Molecular structure-activity relationship study of some non-steroidal antiinflammatory agents using electrostatic potential mapping

A series of 6,11-dihydro-11-oxodibenz[b,e]oxepin-2-acetic acids (DOAA) which are known to be anti-inflammatory agents were studied. The geometries of some of the molecules obtained from X-ray crystallography were used in the calculations as such while the geometries of their derivatives were obtained by local, partial geometry optimization around the Sites of substitution employing the AMI method, keeping the remaining parts of the geometries the same as those in the parent molecules. Molecular electrostatic potential (MEP) mapping was performed for the molecules using optimized hybridization displacement charges (HDC) combined with Lowdin charges, as this charge distribution has been shown earlier to yield near ab initio quality results. A good correlation has been found between the MEP values near the oxygen atoms of the hydroxyl groups of the carboxy groups of the molecules and their anti-inflammatory activities. The result is broadly in agreement with the model proposed earlier by other authors regarding the structure-activity relationship for other similar molecules.

Partial Loss Of Support And Frame-Soil Interaction

An interaction analysis has been conducted to study the effects of a local loss of support beneath the beam footing of a two-bay plane frame. The results of the study indicate that the magnitude of increase in the bending moment and axial force in the structure due to the presence of a void are dependent, not only on the extent of support loss, but also on the relative stiffnesses between foundation beam and soil, and between superstructure and soil. The increase in bending moment even for a void span of 1/12 of the foundation beam length can become so significant as to exceed the safety provisions. The study shows that the effect of a void on the superstructure moments can be greatly minimized by a combination of rigid foundation and flexible superstructure.

Inhibition of Human Two-Pore Domain K+ Channel TREK1 by Local Anesthetic Lidocaine: Negative Cooperativity and Half-of-Sites Saturation Kinetics

TWIK-related K+ channel TREK1, a background leak K+ channel, has been strongly implicated as the target of several general and local anesthetics. Here, using the whole-cell and single-channel patch-clamp technique, we investigated the effect of lidocaine, a local anesthetic, on the human (h) TREK1 channel heterologously expressed in human embryonic kidney 293 cells by an adenoviral-mediated expression system. Lidocaine, at clinical concentrations, produced reversible, concentration-dependent inhibition of hTREK1 current, with IC50 value of 180 mu M, by reducing the single-channel open probability and stabilizing the closed state. We have identified a strategically placed unique aromatic couplet (Tyr352 and Phe355) in the vicinity of the protein kinase A phosphorylation site, Ser348, in the C-terminal domain (CTD) of hTREK1, that is critical for the action of lidocaine. Furthermore, the phosphorylation state of Ser348 was found to have a regulatory role in lidocaine-mediated inhibition of hTREK1. It is interesting that we observed strong intersubunit negative cooperativity (Hill coefficient = 0.49) and half-of-sites saturation binding stoichiometry (half-reaction order) for the binding of lidocaine to hTREK1. Studies with the heterodimer of wild-type (wt)-hTREK1 and Delta 119 C-terminal deletion mutant (hTREK1(wt)-Delta 119) revealed that single CTD of hTREK1 was capable of mediating partial inhibition by lidocaine, but complete inhibition necessitates the cooperative interaction between both the CTDs upon binding of lidocaine. Based on our observations, we propose a model that explains the unique kinetics and provides a plausible paradigm for the inhibitory action of lidocaine on hTREK1.

