High throughput electrophysiology: new perspectives for ion channel drug discovery

Proper function of ion channels is crucial for all living cells. Ion channel dysfunction may lead to a number of diseases, so-called channelopathies, and a number of common diseases, including epilepsy, arrhythmia, and type II diabetes, are primarily treated by drugs that modulate ion channels. A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct characterization of ion channel properties. However, patch clamp is a slow, labor-intensive, and thus expensive, technique. New techniques combining the reliability and high information content of patch clamping with the virtues of high throughput philosophy are emerging and predicted to make a number of ion channel targets accessible for drug screening. Specifically, genuine HTS parallel processing techniques based on arrays of planar silicon chips are being developed, but also lower throughput sequential techniques may be of value in compound screening, lead optimization, and safety screening. The introduction of new powerful HTS electrophysiological techniques is predicted to cause a revolution in ion channel drug discovery.     

基于ADuC841的膜片钳放大器的设计

为降低成本和解决现有膜片钳放大器系统中PC机的干扰问题,研究了一种基于单片机的膜片钳放大器小系统.该系统采用ADI公司生产的ADuC841作为控制核心,并且配置相应的液晶显示模块LCM3202401.模拟电路部分采用高输入阻抗的AD8627实现微电流信号的采集,并由后级电路进行信号的放大和电阻电容的补偿.它具有硬件电路简单、体积小、使用方便的特点.既可以单独作为小系统实现采集和显示,也可以通过红外方式和PC机进行通讯,在PC机上进行信号的处理.     

利用膜片钳-激光扫描共聚焦显微镜同步实时系统观察心肌细胞浆内钙离子的释放

目的:采用膜片钳和激光扫描共聚焦显微镜同步实时系统观察心肌细胞钙离子的释放.方法:在体外培养的单个心室肌细胞上进行全细胞模式膜片钳技术和共聚焦显微镜钙成像技术相结合,同步实时记录钙火花和钙离子浓度变化.结果:在全细胞模式膜片钳记录心肌细胞膜钙电流的同时,激光扫描共聚焦显微镜可准确记录到胞浆内出现的钙火花.此技术有可能对于明确钙火花的特征.准确理解兴奋一收缩偶联的微观机制有重要意义.     

Identification of hidden Markov models for ion channel currents. I.Colored background noise

Signal processing based on hidden Markov models (HMM's) has been applied recently to the characterization of single ion channel currents as recorded with the patch clamp technique from living cells. The estimation of HMM parameters using the traditional forward-backward and Baum-Welch algorithms can be performed at signal-to-noise ratios (SNR's) that are too low for conventional analysis; however, the application of these algorithms relies on the assumption that the background noise is white. In this paper, the observed single channel current is modeled as a vector hidden Markov process. An extension of the forward-backward and Baum-Welch algorithms is described to model ion channel kinetics under conditions of colored noise like that seen in patch clamp recordings. Using simulated data, we demonstrate that the traditional algorithms result in biased estimates and that the vector HMM approach provides unbiased estimates of the parameters of the underlying hidden Markov scheme     

Fairness in network optimal flow control: optimality of productforms

Consideration is given to the problem of optimal flow control in a multiclass telecommunications environment where each user (or class) desires to optimize its performance while being fair to the other users (classes). The Nash (1950) arbitration scheme from game theory is shown to be a suitable candidate for a fair, optimal operation point in the sense that it satisfies certain axioms of fairness and is pareto optimal. This strategy can be realized by defining the product of individuals user performance objectives as the network optimization criterion. This provides the rationale for considering the product of user powers, as has been suggested in the literature. For delay constrained traffic, the constrained optimization problem of maximizing the product of user throughputs subject to the constraints leads to a Nash arbitration point. It is shown that these points are unique in throughput space, and the authors also obtain some convexity properties for power and delays with respect to throughputs in a Jackson network     

Experimental and simulation study of the effect of pipette roughness on giga-seal formation in patch clamping

The effect of pipette tip roughness on giga-seal formation of patch clamp recording has been studied through FEA simulation and patch clamp experiments. FEA simulation results show that the membrane cannot fill up all of the peaks and valleys of a rough pipette tip. As a result in three dimensions the seal between inside and outside is compromised by channels in the order of several nanometres. These channels increase the leakage current between two electrodes, increase the noise and decrease the seal resistance. In contrast focused-ion-beam polished pipettes have very flat tips. Single ion channel currents recorded by FIB polished pipettes show significantly smaller leakage current and noise than the currents recorded by conventional pipettes. Results of FEA simulation are consistent with the results of patch clamp experiments.     

