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This paper is an attempt to develop a prototype virtual union catalogue--SpaceCat--based on physical and virtual model that provides single-window real-time search system designed to display an up-to-date information of collections from the participating Indian Space Research Organization (ISRO) libraries, geographically distributed in India. To understand the working of a union catalogue, the Online Public Access Catalogue (OPAC) functionalities it offers, a feasibility study of the already existing OPACs of union catalogues worldwide was undertaken. This study showed that only a few union catalogues have functions of real-time item-level status of availability; placing holds, single sign-on, personal reading history, late fee calculation, and so on. The global giants in the domain of union catalogue such as WorldCat, Consortium of Online Public Access Catalogues (COPAC) are not providing desired OPAC functionalities in the end-user interfaces. This paper aims to solve this issue by using Integrated Library System--Discovery Interface (ILS--DI) as a standard protocol to interlink front-end search interface that library users interact with, and is often referred to as the 'Online Public Access Catalogue' or OPAC of a union catalogue with back-end of the Koha Integrated Library System (ILS) that is specifically for staff use. The prototype SpaceCat has been developed on the basis of Open Standards and Open Source (OSS) Software. The framework includes Koha ILS as data provider, Open Archives Initiative Protocol for Metadata Harvesting (OAI-PMH) as data harvesting protocol, VuFind as discovery layer, and ILS--DI-based multi-backend driver for generating OPAC functionalities in end-user interface including single sign-on option. The study suggests that the product can act as an information discovery and retrieval system to help end-users of entire ISRO community to quickly access the holdings' information from different geographically distributed ISRO institutes in a pin-pointed, an exhaustive, and an expeditious manner. [ABSTRACT FROM AUTHOR]

The recent demand for developing micro-pin Diamond grinding tools has gained tremendous importance in tool manufacturing industries. A successful development of these tools requires joining Diamond grits to carbide surface firmly. In this context, the present paper demonstrates the joining of Diamond grits to WC-cermet surface via brazing route using Ag-Cu-24.3In-3Ti active alloy (Incusil-ABA). All brazing experiments were conducted using a resistance type heating furnace under a highly controlled vacuum environment to eliminate contamination. Experimental findings of this investigation indicate that both brazing temperature and dwell time have significant influence on microstructure and other related properties of the alloy. Titanium present in the alloy was found to segregate towards Diamond-alloy interface. It was expected that such segregation would ensure a proper wetting by the alloy. However, the overall morphology of the brazed joint revealed that improper melting and poor wetting by alloy on cermet surface were two major challenges. The current study showcases that a careful control on brazing temperature and dwell time demonstrates a remarkable improvement in wetting characteristics and alloy morphology. It has been observed that a brazing temperature of 780 °C and dwell time of 15 min resulted in a good brazed joint morphology. The study also investigated the effect of said brazing temperature on grits physical characteristics using Raman spectroscopy. At the end, scratch test and wear characteristics of the filler are investigated in detail. The outcome of this investigation will be of immense interest to tool manufacturing industries associated with development of brazed micro-pin Diamond grinding tools using alloys having low melting point. [Display omitted] • Diamond has been successfully brazed to WC surface using Incusil-Active Braze Alloy containing 24.3 wt% In and 3 wt% Ti. • CuTi 2 and CuTi formed at brazing temperatures of 750 °C and 780 °C respectively affects the micro-hardness of the alloy. • With an increase in dwell time and brazing temperature, contact angle reduces. • Graphitization of Diamond is successfully prevented with the use of low melting point Incusil-Active Braze alloy. • Single grit scratch test confirmed that in none of the test conditions failure of the braze bond took place. [ABSTRACT FROM AUTHOR]

Snake bite is an occupational hazard in India and important preventable cause of acute kidney injury (AKI). This study was done to estimate the magnitude of snakebite-induced AKI (SAKI)who required renal replacement therapy, prognostic predictors, and final outcome, and to measure the oxidative and carbonyl stress (CS) level in SAKI patient who underwent hemodialysis (HD). All SAKI patients dialyzed between April 2010 and July 2011 in NRS Medical College were included. Demographical, clinical, and biochemical data were analyzed, and patients are followed to discharge or death. Oxidative and CS markers (advanced oxidation protein product [AOPP], advanced glycation end product, pentosidine, dityrosine, thioberbituricacid reactive substance, and methylglyoxal [MG]) were measured in 48 SAKI patient requiring HD. About 155 SAKI patients (M: F 2.2:1 ) received HD. Of them. The age was 36.2 (range 4-74) years. The most common site of the bite was lower limb (88.7%). Oliguria and bleeding manifestation were the common presentation. Hypotension was found in 52 (33.5%) cases, cellulitis and inflammation were found in about 63%. Mean creatinine was 4.56 ± 0.24 mg/dl. About 42 (27.1%) had disseminated intravascular coagulation (DIC). 36 (78.2%) had cellulites, 24 (52.2%) had hypotension or shock at initial presentation (P < 0.05), bleeding manifestation was found in 37 (80.4%), and 22 (47.8%) had DIC (P < 0.05). Forty-six (29.7%) patient died. DIC and hypotension/shock at initial presentation came out as an independent predictor of death. Among all markers measured for oxidative and CS (n = 48) AOPP and MG came out as an independent predictor (P < 0.05) of adverse outcome. Hypotension, DIC, AOPP, and MG were a poor prognostic marker in SAKI patients requiring dialysis. [ABSTRACT FROM AUTHOR]

Endogenous glucocorticoids are essential for mobilizing energy resources, restraining inflammatory responses and coordinating behavior to an immune challenge. Impaired glucocorticoid receptor (GR) function has been associated with impaired metabolic processes, enhanced inflammation and exaggerated sickness and depressive-like behaviors. To discern the molecular mechanisms underlying GR regulation of physiologic and behavioral responses to a systemic immune challenge, GRdim mice, in which absent GR dimerization leads to impaired GR-DNA-binding-dependent mechanisms but intact GR protein-protein interactions, were administered low-dose lipopolysaccharide (LPS). GRdim-LPS mice exhibited elevated and prolonged levels of plasma corticosterone (CORT), interleukin (IL)-6 and IL-10 (but not plasma tumor necrosis factor-α (TNFα)), enhanced early expression of brain TNFα, IL-1β and IL-6 mRNA levels, and impaired later central TNFα mRNA expression. Exaggerated sickness behavior (lethargy, piloerection, ptosis) in the GRdim-LPS mice was associated with increased early brain proinflammatory cytokine expression and late plasma CORT levels, but decreased late brain TNFα expression. GRdim-LPS mice also exhibited sustained locomotor impairment in the open field, body weight loss and metabolic alterations measured by indirect calorimetry, as well as impaired thermoregulation. Taken together, these data indicate that GR dimerization-dependent DNA-binding mechanisms differentially regulate systemic and central cytokine expression in a cytokine- and time-specific manner, and are essential for the proper regulation and recovery of multiple physiologic responses to low-dose endotoxin. Moreover, these results support the concept that GR protein-protein interactions are not sufficient for glucocorticoids to exert their full anti-inflammatory effects and suggest that glucocorticoid responses limited to GR monomer-mediated transcriptional effects could predispose individuals to prolonged behavioral and metabolic sequelae of an enhanced inflammatory state. [ABSTRACT FROM AUTHOR]

