Finding a Way Out of the Ethnographic Paradigm Jungle

In this paper, an attempt has been made to develop a hybrid ethnographic paradigm, taking the best points from the different approaches of ethnographic research. The pioneering proponents of ethnography differed in their conceptualization of the method, resulting in the development of three distinct schools of thought-holistic, semiotic and behavioristic. These three ethnographic paradigms have their respective benefits and shortcomings. Following any one of these approaches may lead to only partial comprehension of the phenomenon by the ethnographer. This study wished to address this issue by developing a best practice approach, which will have the virtues of all the three paradigms. It is hoped that this evolved paradigm will help in making the work of the ethnographer a lot more comprehensive and the experience much richer

Functional and Structural Analyses of CYP1B1 Variants Linked to Congenital and Adult-Onset Glaucoma to Investigate the Molecular Basis of These Diseases

Glaucoma, the leading cause of irreversible blindness, appears in various forms. Mutations in CYP1B1 result in primary congenital glaucoma (PCG) by an autosomal recessive mode of inheritance while it acts as a modifier locus for primary open angle glaucoma (POAG). We investigated the molecular basis of the variable phenotypes resulting from the defects in CYP1B1 by using subclones of 23 CYP1B1 mutants reported in glaucoma patients, in a cell based system by measuring the dual activity of the enzyme to metabolize both retinol and 17β-estradiol. Most variants linked to POAG showed low steroid metabolism while null or very high retinol metabolism was observed in variants identified in PCG. We examined the translational turnover rates of mutant proteins after the addition of cycloheximide and observed that the levels of enzyme activity mostly corroborated the translational turnover rate. We performed extensive normal mode analysis and molecular-dynamics-simulationsbased structural analyses and observed significant variation of fluctuation in certain segmental parts of the mutant proteins, especially at the B-C and F-G loops, which were previously shown to affect the dynamic behavior and ligand entry/exit properties of the cytochrome P450 family of proteins. Our molecular study corroborates the structural analysis,and suggests that the pathologic state of the carrier of CYP1B1 mutations is determined by the allelic state of the gene. To our knowledge, this is the first attempt to dissect biological activities of CYP1B1 for correlation with congenital and adult onset glaucomas

Heat Killed Attenuated Leishmania Induces Apoptosis of HepG2 Cells Through ROS Mediated p53 Dependent Mitochondrial Pathway

Cytotoxic effect of attenuated Leishmania on liver cancer cells by inducing ROS generation. Methods: Spectrophotometric study to analyze cell death and levels of different active caspases. Flow cytometric study was done to analyze apoptosis induction and ROS generation and levels of different protein. Western blot analysis was performed to study the levels of protein. Confocal microscopy was done to ascertain the expression of different apoptotic markers. Results: We have now observed that attenuated Leishmania donovani UR6 also has potentiality towards growth inhibition of HepG2 cells and investigated the mechanism of action. The effect is associated with increased DNA fragmentation, rise in number of annexinV positive cells, and cell cycle arrest at G1 phase. The detection of unregulated levels of active PARP, cleaved caspases 3 and 9, cytosolic cytochrome C, Bax, and Bad, along with the observed downregulation of Bcl-2 and loss of mitochondrial membrane potential suggested the involvement of mitochondrial pathway. Enhanced ROS and p53 levels regulate the apoptosis of HepG2 cells. NAC was found to inhibit p53 production but PFT-α has no effect on ROS generation. In conclusion, Leishmania donovani UR6 efficiently induces apoptosis in HepG2 cells through ROS mediated p53 dependent mitochondrial pathway. Conclusion: It has been reported earlier that some parasites show prominent cytotoxic effect and prevent tumor growth. From our study we found that Leishmania donovani UR6 efficiently induced apoptosis in HepG2 cells through ROS mediated p53 dependent mitochondrial pathway. This study has rejuvenated the age old idea of bio-therap

Signatures of regular black holes from the shadow of Sgr A* and M87*

With the recent release of the black hole image of Sgr A* alongside the earlier image of M87*, one can now really hope to acquire a better understanding of the gravitational physics at the horizon scale. In this paper, we investigate the prospect of the regular black hole scenario with a Minkowski core in explaining the observed shadow of M87* and Sgr A*. Regular black holes generally appear in Einstein gravity coupled to non-linear electrodynamics and are interesting as they can evade the r = 0 curvature singularity arising in general relativity. Using the previously determined mass and distance we compute the observables associated with the black hole shadow. These when compared with the observed angular diameter reveal that the shadow of M87* and Sgr A* favor the regular black hole scenario with a small but non-zero charge. The implications are discussed.Comment: 23 pages, 9 figures, matches published version (JCAP accepted

A PROSPECTIVE AND COMPARATIVE STUDY ON CONCURRENT RADIOTHERAPY WITH GEFITINIB VERSUS RADIOTHERAPY ALONE IN THE TREATMENT OF ELDERLY PATIENTS WITH CARCINOMA OESOPHAGUS

Objective: Concurrent chemoradiotherapy (CTRT) is the primary treatment for inoperable carcinoma esophagus. However, elderly patients are often not capable of tolerating CTRT, leaving radiotherapy as only option available for them. Many studies showed efficacy of anti-EGFR agent Gefitinib with acceptable toxicity profile in carcinoma esophagus patients. Hence, in this study, we compared radiation along with Gefitinib against radiation alone for the treatment of inoperable esophageal carcinoma in elderly patients in terms of locoregional control and toxicity profile. Methods: Patients of 50–70 years age group with inoperable squamous cell carcinoma esophagus were randomized in two groups – the control group received external beam radiotherapy 50.4 Gy in two phases over 5 weeks and the study group received radiotherapy with same dose along with Tab Gefitinib-250 mg daily during the radiotherapy. Response assessment was done after completion of treatment and all patients were followed up weekly during the course of treatment and then at every month for at least 6 months. Results: Overall response rate (complete+partial response) was better in study arm (80% vs. 70%), but not statistically significant (p=0.221). Just after treatment completion dysphagia of grade2 and above was more in control arm but after 3 months there was rise in incidences of dysphagia in study arm (66.6% vs. 60% p=0.632). Although statistically not significant, gefitinib containing study arm showed more incidences of higher grade of diarrhoea (20% vs. 15%, p=0.843) and moderate to severe grade of anaemia (90% vs. 66%, p=0.921). Conclusion: We can say that concomitant treatment with Gefitinib and radiotherapy was well tolerated and effective in elderly patients of inoperable carcinoma esophagus