Kinetic proofreading at single molecular level: aminoacylation of tRNA(Ile) and the role of water as an editor

Proofreading/editing in protein synthesis is essential for accurate translation of information from the genetic code. In this article we present a theoretical investigation of efficiency of a kinetic proofreading mechanism that employs hydrolysis of the wrong substrate as the discriminatory step in enzyme catalytic reactions. We consider aminoacylation of tRNA(Ile) which is a crucial step in protein synthesis and for which experimental results are now available. We present an augmented kinetic scheme and then employ methods of stochastic simulation algorithm to obtain time dependent concentrations of different substances involved in the reaction and their rates of formation. We obtain the rates of product formation and ATP hydrolysis for both correct and wrong substrates (isoleucine and valine in our case, respectively), in single molecular enzyme as well as ensemble enzyme kinetics. The present theoretical scheme correctly reproduces (i) the amplitude of the discrimination factor in the overall rates between isoleucine and valine which is obtained as (1.8x10(2)).(4.33x10(2)) = 7.8x10(4), (ii) the rates of ATP hydrolysis for both Ile and Val at different substrate concentrations in the aminoacylation of tRNA(Ile). The present study shows a non-michaelis type dependence of rate of reaction on tRNA(Ile) concentration in case of valine. The overall editing in steady state is found to be independent of amino acid concentration. Interestingly, the computed ATP hydrolysis rate for valine at high substrate concentration is same as the rate of formation of Ile-tRNA(Ile) whereas at intermediate substrate concentration the ATP hydrolysis rate is relatively low. We find that the presence of additional editing domain in class I editing enzyme makes the kinetic proofreading more efficient through enhanced hydrolysis of wrong product at the editing CP1 domain.

Rack Level Modeling of Air Flow Through Perforated Tile in a Data Center

Effective air flow distribution through perforated tiles is required to efficiently cool servers in a raised floor data center. We present detailed computational fluid dynamics (CFD) modeling of air flow through a perforated tile and its entrance to the adjacent server rack. The realistic geometrical details of the perforated tile, as well as of the rack are included in the model. Generally, models for air flow through perforated tiles specify a step pressure loss across the tile surface, or porous jump model based on the tile porosity. An improvement to this includes a momentum source specification above the tile to simulate the acceleration of the air flow through the pores, or body force model. In both of these models, geometrical details of tile such as pore locations and shapes are not included. More details increase the grid size as well as the computational time. However, the grid refinement can be controlled to achieve balance between the accuracy and computational time. We compared the results from CFD using geometrical resolution with the porous jump and body force model solution as well as with the measured flow field using particle image velocimetry (PIV) experiments. We observe that including tile geometrical details gives better results as compared to elimination of tile geometrical details and specifying physical models across and above the tile surface. A modification to the body force model is also suggested and improved results were achieved.

High-resolution restoration of 3D structures from widefield images with extreme low signal-to-noise-ratio

Four-dimensional fluorescence microscopy-which records 3D image information as a function of time-provides an unbiased way of tracking dynamic behavior of subcellular components in living samples and capturing key events in complex macromolecular processes. Unfortunately, the combination of phototoxicity and photobleaching can severely limit the density or duration of sampling, thereby limiting the biological information that can be obtained. Although widefield microscopy provides a very light-efficient way of imaging, obtaining high-quality reconstructions requires deconvolution to remove optical aberrations. Unfortunately, most deconvolution methods perform very poorly at low signal-to-noise ratios, thereby requiring moderate photon doses to obtain acceptable resolution. We present a unique deconvolution method that combines an entropy-based regularization function with kernels that can exploit general spatial characteristics of the fluorescence image to push the required dose to extreme low levels, resulting in an enabling technology for high-resolution in vivo biological imaging.

Signal Detection in Generalized Gaussian Noise by Nonlinear Wavelet Denoising

In this paper, a nonlinear suboptimal detector whose performance in heavy-tailed noise is significantly better than that of the matched filter is proposed. The detector consists of a nonlinear wavelet denoising filter to enhance the signal-to-noise ratio, followed by a replica correlator. Performance of the detector is investigated through an asymptotic theoretical analysis as well as Monte Carlo simulations. The proposed detector offers the following advantages over the optimal (in the Neyman-Pearson sense) detector: it is easier to implement, and it is more robust with respect to error in modeling the probability distribution of noise.

System-level SoC near-field (NF) emissions: Simulation to measurement correlation

As System-on-Chip (SoC) designs migrate to 28nm process node and beyond, the electromagnetic (EM) co-interactions of the Chip-Package-Printed Circuit Board (PCB) becomes critical and require accurate and efficient characterization and verification. In this paper a fast, scalable, and parallelized boundary element based integral EM solutions to Maxwell equations is presented. The accuracy of the full-wave formulation, for complete EM characterization, has been validated on both canonical structures and real-world 3-D system (viz. Chip + Package + PCB). Good correlation between numerical simulation and measurement has been achieved. A few examples of the applicability of the formulation to high speed digital and analog serial interfaces on a 45nm SoC are also presented.

