Superoxide anion mediated mitochondrial dysfunction leads to hepatocyte apoptosis preferentially in the periportal region during copper toxicity in rats

Chronic exposure to copper induces hepatocellular apoptosis with greater injury in the periportal region compared to the perivenous region. Here we have identified the factors responsible for the development of regional damage in the liver under in vivo conditions. Enhanced production of reactive oxygen species (ROS) with predominance of superoxide radical (O2•−) indicates the contribution of redox imbalance in the process. This may be linked with copper catalyzed oxidation of GSH to GSSG resulting in the generation of O2•−. Downregulation of Cu-Zn SOD in consequence of the degradation of this enzyme, causes decreased dismutation of O2•−, that further contributes to the enhanced level of O2•− in the periportal region. Decreased functioning of Mn SOD activity, reduction in mitochondrial thiol/disulphide ratio and generation of O2•− were much higher in the mitochondria from periportal region, which point to the involvement of this organelle in the regional hepatotoxicity observed during copper exposure. This was supported by copper-mediated enhanced mitochondrial dysfunction as evident from ATP depletion, collapse of mitochondrial membrane potential (MMP) and induction of mitochondrial permeability transition (MPT). Results suggest the active participation of O2•− in inducing mitochondrial dysfunction preferentially in the periportal region that eventually leads to the development of hepatotoxicity due to copper exposure under in vivo condition

Survey of Credit Rating Methodologies of Mutual Funds: Standard and Poor’s and Moody’s

Credit rating literature attracted attention of academics since the subprime crisis 2008. In the wake of the crisis hundred billion dollars’ worth securities that were awarded AAA rating by the world’s leading credit rating agencies downgraded to junk. So is the survey on credit rating methodology. This work intends to survey the methodologies Moody’s and S&P follow in assessing the performance of equity funds and debt funds. The authors conclude that in these rating methodologies of S&P and Moody’s the link between equity fund and debt fund, i.e. how downgrade of debt fund can lead to downgrade of equity fund is not captured. Secondly Moody’s shakes off or manages the risk of loss of goodwill in the wake of failure of short term debt fund rating in the case of certain systemic factors like suspending or discouraging withdrawals and redemptions, by prescribing automatic downgrade to junk

Survey of Credit Rating Methodologies of Mutual Funds: Standard and Poor’s and Moody’s

Credit rating literature attracted attention of academics since the subprime crisis 2008. In the wake of the crisis hundred billion dollars’ worth securities that were awarded AAA rating by the world’s leading credit rating agencies downgraded to junk. So is the survey on credit rating methodology. This work intends to survey the methodologies Moody’s and S&P follow in assessing the performance of equity funds and debt funds. The authors conclude that in these rating methodologies of S&P and Moody’s the link between equity fund and debt fund, i.e. how downgrade of debt fund can lead to downgrade of equity fund is not captured. Secondly Moody’s shakes off or manages the risk of loss of goodwill in the wake of failure of short term debt fund rating in the case of certain systemic factors like suspending or discouraging withdrawals and redemptions, by prescribing automatic downgrade to junk

Purification and Characterization of a Low Molecular Weight Multifunctional Cytotoxic Phospholipase A2 from Russell’s Viper Venom.

A basic toxin from Russell’s viper venom of 7.2 kDa (RVV-7) has been purified to homogeneity after partial unfolding by 4M urea followed by filtration through Centricon-30 membrane. Its N-terminal sequence showed strong homology with snake venom cytotoxins. Cytotoxic activity of RVV-7 has been demonstrated with B16F10 melanoma cells. PLA2 activity was observed in cytotoxin (CX3) from Naja kauthia bearing sequence homology with RVV-7. Phospholipase A2 and trypsin inhibitory activities were also observed with RVV-7. Chemical modification and inhibition studies suggested independent functional sites for these activities. A qualitative assessment of tumor growth inhibition by RVV-7 has been made

Runtime monitoring in continuous deployment by differencing execution behavior model

