Mutations within the selectivity filter of the NMDA receptor-channel influence voltage dependent block by 5-hydroxytryptamine

Background and purpose: Voltage-dependent block by Mg2+ is a cardinal feature of NMDA receptors which acts as a coincidence detector to prevent the receptor from over-activation. Inhibition of NMDA receptor currents by 5-hydroxytryptamine (5-HT) indicated that 5-HT, similar to Mg2+, binds within the membrane electric field. In the present study, we assessed whether point mutations of critical asparagine residues located within the selectivity filter of NR1 and NR2A subunits of NMDA receptor-channel affect voltage-dependent block by 5-HT. Experimental approach: The mode of action of 5-HT and Mg2+ on wild-type and mutated NMDA receptor-channels expressed in Xenopus oocytes was investigated using the two-electrode voltage clamp recording technique. Key results: The mutation within the NR1 subunit NR1(N0S or N0Q) strongly reduced the voltage dependent block by 5-HT and increased the IC50. The corresponding mutations within the NR2 subunits NR2A(N0Q or N + 1Q) reduced the block by 5-HT to a lesser extent. This is in contrast to the block produced by external Mg2+ where a substitution at the NR2A(N0) and NR2A(N + 1) sites but not at the NR1(N0) site significantly reduced Mg2+ block. Conclusion and implications: The block of NMDA receptor-channels by 5-HT depends on the NR1-subunit asparagine residue and to a lesser extent on the NR2A-subunit asparagine residues. These data suggest that the interaction of 5-HT with functionally important residues in a narrow constriction of the pore of the NMDA receptor-channel provides a significant barrier to ionic fluxes through the open channel due to energetic factors governed by chemical properties of the binding site and the electric field.

Direct numerical simulation of turbulent flow and mass transfer around a rotating circular cylinder

Turbulent flow around a rotating circular cylinder has numerous applications including wall shear stress and mass-transfer measurement related to the corrosion studies. It is also of interest in the context of flow over convex surfaces where standard turbulence models perform poorly. The main purpose of this paper is to elucidate the basic turbulence mechanism around a rotating cylinder at low Reynolds numbers to provide a better understanding of flow fundamentals. Direct numerical simulation (DNS) has been performed in a reference frame rotating at constant angular velocity with the cylinder. The governing equations are discretized by using a finite-volume method. As for fully developed channel, pipe, and boundary layer flows, a laminar sublayer, buffer layer, and logarithmic outer region were observed. The level of mean velocity is lower in the buffer and outer regions but the logarithmic region still has a slope equal to the inverse of the von Karman constant. Instantaneous flow visualization revealed that the turbulence length scale typically decreases as the Reynolds number increases. Wavelet analysis provided some insight into the dependence of structural characteristics on wave number. The budget of the turbulent kinetic energy was computed and found to be similar to that in plane channel flow as well as in pipe and zero pressure gradient boundary layer flows. Coriolis effects show as an equivalent production for the azimuthal and radial velocity fluctuations leading to their ratio being lowered relative to similar nonrotating boundary layer flows.

Numerical modelling of unsteady mixed flows

This thesis concerns mixed flows (which are characterized by the simultaneous occurrence of free-surface and pressurized flow in sewers, tunnels, culverts or under bridges), and contributes to the improvement of the existing numerical tools for modelling these phenomena. The classic Preissmann slot approach is selected due to its simplicity and capability of predicting results comparable to those of a more recent and complex two-equation model, as shown here with reference to a laboratory test case. In order to enhance the computational efficiency, a local time stepping strategy is implemented in a shock-capturing Godunov-type finite volume numerical scheme for the integration of the de Saint-Venant equations. The results of different numerical tests show that local time stepping reduces run time significantly (between −29% and −85% CPU time for the test cases considered) compared to the conventional global time stepping, especially when only a small region of the flow field is surcharged, while solution accuracy and mass conservation are not impaired. The second part of this thesis is devoted to the modelling of the hydraulic effects of potentially pressurized structures, such as bridges and culverts, inserted in open channel domains. To this aim, a two-dimensional mixed flow model is developed first. The classic conservative formulation of the 2D shallow water equations for free-surface flow is adapted by assuming that two fictitious vertical slots, normally intersecting, are added on the ceiling of each integration element. Numerical results show that this schematization is suitable for the prediction of 2D flooding phenomena in which the pressurization of crossing structures can be expected. Given that the Preissmann model does not allow for the possibility of bridge overtopping, a one-dimensional model is also presented in this thesis to handle this particular condition. The flows below and above the deck are considered as parallel, and linked to the upstream and downstream reaches of the channel by introducing suitable internal boundary conditions. The comparison with experimental data and with the results of HEC-RAS simulations shows that the proposed model can be a useful and effective tool for predicting overtopping and backwater effects induced by the presence of bridges and culverts.

