43 resultados para chemotherapy-induced nausea and vomiting


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Small angle X-ray scattering (SAXS) studies of poly2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) with varying conjugation, and polyethylene dioxythiophene complexed with polystyrene sulfonate (PEDOT-PSS) in different solvents have shown the importance of the role of pi-electron conjugation and solvent-chain interactions in controlling the chain conformation and assembly. In MEH-PPV, by increasing the extent of conjugation from 30 to 100%, the persistence length (l(p)) increases from 20 to 66 angstrom. Moreover, a pronounced second peak in the pair distribution function has been observed in the fully conjugated chain, at larger length scales. This feature indicates that the chain segments tend to self-assemble as the conjugation along the chain increases. In the case of PEDOT-PSS, the chains undergo solvent induced expansion and enhanced chain organization. The clusters formed by chains are better correlated in dimethyl sulfoxide (DMSO) solution than water, as observed in the scattered intensity profiles. The values of radius of gyration and the exponent (water: 2.6, DMSO: 2.31) of power-law decay, obtained from the unified scattering function (Beaucage) analysis, give evidence for chain expansion from compact (in water) to an extended coil in DMSO solutions, which is consistent with the Kratky plot analysis. The mechanism of this transition and the increase in dc conductivity of PEDOT-PSS in DMSO solution are discussed. The onset frequency for the increase in ac conduction, as well as its temperature dependence, probes the extent of the connectivity in the PEDOT-PSS system. The enhanced charge transport in PEDOT-PSS in DMSO is attributed to the extended chain conformation, as observed in the SAXS results.

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Cobalt(II) complexes of terpyridine bases Co(L)(2)](ClO4)(2) (1-3), where L is 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy in 1), 4'-(9-anthracenyl)-2,2':6',2''-terpyridine (an-tpy in 2) and 4'-(1-pyrenyl)-2,2':6',2''-terpyridine (py-tpy in 3), are prepared and their photo-induced DNA and protein cleavage activity and photocytotoxic property in HeLa cells studied. The 1 : 2 electrolytic and three-electron paramagnetic complexes show a visible band near 550 nm in DMF-Tris-HCl buffer. The complexes 1-3 show emission spectral bands at 355, 421 and 454 nm, respectively, when excited at 287, 368 and 335 nm. The quantum yield values for 1-3 in DMF-H2O (2 : 1 v/v) are 0.025, 0.060 and 0.28, respectively. The complexes are redox active in DMF-0.1 M TBAP. The Co(III)-Co(II) and Co(II)-Co(I) couples appear as quasi-reversible cyclic voltammetric responses near 0.2 and -0.7 V vs. SCE, respectively. Complexes 2 and 3 are avid binders to calf thymus DNA giving K-b value of similar to 10(6) M-1. The complexes show chemical nuclease activity. Complexes 2 and 3 exhibit oxidative cleavage of pUC19 DNA in UV-A and visible light. The DNA photocleavage reaction of 3 at 365 nm shows formation of singlet oxygen and hydroxyl radical species, while only hydroxyl radical formation is evidenced in visible light. Complexes 2 and 3 show non-specific photo-induced bovine serum albumin protein cleavage activity at 365 nm. The an-tpy and py-tpy complexes exhibit significant photocytotoxicity in HeLa cervical cancer cells on exposure to visible light giving IC50 values of 24.2 and 7.6 mu M, respectively. Live cell imaging study shows accumulation of the complexes in the cytosol of HeLa cancer cells.

