Classification of Protein Kinases on the Basis of Both Kinase and Non-Kinase Regions

Background: Protein phosphorylation is a generic way to regulate signal transduction pathways in all kingdoms of life. In many organisms, it is achieved by the large family of Ser/Thr/Tyr protein kinases which are traditionally classified into groups and subfamilies on the basis of the amino acid sequence of their catalytic domains. Many protein kinases are multidomain in nature but the diversity of the accessory domains and their organization are usually not taken into account while classifying kinases into groups or subfamilies. Methodology: Here, we present an approach which considers amino acid sequences of complete gene products, in order to suggest refinements in sets of pre-classified sequences. The strategy is based on alignment-free similarity scores and iterative Area Under the Curve (AUC) computation. Similarity scores are computed by detecting common patterns between two sequences and scoring them using a substitution matrix, with a consistent normalization scheme. This allows us to handle full-length sequences, and implicitly takes into account domain diversity and domain shuffling. We quantitatively validate our approach on a subset of 212 human protein kinases. We then employ it on the complete repertoire of human protein kinases and suggest few qualitative refinements in the subfamily assignment stored in the KinG database, which is based on catalytic domains only. Based on our new measure, we delineate 37 cases of potential hybrid kinases: sequences for which classical classification based entirely on catalytic domains is inconsistent with the full-length similarity scores computed here, which implicitly consider multi-domain nature and regions outside the catalytic kinase domain. We also provide some examples of hybrid kinases of the protozoan parasite Entamoeba histolytica. Conclusions: The implicit consideration of multi-domain architectures is a valuable inclusion to complement other classification schemes. The proposed algorithm may also be employed to classify other families of enzymes with multidomain architecture.

Exact path-integral evaluation of the heat distribution function of a trapped Brownian oscillator

Using path integrals, we derive an exact expression-valid at all times t-for the distribution P(Q,t) of the heat fluctuations Q of a Brownian particle trapped in a stationary harmonic well. We find that P(Q, t) can be expressed in terms of a modified Bessel function of zeroth order that in the limit t > infinity exactly recovers the heat distribution function obtained recently by Imparato et al. Phys. Rev. E 76, 050101(R) (2007)] from the approximate solution to a Fokker-Planck equation. This long-time result is in very good agreement with experimental measurements carried out by the same group on the heat effects produced by single micron-sized polystyrene beads in a stationary optical trap. An earlier exact calculation of the heat distribution function of a trapped particle moving at a constant speed v was carried out by van Zon and Cohen Phys. Rev. E 69, 056121 (2004)]; however, this calculation does not provide an expression for P(Q, t) itself, but only its Fourier transform (which cannot be analytically inverted), nor can it be used to obtain P(Q, t) for the case v=0.

Microcycle conidiation and its genetic basis in Neurospora crassa

Some wild isolates of Neurospora show microcycle conidiation in liquid culture under continuous agitation. Macroconidia from agar-grown mycelial cultures germinated in liquid and the germlings spontaneously produced conidia with no intervening mycelial phase. Three types of microcycle conidiation were seen among progeny of N. crassa Vickramam A x N. crassa a wild-type: (1) multinucleate blastoconidia produced by apical budding and septation, (2) multinucleate arthroconidia produced by holothallic septation and disarticulation of cells, and (3) uninucleate microconidia produced directly from conidiogenous cells of the germlings. Two genes were identified which control specific patterns of microcycle conidiogenesis. A single gene mcb in linkage group VR near al-3 (3.2% recombination) controls blastoconidiation. This gene is epistatic to gene mcm located in linkage group IIL, very near ro-7 (1.4%). mcm controls both microconidiation and arthroconidiation depending on temperature. Strains of genotype mcm produce microconidia almost exclusively at 18-22 degrees C, but arthroconidia with few or no microconidia at 30 degrees C. Because they result in rapid and synchronized conidiation in liquid culture, the two genes should be useful for studies of developmental gene regulation. mcm makes it possible to obtain large quantities of pure microconidia rapidly for experimentation.

