Modelling multiple disulphide loop containing polypeptides by random conformation generation. The test cases of α-conotoxin GI and edothelin I

A general procedure for arriving at 3-D models of disulphiderich olypeptide systems based on the covalent cross-link constraints has been developed. The procedure, which has been coded as a computer program, RANMOD, assigns a large number of random, permitted backbone conformations to the polypeptide and identifies stereochemically acceptable structures as plausible models based on strainless disulphide bridge modelling. Disulphide bond modelling is performed using the procedure MODIP developed earlier, in connection with the choice of suitable sites where disulphide bonds could be engineered in proteins (Sowdhamini,R., Srinivasan,N., Shoichet,B., Santi,D.V., Ramakrishnan,C. and Balaram,P. (1989) Protein Engng, 3, 95-103). The method RANMOD has been tested on small disulphide loops and the structures compared against preferred backbone conformations derived from an analysis of putative disulphide subdatabase and model calculations. RANMOD has been applied to disulphiderich peptides and found to give rise to several stereochemically acceptable structures. The results obtained on the modelling of two test cases, a-conotoxin GI and endothelin I, are presented. Available NMR data suggest that such small systems exhibit conformational heterogeneity in solution. Hence, this approach for obtaining several distinct models is particularly attractive for the study of conformational excursions.

Variations in the copper(I)-copper(I) distances in multinuclear clusters with identical coordination geometries. Short metal-metal contacts induced by oligomerization

Factors contributing to the variations in the Cu(I)-Cu(I) distances in two clusters with identical ligand and coordination geometries have been analyzed. While the hexamer, 4, exhibits metal-metal distances in the range 2.81-3.25 Angstrom, shorter contacts are found in the corresponding tetramer, 3 (2.60-2.77 Angstrom). EHT calculations reveal relatively little attractive interactions in the corresponding Cu-4(4+) and Cu-6(6+) cores. Introduction of the ligands lowers the reduced overlap populations between the metals further. MNDO calculations with model electrophiles have been carried out to determine the bite angle requirements of the ligands. These are satisfactorily met in the structures of both 3 and 4. The key geometric feature distinguishing 3 and 4 is the Cu-S-Cu angle involving the bridging S- unit. In 4, the corresponding angles are about 90 degrees, while the values in 3 are smaller (70-73 degrees). Wider angles are computed to be energetically favored and are characterized by an open three-center bond and a long Cu-Cu distance. The bridging angles are suggested to be primarily constrained by the mode of oligomerization. Implications of these results for the stability and reactivity of these clusters and for short metal-metal distances in d(10) systems in general are discussed.

The Shannon Cipher System With a Guessing Wiretapper: General Sources

The Shannon cipher system is studied in the context of general sources using a notion of computational secrecy introduced by Merhav and Arikan. Bounds are derived on limiting exponents of guessing moments for general sources. The bounds are shown to be tight for i.i.d., Markov, and unifilar sources, thus recovering some known results. A close relationship between error exponents and correct decoding exponents for fixed rate source compression on the one hand and exponents for guessing moments on the other hand is established.

Lipid conformational nomenclature: a general method

We propose a conformational nomenclature for amphiphilic lipid molecules that is general and compatible with the stereospecific numbering scheme, in contrast to earlier methods in which discrepancies with the sn-scheme lead to contradictory assignments of the absolute configuration of the system. The present method can be rationally extended to different classes of lipids, both natural and synthetic. It is simple and provides a convenient framework for conformational studies on widely varying classes of lipids.

Temperature profiles of accretion discs around rapidly rotating strange stars in general relativity: A comparison with neutron stars

We compute the temperature profiles of accretion discs around rapidly rotating strange stars, using constant gravitational mass equilibrium sequences of these objects, considering the full effect of general relativity. Beyond a certain critical value of stellar angular momentum (J), we observe the radius ( $r_{\rm orb}$) of the innermost stable circular orbit (ISCO) to increase with J (a property seen neither in rotating black holes nor in rotating neutron stars). The reason for this is traced to the crucial dependence of ${\rm d}r_{\rm orb}/{\rm d}J$ on the rate of change of the radial gradient of the Keplerian angular velocity at $r_{\rm orb}$ with respect to J. The structure parameters and temperature profiles obtained are compared with those of neutron stars, as an attempt to provide signatures for distinguishing between the two. We show that when the full gamut of strange star equation of state models, with varying degrees of stiffness are considered, there exists a substantial overlap in properties of both neutron stars and strange stars. However, applying accretion disc model constraints to rule out stiff strange star equation of state models, we notice that neutron stars and strange stars exclusively occupy certain parameter spaces. This result implies the possibility of distinguishing these objects from each other by sensitive observations through future X-ray detectors.

