Reactive oxygen and nitrogen species production in cardiomyoblasts during hypoxia and reoxygenation

Hypoxia is a stress condition in which tissues are deprived of an adequate O2 supply; this may trigger cell death with pathological consequences in cardiovascular or neurodegenerative disease. Reperfusion is the restoration of an oxygenated blood supply to hypoxic tissue and can cause more cell injury. The kinetics and consequences of reactive oxygen and nitrogen species (ROS/RNS) production in cardiomyoblasts are poorly understood. The present study describes the systematic characterization of the kinetics of ROS/RNS production and their roles in cell survival and associated protection during hypoxia and hypoxia/reperfusion. H9C2 cells showed a significant loss of viability under 2% O2 for 30min hypoxia and cell death; associated with an increase in protein oxidation. After 4h, apoptosis induction under 2% O2 and 10% O2 was dependent on the production of mitochondrial superoxide (O2-•) and nitric oxide (•NO), partly from nitric oxide synthase (NOS). Both apoptotic and necrotic cell death during 2% O2 for 4h could be rescued by the mitochondrial complex I inhibitor; rotenone and NOS inhibitor; L-NAME. Both L-NAME and the NOX (NADPH oxidase) inhibitor; apocynin reduced apoptosis under 10% O2 for 4h hypoxia. The mitochondrial uncoupler; FCCP significantly reduced cell death via a O2-• dependent mechanism during 2% O2, 30min hypoxia. During hypoxia (2% O2, 4h)/ reperfusion (21% O2, 2h), metabolic activity was significantly reduced with increased production of O2-• and •NO, during hypoxia but, partially restored during reperfusion. O2-• generation during hypoxia/reperfusion was mitochondrial and NOX- dependent, whereas •NO generation depended on both NOS and non-enzymatic sources. Inhibition of NOS worsened metabolic activity during reperfusion, but did not effect this during sustained hypoxia. Nrf2 activation during 2% O2, a sustained hypoxia and reperfusion was O2-•/•NO dependent. Inhibition of NF-?B activation aggravated metabolic activity during 2% O2, 4h hypoxia. In conclusion, mitochondrial O2-•, but, not ATP depletion is the major cause of apoptotic and necrotic cell death in cardiomyoblasts under 2% O2, 4h hypoxia, whereas apoptotic cell death under 10% O2, 4h, is due to NOS-dependent •NO. The management of ROS/RNS rather than ATP is required for improved survival during hypoxia. O2-• production from mitochondria and NOS is cardiotoxic during hypoxia/reperfusion. NF-?B activation during hypoxia and NOS activation during reperfusion is cardiomyoblast protective

Pulse-splitting in light propagation through NN-type atomic media due to an interplay of Kerr-nonlinearity and group velocity dispersion

We investigate the spatio-temporal evolution of a Gaussian probe pulse propagating through a four-level $N$-type atomic medium. At two-photon resonance of probe-and control fields, weaker probe pulses may propagate through the medium with low absorption and pulse shape distortion. In contrast, we find that increasing the probe pulse intensity leads to a splitting of the initially Gaussian pulse into a sequence of subpulses in the time domain. The number of subpulses arising throughout the propagation can be controlled via a suitable choice of the probe and control field parameters. Employing a simple theoretical model for the nonlinear pulse propagation, we conclude that the splitting occurs due to an interplay of Kerr nonlinearity and group velocity dispersion.Comment: 9 pages, 7 figure