Negotiating social and moral order in internet relay chat

Although internet chat is a significant aspect of many internet users’ lives, the manner in which participants in quasi-synchronous chat situations orient to issues of social and moral order remains to be studied in depth. The research presented here is therefore at the forefront of a continually developing area of study. This work contributes new insights into how members construct and make accountable the social and moral orders of an adult-oriented Internet Relay Chat (IRC) channel by addressing three questions: (1) What conversational resources do participants use in addressing matters of social and moral order? (2) How are these conversational resources deployed within IRC interaction? and (3) What interactional work is locally accomplished through use of these resources? A survey of the literature reveals considerable research in the field of computer-mediated communication, exploring both asynchronous and quasi-synchronous discussion forums. The research discussed represents a range of communication interests including group and collaborative interaction, the linguistic construction of social identity, and the linguistic features of online interaction. It is suggested that the present research differs from previous studies in three ways: (1) it focuses on the interaction itself, rather than the ways in which the medium affects the interaction; (2) it offers turn-by-turn analysis of interaction in situ; and (3) it discusses membership categories only insofar as they are shown to be relevant by participants through their talk. Through consideration of the literature, the present study is firmly situated within the broader computer-mediated communication field. Ethnomethodology, conversation analysis and membership categorization analysis were adopted as appropriate methodological approaches to explore the research focus on interaction in situ, and in particular to investigate the ways in which participants negotiate and co-construct social and moral orders in the course of their interaction. IRC logs collected from one chat room were analysed using a two-pass method, based on a modification of the approaches proposed by Pomerantz and Fehr (1997) and ten Have (1999). From this detailed examination of the data corpus three interaction topics are identified by means of which participants clearly orient to issues of social and moral order: challenges to rule violations, ‘trolling’ for cybersex, and experiences regarding the 9/11 attacks. Instances of these interactional topics are subjected to fine-grained analysis, to demonstrate the ways in which participants draw upon various interactional resources in their negotiation and construction of channel social and moral orders. While these analytical topics stand alone in individual focus, together they illustrate different instances in which participants’ talk serves to negotiate social and moral orders or collaboratively construct new orders. Building on the work of Vallis (2001), Chapter 5 illustrates three ways that rule violation is initiated as a channel discussion topic: (1) through a visible violation in open channel, (2) through an official warning or sanction by a channel operator regarding the violation, and (3) through a complaint or announcement of a rule violation by a non-channel operator participant. Once the topic has been initiated, it is shown to become available as a topic for others, including the perceived violator. The fine-grained analysis of challenges to rule violations ultimately demonstrates that channel participants orient to the rules as a resource in developing categorizations of both the rule violation and violator. These categorizations are contextual in that they are locally based and understood within specific contexts and practices. Thus, it is shown that compliance with rules and an orientation to rule violations as inappropriate within the social and moral orders of the channel serves two purposes: (1) to orient the speaker as a group member, and (2) to reinforce the social and moral orders of the group. Chapter 6 explores a particular type of rule violation, solicitations for ‘cybersex’ known in IRC parlance as ‘trolling’. In responding to trolling violations participants are demonstrated to use affiliative and aggressive humour, in particular irony, sarcasm and insults. These conversational resources perform solidarity building within the group, positioning non-Troll respondents as compliant group members. This solidarity work is shown to have three outcomes: (1) consensus building, (2) collaborative construction of group membership, and (3) the continued construction and negotiation of existing social and moral orders. Chapter 7, the final data analysis chapter, offers insight into how participants, in discussing the events of 9/11 on the actual day, collaboratively constructed new social and moral orders, while orienting to issues of appropriate and reasonable emotional responses. This analysis demonstrates how participants go about ‘doing being ordinary’ (Sacks, 1992b) in formulating their ‘first thoughts’ (Jefferson, 2004). Through sharing their initial impressions of the event, participants perform support work within the interaction, in essence working to normalize both the event and their initial misinterpretation of it. Normalising as a support work mechanism is also shown in relation to participants constructing the ‘quiet’ following the event as unusual. Normalising is accomplished by reference to the indexical ‘it’ and location formulations, which participants use both to negotiate who can claim to experience the ‘unnatural quiet’ and to identify the extent of the quiet. Through their talk participants upgrade the quiet from something legitimately experienced by one person in a particular place to something that could be experienced ‘anywhere’, moving the phenomenon from local to global provenance. With its methodological design and detailed analysis and findings, this research contributes to existing knowledge in four ways. First, it shows how rules are used by participants as a resource in negotiating and constructing social and moral orders. Second, it demonstrates that irony, sarcasm and insults are three devices of humour which can be used to perform solidarity work and reinforce existing social and moral orders. Third, it demonstrates how new social and moral orders are collaboratively constructed in relation to extraordinary events, which serve to frame the event and evoke reasonable responses for participants. And last, the detailed analysis and findings further support the use of conversation analysis and membership categorization as valuable methods for approaching quasi-synchronous computer-mediated communication.

