Bulk Kalb-Ramond field in Randall Sundrum scenario

We have considered the most general gauge invariant five-dimensional action of a second rank antisymmetric Kalb-Ramond tensor gauge theory, including a topological term of the form $\epsilon^{ABLMN}B_{AB}H_{LMN}$ in a Randall-Sundrum scenario. Such a tensor field $B_{AB}$ (whose rank-3 field strength tensor is $H_{LMN}$), which appears in the massless sector of a heterotic string theory, is assumed to coexist with the gravity in the bulk. The third rank field strength corresponding to the Kalb-Ramond field has a well-known geometric interpretation as the spacetime torsion. The only non-trivial classical solutions corresponding to the effective four-dimensional action are found to be self-dual or anti-selfdual Kalb-Ramond fields. This ensures that the four-dimensional effective action on the brane is parity-conserving. The massive modes for both cases, lying in the TeV range, are related to the fundamental parameters of the theory. These modes can be within the kinematic reach of forthcoming TeV scale experiments. However, the couplings of the massless as well as massive Kalb-Ramond modes with matter on the visible brane are found to be suppressed vis-a-vis that of the graviton by the warp factor, whence the conclusion is that both the massless and the massive torsion modes appear much weaker than curvature to an observer on the visible brane.Comment: 15 Pages,2 figures,Late

Phronesis of AI in radiology: Superhuman meets natural stupidity

Advances in AI in the last decade have clearly made economists, politicians, journalists, and citizenry in general believe that the machines are coming to take human jobs. We review 'superhuman' AI performance claims in radiology and then provide a self-reflection on our own work in the area in the form of a critical review, a tribute of sorts to McDermotts 1976 paper, asking the field for some self-discipline. Clearly there is an opportunity to replace humans, but there are better opportunities, as we have discovered to fit cognitive abilities of human and non-humans. We performed one of the first studies in radiology to see how human and AI performance can complement and improve each others performance for detecting pneumonia in chest X-rays. We question if there is a practical wisdom or phronesis that we need to demonstrate in AI today as well as in our field. Using this, we articulate what AI as a field has already and probably can in the future learn from Psychology, Cognitive Science, Sociology and Science and Technology Studies

OXIDATIVE STRESS-BASED HEPATOTOXICITY OF DULOXETINE IN WISTAR RATS

Objective: Duloxetine, a selective serotonin and noradrenaline reuptake inhibitor used in major depressive disorders, urinary incontinence and diabetic peripheral neuropathic pain. It is reported to be associated with several types of liver injuries, including hepatocellular, cholestatic and mixed hepatocellular-cholestatic patterns. The objective of this study was to assess the effect of duloxetine or its metabolites on oxidative stress-induced liver damages.Methods: In this study, animals were divided into five groups. In the first group, the only vehicle was given orally for 21 d. The second group has been considered as hepatotoxic control group where Erythromycin was given orally for 14 d and remaining three groups have been considered as test groups where duloxetine, fluvoxamine and duloxetine along with fluvoxamine were administered orally for 21 d. Liver GSH, oxidised lipid (malonaldehyde MDA), superoxide dismutase (SOD), catalase (CAT), protein carbonyl (PC) and plasma alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels were measured to determine the level of hepatotoxicity. Scanning electron microscopy (SEM) study of liver tissues was also performed to examine the liver injuries.Results: GSH and SOD levels were found to be decreased in duloxetine-treated groups with respect to the hepatotoxic control group, whereas increased level of MDA, CAT and PC signify the damages of liver cells. Increased level of plasma ALT, AST and ALP at the same time indicated liver tissue damage. Opposite effects were observed in the case of duloxetine and fluvoxamine-treated groups. SEM of liver tissues revealed that the tissue injury occurred in Duloxetin treated groups, whereas the restoration of normal tissue architecture took place due to the administration of duloxetine and fluvoxamine-treated groups.Conclusion: Our results collectively indicated that hydroxylated and epoxide metabolites of duloxetine might have hepatotoxic potential due to oxidative stress produced by the release of free radicals or reactive oxygen species

A novel pathway for amyloids self-assembly in aggregates at nanomolar concentration mediated by the interaction with surfaces.