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Selective separation of haematite from alumina and silica/calcite was achieved through microbiologically induced flotation and flocculation in presence of Bacillus subtilis. Bacterial metabolites containing extracellular proteins were characterized from mineral-grown bacterial cell free extract. Bacteria can adhere to mineral surfaces and influence subsequent flotation of the minerals. Cells and metabolic products of bacteria were used in flotation, flocculation and adsorption studies on oxide minerals. Bacteria functions as a stronger depressant for haematite. Selective affinity of the bacterial cells towards the mineral surface was observed through adsorption studies. Bacterial byproduct like extracellular protein (EP) was isolated from bacteria. The protein profile of the EP of bacterial cells grown in presence and absence of minerals (haematite, corundum, quartz and calcite) was also studied. The role of such proteins in selective mineral separation was demonstrated through microbially induced selective flotation. This study has demonstrated the utility and amenability of microbially induced mineral beneficiation through the use of bacterially generated metabolic products and mineral-grown bacterial cells. (C) 2011 Elsevier B.V. All rights reserved.

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Cells of Saccharomyces cerevisiae and their metabolites were successfully utilized to achieve selective separation of quartz and calcite through microbially induced flotation and flocculation. S. cerevisiae was adapted to calcite and quartz minerals. Adsorption studies and electrokinetic investigations were carried out to understand the changes in the surface chemistry of yeast cells and the minerals after mutual interaction. Possible mechanisms in microbially induced flotation and flocculation are outlined. (C) 2011 Elsevier B.V. All rights reserved.

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Boundary layer transition induced by the wake of a circular cylinder in the free stream has been investigated using the particle image velocimetry technique. Some differences between simulation and experimental studies have been reported in the literature, and these have motivated the present study. The appearance of spanwise vortices in the early stage is further confirmed here. Lambda spanwise vortex appears to evolve into a Lambda/hairpin vortex; the flow statistics also confirm such vortices. With increasing Reynolds number, based on the cylinder diameter, and with decreasing cylinder height from the plate, the physical size of these hairpin-like structures is found to decrease. Some mean flow characteristics, including the streamwise growth of the disturbance energy, in a wake-induced transition resemble those in bypass transition induced by free stream turbulence. Streamwise velocity streaks that are eventually generated in the late stage often undergo sinuous-type oscillations. Similar to other transitional flows, an inclined shear layer in the wall-normal plane is often seen to oscillate and shed vortices. The normalized shedding frequency of these vortices, estimated from the spatial spacing and the convection velocity of these vortices, is found to be independent of the Reynolds number, similar to that in ribbon-induced transition. Although the nature of free stream disturbance in a wake-induced transition and that in a bypass transition are different, the late-stage features including the flow breakdown characteristics of these two transitions appear to be similar.

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We report a series of new glitazones incorporated with phenylalanine and tyrosine. All the compounds were tested for their in vitro glucose uptake activity using rat-hemidiaphragm, both in presence and absence of insulin. Six of the most active compounds from the in vitro screening were taken forward for their in vivo triglyceride and glucose lowering activity against dexamethazone induced hyperlipidemia and insulin resistance in Wistar rats. The liver samples of rats that received the most active compounds, 23 and 24, in the in vivo studies, were subjected to histopathological examination to assess their short term hepatotoxicity. The investigations on the in vitro glucose uptake, in vivo triglyceride and glucose lowering activity are described here along with the quantitative structure-activity relationships. (C) 2012 Elsevier Inc. All rights reserved.

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Theoretical and computational frameworks for synaptic plasticity and learning have a long and cherished history, with few parallels within the well-established literature for plasticity of voltage-gated ion channels. In this study, we derive rules for plasticity in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, and assess the synergy between synaptic and HCN channel plasticity in establishing stability during synaptic learning. To do this, we employ a conductance-based model for the hippocampal pyramidal neuron, and incorporate synaptic plasticity through the well-established Bienenstock-Cooper-Munro (BCM)-like rule for synaptic plasticity, wherein the direction and strength of the plasticity is dependent on the concentration of calcium influx. Under this framework, we derive a rule for HCN channel plasticity to establish homeostasis in synaptically-driven firing rate, and incorporate such plasticity into our model. In demonstrating that this rule for HCN channel plasticity helps maintain firing rate homeostasis after bidirectional synaptic plasticity, we observe a linear relationship between synaptic plasticity and HCN channel plasticity for maintaining firing rate homeostasis. Motivated by this linear relationship, we derive a calcium-dependent rule for HCN-channel plasticity, and demonstrate that firing rate homeostasis is maintained in the face of synaptic plasticity when moderate and high levels of cytosolic calcium influx induced depression and potentiation of the HCN-channel conductance, respectively. Additionally, we show that such synergy between synaptic and HCN-channel plasticity enhances the stability of synaptic learning through metaplasticity in the BCM-like synaptic plasticity profile. Finally, we demonstrate that the synergistic interaction between synaptic and HCN-channel plasticity preserves robustness of information transfer across the neuron under a rate-coding schema. Our results establish specific physiological roles for experimentally observed plasticity in HCN channels accompanying synaptic plasticity in hippocampal neurons, and uncover potential links between HCN-channel plasticity and calcium influx, dynamic gain control and stable synaptic learning.

