110 resultados para Development of drugs


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The present study investigates the critical role of deformation twinning and Bs-type shear bands in the evolution of deformation texture in a low stacking fault energy Ni-60Co alloy up to very large rolling strain (epsilon(t) approximate to 4). The alloy develops a strong brass-type rolling texture, and its formation is initiated at the early stages of deformation. Extensive twinning is observed at the intermediate stages of deformation, which causes significant texture reorientation towards alpha-fiber. A pseudo-in-situ electron back-scattered diffraction technique adopted to capture orientation changes within individual grains during the early stages suggests that twinning should be subsequently aided by crystallographic slip to attain alpha-fiber (< 1 1 0 >parallel to ND) orientations. Beyond 40% reduction, deformation is dominated by Bs-type shear bands, and the banding coincides with the evolution of < 1 1 1 >parallel to ND components. The volume fraction of shear bands is significant at higher strains, and crystallites within the bands preferentially show < 1 1 0 >parallel to ND components. The absence of the Cu {1 1 2}< 1 1 1 > component in the initial texture, and subsequently during rolling, indicates that, for the evolution of a brass-type texture, the presence of the Cu component is not a necessary condition. The final rolling texture is a synergistic effect of deformation twinning and shear banding. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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Introduction: Immunomodulators are agents, which can modulate the immune response to specific antigens, while causing least toxicity to the host system. Being part of the modern vaccine formulations, these compounds have contributed remarkably to the field of therapeutics. Despite the successful record maintained by these agents, the requirement of novel immunomodulators keeps increasing due to the increasing severity of diseases. Hence, research regarding the same holds great importance. Areas covered: In this review, we discuss the role of immunomodulators in improving performance of various vaccines used for counteracting most threatening infectious diseases, mechanisms behind their action and criteria for development of novel immunomodulators. Expert opinion: Understanding the molecular mechanisms underlying immune response is a prerequisite for development of effective therapeutics as these are often exploited by pathogens for their own propagation. Keeping this in mind, the present research in the field of immunotherapy focuses on developing immunomodulators that would not only enhance the protection against pathogen, but also generate a long-term memory response. With the introduction of advanced formulations including combination of different kinds of immunomodulators, one can expect tremendous success in near future.

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In this paper we discuss the fabrication, working and characteristics of a thermoelectric generator made up of p and n type semiconductor materials. The device consists of Fe0.2Co3.8Sb11.5Te0.5 (zT = 1.04 at 818 K) as the n-type and Zn4Sb3 (zT= 0.8 at 550 K) as the p-type material synthesized by vacuum hot press method. Carbon paste has been used to join the semiconductor legs to metal (Molybdenum) electrodes to reduce the contact resistance. The multi-couple (4 legs) generator results a maximum output power of 1.083 mW at a temperature difference of 240 K between the hot and cold sides. In this investigation, an I-V characteristic, maximum output power of the thermoelectric module is presented. The efficiency of thermoelectric module is obtained as eta= 0.273 %.

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Cryosorption pump is the only possible device to pump helium, hydrogen and its isotopes in fusion environment, such as high magnetic field and high plasma temperatures. Activated carbons are known to be the most suitable adsorbent in the development of cryosorption pumps. For this purpose, the data of adsorption characteristics of activated carbons in the temperature range 4.5 K to 77 K are needed, but are not available in the literature. For obtaining the above data, a commercial micro pore analyzer operating at 77 K has been integrated with a two stage GM cryocooler, which enables the cooling of the sample temperature down to 4.5 K. A heat switch mounted between the second stage cold head and the sample chamber helps to raise the sample chamber temperature to 77 K without affecting the performance of the cryocooler. The detailed description of this system is presented elsewhere. This paper presents the results of experimental studies of adsorption isotherms measured on different types of activated carbons in the form of granules, globules, flake knitted and non-woven types in the temperature range 4.5 K to 10 K using Helium gas as the adsorbate. The above results are analyzed to obtain the pore size distributions and surface areas of the activated carbons. The effect of adhesive used for bonding the activated carbons to the panels is also studied. These results will be useful to arrive at the right choice of activated carbon to be used for the development of cryosorption pumps.

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The development of high-strength aluminum alloys that can operate at 250 degrees C and beyond remains a challenge to the materials community. In this paper we report preliminary development of nanostructural Al-Cu-Ni ternary alloys containing alpha-Al, binary Al2Cu and ternary Al2Cu4Ni intermetallics. The alloys exhibits fracture strength of similar to 1 GPa with similar to 9% fracture strain at room temperature. At 300 degrees C, the alloy retains the high strength. The reasons for such significant mechanical properties are rationalized by unraveling the roles and response of various microstructural features. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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SnS quantum dot solar cell is fabricated by Successive Ionic Layer Adsorption and Reaction (SILAR) method. SnS layer is optimized by different SILAR cycles of deposition. The particle size increased with the increase in number of SILAR cycles. Cu2S coated FTO is used as counter electrode against the conventional Platinum electrode. On comparison with a cell having a counter electrodeelectrolyte combination of Platinum-Iodine, Cu2S-polysulfide combination is found to improve both the short circuit current and fill factor of the solar cell. A maximum efficiency of 0.54% is obtained with an open circuit voltage of 311 mV and short circuit current density of 4.86 mA/cm. (C) 2014 Elsevier Ltd. All rights reserved.

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Flow cytometry is a benchmark technique used for basic research and clinical diagnosis of various diseases. Despite being a high-throughput technique, it fails in capturing the morphology of cells being analyzed. Imaging flow cytometry is a combination of flow-cytometry and digital microscopy, which offers advantages of both the techniques. In this paper, we report on the development of an indigenous Imaging Flow Cytometer, realized with the combination of Optics, Microfluidics, and High-speed imaging. A custom-made bright-field transmission microscope is used to capture images of cells flowing across the microfluidic device. High-throughput morphological analysis on suspension of yeast cells is presented.

