Channel Module Research Articles

Role for SUR2A ED Domain in Allosteric Coupling within the KATP Channel Complex

Allosteric regulation of heteromultimeric ATP-sensitive potassium (KATP) channels is unique among protein systems as it implies transmission of ligand-induced structural adaptation at the regulatory SUR subunit, a member of ATP-binding cassette ABCC family, to the distinct pore-forming K+ (Kir6.x) channel module. Cooperative interaction between nucleotide binding domains (NBDs) of SUR is a prerequisite for KATP channel gating, yet pathways of allosteric intersubunit communication remain uncertain. Here, we analyzed the role of the ED domain, a stretch of 15 negatively charged aspartate/glutamate amino acid residues (948–962) of the SUR2A isoform, in the regulation of cardiac KATP channels. Disruption of the ED domain impeded cooperative NBDs interaction and interrupted the regulation of KATP channel complexes by MgADP, potassium channel openers, and sulfonylurea drugs. Thus, the ED domain is a structural component of the allosteric pathway within the KATP channel complex integrating transduction of diverse nucleotide-dependent states in the regulatory SUR subunit to the open/closed states of the K+-conducting channel pore.

The K+-translocating KdpFABC complex from Escherichia coli: A P-type ATPase with unique features

The prokaryotic KdpFABC complex from the enterobacterium Escherichia coli represents a unique type of P-type ATPase composed of four different subunits, in which a catalytically active P-type ATPase has evolutionary recruited a potassium channel module in order to facilitate ATP-driven potassium transport into the bacterial cell against steep concentration gradients. This unusual composition entails special features with respect to other P-type ATPases, for example the spatial separation of the sites of ATP hydrolysis and substrate transport on two different polypeptides within this multisubunit enzyme complex, which, in turn, leads to an interesting coupling mechanism. As all other P-type ATPases, also the KdpFABC complex cycles between the so-called E1 and E2 states during catalysis, each of which comprises different structural properties together with different binding affinities for both ATP and the transport substrate. Distinct configurations of this transport cycle have recently been visualized in the working enzyme. All typical features of P-type ATPases are attributed to the KdpB subunit, which also comprises strong structural homologies to other P-type ATPase family members. However, the translocation of the transport substrate, potassium, is mediated by the KdpA subunit, which comprises structural as well as functional homologies to MPM-type potassium channels like KcsA from Streptomyces lividans. Subunit KdpC has long been thought to exhibit an FXYD protein-like function in the regulation of KdpFABC activity. However, our latest results are in favor of the notion that KdpC might act as a catalytical chaperone, which cooperatively interacts with the nucleotide to be hydrolyzed and, thus, increases the rather untypical weak nucleotide binding affinity of the KdpB nucleotide binding domain.

Coolant channel module CCM: An universally applicable thermal-hydraulic drift-flux based mixture-fluid 1D model and code

