Regional Climate Simulations on EU-INDIA Grid Infrastructures: Methodologies and Performance

In this paper, we present a possible approach to use different Grid infrastructures across Europe and India for regional climate simulations and discuss in details the advantages and limitations in using them. The application taken into consideration is the Regional Climate Model RegCM4, which has been recently re-written for making it more efficient and easier to be fully exploited on any kind of computational infrastructure. We describe here the methods applied to port this package on the Grid infrastructures made available by the EU-IndiaGrid project. We also discuss different approaches, the way to run the model on both European and Indian infrastructures and our promising approach to deal with data management issues. Use of RegCM on Grid infrastructure has further been compared with that on HPC resources. The domain worked upon for these tests is the South-Asia CORDEX domain, which is of great importance for the Indian Summer Monsoon. Our final conclusion is that, for certain class of experiments, RegCM4 model can be efficiently and easily integrated on Grid infrastructures, by means of the procedures described in this paper.     

ICOSL Stimulation by ICOS-Fc Accelerates Cutaneous Wound Healing In Vivo

Background: ICOS and its ligand ICOSL are immune receptors whose interaction triggers bidirectional signals that modulate the immune response and tissue repair. Aim: The aim of this study was to assess the in vivo effects of ICOSL triggering by ICOS-Fc, a recombinant soluble form of ICOS, on skin wound healing. Methods: The effect of human ICOS-Fc on wound healing was assessed, in vitro, and, in vivo, by skin wound healing assay using ICOS^−/− and ICOSL^−/− knockout (KO) mice and NOD-SCID-IL2R null (NSG) mice. Results: We show that, in wild type mice, treatment with ICOS-Fc improves wound healing, promotes angiogenesis, preceded by upregulation of IL-6 and VEGF expression; increases the number of fibroblasts and T cells, whereas it reduces that of neutrophils; and increases the number of M2 vs. M1 macrophages. Fittingly, ICOS-Fc enhanced M2 macrophage migration, while it hampered that of M1 macrophages. ICOS^−/− and ICOSL^−/− KO, and NSG mice showed delayed wound healing, and treatment with ICOS-Fc improved wound closure in ICOS^−/− and NSG mice. Conclusion: These data show that the ICOS/ICOSL network cooperates in tissue repair, and that triggering of ICOSL by ICOS-Fc improves cutaneous wound healing by increasing angiogenesis and recruitment of reparative macrophages.     

Morphology,Mineralogy and Mixing of Individual Atmospheric Particles Over Kanpur (IGP): Relevance of Homogeneous Equivalent Sphere Approximation in Radiative Models

Estimation of the direct radiative forcing (DRF) by atmospheric particles is uncertain to a large extent owing to uncertainties in their morphology (shape and size), mixing states, and chemical composition. A region-specific database of the aforementioned physico-chemical properties (at individual particle level) is necessary to improve numerically-estimated optical and radiative properties. Till date, there is no detailed observation of the above mentioned properties over Kanpur in the Indo-Gangetic Plain (IGP). To fill this gap, an experiment was carried out at Kanpur (IITK; 26.52°N, 80.23°E, 142 m msl), India from April to July, 2011. Particle types broadly classified as (a) Cu-rich particles mixed with carbon and sulphur (b) dust and clays mixed with carbonaceous species (c) Fe-rich particles mixed with carbon and sulfur and (d) calcite (CaCO₃) particles aged with nitrate, were observed. The frequency distributions of aspect ratio (AR; indicator of extent of particle non-sphericity) of total 708 particles from April to June reveal that particles with aspect ratio range >1.2 to ≤1.4 were abundant throughout the experiment except during June when it was found to shift to high AR range, >1.4 to ≤1.6 (followed with another peak of AR i.e. >2 to ≤2.4) due to dust storm conditions enhancing the occurrence of more non-spherical particles over the sampling site. The spherical particles (and close to spherical shape; AR range, 1.0 to ≤1.2) were found to be <20% throughout the experiment with a minimum (11.5%) during June. Consideration of Homogeneous Equivalent Sphere Approximation (HESA) in the optical/radiative model over the study region is found to be irrelevant during the campaign.     

