The repertoire of protein kinases encoded in the draft version of the human genome: atypical variations and uncommon domain combinations

Background: Phosphorylation by protein kinases is central to cellular signal transduction. Abnormal functioning of kinases has been implicated in developmental disorders and malignancies. Their activity is regulated by second messengers and by the binding of associated domains, which are also influential in translocating the catalytic component to their substrate sites, in mediating interaction with other proteins and carrying out their biological roles. Results: Using sensitive profile-search methods and manual analysis, the human genome has been surveyed for protein kinases. A set of 448 sequences, which show significant similarity to protein kinases and contain the critical residues essential for kinase function, have been selected for an analysis of domain combinations after classifying the kinase domains into subfamilies. The unusual domain combinations in particular kinases suggest their involvement in ubiquitination pathways and alternative modes of regulation for mitogen-activated protein kinase kinases (MAPKKs) and cyclin-dependent kinase (CDK)-like kinases. Previously unexplored kinases have been implicated in osteoblast differentiation and embryonic development on the basis of homology with kinases of known functions from other organisms. Kinases potentially unique to vertebrates are involved in highly evolved processes such as apoptosis, protein translation and tyrosine kinase signaling. In addition to coevolution with the kinase domain, duplication and recruitment of non-catalytic domains is apparent in signaling domains such as the PH, DAG-PE, SH2 and SH3 domains. Conclusions: Expansion of the functional repertoire and possible existence of alternative modes of regulation of certain kinases is suggested by their uncommon domain combinations. Experimental verification of the predicted implications of these kinases could enhance our understanding of their biological roles.

Phase transitions in the anchored organic bilayers of long-chain alkylammonium lead iodides (CnH2n+1NH3)(2)PbI4; n=12, 16, 18

The single perovskite slab alkylammonium lead iodides (CnH2n+1NH3)(2)PbI4, n = 12, 16, 18, display two phase transitions, just above room temperature, associated with changes in the alkylammonium chains. We have followed these two phase transitions using scanning calorimetry, X-ray powder diffraction, and IR and Raman spectroscopies. We find the first phase transition to be associated with symmetry changes arising from a dynamic rotational disordering of the ammonium headgroup of the chain whereas the second transition, the melting of the chains in two dimensions, is characterized by an increased conformational disorder of the methylene units of the alkyl chains. We examine these phase transitions in light of the interesting optical properties of these materials, as well as the relevance of these systems as models for phase transitions in lipid bilayers.

Reinforcement learning with average cost for adaptive control of traffic lights at intersections

We propose for the first time two reinforcement learning algorithms with function approximation for average cost adaptive control of traffic lights. One of these algorithms is a version of Q-learning with function approximation while the other is a policy gradient actor-critic algorithm that incorporates multi-timescale stochastic approximation. We show performance comparisons on various network settings of these algorithms with a range of fixed timing algorithms, as well as a Q-learning algorithm with full state representation that we also implement. We observe that whereas (as expected) on a two-junction corridor, the full state representation algorithm shows the best results, this algorithm is not implementable on larger road networks. The algorithm PG-AC-TLC that we propose is seen to show the best overall performance.

The 18 September 2011, North Sikkim earthquake

The 18 September 2011, magnitude Mw 6.9 earthquake close to the Nepal-Sikkim border caused significant damage due to ground shaking and caused several landslides. Observations from the post-earthquake surveys in the affected areas within Sikkim suggest that the poorly engineered, multistoried structures were relatively more impacted. Those located on alluvial terraces were also affected. The morphology of the region is prone to landslides and the possibility for their increased intensity during the forthcoming monsoon need to be considered seriously. From the seismotectonic perspective, the mid-crustal focal depth of the North Sikkim earthquake reflects the ongoing deformation of the subducting Indian plate.

Role of water contamination within the GC column of a GasBench II peripheral on the reproducibility of O-18/O-16 ratios in water samples

The GasBench II peripheral along with MAT 253 combination provides a more sensitive platform for the determination of water isotope ratios. Here, we examined the role of adsorbed moisture within the gas chromatography (GC) column of the GasBench II on measurement uncertainties. The uncertainty in O-18/O-16 ratio measurements is determined by several factors, including the presence of water in the GC. The contamination of GC with water originating from samples as water vapour over a longer timeframe is a critical factor in determining the reproducibility of O-18/O-16 ratios in water samples. The shift in isotope ratios observed in the experiment under dry and wet conditions correlates strongly with the retention time of analyte CO2, indicating the effect of accumulated moisture. Two possible methods to circumvent or minimise the effect of adsorbed water on isotope ratios are presented here. The proposed methodology includes either the regular baking of the GC column at a higher temperature (120 degrees C) after analysis of a batch of 32 sample entries or conducting the experiment at a low GC column temperature (22.5 degrees C). The effects of water contamination on long-term reproducibility of reference water, with and without baking protocol, have been described.