\u3cp\u3eContinuous deployment techniques support rapid deployment of new software versions. Usually a new version is deployed on a limited scale, its behavior is monitored and compared against the previously deployed version and either the deployment of the new version is broadened, or one reverts to the previous version. The existing monitoring approaches, however, do not capture the differences in the execution behavior between the new and the previously deployed versions. We propose an approach to automatically discover execution behavior models for the deployed and the new version using the execution logs. Differences between the two models are identified and enriched such that spurious differences, e.g., due to logging statement modifications, are mitigated. The remaining differences are visualized as cohesive diff regions within the discovered behavior model, allowing one to effectively analyze them for, e.g., anomaly detection and release decision making. To evaluate the proposed approach, we conducted case study on Nutch, an open source application, and an industrial application. We discovered the execution behavior models for the two versions of applications and identified the diff regions between them. By analyzing the regions, we detected bugs introduced in the new versions of these applications. The bugs have been reported and later fixed by the developers, thus, confirming the effectiveness of our approach.\u3c/p\u3

Therapeutic use of quercetin in the control of infection and anemia associated with visceral leishmaniasis

Flavonoids are a broad class of plant phenolics that are known to possess a well-established protective effect against membrane lipoperoxidative damages. Oxidative damage of erythrocytes has been implicated in the reduced survival of erythrocytes during leishmanial infection. This study reveals the efficacy of five naturally occurring flavonoids in arresting the development of anemia during the postinfection period. Among the compounds studied, quercetin was most successful in inhibiting the oxidation of proteins and lipids on the red cell membranes of infected animals. Apart from its antianemic property, quercetin also seemed to be highly potent in lowering the parasite load in the spleen. Combination therapy of quercetin with the antileishmanial drug stibanate produced a better decay of SOH in the erythrocytes of the infected animals compared to that induced by quercetin or drug treatment alone. Similar results were obtained in successful prevention of proteolytic degradation resulting in an aversion to early lysis of red cells after simultaneous treatment with quercetin and stibanate. Subsequent studies demonstrated the therapeutic efficacy of the combination treatment in the abatement of both anemia and parasitemia under the diseased conditio

“On Water’’ Promoted Ullmann-Type C–N Bond-Forming Reactions: Application to Carbazole Alkaloids by Selective N‑Arylation of Aminophenols

The Ullmann-type cross coupling of a variety of aromatic, aliphatic amines with aryl halides is reported using a CuI-based catalytic system in combination with an easily accessible prolinamide ligand in aqueous media. The method is mild and tolerant to air, moisture, and a wide range of functional groups, providing a novel way to access a variety of aminated products. Secondary amines like heteroaromatic amines and nucleobases have also been used, affording the corresponding coupling products in good to excellent yields. Moreover, this method has been employed for chemoselective C–N arylation of aminophenols and further utilized for the synthesis of carbazole natural products, avoiding the protection and deprotection steps

Runtime monitoring in continuous deployment by differencing execution behavior model

Continuous deployment techniques support rapid deployment of new software versions. Usually a new version is deployed on a limited scale, its behavior is monitored and compared against the previously deployed version and either the deployment of the new version is broadened, or one reverts to the previous version. The existing monitoring approaches, however, do not capture the differences in the execution behavior between the new and the previously deployed versions. We propose an approach to automatically discover execution behavior models for the deployed and the new version using the execution logs. Differences between the two models are identified and enriched such that spurious differences, e.g., due to logging statement modifications, are mitigated. The remaining differences are visualized as cohesive diff regions within the discovered behavior model, allowing one to effectively analyze them for, e.g., anomaly detection and release decision making. To evaluate the proposed approach, we conducted case study on Nutch, an open source application, and an industrial application. We discovered the execution behavior models for the two versions of applications and identified the diff regions between them. By analyzing the regions, we detected bugs introduced in the new versions of these applications. The bugs have been reported and later fixed by the developers, thus, confirming the effectiveness of our approach