A complete and detailed description of the theoretical background of an ‘(1D) thermal-hydraulic drift-flux based mixture-fluid’ coolant channel model and its resulting module CCM will be presented. The objective of this module is to simulate as universally as possible the steady state and transient behaviour of the key characteristic parameters of a single- or two-phase fluid flowing within any type of heated or non-heated coolant channel. Due to the possibility that different flow regimes can appear along any channel, such a ‘basic (BC)’ 1D channel is assumed to be subdivided into a number of corresponding sub-channels (SC-s). Each SC can belong to only two types of flow regime, an SC with just a single-phase fluid, containing exclusively either sub-cooled water or superheated steam, or an SC with a two-phase mixture flow. After an appropriate nodalisation of such a BC (and therefore also its SC-s) a ’modified finite volume method’ has been applied for the spatial discretisation of the partial differential equations (PDE-s) which represent the basic conservation equations of thermal-hydraulics. Special attention had to be given to the possibility of variable SC entrance or outlet positions (which describe boiling boundaries or mixture levels) and thus the fact that an SC can even disappear or be created anew. The procedure yields for each SC type (and thus the entire BC), a set of non-linear ordinary 1st order differential equations (ODE-s). To link the resulting mean nodal with the nodal boundary function values, both of which are present in the discretised differential equations, a special quadratic polygon approximation procedure (PAX) had to be constructed. Together with the very thoroughly tested packages for drift-flux, heat transfer and single- and two-phase friction factors this procedure represents the central part of the here presented ‘Separate-Region’ approach, a theoretical model which provides the basis to the very effective working code package CCM. This package can be adopted as a general element in the simulation of thermal-hydraulic situations of complex systems consisting of a number of special channels. Such systems can represent different types of steam generators, 3D nuclear reactor cores with special attention to the calculation of the mass flow distribution into different parallel channels after non-symmetric perturbations, each of them distinguished by their key numbers. The resulting set of equations can be combined with other ODE-s and constitutive equations from additional parts of such a comprehensive model. The complete system of equations can then (outside of the CCM) be solved by applying appropriate integration routines. Verification and validation test runs over a wide application range have yielded very satisfactory results demonstrating therefore in a convincing way the quality of the CCM. This approach offers an alternative to the currently dominant ‘Separate-Phase Models’ where each phase within a coolant channel is treated separately. The advantages and disadvantages of these two approaches are discussed in this paper.

ICONE15-10206 APPLICATION OF THE MIXTURE-FLUID CHANNEL ELEMENT CCM WITHIN THE U-TUBE STEAM GENERATOR CODE UTSG-3 FOR TRANSIENT THERMAL-HYDRAULIC CALCULATIONS

An universally applicable thermal-hydraulic 'Coolant Channel Module' and code package CCM has been constructed with the objective to simulate in an as general as possible way the steady state and transient behaviour of characteristic parameters of a single- or two-phase fluid flowing within any type of heated or non-heated coolant channel. It can then be used to describe in a very effective way the thermal-hydraulic situation of a number of complex physical systems. These can be different types of steam generators, 1D and 3D nuclear reactor cores with special attention to the calculation of the mass flow distribution into different parallel channels after non-symmetric perturbations etc. Applied within the natural-circulation U-tube steam generator code UTSG-3 three of the most characteristic channel elements of such an U-tube steam generator, namely the primary and secondary side of the heat exchange region and the riser region, have been represented by adequate CCM modules. The way of working of the code UTSG-3 (and thus the module CCM) will be demonstrated on hand of the characteristic test case 'Loss of main feedwater (but auxiliary and emergency feedwater cooling still available) with turbine trip but a defect in the scram system (ATWS case)' followed by a corresponding sequence in BOP actions.

Initial version of an integrated thermal hydraulics and neutron kinetics 3D code X3D

A theoretical concept for the description of 3D nuclear kinetics, heat conduction and the thermal-hydraulic single and two-phase flow phenomena in a 3D light water reactor core simulated by parallel channels is presented. The heat generation within each fuel element is described by a 3D core kinetics code employing a two-group diffusion theory model. Finite differences are used to approximate the diffusion equations for fast and thermal neutron fluxes. The resulting algebraic equations are solved by an iterative procedure. The heat transport out of a fuel element is determined from a finite difference version of the Fourier heat conduction equation applied in the radial direction only. An implicit solution for the temperature in each radial cell is found using a tri-diagonal algorithm. The heat transfer rate into the coolant channel is calculated from the clad and coolant temperatures. The thermal-hydraulic part of the code is based on the generally applicable and self-contained ‘coolant channel module’ (CCM) developed by Hoeld [Hoeld, A., 2004a, A theoretical concept for a thermal-hydraulic 3D parallel channel core model. PHYSOR 2004, April 25–29, Chicago, USA; Hoeld, A., 2004b, Are separate-phase thermal-hydraulic models better than mixture-fluid approaches. It depends. Rather not. International Conference on ‘Nuclear Engineering for New Europe 2004’. September 6–9, Portoroz, Slov; Hoeld, A., 2005, A thermal-hydraulic drift-flux based mixture-fluid model for the description of single- and two-phase flow along a general coolant channel. NURETH-11, October 2–6, Avignon, France], which offers a new approach for the simulation of steady state and transient behaviour of single- or two-phase flow within a general coolant channel. The concept is demonstrated in the experimental code X3D, concentrating in a first stage on the steady state behaviour of a hypothetical BWR or PWR core which consists of a central channel and four quadrants. Initial results are presented to demonstrate the viability of the proposed concept. This code therefore tests a different theoretical approach of how to determine the essential 3D thermal-hydraulic mass flow distribution into parallel channels by maintaining equal pressure decrease terms over all channels.