A landscape-level assessment of Asian elephant habitat, its population and elephant-human conflict in the Anamalai hill ranges of southern Western Ghats, India

Spatial information at the landscape scale is extremely important for conservation planning, especially in the case of long-ranging vertebrates. The biodiversity-rich Anamalai hill ranges in the Western Ghats of southern India hold a viable population for the long-term conservation of the Asian elephant. Through rapid but extensive field surveys we mapped elephant habitat, corridors, vegetation and land-use patterns, estimated the elephant population density and structure, and assessed elephant-human conflict across this landscape. GIS and remote sensing analyses indicate that elephants are distributed among three blocks over a total area of about 4600 km(2). Approximately 92% remains contiguous because of four corridors; however, under 4000 km2 of this area may be effectively used by elephants. Nine landscape elements were identified, including five natural vegetation types, of which tropical moist deciduous forest is dominant. Population density assessed through the dung count method using line transects covering 275 km of walk across the effective elephant habitat of the landscape yielded a mean density of 1.1 (95% Cl = 0.99-1.2) elephant/km(2). Population structure from direct sighting of elephants showed that adult male elephants constitute just 2.9% and adult females 42.3% of the population with the rest being subadults (27.4%), juveniles (16%) and calves (11.4%). Sex ratios show an increasing skew toward females from juvenile (1:1.8) to sub-adult (1:2.4) and adult (1:14.7) indicating higher mortality of sub-adult and adult males that is most likely due to historical poaching for ivory. A rapid questionnaire survey and secondary data on elephant-human conflict from forest department records reveals that villages in and around the forest divisions on the eastern side of landscape experience higher levels of elephant-human conflict than those on the western side; this seems to relate to a greater degree of habitat fragmentation and percentage farmers cultivating annual crops in the east. We provide several recommendations that could help maintain population viability and reduce elephant-human conflict of the Anamalai elephant landscape. (C) 2013 Deutsche Gesellschaft far Saugetierkunde. Published by Elsevier GmbH. All rights reserved.

A Three-Level Common-Mode Voltage Eliminated Inverter With Single DC Supply Using Flying Capacitor Inverter and Cascaded H-Bridge

A three-level common-mode voltage eliminated inverter with single dc supply using flying capacitor inverter and cascaded H-bridge has been proposed in this paper. The three phase space vector polygon formed by this configuration and the polygon formed by the common-mode eliminated states have been discussed. The entire system is simulated in Simulink and the results are experimentally verified. This system has an advantage that if one of devices in the H-bridge fails, the system can still be operated as a normal three-level inverter at full power. This inverter has many other advantages like use of single dc supply, making it possible for a back-to-back grid-tied converter application, improved reliability, etc.

A multi-level multi-scale approach to study essential genes in Mycobacterium tuberculosis

Background: The set of indispensable genes that are required by an organism to grow and sustain life are termed as essential genes. There is a strong interest in identification of the set of essential genes, particularly in pathogens, not only for a better understanding of the pathogen biology, but also for identifying drug targets and the minimal gene set for the organism. Essentiality is inherently a systems property and requires consideration of the system as a whole for their identification. The available experimental approaches capture some aspects but each method comes with its own limitations. Moreover, they do not explain the basis for essentiality in most cases. A powerful prediction method to recognize this gene pool including rationalization of the known essential genes in a given organism would be very useful. Here we describe a multi-level multi-scale approach to identify the essential gene pool in a deadly pathogen, Mycobacterium tuberculosis. Results: The multi-level workflow analyses the bacterial cell by studying (a) genome-wide gene expression profiles to identify the set of genes which show consistent and significant levels of expression in multiple samples of the same condition, (b) indispensability for growth by using gene expression integrated flux balance analysis of a genome-scale metabolic model, (c) importance for maintaining the integrity and flow in a protein-protein interaction network and (d) evolutionary conservation in a set of genomes of the same ecological niche. In the gene pool identified, the functional basis for essentiality has been addressed by studying residue level conservation and the sub-structure at the ligand binding pockets, from which essential amino acid residues in that pocket have also been identified. 283 genes were identified as essential genes with high-confidence. An agreement of about 73.5% is observed with that obtained from the experimental transposon mutagenesis technique. A large proportion of the identified genes belong to the class of intermediary metabolism and respiration. Conclusions: The multi-scale, multi-level approach described can be generally applied to other pathogens as well. The essential gene pool identified form a basis for designing experiments to probe their finer functional roles and also serve as a ready shortlist for identifying drug targets.