Path-integral derivation of the superconformal anomaly for the N=1 supersymmetric Yang-Mills theory

Fujikawa's method of evaluating the supercurrent and the superconformal current anomalies, using the heat-kernel regularization scheme, is extended to theories with gauge invariance, in particular, to the off-shell N=1 supersymmetric Yang-Mills (SSYM) theory. The Jacobians of supersymmetry and superconformal transformations are finite. Although the gauge-fixing term is not supersymmetric and the regularization scheme is not manifestly supersymmetric, we find that the regularized Jacobians are gauge invariant and finite and they can be expressed in such a way that there is no one-loop supercurrent anomaly for the N=1 SSYM theory. The superconformal anomaly is nonzero and the anomaly agrees with a similar result obtained using other methods.

Path-integral derivation of the superconformal anomaly for the Wess-Zumino model

Fujikawa's method of evaluating the anomalies is extended to the on-shell supersymmetric (SUSY) theories. The supercurrent and the superconformal current anomalies are evaluated for the Wess-Zumino model using the background-field formulation and heat-kernel regularization. We find that the regularized Jacobians for SUSY and superconformal transformations are finite. The results can be expressed in a form such that there is no supercurrent anomaly but a finite nonzero superconformal anomaly, in agreement with similar results obtained using other methods.

Use of adult male bonnet monkeys (Macaca radiata) for testing the biological activity of gonadotropin releasing hormone and its analogues

The effect of injecting agonistic and antagonistic analogues of gonadotropin releasing hormone analogues on serum testosterone levels was checked in adult and immature male bonnet monkeys. Of the agonistic analogues Buserelin, Ovurelin and D-Phe6 Gln8 GnRH were found to be most potent in increasing serum testosterone levels in the adult male bonnet monkeys. While 27-month-old monkeys responded well to des Gly10 GnRH, only marginal response was observed in the case of 15-month-old monkeys. Studies carried out with Ovurelin indicated that it was not effective in causing desensitization in adult monkeys. The antagonistic analogue was effective in blocking nocturnal surge of serum testosterone. Based on these studies it is suggested the adult male bonnet monkeys can be effectively used for testing the activity of GnRH analogues.

Testing the efficacy of a chilli-tobacco rope fence as a deterrent against crop-raiding elephants

Chilli-based repellents have shown promise as deterrents against crop-raiding elephants in Africa. We experimented with ropes coated with chilli-based repellent as a cheap alternative to existing elephant cropraid deterrent methods in India. Three locations (Buxa Tiger Reserve, Wyanad Wildlife Sanctuary and Hosur Forest Division) representing varying rainfall regimes from high to low, and with histories of intense elephant-agriculture conflict, were selected for the experiments that were conducted over 2-3 months during the pre-harvest period of the kharif season in late 2006. Chilli and tobacco powder mixed with waste oil was applied to ropes strung around agricultural fields of 1.4-5.5 km perimeter and elephant approaches were monitored. Elephants breached the rope fences a few times at all three study sites. Female-led herds were far more deterred (practically 100% reduction) than were solitary males (c. 50%) by the chilli-tobacco rope. Efficacy of this method as a deterrent was significantly better in the low-rainfall regime relative to medium and high-rainfall regimes. The initial promising results present a case for more rigorous experimentation; these would help determine if the elephants avoiding the rope are responding physiologically to the chilli-tobacco smell or merely reacting cautiously to a novel substance in their environment.

Performance study of a pressure transducer with meandering-path thin film strain gauges

The performance of a pressure transducer with meandering-path thin film strain gauges has been studied. Details of the procedure followed to prepare the thin film strain gauge system on the pressure transducer diaphragm are given. The effect of post-deposition heat treatment on the resistance of the sensing films of the strain gauges and the insulating base layers are discussed. The output of the pressure transducer was studied with various input pressures and excitation voltages. It was found that up to a maximum of 10 V bridge excitation the output was stable and repetitive. The maximum non-linearity and hysteresis observed are ±0.15%, ±0.16% and ±0.14% FSO (full-scale output) for 5, 7.5 and 10 V excitation respectively. Information on the output behaviour of the pressure transducer with temperature is also included.

Path integral quantisation of topological field theories

Conditions for quantum topological invariance of classically topological field theories in the path integral formulation are discussed. Both the three-dimensional Chern-Simons system and a Witten-type topological field theory are shown to satisfy these conditions.