Status and distribution of different forms of sulphur from the surface (0. to 25 cm) sulphur and subsurface (25 to 50 cm) soils of 12 different established soil series of Entisols in West Bengal was studied. Regarding different forms of sulphur, the inorganic sulphate sulphur, organic and total sulphur seemed to vary from 8.4 ppm to 16 ppm, 108 to 286 ppm and 120 ppm to 300 ppm respectively. A general decreasing trend over the subsurface horizon was found in all the three forms (excepting Bamundanga, Khagrabari and Poshgarh series). The physicochemical properties of these soils showed almost the decreasing trend down the horizon The inorganic sulphate sulphur, the plant available sulphur was found to be medium to low in sulphur status. Taxonomic analysis of mean values of all the three forms of sulphur was performed for different soil series of Entisols originated under different agroecological conditions of West Bengal. [ABSTRACT FROM AUTHOR]

The spatio-temporal variability of Indian Summer Monsoon is well studied based on different types of rainfall data. However, very few attempts have been made to study the underlying role of clouds and its hydromeseors on Mon- soon Intrascasonal Oscillations. The northward propagating Monsoon Intraseasonal Oscillations and its characteristics remain a challenge for the numerical modelers even today. In view of this, we have set out to analyze the role of cloud hydrometeors and their linkage with northward propagating Monsoon Intraseasonal Oscillations. The science question that we intend to address here is whether the different phases of the cloud hydrumeteors show similar propagation characteristics as that of rainfall, and what are the relations of their phases with the convection centre using Tropical Rainfall Measuring Mission data. In answering the question, we have analyzed ten years of Tropical Rainfall Measuring Mission 2A12 hydrometeor data over Indian region. Our analyses show that the cloud water and cloud ice do show a large scale organization during the Indian Summer Monsoon regime of June-September, and systematically progress northward getting initiated over equatorial Indian Ocean. On further analyses, we found that cloud water actually leads the rainfall and cloud ice lags the rainfall. We have further demonstrated the process by analyzing dynamical parameters from Modern Era-Retrospective Analysis for Research and Applications. The presence of cloud water in the lower troposphere in the leading edge of rainfall indicates the lower level moistening and preconditioning of the convective instability due to enhanced moisture convergence. Subsequently, deep convection is triggered, which generates hydrometeor above freezing level and cloud ice in the upper troposphere. To quantify objectively the relation among cloud liquid water, cloud ice and rainfall, the lag correlation is computed with respect to convection center, where the above hypothesis is established that cloud liquid water leads the rainfall and cloud ice lag. This relation among hydrometeors may help the numerical modelers to incorporate such processes for capturing the characteristics of Monsoon Intraseasonal Oscillations. [ABSTRACT FROM AUTHOR]

Background and Purpose: Activation of cannabinoid CB(2) receptors protects against various forms of ischaemia-reperfusion (I/R) injury. Δ(8) -Tetrahydrocannabivarin (Δ(8) -THCV) is a synthetic analogue of the plant cannabinoid Δ(9) -tetrahydrocannabivarin, which exhibits anti-inflammatory effects in rodents involving activation of CB(2) receptors. Here, we assessed effects of Δ(8) -THCV and its metabolite 11-OH-Δ(8) -THCV on CB(2) receptors and against hepatic I/R injury.Experimental Approach: Effects in vitro were measured with human CB(2) receptors expressed in CHO cells. Hepatic I/R injury was assessed in mice with 1h ischaemia and 2, 6 or 24h reperfusion in vivo.Key Results: Displacement of [(3) H]CP55940 by Δ(8) -THCV or 11-OH-Δ(8) -THCV from specific binding sites in CHO cell membranes transfected with human CB(2) receptors (hCB(2) ) yielded K(i) values of 68.4 and 59.95 nM respectively. Δ(8) -THCV or 11-OH-Δ(8) -THCV inhibited forskolin-stimulated cAMP production by hCB(2) CHO cells (EC(50) = 12.95 and 14.3 nM respectively). Δ(8) -THCV, given before induction of I/R, attenuated hepatic injury (measured by serum alanine aminotransferase and aspartate aminotransferase levels), decreased tissue protein carbonyl adducts, 4-hydroxy-2-nonenal, the chemokines CCL3 and CXCL2,TNF-α, intercellular adhesion molecule 1 (CD54) mRNA levels, tissue neutrophil infiltration, caspase 3/7 activity and DNA fragmentation. Protective effects of Δ(8) -THCV against liver damage were still present when the compound was given at the beginning of reperfusion. Pretreatment with a CB(2) receptor antagonist attenuated the protective effects of Δ(8) -THCV, while a CB(1) antagonist tended to enhance it.Conclusions and Implications: Δ(8) -THCV activated CB(2) receptors in vitro, and decreased tissue injury and inflammation in vivo, associated with I/R partly via CB(2) receptor activation.Linked Articles: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. [ABSTRACT FROM AUTHOR]

In recent times ytterbium (Yb) doped fibre-based mode-locked master oscillator and power amplifier have attracted a great deal of interest because of their inherent advantages like flexibility, reliability, compactness, high power handling capability and diffraction limited output beam quality as compared to the solid-state counterpart. But, to successfully develope of high-power femtosecond oscillator-amplifier system based on Ybdoped fibre, an appropriate choice of the mode-locking regime and the amplifier geometry are required. Development of an all-fibre integrated high-power Yb-doped fibre oscillator-amplifier system in which the advantages of a fibre-based system can be fully exploited remained a challenge as it requires the careful optimization of dispersion, nonlinearity, gain and ASE contribution. In this article, femto-second pulse generation in Yb-doped fibre oscillator in different mode-locking regimes are reviewed and the details of development and characterization of an all-fibre, high-power, low-noise amplifier system seeded by an all-normal-dispersion mode-locked Yb-doped fibre laser oscillator is described. More than 10 W of average power is obtained from the fibre oscillator-amplifier system at a repetition rate of 43 MHz with diffraction-limited beam quality. Amplified pulses are de-chirped to sub-160 fs duration in a grating compressor. This is the first 10 W-level source of femtosecond pulses with completely fibre-integrated amplification comprised of commercially available components. [ABSTRACT FROM AUTHOR]

