763 research outputs found
Conventional Ultrafiltration Versus Combined Conventional and Modified Ultrafiltration on Clinical Outcomes of Pediatric Cardiac Surgery
No full text*Corresponding author: Dr Sanjeev Singh, Department of Anaesthesiology and Intensive Care, Kwame Nkrumah University of Science and Technology, Kumasi,
Ghana, E-mail: [email protected]
J Anesth Clin Res, an open access journal
ISSN: 2155-614
Effect of artemisinins and amino alcohol partner antimalarials on mammalian sarcoendoplasmic reticulum calcium adenosine triphosphatase activity.
No full textThe aim of this study was to assess the ability of currently deployed antimalarials to inhibit mammalian sarcoendoplasmic reticulum calcium adenosine triphosphatase (SERCA). Artemisinins exert their antiplasmodial action by inhibiting parasite PfATP6, a SERCA enzyme, and possess neurotoxic potential; mefloquine is neurotoxic and inhibits mammalian SERCA, an orthologue of PfATP6. SERCA in rabbit muscle was tested in vitro for inhibition by artemisinin and amino alcohol antimalarials. Significant inhibition of mammalian SERCA, as mean difference from uninhibited, control values was seen with both enantiomers of mefloquine: (+)-mefloquine (10 microM: -35.83, 95% CI -59.63 to -12.03; 50 microM: -54.06, 95% CI -77.86 to -30.26); (-)-mefloquine (10 microM: -24.35, 95% CI -41.56 to -7.15; 50 microM: -58.42, 95% CI -75.62 to -41.22); lumefantrine (1 microM: -25.46, 95% CI -45.82 to -5.10; 5 microM -34.83, 95% CI -60.08 to -9.58; 10 microM: -25.80, 95% CI -51.05 to -0.55); desbutyl-lumefantrine (5 microM: -50.16, 95% CI -84.24 to -16.08); dihydroartemisinin (1 microM: -39.25, 95% CI -63.74 to -14.76; 5 microM: -39.30, 95% CI -64.88 to -13.72). Dihydroartemisinin in higher concentrations (10 microM) stimulated SERCA activity: (+40.90, 95% CI 11.37 to 70.44). No statistically significant inhibition was seen with artemether at 1, 5 and 10 microM. Equimolar combinations of artemether and lumefantrine or of dihydroartemisinin and lumefantrine, when studied at concentrations that inhibit SERCA individually, failed to show any inhibition. Dihydroartemisinin, mefloquine, lumefantrine and desbutyl lumefantrine inhibit mammalian SERCA at periphysiological concentrations, although the neurotoxicity of mefloquine is not wholly attributable to this property. Candidate antimalarials should be screened pre-clinically for SERCA inhibition
Tapping Economies of Scale and Scope in Consumer Cooperation - A Case Analysis of Possible Cooperation among selected Cooperatives
No full textBecause of its narrow and negative perspective of safeguarding the interests of only poor consumers against unethical practices of the private traders, consumer cooperation in India seems to have failed, except probably in some isolated pockets. A number of social welfare functions like poverty alleviation and public distribution of essential items of consumption have been imposed on them at the cost of their basic economics. With the basic micro and macro-economic rationale for consumer cooperatives as a positive form of economic organization being lost sight of, they seem to be facing enormous problems both historically as well as currently in a era of economic liberalization. Their worries seem to have been compounded with the threat of impending competition from large private enterpriss - both domestic and foreign, which highlights the need for evolving strategies to rectivy their systemic weaknesses and tackling the competition head on. This case has attempted to document just such an initiative through a round table conference with several doyens of the consumer cooperative movement in India such as Warana Bazar and Amalsad Mandali as well as some fledging consumer cooperatives from West Bengal which are already in existence for some time or contemplating entry into this field. The roundtable conference organized in the spirit of Cooperation among Cooperatives attempted to evolve strategies to capture economies of scale and scope in order to take on the competition, as well as to facilitate dissemination of ideas and information across the country.
