Conserved water-mediated recognition and dynamics of NAD(+) (carboxamide group) to hIMPDH enzyme: water mimic approach toward the design of isoform-selective inhibitor

Inosine monophosphate dehydrogenase (IMPDH) enzyme involves in GMP biosynthesis pathway. Type I hIMPDH is expressed at lower levels in all cells, whereas type II is especially observed in acute myelogenous leukemia, chronic myelogenous leukemia cancer cells, and 10 ns simulation of the IMP-NAD(+) complex structures (PDB ID. 1B3O and 1JCN) have revealed the presence of a few conserved hydrophilic centers near carboxamide group of NAD(+). Three conserved water molecules (W1, W, and W1 `) in di-nucleotide binding pocket of enzyme have played a significant role in the recognition of carboxamide group (of NAD(+)) to D274 and H93 residues. Based on H-bonding interaction of conserved hydrophilic (water molecular) centers within IMP-NAD(+)-enzyme complexes and their recognition to NAD(+), some covalent modification at carboxamide group of di-nucleotide (NAD(+)) has been made by substituting the -CONH(2)group by -CONHNH2 (carboxyl hydrazide group) using water mimic inhibitor design protocol. The modeled structure of modified ligand may, though, be useful for the development of antileukemic agent or it could be act as better inhibitor for hIMPDH-II.

Gammatone Wavelet Cepstral Coefficients for Robust Speech Recognition

We develop noise robust features using Gammatone wavelets derived from the popular Gammatone functions. These wavelets incorporate the characteristics of human peripheral auditory systems, in particular the spatially-varying frequency response of the basilar membrane. We refer to the new features as Gammatone Wavelet Cepstral Coefficients (GWCC). The procedure involved in extracting GWCC from a speech signal is similar to that of the conventional Mel-Frequency Cepstral Coefficients (MFCC) technique, with the difference being in the type of filterbank used. We replace the conventional mel filterbank in MFCC with a Gammatone wavelet filterbank, which we construct using Gammatone wavelets. We also explore the effect of Gammatone filterbank based features (Gammatone Cepstral Coefficients (GCC)) for robust speech recognition. On AURORA 2 database, a comparison of GWCCs and GCCs with MFCCs shows that Gammatone based features yield a better recognition performance at low SNRs.

Effect of quantum nuclear motion on hydrogen bonding

This work considers how the properties of hydrogen bonded complexes, X-H center dot center dot center dot Y, are modified by the quantum motion of the shared proton. Using a simple two-diabatic state model Hamiltonian, the analysis of the symmetric case, where the donor (X) and acceptor (Y) have the same proton affinity, is carried out. For quantitative comparisons, a parametrization specific to the O-H center dot center dot center dot O complexes is used. The vibrational energy levels of the one-dimensional ground state adiabatic potential of the model are used to make quantitative comparisons with a vast body of condensed phase data, spanning a donor-acceptor separation (R) range of about 2.4-3.0 angstrom, i.e., from strong to weak hydrogen bonds. The position of the proton (which determines the X-H bond length) and its longitudinal vibrational frequency, along with the isotope effects in both are described quantitatively. An analysis of the secondary geometric isotope effect, using a simple extension of the two-state model, yields an improved agreement of the predicted variation with R of frequency isotope effects. The role of bending modes is also considered: their quantum effects compete with those of the stretching mode for weak to moderate H-bond strengths. In spite of the economy in the parametrization of the model used, it offers key insights into the defining features of H-bonds, and semi-quantitatively captures several trends. (C) 2014 AIP Publishing LLC.