In an attempt to develop a better simulation of the climatology of monsoon precipitation in climate models, this paper investigates the impacts of different convective closures on systematic biases of an Indian monsoon precipitation climatology in a high-resolution regional climate model. For this purpose, the Weather Research Forecast (WRF) model is run at 45- and 15-km (two-way nested) resolution with three convective parameterization schemes, namely the Grell–Devenyi (GD), the Betts–Miller–Janjić (BMJ), and the Kain–Fritsch (KF), for the period 1 May–31 October 2001–07. The model is forced with the NCEP–NCAR reanalysis data as the initial and boundary conditions. The simulated June–September (JJAS) mean monsoon rainfall with the three convective schemes is compared with the observations. KF is found to have a high moist bias over the central and western coastal Indian region while GD shows the opposite. Among the three, BMJ is able to produce a reasonable mean monsoon pattern. In an attempt to get further insight into the seasonal bias and its evolution, the probability distribution function (PDF) of different rain-rate categories and their percentage contribution to the seasonal total are computed. BMJ and KF underestimate the observations for lighter rain rates and overestimate for rain-rate categories of more than 10 mm day−1. GD shows an overestimation for lighter rain and an underestimation of PDF for moderate categories. The seasonal patterns of evolution of PDF plots of three rain-rate categories are analyzed to determine whether the convective schemes show any systematic bias throughout the season or if they have problems during certain phases of the monsoon. This shows that the GD systematically overestimates the lighter rain rate and underestimates the moderate rain rate throughout the season, whereas BMJ and KF have problems in the initial stages. The heavy rain category is systematically overestimated by the KF compared to the other two. To further evaluate the proportionate contribution of each rain-rate bin to the total rain, the percentage contribution of each rain rate to the seasonal total is computed. Analyzing all the rain-rate simulations produced by the three schemes, it is found that KF has a moist bias and GD has a dry bias in the spatiotemporal distribution of the monsoon precipitation. Further, this paper investigates the causes behind the mean monsoon precipitation bias. It is shown that GD produces a model climate where the vertical velocity is less than that of the observations up to 500 hPa and the vertically integrated moist instability is also weaker. KF, on the other hand, shows a higher than the observed vertical velocity and a stronger moist instability. Along with this, the vertical profile of heating suggests a warmer middle level in the KF case and significantly reduced midlevel heating for GD. Thus, KF (GD) has produced a model atmosphere that has a stronger (weaker) convective instability to produce the observed bias in the model precipitation. BMJ is found to simulate a reasonable heating profile, along with the realistic moist instability and seasonal cycle of evaporation and condensation. Insight derived from the analysis is expected to help improve the convective parameterizations. [ABSTRACT FROM AUTHOR]

Background and Purpose: Vascular smooth muscle proliferation and migration triggered by inflammatory stimuli are involved in the development and progression of atherosclerosis and restenosis. Cannabinoids may modulate cell proliferation in various cell types through cannabinoid 2 (CB2) receptors. Here, we investigated the effects of CB2 receptor agonists on TNF-alpha-induced proliferation, migration and signal transduction in human coronary artery smooth muscle cells (HCASMCs).Experimental Approach: HCASMCs were stimulated with TNF-alpha. Smooth muscle proliferation was determined by the extent of BrdU incorporation and the migration was assayed by modified Boyden chamber. CB2 and/or CB1 receptor expressions were determined by immunofluorescence staining, western blotting, RT-PCR, real-time PCR and flow cytometry.Key Results: Low levels of CB2 and CB1 receptors were detectable in HCASMCs compared to the high levels of CB2 receptors expressed in THP-1 monocytes. TNF-alpha triggered up to approximately 80% increase (depending on the method used) in CB2 receptor mRNA and/or protein expression in HCASMCs, and induced Ras, p38 MAPK, ERK 1/2, SAPK/JNK and Akt activation, while increasing proliferation and migration. The CB2 agonists, JWH-133 and HU-308, dose-dependently attenuated these effects of TNF-alpha.Conclusions and Implications: Since the above-mentioned TNF-alpha-induced phenotypic changes are critical in the initiation and progression of atherosclerosis and restenosis, our findings suggest that CB2 agonists may offer a novel approach in the treatment of these pathologies by decreasing vascular smooth muscle proliferation and migration. [ABSTRACT FROM AUTHOR]

Abstract: This paper introduces an advanced recrystallization model, based on the principles of cellular automata. The model employs a scalable subgrid technique for efficient tracking of local variations during recrystallization and provides excellent statistics of grain size and texture after recrystallization. Grain boundary nucleation, transition band nucleation and particle-stimulated nucleation were incorporated in the model. This model can interface with other microstructural models, such as a deformation texture model, a dislocation density based flow stress model and a precipitation model. The sensitivity of the model with respect to minute changes of microstructure and microchemistry was tested. Finally, a through-process exercise was conducted to assess the performance of the model in multi-step simulations. [Copyright &y& Elsevier]

Spontaneous perirenal hematoma following ruptured microaneurysm is an unusual but serious complication of polyarteritis nodosa. We describe a young male who presented with spontaneous perirenal hematoma and was subsequently diagnosed to have polyarteritis nodosa. He was managed with immunosuppressive medications with no recurrence of symptoms. [ABSTRACT FROM AUTHOR]

The rare occurrence of human immunodeficiency virus (HIV) transmission through organ transplantation cannot override the huge impact that it has on the patient. We report a case of HIV transmission by renal transplantation in a 33-year-old housewife, who received a living related transplantation from her sister. Both the patient and her donor were negative by HIV antibody testing prior to transplantation, but were found to be infected in the ninth month after transplant. Further testing suggested that the donor was in the window period at the time of organ donation after having acquired the infection from her husband. [ABSTRACT FROM AUTHOR]

The article offers the views of the author regarding quality of higher education in India. The author mentions that for the attainment of autonomy by colleges it is important for faculty members to have academic and research achievements. The article provides a historical background of autonomous colleges in India. The methods of analyzing a hypothesis of autonomous college with the help of 100 colleges in the National Institutional Ranking Framework (NIRF) 2017 is offered.

The seasonal prediction skill of climate forecast system model with two different resolutions, namely T126 and T382, is studied using hindcast data. Using novel diagnostic tools such as total variation distance and two‐state Markov Chain analysis, it is shown that increasing the horizontal resolution of the model has minimal impact on the quality of seasonal prediction. The underlying rain distribution and associated transition probabilities are very similar in both model versions. The Markov chain analysis also provides critical clues about the issues associated with convective processes in the model. Both the models produce longer (shorter) wet (dry) spells compared to the observations. Models are trying to bring the atmosphere closer to convective quasi‐equilibrium, leading to a substantial departure from observed features. Although the conventional error metrics are helpful to assess the prediction skills, the new metrics used in the study provide further insights on possible pathways to improve model moist physics. Plain Language Summary: The state of the art in respect to the prediction of Indian summer monsoon uses coupled climate models. Models, in general, have a hard time producing an accurate forecast of seasonal mean monsoon. Serious effort is being put globally to improve the quality of the forecast. One of the simple and easy to comprehend approaches among the scientific community is to increase the model's horizontal resolution to improve the accuracy of the predictions. The present study indicates that this approach alone is not very useful as there is an only marginal improvement with an increase in the resolutions. Key Points: Novel metrics have been used to compare model hindcast at different horizontal resolutionsPrevious studies claiming an improved simulation of monsoon with higher resolutions climate forecast system model require further investigationOnly a marginal improvement is seen in the fidelity of the model with an increase in horizontal resolution [ABSTRACT FROM AUTHOR]

In the present study, we analyze the Climate Forecast System version 2 (CFSv2) model in three resolutions, T62, T126, and T382. We evaluated the performance of all three resolutions of CFSv2 in simulating the Monsoon Intraseasonal Oscillation (MISO) of the Indian summer monsoon (ISM) by analyzing a suite of dynamic and thermodynamic parameters. Results reveal a slower northward propagation of MISO in all models with the characteristic northwest–southeast tilted rain band missing over India. The anomalous moisture convergence and vorticity were collocated with the convection center instead of being northwards. This affected the northward propagation of MISO. The easterly shear to the north of the equator was better simulated by the coarser resolution models than CFS T382. The low level specific humidity showed improvement only in CFS T382 until ~15° N. The analyses of the vertical profiles of moisture and its relation to rainfall revealed that all CFSv2 resolutions had a lower level of moisture in the lower level (< 850 hPa) and a drier level above. This eventually hampered the growth of deep convection in the model. These model shortcomings indicate a possible need of improvement in moist process parameterization in the model in tune with the increase in resolution. [ABSTRACT FROM AUTHOR]

The article discusses a workshop on improvement in climate and weather models that was held from February 13-16, 2018, at Indian Institute of Tropical Meteorology, Pune.