Effective Cloud-Based Strategies For Managing Online Reputations

Leasing computing resources are now feasible thanks to the Infrastructure as a Service (IaaS) concept made available by cloud computing. In spite of the fact that leased computing resources provide a more financially advantageous answer to the requirements of virtual networks, customers are reluctant to make use of them due to low levels of trust in these resources. Multi-tenancy is a method for reducing operating expenses by allocating a single set of computer resources to serve the needs of several users simultaneously. The fact that computer resources and communication methods are being shared gives rise to concerns over the security and integrity of the data. Since the users are anonymous, it may be difficult for a person to decide who among their neighbours can be trusted. This may make it difficult for an individual to choose a place to live. It is very necessary to have faith in the capacity of the cloud provider (CP) to match customers with dependable co-tenants. Yet, it is in the CP's best interest to make the most of the usage of the resources. So, it enables the maximum possible degree of co-tenancy, which is unaffected by the actions of the user. We provide a powerful reputation management system that pays CPs for discriminating between genuine and malicious users. This prevents resource sharing across CPs in a federated cloud environment, which is one of the goals of our system. Through a combination of theoretical and empirical research, we demonstrate that the proposed method for managing reputations is effective and legitimate

Reactive oxygen and nitrogen species production in cardiomyoblasts during hypoxia and reoxygenation

Hypoxia is a stress condition in which tissues are deprived of an adequate O2 supply; this may trigger cell death with pathological consequences in cardiovascular or neurodegenerative disease. Reperfusion is the restoration of an oxygenated blood supply to hypoxic tissue and can cause more cell injury. The kinetics and consequences of reactive oxygen and nitrogen species (ROS/RNS) production in cardiomyoblasts are poorly understood. The present study describes the systematic characterization of the kinetics of ROS/RNS production and their roles in cell survival and associated protection during hypoxia and hypoxia/reperfusion. H9C2 cells showed a significant loss of viability under 2% O2 for 30min hypoxia and cell death; associated with an increase in protein oxidation. After 4h, apoptosis induction under 2% O2 and 10% O2 was dependent on the production of mitochondrial superoxide (O2-•) and nitric oxide (•NO), partly from nitric oxide synthase (NOS). Both apoptotic and necrotic cell death during 2% O2 for 4h could be rescued by the mitochondrial complex I inhibitor; rotenone and NOS inhibitor; L-NAME. Both L-NAME and the NOX (NADPH oxidase) inhibitor; apocynin reduced apoptosis under 10% O2 for 4h hypoxia. The mitochondrial uncoupler; FCCP significantly reduced cell death via a O2-• dependent mechanism during 2% O2, 30min hypoxia. During hypoxia (2% O2, 4h)/ reperfusion (21% O2, 2h), metabolic activity was significantly reduced with increased production of O2-• and •NO, during hypoxia but, partially restored during reperfusion. O2-• generation during hypoxia/reperfusion was mitochondrial and NOX- dependent, whereas •NO generation depended on both NOS and non-enzymatic sources. Inhibition of NOS worsened metabolic activity during reperfusion, but did not effect this during sustained hypoxia. Nrf2 activation during 2% O2, a sustained hypoxia and reperfusion was O2-•/•NO dependent. Inhibition of NF-?B activation aggravated metabolic activity during 2% O2, 4h hypoxia. In conclusion, mitochondrial O2-•, but, not ATP depletion is the major cause of apoptotic and necrotic cell death in cardiomyoblasts under 2% O2, 4h hypoxia, whereas apoptotic cell death under 10% O2, 4h, is due to NOS-dependent •NO. The management of ROS/RNS rather than ATP is required for improved survival during hypoxia. O2-• production from mitochondria and NOS is cardiotoxic during hypoxia/reperfusion. NF-?B activation during hypoxia and NOS activation during reperfusion is cardiomyoblast protective.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The Moderating Role of Bank Performance Indicators on Credit Risk of Indian Public Sector Banks

