had no effect of the pace-maker f-channel. Computer simulations of all IPA effects on the ion currents were consistent with a reduced excitability. They also showed that the effect on the sodium channel played a large role for IPAs ability to reduce the action potential frequency. Finally, induced arrhythmia in the HL-1 cells was shown to be reversed by IPA. In conclusion, low concentrations of IPA reduced the action potential frequency and reversed arrhythmic firing via a new pharmacological mechanism. These findings can form the basis for a new pharmacological strategy to treat atrial fibrillation.

Hydraulics, Dimensional Analysis and Visualization of Flow through Unpressurized Gating Systems Using Water Models

During recent years, foundry industry has witnessed an increasing awareness about the importance of the filling stage for the production of metallurgically sound and dimensionally stable castings. The metallurgical soundness of a casting is strongly influenced by the way the liquid metal flows through various parts of the gating system and fills the mould cavity. Owing to the importance of filling stage, extensive research has been directed towards the determination of optimum filling conditions as well as on the influence of gating parameters. In this study, the hydraulics and flow behaviour of an aluminium alloy in a pressurized, horizontal gating system with a gating ratio of 1:2:1 incorporating multiple ingates attached to a horizontally cast plate mould is investigated using transparent water models. Similitude considerations between water and aluminium were invoked in the design of water models so that the conclusions drawn from water model experiments become applicable to real casting. Runners with two different aspect ratios and four different types of ingates were examined for their influence on hydraulics and flow behaviour. Flow behaviour was visualized using a high speed camera capable of capturing images up to 10,000 frames per second. Comparison of the filling patterns between water model experiments and real time experiments with molten metal in sand moulds provided useful insights into the performance of pressurized, horizontal gating system with multiple ingates and on the utility of flow visualization using water models.

Toward harmonized phenotyping of human myeloid-derived suppressor cells by flow cytometry: results from an interim study.

There is an increasing interest for monitoring circulating myeloid-derived suppressor cells (MDSCs) in cancer patients, but there are also divergences in their phenotypic definition. To overcome this obstacle, the Cancer Immunoguiding Program under the umbrella of the Association of Cancer Immunotherapy is coordinating a proficiency panel program that aims at harmonizing MDSC phenotyping. After a consultation period, a two-stage approach was designed to harmonize MDSC phenotype. In the first step, an international consortium of 23 laboratories immunophenotyped 10 putative MDSC subsets on pretested, peripheral blood mononuclear cells of healthy donors to assess the level of concordance and define robust marker combinations for the identification of circulating MDSCs. At this stage, no mandatory requirements to standardize reagents or protocols were introduced. Data analysis revealed a small intra-laboratory, but very high inter-laboratory variance for all MDSC subsets, especially for the granulocytic subsets. In particular, the use of a dead-cell marker altered significantly the reported percentage of granulocytic MDSCs, confirming that these cells are especially sensitive to cryopreservation and/or thawing. Importantly, the gating strategy was heterogeneous and associated with high inter-center variance. Overall, our results document the high variability in MDSC phenotyping in the multicenter setting if no harmonization/standardization measures are applied. Although the observed variability depended on a number of identified parameters, the main parameter associated with variation was the gating strategy. Based on these findings, we propose further efforts to harmonize marker combinations and gating parameters to identify strategies for a robust enumeration of MDSC subsets.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-015-1782-5) contains supplementary material, which is available to authorized users.