Agricultural landscapes referred to as 'agro-ecosystems' provide both marketable and non-marketable ecosystem services. The ability of agro-ecosystems to provide ecosystem services is limited by the nature of production systems and production method. Promotion of input-intensive production systems results in short-term productivity gains along with long-term ecological and environmental losses. India's agriculture suffers from various ecological problems such as soil pollution, overexploitation of groundwater and loss of biodiversity. Policy measures aimed at improving agriculture should shift from a purely 'productivity enhancement' objective towards promotion of ecologically sustainable pro-environmental agricultural production (PAP) practices to realize the goal of 'productivity in perpetuity'. This article examines the feasibility of 'nudges and incentives' in payment for ecosystem services/agri-environmental schemes (PES/AES) type schemes in India which could be a possible policy solution. It could nudge farmers to PAP practices and would be fiscally feasible even for individual states to adopt in a federal system of governance. [ABSTRACT FROM AUTHOR]

We here report on studies of low temperature dynamic elastic properties of an amorphous ribbon of a FINEMET alloy, with and without magnetic field. Characterization with XRD and SEM showed that the sample was partially amorphous. Magnetization study showed the system as ferromagnetic and there was no transition in resistivity, anomalous peaks in sound velocity and internal friction measurements, with a small hysteresis and strong magnetic field dependence, were found in this temperature range. After analysing the data we concluded that it was magnetic in origin. This is reported for the first time in the FINEMET system. [ABSTRACT FROM AUTHOR]

An analysis of a 5-yr (from 1 January 2009 to 31 December 2013) free run of the superparameterized (SP) Climate Forecast System (CFS) version 2 (CFSv2) (SP-CFS), implemented for the first time at a spectral triangular truncation at wavenumber 62 (T62) atmospheric horizontal resolution, is presented. The SP-CFS simulations are evaluated against observations and traditional convection parameterized CFSv2 simulations at T62 resolution as well as at some higher resolutions. The metrics for evaluating the model performance are chosen in order to mainly address the improvement in systematic biases observed in the CFSv2 documented in earlier studies. While the primary focus of this work is on evaluating the improvement of the simulation of the Indian summer monsoon (ISM) by the SP-CFS model, some results are also presented within the context of the global climate. The SP-CFS significantly reduces the dry bias of precipitation over the Indian subcontinent and better captures the monsoon intraseasonal oscillation (MISO) modes. SP-CFS also improves the northward and eastward propagation of high- and low-frequency modes of ISM. Compared to CFSv2, the SP-CFS model simulates improved convectively coupled equatorial waves; better temperature structures both spatially and vertically, leading to a significantly improved relative distribution of variance for the synoptic disturbances and low-frequency tropical intraseasonal oscillations (ISOs). This analysis of the development of SP-CFS is particularly important as it shows promise for improving the cloud process representation through an SP framework and is able to improve the mean as well as intraseasonal characteristics of CFSv2 within the context of the ISM. [ABSTRACT FROM AUTHOR]

In the present study, the Weather Research and Forecasting (WRF) model was used to simulate the features associated with a severe thunderstorm over India while examining the sensitivity of the simulation to three microphysical (MP) schemes (WDM6, Thompson and Morrison). The model simulated results (e.g., surface temperature, relative humidity, pressure, reflectivity and rainfall) for all sensitivity experiments are compared with observations (e.g., AWS, TRMM and DWR). There are major differences in the simulations of the thunderstorm among the MP schemes. The Morrison scheme simulates CAPE, surface properties, wind speed, vertical velocity, reflectivity and precipitation reasonably well, compared to other MP schemes, though there are some uncertainties. Therefore, an attempt is made to improve the simulation through modifications in the Morrison scheme. Different heterogeneous ice nucleation formulations have been tested into the Morrison double-moment bulk cloud MP scheme. We hypothesize that the improvement in cloud ice generation and its subsequent influence in cloud microphysics and dynamics through latent heat release may eventually lead to an improvement in thunderstorm simulation. The results demonstrate that the modification in the microphysical scheme better reproduces CAPE, wind speed, maximum reflectivity, vertical velocity and cloud hydrometeors (ice and mixed-phase processes) than the default Morrison and other schemes and compared to observations. The modified MP-scheme produces greater latent heating due to deposition in the upper troposphere and gives rise to increased updraft. This seems to be one of the most responsible processes that enhance the intensity of the storm compared to existing microphysical schemes. This study therefore provides a framework for the improvement of thunderstorm simulation through the modification of the cloud ice parameterization of the model. [ABSTRACT FROM AUTHOR]

Glomerular diseases are an important cause of chronic renal failure in developing countries. The spectrum of diseases causing nephrotic syndrome is changing globally in the last few decades. The aim of this prospective study was to look at this spectrum at a tertiary care center in North India and to analyze the changing trends over the last five decades. Patients in the age group 18-60 years with nephrotic syndrome were consecutively included in the study. Renal biopsies were performed in all patients and were subjected to light microscopy, immunofluorescence (IF) and electron microscopy (EM). While the IF was performed in 78% of cases, EM was available in one-fourth of cases. During 2002-2007, 364 patients (60.2% males) were included in the study. The mean age was 31.5 years. Primary glomerular diseases accounted for 89% of cases while lupus nephritis was the most common secondary glomerular disease. Focal segmental glomerulosclerosis (FSGS) accounted for 30.6% of primary glomerular diseases making it the most common cause of nephrotic syndrome. It was followed by membranous glomerulonephritis (MGN) in 24.4%, mesangiocapillary glomerulonephritis in 17.9% and minimal change disease in 14.8%. In the age group >40 years, MGN was the most common lesion (32.5%) followed by FSGS (27.7%). Over the last five decades, there was a nearly five-fold increase in the incidence of FSGS, 3-fold increase in MGN and a 10-fold reduction in diffuse proliferative glomerulonephritis while there was no major change in incidence of other diseases. The biopsy diagnosis of FSGS has increased considerably in last few decades and it is now the most common cause of nephrotic syndrome in adults in North India. MGN is the most common lesion in patients over 40 years of age. [ABSTRACT FROM AUTHOR]