Finding hidden females in a crowd: Mate recognition in fig wasps

Multi-species mating aggregations are crowded environments within which mate recognition must occur. Mating aggregations of fig wasps can consist of thousands of individuals of many species that attain sexual maturity simultaneously and mate in the same microenvironment, i.e, in syntopy, within the close confines of an enclosed globular inflorescence called a syconium - a system that has many signalling constraints such as darkness and crowding. All wasps develop within individual galled flowers. Since mating mostly occurs when females are still confined within their galls,, male wasps have the additional burden of detecting conspecific females that are ``hidden'' behind barriers consisting of gall walls. In Ficus racemosa, we investigated signals used by pollinating fig wasp males to differentiate conspecific females from females of other syntopic fig wasp species. Male Ceratosolen fusciceps could detect conspecific females using cues from galls containing females, empty galls, as well as cues from gall volatiles and gall surface hydrocarbons. In many figs, syconia are pollinated by single foundress wasps, leading to high levels of wasp inbreeding due to sibmating. In F. racemosa, as most syconia contain many foundresses, we expected male pollinators to prefer non-sib females to female siblings to reduce inbreeding. We used galls containing females from non-natal figs as a proxy for non-sibs and those from natal figs as a proxy for sibling females. We found that males preferred galls of female pollinators from natal figs. However, males were undecided when given a choice between galls containing non-pollinator females from natal syconia and pollinator females from non-natal syconia, suggesting olfactory imprinting by the natal syconial environment. (C) 2013 Elsevier Masson SAS. All rights reserved.

Design of fully rotatable, roller-crank-driven, cam mechanisms for arbitrary motion specifications

The design of a non-traditional cam and roller-follower mechanism is described here. In this mechanism, the roller-crank rather than the cam is used as the continuous input member, while both complete a full rotation in each revolution and remain in contact throughout. It is noted that in order to have the cam fully rotate for every full rotation of the roller-crank, the cam cannot be a closed profile, rather the roller traverses the open cam profile twice in each cycle. Using kinematic analysis, the angular velocity of the cam when the roller traverses the cam profile in one direction, is related to the angular velocity of the cam when the roller retraces its path on the cam in the other direction. Thus, one can specify any arbitrary function relating the motion of the cam to the motion of the roller-crank for only 180 degrees of rotation in the angular velocity space. The motion of the cam in the remaining portion is then automatically determined. In specifying the arbitrary motion, many desirable characteristics such as multiple dwells, low acceleration and jerk, etc., can be obtained. Useful design equations are derived for this purpose. Using the kinematic inversion technique, the cam profile is readily obtained once the motion is specified in the angular velocity space. The only limitation to the arbitrary motion specification is making sure that the transmission angle never gets too low, so that the force will be transmitted efficiently from roller to cam. This is addressed by incorporating a transmission index into the motion specification in the synthesis process. Consequently, in this method we can specify any arbitrary motion within a permissible rone, such that the transmission index is higher than the specified minimum value. Single-dwell, double-dwell and a long hesitation motion are used as examples to demonstrate the ffectiveness of the design method. Force closure using an optimally located spring and quasi-kinetostatic analysis are also discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.

FOLD TYPE II PYRIDOXAL 5 `-PHOSPHATE DEPENDENT ENZYMES: STRUCTURE, SUBSTRATE RECOGNITION AND CATALYSIS

Enzymes utilizing pyridoxal 5'-phosphate dependent mechanism for catalysis are observed in all cellular forms of living organisms. PLP-dependent enzymes catalyze a wide variety of reactions involving amino acid substrates and their analogs. Structurally, these ubiquitous enzymes have been classified into four major fold types. We have carried out investigations on the structure and function of fold type I enzymes serine hydroxymethyl transferase and acetylornithine amino transferase, fold type n enzymes catabolic threonine deaminase, D-serine deaminase, D-cysteine desulfhydrase and diaminopropionate ammonia lyase. This review summarizes the major findings of investigations on fold type II enzymes in the context of similar studies on other PLP-dependent enzymes. Fold type II enzymes participate in pathways of both degradation and synthesis of amino acids. Polypeptide folds of these enzymes, features of their active sites, nature of interactions between the cofactor and the polypeptide, oligomeric structure, catalytic activities with various ligands, origin of specificity and plausible regulation of activity are briefly described. Analysis of the available crystal structures of fold type II enzymes revealed five different classes. The dimeric interfaces found in these enzymes vary across the classes and probably have functional significance.