Verification of Fall Experiences Identification Method of Healthy Elderly People Using Gate Parameters during Dual Task Walk

Verification of Fall Experiences Identification Method of Healthy Elderly People Using Gate Parameters during Dual Task Walk

Optimization of GATE and PHITS Monte Carlo code parameters for spot scanning proton beam based on simulation with FLUKA general-purpose code

Spot scanning, owing to its superior dose-shaping capability, provides unsurpassed dose conformity, in particular for complex targets. However, the robustness of the delivered dose distribution and prescription has to be verified. Monte Carlo (MC) simulation has the potential to generate significant advantages for high-precise particle therapy, especially for medium containing inhomogeneities. However, the inherent choice of computational parameters in MC simulation codes of GATE, PHITS and FLUKA that is observed for uniform scanning proton beam needs to be evaluated. This means that the relationship between the effect of input parameters and the calculation results should be carefully scrutinized. The objective of this study was, therefore, to determine the optimal parameters for the spot scanning proton beam for both GATE and PHITS codes by using data from FLUKA simulation as a reference. The proton beam scanning system of the Indiana University Health Proton Therapy Center was modeled in FLUKA, and the geometry was subsequently and identically transferred to GATE and PHITS. Although the beam transport is managed by spot scanning system, the spot location is always set at the center of a water phantom of 600×600×300mm3, which is placed after the treatment nozzle. The percentage depth dose (PDD) is computed along the central axis using 0.5×0.5×0.5mm3 voxels in the water phantom. The PDDs and the proton ranges obtained with several computational parameters are then compared to those of FLUKA, and optimal parameters are determined from the accuracy of the proton range, suppressed dose deviation, and computational time minimization. Our results indicate that the optimized parameters are different from those for uniform scanning, suggesting that the gold standard for setting computational parameters for any proton therapy application cannot be determined consistently since the impact of setting parameters depends on the proton irradiation technique. We therefore conclude that customization parameters must be set with reference to the optimized parameters of the corresponding irradiation technique in order to render them useful for achieving artifact-free MC simulation for use in computational experiments and clinical treatments.

Nontrivial magnetoresistive behavior of a single-wall carbon nanotube with an attached molecular magnet

The spin-resolved transport properties of a single-wall carbon nanotube quantum dot, with an attached single molecular magnet, are studied theoretically. With the aid of the real-time diagrammatic technique in the lowest-order perturbation expansion with respect to the tunnel coupling, the current, differential conductance, and the tunnel magnetoresistance (TMR) are determined in both the linear and nonlinear response regimes. It is shown that transport properties depend greatly on both the shell filling sequence of the carbon nanotube and the type of exchange interaction between the molecular magnet and nanotube. This results in highly nontrivial behavior of the TMR, which is especially visible in the low bias voltage regime. Depending on the gate voltage and parameters of the system, we find transport regimes where either a greatly enhanced or negative TMR develops. The mechanism leading to such behavior is associated with nonequilibrium spin accumulation, which builds up in the antiparallel magnetic configuration of the device. We show that it is crucial whether the spin accumulation occurs in the highest-weight spin states or in states with lower spin values. While in the former case it leads to enhanced TMR, in the latter case it may result in negative tunnel magnetoresistance. In addition, we analyze how the above effects depend on the magnitude of the molecular magnet's spin, and show that this dependence is generally nonmonotonic.

Identification and Functional Characterization of CLCN1 Mutations Found in Nondystrophic Myotonia Patients.

Mutations in the gene coding for the skeletal muscle Cl(-) channel (CLCN1) lead to dominant or recessive myotonia. Here, we identified and characterized CLCN1 mutations in Costa Rican patients, who had been clinically diagnosed with myotonic dystrophy type 1 but who were negative for DM1 mutations. CLCN1 mutations c.501C>G, p.F167L and c.1235A>C, p.Q412P appeared to have recessive inheritance but patients had atypical clinical phenotypes; c.313C>T, p.R105C was found in combination with c.501C>G, p.F167L in an apparently recessive family and the c.461A>G, p.Q154R variant was associated with a less clear clinical picture. In Xenopus oocytes, none of the mutations exhibited alterations of fast or slow gating parameters or single channel conductance, and mutations p.R105C, p.Q154R, and p.F167L were indistinguishable from wild-type (WT). p.Q412P displayed a dramatically reduced current density, surface expression and exerted no dominant negative effect in the context of the homodimeric channel. Fluorescently tagged constructs revealed that p.Q412P is expressed inefficiently. Our study confirms p.F167L and p.R105C as myotonia mutations in the Costa Rican population, whereas p.Q154R may be a benign variant. p.Q412P most likely induces a severe folding defect, explaining the lack of dominance in patients and expression systems, but has WT properties once expressed in the plasma membrane.

