Papers by jay prakash sharma
Caste, COVID-19, and Inequalities of Care, 2022
The COVID-19 pandemic has caused an unprecedented impact upon human society across the globe. Evi... more The COVID-19 pandemic has caused an unprecedented impact upon human society across the globe. Evidently, it is going to have far-reaching consequences touching upon almost every single aspect of our lives, yet the magnitude and severity of sufferings will remain as differentiated as our societies and people are around us. The horrific suffering endured by migrant workers during their mass exodus from Indian cities in the wake of the government-imposed lockdown leading to a humanitarian crisis is a telling example. Through this chapter, I explore how a pandemic of this scale was perceived, experienced and responded to in a small village in the West Singbhum district of Jharkhand inhabited predominantly by the Ho tribe. To that end I will be discussing different phases of the pandemic-initial infection spread, economic lockdown and restriction upon people's movement; arrival of the migrants; staggered unlocking and everyday life-from a perspective informed by the Ho community. I argue that although the narratives around the pandemic made their way into the village through mainstream, popular and social media, the Ho community's response to it was mediated by local socio-cultural and political contexts. The pandemic, indeed, elicited varying feelings ranging from anxiety and hopelessness to indifference and factitious reactions; however, their responses during each phase mentioned above were expressed through idioms that sit uncomfortably with the mainstream narratives. These inconsistencies in the narrative must also be seen from the backdrop of a history checkered with practices of exploitation, oppression and alienation.
We investigate whether sentiment derived from micro-blogging site Twitter can be used to identify... more We investigate whether sentiment derived from micro-blogging site Twitter can be used to identify important events (product launch, quarter results etc.) and help to infer the future movement of the stock. We used the volume and key performance index of Apple Company's financial tweets to identify important events and infer the future movement. We present the results of machine learning algorithms (Na?ve Bayes, Maximum Entropy, and SVM) for classifying the sentiment of Apple Company's financial tweets. Statistical analysis using Granger causality test showed that we were able to infer the movement of Apple Company's stock close price in advance.
Molecular and cellular biochemistry, Jan 24, 2018
Since PI3K/Akt/mTOR and sonic hedgehog (SHH) signaling pathways are highly activated in glioblast... more Since PI3K/Akt/mTOR and sonic hedgehog (SHH) signaling pathways are highly activated in glioblastoma-initiating cells (GICs), we examined the effects of inhibiting these pathways on GIC characteristics and tumor growth in mice. NVP-LDE-225 (inhibitor of Smoothened) inhibited the expression of Gli1, Gli2, Smoothened, Patched1, and Patched2, and induced the expression of SuFu, whereas NVP-BEZ-235 (dual inhibitor of PI3K and mTOR) inhibited the expression of p-PI3K, p-Akt, p-mTOR, and p-p70S6K. NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting the self-renewal capacity of GICs, expression of pluripotency maintaining factors (Nanog, c-Myc, Oct4, and Sox2), Musashi1, cyclin D1, and Bcl-2, and transcription and expression of Gli, and in inducing the expression of cleaved caspase-3, cleaved PARP and Bim. Additionally, NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting epithelial-mesenchymal transition. Finally, the combination of NVP-LDE-225 and NVP-BEZ-235 was superior in inhibit...
Oncotarget, 2017
The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. The... more The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. These stalled replication forks then collapse to form one sided double-strand breaks, leading to apoptosis. However, colorectal cancer (CRC) stem cells rapidly repair the stalled/collapsed replication forks and overcome treatment effects. Recent evidence suggests a critical role of checkpoint kinase 1 (Chk1) in preventing the replicative stress. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents. In the present study, we have identified a novel orphan molecule NSC30049 (NSC49L) that is effective alone, and in combination potentiates 5-FU-mediated growth inhibition of CRC heterogeneous bulk and FOLFOX-resistant cell lines in culture with minimal effect on normal colonic epithelial cells. It also inhibits the sphere forming activity of CRC stem cells, and decreases the expression levels of mRNAs of CRC stem cell marker genes. Results showed that NSC49L induces 5-FU-mediated S-phase cell cycle arrest due to increased load of DNA damage and increased γ-H2AX staining as a mechanism of cytotoxicity. The pharmacokinetic analysis showed a higher bioavailability of this compound, however, with a short plasma half-life. The drug is highly tolerated by animals with no pathological aberrations. Furthermore, NSC49L showed very potent activity in a HDTX model of CRC stem cell tumors either alone or in combination with 5-FU. Thus, NSC49L as a single agent or combined with 5-FU can be developed as a therapeutic agent by targeting the Chk1 pathway in 5-FU-resistant CRC heterogeneous bulk and CRC stem cell populations.