Effect of zinc content on the processing map for hot working of α brass

The hot deformation behavior of α brass with varying zinc contents in the range 3%–30% was characterized using hot compression testing in the temperature range 600–900 °C and strain rate range 0.001–100 s−1. On the basis of the flow stress data, processing maps showing the variation of the efficiency of power dissipation (given by Image where m is the strain rate sensitivity) with temperature and strain rate were obtained. α brass exhibits a domain of dynamic recrystallization (DRX) at temperatures greater than 0.85Tm and at strain rates lower than 1 s−1. The maximum efficiency of power dissipation increases with increasing zinc content and is in the range 33%–53%. The DRX domain shifts to lower strain rates for higher zinc contents and the strain rate for peak efficiency is in the range 0.0001–0.05 s−1. The results indicate that the DRX in α brass is controlled by the rate of interface formation (nucleation) which depends on the diffusion-controlled process of thermal recovery by climb.

Path integral description of polymers using fractional Brownian walks

The statistical properties of fractional Brownian walks are used to construct a path integral representation of the conformations of polymers with different degrees of bond correlation. We specifically derive an expression for the distribution function of the chains’ end‐to‐end distance, and evaluate it by several independent methods, including direct evaluation of the discrete limit of the path integral, decomposition into normal modes, and solution of a partial differential equation. The distribution function is found to be Gaussian in the spatial coordinates of the monomer positions, as in the random walk description of the chain, but the contour variables, which specify the location of the monomer along the chain backbone, now depend on an index h, the degree of correlation of the fractional Brownian walk. The special case of h=1/2 corresponds to the random walk. In constructing the normal mode picture of the chain, we conjecture the existence of a theorem regarding the zeros of the Bessel function.

Processing maps for hot-working of powder metallurgy 1100 Al-10 vol % SiC-particulate metal-matrix composite

The hot-working characteristics of the metal-matrix composite (MMC) Al-10 vol % SiC-particulate (SiCp) powder metallurgy compacts in as-sintered and in hot-extruded conditions were studied using hot compression testing. On the basis of the stress-strain data as a function of temperature and strain rate, processing maps depicting the variation in the efficiency of power dissipation, given by eegr = 2m/(m+1), where m is the strain rate sensitivity of flow stress, have been established and are interpreted on the basis of the dynamic materials model. The as-sintered MMC exhibited a domain of dynamic recrystallization (DRX) with a peak efficiency of about 30% at a temperature of about 500°C and a strain rate of 0.01 s�1. At temperatures below 350°C and in the strain rate range 0.001�0.01 s�1 the MMC exhibited dynamic recovery. The as-sintered MMC was extruded at 500°C using a ram speed of 3 mm s�1 and an extrusion ratio of 10ratio1. A processing map was established on the extruded product, and this map showed that the DRX domain had shifted to lower temperature (450°C) and higher strain rate (1 s�1). The optimum temperature and strain rate combination for powder metallurgy billet conditioning are 500°C and 0.01 s�1, and the secondary metal-working on the extruded product may be done at a higher strain rate of 1 s�1 and a lower temperature of 425°C.

Symmetry adaptation of correlated states in the valence bond basis

Symmetry?adapted linear combinations of valence?bond (VB) diagrams are constructed for arbitrary point groups and total spin S using diagrammatic VB methods. VB diagrams are related uniquely to invariant subspaces whose size reflects the number of group elements; their nonorthogonality leads to sparser matrices and is fully incorporated into a binary integer representation. Symmetry?adapated linear combinations of VB diagrams are constructed for the 1764 singlets of a half?filled cube of eight sites, the 2.8 million ??electron singlets of anthracene, and for illustrative S?0 systems.

Microtensile testing of a free-standing Pt-aluminide bond coat

A finite element method (FEM)-based study has been carried out for the design of flat microtensile samples to evaluate tensile properties of Pt-aluminide (PtAl) bond coats. The critical dimensions of the sample have been determined using a two-dimensional elastic stress analysis. In the present testing scheme, the ratio of the dimensions of the holding length to the fillet radius of the sample was found important to achieve failure within the gage length. The effect of gage length and grip head length also has been examined. The simulation predictions have been experimentally verified by conducting microtensile test of an actual PtAl bond coat at room temperature. The sample design and testing scheme suggested in this study have also been found suitable for evaluation of tensile properties at high temperature. (C) 2010 Elsevier Ltd. All rights reserved.