LOCAL TWO-DIMENSIONAL PARTICLE-IN-CELL SIMULATIONS OF THE COLLISIONLESS MAGNETOROTATIONAL INSTABILITY

The magnetorotational instability (MRI) is a crucial mechanism of angular momentum transport in a variety of astrophysical accretion disks. In systems accreting at well below the Eddington rate, such as the central black hole in the Milky Way (Sgr A*), the plasma in the disk is essentially collisionless. We present a nonlinear study of the collisionless MRI using first-principles particle-in-cell plasma simulations. We focus on local two-dimensional (axisymmetric) simulations, deferring more realistic three-dimensional simulations to future work. For simulations with net vertical magnetic flux, the MRI continuously amplifies the magnetic field, B, until the Alfven velocity, v(A), is comparable to the speed of light, c (independent of the initial value of v(A)/c). This is consistent with the lack of saturation of MRI channel modes in analogous axisymmetric MHD simulations. The amplification of the magnetic field by the MRI generates a significant pressure anisotropy in the plasma (with the pressure perpendicular to B being larger than the parallel pressure). We find that this pressure anisotropy in turn excites mirror modes and that the volume-averaged pressure anisotropy remains near the threshold for mirror mode excitation. Particle energization is due to both reconnection and viscous heating associated with the pressure anisotropy. Reconnection produces a distinctive power-law component in the energy distribution function of the particles, indicating the likelihood of non-thermal ion and electron acceleration in collisionless accretion disks. This has important implications for interpreting the observed emission-from the radio to the gamma-rays-of systems such as Sgr A*.

A Phase Transition for the Uniform Distribution in the Pattern Maximum Likelihood Problem

In this paper, we consider the setting of the pattern maximum likelihood (PML) problem studied by Orlitsky et al. We present a well-motivated heuristic algorithm for deciding the question of when the PML distribution of a given pattern is uniform. The algorithm is based on the concept of a ``uniform threshold''. This is a threshold at which the uniform distribution exhibits an interesting phase transition in the PML problem, going from being a local maximum to being a local minimum.

Wireless scheduling with partial channel state information: large deviations and optimality

We consider a server serving a time-slotted queued system of multiple packet-based flows, where not more than one flow can be serviced in a single time slot. The flows have exogenous packet arrivals and time-varying service rates. At each time, the server can observe instantaneous service rates for only a subset of flows ( selected from a fixed collection of observable subsets) before scheduling a flow in the subset for service. We are interested in queue length aware scheduling to keep the queues short. The limited availability of instantaneous service rate information requires the scheduler to make a careful choice of which subset of service rates to sample. We develop scheduling algorithms that use only partial service rate information from subsets of channels, and that minimize the likelihood of queue overflow in the system. Specifically, we present a new joint subset-sampling and scheduling algorithm called Max-Exp that uses only the current queue lengths to pick a subset of flows, and subsequently schedules a flow using the Exponential rule. When the collection of observable subsets is disjoint, we show that Max-Exp achieves the best exponential decay rate, among all scheduling algorithms that base their decision on the current ( or any finite past history of) system state, of the tail of the longest queue. To accomplish this, we employ novel analytical techniques for studying the performance of scheduling algorithms using partial state, which may be of independent interest. These include new sample-path large deviations results for processes obtained by non-random, predictable sampling of sequences of independent and identically distributed random variables. A consequence of these results is that scheduling with partial state information yields a rate function significantly different from scheduling with full channel information. In the special case when the observable subsets are singleton flows, i.e., when there is effectively no a priori channel state information, Max-Exp reduces to simply serving the flow with the longest queue; thus, our results show that to always serve the longest queue in the absence of any channel state information is large deviations optimal.

Generalized Partial Response Equalization and Data-Dependent Noise Predictive Signal Detection Over Media Models for TDMR

Two-dimensional magnetic recording (2-D TDMR) is an emerging technology that aims to achieve areal densities as high as 10 Tb/in(2) using sophisticated 2-D signal-processing algorithms. High areal densities are achieved by reducing the size of a bit to the order of the size of magnetic grains, resulting in severe 2-D intersymbol interference (ISI). Jitter noise due to irregular grain positions on the magnetic medium is more pronounced at these areal densities. Therefore, a viable read-channel architecture for TDMR requires 2-D signal-detection algorithms that can mitigate 2-D ISI and combat noise comprising jitter and electronic components. Partial response maximum likelihood (PRML) detection scheme allows controlled ISI as seen by the detector. With the controlled and reduced span of 2-D ISI, the PRML scheme overcomes practical difficulties such as Nyquist rate signaling required for full response 2-D equalization. As in the case of 1-D magnetic recording, jitter noise can be handled using a data-dependent noise-prediction (DDNP) filter bank within a 2-D signal-detection engine. The contributions of this paper are threefold: 1) we empirically study the jitter noise characteristics in TDMR as a function of grain density using a Voronoi-based granular media model; 2) we develop a 2-D DDNP algorithm to handle the media noise seen in TDMR; and 3) we also develop techniques to design 2-D separable and nonseparable targets for generalized partial response equalization for TDMR. This can be used along with a 2-D signal-detection algorithm. The DDNP algorithm is observed to give a 2.5 dB gain in SNR over uncoded data compared with the noise predictive maximum likelihood detection for the same choice of channel model parameters to achieve a channel bit density of 1.3 Tb/in(2) with media grain center-to-center distance of 10 nm. The DDNP algorithm is observed to give similar to 10% gain in areal density near 5 grains/bit. The proposed signal-processing framework can broadly scale to various TDMR realizations and areal density points.