Aims: The objective of the paper is to study the role of partogram in the outcome of spontaneous labour in primigravidae at term with singleton pregnancy and vertex as the presenting part. Methods: This prospective observational study was carried out in the labour room of the department of Gynaecology and Obstetrics of Medical College & Hospital, Kolkata, over a period of one year i.e. from June 2011 to May 2012 after obtaining approval from the institutional ethical committee. Analysis of the progress of labour was done in five hundred women with the help of modified WHO partograph. The study population was divided into three groups. Group I had a total observed duration of active stage six hours or less and their cervicograph remained on or to the left of the alert line. Group II had total observed duration of active phase between more than six hours and less than ten hours and their cervicograph remained between the alert and action line. Group III, who had the duration of observed active phase more than 10 hours, had their cervicograph crossing the action line. The different types of abnormal labor were studied. The maternal and fetal outcomes were assessed. Results: 80.8% of the women belonged to group I, 15.2% to group II and 4% to group III. Surgical interference increased as the labour curve moved to the right of the alert line. Use of partogram helped in overall reduction in the duration of labour. Timely intervention reduced the incidence of prolonged labour and its sequelae. 19.2% of the women showed abnormal labour. Severe complications were successfully averted. There were no cases of maternal death, puerperal sepsis, ruptured uterus or fresh still births. Overall neonatal mortality rate was also reduced. Conclusions: The use of modified WHO partograph significantly improves the outcome of labour in both maternal & neonatal perspective. The WHO partograph should be used in all maternity units with incorporated management guidelines. [ABSTRACT FROM AUTHOR]

Elastic modulus is the core of mechanical spectroscopy to study the actuation-based performance, lifetime, reliability, and stability of pure metals as well as alloys. In this investigation, a prototype system has been discussed for measuring the elastic properties of pure metals such as Cu (99.99%), Al (99.99%), and Ni (99.99%) using electrostatic force. The samples were processed by cold rolling producing specimens of 10–100 microns thickness. A variable potential difference ranging from 1 to 370 V DC was supplied, thus applying a variable electrostatic force to the specimen. The whole system is concentrated on the measurement of micro- to macroscale levels, and a powerful optical microscope evaluates the deflection. The current system has been used to estimate the samples' elastic moduli and then compare it with those obtained by the well-known tensile stress–strain testing method. Finally, the experimental principle of measuring elastic modulus was developed to conduct further research on the metallic materials that are induced by external stimuli like magnetic fields, lasers, and/or heat. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cannabinoid CB(2) receptor activation has been reported to attenuate myocardial, cerebral and hepatic ischaemia-reperfusion (I/R) injury.Experimental Approach: We have investigated the effects of a novel CB(2) receptor agonist ((1S,4R)-2-(2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl)-7,7-dimethylbicyclo[2.2.1]hept-2-en-1-yl)methanol (HU-910) on liver injury induced by 1 h of ischaemia followed by 2, 6 or 24 h of reperfusion, using a well-established mouse model of segmental hepatic I/R.Key Results: Displacement of [(3) H]CP55940 by HU-910 from specific binding sites in CHO cell membranes transfected with human CB(2) or CB(1) receptors (hCB(1/2) ) yielded K(i) values of 6 nM and 1.4 µM respectively. HU-910 inhibited forskolin-stimulated cyclic AMP production by hCB(2) CHO cells (EC(50) = 162 nM) and yielded EC(50) of 26.4 nM in [(35) S]GTPγS binding assays using hCB(2) expressing CHO membranes. HU-910 given before ischaemia significantly attenuated levels of I/R-induced hepatic pro-inflammatory chemokines (CCL3 and CXCL2), TNF-α, inter-cellular adhesion molecule-1, neutrophil infiltration, oxidative stress and cell death. Some of the beneficial effect of HU-910 also persisted when given at the beginning of the reperfusion or 1 h after the ischaemic episode. Furthermore, HU-910 attenuated the bacterial endotoxin-triggered TNF-α production in isolated Kupffer cells and expression of adhesion molecules in primary human liver sinusoidal endothelial cells stimulated with TNF-α. Pretreatment with a CB(2) receptor antagonist attenuated the protective effects of HU-910, while pretreatment with a CB(1) antagonist tended to enhance them.Conclusion and Implications: HU-910 is a potent CB(2) receptor agonist which may exert protective effects in various diseases associated with inflammation and tissue injury.Linked Articles: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. [ABSTRACT FROM AUTHOR]

52-W green laser at 532 nm by extra-cavity second-harmonic generation in a coupled-cavity configuration is demonstrated. The fundamental laser is a diode-side-pumped acousto-optic (AO) Q-switched Nd:YAG rod laser producing 84 W of average power at 1064 nm at 8 kHz repetition rate. Type-II phase-matched polished KTP crystal is used as the nonlinear crystal for second-harmonic generation. The individual green pulse width is 50 ns and the fundamental to second harmonic conversion efficiency is 61.8%. [ABSTRACT FROM AUTHOR]

Dual wavelength operation at 1062.8 nm and 1064.1 nm in a diode-pumped hybrid laser comprising of Nd-doped birefringent YVO and GdVO crystals is demonstrated. A detailed characterization of the laser is performed under CW and pulsed operation. Under Q-switching, 4 W of average power at 5 kHz repetition rate is obtained with 32 ns FWHM pulse duration corresponding to 25 kW of the peak power. The intensity and the polarization of the individual spectral components can be easily controlled by changing the relative gain and the relative orientation of the two crystals. The resulting pulsed dual-wavelength laser has the potential to be used as a source for generating terahertz radiation. [ABSTRACT FROM AUTHOR]

Studies on intracavity frequency doubling of acousto-optically Q-switched Nd:YAG rod laser using 18 mm long type-II phase-matched LBO crystal in a relay-imaged cavity is reported. A single pump head comprised of Nd:YAG rod, diffusive reflectors and linear array laser diode bars is used. 101 W of average green power at a total diode pumping power of 700 W is obtained corresponding to 14.4% optical-to-optical conversion efficiency. The pulse repetition rate is 30 kHz with an individual pulse duration of 200 ns. [ABSTRACT FROM AUTHOR]

3-Allyl-4-hydroxycoumarins and 4-allyl-3-hydroxycoumarins are obtained in 90%–92% yields by the thermal [3,3] sigmatropic rearrangement of the corresponding ethers. 3-Allyl-4-hydroxy-6-methylpyrone is obtained from the direct alkylation of 4-hydroxy-6-methylpyrone with allyl halide. These substrates on treatment with SnCl4–I2 at 25 °C give a mixture of both 5-exo- and 6-endo-cyclization products. However, regioselective formation of 5-exo products is observed when the reactions are conducted at lower temperatures (0–5 °C, kinetically controlled), while the reaction at a higher temperature (50 °C, thermodynamically controlled) affords regioselectively 6-endo cyclization products. [ABSTRACT FROM AUTHOR]

Presents a comparative study of classical and desmoplastic medulloblastomas. Markers of biological aggressiveness in the two variants; Differences in age distribution and location; Apoptotic indexes; Histological variants of medulloblastoma; Biological parameters of aggressiveness.