Development of a microplate reader compatible microfluidic device for enzyme assay

We report a novel platform technology of enzyme assay using microfluidic channel. Employing the patterns of microfluidic channel on a plastic chip, the dilution of substrate solution and enzyme reactions are sequentially carried out in microfluidic channels. The microfluidic device is fabricated by micromolding processes with polydimethylsiloxane (PDMS) polymer. The device consists of microfluidic channel modules running four assay tests on a single device and each module comprises six reaction chambers linked with microfluidic channels. Overall dimension of the microfluidic device is the same size as a 96-well microtiter plate and 24 reaction chambers in device adapt to the conventional 96-well architecture to be detected by a microplate reader. This provides the method to overcome the limitations of conventional assay platform which requires a special detection instrument, the manual dilution of the substrate solution and individual measurement of enzyme reactions. Enzyme reactions simultaneously occur in six reaction chambers of each microfluidic assay module filled with different concentrations of substrate solution generated by microfluidic channel network. Enzyme activity is measured with continuous methods and is determined by V max obtained by Michaelis–Menten relationship. In this study, alkaline phosphatase (ALP) and p-nitrophenyl phosphate ( p-NPP) have been used as an enzyme-substrate model system and demonstrated for microfluidic enzyme assay experiments.

Application of monolithic strip line radiation detector based on semi-insulating GaAs in X-ray portable scanner

The Schottky barrier line-scanning X- and γ-ray detector is presented, based on bulk undoped semi-insulating (SI) GaAs suitable for radiography imaging with a high position resolution (the lowest pitch 0.125mm). Basic electrical and detection characteristics of the detector (I–V dependences, pulse height spectra of 241Am gamma source) together with evaluated parameters are demonstrated. The detector is irradiated from the edge with an estimated active area of the strip input cross-section (0.125–0.25)×0.25mm2 and absorption length 1.25 or 2.5mm. A photon-counting readout electronics with 480 channels has been developed, giving a total length of the scanner line of about 12cm, using detectors with pitch 0.25mm. The readout system is based on a 16 channel VLSI chip or on 24 channel modules produced with discrete components in SMD technology. Overall detection efficiency of the developed strip SI GaAs radiation detector reaches a value higher than 50% of the theoretical one (∼75%) for detection of 60keV photons. The status of the development of a modular portable X-ray scanner based on the developed detectors is also presented.

Mass transfer coefficient with suction for turbulent non-Newtonian flow in application to membrane separations

The expression of mass transfer coefficient is derived from first principles for the turbulent non-Newtonian fluid flow in the membrane modules. The effects of suction are incorporated in the mass transfer coefficient from a theoretical basis. The analysis is carried out for a power law fluid, the common rheology for fruit juices and other food products. The analysis shows that there is significant effect of suction on mass transfer coefficient. The effects of the operating conditions, e.g., Reynolds number, permeate flux and the rheological nature of the fluid (pseudoplastic or dilatant) on the mass transfer coefficient are also investigated. Both rectangular thin channel and tubular modules are considered.