Mechanism of Fragility at BCL2 Gene Minor Breakpoint Cluster Region during t(14;18) Chromosomal Translocation

The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Breaks in chromosome 18 are localized at the 3'-UTR of BCL2 gene or downstream and are mainly clustered in either the major breakpoint region or the minor breakpoint cluster region (mcr). The recombination activating gene (RAG) complex induces breaks at IgH locus of chromosome 14, whereas the mechanism of fragility at BCL2 mcr remains unclear. Here, for the first time, we show that RAGs can nick mcr; however, the mechanism is unique. Three independent nicks of equal efficiency are generated, when both Mg2+ and Mn2+ are present, unlike a single nick during V(D)J recombination. Further, we demonstrate that RAG binding and nicking at the mcr are independent of nonamer, whereas a CCACCTCT motif plays a critical role in its fragility, as shown by sequential mutagenesis. More importantly, we recapitulate the BCL2 mcr translocation and find that mcr can undergo synapsis with a standard recombination signal sequence within the cells, in a RAG-dependent manner. Further, mutation to the CCACCTCT motif abolishes recombination within the cells, indicating its vital role. Hence, our data suggest a novel, physiologically relevant, nonamer-independent mechanism of RAG nicking at mcr, which may be important for generation of chromosomal translocations in humans.

Synthesis and spectral characterization of cyclotriphosphazene based 18-membered macrocycles

New 18-membered cyclotriphosphazene-containing macrocycles 7-10 were obtained by 1 + 1 condensation reaction of dispiro-N3P3(C12H8O2)(2)((N(Me)N=CH)(2) N4C20H26)] (2) with N,N'-dimethyl-ethylenediamine-1,4-diyldimethylenebis(4-methyl-2-formylph enol) (3), N,N'-dimethyl-ethylenediamine-1,4-diyldimethylenebis(4,5-dimethyl-2-form ylphenol) (4), N,N'-dimethyl-ethylenediamine-1,4-diyldimethylenebis(5-chloro-2-formylph enol) (5) and N,N'-dimethyl-ethylenediamine-1,4-diyldimethylenebis(5-bromo-2-formylphe nol) (6), respectively. (C) 2012 Elsevier B.V. All rights reserved.

Improving query focused summarization using look-ahead strategy

Query focused summarization is the task of producing a compressed text of original set of documents based on a query. Documents can be viewed as graph with sentences as nodes and edges can be added based on sentence similarity. Graph based ranking algorithms which use 'Biased random surfer model' like topic-sensitive LexRank have been successfully applied to query focused summarization. In these algorithms, random walk will be biased towards the sentences which contain query relevant words. Specifically, it is assumed that random surfer knows the query relevance score of the sentence to where he jumps. However, neighbourhood information of the sentence to where he jumps is completely ignored. In this paper, we propose look-ahead version of topic-sensitive LexRank. We assume that random surfer not only knows the query relevance of the sentence to where he jumps but he can also look N-step ahead from that sentence to find query relevance scores of future set of sentences. Using this look ahead information, we figure out the sentences which are indirectly related to the query by looking at number of hops to reach a sentence which has query relevant words. Then we make the random walk biased towards even to the indirect query relevant sentences along with the sentences which have query relevant words. Experimental results show 20.2% increase in ROUGE-2 score compared to topic-sensitive LexRank on DUC 2007 data set. Further, our system outperforms best systems in DUC 2006 and results are comparable to state of the art systems.

PocketMatch (version 2.0): A parallel algorithm for the detection of structural similarities between protein ligand binding-sites

Knowledge of protein-ligand interactions is essential to understand several biological processes and important for applications ranging from understanding protein function to drug discovery and protein engineering. Here, we describe an algorithm for the comparison of three-dimensional ligand-binding sites in protein structures. A previously described algorithm, PocketMatch (version 1.0) is optimised, expanded, and MPI-enabled for parallel execution. PocketMatch (version 2.0) rapidly quantifies binding-site similarity based on structural descriptors such as residue nature and interatomic distances. Atomic-scale alignments may also be obtained from amino acid residue pairings generated. It allows an end-user to compute database-wide, all-to-all comparisons in a matter of hours. The use of our algorithm on a sample dataset, performance-analysis, and annotated source code is also included.