The disorder-to-order reaction in the stoichiometric Ni3V alloy is a typical cubic-to-tetragonal type (A1 to D022) transformation. Microstructural evolution has been studied at different temperatures below the ordering temperature in samples of this alloy having the same initial microstructure produced by solution treatment followed by water quenching. The ordered phase has been observed to evolve through a series of structural changes, starting with the impingement and alignment of fine ordered domains corresponding to all the three variants of the ordered phase, followed by the appearance of a two-variant lamellar structure which ultimately gets converted to a structure in which each Ni3V grain comprises a single variant. The lamellar structure is found to be quite stable with regard to coarsening in response to heat treatments. Evidence has been found which indicates that a discontinuous coarsening type of reaction is one of the possible mechanisms driving the two-variant lamellar to single-variant morphological transition. It has also been observed that coarsening of domains takes place in a manner similar to Ostwald ripening wherein larger domains coarsen at the expense of smaller domains. [Copyright &y& Elsevier]

A Winter Fog Experiment (WiFEX) was conducted to study the genesis of fog formation between winters 2016–17 and 2017–18 at Indira Gandhi International Airport (IGIA), Delhi, India. To support the WiFEX field campaign, the Weather Research and Forecasting (WRF) Model was used to produce real-time forecasts at 2-km horizontal grid spacing. This paper summarizes the performance of the model forecasts for 43 very dense fog episodes (visibility < 200 m) and preliminary evaluation of the model against the observations. Similarly, near-surface liquid water content (LWC) from models and continuous visibility observations are used as a metric for model evaluation. Results show that the skill score is relatively promising for the hit rate with a value of 0.78, whereas the false alarm rate (0.19) and missing rate (0.32) are quite low. This indicates that the model has reasonable predictive accuracy, and the performance of the real-time forecast is better for both dense fog events and no-fog events. For success cases, the model accurately captured the near-surface meteorological conditions, particularly the low-level moisture, wind fields, and temperature inversion. In contrast, for failed cases, the WRF Model shows large error in near-surface relative humidity and temperature compared to the observations, although it captures temperature inversions reasonably well. Our results also suggest that the model is able to capture the variability in fog onset for consecutive fog events. Errors in near-surface variables during failed cases are found to be affected by the errors in the initial conditions taken from the Indian Institute of Tropical Meteorology Global Forecasting System (IITM-GFS) spectral model forecast. Further evaluation of the operational forecasts for dense fog cases indicates that the error in predicting fog onset stage is relatively large (mean error of 4 h) compared to the dissipation stage. [ABSTRACT FROM AUTHOR]

In spite of the summer monsoon's importance in determining the life and economy of an agriculture-dependent country like India, committed efforts toward improving its prediction and simulation have been limited. Hence, a focused mission mode program Monsoon Mission (MM) was founded in 2012 to spur progress in this direction. This article explains the efforts made by the Earth System Science Organization (ESSO), Ministry of Earth Sciences (MoES), Government of India, in implementing MM to develop a dynamical prediction framework to improve monsoon prediction. Climate Forecast System, version 2 (CFSv2), and the Met Office Unified Model (UM) were chosen as the base models. The efforts in this program have resulted in 1) unparalleled skill of 0.63 for seasonal prediction of the Indian monsoon (for the period 1981–2010) in a high-resolution (∼38 km) seasonal prediction system, relative to present-generation seasonal prediction models; 2) extended-range predictions by a CFS-based grand multimodel ensemble (MME) prediction system; and 3) a gain of 2-day lead time from very high-resolution (12.5 km) Global Forecast System (GFS)-based short-range predictions up to 10 days. These prediction skills are on par with other global leading weather and climate centers, and are better in some areas. Several developmental activities like coupled data assimilation, changes in convective parameterization, cloud microphysics schemes, and parameterization of land surface processes (including snow and sea ice) led to the improvements such as reducing the strong model biases in the Indian summer monsoon simulation and elsewhere in the tropics. [ABSTRACT FROM AUTHOR]

Background Whole-genome sequencing (WGS) is a powerful method for revealing the diversity and complexity of the somatic mutation burden of tumours. Here, we investigated the utility of tumour and matched germline WGS for understanding aetiology and treatment opportunities for high-risk individuals with familial breast cancer. Patients and methods We carried out WGS on 78 paired germline and tumour DNA samples from individuals carrying pathogenic variants in BRCA1 (n  = 26) or BRCA2 (n  = 22) or from non-carriers (non- BRCA1/2 ; n  = 30). Results Matched germline/tumour WGS and somatic mutational signature analysis revealed patients with unreported, dual pathogenic germline variants in cancer risk genes (BRCA1 / BRCA2 ; BRCA1 / MUTYH). The strategy identified that 100% of tumours from BRCA1 carriers and 91% of tumours from BRCA2 carriers exhibited biallelic inactivation of the respective gene, together with somatic mutational signatures suggestive of a functional deficiency in homologous recombination. A set of non- BRCA1/2 tumours also had somatic signatures indicative of BRCA -deficiency, including tumours with BRCA1 promoter methylation, and tumours from carriers of a PALB2 pathogenic germline variant and a BRCA2 variant of uncertain significance. A subset of 13 non- BRCA1/2 tumours from early onset cases were BRCA-proficient, yet displayed complex clustered structural rearrangements associated with the amplification of oncogenes and pathogenic germline variants in TP53 , ATM and CHEK2. Conclusions Our study highlights the role that WGS of matched germline/tumour DNA and the somatic mutational signatures can play in the discovery of pathogenic germline variants and for providing supporting evidence for variant pathogenicity. WGS-derived signatures were more robust than germline status and other genomic predictors of homologous recombination deficiency, thus impacting the selection of platinum-based or PARP inhibitor therapy. In this first examination of non- BRCA1/2 tumours by WGS, we illustrate the considerable heterogeneity of these tumour genomes and highlight that complex genomic rearrangements may drive tumourigenesis in a subset of cases. [ABSTRACT FROM AUTHOR]

A stochastic multicloud model (SMCM) convective parameterization, which mimics the interactions at subgrid scales of multiple cloud types, is incorporated into the National Centers for Environmental Prediction (NCEP) Climate Forecast System, version 2 (CFSv2), model (CFSsmcm) in lieu of the preexisting simplified Arakawa–Schubert (SAS) cumulus scheme. A detailed analysis of the tropical intraseasonal variability (TISV) and convectively coupled equatorial waves (CCEW) in comparison with the original (control) model and with observations is presented here. The last 10 years of a 15-yr-long climate simulation are analyzed. Significant improvements are seen in the simulation of the Madden–Julian oscillation (MJO) and most of the CCEWs as well as the Indian summer monsoon (ISM) intraseasonal oscillation (MISO). These improvements appear in the form of improved morphology and physical features of these waves. This can be regarded as a validation of the central idea behind the SMCM according to which organized tropical convection is based on three cloud types, namely, the congestus, deep, and stratiform cloud decks, that interact with each other and form a building block for multiscale convective systems. An adequate accounting of the dynamical interactions of this cloud hierarchy thus constitutes an important requirement for cumulus parameterizations to succeed in representing atmospheric tropical variability. SAS fails to fulfill this requirement, which is evident in the unrealistic physical structures of the major intraseasonal modes simulated by CFSv2 as documented here. [ABSTRACT FROM AUTHOR]