Transportation Research Record, 1985
Presented in the paper are the results of monitoring seasonal changes in surface deflections, tem... more Presented in the paper are the results of monitoring seasonal changes in surface deflections, temperatures, moisture contents, and calculated layer moduli for six test sites in the state of Washington. The goal of the data collection and analysis was to evaluate the Washington State Department of Transportation (WSDOT) load restriction tables used on some state routes during the spring thaw. Further, a criterion was developed to estimate when seasonal load restrictions need to be applied to those pavement sections that require them. Extensive use was made in the study of the WSDOT falling weight deflectometer to obtain pavement surface deflection basins and of multilayered elastic computer programs to analyze the data.
Journal of Progressive Agriculture, 2012
Consistent and indiscriminate uses of chemical as fertilizers, insecticides, pesticides and hormo... more Consistent and indiscriminate uses of chemical as fertilizers, insecticides, pesticides and hormones have caused serious damage to human health. Erratically used chemicals remain as residues and present risks like nervous breakdown, sterility, cancers, immunological disorders in adults and Blue baby syndrome, brain cancer, leukemia and birth defects in children.
<p>(A), Pancreatic CSCs were treated with resveratrol (0–20 µM) for 24 h. The expression of... more <p>(A), Pancreatic CSCs were treated with resveratrol (0–20 µM) for 24 h. The expression of Nanog, Sox-2 and cMyc was measured by qRT-PCR. Data represent mean ± SD. * and @ = significantly different from control, P<0.05. (B), Pancreatic CSCs were treated with resveratrol (0–30 µM) for 48 h. The expression of Nanog, Oct-4 and Sox-2 was measured by the Western blot analysis. GAPDH was used as a loading control. (C), Inhibition of Nanog transcription by resveratrol. Pancreatic CSCs were transduced with Nanog reporter construct. Transduced cells were treated with resveratrol to examine the Nanog transcriptional activity. Data represent mean ± SD. *, #, @, & and ** = significantly different from control, P<0.05. (D), Pancreatic CSCs were treated with resveratrol (0–30 µM) for 36 h. The expression of ABCG2 was measured by qRT-PCR. Data represent mean ± SD. * and # = significantly different from control, P<0.05.</p
Oncotarget, Jan 5, 2015
Cancer stem cells (CSCs) play major roles in cancer initiation, progression, and metastasis. It i... more Cancer stem cells (CSCs) play major roles in cancer initiation, progression, and metastasis. It is evident from growing reports that PI3K/Akt/mTOR and Sonic Hedgehog (Shh) signaling pathways are aberrantly reactivated in pancreatic CSCs. Here, we examined the efficacy of combining NVP-LDE-225 (PI3K/mTOR inhibitor) and NVP-BEZ-235 (Smoothened inhibitor) on pancreatic CSCs characteristics, microRNA regulatory network, and tumor growth. NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting pancreatic CSC's characteristics and tumor growth in mice by acting at the level of Gli. Combination of NVP-LDE-225 and NVP-BEZ-235 inhibited self-renewal capacity of CSCs by suppressing the expression of pluripotency maintaining factors Nanog, Oct-4, Sox-2 and c-Myc, and transcription of Gli. NVP-LDE-225 co-operated with NVP-BEZ-235 to inhibit Lin28/Let7a/Kras axis in pancreatic CSCs. Furthermore, a superior interaction of these drugs was observed on spheroid formation by pancreatic CSCs isolat...
