Noncommmutative theorems: Gelfand Duality, Spectral, Invariant Subspace, and Pontryagin Duality

We extend the Gelfand-Naimark duality of commutative C*-algebras, "A COMMUTATIVE C*-ALGEBRA -- A LOCALLY COMPACT HAUSDORFF SPACE" to "A C*-ALGEBRA--A QUOTIENT OF A LOCALLY COMPACT HAUSDORFF SPACE". Thus, a C*-algebra is isomorphic to the convolution algebra of continuous regular Borel measures on the topological equivalence relation given by the above mentioned quotient. In commutative case this reduces to Gelfand-Naimark theorem. Applications: 1) A simultaneous extension, to arbitrary Hilbert space operators, of Jordan Canonical Form and Spectral Theorem of normal operators 2) A functional calculus for arbitrary operators. 3) Affirmative solution of Invariant Subspace Problem. 4) Extension of Pontryagin duality to nonabelian groups, and inevitably to groups whose underlying topological space is noncommutative.Comment: 10 page

Sensitive allele specific oligonucleotide-polymerase chain reaction in detection of preexisting mutations in imatinib-resistant chronic myelogenous leukemia patients: A retrospective analysis

Introduction: Pre-existing BCR-ABL kinase domain mutation leads to Imatinib resistance. Methods: Retrospective analysis of 50 patients of Imatinib resistance was done in GCRI, from January 2014 till May 2014. Allelle Specific Oligonucleotide–Polymerase Chain Reaction (ASO-PCR) was performed on Genomic DNA, of peripheral blood mononuclear cells (PBMCs). Results: 47 (94%) were in Chronic phase, 2 (4%) in accelerated phase, 1 (2%) in blastic crisis. Median duration of Imatinib was 48 months. 43/50 had one or more than 1 mutation, T315I mutation in 5 (10%) patients, M351T in 32% (16/50) and F311L in 8. Conclusion: We report low cytogenetic response (25%) and durability of response to 600 mg of Imatinib, even in M351T mutation

Coagonist of GLP-1 and glucagon receptors ameliorates non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is often associated with obesity and type 2 diabetes. Coagonist of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) are under clinical investigation for the treatment of obesity and type 2 diabetes. In this study, we have demonstrated the effect of a balanced coagonist in the treatment of NAFLD using mice models. GLP-1R agonist exendin-4, glucagon, and coagonist (Aib2 C24 Chimera2) were administered to C57BL6/J mice, in which NAFLD was induced by carbon tetrachloride (CCl4) treatment after in high fat diet (HFD) feeding, and CDAHFD (choline-deficient, L-amino acid-defined, HFD). Repeated dose administration of coagonist significantly attenuated liver inflammation and steatosis induced by acute and long-term treatment with CCl4 in HFD-fed mice. Coagonist markedly attenuated the CDAHFD-induced expression of TIMP-1, MMP-9, TNF-Îą, MCP-1, COL1A1 and Îą-SMA. It also inhibited progression of hepatic steatosis and fibrosis in mice. Exendin-4 was better than glucagon, but coagonist was most effective in reduction of hepatic inflammation as well as steatosis. Coagonist of GLP-1R and GCGR improved NAFLD in C57BL6/J mice. This effect is mediated by reduction in lipotoxicity and inflammation in liver.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state

Many anemic chronic kidney disease (CKD) patients are refractory to erythropoietin (EPO) effects due to inflammation, deranged iron utilization, and generation of EPO antibodies. This work assessed the effect of desidustat, an inhibitor of hypoxia inducible factor (HIF) prolyl hydroxylase (PHD), on EPO-refractory renal anemia. Sprague Dawley rats were made anemic by cisplatin (5 ​mg/kg, IP, single dose) and turpentine oil (5 ​mL/kg, SC, once a week). These rats were given recombinant human EPO (rhEPO, 1 ​μg/kg) and desidustat (15 or 30 ​mg/kg) for eight weeks. Separately, rhEPO (1–5 ​μg/kg) was given to anemic rats to sustain the normal hemoglobin levels and desidustat (15 ​mg/kg) for eight weeks. In another experiment, the anemic rats were treated rhEPO (5 ​μg/kg) for two weeks and then desidustat (15 ​mg/kg) for the next two weeks. Dosing of rhEPO was thrice a week, and for desidustat, it was on alternate days. Desidustat inhibited EPO-resistance caused by rhEPO treatment, decreased hepcidin, IL-6, IL-1β, and increased iron and liver ferroportin. Desidustat reduced EPO requirement and anti-EPO antibodies. Desidustat also maintained normal hemoglobin levels after cessation of rhEPO treatment. Thus, novel prolyl hydroxylase inhibitor desidustat can treat EPO resistance via improved iron utilization and decreased inflammation