MATtrack: A MATLAB-Based Quantitative Image Analysis Platform for Investigating Real-Time Photo-Converted Fluorescent Signals in Live Cells.

We introduce here MATtrack, an open source MATLAB-based computational platform developed to process multi-Tiff files produced by a photo-conversion time lapse protocol for live cell fluorescent microscopy. MATtrack automatically performs a series of steps required for image processing, including extraction and import of numerical values from Multi-Tiff files, red/green image classification using gating parameters, noise filtering, background extraction, contrast stretching and temporal smoothing. MATtrack also integrates a series of algorithms for quantitative image analysis enabling the construction of mean and standard deviation images, clustering and classification of subcellular regions and injection point approximation. In addition, MATtrack features a simple user interface, which enables monitoring of Fluorescent Signal Intensity in multiple Regions of Interest, over time. The latter encapsulates a region growing method to automatically delineate the contours of Regions of Interest selected by the user, and performs background and regional Average Fluorescence Tracking, and automatic plotting. Finally, MATtrack computes convenient visualization and exploration tools including a migration map, which provides an overview of the protein intracellular trajectories and accumulation areas. In conclusion, MATtrack is an open source MATLAB-based software package tailored to facilitate the analysis and visualization of large data files derived from real-time live cell fluorescent microscopy using photoconvertible proteins. It is flexible, user friendly, compatible with Windows, Mac, and Linux, and a wide range of data acquisition software. MATtrack is freely available for download at eleceng.dit.ie/courtney/MATtrack.zip.

Direct Estimation of CaV1.2 Gating Parameters: Quantification of Voltage Sensor - Pore Transductions and their Modulation by FLP 64176.

Calcium agonists such as FPL 64174 increase macroscopic calcium channel currents and induce substantial changes in current kinetics. Their molecular mechanism of action is currently unknown. Here we propose a technique enabling the estimation of FPL 64174 effects on rate constants of the voltage sensing machinery and pore transitions from macroscopic CaV1.2 current kinetics making use of a hybrid stochastic-deterministic optimization procedure. Current traces of wild type CaV1.2, a channel construct with neutralized segment IIS4 (IIS4N) and a pore mutant (A780T) were fitted to a circular four-state (rest, activated, open, deactivated) channel model in control and FPL 64174 (1 µM). The estimated rate constants provided novel insights in how structural elements of the voltage sensing unit and the channel pore influence the action of FPL 64174. The new approach may be applicable for the analysis of drug effects on other ion channels as well as for quantification of VS transitions and rate constants of pore gating from macroscopic current kinetics.

Conductance hysteresis in the voltage-dependent anion channel.

Hysteresis in the conductance of voltage-sensitive ion channels is observed when the transmembrane voltage is periodically varied with time. Although this phenomenon has been used in studies of gating of the voltage-dependent anion channel, VDAC, from the outer mitochondrial membrane for nearly four decades, full hysteresis curves have never been reported, because the focus was solely on the channel opening branches of the hysteresis loops. We studied the hysteretic response of a multichannel VDAC system to a triangular voltage ramp the frequency of which was varied over three orders of magnitude, from 0.5mHz to 0.2Hz. We found that in this wide frequency range the area encircled by the hysteresis curves changes by less than a factor of three, suggesting broad distribution of the characteristic times and strongly non-equilibrium behavior. At the same time, quasi-equilibrium two-state behavior is observed for hysteresis branches corresponding to VDAC opening. This enables calculation of the usual equilibrium gating parameters, gating charge and voltage of equipartitioning, which were found to be almost insensitive to the ramp frequency. To rationalize this peculiarity, we hypothesize that during voltage-induced closure and opening the system explores different regions of the complex free energy landscape, and, in the opening branch, follows quasi-equilibrium paths.