Monsoon Regimes and Processes in CCSM4. Part I: The Asian-Australian Monsoon

The simulation characteristics of the Asian-Australian monsoon are documented for the Community Climate System Model, version 4 (CCSM4). This is the first part of a two part series examining monsoon regimes in the global tropics in the CCSM4. Comparisons are made to an Atmospheric Model Intercomparison Project (AMIP) simulation of the atmospheric component in CCSM4 Community Atmosphere Model, version 4, (CAM4)] to deduce differences in the monsoon simulations run with observed sea surface temperatures (SSTs) and with ocean-atmosphere coupling. These simulations are also compared to a previous version of the model (CCSM3) to evaluate progress. In general, monsoon rainfall is too heavy in the uncoupled AMIP run with CAM4, and monsoon rainfall amounts are generally better simulated with ocean coupling in CCSM4. Most aspects of the Asian-Australian monsoon simulations are improved in CCSM4 compared to CCSM3. There is a reduction of the systematic error of rainfall over the tropical Indian Ocean for the South Asian monsoon, and well-simulated connections between SSTs in the Bay of Bengal and regional South Asian monsoon precipitation. The pattern of rainfall in the Australian monsoon is closer to observations in part because of contributions from the improvements of the Indonesian Throughflow and diapycnal diffusion in CCSM4. Intraseasonal variability of the Asian-Australian monsoon is much improved in CCSM4 compared to CCSM3 both in terms of eastward and northward propagation characteristics, though it is still somewhat weaker than observed. An improved simulation of El Nino in CCSM4 contributes to more realistic connections between the Asian-Australian monsoon and El Nino-Southern Oscillation (ENSO), though there is considerable decadal and century time scale variability of the strength of the monsoon-ENSO connection.

A general methodology for calculating mixed mode stress intensity factors and fracture toughness of solder joints with interfacial cracks

Solder joints in electronic packages undergo thermo-mechanical cycling, resulting in nucleation of micro-cracks, especially at the solder/bond-pad interface, which may lead to fracture of the joints. The fracture toughness of a solder joint depends on material properties, process conditions and service history, as well as strain rate and mode-mixity. This paper reports on a methodology for determining the mixed-mode fracture toughness of solder joints with an interfacial starter-crack, using a modified compact mixed mode (CMM) specimen containing an adhesive joint. Expressions for stress intensity factor (K) and strain energy release rate (G) are developed, using a combination of experiments and finite element (FE) analysis. In this methodology, crack length dependent geometry factors to convert for the modified CMM sample are first obtained via the crack-tip opening displacement (CTOD)-based linear extrapolation method to calculate the under far-field mode I and II conditions (f(1a) and f(2a)), (ii) generation of a master-plot to determine a(c), and (iii) computation of K and G to analyze the fracture behavior of joints. The developed methodology was verified using J-integral calculations, and was also used to calculate experimental fracture toughness values of a few lead-free solder-Cu joints. (C) 2014 Elsevier Ltd. All rights reserved.

Targeting Mycobacterium tuberculosis Topoisomerase I by Small-Molecule Inhibitors

We describe inhibition of Mycobacterium tuberculosis topoisomerase I (MttopoI), an essential mycobacterial enzyme, by two related compounds, imipramine and norclomipramine, of which imipramine is clinically used as an antidepressant. These molecules showed growth inhibition of both Mycobacterium smegmatis and Mycobacterium tuberculosis cells. The mechanism of action of these two molecules was investigated by analyzing the individual steps of the topoisomerase I (topoI) reaction cycle. The compounds stimulated cleavage, thereby perturbing the cleavage-religation equilibrium. Consequently, these molecules inhibited the growth of the cells overexpressing topoI at a low MIC. Docking of the molecules on the MttopoI model suggested that they bind near the metal binding site of the enzyme. The DNA relaxation activity of the metal binding mutants harboring mutations in the DxDxE motif was differentially affected by the molecules, suggesting that the metal coordinating residues contribute to the interaction of the enzyme with the drug. Taken together, the results highlight the potential of these small molecules, which poison the Mycobacterium tuberculosis and Mycobacterium smegmatis topoisomerase I, as leads for the development of improved molecules to combat mycobacterial infections. Moreover, targeting metal coordination in topoisomerases might be a general strategy to develop new lead molecules.