Read/Write Electronics Front-End Systems for Hard Disk Drives

The proper design of a disk drive's channel front-end is important to ensure data integrity and to achieve future high data rates. The front-end contains various interconnects which link the read/write (R/W) electronics with the recording heads and the channel module. This paper discusses the design aspects, which are to guarantee that the read path and the write path pass-on the signals and maintain the proper signal wave shape for high data recording. Impedance matching, line losses, signal-to-noise ratio, and crosstalk all are important aspects of a front-end system, and are therefore reviewed. The R/W electronics are to provide low-noise signal amplification and write head excitation. Various requirements which need to be satisfied to achieve this are discussed such as "cold" termination resistance, symmetrical write drivers, etc.

Study of ultrafiltration of a single and binary protein solution in a thin spiral channel module

The aim of this paper is to demonstrate the factors influencing a protein filtration process. Therefore single and mixed solutions of lysozyme and myoglobin were ultrafiltered through a hydrophilic membrane (cellulose acetate type) with a molecular weight cutoff (MWCO) of 30 kDa. The proteins are of similar molar mass and size. Filtration was done using a thin spiral channel module (TCF10). The change in transmission and flux was evaluated and the data of the single protein solutions compared with the binary protein mixture. Further, the effects of Dean vortex formation, was evaluated. From the collected data the effects of the parameters dominating the filtration process were assessed. By comparing the experimentally obtained mass transfer coefficients with literature data, it can be seen that the curved channel led to an increased mass transfer as compared with classical modules. For both proteins, a Sherwood correlation was derived and based on these data a separation process was modeled. Results obtained from separation experiments correlated well with the developed model. It could be shown that the separation of proteins by ultrafiltration is possible, but for proteins bearing similar molar masses it is a difficult task. Separation factors up to 2.5 were achieved. As expected the selectivity increases with the crossflow velocity and decreasing transmembrane pressure (TMP). The separation process requires careful choice of the pH value and the ionic strength. Further, attention has to be paid to the membrane stability and protein solubility while varying the pH value.

Mass transfer coefficient with suction for laminar non-Newtonian flow in application to membrane separations

The expression of mass transfer coefficient is derived from first principles for the laminar non-Newtonian fluid flow in membrane modules. The effects of suction is incorporated in the mass transfer coefficient from a theoretical basis. The analysis is carried out for a power law fluid, the common rheology for fruit juices and other food products. The analysis shows that there is a significant effect of suction on mass transfer coefficient. The effects of the operating conditions, e.g., Reynolds number, permeate flux and the rheological nature of the fluid (pseudoplastic or dilatant) on the mass transfer coefficient are also investigated. Both rectangular thin channel and tubular modules are considered.

An object-oriented design tool for associative cooling channels in plastic-injection moulds

Due to the demand for short product development cycles, plastic injection mould designers are required to compress their design time and to accommodate more late changes. This paper describes an associative design approach embedded in a cooling channel module of a mould design software package. It gives a set of comprehensive object definitions for cooling circuits, and addresses balanced or unbalanced designs. CAD algorithms that have been developed are briefly explained. With this new approach, mould designers can easily propagate changes between mould plates or inserts and the cooling system without the need for tedious rework. Hence, this approach can significantly reduce the total design time and the impact of late changes.

The high resolution versatile digital spectrometer of HIFI-HSO

We present a versatile digital autocorrelation spectrometer designed to suit the needs of HIFI, the sub-millimeter heterodyne instrument of the ESAs HSO satellite. This spectrometer will offer a set of four observing modes with different “on-line resolution/total bandwidth” combinations. An original architecture, based on mixed gallium arsenide and silicon technologies, allowed us to realize a 512 channel, low-power consumption and high speed correlation module. We give some details on the optimization of the design (quantization scheme, readout format) performed to fit the HSO-HIFI requirements. We also describe an approach to distortion correction which takes into account the non-rigorous adjustment of the comparison thresholds of the spectrometer’s analog to digital converter. Up to now, the efficiency of a spectrometer has been described as depending only on the quantization scheme used. In this paper, we show that the efficiency varies within the spectrum and we introduce the “spectral efficiency”, which is connected to the input signal band shape.