Prediction of in vivo drug performance using in vitro dissolution coupled with STELLA: a study with selected drug products

Prediction of the in vivo performance of the drug product from the in vitro studies is the major challenging job for the pharmaceutical industries. From the current regulatory perspective, biorelevant dissolution media should now be considered as quality control media in order to avoid the risk associated. Physiological based pharmacokinetic models (PBPK) coupled with biorelevant dissolution medium is widely used in simulation and prediction of the plasma drug concentration and in vivo drug performance. The present investigation deals with the evaluation of biorelevant dissolution media as well as in vivo drug performance by PBPK modelling using STELLA® simulation software. The PBPK model was developed using STELLA® using dissolution kinetics, solubility, standard gastrointestinal parameters and post-absorptive disposition parameters. The drug product selected for the present study includes Linezolid film-coated immediate-release tablets (Zyvox), Tacrolimus prolonged-release capsules (Advagraf), Valganciclovir tablets (Valcyte) and Mesalamine controlled-release capsules (Pentasa) each belonging to different biopharmaceutics classification system (BCS). The simulated plasma drug concentration was analyzed and pharmacokinetic parameters were calculated and compared with the reported values. The result from the present investigation indicates that STELLA® when coupled with biorelevant dissolution media can predict the in vivo performance of the drug product with prediction error less than 20% irrespective of the dosage form (immediate release versus modified release) and BCS Classification. Thus, STELLA® can be used for in vivo drug prediction which will be helpful in generic drug development.     

THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors

Multiple myeloma (MM) is a hematological disease marked by abnormal growth of B cells in bone marrow. Inherent chromosomal instability and DNA damage are major hallmarks of MM, which implicates an aberrant DNA repair mechanism. Studies have implicated a role for CDK12 in the control of expression of DNA damage response genes. In this study, we examined the effect of a small molecule inhibitor of CDK12–THZ531 on MM cells. Treatment of MM cells with THZ531 led to heightened cell death accompanied by an extensive effect on gene expression changes. In particular, we observed downregulation of genes involved in DNA repair pathways. With this insight, we extended our study to identify synthetic lethal mechanisms that could be exploited for the treatment of MM cells. Combination of THZ531 with either DNA-PK inhibitor (KU-0060648) or PARP inhibitor (Olaparib) led to synergistic cell death. In addition, combination treatment of THZ531 with Olaparib significantly reduced tumor burden in animal models. Our findings suggest that using a CDK12 inhibitor in combination with other DNA repair inhibitors may establish an effective therapeutic regimen to benefit myeloma patients.     

The Enriched Feature Enhancement Technique for Satellite Image Based on Transforms Using PCNN

The features of the satellite images can be improved by fusing or combining two images with complementary property. By fusing these two images the spatial property of the resultant image is improved. Satellite images are one of the agents that give the features of the earth’s surface. Processing these satellite images will provide more geographical information hidden in the images. This research paper have an detailed insight study of two types of the satellite images one is Panchromatic (PAN) and other Multispectral (MS). The PAN image with high spatial resolution and MS image with spectral resolution are fused to get better resultant output. For fusion process Nonsubsampled Contour let Transform is used to decompose the images into low and high frequency values. Pulse Coupled Neural Network is used to motivate the low frequency pixel and Morphological filter is applied to the edge detected image for finding the features in the images. This is an real time transformations which will give better results in SAR image processing, video processing, stereo based reconstruction of depth and width of the features present in the image.

     

Screening selected strains of probiotic lactic acid bacteria for their ability to produce biogenic amines (histamine and tyramine)

The aim of this study was to investigate the production of biogenic amines (BA), histamine and tyramine by some probiotic lactic acid bacteria (LAB). Fifteen strains representing six LAB species were screened qualitatively by growing them in a decarboxylase medium. Quantitative analysis was carried out by HPLC analysis with direct derivatization of acid extracts. Lactobacillus casei (TISTR 389) and Lactobacillus delbrueckii subsp. bulgaricus (TISTR 895) were found to produce BA. The highest levels of histamine (1820.9 ± 3.5 mg L^?1) and tyramine (5486.99 ± 47.6 mg L^?1) formation were observed for the TISTR 389 strain, while TISTR 895 produced only histamine (459.1 ± 0.63 mg L^?1) in the decarboxylase broth. Biogenic amine potential was not observed for the Lactobacillus acidophilus, Lactobacillus lactis subsp. lactis, Lactococcus lactis subsp. lactis, and Lactobacillus plantarum strains studied. This study confirmed that BA formation is strain dependent and not related to the species. Therefore, careful screening for amino acid decarboxylase activity is recommended before selecting LAB as appropriate starter or probiotic strains in food and dairy industry.