Factor Affecting Customer Service in Supply Chain Management of Small and Medium Enterprises: An Empirical Study of Jammu Region
No full textFactor Affecting Customer Service in Supply Chain Management of Small and Medium Enterprises: An Empirical Study of Jammu Region
Author / Authors : Sanjeev Lalhotra and Prof. B.C Sharma
Page no.149-165
Discipline : Applied Economics/ Management/ Commerce
Script/language : Roman/English
Category : Research paper
Keywords: Customer services, Supply Chain Management, Small and Medium Enterprises
Dataset in support of the thesis 'Speech enhancement by using deep learning algorithms'
No full text The source code and audio datasets of my PhD project.
1. https://www.openslr.org/12
LibriSpeech is a corpus of approximately 1000 hours of 16kHz read English speech, prepared by Vassil Panayotov with the assistance of Daniel Povey. The data is derived from read audiobooks from the LibriVox project, and has been carefully segmented and aligned.
Acoustic models, trained on this data set, are available at kaldi-asr.org and language models, suitable for evaluation can be found at http://www.openslr.org/11/.
For more information, see the paper "LibriSpeech: an ASR corpus based on public domain audio books", Vassil Panayotov, Guoguo Chen, Daniel Povey and Sanjeev Khudanpur, ICASSP 2015
2.https://www.openslr.org/17
MUSAN is a corpus of music, speech, and noise recordings.
This work was supported by the National Science Foundation Graduate Research Fellowship under Grant No. 1232825 and by Spoken Communications.
You can cite the data using the following BibTeX entry:
@misc{musan2015,
author = {David Snyder and Guoguo Chen and Daniel Povey},
title = {{MUSAN}: {A} {M}usic, {S}peech, and {N}oise {C}orpus},
year = {2015},
eprint = {1510.08484},
note = {arXiv:1510.08484v1}
}
3. source_code.zip
The program from parts of my PhD project.
4.SJ_EXP.zip
The program of the subjective experiment corresponding to the last chapter.</span
Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections.
No full textBACKGROUND: Monitoring resistance phenotypes for Plasmodium falciparum, using in vitro growth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins.
METHODS: Plasmodium falciparum isolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations in pfatp6 and pfmdr1.
RESULTS: Resistance to artemether in vitro was significantly associated with a pfatp6 haplotype encoding two amino acid substitutions (pfatp6 A623E and S769N; (mean IC50 (95% CI) values of 8.2 (5.7 - 10.7) for A623/S769 versus 623E/769 N 13.5 (9.8 - 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number of pfmdr1 was not itself associated with increased IC50 values for artemether, but when interactions between the pfatp6 haplotype and increased copy number of pfmdr1 were examined together, a highly significant association was noted with IC50 values for artemether (mean IC50 (95% CI) values of 8.7 (5.9 - 11.6) versus 16.3 (10.7 - 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs in pfmdr1 are also associated with differences in sensitivity to some artemisinins.