A stochastic multicloud model (SMCM) convective parameterization, which mimics the interactions at subgrid scales of multiple cloud types, is incorporated into the National Centers for Environmental Prediction (NCEP) Climate Forecast System, version 2 (CFSv2), model (CFSsmcm) in lieu of the preexisting simplified Arakawa-Schubert (SAS) cumulus scheme. A detailed analysis of the tropical intraseasonal variability (TISV) and convectively coupled equatorial waves (CCEW) in comparison with the original (control) model and with observations is presented here. The last 10 years of a 15-yr-long climate simulation are analyzed. Significant improvements are seen in the simulation of the Madden-Julian oscillation (MJO) and most of the CCEWs as well as the Indian summer monsoon (ISM) intraseasonal oscillation (MISO). These improvements appear in the form of improved morphology and physical features of these waves. This can be regarded as a validation of the central idea behind the SMCM according to which organized tropical convection is based on three cloud types, namely, the congestus, deep, and stratiform cloud decks, that interact with each other and form a building block for multiscale convective systems. An adequate accounting of the dynamical interactions of this cloud hierarchy thus constitutes an important requirement for cumulus parameterizations to succeed in representing atmospheric tropical variability. SAS fails to fulfill this requirement, which is evident in the unrealistic physical structures of the major intraseasonal modes simulated by CFSv2 as documented here. [ABSTRACT FROM AUTHOR]

A comparative analysis of fourteen 5 year long climate simulations produced by the National Centers for Environmental Predictions (NCEP) Climate Forecast System version 2 (CFSv2), in which a stochastic multicloud (SMCM) cumulus parameterization is implemented, is presented here. These 5 year runs are made with different sets of parameters in order to figure out the best model configuration based on a suite of state-of-the-art metrics. This analysis is also a systematic attempt to understand the model sensitivity to the SMCM parameters. The model is found to be resilient to minor changes in the parameters used implying robustness of the SMCM formulation. The model is found to be most sensitive to the midtropospheric dryness parameter (MTD) and to the stratiform cloud decay timescale ( τ30). MTD is more effective in controlling the global mean precipitation and its distribution while τ30 has more effect on the organization of convection as noticed in the simulation of the Madden-Julian oscillation (MJO). This is consistent with the fact that in the SMCM formulation, midtropospheric humidity controls the deepening of convection and stratiform clouds control the backward tilt of tropospheric heating and the strength of unsaturated downdrafts which cool and dry the boundary layer and trigger the propagation of organized convection. Many other studies have also found midtropospheric humidity to be a key factor in the capacity of a global climate model to simulate organized convection on the synoptic and intraseasonal scales. [ABSTRACT FROM AUTHOR]

The National Centre for Environmental Prediction (NCEP) Climate Forecast System (CFS) is being used for operational monsoon prediction over the Indian region. Recent studies indicate that the moist convective process in CFS is one of the major sources of uncertainty in monsoon predictions. In this study, the existing simple cloud microphysics of CFS is replaced by the six-class Weather Research Forecasting (WRF) single moment (WSM6) microphysical scheme. Additionally, a revised convective parameterization is employed to improve the performance of the model in simulating the boreal summer mean climate and intraseasonal variability over the Indian summer monsoon (ISM) region. The revised version of the model (CFSCR) exhibits a potential to improve shortcomings in the seasonal mean precipitation distribution relative to the standard CFS (CTRL), especially over the ISM region. Consistently, notable improvements are also evident in other observed ISM characteristics. These improvements are found to be associated with a better simulation of spatial and vertical distributions of cloud hydrometeors in CFSCR. A reasonable representation of the subgrid-scale convective parameterization along with cloud hydrometeors helps to improve the convective and large-scale precipitation distribution in the model. As a consequence, the simulated low-frequency boreal summer intraseasonal oscillation (BSISO) exhibits realistic propagation and the observed northwest-southeast rainband is well reproduced in CFSCR. Additionally, both the high and low-frequency BSISOs are better captured in CFSCR. The improvement of low and high-frequency BSISOs in CFSCR is shown to be related to a realistic phase relationship of clouds. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus produces a particular morphological variant called small colony variant (SCV) which is responsible for persistent subclinical infections in predisposed individuals and is usually resistant to aminoglycosides and cell wall active antibiotics. Infections by SCV of S. aureus are an upcoming problem due to difficulty in laboratory diagnosis and resistance to antimicrobial chemotherapy. We here report a case of infective endocarditis caused by SCV of Staphylococcus aureus in a pediatric patient. [ABSTRACT FROM AUTHOR]

Susceptibility to most common cancers is likely to involve interaction between multiple low risk genetic variants. Although there has been great progress in identifying such variants, their effect on phenotype and the mechanisms by which they contribute to disease remain largely unknown. We have developed a mouse melanoma model harboring two mutant oncogenes implicated in human melanoma, CDK4R24C and NRASQ61K. In these mice, tumors arise from benign precursor lesions that are a recognized strong risk factor for this neoplasm in humans. To define molecular events involved in the pathway to melanoma, we have for the first time applied the Collaborative Cross (CC) to cancer research. The CC is a powerful resource designed to expedite discovery of genes for complex traits. We characterized melanoma genesis in more than 50 CC strains and observed tremendous variation in all traits, including nevus and melanoma age of onset and multiplicity, anatomical site predilection, time for conversion of nevi to melanoma and metastases. Intriguingly, neonatal ultraviolet radiation exposure exacerbated nevus and melanoma formation in most, but not all CC strain backgrounds, suggesting that genetic variation within the CC will help explain individual sensitivity to sun exposure, the major environmental skin carcinogen. As genetic variation brings about dramatic phenotypic diversity in a single mouse model, melanoma-related endophenotype comparisons provide us with information about mechanisms of carcinogenesis, such as whether melanoma incidence is dependent upon the density of pre-existing nevus cells. Mouse models have been used to examine the functional role of gene mutations in tumorigenesis. This work represents their next phase of development to study how biological variation greatly influences lesion onset and aggressiveness even in the setting of known somatic driver mutations. [ABSTRACT FROM AUTHOR]

Magnetic behavior of equiatomic FeAl alloy is still not satisfactorily understood. In this work, we studied the magnetic properties of disordered FeAl alloy both experimentally and using first-principles theories and revisited the alloy system in perspective of the inhomogeneity present in the system. After obtaining magnetic exchange interactions from first-principles theories, we carried out Monte-Carlo simulations on special quasi-random structures (SQS) and compared the results with experimental measurements. We tried to understand the plethora of often differing results and explain them in terms of possible inhomogeneities in the system. [ABSTRACT FROM AUTHOR]

In a thermally birefringence-compensated linear cavity configuration, ∼160 W of average green power by intracavity frequency doubling of AO Q-switched Nd:YAG/LBO-based laser is demonstrated. The corresponding optical to optical conversion efficiency is estimated to be ∼ 12.7%. The pulse repetition rate is 20 kHz with the individual pulse duration of 73 ns. The beam quality parameter is measured to be 18. [ABSTRACT FROM AUTHOR]

We present our studies on dual wavelength operation using a single Nd:YVO crystal and its intracavity sum frequency generation by considering the influence of the thermal lensing effect on the performance of the laser. A KTP crystal cut for type-II phase matching was used for intracavity sum frequency generation in the cavity at an appropriate location for efficient and stable yellow output power. More than 550 mW of stable CW yellow-orange beam at 593.5 nm with beam quality parameter ( M) ∼4. 3 was obtained. The total pump to yellow beam conversion efficiency was estimated to be 3.83%. [ABSTRACT FROM AUTHOR]