PLOS ONE, 2015
Recently approved chemotherapeutic agents to treat colorectal cancer (CRC) have made some impact;... more Recently approved chemotherapeutic agents to treat colorectal cancer (CRC) have made some impact; however, there is an urgent need for newer targeted agents and strategies to circumvent CRC growth and metastasis. CRC frequently exhibits natural resistance to chemotherapy and those who do respond initially later acquire drug resistance. A mechanism to potentially sensitize CRC cells is by blocking the DNA polymerase β (Pol-β) activity. Temozolomide (TMZ), an alkylating agent, and other DNA-interacting agents exert DNA damage primarily repaired by a Pol-β-directed base excision repair (BER) pathway. In previous studies, we used structure-based molecular docking of Pol-β and identified a potent small molecule inhibitor (NSC666715). In the present study, we have determined the mechanism by which NSC666715 and its analogs block Fen1-induced strand-displacement activity of Pol-β-directed LP-BER, cause apurinic/apyrimidinic (AP) site accumulation and induce S-phase cell cycle arrest. Induction of S-phase cell cycle arrest leads to senescence and apoptosis of CRC cells through the p53/p21 pathway. Our initial findings also show a 10-fold reduction of the IC 50 of TMZ when combined with NSC666715. These results provide a guide for the development of a target-defined strategy for CRC chemotherapy that will be based on the mechanisms of action of NSC666715 and TMZ. This combination strategy can be used as a framework to further reduce the TMZ dosages and resistance in CRC patients.
Cancer Research, 2014
Melanoma is one of the most aggressive cancers, and its incidence and mortality rate are on rise ... more Melanoma is one of the most aggressive cancers, and its incidence and mortality rate are on rise since no treatment options are available for metastatic disease. Recent evidences from in vitro and in vivo studies have demonstrated that aberrant reactivation of the Sonic Hedgehog (SHH) signaling pathway regulates genes that promote cellular proliferation in various human cancer stem cells (CSC) 36118-45. In melanoma cells, RAS-MEK and AKT signaling has also been shown to regulate the nuclear localization and transcriptional activity of Gli-1. Therefore, the agents that inhibit activation of Gli transcription factors have emerged as promising novel therapeutic drugs for pancreatic cancer. Through extensive structure-activity studies in our laboratory, based on naturally occurring isothiocyanates (ITCs) and their isosteric selenium analogs, we have recently identified phenylbutyl isoselecynate (ISC-4) as a promising agent that significantly retarded melanoma tumor growth without any systemic toxicity. We demonstrate here the effect of ISC-4 on the proliferation of CSC and 36118-45CTC (circulating tumor cell) cells isolated from a melanoma patient. ISC-4 treatments resulted in a dose-dependent inhibition of SHH signaling (SMO, PTCH-1, Gli1, Gli2, and Gli3) and induced significant growth inhibition of CSC and CTC cells. The data demonstrate that Hh signaling regulates proliferation of CSC and CTC of human melanoma and treatment with agents like ISC-4 might be a novel approach to prevent growth and metastasis of human melanoma. Citation Format: Arun K. Sharma, Jitesh Jani, Cristian Sharma, Patrick Cleary, Michael Sharma, Shruthi Satish, Esteban Gomez, Michael Prez, Natalee Amezcua, Mariam Navel, Deepkamal N. Karelia, Dhimant Desai, Shantu Amin, Jay Sharma. ISC-4, a novel inhibitor of hedgehog-Gli signaling, inhibits growth of CSC and CTC of melanoma patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2712. doi:10.1158/1538-7445.AM2014-2712
Cancer Research, 2014
Cancer stem cells (CSCs) are critical for engraftment and long-term growth of many tumors, includ... more Cancer stem cells (CSCs) are critical for engraftment and long-term growth of many tumors, including pancreatic cancer. The Cancer Stem cells are less sensitive to conventional chemotherapies and radiation therapies, and treatments that can target CSCs are critically needed. Human Pancreatic Cancer is a heterogeneous tumor composed of tumor cells and small fraction of cancer stem cells, with high tumorigenic potential. Pancreatic cancer stem cells are phenotypically similar to the normal stem cells, they express CD133 gene and other genes characteristic of neural stem cells (Nestin) and posses self-renewal potential. The CD133+ Pancreatic CSCs have been isolated with Celprogen Media and ECM and characterized as chemo-/radio-resistant tumor-initiating cells which are responsible as one of the major factors involved in post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ Pancreatic CSCs that resist treatment, we isolated CD133+ Pancreatic CSCs ...