Stream Tables and Watershed Geomorphology Education

Watersheds are basic landscape units that are fundamental to understanding resource and environ- mental issues. Stream tables may be an effective way to learn about watersheds and the dynamic processes, factors, and landforms within. We review the copious stream table literature, present new ideas for assembling stream tables, and provide a watershed approach to stream table exercises. Our stream table's compact size and low cost permits the purchase and use of multiple units to maximize active learning. The included stream table modules allow introductory students to experiment and observe the effects of factors–i.e., climate (Module A–Precipitation, Overland Flow, and Channel Initiation and Module B–Stream Discharge and Channel Formation), topography (Module C–Watershed Topography and Channel Formation), land cover (Module D–Watershed Cover Types and Channel Formation), and base level (Module E–Local Base Level Changes via Dams and Reservoirs) –on fluvial processes and landforms in a watershed. Course evaluations and exams show that students enjoy the stream table exercise more, and learn the concepts of fluvial geomorphology better, than via traditional topographic map and aerial photograph interpretation exercises.

Separation characteristics of sodium fusidate in ultrafiltration

The aim of this study is the investigation of the separation characteristics of sodium fusidate by means of ultrafiltration. The influence of several parameters, such as feed concentration, applied transmembrane pressure, pH, ionic strength, temperature and membrane material, on the retention and flux behavior have been investigated. The experiments were performed in a thin channel module, with four different ultrafiltration membranes, in order to choose a membrane with a proper retention and good operating conditions. In addition, the influence of the hydraulic permeability of the membranes, taking into account each experiment and contact time with solutions of sodium fusidate and dextran, was also analyzed in this work. The film theory model was used to estimate the mass transfer coefficient by means of the variation velocity method. The membrane-sodium fusidate interactions were studied by measuring the water flux of the membranes and by using the finely pore model, which combines both the viscous flow and frictional models. The present study gives good insight on the interactions within membrane filtration in the downstream processing of sodium fusidate. However, the situation is often more complex in real fermentation broth, since fermentation media contain hydrophobic or surface active substances which strongly influence the performance of the membrane.

Flat Ceramic Ultrafiltration Membranes and Modules Coated by the Sol-Gel Technique

Sol-gel techniques are common in preparing inorganic ultrafiltration membranes. Since applicable membranes should exhibit improved chemical and thermal stability with respect to phase transition, pore size and particle growth, the authors developed a new method for preparing an inorganic ultrafiltration membrane made of magnesium aluminum spinel, MgAl{sub 2}O{sub 4}. This membrane is supported by a flat ceramic microfilter ({alpha}-Al{sub 2}O{sub 3}) produced via the tape casting process, which offers the opportunity of improved processing techniques and new module concepts compared to the widely used extruded multi channel modules. Membrane characteristics and some applications will be shown.

A large 2D PSD for thermal neutron detection

A 2D PSD based on a MWPC has been constructed for a small angle neutron scattering instrument. The active area of the detector was 640 × 640 mm 2. To meet the specifications for neutron detection efficiency and spatial resolution, and to minimise parallax, the gas mixture was 190 kPa 3He plus 100 kPa CF 4, and the active volume had a thickness of 30 mm. The design maximum neutron count rate of the detector was 10 5 events per secod. The (calculated) neutron detection efficiency was 60% for 2 Å neutrons and the (measured) neutron energy resolution on the anode grid was typically 20% (fwhm). The location of a neutron detection event within the active area was determined using the wire-by-wire method: the spatial resolution (5 × 5 mm 2) was thereby defined by the wire geometry. A 16-channel charge-sensitive preamplifier/amplifier/comparator module has been developed with a channel sensitivity of 0.1 V/fC, noise line width of 0.4 fC (fwhm) and channel-to-channel cross-talk of less than 5%. The Proportional Counter Operating System (PCOS III) (LeCroy Corp, USA) was used for event encoding. The ECL signals produced by the 16 channel modules were latched in PCOS III by a trigger pulse from the anode and the fast encoders produce a position and width for each event. The information was transferred to a UNIX workstation for accumulation and online display.