Performance enhancement of online handwritten Tamil symbol recognition with reevaluation techniques

In this article, we aim at reducing the error rate of the online Tamil symbol recognition system by employing multiple experts to reevaluate certain decisions of the primary support vector machine classifier. Motivated by the relatively high percentage of occurrence of base consonants in the script, a reevaluation technique has been proposed to correct any ambiguities arising in the base consonants. Secondly, a dynamic time-warping method is proposed to automatically extract the discriminative regions for each set of confused characters. Class-specific features derived from these regions aid in reducing the degree of confusion. Thirdly, statistics of specific features are proposed for resolving any confusions in vowel modifiers. The reevaluation approaches are tested on two databases (a) the isolated Tamil symbols in the IWFHR test set, and (b) the symbols segmented from a set of 10,000 Tamil words. The recognition rate of the isolated test symbols of the IWFHR database improves by 1.9 %. For the word database, the incorporation of the reevaluation step improves the symbol recognition rate by 3.5 % (from 88.4 to 91.9 %). This, in turn, boosts the word recognition rate by 11.9 % (from 65.0 to 76.9 %). The reduction in the word error rate has been achieved using a generic approach, without the incorporation of language models.

Skip Decision and Reference Frame Selection for Low-Complexity H.264/AVC Surveillance Video Coding

H. 264/advanced video coding surveillance video encoders use the Skip mode specified by the standard to reduce bandwidth. They also use multiple frames as reference for motion-compensated prediction. In this paper, we propose two techniques to reduce the bandwidth and computational cost of static camera surveillance video encoders without affecting detection and recognition performance. A spatial sampler is proposed to sample pixels that are segmented using a Gaussian mixture model. Modified weight updates are derived for the parameters of the mixture model to reduce floating point computations. A storage pattern of the parameters in memory is also modified to improve cache performance. Skip selection is performed using the segmentation results of the sampled pixels. The second contribution is a low computational cost algorithm to choose the reference frames. The proposed reference frame selection algorithm reduces the cost of coding uncovered background regions. We also study the number of reference frames required to achieve good coding efficiency. Distortion over foreground pixels is measured to quantify the performance of the proposed techniques. Experimental results show bit rate savings of up to 94.5% over methods proposed in literature on video surveillance data sets. The proposed techniques also provide up to 74.5% reduction in compression complexity without increasing the distortion over the foreground regions in the video sequence.

Computational framework to integrate the effect of antigen recognition on disease epidemiology outcome: multi-scale approach

Human Leukocyte Antigen (HLA) plays an important role, in presenting foreign pathogens to our immune system, there by eliciting early immune responses. HLA genes are highly polymorphic, giving rise to diverse antigen presentation capability. An important factor contributing to enormous variations in individual responses to diseases is differences in their HLA profiles. The heterogeneity in allele specific disease responses decides the overall disease epidemiological outcome. Here we propose an agent based computational framework, capable of incorporating allele specific information, to analyze disease epidemiology. This framework assumes a SIR model to estimate average disease transmission and recovery rate. Using epitope prediction tool, it performs sequence based epitope detection for a given the pathogenic genome and derives an allele specific disease susceptibility index depending on the epitope detection efficiency. The allele specific disease transmission rate, that follows, is then fed to the agent based epidemiology model, to analyze the disease outcome. The methodology presented here has a potential use in understanding how a disease spreads and effective measures to control the disease.

The interaction of N-trifluoroacetylgalactosamine and its derivatives with winged bean (Psophocarpus tetragonolobus) basic agglutinin reveals differential mechanism of their recognition: a fluorine-19 nuclear magnetic resonance study

