Draft Genome Sequence of Staphylococcus aureus ST672, an Emerging Disease Clone from India

We report the draft genome sequence of methicillin-resistant Staphylococcus aureus (MRSA) strain ST672, an emerging disease clone in India, from a septicemia patient. The genome size is about 2.82 Mb with 2,485 open reading frames (ORFs). The staphylococcal cassette chromosome mec (SCCmec) element (type V) and immune evasion cluster appear to be different from those of strain ST772 on preliminary examination.

Dynamics of the North American continent

The forces that cause deformation of western North America have been debated for decades. Recent studies, primarily based on analysis of crustal stresses in the western United States, have suggested that the deformation of the region is mainly controlled by gravitational potential energy (GPE) variations and boundary loads, with basal tractions due to mantle flow playing a relatively minor role. We address these issues by modelling the deviatoric stress field over western North America from a 3-D finite element mantle circulation model with lateral viscosity variations. Our approach takes into account the contribution from both topography and shallow lithosphere structure (GPE) as well as that from deeper mantle flow in one single model, as opposed to separate lithosphere and circulation models, as has been done so far. In addition to predicting the deviatoric stresses we also jointly fit the constraints of geoid, dynamic topography and plate motion both globally and over North America, in order to ensure that the forces that arise in our models are dynamically consistent. We examine the sensitivity of the dynamic models to different lateral viscosity variations. We find that circulation models that include upper mantle slabs yield a better fit to observed plate velocities. Our results indicate that a model of GPE variations coupled with mantle convection gives the best fit to the observational constraints. We argue that although GPE variations control a large part of the deformation of the western United States, deeper mantle tractions also play a significant role. The average deviatoric stress magnitudes in the western United States range 30-40 MPa. The cratonic region exhibits higher coupling to mantle flow than the rest of the continent. We find that a relatively strong San Andreas fault gives a better fit to the observational constraints, especially that of plate velocity in western North America.

Corporate social responsibilities of Indian public sector enterprises-a case study of Bharat Heavy Electricals Limited (BHEL)

The high level of public accountability attached to Public Sector Enterprises as a result of public ownership makes them socially responsible. The Committee of Public Undertakings in 1992 examined the issue relating to social obligations of Central Public Sector Enterprises and observed that ``being part of the `State', every Public Sector enterprise has a moral responsibility to play an active role in discharging the social obligations endowed on a welfare state, subject to the financial health of the enterprise''. It issued the Corporate Social Responsibility Guidelines in 2010 where all Central Public Enterprises, through a Board Resolution, are mandated to create a CSR budget as a specified percentage of net profit of the previous year. This paper examines the CSR activities of the biggest engineering public sector organization in India, Bharath Heavy Electricals Limited. The objectives are twofold, one, to develop a case study of the organization about the funds allocated and utilized for various CSR activities, and two, to examine its status with regard to other organizations, the 2010 guidelines, and the local socio-economic development. Secondary data analysis results show three interesting trends. One, it reveals increasing organizational social orientation with the formal guidelines in place. Two, Firms can no longer continue to exploit environmental resources and escape from their responsibilities by acting separate entities regardless of the interest of the society and Three the thrust of CSR in public sector is on inclusive growth, sustainable development and capacity building with due attention to the socio-economic needs of the neglected and marginalized sections of the society.

Simultaneous attitude control and trajectory tracking of a micro quadrotor: a SNAC aided nonlinear dynamic inversion approach

This paper presents an advanced single network adaptive critic (SNAC) aided nonlinear dynamic inversion (NDI) approach for simultaneous attitude control and trajectory tracking of a micro-quadrotor. Control of micro-quadrotors is a challenging problem due to its small size, strong coupling in pitch-yaw-roll and aerodynamic effects that often need to be ignored in the control design process to avoid mathematical complexities. In the proposed SNAC aided NDI approach, the gains of the dynamic inversion design are selected in such a way that the resulting controller behaves closely to a pre-synthesized SNAC controller for the output regulation problem. However, since SNAC is based on optimal control theory, it makes the dynamic inversion controller to operate near optimal and enhances its robustness property as well. More important, it retains two major benefits of dynamic inversion: (i) closed form expression of the controller and (ii) easy scalability to command tracking application even without any apriori knowledge of the reference command. Effectiveness of the proposed controller is demonstrated from six degree-of-freedom simulation studies of a micro-quadrotor. It has also been observed that the proposed SNAC aided NDI approach is more robust to modeling inaccuracies, as compared to the NDI controller designed independently from time domain specifications.