Characterization of hot deformation behavior of brasses using processing maps: Part II. β Brass and α-β brass

The hot deformation behaviors of β brass in the temperature range of 550°C to 800°C and α-β brass in the temperature range of 450°C to 800°C have been characterized in the strain rate range of 0.001 to 100 s−1 using processing maps developed on the basis of the Dynamic Materials Model. The map for β brass revealed a domain of superplasticity in the entire temperature range and at strain rates lower than 1 s−1, with a maximum efficiency of power dissipation of about 68 pct. The temperature variation of the efficiency of power dissipation in the domain is similar to that of the diffusion coefficient for zinc in β brass, confirming that the diffusion-accommodated flow controls the superplasticity. The material undergoes microstructural instability in the form of adiabatic shear bands and strain markings at temperatures lower than 700°C and at strain rates higher than 10 s−1. The map for α-β brass revealed a wide domain for processing in the temperature range of 550°C to 800°C and at strain rates lower than 1 s−1, with a maximum efficiency of 54 pct occurring at about 750°C and 0.001 s−1. In the domain, the α phase undergoes dynamic recrystallization and controls the hot deformation of the alloy, while the β phase deforms superplastically. At strain rates greater than 1 s−1, α-β brass exhibits microstructural instabilities manifested as flow rotations at lower temperatures and localized shear bands at higher temperatures.

Direct numerical simulation of turbulent spots

A group of high-order finite-difference schemes for incompressible flow was implemented to simulate the evolution of turbulent spots in channel flows. The long-time accuracy of these schemes was tested by comparing the evolution of small disturbances to a plane channel flow against the growth rate predicted by linear theory. When the perturbation is the unstable eigenfunction at a Reynolds number of 7500, the solution grows only if there are a comparatively large number of (equispaced) grid points across the channel. Fifth-order upwind biasing of convection terms is found to be worse than second-order central differencing. But, for a decaying mode at a Reynolds number of 1000, about a fourth of the points suffice to obtain the correct decay rate. We show that this is due to the comparatively high gradients in the unstable eigenfunction near the walls. So, high-wave-number dissipation of the high-order upwind biasing degrades the solution especially. But for a well-resolved calculation, the weak dissipation does not degrade solutions even over the very long times (O(100)) computed in these tests. Some new solutions of spot evolution in Couette flows with pressure gradients are presented. The approach to self-similarity at long times can be seen readily in contour plots.

Chapman-Enskog analysis for finite-volume formulation of lattice Boltzmann equation

The classical Chapman-Enskog expansion is performed for the recently proposed finite-volume formulation of lattice Boltzmann equation (LBE) method D.V. Patil, K.N. Lakshmisha, Finite volume TVD formulation of lattice Boltzmann simulation on unstructured mesh, J. Comput. Phys. 228 (2009) 5262-5279]. First, a modified partial differential equation is derived from a numerical approximation of the discrete Boltzmann equation. Then, the multi-scale, small parameter expansion is followed to recover the continuity and the Navier-Stokes (NS) equations with additional error terms. The expression for apparent value of the kinematic viscosity is derived for finite-volume formulation under certain assumptions. The attenuation of a shear wave, Taylor-Green vortex flow and driven channel flow are studied to analyze the apparent viscosity relation.