Development and Evaluation of Statistical Downscaling Models for Monthly Precipitation

Several statistical downscaling models have been developed in the past couple of decades to assess the hydrologic impacts of climate change by projecting the station-scale hydrological variables from large-scale atmospheric variables simulated by general circulation models (GCMs). This paper presents and compares different statistical downscaling models that use multiple linear regression (MLR), positive coefficient regression (PCR), stepwise regression (SR), and support vector machine (SVM) techniques for estimating monthly rainfall amounts in the state of Florida. Mean sea level pressure, air temperature, geopotential height, specific humidity, U wind, and V wind are used as the explanatory variables/predictors in the downscaling models. Data for these variables are obtained from the National Centers for Environmental Prediction-National Center for Atmospheric Research (NCEP-NCAR) reanalysis dataset and the Canadian Centre for Climate Modelling and Analysis (CCCma) Coupled Global Climate Model, version 3 (CGCM3) GCM simulations. The principal component analysis (PCA) and fuzzy c-means clustering method (FCM) are used as part of downscaling model to reduce the dimensionality of the dataset and identify the clusters in the data, respectively. Evaluation of the performances of the models using different error and statistical measures indicates that the SVM-based model performed better than all the other models in reproducing most monthly rainfall statistics at 18 sites. Output from the third-generation CGCM3 GCM for the A1B scenario was used for future projections. For the projection period 2001-10, MLR was used to relate variables at the GCM and NCEP grid scales. Use of MLR in linking the predictor variables at the GCM and NCEP grid scales yielded better reproduction of monthly rainfall statistics at most of the stations (12 out of 18) compared to those by spatial interpolation technique used in earlier studies.

Influence of the upwelling events on the delta C-13 and delta O-18 of the benthic bivalve shells of the South Western Continental Margin of India

In this study, the influence of the spatial and temporal variability of upwelling intensity and the associated biological productivity observed during different phases of summer monsoon along the southwestern continental margin of India (SWCMI) on the delta C-13 and delta O-18 of the inorganic biogenic carbonate shells was investigated. Multispecies benthic bivalve shells (1-5 mm) separated from ten surface sediment samples of SWCMI (off 12 degrees N, 10 degrees N and 9 degrees N) collected during the onset (OSM) and peak (PSM) phase of the summer monsoon of 2009 were analysed for delta C-13 and delta O-18. Sea surface temperature along the study region indicates prominent upwelling in PSM than in OSM. A comparison of analytical and predicted values for delta O-18 in the bivalve shells confirmed their in situ origin during both the sampling periods. During PSM, the delta C-13 values in the benthic bivalve shells were more depleted in C-13 than during OSM which recorded lower values of delta C-13 in dissolved inorganic carbon of bottom waters expected in the study region in PSM due to the upwelled waters, high surface productivity and the associated high degradation of the organic matter in the subsurface and bottom waters. However, this depletion of delta C-13 was not observed in benthic bivalve shells obtained from 10 degrees N, since it is influenced by high export fluxes of carbon from the Cochin estuary since early monsoon months.

Productividad y concentración de nutrientes del Taiwán Cubano (Pennisetum purpureum X Pennisetum tiphoides), CT 115, en época lluviosa, 2010 en la Fincas Santa Rosa

Con el objetivo de evaluar la Productividad y concentración de nutrientes del pasto cubano (Pennisetum purpureum x Pennisetum typhoides) cv CT – 115, se llevó a cabo la presente investigación en la finca Santa Rosa propiedad de la Universidad Nacional Agraria (UNA) Managua, Nicaragua. Localizada geográficamente a los 12° 08´ 33"de latitud norte y, 86° 10´ 31" de longitud oeste (INETER, 2006). Para ello se utilizó un área total de 33 m2 la cual se subdividió en tres parcelas de 10 m2 cada una donde se realizaron cortes cada 15 días hasta llegar a los 75 días. Se evaluaron las variables : altura, (cm) biomasa fresca (kg ha-1), Materia Seca (%), Biomasa seca (kg ha-1), Nitrógeno (%), Fósforo (%), Potasio (%),Calcio (%), Magnesio (%), Hierro (ppm), Manganeso (ppm), Zinc (ppm). Para la determinación de la producción de biomasa verde y seca (kg ha-1), se utilizó la metodología propuesta por la Red Internacional de evaluación de Pasturas Tropicales (CIAT, 1982). Para determinar los parámetros MS (%) se utilizó la metodología del análisis de Weende o análisis proximal (AOAC. 1990). Para el análisis de correlación se utilizo el programa SAS VERSION 9 para cada uno de las variables evaluadas, para la determinación de las curvas de mejor ajuste se utilizó el programa CVXP32. Durante el ensayo no se aplico ningún tipo de tratamiento agronómico (fertilización, riego). Los resultados obtenidos fueron: Altura 220 cm Biomasa fresca 31,764 kg ha-1 Materia seca 24% Biomasa seca 7529 kg ha-1. Las mayores concentraciones de nutrientes en la planta fueron: N 3.21% P 0.38% K 4.94% Ca 0.24% Mg 0.18% Fe 105.0ppm Mn 53.33ppm Zn 50ppm. Los modelos de mejor ajuste son: Modelo Múltiple Multiplicativo, Modelo Richards, Modelo Harris, Función Rotacional, Tercer Grado Polinomial y Asociación Exponencial.