A Seventeen-level Inverter With a Single DC-link For Motor Drives

In the present paper, a novel topology for generating a 17-level inverter using three-level flying capacitor inverter and cascaded H-bridge modules with floating capacitors. The proposed circuit is analyzed and various aspects of it are presented in the paper. This circuit is experimentally verified and the results are shown. The stability of the capacitor balancing algorithm has been verified during sudden acceleration. This circuit has many pole voltage redundancies. This circuit has an advantage of balancing all the capacitor voltages instantaneously by switching through the redundancies. Another advantage of this topology is its ability to generate all the 17 pole voltages from a single DC link which enables back to back converter operation. Also, the proposed inverter can be operated at all load power factors and modulation indices. Another advantage is, if one of the H-bridges fail, the inverter can still be operated at full load with reduced number of levels.

Nearly Constant Switching Frequency Hysteresis Current Controller with Fast Online Computation of Boundary for a 2-Level Induction Motor Drive

A nearly constant switching frequency current hysteresis controller for a 2-level inverter fed induction motor drive is proposed in this paper: The salient features of this controller are fast dynamics for the current, inherent protection against overloads and less switching frequency variation. The large variation of switching frequency as in the conventional hysteresis controller is avoided by defining a current-error boundary which is obtained from the current-error trajectory of the standard space vector PWM. The current-error boundary is computed at every sampling interval based on the induction machine parameters and from the estimated fundamental stator voltage. The stator currents are always monitored and when the current-error exceeds the boundary, voltage space vector is switched to reduce the current-error. The proposed boundary computation algorithm is applicable in linear and over-modulation region and it is simple to implement in any standard digital signal processor: Detailed experimental verification is done using a 7.5 kW induction motor and the results are given to show the performance of the drive at various operating conditions and validate the proposed advantages.

Origin of noise in two dimensionally doped Silicon and Germanium

We present the study of low-frequency noise, or 1/f noise, in degenerately doped Si: P and Ge: P delta-layers at low temperatures. For the Si: P d-layers we find that the noise is several orders of magnitude lower than that of bulk Si: P systems in the metallic regime and is one of the lowest values reported for doped semiconductors. Ge: P d-layers as a function of perpendicular magnetic field, shows a factor of two reduction in noise magnitude at the scale of B-phi, where B-phi is phase breaking field. We show that this is a characteristic feature of universal conductance fluctuations.

A Committee Machine Approach for Compressed Sensing Signal Reconstruction

Although many sparse recovery algorithms have been proposed recently in compressed sensing (CS), it is well known that the performance of any sparse recovery algorithm depends on many parameters like dimension of the sparse signal, level of sparsity, and measurement noise power. It has been observed that a satisfactory performance of the sparse recovery algorithms requires a minimum number of measurements. This minimum number is different for different algorithms. In many applications, the number of measurements is unlikely to meet this requirement and any scheme to improve performance with fewer measurements is of significant interest in CS. Empirically, it has also been observed that the performance of the sparse recovery algorithms also depends on the underlying statistical distribution of the nonzero elements of the signal, which may not be known a priori in practice. Interestingly, it can be observed that the performance degradation of the sparse recovery algorithms in these cases does not always imply a complete failure. In this paper, we study this scenario and show that by fusing the estimates of multiple sparse recovery algorithms, which work with different principles, we can improve the sparse signal recovery. We present the theoretical analysis to derive sufficient conditions for performance improvement of the proposed schemes. We demonstrate the advantage of the proposed methods through numerical simulations for both synthetic and real signals.

Nonequilibrium noise in electrophoresis: The microion wind

A colloid supported against gravitational settling by means of an imposed electric field behaves, on average, as if it is at equilibrium in a confining potential T. M. Squires, J. Fluid Mech. 443, 403 (2001)]. We show, however, that the effective Langevin equation for the colloid contains a nonequilibrium noise source, proportional to the field, arising from the thermal motion of dissolved ions. The position fluctuations of the colloid show strong, experimentally testable signatures of nonequilibrium behavior, including a highly anisotropic, frequency-dependent ``effective temperature'' obtained from the fluctuation-dissipation ratio.

Hysteresis current controller for a general n-level inverter fed drive with online current error boundary computation and nearly constant switching frequency

A space vector-based hysteresis current controller for any general n-level three phase inverter fed induction motor drive is proposed in this study. It offers fast dynamics, inherent overload protection and low harmonic distortion for the phase voltages and currents. The controller performs online current error boundary calculations and a nearly constant switching frequency is obtained throughout the linear modulation range. The proposed scheme uses only the adjacent voltage vectors of the present sector, similar to space vector pulse-width modulation and exhibits fast dynamic behaviour under different transient conditions. The steps involved in the boundary calculation include the estimation of phase voltages from the current ripple, computation of switching time and voltage error vectors. Experimental results are given to show the performance of the drive at various speeds, effect of sudden change of the load, acceleration, speed reversal and validate the proposed advantages.