Morphological transitions and buckling characteristics in a nanoparticle-laden sessile droplet resting on a heated hydrophobic substrate

In this work, we have established the evaporation-liquid flow coupling mechanism by which sessile nanofluid droplets on a hydrophobic substrate evaporate and agglomerate to form unique morphological features under controlled external heating. It is well understood that evaporation coupled with internal liquid flow controls particle transport in a spatiotemporal sense. Flow characteristics inside the heated droplet are investigated and found to be driven by the buoyancy effects. Velocity magnitudes are observed to increase by an order at higher temperatures with similar looking flow profiles. The recirculating flow induced particle transport coupled with collision of particles and shear interaction between them leads to the formation of dome shaped viscoelastic shells of different dimensions depending on the surface temperature. These shells undergo sol-gel transition and subsequently undergo buckling instability leading to the formation of daughter cavities. With an increase in the surface temperature, droplets exhibit buckling from multiple sites over a larger sector in the top half of the droplet. Irrespective of the initial nanoparticle concentration and substrate temperature, growth of a daughter cavity (subsequent to buckling) inside the droplet is found to be controlled by the solvent evaporation rate from the droplet periphery and is shown to exhibit a universal trend.

Probe for Measurements of Density/Conductivity in Flows of Conducting Fluids

A probe utilizing the bipolar pulse method to measure the density of a conducting fluid has been developed. The probe is specially designed such that the concentration of a stream tube can be sampled continuously. The density was determined indirectly from the measurement of solution conductivity. The probe was calibrated using standard NaCl solutions of varying molarity and was able to rapidly determine the density of a fluid with continuously varying conductance. Measurements of the conductivity profiles, corresponding density profiles, and their fluctuation levels are demonstrated in a channel flow with an electrolyte injected from a slot in one wall.

Effects Of Subgrid-Scale Modeling On Lagrangian Statistics In Large-Eddy Simulation

The application of large-eddy simulation (LES) to turbulent transport processes requires accurate prediction of the Lagrangian statistics of flow fields. However, in most existing SGS models, no explicit consideration is given to Lagrangian statistics. In this paper, we focus on the effects of SGS modeling on Lagrangian statistics in LES ranging from statistics determining single-particle dispersion to those of pair dispersion and multiparticle dispersion. Lagrangian statistics in homogeneous isotropic turbulence are extracted from direct numerical simulation (DNS) and the LES with a spectral eddy-viscosity model. For the case of longtime single-particle dispersion, it is shown that, compared to DNS, LES overpredicts the time scale of the Lagrangian velocity correlation but underpredicts the Lagrangian velocity fluctuation. These two effects tend to cancel one another leading to an accurate prediction of the longtime turbulent dispersion coefficient. Unlike the single-particle dispersion, LES tends to underestimate significantly the rate of relative dispersion of particle pairs and multiple-particles, when initial separation distances are less than the minimum resolved scale due to the lack of subgrid fluctuations. The overprediction of LES on the time scale of the Lagrangian velocity correlation is further confirmed by a theoretical analysis using a turbulence closure theory.

二维槽道湍流的标度律分析

对不同Reynolds数的二维不可压槽道湍流（即二维槽道流动的扰动饱和态）进行了标度律分析。指出二维槽道湍流中存在明显的标度律及扩展自相似性；分析了标度数随着流动Reynolds数的变化，指出随着Reynolds数的增长，标度指数的奇异性并没有减小的趋势；由此推测充分发展的二维槽道湍流的标度指数也是奇异的。将所得计算值和佘振苏等人的SL标度律预测值相比较，认为佘等人的SL标度律公式能很好描述二维湍流。