Metabolic Brain Disease, 2014
Despite major advances in the understanding about ethanol actions, the precise underlying neurobi... more Despite major advances in the understanding about ethanol actions, the precise underlying neurobiological mechanisms for ethanol dependence remain largely elusive. We recently reported that inhibition of dipeptidyl-peptidase IV (DPP-IV), an enzyme responsible for metabolism of endogenous glucagon-like peptide-1 (GLP-1), delays tolerance to anti-anxiety effect of ethanol and withdrawal-induced anxiety in rats. Intrigued with this report, present study examined the role of glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide in (1) acute anti-anxiety effect of ethanol; (2) tolerance to ethanol&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s anti-anxiety-effect and (3) ethanol withdrawal-induced anxiety using elevated plus maze (EPM) test in rats. Ethanol (2 g/kg, i.p.; 8 % w/v) and liraglutide (50 μg/kg, i.p.) treatments exhibited anti-anxiety effect in EPM test. Doses of ethanol (1.0 or 1.5 g/kg, i.p.) that were not effective per se elicited anti-anxiety when combined with sub-effective dose of liraglutide (25 μg/kg, i.p.). Rats consuming ethanol-diet (6 % v/v) exhibited tolerance to anti-anxiety effect of ethanol from day-7 of ethanol consumption. Peak ethanol withdrawal-induced anxiety was observed at 8-10 h upon abstinence from ethanol-diet after 15-days consumption. Rats on simultaneous once-daily liraglutide treatment (50 μg/kg, i.p.) neither had any signs of tolerance to anti-anxiety effect of ethanol nor did they exhibit withdrawal-induced anxiety. In conclusion: (1) GLP-1 agonist, liraglutide exhibited anti-anxiety effect per se; (2) potentiated anti-anxiety effect of ethanol; (3) prevented development tolerance to anti-anxiety effect of ethanol and (4) prevented withdrawal-induced anxiety. Further studies examining intracellular cascade of events contributing to these effects may help to improve understanding about role of GLP-1 receptors in ethanol mediated behaviors.
Proceedings of the IEEE INDICON 2004. First India Annual Conference, 2004.
... KHARAGPUR 721302, DECEMBER 20-22,2004 103 Counterpropagation Network for Voltage Contingency ... more ... KHARAGPUR 721302, DECEMBER 20-22,2004 103 Counterpropagation Network for Voltage Contingency Ranking Exploiting Coherency for Feature Selection Manjaree Pandit, Laxmi Srivastava and Jaydev Sharma Abstract ... SR/S3/EECE/14/2003-SERC dated 11/5/2004. ...
International Journal of Electrical Power & Energy Systems, 2001
many advantages, such as excellent performance and enhanced safety. The performance improvement i... more many advantages, such as excellent performance and enhanced safety. The performance improvement is achieved because of strong mechanical integrity (cycle life) and absence of binder (shelf life) in CC composite. The enhancement in safety comes from high thermal conductivity, fire retardant characteristics and an acceptable ability to overcharge and overdischarge.
International Journal of Power and Energy Systems, 2005
ABSTRACT
Annals of the rheumatic diseases, Jan 6, 2014
In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) that line joint synovial membran... more In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) that line joint synovial membranes aggressively invade the extracellular matrix, destroying cartilage and bone. As signal transduction in FLS is mediated through multiple pathways involving protein tyrosine phosphorylation, we sought to identify protein tyrosine phosphatases (PTPs) regulating the invasiveness of RA FLS. We describe that the transmembrane receptor PTPκ (RPTPκ), encoded by the transforming growth factor (TGF) β-target gene, PTPRK, promotes RA FLS invasiveness. Gene expression was quantified by quantitative PCR. PTP knockdown was achieved using antisense oligonucleotides. FLS invasion and migration were assessed in transwell or spot assays. FLS spreading was assessed by immunofluorescence microscopy. Activation of signalling pathways was analysed by Western blotting of FLS lysates using phosphospecific antibodies. In vivo FLS invasiveness was assessed by intradermal implantation of FLS into nude mice. The...
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Papers by jay prakash sharma