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The telecommunication, broadcasting and other instrumented towers carry power and/or signal cables from their ground end to their upper regions. During a direct hit to the tower, significant induction can occur to these mounted cables. In order to provide adequate protection to the equipments connected to them, protection schemes have been evolved in the literature. Development of more effective protection schemes requires a quantitative knowledge on various parameters. However, such quantitative knowledge is difficult to find at present. Amongst several of these aspects, the present work aims to investigate on the two important aspects: (i) what would be the nature of the induced currents and (ii) what will be the current sharing if as per the practice, the sheath of the cable is connected to the down conductor/tower. These aspects will be useful in design of protection schemes and also in analyzing the field structure around instrumented towers.

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Cells and metabolic products of Bacillus subtilis were used in microbially-induced flocculation and flotation to separate pyrite from galena. Enhanced selective affinity of bacterial cells towards pyrite was observed when compared to galena through adsorption studies. Both extracellular (EP) and intracellular (IP) bacterial proteins were isolated from B. subtilis before and after interaction with the minerals and their profiles established through SDS-PAGE. Protein fractions exhibited significant surface affinity towards galena when compared to pyrite. Presence of galena during bacterial growth promoted increased generation of extracellular proteins, while that of pyrite resulted in enhanced production of exopolysaccharides. Galena surfaces were rendered hydrophobic after bacterial interaction.

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Recent reports suggest the existence of a subpopulation of stem-like cancer cells, termed as cancer stem cells (CSCs), which bear functional and phenotypic resemblance with the adult, tissue-resident stem cells. Side population (SP) assay based on differential efflux of Hoechst 33342 has been effectively used for the isolation of CSCs. The drug resistance properties of SP cells are typically due to the increased expression of ABC transporters leading to drug efflux. Conventionally used chemotherapeutic drugs may often leads to an enrichment of SP, revealing their inability to target the drug-resistant SP and CSCs. Thus, identification of agents that can reduce the SP phenotype is currently in vogue in cancer therapeutics. Withania somnifera (WS) and Tinospora cordifolia (TC) have been used in Ayurveda for treating various diseases, including cancer. In the current study, we have investigated the effects of ethanolic (ET) extracts of WS and TC on the cancer SP phenotype. Interestingly, we found significant decrease in SP on treatment with TC-ET, but not with WS-ET. The SP-inhibitory TC-ET was further fractionated into petroleum ether (TC-PET), dichloromethane (TC-DCM), and n-butyl alcohol (TC-nBT) fractions using bioactivity-guided fractionation. Our data revealed that TC-PET and TC-DCM, but not TC-nBT, significantly inhibited SP in a dose-dependent manner. Furthermore, flow cytometry-based functional assays revealed that TC-PET and TC-DCM significantly inhibited ABC-B1 and ABC-G2 transporters and sensitized cancer cells toward chemotherapeutic drug-mediated cytotoxicity. Thus, the TC-PET and TC-DCM may harbor phytochemicals with the potential to reverse the drug-resistant phenotype, thus improving the efficacy of cancer chemotherapy.