CONCLUSIONS: These findings were further explored in molecular modelling experiments that suggest mutations in pfatp6 are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations in pfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed
Sanjeev Coke, a Critique - An Evaluation of Article 39(B)
No full textThis paper seeks to look at the Directive Principle enshrined in Article 39(b) of the Constitution of India and analyze it in light of the Fundamental Rights enshrined in the Constitution. The author shall demonstrate that the Supreme Court of India has been mistaken in its analysis of the scope of Article 39(b); particularly in relation to Article 31C, and generally in relation to Part III of the Constitution. The interpretation placed by the Court in Sanjeev Coke is currently being reviewed by a larger Bench of nine judges. This paper attempts to posit the argument that Article39 (b) should not be deployed towards the nationalization of private property or the collection of assets/resources by the State, but must, instead, be interpreted such that it applies to the stage of distribution, as distinct from the stage of collection, of assets
Sanjeev Coke, a Critique - An Evaluation of Article 39(B)
No full textThis paper seeks to look at the Directive Principle enshrined in Article 39(b) of the Constitution of India and analyze it in light of the Fundamental Rights enshrined in the Constitution. The author shall demonstrate that the Supreme Court of India has been mistaken in its analysis of the scope of Article 39(b); particularly in relation to Article 31C, and generally in relation to Part III of the Constitution. The interpretation placed by the Court in Sanjeev Coke is currently being reviewed by a larger Bench of nine judges. This paper attempts to posit the argument that Article39 (b) should not be deployed towards the nationalization of private property or the collection of assets/resources by the State, but must, instead, be interpreted such that it applies to the stage of distribution, as distinct from the stage of collection, of assets
Hexose transport in asexual stages of Plasmodium falciparum and Kinetoplastidae
No full textThe hexose sugar, glucose, is a vital energy source for most organisms and an essential nutrient for asexual stages of Plasmodium falciparum. Kinetoplastid organisms (e.g. Trypanosoma and Leishmania spp) also require glucose at certain critical stages of their life cycles. Although phylogenetically unrelated, these organisms share many common challenges during the mammalian stages of a parasitic life cycle, and possess hexose uptake mechanisms that are amenable to study using similar methods. Defining hexose permeation pathways into parasites might expose an Achilles’ heel at which both antidisease and antiparasite measures can be aimed. Understanding the mode of entry of glucose also presents a good general model for substrate acquisition in multicompartment systems. In this review, Sanjeev Krishna and colleagues summarize current understanding of hexose transport processes in P. falciparum and provide a comparison with data obtained from kinetoplastids
Les études sur les mécanismes d'action de l'artémisinine et le rôle des PfATP6
No full textLa pompe ATPase Ca2+ du réticulum sarco-endoplasmique Plasmodium falciparum (PfATP6) est une protéine de dix transmembranes, impliqué dans la régulation de l'homéostasie du calcium dans le parasite. L'importance d'étudier cette protéine repose sur l'hypothèse d'être engagé dans le mécanisme d'action et de résistance des artémisinines. Des travaux précédents, fondé sur l'expression hétérologue dans des ovocytes de Xenopus laevis et Saccharomyces cerevisiae, ont montré des résultats opposés, générant de nombreux corollaires vérifiables. Par conséquent, des travaux supplémentaires sont nécessaires pour mieux comprendre la nature des interactions entre les artémisinines et transporteurs de type SERCA.Afin d'évaluer le caractère essentiel du gène de Plasmodium spp., une approche de génétique inverse a été utilisée. Knockout du gène, soit P. falciparum et berghei, ne pouvant pas être obtenu. La complémentation de sauvetage épisomique a été jugée impossible. Marquage à la fin 3' de PfATP6 et PbATP6 a été, également, tenté pour étudier la localisation et l'expression de la protéine chez les parasites. La manipulation des gènes à cette place n'a pas permis la survie du parasite. Nos résultats, pris ensemble, montrent que ATP6 est essentiel dans Plasmodium spp..Au cours de nos études génétiques, un phénotype stable et particulier de parasites du genre Plasmodium falciparum 3D7 a été distingué. Les étranges parasites “monstres" contiennent une vacuole digestive inhabituelle gonflées à travers toutes les étapes du développement du parasite. Caractérisation de l'insolite Plasmodium a été réalisée, montrant une sensibilité accrue à la chloroquine, mais pas à l'artémisinine ou de la méfloquine. Tenant