Ranking general circulation models for India using TOPSIS

Eleven general circulation models/global climate models (GCMs) - BCCR-BCCM2.0, INGV-ECHAM4, GFDL2.0, GFDL2.1, GISS, IPSL-CM4, MIROC3, MRI-CGCM2, NCAR-PCMI, UKMO-HADCM3 and UKMO-HADGEM1 - are evaluated for Indian climate conditions using the performance indicator, skill score (SS). Two climate variables, temperature T (at three levels, i.e. 500, 700, 850 mb) and precipitation rate (Pr) are considered resulting in four SS-based evaluation criteria (T500, T700, T850, Pr). The multicriterion decision-making method, technique for order preference by similarity to an ideal solution, is applied to rank 11 GCMs. Efforts are made to rank GCMs for the Upper Malaprabha catchment and two river basins, namely, Krishna and Mahanadi (covered by 17 and 15 grids of size 2.5 degrees x 2.5 degrees, respectively). Similar efforts are also made for India (covered by 73 grid points of size 2.5 degrees x 2.5 degrees) for which an ensemble of GFDL2.0, INGV-ECHAM4, UKMO-HADCM3, MIROC3, BCCR-BCCM2.0 and GFDL2.1 is found to be suitable. It is concluded that the proposed methodology can be applied to similar situations with ease.

Reduction in DNA topoisomerase I level affects growth, phenotype and nucleoid architecture of Mycobacterium smegmatis

The steady-state negative supercoiling of eubacterial genomes is maintained by the action of DNA topoisomerases. Topoisomerase distribution varies in different species of mycobacteria. While Mycobacterium tuberculosis (Mtb) contains a single type I (Topol) and a single type II (Gyrase) enzyme, Mycobacterium smegmatis (Msm) and other members harbour additional relaxases. Topol is essential for Mtb survival. However, the necessity of Topol or other relaxases in Msm has not been investigated. To recognize the importance of Topol for growth, physiology and gene expression of Msm, we have developed a conditional knock-down strain of Topol in Msm. The Topol-depleted strain exhibited extremely slow growth and drastic changes in phenotypic characteristics. The cessation of growth indicates the essential requirement of the enzyme for the organism in spite of having additional DNA relaxation enzymes in the cell. Notably, the imbalance in Topol level led to the altered expression of topology modulatory proteins, resulting in a diffused nucleoid architecture. Proteomic and transcript analysis of the mutant indicated reduced expression of the genes involved in central metabolic pathways and core DNA transaction processes. RNA polymerase (RNAP) distribution on the transcription units was affected in the Topol-depleted cells, suggesting global alteration in transcription. The study thus highlights the essential requirement of Topol in the maintenance of cellular phenotype, growth characteristics and gene expression in mycobacteria. A decrease in Topol level led to altered RNAP occupancy and impaired transcription elongation, causing severe downstream effects.

General relativity and relativistic astrophysics

Einstein established the theory of general relativity and the corresponding field equation in 1915 and its vacuum solutions were obtained by Schwarzschild and Kerr for, respectively, static and rotating black holes, in 1916 and 1963, respectively. They are, however, still playing an indispensable role, even after 100 years of their original discovery, to explain high energy astrophysical phenomena. Application of the solutions of Einstein's equation to resolve astrophysical phenomena has formed an important branch, namely relativistic astrophysics. I devote this article to enlightening some of the current astrophysical problems based on general relativity. However, there seem to be some issues with regard to explaining certain astrophysical phenomena based on Einstein's theory alone. I show that Einstein's theory and its modified form, both are necessary to explain modern astrophysical processes, in particular, those related to compact objects.

General Solution to Two-Dimensional Nonslipping JKR Model with a Pulling Force in an Arbitrary Direction

In this paper, a generalized JKR model is investigated, in which an elastic cylinder adhesively contacts with an elastic half space and the contact region is assumed to be perfect bonding. An external pulling force is acted on the cylinder in an arbitrary direction. The contact area changes during the pull-off process, which can be predicted using the dynamic Griffith energy balance criterion as the contact edge shifts. Full coupled solution with an oscillatory singularity is obtained and analyzed by numerical calculations. The effect of Dundurs' parameter on the pull-off process is analyzed, which shows that a nonoscillatory solution can approximate the general one under some conditions, i.e., larger pulling angle (pi/2 is the maximum value), smaller a/R or larger nondimensional parameter value of Delta gamma/E*R. Relations among the contact half width, the external pulling force and the pulling angle are used to determine the pull-off force and pull-off contact half width explicitly. All the results in the present paper as basic solutions are helpful and applicable for experimenters and engineers.