Enhancement in creep resistance of Ti-6Al-4V alloy due to boron addition

The addition of B, up to about 0.1 wt%, to Ti-6Al-4V (Ti64) reduces its as-cast grain and colony sizes by an order of magnitude. In this paper, the creep resistance of this alloy modified with 0.06 and 0.11 wt% B additions was investigated in the temperature range of 475-550 degrees C and compared with that of the base alloy. Conventional dead-weight creep tests as well as stress relaxation tests were employed for this purpose. Experimental results show that the B addition enhances both elevated temperature strength and creep properties of Ti64, especially at the lower end of the temperatures investigated. The steady state creep rate in the alloy with 0.11 wt% B was found to be an order of magnitude lower than that in the base alloy, and both the strain at failure as well as the time for rupture increases with the B content. These marked improvements in the creep resistance due to B addition to Ti64 were attributed primarily to the increased number of inter-phase interfaces - a direct consequence of the microstructural refinement that occurs with the B addition - that provide resistance to dislocation motion. (C) 2014 Elsevier B.V. All rights reserved.

The HORMA domain: an evolutionarily conserved domain discovered in chromatin-associated proteins, has unanticipated diverse functions

The HORMA domain (for Hop1p, Rev7p and MAD2) was discovered in three chromatin-associated proteins in the budding yeast Saccharomyces cerevisiae. This domain has also been found in proteins with similar functions in organisms including plants, animals and nematodes. The HORMA domain containing proteins are thought to function as adaptors for meiotic checkpoint protein signaling and in the regulation of meiotic recombination. Surprisingly, new work has disclosed completely unanticipated and diverse functions for the HORMA domain containing proteins. A. M. Villeneuve and colleagues (Schvarzstein et al., 2013) show that meiosis-specific HORMA domain containing proteins plays a vital role in preventing centriole disengagement during Caenorhabditis elegans spermatocyte meiosis. Another recent study reveals that S. cerevisiae Atg13 HORMA domain acts as a phosphorylation-dependent conformational switch in the cellular autophagic process. (C) 2014 Elsevier B.V. All rights reserved.

Salts of hexamethylenetetramine with organic acids: Enhanced anomeric interactions with a lowering of molecular symmetry revealed by crystal structures

The hexamethylenetetramine (HMT) framework displays interesting stereoelectronic interactions of the anomeric type. In the highly symmetrical parent system, the nitrogen centres act as both donors and acceptors. Protonation lowers symmetry and also leads to an enhancement of the anomeric interaction around the protonated centre. X-ray diffraction crystal structures of four derivatives of HMT - with succinic, (DL)-malic, phthalic and 4-hydroxybenzoic acids - reveal significant trends. (The first three form well-defined salts, 4-hydroxybenzoic acid forming a co-crystalline compound.) Each molecular structure is essentially characterised by a major anomeric interaction involving the protonated centre as acceptor. In two cases (succinic and 4-hydroxybenzoic), secondary protonation leads to a weaker anomeric interaction site that apparently competes with the dominant one. Bond length changes indicate that the anomeric interaction decreases as malic > phthalic > succinic > 4-hydroxybenzoic, which correlates with the degree of proton transfer to the nitrogen centre. Along with other bond length and angle changes, the results offer insight into the applicability of the antiperiplanar lone pair hypothesis (ALPH) in a rigid system. (C) 2014 Elsevier B.V. All rights reserved.

Salts of hexamethylenetetramine with organic acids: Enhanced anomeric interactions with a lowering of molecular symmetry revealed by crystal structures

The hexamethylenetetramine (HMT) framework displays interesting stereoelectronic interactions of the anomeric type. In the highly symmetrical parent system, the nitrogen centres act as both donors and acceptors. Protonation lowers symmetry and also leads to an enhancement of the anomeric interaction around the protonated centre. X-ray diffraction crystal structures of four derivatives of HMT - with succinic, (DL)-malic, phthalic and 4-hydroxybenzoic acids - reveal significant trends. (The first three form well-defined salts, 4-hydroxybenzoic acid forming a co-crystalline compound.) Each molecular structure is essentially characterised by a major anomeric interaction involving the protonated centre as acceptor. In two cases (succinic and 4-hydroxybenzoic), secondary protonation leads to a weaker anomeric interaction site that apparently competes with the dominant one. Bond length changes indicate that the anomeric interaction decreases as malic > phthalic > succinic > 4-hydroxybenzoic, which correlates with the degree of proton transfer to the nitrogen centre. Along with other bond length and angle changes, the results offer insight into the applicability of the antiperiplanar lone pair hypothesis (ALPH) in a rigid system. (C) 2014 Elsevier B.V. All rights reserved.

