We predict the effect of the charm structure function on the longitudinal structure function at small x. In NLO analysis we find that the hard Pomeron behavior gives a good description of FL and Fk^c （k = 2, L） at s...We predict the effect of the charm structure function on the longitudinal structure function at small x. In NLO analysis we find that the hard Pomeron behavior gives a good description of FL and Fk^c （k = 2, L） at small x values. We conclude that a direct relation between FL∝ F2^c would provide useful information on how to measure longitudinal structure function at high 0,2 values. Having checked that this model gives a good description of the data, when compared with other models.展开更多
Background:The JAK2^(V617F)mutation plays a crucial part in the pathogenesis of myeloproliferative neoplasms(MPN),which includes polycythemia vera(PV),essential thrombocythemia(ET),and primary myelofibrosis(PMF)leadin...Background:The JAK2^(V617F)mutation plays a crucial part in the pathogenesis of myeloproliferative neoplasms(MPN),which includes polycythemia vera(PV),essential thrombocythemia(ET),and primary myelofibrosis(PMF)leading to aberrant proliferation and survival of hematopoietic cells.Alongside the challenges of drug resistance and side effects,identifying novel compounds that selectively target JAK2^(V617F)could provide more effective and safer therapeutic options for patients with MPNs.Materials and Methods:We employed computational approaches like high-throughput virtual screening,molecular dynamics simulations(MDS),and binding free energy calculations to identify inhibitors targeting wild and mutant JAK2 kinases.JAK2^(V617F)positive HEL,wild type JAK2 positive TF-1,and non-cancerous Vero cells were used for in vitro validations.Results:SBLJ23 emerged as a top candidate inhibitor with specificity for JAK2^(V617F).Protein-ligand interaction studies and MDS revealed stable interactions and binding of SBLJ23 over the simulation period,with Root Mean Square Deviation(RMSD)indicating consistent binding after 1t15ns.SBLJ23 displayed a half maximal inhibitory concentration(IC_(50))value of 522.4 nM against the JAK2 enzyme.The compound exhibited inhibition of cell proliferation in HEL and TF-1 cells,with half maximal cell growth inhibitory concentration(GI 50)values of 2.51 and 15.87μM,respectively.Moreover,SBLJ23 induced G 2/M cell cycle arrest in HEL cells to facilitate apoptosis in these cell lines.The compound significantly reduced the percentage of phospho JAK2 and phospho STAT3 in HEL cells.Conclusion:High binding affinity,stable interaction profile,favorable binding free energy,and in vitro validations claim SBLJ23 as a potential lead compound against JAK2^(V617F)and suggest further development and optimization towards clinical application in managing myeloproliferative neoplasms.展开更多
文摘We predict the effect of the charm structure function on the longitudinal structure function at small x. In NLO analysis we find that the hard Pomeron behavior gives a good description of FL and Fk^c （k = 2, L） at small x values. We conclude that a direct relation between FL∝ F2^c would provide useful information on how to measure longitudinal structure function at high 0,2 values. Having checked that this model gives a good description of the data, when compared with other models.
文摘Background:The JAK2^(V617F)mutation plays a crucial part in the pathogenesis of myeloproliferative neoplasms(MPN),which includes polycythemia vera(PV),essential thrombocythemia(ET),and primary myelofibrosis(PMF)leading to aberrant proliferation and survival of hematopoietic cells.Alongside the challenges of drug resistance and side effects,identifying novel compounds that selectively target JAK2^(V617F)could provide more effective and safer therapeutic options for patients with MPNs.Materials and Methods:We employed computational approaches like high-throughput virtual screening,molecular dynamics simulations(MDS),and binding free energy calculations to identify inhibitors targeting wild and mutant JAK2 kinases.JAK2^(V617F)positive HEL,wild type JAK2 positive TF-1,and non-cancerous Vero cells were used for in vitro validations.Results:SBLJ23 emerged as a top candidate inhibitor with specificity for JAK2^(V617F).Protein-ligand interaction studies and MDS revealed stable interactions and binding of SBLJ23 over the simulation period,with Root Mean Square Deviation(RMSD)indicating consistent binding after 1t15ns.SBLJ23 displayed a half maximal inhibitory concentration(IC_(50))value of 522.4 nM against the JAK2 enzyme.The compound exhibited inhibition of cell proliferation in HEL and TF-1 cells,with half maximal cell growth inhibitory concentration(GI 50)values of 2.51 and 15.87μM,respectively.Moreover,SBLJ23 induced G 2/M cell cycle arrest in HEL cells to facilitate apoptosis in these cell lines.The compound significantly reduced the percentage of phospho JAK2 and phospho STAT3 in HEL cells.Conclusion:High binding affinity,stable interaction profile,favorable binding free energy,and in vitro validations claim SBLJ23 as a potential lead compound against JAK2^(V617F)and suggest further development and optimization towards clinical application in managing myeloproliferative neoplasms.