Credit risk is inherent in banking. With its pervasive impact, it poses significant threat to the existence, stability and growth of the banking industry. The present study investigates the moderating role of various bank performance indicators on the relationship between lending and credit risk, i.e., Non Performing Assets (NPA) during the period 2000-01 to 2011-12. The study concentrates on Indian Public Sector Banks. Basically, NPA results from advances. This relationship is often more complex because it is modified by the changes in both bank performance indicators and macroeconomic indicators. The bank performance indicators moderate the relationship between advances and NPA. In order to achieve the stated objectives, the study utilized correlation, regression and ANOVA with moderation effect. The study revealed that the selected bank performance variables exercise a moderating role in the relationship between advances and NPA. The conclusion derived from the analysis can be utilized to improve the credit risk management in banks. Keywords: Non Performing Assets, Advances, Moderation, Performance Indicator

Compatibility of RuO₂ electrodes with PZT ceramics

Because of its high electrical conductivity and good diffusion barrier properties ruthenium dioxide (RuO2) is a good electrode material for use with ferroelectric lead zirconate–titanate (PZT) solid solutions. Under certain conditions, RuO2 can react with PZT to form lead ruthenate (Pb2Ru2O6⋅5) during processing at elevated temperatures resulting in lead depletion from PZT. The standard Gibbs energies of formation of RuO2 and Pb2Ru2O6⋅5 and activities of components of the PZT solid solution have been determined recently. Using this data along with older thermodynamic information on PbZrO3 and PbTiO3, the stability domain of Pb2Ru2O6⋅5 is computed as a function of PZT composition, temperature and oxygen partial pressure in the gas phase. The results show PbZrO3-rich compositions are more prone to react with RuO2 at all temperatures. Increasing temperature and decreasing oxygen partial pressure suppress the reaction. Graphically displayed are the reaction zones as a function of oxygen partial pressure and PZT composition at temperatures 973, 1173 and 1373 K

Diabetic Retinopathy Diagnosis Categorization Using Deep Learning

Diabetic Retinopathy (DR) is an eye disease associated with chronic diabetes. DR is the leading cause of blindness among working aged adults around the world and estimated it may affect more than 93 million people. Progression to vision impairment can be slowed or controlled if DR is detected in time, however this can be difficult as the disease often shows few symptoms until it is too late to provide effective treatment. Currently, detecting DR is a time-consuming and manual process, which requires an ophthalmologist or trained clinician to examine and evaluate digital color fundus photographs of the retina, to identify DR by the presence of lesions associated with the vascular abnormalities caused by the disease. The automated method of DR screening will speed up the detection and decision-making process, which will help to control or manage DR progression. This paper presents an automated classification system, in which it analyzes fundus images with varying illumination and fields of view and generates a severity grade for diabetic retinopathy (DR) using machine learning models such as CNN, VGG-16 and VGG-19.This system achieves 80% sensitivity, 82% accuracy, 82% specificity, and 0.904 AUC for classifying images into 5 categories ranging from 0 to 4, where 0 is no DR and 4 is proliferative DR

A RAPID AND COST EFFECTIVE UV SPECTROPHOTOMETRIC METHOD DEVELOPMENT AND VALIDATION FOR THE QUANTITATIVE ESTIMATION OF INDINAVIR SULPHATE IN CAPSULES

Objective: To develop a cheap and rapid UV spectrophotometric method for the quantitative estimation of Indinavir sulphate (400mg) in capsules and validate as per ICH guidelines. Methods: The optimized method uses a diluent 100% potassium dihydrogen ortho phosphate buffer (pH 3.0) for the estimation of assay of Indinavir sulphate whose lmax is 259 nm. Results: The developed method resulted in Indinavir sulphate exhibiting linearity in the range 20-80 μg/ml. The precision is exemplified by relative standard deviation of 1.49%. Percentage Mean recovery was found to be in the range of 98â€102, during accuracy studies. The limit of detection (LOD) and limit of quantitiation (LOQ) were found to be 5 mg/ml, and 16.27 mg/ml respectively. Conclusion: A cheap and rapid UV spectrophotometric method was developed and validated for the quantitative estimation of Indinavir sulphate in capsules as per ICH guidelines and hence it can be used for the routine analysis in various pharmaceutical industries