槽道湍流的直接数值模拟

通过直接数值模拟(DNS)研究槽道湍流的性质和机理。包含五个部分：1）湍流直接数值模拟的差分方法研究。2）求解不可压N－S方程的高效算法和不可压槽道湍流的直接数值模拟。3）可压缩槽道湍流的直接数值模拟和压缩性机理分析。4）“二维湍流”的机理分析。5）槽道湍流的标度律分析。1．针对壁湍流计算网格变化剧烈的特点，构造了基于非等距网格的的迎风紧致格式。该方法直接针对计算网格构造格式中的系数，克服了传统方法采用 Jacobian 变换因网格变化剧烈而带来的误差。针对湍流场的多尺度特性分析了差分格式的精度、网格尺度与数值模拟能分辨的最小尺度的关系，给出不同差分格式对计算网格步长的限制。同时分析了计算中混淆误差的来源和控制方法，指出了迎风型紧致格式能很好地控制混淆误差。2．将上述格式与三阶精度的Adams半隐格式相结合，构造了不可压槽道湍流直接数值模拟的高效算法。该算法利用基于交错网格的离散形式的压力Poisson方程求解压力项，避免了压力边界条件处理的困难。利用FFT对方程中的隐式部分进行解耦，解耦后的方程采用追赶法（LU分解法）求解，大大减少了计算量。为了检验该方法，进行了三维不可压槽道湍流的直接数值模拟，得到了Re＝2800的充分发展不可压槽道湍流，并对该湍流场进行了统计分析。包括脉动速度偏斜因子在内的各阶统计量与实验结果及Kim等人的计算结果吻合十分理想，说明本方法是行之有效的。3．进行了三维充分发展的可压缩槽道湍流的直接数值模拟。得到了 Re=3300，Ma=0.8的充分发展可压槽道湍流的数据库。流场的统计特征（如等效平均速度分布，“半局部”尺度无量纲化的脉动速度均方根）和他人的数值计算结果吻合。得到了可压槽道湍流的各阶统计量，其中脉动速度的偏斜因子和平坦因子等高阶统计量尚未见其他文献报道。同时还分析了压缩性效应对壁湍流影响的机理，指出近壁处的压力－膨胀项将部分湍流脉动的动能转换成内能，使得可压湍流近壁速度条带结构更加平整。4．模拟了二维不可压槽道流动的饱和态（所谓“二维湍流”），分析了“二维槽道湍流”的非线性行为特征。分析了流场中的上抛－下扫和间歇现象，研究了“二维湍流”与三维湍流的区别。指出“二维湍流”反映了三维湍流的部分特征，同时指出了展向扰动对于湍流核心区发展的重要性。5．首次对可压缩槽道湍流及“二维槽道湍流”标度律进行了分析，得出了以下结论：a）槽道湍流中，在槽道中心线附近较宽的区域，存在标度律。b）该区域流场存在扩展自相似性（ESS）。c）在Mach数不是很高时，压缩性对标度指数影响不大。本文结果同SL标度律的理论值吻合较好，有效支持了该理论。对“二维槽道湍流”也有相似的结论，但与三维湍流不同的是，“二维槽道湍流”存在标度律的区域更宽，近壁处的标度指数比中心处有所升高。

Hydroelectric Voltage Generation Based On Water-Filled Single-Walled Carbon Nanotubes

A DFT/MD mutual iterative method was employed to give insights into the mechanism of voltage generation based on water-fitted single-walled carbon nanotubes (SWCNTs). Our calculations showed that a constant voltage difference of several mV would generate between the two ends of a carbon nanotube, due to interactions between the water dipole chains and charge carriers in the tube. Our work validates this structure of a water-fitted SWCNT as a promising candidate for a synthetic nanoscale power cell, as well as a practical nanopower harvesting device at the atomic level. 

Transport Properties And Induced Voltage In The Structure Of Water-Filled Single-Walled Boron-Nitrogen Nanotubes

Density functional theory/molecular dynamics simulations were employed to give insights into the mechanism of voltage generation based on a water-filled single-walled boron-nitrogen nanotube (SWBNNT). Our calculations showed that (1) the transport properties of confined water in a SWBNNT are different from those of bulk water in view of configuration, the diffusion coefficient, the dipole orientation, and the density distribution, and (2) a voltage difference of several millivolts would generate between the two ends of a SWBNNT due to interactions between the water dipole chains and charge carriers in the tube. Therefore, this structure of a water-filled SWBNNT can be a promising candidate for a synthetic nanoscale power cell as well as a practical nanopower harvesting device.

Transport properties and induced voltage in the structure of water-filled single-walled boron-nitrogen nanotubes

Density functional theory/molecular dynamics simulations were employed to give insights into the mechanism of voltage generation based on a water-filled single-walled boron-nitrogen nanotube (SWBNNT). Our calculations showed that (1) the transport properties of confined water in a SWBNNT are different from those of bulk water in view of configuration the diffusion coefficient the dipole orientation and the density distribution and (2) a voltage difference of several millivolts would generate between the two ends of a SWBNNT due to interactions between the water dipole chains and charge carriers in the tube. Therefore this structure of a water-filled SWBNNT can be a promising candidate for a synthetic nanoscale power cell as well as a practical nanopower harvesting device.