Estudio para la rehabilitación y desarrollo de la pequeña ganadería de la zona seca Sur de la Región I, Nicaragua

El presente estudio se realizó con el objetivo de contribuir a impulsar un programa de rehabilitación y desarrollo sostenido de la pequeña ganadería a corto y mediano plazo en la zona seca sur de la Región l. El estudio estuvo integrado por seis componentes: la Caracterización Biofísica y Socio Económica de la Zona, la Situación de la Ganadería en Nicaragua, la Situación de la Ganadería en la Región 1, Caracterización de la Pequeña Ganadería, Conclusiones y el Plan de Acciones. La información necesaria para el estudio fue obtenida a través de datos primarios (Observación de Campo) y apoyada por la elaboración de una ficha de entrevista, la información secundaria fue obtenida a través de revisión bibliográfica y consultas con Personal de Instituciones como BND, MED, MAG, Casas Comerciales, etc. Los resultados del estudio se consolidaron y analizaron estadísticamente; finalmente se presentaron conclusiones y limitantes encontradas, así como las recomendaciones tendientes a superar los problemas encontrados. En general la situación de la pequeña ganadería en la zona seca evidencian un potencial deterioro; sus índices técnicos, el bajo nivel tecnológico adoptado y la baja rentabilidad encontrada refuerzan esta aseveración. Concluyéndose que existe una diversidad de prácticas las que no tienen ningún fundamento técnico; que el subsistema pecuario es susceptible de considerables mejoras a pesar de su ingreso neto favorable; que existe la necesidad de organizar a los productores para mejorar la comercialización de sus productos. Basados en la realidad se planteó un plan de acciones el cual se diseñó en función de cumplir con los objetivos de: Realizar un reordenamiento de los recursos de la finca para aprovechar al máximo las interacciones de los subsistemas, Maximizar el uso de los recursos de la finca y el proceso de producción. Se diseñó un plan de manejo sanitario, reproductivo y de alimentación bovina, así como las medidas de acompañamiento para la introducción de vientres y sementales, las que se relacionan con la raza de animales a introducir, zonas de intervención, capacitación y mecanismos de divulgación tecnológica.

Finite Element Solutions for Plane Strain Mode I Crack with Strain Grading Effect

In this paper, a new phenomenological theory with strain gradient effects is proposed to account for the size dependence of plastic deformation at micro- and submicro-length scales. The theory fits within the framework of general couple stress theory and three rotational degrees of freedom omega(i) are introduced in addition to the conventional three translational degrees of freedom mu(i). omega(i) is called micro-rotation and is the sum of material rotation plus the particles' relative rotation. While the new theory is used to analyze the crack tip field or the indentation problems, the stretch gradient is considered through a new hardening law. The key features of the theory are that the rotation gradient influences the material character through the interaction between the Cauchy stresses and the couple stresses; the term of stretch gradient is represented as an internal variable to increase the tangent modulus. In fact the present new strain gradient theory is the combination of the strain gradient theory proposed by Chen and Wang (Int. J. Plast., in press) and the hardening law given by Chen and Wang (Acta Mater. 48 (2000a) 3997). In this paper we focus on the finite element method to investigate material fracture for an elastic-power law hardening solid. With remotely imposed classical K fields, the full field solutions are obtained numerically. It is found that the size of the strain gradient dominance zone is characterized by the intrinsic material length l(1). Outside the strain gradient dominance zone, the computed stress field tends to be a classical plasticity field and then K field. The singularity of stresses ahead of the crack tip is higher than that of the classical field and tends to the square root singularity, which has important consequences for crack growth in materials by decohesion at the atomic scale. (C) 2002 Elsevier Science Ltd. All rights reserved.

Estrategias discursivas y proverbios en la poesía del Marqués de Santillana recopilada en el Cancionero General de 1511

Integran este número de la revista ponencias presentadas en Studia Hispanica Medievalia VIII : Actas de las X Jornadas Internacionales de Literatura Española Medieval, 2011, y de Homenaje al Quinto Centenario del Cancionero General de Hernando del Castillo.