A limitation of the amyloid hypothesis in explaining the development of neurodegenerative diseases is that the level of amyloidogenic polypeptide in vivo is below the critical concentration required to form the aggregates observed in post-mortem brains. We discovered a novel, on-surface aggregation pathway of amyloidogenic polypeptide that eliminates this long-standing controversy. We applied atomic force microscope (AFM) to demonstrate directly that on-surface aggregation takes place at a concentration at which no aggregation in solution is observed. The experiments were performed with the full-size Aβ protein (Aβ42), a decapeptide Aβ(14-23) and α-synuclein; all three systems demonstrate a dramatic preference of the on-surface aggregation pathway compared to the aggregation in the bulk solution. Time-lapse AFM imaging, in solution, show that over time, oligomers increase in size and number and release in solution, suggesting that assembled aggregates can serve as nuclei for aggregation in bulk solution. Computational modeling performed with the all-atom MD simulations for Aβ(14-23) peptide shows that surface interactions induce conformational transitions of the monomer, which facilitate interactions with another monomer that undergoes conformational changes stabilizing the dimer assembly. Our findings suggest that interactions of amyloidogenic polypeptides with cellular surfaces play a major role in determining disease onset

ANTIPROLIFERATIVE EFFECT OF FLOWER EXTRACTS OF SPILANTHES PANICULATA ON HEPATIC CARCINOMA CELLS

Objective: The development and evaluation of new antiproliferative drugs obtained from natural resources has gained its importance because of their less cytotoxic properties. There is no such report regarding antiproliferative effect of Spilanthes paniculata Linn. flower. Therefore, the present study was undertaken to evaluate the antiproliferative effect of Spilanthes paniculata Linn. flower.Methods: In order to achieve this goal, the dried flowers were extracted in petroleum ether, ethyl acetate and ethanol. All these three extracts of varying concentrations were subjected to further evaluation of antiproliferative action on human hepatoma cell line (Huh-7 cells). In order to understand the mechanism of antiproliferative effect of these three extracts, various studies like caspase-3 enzyme assay, DNA transillumination assay and receptor tyrosine kinase profiling were performed. Separately, we estimated total flavonoid and phenolic contents and in vitro free radical scavenging properties of these extracts.Results: The results indicated that both ethyl acetate and ethanol extracts possessed antiproliferative effect on Huh-7 cells because of their induction of caspase-3 enzymes and inhibition of phosphorylation of various tyrosine kinases. It was observed that during the transillumination assay of the ethyl acetate and ethanol extracts, DNA of Huh-7 cells were also degraded. It was also found that these two extracts possessed potent antiproliferative effect on Huh-7 cells due to the presence of rich amount of phenols and flavonoids.Conclusion: Based on our data, both ethyl acetate and ethanol extracts might be beneficial for the future development of antiproliferative therapeutics in drug design perspective. Â

Phronesis of AI in radiology: Superhuman meets natural stupidity

Advances in AI in the last decade have clearly made economists, politicians, journalists, and citizenry in general believe that the machines are coming to take human jobs. We review 'superhuman' AI performance claims in radiology and then provide a self-reflection on our own work in the area in the form of a critical review, a tribute of sorts to McDermotts 1976 paper, asking the field for some self-discipline. Clearly there is an opportunity to replace humans, but there are better opportunities, as we have discovered to fit cognitive abilities of human and non-humans. We performed one of the first studies in radiology to see how human and AI performance can complement and improve each others performance for detecting pneumonia in chest X-rays. We question if there is a practical wisdom or phronesis that we need to demonstrate in AI today as well as in our field. Using this, we articulate what AI as a field has already and probably can in the future learn from Psychology, Cognitive Science, Sociology and Science and Technology Studies

Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach

One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED) and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM) or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches

Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition

Hedgehog signaling drives oncogenesis in several cancers and strategies targeting this pathway have been developed, most notably through inhibition of Smoothened. However, resistance to Smoothened inhibitors occurs via genetic changes of Smoothened or other downstream Hedgehog components. Here, we overcome these resistance mechanisms by modulating GLI transcription via inhibition of BET bromodomain proteins. We show the BET bromodomain protein, BRD4, regulates GLI transcription downstream of SMO and SUFU and chromatin immunoprecipitation studies reveal BRD4 directly occupies GLI1 and GLI2 promoters, with a substantial decrease in engagement of these sites upon treatment with JQ1, a small molecule inhibitor targeting BRD4. Globally, genes associated with medulloblastoma-specific GLI1 binding sites are downregulated in response to JQ1 treatment, supporting direct regulation of GLI activity by BRD4. Notably, patient- and GEMM-derived Hedgehog-driven tumors (basal cell carcinoma, medulloblastoma and atypical teratoid/rhabdoid tumor) respond to JQ1 even when harboring genetic lesions rendering them resistant to Smoothened antagonists

A review on TORCH groups of congenital infection during pregnancy

Abstract TORCH, includes Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19, Hepatitis B), Rubella, Cytomegalovirus (CMV), and Herpes infections are some of the most common infections associated with congenital anomalies. Most of the TORCH infections have serious fetal consequences and there has no impact on fetal outcome. In the present article, we wanted to discuss about the causative agents/organism, mode of infection, symptoms, treatment, vaccination, available molecular biological techniques and public awareness regarding this infection