Efecto de diferentes dosis de fertilizantes de la fórmula 18-46-0 y densidades de siembra sobre el crecimiento y rendimiento del frijol común (Phaseolus vulgaris) y la dinámica de las malezas

El presente experimento fue realizado en la Estación Experimental La Compañía, San Marcos, departamento de Carazo, durante la época de postrera del año 1991 con el fin de evaluar el efecto de diferentes dosis de fertilizante y densidades de siembra sobre la cenosis de las malezas, el crecimiento y rendimiento del frijol común. Los tratamientos, consistieron en combinar tres dosis de fertilizante de la fórmula 1846-0 (Testigo, 1 y 2 qq/mz de fertilizante) con tres densidades de siembra (15, 30 y 45 semillas/m2). Los resultados obtenidos en este trabajó muestran que bajo las condiciones en las que fue realizado el experimento, la aplicación de 2 qq/mz del fertilizante y una densidad de siembra de 45 semillas/m2, produjo la menor abundancia y cobertura de malezas. A dosis de 1 qq/mz y densidad de 30 semillas/m2 se obtuvo el menor peso seco de malezas. Durante el ciclo del cultivo la mayor diversidad de especies se registró en la clase monocotiledónea. En cuanto al cultivo, aun cuando se observó una ligera tendencia a disminuir el rendimiento a medida que aumentó la dosis de fertilizante aplicada no hubo diferencias. En el caso de las densidades, se obtuvo el mayor número de ramas y vainas con 15 semillas/m2 y el mayor número de plantas, peso de mil granos y rendimiento con 45 semillas/m2, aunque en todos los casos las diferencias fueron mínimas.

A New Version of Smoothed Point Method to Simulate Linear Elastic Wave Propagation

By using the kernel function of the smoothed particle hydrodynamics (SPH) and modification of statistical volumes of the boundary points and their kernel functions, a new version of smoothed point method is established for simulating elastic waves in solid. With the simplicity of SPH kept, the method is easy to handle stress boundary conditions, especially for the transmitting boundary condition. A result improving by de-convolution is also proposed to achieve high accuracy under a relatively large smooth length. A numerical example is given and compared favorably with the analytical solution.

La traducción de la Divina Comedia de Villegas: problemas de datación y filiación de testimonios

Resumen: En 1515 se difunde en Burgos la primera traducción impresa de la Divina Comedia, a cargo de Pedro Fernández de Villegas, traducción bastante olvidada y poco estudiada por la crítica. El único manuscrito que se conserva (ms. B2183 de la Hispanic Society of America) es, según la descripción de Dutton (1982: 4659), autógrafo, conclusión a la que llega basándose en la reiteración de la tapa. Faulhaber (1983: 516-18), por su parte, data al manuscrito a fines del XV y asume que fue el texto fuente usado por la imprenta en 1515. Los datos otorgados por estos estudiosos han sido poco problematizados, tal vez por la falta de un estudio minucioso que aborde el manuscrito y sus problemas ecdóticos. En el presente trabajo intentaremos, por un lado, redefinir el terminus a quo de la traducción, basándonos en el estudio del contexto histórico de producción y en alusiones del mismo prólogo y de ciertos pasajes del comentario que, en el impreso, se encuentra envolviendo cada copla traducida. Por otro lado, a partir del cotejo entre los versos del manuscrito y el impreso, enfocándonos especialmente en los versos que aparecen enmendados en el primero, intentaremos problematizar la relación de filiación que se ha dado por sentada entre las dos versiones. A manera de adelanto, podríamos decir, por un lado, que la traducción no se podría haber empezado antes de 1502 y, por el otro, que el texto que nos transmite el manuscrito correspondería a una segunda etapa en el proceso de traducción, posterior a la del texto que nos transmite el impreso