Cloud dynamics played a fundamental role in defining Indian summer monsoon ( ISM) rainfall during drought of 2009. The anomalously negative precipitation was consistent with cloud properties. Although, aerosols inhibited the growth of cloud effective radius in the background of sparse water vapor, their role is secondary. The primary role, however, is played by the interactive feedback between cloud microphysics and dynamics owing to reduced efficient cloud droplet growth, lesser latent heating release and shortage of water content. Cloud microphysical processes were instrumental for the occurrence of ISM drought 2009. [ABSTRACT FROM AUTHOR]

There are few effective treatments for metastatic melanoma. Checkpoint kinase 1 (Chk1) inhibitors are being trialled for their efficacy in enhancing conventional chemotherapeutic agents, but their effectiveness as single agents is not known. We have examined the effectiveness of two novel Chk1 selective inhibitors, AR323 and AR678, in a panel of melanoma cell lines and normal cell types. We demonstrate that these drugs display single-agent activity, with IC50s in the low nanomolar range. The drugs produce cytotoxic effects in cell lines that are most sensitive to these drugs, whereas normal cells are only sensitive to these drugs at the higher concentrations where they have cytostatic activity. The cytotoxic effect is the consequence of inhibition of S-phase Chk1, which drives cells prematurely from late S phase into an aberrant mitosis and results in either failure of cytokinesis or cell death through an apoptotic mechanism. The sensitivity to the Chk1 inhibitors was correlated with the level of endogenous DNA damage indicating replicative stress. Chk1 inhibitors are viable single-agent therapies that target melanoma cells with high levels of endogenous DNA damage. This sensitivity suggests that Chk1 is a critical component of an adaptation to replicative stress in these cells. It also suggests that markers of DNA damage may be useful in identifying the melanomas and potentially other tumour types that are more likely to be sensitive to Chk1 inhibitors as single agents. [ABSTRACT FROM AUTHOR]

MUC16/CA125 is a tumor marker currently used in clinics for the follow-up of patients with ovarian cancer. However, MUC16 expression is not entirely restricted to ovarian malignancies and has been reported in other cancers including breast cancer. Although it is well established as a biomarker, function of MUC16 in cancer remains to be elucidated. In the present study, we investigated the role of MUC16 in breast cancer and its underlying mechanisms. Interestingly, our results showed that MUC16 is overexpressed in breast cancer tissues whereas not expressed in non-neoplastic ducts. Further, stable knockdown of MUC16 in breast cancer cells (MDA MB 231 and HBL100) resulted in significant decrease in the rate of cell growth, tumorigenicity and increased apoptosis. In search of a mechanism for breast cancer cell proliferation we found that MUC16 interacts with the ezrin/radixin/moesin domain-containing protein of Janus kinase (JAK2) as demonstrated by the reciprocal immunoprecipitation method. These interactions mediate phosphorylation of STAT3 (Tyr705), which might be a potential mechanism for MUC16-induced proliferation of breast cancer cells by a subsequent co-transactivation of transcription factor c-Jun. Furthermore, silencing of MUC16 induced G2/M arrest in breast cancer cells through downregulation of Cyclin B1 and decreased phosphorylation of Aurora kinase A. This in turn led to enhanced apoptosis in the MUC16-knockdown breast cancer cells through Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated extrinsic apoptotic pathway with the help of c-Jun N-terminal kinase signaling. Collectively, our results suggest that MUC16 has a dual role in breast cancer cell proliferation by interacting with JAK2 and by inhibiting the apoptotic process through downregulation of TRAIL. [ABSTRACT FROM AUTHOR]

There is considerable interest in understanding how inflammatory responses influence cell proliferation and cancer. In this study, we show that the receptor-interacting protein (RIP1), a critical mediator of inflammation and stress-induced NF-κB activation, regulates the expression of the epidermal growth factor receptor (EGFR). Mouse embryo fibroblasts (MEFs) derived from RIP1 knockout mice express very high levels of the EGFR. Reconstitution of RIP1−/− MEFs with RIP1 results in a lowering of EGFR levels. RIP1 influences EGFR at the mRNA level by regulating the EGFR promoter. Expression of RIP1 inhibits the EGFR promoter. RIP1 downregulates EGFR expression by interfering with the function of Sp1, which is a key activator of EGFR transcription. RIP1 suppresses Sp1 activity and overexpression of Sp1 reverses RIP1-mediated repression of the EGFR promoter. RIP1 is present both in the cytoplasm and in the nucleus. RIP1 coimmunoprecipitates with Sp1 in vivo and binds directly to Sp1 in vitro. A RIP1 mutant lacking the death domain fails to suppress Sp1 activity and the EGFR promoter, suggesting a critical role for the RIP1 death domain in EGFR regulation. Thus, our study identifies a new link between inflammatory and growth factor signaling pathways mediated by RIP1 and provides insight into the mechanism used by RIP1 to regulate EGFR levels.Cell Death and Differentiation (2008) 15, 344–353; doi:10.1038/sj.cdd.4402268; published online 16 November 2007 [ABSTRACT FROM AUTHOR]

Abstract: This paper reports the evolution of order in stoichiometric Ni–25at.%V alloys with different thermal histories. In these alloys, the face-centred cubic structure of the disordered matrix transforms to a tetragonal (D022) structure during ordering. In such types of transformation, the process of order evolution involves a number of nucleation and growth processes, which are often competitive in nature. In the present work, evolution of the order has been studied in two sets of samples, one in which samples were subjected to order annealing treatment in the “melt-spun state” and the other in which samples were annealed in the “solid solution state”. Different sequences of the order evolution have been observed in the two sets of samples. In the first set of samples, grain boundary aided heterogeneous nucleation and growth of ordered domains dominated the order evolution process, whereas in the second set of samples the intragranular nucleation and growth of ordered domains dominated the ordering process. As a manifestation of different evolution sequences, different morphological changes occurred in the two sets of samples. The difference in the evolution sequences has been rationalized on the basis of driving forces influencing the ordering transformation in the two cases. [Copyright &y& Elsevier]

Background Declining costs of next-generation sequencing technologies has led to their more widespread use for the identification of targetable mutations. Nonetheless, while multigene panels are being assimilated into clinical practice, the use of whole-exome and whole-genome sequencing (WES and WGS) remains limited, as its added value is unclear in the clinic. Methods In our study, we have used the Cancer Genome Interpreter (CGI) to identify the actionable variants that are detected by WGS and compared this to in-silico down-sampled regions of WES and a hotspot panel. Results We show that within some tumour types, WGS is invaluable in identifying actionable variants that involve copy number defects and structural aberrations. Moreover, WGS successfully identifies many resistance biomarkers that would have otherwise been missed by WES and panels, particularly in the breast cancer dataset studied. WGS is more valuable of the detection of actionable variants in some tumour types, whereas hotspot panels perform well for other tumour types. Additionally, we show that a tumour type-agnostic approach to selecting genomic biomarker-based drug allocation increases the number of possible FDA-approved and clinical trial-based drug prescriptions for any given genomic biomarker in the patient cohorts studied. Conclusions Taken together, we show that WGS has the potential to impact patient care by identifying more targetable mutations and therefore expand drug options available for the patient. Furthermore, we illustrate the potential of tumour type-agnostic drug repurposing in nine cancer datasets. Legal entity responsible for the study QIMR Berghofer Medical Research Institute. Funding QIMR Berghofer Medical Research Institute. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]