Individual and combined additions of calcium and antimony on microstructure and mechanical properties of squeeze-cast AZ91D magnesium alloy

The effects of combined additions of Ca and Sb on the microstructure and tensile properties of AZ91D alloy fabricated by squeeze-casting have been investigated. For comparison, the same has also been studied with and without individual additions of Ca and Sb. The results indicate that both individual and combined additions refine the grain size and beta-Mg17Al12 phase, which is more pronounced with combined additions. Besides alpha-Mg and beta-Mg17Al12 phases, a new reticular Al2Ca and rod-shaped Mg3Sb2 phases are formed following individual additions of Ca and Sb in the AZ91D alloy. With combined additions, an additional Ca2Sb phase is formed suppressing Mg3Sb2 phase. Additions of both Ca and Sb increase yield strength (YS) at both ambient and elevated temperatures up to 200 degrees C. However, both ductility and ultimate tensile strength (UTS) decrease first up to 150 degrees C and then increase at 200 degrees C. The increase in YS is attributed to the refinement of grain size, whereas, ductility and UTS are deteriorated by the presence of brittle Al2Ca, Mg3Sb2 and Ca2Sb phases. The best tensile properties are obtained in the AZXY9110 alloy owing to the presence of lesser amount of brittle Al2Ca and Ca2Sb phases resulted from the optimum content of 1.0Ca and 0.3Sb (wt%). The fracture surface of the tensile specimen tested at ambient temperature reveals cleavage failure that changes to quasi-cleavage at 200 degrees C. The squeeze-cast alloys exhibited better tensile properties as compared to that of the gravity-cast alloys nullifying the detrimental effects of Ca and/or Sb additions. (C) 2014 Elsevier B.V. All rights reserved.

WNT-Inflammasome Signaling Mediates NOD2-Induced Development of Acute Arthritis in Mice

In addition to its role in innate immunity, the intracellular pathogen sensor nucleotide-binding oligomerization domain 2 (NOD2) has been implicated in various inflammatory disorders, including the development of acute arthritis. However, the molecular mechanisms involved in the development of NOD2-responsive acute arthritis are not clear. In this study, we demonstrate that NOD2 signals to a cellular protein, Ly6/PLAUR domain-containing protein 6, in a receptor-interacting protein kinase 2-TGF-beta-activated kinase 1-independent manner to activate the WNT signaling cascade. Gain- or loss-of-function of the WNT signaling pathway in an in vivo experimental mouse arthritis model or in vitro systems established the role for WNT-responsive X-linked inhibitor of apoptosis during the development of acute arthritis. Importantly, WNT-stimulated X-linked inhibitor of apoptosis mediates the activation of inflammasomes. The subsequent caspase-1 activation and IL-1 beta secretion together contribute to the phenotypic character of the inflammatory condition of acute arthritis. Thus, identification of a role for WNT-mediated inflammasome activation during NOD2 stimulation serves as a paradigm to understand NOD2-associated inflammatory disorders and develop novel therapeutics.

Bioengineering of AAV2 Capsid at Specific Serine, Threonine, or Lysine Residues Improves Its Transduction Efficiency in Vitro and in Vivo

We hypothesized that the AAV2 vector is targeted for destruction in the cytoplasm by the host cellular kinase/ubiquitination/proteasomal machinery and that modification of their targets on AAV2 capsid may improve its transduction efficiency. In vitro analysis with pharmacological inhibitors of cellular serine/threonine kinases (protein kinase A, protein kinase C, casein kinase II) showed an increase (20-90%) on AAV2-mediated gene expression. The three-dimensional structure of AAV2 capsid was then analyzed to predict the sites of ubiquitination and phosphorylation. Three phosphodegrons, which are the phosphorylation sites recognized as degradation signals by ubiquitin ligases, were identified. Mutation targets comprising eight serine (S) or seven threonine (T) or nine lysine (K) residues were selected in and around phosphodegrons on the basis of their solvent accessibility, overlap with the receptor binding regions, overlap with interaction interfaces of capsid proteins, and their evolutionary conservation across AAV serotypes. AAV2-EGFP vectors with the wild-type (WT) capsid or mutant capsids (15 S/T -> alanine A] or 9 K -> arginine R] single mutant or 2 double K -> R mutants) were then evaluated in vitro. The transduction efficiencies of 11 S/T -> A and 7 K -> R vectors were significantly higher (similar to 63-90%) than the AAV2-WT vectors (similar to 30-40%). Further, hepatic gene transfer of these mutant vectors in vivo resulted in higher vector copy numbers (up to 4.9-fold) and transgene expression (up to 14-fold) than observed from the AAV2-WT vector. One of the mutant vectors, S489A, generated similar to 8-fold fewer antibodies that could be cross-neutralized by AAV2-WT. This study thus demonstrates the feasibility of the use of these novel AAV2 capsid mutant vectors in hepatic gene therapy.