Two-Dimensional Noise-Predictive Maximum Likelihood Method for Magnetic Recording Channels

Noise-predictive maximum likelihood (NPML) is a well known signal detection technique used in partial response maximum likelihood (PRML) scheme in 1D magnetic recording channels. The noise samples colored by the partial response (PR) equalizer are predicted/ whitened during the signal detection using a Viterbi detector. In this paper, we propose an extension of the NPML technique for signal detection in 2D ISI channels. The impact of noise prediction during signal detection is studied in PRML scheme for a particular choice of 2D ISI channel and PR targets.

Homology between jacalin and artocarpin from jackfruit (Artocarpus integrifolia) seeds. Partial sequence and preliminary crystallographic studies of artocarpin

Jacalin and artocarpin, the two lectins from jackfruit (Artocarpus integrifolia) seeds, have different physicochemical properties and carbohydrate-binding specificities. However, comparison of the partial amino-acid sequence of artocarpin with the known sequence of jacalin indicates close to 50% sequence identity. Artocarpin crystallizes in two forms, both monoclinic P2(1), with one and two tetramic molecules, respectively, in the asymmetric units of form I (a = 69.9, b = 73.7, c = 60.6 Angstrom and beta = 95.1 degrees) and form II (a = 87.6, b = 72.2, c = 92.6 Angstrom and beta = 101.1 degrees). Both the crystal structures have been solved by the molecular replacement method using the known structure of jacalin as the search model and ope of them partially refined, confirming that the two lectins are indeed homologous.

Field and potential around local scatterers in thin metal films studied by scanning tunneling potentiometry

We report the direct observation of electrochemical potential and local transport field variations near scatterers like grain boundaries, triple points, and voids in thin platinum films studied by scanning tunneling potentiometry. The field is highest at a void, followed by a triple point and a grain boundary. The local transport field near a void can even be four orders of magnitude higher than the macroscopic field, indicating that the void is the most likely place for an electromigration induced failure. The field build up for a particular type of scatterer depends on the grain connectivity. We estimate an average grain boundary reflection coefficient for the film from the temperature dependence of its resistivity.

Extended Kalman filters using explicit and derivative-free local linearizations

We propose three variants of the extended Kalman filter (EKF) especially suited for parameter estimations in mechanical oscillators under Gaussian white noises. These filters are based on three versions of explicit and derivative-free local linearizations (DLL) of the non-linear drift terms in the governing stochastic differential equations (SDE-s). Besides a basic linearization of the non-linear drift functions via one-term replacements, linearizations using replacements through explicit Euler and Newmark expansions are also attempted in order to ensure higher closeness of true solutions with the linearized ones. Thus, unlike the conventional EKF, the proposed filters do not need computing derivatives (tangent matrices) at any stage. The measurements are synthetically generated by corrupting with noise the numerical solutions of the SDE-s through implicit versions of these linearizations. In order to demonstrate the effectiveness and accuracy of the proposed methods vis-à-vis the conventional EKF, numerical illustrations are provided for a few single degree-of-freedom (DOF) oscillators and a three-DOF shear frame with constant parameters.