Random access for a multibeam satellite with dynamic transponderswitching

A multibeam satellite communications network serving multiple zones with S-ALOHA random access uplinks and dynamically switched transponders in the downlinks is studied. The overhead of switching transponders between zones may degrade the performance of the system significantly. Two different strategies are introduced and studied. In the guard time strategy, each slot time is equal to the packet transmission time plus the transponder switching time, allowing the transponder to be pointed to a new zone at the beginning of each slot. In the idle waiting strategy, each slot time is equal to the packet transmission time. If a transponder is switched to a new zone, it will take k slot time where k is the smallest integer greater than the switching time divided by the slot time. The throughputs of these two strategies are analyzed and compared     

Frequency Tunable Microstrip Patch Antenna Using RF MEMS Technology

A novel reconfigurable microstrip patch antenna is presented that is monolithically integrated with RF microelectromechanical systems (MEMS) capacitors for tuning the resonant frequency. Reconfigurability of the operating frequency of the microstrip patch antenna is achieved by loading it with a coplanar waveguide (CPW) stub on which variable MEMS capacitors are placed periodically. MEMS capacitors are implemented with surface micromachining technology, where a 1-mum thick aluminum structural layer is placed on a glass substrate with a capacitive gap of 1.5 mum. MEMS capacitors are electrostatically actuated with a low tuning voltage in the range of 0-11.9 V. The antenna resonant frequency can continuously be shifted from 16.05 GHz down to 15.75 GHz as the actuation voltage is increased from 0 to 11.9 V. These measurement results are in good agreement with the simulation results obtained with Ansoft HFSS. The radiation pattern is not affected from the bias voltage. This is the first monolithic frequency tunable microstrip patch antenna where a CPW stub loaded with MEMS capacitors is used as a variable load operating at low dc voltages     

Microstructured apertures in planar glass substrates for ion channel research

We have developed planar glass chip devices for patch clamp recording. Glass has several key advantages as a substrate for planar patch clamp devices. It is a good dielectric, is well-known to interact strongly with cell membranes and is also a relatively in-expensive material. In addition, it is optically neutral. However, microstructuring processes for glass are less well established than those for silicon-based substrates. We have used ion-track etching techniques to produce micron-sized apertures into borosilicate and quartz-glass coverslips. These apertures, which can be easily produced in arrays, have been used for high resolution recording of single ion channels as well as for whole-cell current recordings from mammalian cell lines. An additional attractive application that is greatly facilitated by the combination of planar geometry with the optical neutrality of the substrate is single-molecule fluorescence recording with simultaneous single-channel measurements.     

Optical CDMA random access protocols with and without pretransmission coordination

The link layer of an optical direct-detection code-division multiple-access (CDMA) packet network is considered. Two different protocols that need pretransmission coordination are proposed. A variation of the second protocol that does not need pretransmission coordination is discussed. Both system throughput and average packet delay are derived and investigated for two different receiver models: the correlation and chip-level receivers. Both multiple-access interference and the photodetector's shot noise are taken into account in the analysis. The case where the number of users exceeds the available number of CDMA codes is numerically investigated. Our results reveal that the proposed protocols yield competitive system throughputs when used with the correlation receivers. Further, significant improvement in the throughput is achieved when using chip-level receivers along with the second protocol.     

Transient analysis of a space-borne microstrip patch antennailluminated by an electromagnetic pulse

The transient response of a microstrip patch antenna excited by a plane wave is studied using a finite difference algorithm applied to a total field version of Maxwell's curl equations in the time domain. A wide bandwidth study shows different behavior in the antenna, depending on the frequency and angle of incidence of the wave. At low frequencies, the voltage in a 50 Ω load is proportional to the derivative of the incident Eⁱ field. With increasing frequency, parasitic oscillations appear to be due to the short-circuited patch. In addition, at high frequencies, antenna sizes and wavelength are of the same order. The voltage contains oscillations at the frequency of the TM mode of the antenna. Two patterns of coupling appear: (1) capacitive coupling, where the current on the patch rises at the wire-metallic plane junction and spreads on the patch and on the finite ground plane; and (2) coupling due to the scattering, where the current rises at the edges of the patch and on the finite ground plane     

Regular VLSI architectures for multiplication modulo(2n+1)

The authors describe VLSI architectures for multiplication modulo p, where p is a Fermat prime. With increasing p , ROM-based table lookup methods become unattractive for integration due to excessive memory requirements. Three novel methods are discussed and compared to ROM implementations with regard to their speed and complexity characteristics. The first method is based on an ( n+1)×(n+1)-bit array multiplier, the second on modulo p carry-save addition, and the third on modulo (p -1) carry-save addition using a bit-pair recoding scheme. All allow very high throughputs in pipelined implementations. While the former is very convenient for CAD (computer-aided design) environments providing a pipelined multiplier macrocell, the latter two are well-suited to full-custom implementation     

计算机图形学在RCS预估中的应用

本文论述用计算机图形学方法进行复杂目标RCS预估的方法。用这种方法可实现几何模型构造、消隐、几何数据提取、面元剖分、RCS计算及可视化显示。实验说明，用这种方法建立复杂目标的电磁散射模型，对于过程的自动化、精确性和实时性、软件系统界面的优化等方面都十分有利。     

膜片钳放大器的低噪声设计

本文论述用于测量细胞膜离子通道电流的放大器的电路方案.因被测电流在1pA到nA级的范围内,而输出电压要求达到计算机便于处理的数值.故需采用多级放大电路.被测电流属极微弱的信号,噪声问题是设计中的关键.对于多级放大器来说,前置放大级(探头电路)的低噪声设计至关重要.文中分析放大电路中的主要元、器件的背景噪声,用噪声电流和噪声电压的功率密度谱(PDS)S_I(f)和S_v(f)来表征其特性.给出了所设计的PC-Ⅱ型膜片钳放大器的主要性能参数和记录的电流波形.     