An Eighteen Serum Cytokine Signature for Discriminating Glioma from Normal Healthy Individuals

Glioblastomas (GBM) are largely incurable as they diffusely infiltrate adjacent brain tissues and are difficult to diagnose at early stages. Biomarkers derived from serum, which can be obtained by minimally invasive procedures, may help in early diagnosis, prognosis and treatment monitoring. To develop a serum cytokine signature, we profiled 48 cytokines in sera derived from normal healthy individuals (n = 26) and different grades of glioma patients (n = 194). We divided the normal and grade IV glioma/GBM serum samples randomly into equal sized training and test sets. In the training set, the Prediction Analysis for Microarrays (PAM) identified a panel of 18 cytokines that could discriminate GBM sera fromnormal sera with maximum accuracy (95.40%) and minimum error (4.60%). The 18-cytokine signature obtained in the training set discriminated GBM sera from normal sera in the test set as well (accuracy 96.55%; error 3.45%). Interestingly, the 18-cytokine signature also differentiated grade II/Diffuse Astrocytoma (DA) and grade III/Anaplastic Astrocytoma (AA) sera from normal sera very efficiently (DA vs. normal-accuracy 96.00%, error 4.00%; AA vs. normal-accuracy 95.83%, error 4.17%). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using 18 cytokines resulted in the enrichment of two pathways, cytokine-cytokine receptor interaction and JAK-STAT pathways with high significance. Thus our study identified an 18-cytokine signature for distinguishing glioma sera fromnormal healthy individual sera and also demonstrated the importance of their differential abundance in glioma biology.

Designing Novel Sulphate-based Ceramic Materials as Insertion Host Compounds for Secondary Batteries

Rechargeable batteries have propelled the wireless revolution and automobiles market over the past 25 years. Developing better batteries with improved energy density demands unveiling of new cathode ceramic materials with suitable diffusion channels and open framework structure. In this pursuit of achieving higher energy density, one approach is to realize enhanced redox voltage of insertion of ceramic compounds. This can be accomplished by incorporating highly electronegative anions in the cathode ceramics. Building on this idea, recently various sulphate- based compounds have been reported as high voltage cathode materials. The current article highlights the use of sulphate (SO4) based cathodes to realize the highest ever Fe3+/Fe2+ redox potentials in Li-ion batteries (LiFeSO4F fluorosulphate: 3.9V vs Li/Li+) and Na-ion batteries (Na2Fe2(SO4)(3) polysulphate: 3.8V vs Na/Na+). These sulphate-based cathode ceramic compounds pave way for newer avenues to design better batteries for future applications.

Evaluación de los anabólicos de crecimiento implix, ganamax, ralgro en novillos (finalización) en el trópico seco de Nicaragua

Con el propósito de evaluar el efecto de tres promotores de crecimiento Implix, Ralqro, Ganamax y un qrupo Testiqo (4 tratamientos), sobre variables de rendimiento en novillos de repasto Criollos x Brahaman con niveles de encaste desconocido, en el trópico seco de Nicaragua (Nandaime) 20 novillos fueron distribuidos al azar, 5 novillos por tratamiento. El estudio tuvo una duración de 3 meses, tiempo en el cual los animales fueron Implantados con los anabólicos antes mencionados. Las variables estudiadas fueron ganancia media diaria (GMD), peso de la canal (PCC), peso a los 90 días (P90d). Los datos obtenidos para determinar estas variables fueron peso inicial, peso a los 15 días, peso final. Los datos obtenidos para determinar estas variables se sometieron a un análisis de varianza y luego a una separación de medios a través de la prueba de DUNCAN. Los tratamientos no tuvieron efecto (P>0.05) sobre la características física de la canal; sin embargo se obtuvo mayor porcentaje de carne maqra y menos grasa en los animales implantados. Los resultados de las variables en estudio presentaron los siguientes valores: Ganamax (T1)tuvo una GMD de 380 grs, peso a los 90 días 392 kq y rendimiento en canal caliente de 194 kq, sequido de Implix (T2l con GMD 360 grs, peso 90 días de 380 kq y rendimiento en canal caliente 189 kg, el tratamiento Ralqro (T3) tuvo un peso a los 90 días de 375 kq obteniendo un peso final igual que el tratamiento Testigo, GMD 260 grs para Ralgro y 300 grs para el tratamiento Testigo, un rendimiento en canal caliente 186 kq para e1 tratamiento Ralqro Y 185 kq para el tratamiento Testigo.