Local structure of Sr2FeMoxW1-xO6 double perovskites across the composition-driven metal to insulator transition

Sr2FeMoO6 oxides exhibit a half-metallic ferromagnetic (HM-FM) ground state and peculiar magnetic and magnetotransport properties, which are interesting for applications in the emerging field of spintronics and attractive for fundamental research in the field of heavily correlated electron systems. Sr2FeWO6 is an insulator with an antiferromagnetic (I-AFM) ground state. The solid solutions Sr2FeMoxW1-xO6 also have peculiar properties-W doping enhances chemical order which allows stabilization of the HM-FM state; as the W content exceeds a certain value a metal to insulator transition (MIT) occurs. The role of W in determining the physical properties of Sr2FeMoxW1-xO6 systems has been a matter of intense investigation. This work deals with the problem of the structural and electronic changes related to the MIT from a local perspective by means of x-ray absorption spectroscopy (XAS). This technique allows one to probe in detail the local structure and electronic modifications around selected absorber ions (W, Mo, Fe and Sr in our case). The results of XAS analysis in the whole composition range (0 <= x <= 1), in the near edge (XANES) and extended (EXAFS) regions, demonstrate an abrupt change of the local structure around the Fe and Mo sites at the critical composition, x(c). This change represents the microstructural counterpart associated with the MIT. Conversely, the local structure and electronic configuration of W ions remain unaltered in the whole composition range, suggesting indirect participation of W in the MIT.

Partial discharges at low pressures in a dielectric interface between uniform field electrodes

Partial discharges in a gaseous interface due to the presence of a dielectric between two uniform field electrodes in air at different pressures from 0.5 to 685 mm Hg have been studied and measurements of inception and extinction voltages, number of pulses and their charge magnitudes at inception are reported. It has been observed that the extinction voltage can be as low as 70% of the inception voltage suggesting that the working voltage in such cases should be about 30% lower than the observed inception voltage. Small magnitude pulses are found to be more in number than large magnitude pulses. The charge is found to be pressure dependent. The results have been explained on the basis of an equivalent circuit consisting of resistance and capacitance in which the discharge gap functions as a switch.

Effect of a magnetic field on the flow and blood oxygenation in channels of variable cross-section

The effect of a magnetic field on the flow and oxygenation of an incompressible Newtonian conducting fluid in channels with irregular boundaries has been investigated. The geometric parameter δ, which is a ratio of the mean half width of the channel d to the characteristic length λ along the channel over which the significant changes in the flow quantities occur, has been used for perturbing the governing equations. Closed form solutions of the various order equations are presented for the stream function. The equations for oxygen partial pressure remain nonlinear even after perturbation, therefore a numerical solution is presented. The expressions for shear stress at a wall and pressure distributions are derived. Here the separation in the flow occurs at a higher Reynolds number than the corresponding non-magnetic case. It is found that the magnetic field has an effect on local oxygen concentration but has a little effect on the saturation length.

Low PAPR Square STBCs from Complex Partial-Orthogonal Designs (CPODs)

Space-time codes from complex orthogonal designs (CODs) with no zero entries offer low Peak to Average Power Ratio (PAPR) and avoid the problem of switching off antennas. But square CODs for 2(a) antennas with a + 1. complex variables, with no zero entries were discovered only for a <= 3 and if a + 1 = 2(k), for k >= 4. In this paper, a method of obtaining no zero entry (NZE) square designs, called Complex Partial-Orthogonal Designs (CPODs), for 2(a+1) antennas whenever a certain type of NZE code exists for 2(a) antennas is presented. Then, starting from a so constructed NZE CPOD for n = 2(a+1) antennas, a construction procedure is given to obtain NZE CPODs for 2n antennas, successively. Compared to the CODs, CPODs have slightly more ML decoding complexity for rectangular QAM constellations and the same ML decoding complexity for other complex constellations. Using the recently constructed NZE CODs for 8 antennas our method leads to NZE CPODs for 16 antennas. The class of CPODs do not offer full-diversity for all complex constellations. For the NZE CPODs presented in the paper, conditions on the signal sets which will guarantee full-diversity are identified. Simulation results show that bit error performance of our codes is same as that of the CODs under average power constraint and superior to CODs under peak power constraint.