compte de la similitude du PfATP6 avec la pompe SERCA orthologue mammifère, de nouvelles molécules, connu et synthétisé pour cibler spécifiquement la protéine chez les mammifères, ont été testés sur P. falciparum. Quatre classes différentes de composés (sHA 14-1, BHQ, chalcone et des analogues de l'ACP) a montré le blocage de la croissance in vitro du P. falciparum 3D7 et Dd2 à des concentrations inférieure au range micromolaire. En outre, une nouvelle classe de molécules (thaperoxides), conçu comme un hybride entre l'artémisinine et thapsigargine, a été testé contre le type sauvage 7G8 et la ligne muté L263E. Ce dernier porte une mutation ponctuelle unique de nucléotides dans PfATP6, déjà connu d'être impliqué dans la résistance du l'artémisinine.Compte tenu de la difficulté à manipuler les gènes du parasite, et afin de mieux caractériser PfATP6, un gène synthétique a été optimisé pour l'expression hétérologue chez S. cerevisiae. De cette façon, la complémentation d'une ligne de levure mutée (K616) sans les pompes endogènes Ca2+ de type P a été permis avec succès, montrant le sauvetage de la croissance de la levure en présence de forte concentration de calcium libre. Différents inhibiteurs de SERCA, comme la thapsigargine et l'acide cyclopiazonique, ont été testés sur la levure complémenté K616 PfATP6, afin de vérifier l'inhibition de la croissance. Tous les composés ont bloqué la croissance de levure sélectivement ciblant le PfATP6. En outre, le test a été développé comme un criblage de haute performance, afin de tester de nouvelles molécules pour leur activité. La méthode s'est révélée être un outil rapide et très fiable et reproductible pour l'identification de nouveaux composés actifs.The Plasmodium falciparum sarco-endoplasmic reticulum ATPase Ca2+ pump (PfATP6) is a ten transmembrane protein involved in the regulation of the calcium homeostasis in the parasite. The importance of studying this protein relies on the fact that it has been hypothesized to be involved in the mechanism of action and resistance of artemisinins. Previous works, based on heterologous expression in Xenopus laevis oocytes and Saccharomyces cerevisiae, have shown contrasting results, generating many testable corollaries. Therefore, further work is needed to better understand the nature of interactions between artemisinins and SERCA-type transporters.In order to assess the essentiality of the gene in Plasmodium spp., a reverse genetics approach has been used. Knockout of the gene, in either P. falciparum and berghei, could not be achieved. Complementation for episomal rescue was found to be not possible. Tagging at the 3' end of PfATP6 and PbATP6 has been, also, attempted to study localization and expression of the protein in parasites. Manipulation of the gene at this position did not permit parasite survival. Our results, taken together, show that ATP6 is essential in Plasmodium spp..During our genetic studies, a stable and peculiar phenotype of Plasmodium falciparum 3D7 parasites has been noticed. The odd “monster” parasites contain an unusual swollen food vacuole throughout all stages of parasite development. Characterization of the unusual Plasmodium has been carried out, showing an increased sensitivity to chloroquine, but not to artemisinin or mefloquine. Taking into account the similarity of PfATP6 with the mammalian orthologue SERCA pump, new molecules, designed and synthesized to specifically target the mammalian protein, were tested on P. falciparum parasites. Four different classes of compounds (sHA 14-1, BHQ, chalcone and CPA analogues) showed to inhibit P. falciparum 3D7 and Dd2 growth in vitro at concentrations in the lower micromolar range. In addition, a novel class of molecules (thaperoxides), designed as an hybrid between artemisinin and thapsigargin, has been tested against 7G8 wild type and mutated L263E line. The latter carries a single nucleotide point mutation in PfATP6 that has been previously shown to be involved in artemisinin resistance. Considering the difficulty in manipulating the gene in the parasite and in order to better characterize PfATP6, a synthetic gene was optimized for heterologous expression in S. cerevisiae. This enabled successful complementation of a mutated yeast line (K616) lacking the endogenous P-type Ca2+ pumps, showing rescue of the yeast growth in presence of high concentration of free calcium. Different SERCA inhibitors, such as thapsigargin and cyclopiazonic acid, have been tested on K616 PfATP6 complemented yeast, in order to check for growth inhibition. All compounds showed to inhibit yeast growth selectively targeting PfATP6. In addition, the assay has been developed as a high throughput screening, in order to test new molecules for their activity. The method has proved to be a fast, highly reliable and reproducible tool for identification of new active compounds
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