A bandwidth scalable OFDM passive optical network for future access network

In order to reduce the cost for delivering the ever increasing broadband services, network providers need to simplify their network architectures and have a better control of the bandwidth. In this article, we propose a simple and cost-effective bandwidth scalable passive optical network (PON) based on orthogonal frequency division multiplexing (BSOFDM-PON). We report performance analysis in terms of the signal-to-noise ratio (SNR), bit-error-rate (BER), and error vector magnitude (EVM) of a PON system accommodating 32 optical network units (ONUs). Our simulations have successfully demonstrated that throughputs of 35.5 and 53.2 Gbps can be achieved using 16 and 64 QAM, respectively, within a total distance ranging from 20 to 30 km. It gives throughputs of 1.10 and 1.66 Gbps per ONU.     

Flow‐level performance analysis of a multi‐rate system supporting stream and elastic services

We consider a multi‐rate system where stream and elastic flows receive service. Both the stream and the elastic classes are associated with peak rate limitation. In contrast to the constant bit rate stream flows, the elastic flows tolerate bandwidth compression while in service. Because of the occasional bandwidth compression, the holding time of elastic flows depends on their perceived throughput. Although this model is Markovian under quite non‐restrictive assumptions, the model's state space grows exponentially with the number of traffic classes. The model is not quasi‐reversible, and therefore, it cannot be evaluated by efficient recursive formulae. We propose a method whereby the original state space is mapped to a two‐dimensional one, independently of the number of the stream and the elastic traffic classes. The special structure of the two‐dimensional model allows us to develop an efficient method that approximates the average throughputs of elastic flows. The state space reduction together with the proposed approximation provides a powerful tool for the performance analysis of this model as it allows the approximation of the average throughputs of elastic flows reasonably accurately in large models as well. Copyright © 2012 John Wiley & Sons, Ltd.     

The effect of capture on performance of multichannel slotted ALOHAsystems

The author presents an exact analysis to evaluate the effect of capture on the multichannel slotted ALOHA protocol. The author derives the probabilities of the successful transmission. These probabilities are used to calculate the throughputs, average packet delays for both IFT (immediate-first-transmission) and delayed-first-transmission protocols and numerically compare the performance of the systems with and without capture. Numerical results show that when a quantitative capture restriction u is considered, in a multichannel system having a fixed total bandwidth, depending on parameter u and channel number M, an improved system performance such as the average channel utilization and average packet delay can be obtained     

Trellis Coded Hybrid Selective Repeat ARQ Schemes for Point-to-Multipoint Communication over Rayleigh Fading Channels

In this paper, the hybrid selective repeat (SR) automatic repeat request (ARQ) scheme using trellis coded modulation (TCM) proposed by Tellambura and Bhargava [21] is generalized to point-to-multipoint communications for Rayleigh fading channel. Analytical expressions are derived for the throughputs of the point-to-multipoint communication schemes with and without code combining technique. Numerical results show that the protocol using code combining technique yields better throughput than the protocol without code combining and the throughputs decrease when the number of receivers and the value of erasure threshold increase. When the number of receivers equals 1, the scheme without code combining becomes the point-to-point communication scheme proposed in [21].     

Co-channel Interference Energy Harvesting for Decode-and-Forward Relaying

In this paper, co-channel interferences are exploited for energy harvesting in a Cooperative Network (CICN) in which a power constrained relay uses a power splitting architecture (CICN-PS) and a time switching architecture (CICN-TS) to harvest energy from the radio-frequency signals received from a source node and co-channel interferences. In the proposed CICN-PS and CICN-TS protocols, the relay applies decode-and-forward technology to decode the information of the source node, and then forwards the recoded information to a destination with the overall harvested energies. The system performance of the proposed protocols is discussed and evaluated using the exact throughput analyses and is then checked using Monte Carlo simulations over Rayleigh fading channels. The optimal power splitting ratio and energy harvesting time are derived by the Golden Section Search method, and throughput performance evaluations are performed. Our numerical and simulation results show distributions as follows. Firstly, the CICN-PS protocol outperforms the CICN-TS protocol. Secondly, the proposed protocols strictly depend on the location, amount and power of the co-channel interferences. Thirdly, when signal-to-noise ratio increases, the proposed CICN-PS protocol achieves the perfect throughputs where the cooperative relay applies the ideal receiver and co-channel interferences do not affect the destination. Finally, the numerical analyses agree well with the simulation results.