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Large-scale estimates of the area of terrestrial surface waters have greatly improved over time, in particular through the development of multi-satellite methodologies, but the generally coarse spatial resolution (tens of kms) of global observations is still inadequate for many ecological applications. The goal of this study is to introduce a new, globally applicable downscaling method and to demonstrate its applicability to derive fine resolution results from coarse global inundation estimates. The downscaling procedure predicts the location of surface water cover with an inundation probability map that was generated by bagged derision trees using globally available topographic and hydrographic information from the SRTM-derived HydroSHEDS database and trained on the wetland extent of the GLC2000 global land cover map. We applied the downscaling technique to the Global Inundation Extent from Multi-Satellites (GIEMS) dataset to produce a new high-resolution inundation map at a pixel size of 15 arc-seconds, termed GIEMS-D15. GIEMS-D15 represents three states of land surface inundation extents: mean annual minimum (total area, 6.5 x 10(6) km(2)), mean annual maximum (12.1 x 10(6) km(2)), and long-term maximum (173 x 10(6) km(2)); the latter depicts the largest surface water area of any global map to date. While the accuracy of GIEMS-D15 reflects distribution errors introduced by the downscaling process as well as errors from the original satellite estimates, overall accuracy is good yet spatially variable. A comparison against regional wetland cover maps generated by independent observations shows that the results adequately represent large floodplains and wetlands. GIEMS-D15 offers a higher resolution delineation of inundated areas than previously available for the assessment of global freshwater resources and the study of large floodplain and wetland ecosystems. The technique of applying inundation probabilities also allows for coupling with coarse-scale hydro-climatological model simulations. (C) 2014 Elsevier Inc All rights reserved.

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A comprehensive design flow is proposed for the design of Micro Electro Mechanical Systems that are fabricated using SOIMUMPs process. Many of the designers typically do not model the temperature dependency of electrical conductivity, thermal conductivity and convection coefficient, as it is very cumbersome to create/incorporate the same in the existing FEM simulators. Capturing these dependencies is very critical particularly for structures that are electrically actuated. Lookup tables that capture the temperature dependency of electrical conductivity, thermal conductivity and convection coefficient are created. These look up tables are taken as inputs for a commercially available FEM simulator to model the semiconductor behavior. It is demonstrated that when temperature dependency for all the above mentioned parameters is not captured, then the error in estimation of the maximum temperature (for a given structure) could be as high as 30%. Error in the estimated resistance value under the same conditions is as high as 40%. When temperature dependency of the above mentioned parameters is considered then error w.r.t the measured values is less than 5%. It is evident that error in temperature estimates leads to erroneous results from mechanical simulations as well.

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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.

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Biogenesis of the iron-sulfur (Fe-S) cluster is an indispensable process in living cells. In mammalian mitochondria, the initial step of the Fe-S cluster assembly process is assisted by the NFS1-ISD11 complex, which delivers sulfur to scaffold protein ISCU during Fe-S cluster synthesis. Although ISD11 is an essential protein, its cellular role in Fe-S cluster biogenesis is still not defined. Our study maps the important ISD11 amino acid residues belonging to putative helix 1 (Phe-40), helix 3 (Leu-63, Arg-68, Gln-69, Ile-72, Tyr-76), and C-terminal segment (Leu-81, Glu-84) are critical for in vivo Fe-S cluster biogenesis. Importantly, mutation of these conserved ISD11 residues into alanine leads to its compromised interaction with NFS1, resulting in reduced stability and enhanced aggregation of NFS1 in the mitochondria. Due to altered interaction with ISD11 mutants, the levels of NFS1 and Isu1 were significantly depleted, which affects Fe-S cluster biosynthesis, leading to reduced electron transport chain complex (ETC) activity and mitochondrial respiration. In humans, a clinically relevant ISD11 mutation (R68L) has been associated in the development of a mitochondrial genetic disorder, COXPD19. Our findings highlight that the ISD11 R68A/R68L mutation display reduced affinity to form a stable subcomplex with NFS1, and thereby fails to prevent NFS1 aggregation resulting in impairment of the Fe-S cluster biogenesis. The prime affected machinery is the ETC complex, which showed compromised redox properties, causing diminished mitochondrial respiration. Furthermore, the R68L ISD11 mutant displayed accumulation of mitochondrial iron and reactive oxygen species, leading to mitochondrial dysfunction, which correlates with the phenotype observed in COXPD19 patients.

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Several soil microbes are present in the rhizosphere zone, especially plant growth promoting rhizobacteria (PGPR), which are best known for their plant growth promoting activities. The present study reflects the effect of gold nanoparticles (GNPs) at various concentrations on the growth of PGPR. GNPs were synthesized chemically, by reduction of HAuCl 4, and further characterized by UV-Vis spectroscopy, X-ray diffraction technique (XRD), and transmission electron microscopy (TEM), etc. The impact of GNPs on PGPR was investigated by Clinical Laboratory Standards Institute (CLSI) recommended Broth-Microdilution technique against four selected PGPR viz., Pseudomonas fluorescens, Bacillus subtilis, Paenibacillus elgii, and Pseudomonas putida. Neither accelerating nor reducing impact was observed in P. putida due to GNPs. On the contrary, significant increase was observed in the case of P. fluorescens, P. elgii, and B. subtilis, and hence, GNPs can be exploited as nano-biofertilizers.