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Insulin like growth factor binding protein 2 (IGFBP2) is highly up regulated in glioblastoma (GBM) tissues and has been one of the prognostic indicators. There are compelling evidences suggesting important roles for IGFBP2 in glioma cell proliferation, migration and invasion. Extracellular IGFBP2 through its carboxy terminal arginine glycine aspartate (RGD) motif can bind to cell surface alpha 5 beta 1 integrins and activate pathways downstream to integrin signaling. This IGFBP2 activated integrin signaling is known to play a crucial role in IGFBP2 mediated invasion of glioma cells. Hence a molecular inhibitor of carboxy terminal domain of IGFBP2 which can inhibit IGFBP2-cell surface interaction is of great therapeutic importance. In an attempt to develop molecular inhibitors of IGFBP2, we screened single chain variable fragment (scFv) phage display libraries, Tomlinson I (Library size 1.47 x 10(8)) and Tomlinson J (Library size 1.37 x 10(8)) using human recombinant IGFBP2. After screening we obtained three IGFBP2 specific binders out of which one scFv B7J showed better binding to IGFBP2 at its carboxy terminal domain, blocked IGFBP2-cell surface association, reduced activity of matrix metalloprotease 2 in the conditioned medium of glioma cells and inhibited IGFBP2 induced migration and invasion of glioma cells. We demonstrate for the first time that in vitro inhibition of extracellular IGFBP2 activity by using human scFv results in significant reduction of glioma cell migration and invasion. Therefore, the inhibition of IGFBP2 can serve as a potential therapeutic strategy in the management of GBM.

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We explore the effect of modification to Einstein's gravity in white dwarfs for the first time in the literature, to the best of our knowledge. This leads to significantly sub- and super-Chandrasekhar limiting masses of white dwarfs, determined by a single model parameter. On the other hand, type Ia supernovae (SNeIa), a key to unravel the evolutionary history of the universe, are believed to be triggered in white dwarfs having mass close to the Chandrasekhar limit. However, observations of several peculiar, under- and over-luminous SNeIa argue for exploding masses widely different from this limit. We argue that explosions of the modified gravity induced sub- and super-Chandrasekhar limiting mass white dwarfs result in under- and over-luminous SNeIa respectively, thus unifying these two apparently disjoint sub-classes and, hence, serving as a missing link. Our discovery raises two fundamental questions. Is the Chandrasekhar limit unique? Is Einstein's gravity the ultimate theory for understanding astronomical phenomena? Both the answers appear to be no!

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Electromagnetic field produced by a lightning strike to ground causes significant induction to tall objects in the vicinity. The frequency of occurrence of such nearby ground strikes can be higher than the number of direct strikes. Therefore, a complete knowledge on these induced currents is of practical relevance. However, limited efforts towards the characterisation of such induced currents in tall down-conductors could be seen in the literature. Due to the intensification of the background field caused by the descending stepped leader, tall towers/down-conductors can launch upward leaders of significant length. The nonlinearity in the conductance of upward leader and the surrounding corona sheath can alter the characteristics of the induced currents. Preliminary aspects of this phenomenon have been studied by the author previously and the present work aims to perform a detailed investigation on the role of upward leaders in modifying the characteristics of the induced currents. A consistent model for the upward leader, which covers all the essential electrical aspects of the phenomena, is employed. A first order arc model for representing the conductance of upward leader and a field dependant quadratic conductivity model for the corona sheath is employed. The initial gradient in the upward leader and the field produced by the return stroke forms the excitation. The dynamic electromagnetic response is determined by solving the wave equation using thin-wire time-domain formulation. Simulations are carried out initially to ascertain the role of individual parameters, including the length of the upward leader. Based on the simulation results, it is shown that the upward leader enhances the induced current, and when significant in length, can alter the waveshape of induced current from bipolar oscillatory to unipolar. The duration of the induced current is governed by the length of upward leader, which in turn is dependant on the return stroke current and the effective length of the down-conductor. If the current during the upward leader developmental phase is considered along with that after the stroke termination to ground, it would present a bipolar current pulse. (C) 2015 Elsevier Ltd. All rights reserved.