CFD-assisted thin channel membrane characterization module design

This project involved the design of a thin channel cross-flow module for the characterization of flat ceramic membranes. A primary objective of this work was to ensure that the flow characteristics over the permeating area were uniform. To house these membranes, a thin channel module with a long rectangular base was envisioned. The module feed is supplied by a multi-inlet tube-type plenum meant to provide a uniform flow distribution through pressure equilibration attained in its volume. The design criteria for the module were minimization of both the flow non-uniformity and the pressure drop across the permeating area which was a central rectangular portion of a larger slab-style cell. The flow non-uniformity was taken as the normalized standard deviation of the velocity field above the permeating area. The pressure drops considered were those across the inlet plenum and across the permeating area normalized with respect to the outlet pressure. The computational fluid dynamics (CFD) scheme which calculated the above module characteristics was a k- ε based turbulent transport model which used the finite difference method. Design variables considered were: the plenum diameter, module width, height and length, and the diameters, distribution and number of the inlets on the plenum. The distribution of the inlet diameters was determined by two variables: either a linear or parabolic profile of variable slope and model coefficient. The operating variables were the cross-flow velocity and the plenum inlet pressure. A two-level factorial design was used to screen the design variables. A refined three-level factorial design was used with a reduced set of design variables to optimize the module and study the response surface. The final module design parameters were chosen such that the design criteria of flow uniformity and low pressure drop were met under a preset range of operating conditions. The local gradients of the response surface were used to verify that the design criteria were not overly sensitive to the selected module design parameters.

Initial transient effects during cross flow microfiltration of yeast suspensions

In order to better understand the effect of transient filtration parameters on the filtration performance during cross flow microfiltration of yeast suspensions, a laser distance sensor was used to measure on-line the height of the filter cake in a specially designed flat channel module. The data obtained with an accuracy of ±2 μm were used to fit a model describing the build-up of the filter cake and the related flux decline. The model is based on a volume balance over the deposited particles, with the flux of the particles back into the concentrate stream proportional to the average cross flow velocity at the centre of a particle placed on the surface of the filter cake. An empirical back transport coefficient was introduced to fit the data to the model. The results showed that with yeast suspensions membrane fouling is limiting the filtration performance. Also the performance cannot be improved by transient pressure conditions generated by an alternation of the flow direction in the module.

High-throughput DNA synthesis in a multichannel format.

We describe an approach to high-throughput parallel DNA synthesis in which a multiwell format is used. The reactions are carried out in open wells using an argon ambient atmosphere to prevent reagent contamination. The controlled-pore glass beads which form the substrate for synthesis are held in individual wells with high-density polyethylene filter bottoms through which reagents are drawn into a vacuum manifold. The synthesis is carried out using direct reagent dispensing into the individual reaction wells. A computer controls the sequence in which reagents are dispensed and the timing of the periodic vacuum pulses required to synthesize the desired sequence. Experiments to date have demonstrated the viability of the approach for a variety of test sequences. Results obtained with HPLC analysis demonstrate coupling efficiencies as high as 99.5% under optimized conditions. Use of the oligomers for DNA sequencing templates and as PCR primers has been demonstrated in production applications. The current instrument design consists of a series of discrete reaction chambers in a 12 channel module which can be multiplexed in a 12 x n format where n can be 1-8, i.e. 96 wells. A projected time interval for 12 parallel syntheses is 2.5 h, with 96 syntheses in 3.5 h. Because of the reduced volume of reagents required in the open well format, significant cost savings are projected.