Master of Science

thesisVerification of analog circuits is becoming a bottle-neck for the verification of complex analog/mixed-signal (AMS) circuits. In order to assist functional verification of complex AMS system-on-chips (SoCs), there is a need to represent the transistor-level circuits in the form of abstract models. The ability to represent the analog circuits as behavioral models is necessary, but not sufficient. Though there exist languages like Verilog-AMS and VHDL-AMS for modeling AMS circuits, there is no easy method for generating these models directly from the transistor-level descriptions. This thesis presents an improved method for extracting behavioral models from the simulations of AMS circuits. This method generates labeled Petri net (LPN) models that can be used in the formal verification of circuits, and SystemVerilog models that can be used in the system-level simulations

Expression and Function of a Putative Cox-Like Gene in D. melanogaster

Cyclooxygenases (COX) are the enzymes that catalyze the conversion of arachidonic acid into prostaglandins. In mammals, isoform COX-1 is constitutively expressed, whereas the isoform COX-2 gene expression is induced, primarily at sites of inflammation. While eicosanoids play a major role in inflammation in insects, their existence in fruit flies has not been reported. Recent computational analyses by Qi and Singh (2014) have identified putative COX-like enzymes in the fruit fly Drosophila melanogaster. Here we compare the expression patterns of these enzymes and the effects of their knockdown in immune cells of D. melanogaster third instar larvae. Because of high genetic and biochemical conservation in metabolism and inflammation between flies and humans, comparative studies of this important class of enzymes is of fundamental importance and will also have therapeutic potential. Cyclooxygenases (COX) are the enzymes that catalyze the conversion of arachidonic acid into prostaglandins. In mammals, isoform COX-1 is constitutively expressed, whereas the isoform COX-2 gene expression is induced, primarily at sites of inflammation. While eicosanoids play a major role in inflammation in insects, their existence in fruit flies has not been reported. Recent computational analyses by Qi and Singh (2014) have identified putative COX-like enzymes in the fruit fly Drosophila melanogaster. Here we compare the expression patterns of these enzymes and the effects of their knockdown in immune cells of D. melanogaster third instar larvae. Because of high genetic and biochemical conservation in metabolism and inflammation between flies and humans, comparative studies of this important class of enzymes is of fundamental importance and will also have therapeutic potential

Incorporating Fault-Tolerant Features into Message-Passing Middleware

The popularity of MPI-based middleware and applications has led to their wide deployment. Such systems, however, are not inherently reliable and cannot tolerate external faults. This thesis presents a novel model-based approach for exploiting application features and other characteristics to categorize and create AEMs (Application Execution Model). This work realizes MPI/FT(tm), a middleware derived by selective incorporation of fault-tolerant features into MPI/Pro(tm) for two relevant AEMs. This thesis proves the following hypothesis: it is possible to successfully complete select MPI applications even in the presence of external faults, and such fault-tolerance can be achieved with acceptable performance overhead. This work defines parameters to measure the impact of this middleware on performance through faultree and fault-injected overheads. The hypothesis is validated through experimentation and measurement of sample MPI applications for two AEMs

EXPLORATION OF MICROORGANISMS AS A POTENTIAL SOURCE OF XANTHINE OXIDASE INHIBITORS: AN UPDATED REVIEW

Nowadays the prevalence of hyperuricemia has significantly increased in which serum uric acid levels are exceeding the normal range. Gout is the predominant clinical implication of the hyperuricemia, but many clinical investigations have confirmed that hyperuricemia is an independent risk factor for cardiovascular disease (CVD), hypertension, diabetes, and many other diseases. The xanthine oxidase (XO) converts hypoxanthine to xanthine and ultimately to uric acid, and the irreversibly accumulated uric acid causes hyperuricemia associated with gout. Hence specific and selective xanthine oxidase inhibitors (XOI) are potentially powerful tools for inactivating target XO in the pathogenic process of hyperuricemia (Gout). The objective of the current study was to overview the various XOI isolated from the microorganisms. Microorganisms have been employed for several decades for the large-scale production of a variety of bio-chemicals ranging from alcohol to antibiotics and as well as enzyme inhibitors. Currently available XOI (allopurinol and febuxostat) for the treatment of gout have been exhibiting serious side effects. Thus, there is a need to search for new molecules to treat hyperuricemia and its associated disorders. At present, microbes have been unexplored in the development of successful products for the management of XO-related diseases. Hence, the present review focused on novel XOI produced from various microbial species such as Actinobacteria, lichens, bacteria, endophytic fungi and mushrooms, which can be expected to play an important role in the ongoing transition from the empirical screening to the real rational drug design.Â

BIOCHEMICAL ROLE OF XANTHINE OXIDOREDUCTASE AND ITS NATURAL INHIBITORS: AN OVERVIEW

Xanthine oxidoreductase (XOR) is a widely distributed housekeeping enzyme in mammals that catalyzes the last two steps in human purine catabolism to produce uric acid. The enzyme exists as a homodimer with independent electron transfer in each monomer. This has been studied extensively as a major constituent of the milk fat globule membrane (MFGM) which surrounds fat globules in cow's milk even though purine catabolism is the most accepted function of XOR. A huge number of literature highlights on the different catalytic forms of XOR and their importance in the generation of reactive oxygen species/reactive nitrogen species (ROS/RNS) and synthesis of uric acid which are involved in many physiological and pathological processes. However, a slight ambiguity resides in their biochemical functions. The aim of this article was to review the literature published on the structural, catalytical, physiological and pathological role of XOR and to resolve the ambiguity in biochemical processes and to firm up various natural inhibitors of XOR collectively. Uric acid, the product of purine catabolism shows antioxidant activity, and XOR-derived ROS and RNS play a role in innate immunity, milk secretion and also be involved in signaling and metabolism of xenobiotics. Furthermore, XOR is likely to be engaged in pathology because of excessive production of uric acid and ROS/RNS. This review also reports natural XOR inhibitors in plants which inhibit the enzyme to treat XOR associated pathology