Letteratura scientifica selezionata sul tema "Ekta Parishad (New Delhi, India)"

Abstract Professor G.C. Sharma is well recognized leading mathematician well associated with Vijñāna Parishad of India since 1990. He was honored by DISTINGUISHED SERVICE AWARD of VPI in 1996 during 6ᵗʰ Annual Conference of VPI held at Bundelkhand Institute of Engineering and Technology, Jhansi, Uttar Pradesh, India [December 26-28, 1996]. Professor G.C. Sharma has credit to grace the chair of President of VPI [April 2008- March 2011]. He was elected as Honorary Fellow of VPI (FVPI) in 2007 during 12ᵗʰ Annual Conference of VPI held at J.N.V. University, Jodhpur, Rajasthan, India [October 25-27,2007]. Professor Sharma was also honored by Highest Prestigius VPI Award “LIFE-LONG ACHIEVEMENT AWARD” during 20ᵗʰ Annual Conference of VPI held at Manipal University, Jaipur, Rajasthan, India [November 24-26, 2017]. Professor Sharma was recently honored by “VPI GOLDEN JUBILEE AWARD” during 5ᵗʰ International Conference and Goden Jubilee Celebrations of VPI held at J. N. U., New Delhi, India [June 16-18,2022]. Professor G. C. Sharma is also active member on Editorial Board of Jñānābha.

Abstract An endeavour has been made to assess the spatial fluctuation of the profundity of endured and designing bedrock in Gorakhpur Uttar Pradesh, North India utilizing Multichannel Analysis of Surface Wave (MASW) study. One-layered MASW study has been done at Madan Mohan Malaviya University of Technology, Gorakhpur campus and Shear-wave Velocity V S 30 are estimated. MASW overview at 3 location and a Standard Penetration Test SPT-N from the profound geotechnical boreholes data used for comparison of site classification. The deduction of this work might be utilized as contributions for seismic tremor risk the board by lessening the seriousness of earthquake shaking through plan of tremor Earthquake risk resilient structure strong designs. The data that collected from the MASW experimental setup is feed using the software ParkSEIS (v.3.0), we obtain Shear Wave Velocity (VS30 ). The obtained V S 30 is used to plot Response Spectra for MMMUT Gorakhpur. The Time History data used in this thesis is Nepal Earthquake 2015 data which is collected from Indian Metrological Department (IMD) Delhi, India. SPT-N value data is collected from Awas Vikas Parishad for the New Administration Building build at MMMUT campus Gorakhpur. The Time History data of Nepal Earthquake 2015 is analysed using DEEPSOIL v7 Software and a systematic layer wise study of MMMUT Campus soil is carried out, results such as Ground Motion Parameters, Response Spectra, Spectral acceleration vs Frequency plot, Tripartite Spectrum and Response spectra corresponding to 5% damping are obtained.

BackgroundHematopoietic progenitor kinase 1 (HPK1, MAP4K1), is a negative regulator of T and B cell receptor signaling.1 2 3 A strong anti-tumor immunogenic response and tumor rejection was observed in mice with HPK1 gene knocked out.3 Treatment of HPK1 kinase dead mice with immune check-point blockers (ICBs) demonstrated enhanced tumor growth inhibition.3 Hence, HPK1 is an attractive therapeutic strategy for immuno-oncology based treatment in cancers. In comparison to our previous HPK1 small molecule inhibitor, PCC,4 we present here a differentiated novel HPK1 inhibitor, PCC-1 with good anti-T cell kinases selectivity and stronger anti-tumor efficacy in CT26 tumor model. In addition, using the syngeneic model of MC38 expressing human PD-L1, we present for the first time, the combination efficacy of a HPK1 inhibitor with the clinical ICB, Atezolizumab.MethodsIntuitive medicinal chemistry complemented by structure-based drug design was used to identify & develop potent inhibitors of HPK1 with optimal kinase selectivity, PK and in vivo efficacy profile. The SAR efforts were guided by biochemical assays, functional read-outs and primary human in vitro T-cell activation assays. In vivo target engagement and pharmacodynamic data was generated using CT26 and MC38-hPD-L1 tumor models.ResultsPCC-1 has sub-nanomolar HPK1 inhibition potency and strong target engagement resulting in pSLP76 inhibition, enhanced anti-tumor cytokine production of IL-2 and/or IFNgamma in Jurkat cells, human PBMCs and human whole blood. PCC-1 also demonstrated nanomolar potency in inducing a complete reversal of PGE2 or adenosine mediated immunosuppression. Oral dosing of PCC-1 as a single agent, induced strong tumor growth inhibition (TGI) in the syngeneic model of CT26 and MC38-hPD-L1 tumor models. Combination of PCC-1 with anti-CTLA4 in CT26 tumor model induced significantly greater TGI than anti-CTLA4 alone. Moreover, as a first, the combination of PCC-1 with clinical ICB, Atezolizumab in MC38-hPD-L1 induced enhanced rejection of tumors. These results strongly suggest PCC-1 as a promising candidate for HPK1 inhibition and as a combination partner with ICBs in clinic.ConclusionsPCC-1 is a novel, orally active HPK1 inhibitor that demonstrates excellent stand-alone efficacy and enhances current immunotherapy efficacy. Further evaluation of PCC-1 is ongoing to advance towards clinic.AcknowledgementsWe thank Dnyaneshwar Dahale, Sanjay Patale, Sandip Patil, Vidya Kattige, Jiju Mani, Namrata Singh, Ekta Kashyap, Sandeep Thorat, Pankaj Jain and Pramod Sagar for their contributions to the projectTrial RegistrationN/AReferencesKiefer F, et al. The EMBO Journal 1996.Hu, et al. Genes and Development 1996.Sawasdikosol, Burakoff. eLife 2020;9:e55122.Sachin S Chaudhari, et al. Poster#1709, AACR Annual Meeting April-May 2021.Ethics ApprovalThe studies involving animals have obtained ethics approval from Institutional Animal Ethics Committee (IAEC), The Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), New Delhi, India, GRC/IAEC/472/2020-1. Participants of the studies have given informed consent before taking part.