Here, we show the binding results of a leguminosae lectin, winged bean basic agglutinin (WBA I) to N-trifluoroacetylgalactosamine (NTFAGalN), methyl-alpha-N-trifluoroacetylgalactosamine (Me alpha NTFAGalN) and methyl-beta-tifluoroacetylgalactosamine (Me beta NTFAGalN) using (19) F NMR spectroscopy. No chemical shift difference between the free and bound states for NTFAGalN and Me beta NTFAGalN, and 0.01-ppm chemical shift change for Me alpha NTFAGalN, demonstrate that the Me alpha NTFAGalN has a sufficiently long residence time on the protein binding site as compared to Me beta NTFAGalN and the free anomers of NTFAGalN. The sugar anomers were found in slow exchange with the binding site of agglutinin. Consequently, we obtained their binding parameters to the protein using line shape analyses. Aforementioned analyses of the activation parameters for the interactions of these saccharides indicate that the binding of alpha and beta anomers of NTFAGalN and Me alpha NTFAGalN is controlled enthalpically, while that of Me beta NTFAGalN is controlled entropically. This asserts the sterically constrained nature of the interaction of the Me beta NTFAGalN with WBA I. These studies thus highlight a significant role of the conformation of the monosaccharide ligands for their recognition by WBA I.

Coded Illumination for Motion-blur Free Imaging of Cells on Cell-phone Based Imaging Flow Cytometer

Cell-phone based imaging flow cytometry can be realized by flowing cells through the microfluidic devices, and capturing their images with an optically enhanced camera of the cell-phone. Throughput in flow cytometers is usually enhanced by increasing the flow rate of cells. However, maximum frame rate of camera system limits the achievable flow rate. Beyond this, the images become highly blurred due to motion-smear. We propose to address this issue with coded illumination, which enables recovery of high-fidelity images of cells far beyond their motion-blur limit. This paper presents simulation results of deblurring the synthetically generated cell/bead images under such coded illumination.

Crowd Flow Segmentation based on Motion Vectors in H.264 Compressed Domain

In this work, we have explored the prospect of segmenting crowd flow in H. 264 compressed videos by merely using motion vectors. The motion vectors are extracted by partially decoding the corresponding video sequence in the H. 264 compressed domain. The region of interest ie., crowd flow region is extracted and the motion vectors that spans the region of interest is preprocessed and a collective representation of the motion vectors for the entire video is obtained. The obtained motion vectors for the corresponding video is then clustered by using EM algorithm. Finally, the clusters which converges to a single flow are merged together based on the bhattacharya distance measure between the histogram of the of the orientation of the motion vectors at the boundaries of the clusters. We had implemented our proposed approach on the complex crowd flow dataset provided by 1] and compared our results by using Jaccard measure. Since we are performing crowd flow segmentation in the compressed domain using only motion vectors, our proposed approach performs much faster compared to other pixel domain counterparts still retaining better accuracy.

Hierarchical sampling for metastable conformers determines biomolecular recognition: the case of malectin and diglucosylated N-glycan interactions

Structural information over the entire course of binding interactions based on the analyses of energy landscapes is described, which provides a framework to understand the events involved during biomolecular recognition. Conformational dynamics of malectin's exquisite selectivity for diglucosylated N-glycan (Dig-N-glycan), a highly flexible oligosaccharide comprising of numerous dihedral torsion angles, are described as an example. For this purpose, a novel approach based on hierarchical sampling for acquiring metastable molecular conformations constituting low-energy minima for understanding the structural features involved in a biologic recognition is proposed. For this purpose, four variants of principal component analysis were employed recursively in both Cartesian space and dihedral angles space that are characterized by free energy landscapes to select the most stable conformational substates. Subsequently, k-means clustering algorithm was implemented for geometric separation of the major native state to acquire a final ensemble of metastable conformers. A comparison of malectin complexes was then performed to characterize their conformational properties. Analyses of stereochemical metrics and other concerted binding events revealed surface complementarity, cooperative and bidentate hydrogen bonds, water-mediated hydrogen bonds, carbohydrate-aromatic interactions including CH-pi and stacking interactions involved in this recognition. Additionally, a striking structural transition from loop to beta-strands in malectin CRD upon specific binding to Dig-N-glycan is observed. The interplay of the above-mentioned binding events in malectin and Dig-N-glycan supports an extended conformational selection model as the underlying binding mechanism.