CoPhy: A Scalable, Portable, and Interactive Index Advisor for Large Workloads

Index tuning, i.e., selecting the indexes appropriate for a workload, is a crucial problem in database system tuning. In this paper, we solve index tuning for large problem instances that are common in practice, e.g., thousands of queries in the workload, thousands of candidate indexes and several hard and soft constraints. Our work is the first to reveal that the index tuning problem has a well structured space of solutions, and this space can be explored efficiently with well known techniques from linear optimization. Experimental results demonstrate that our approach outperforms state-of-the-art commercial and research techniques by a significant margin (up to an order of magnitude).Comment: VLDB201

Label-free colorimetric estimation of proteins using nanoparticles of silver

Metallic nanoparticles have received considerable attention in bioassays and diagnostics due to their unique surface plasmon resonance (SPR) properties. Gold nanoparticles have been employed for the development of SPR-based colorimetric bioassays. In the present report we have described a sensitive colorimetric approach for estimation of proteins, within a detection limit of 10∼80 μg/mL, using unmodified silver nanoparticles. Besides the common advantages of colorimetric assay such as simplicity, high sensitivity, and low cost, our method has a label-free design and provides an important and attractive alternative to classical sensing probes and systems. The present work will contribute to the development of nanotechnology-based diagnostic tools

Biochemical studies on methylglyoxal-mediated glycated histones: implications for presence of serum antibodies against the glycated histones in patients with type 1 diabetes mellitus

Reactive carbonyl species (RCS) mainly reacts with lysine and arginine residues of proteins to form advanced glycation end products (AGEs). Histone was glycoxidated with glyoxal and methylglyoxal. It was characterized by polyacrylamide gel electrophoresis and quenching studies involving penicillamine and aminoguanidine as carbonyl scavengers. Further characterization of histone modified with methylglyoxal was done by UV, fluorescence, and IR spectrophotometry. Spectral analysis of the protein clearly demonstrates structural perturbation in the histone by methylglyoxal. Methylglyoxal-induces cross-linking in the protein leading to aggregation. Role of methylglyoxal mediated glycoxidation of histone in type 1 diabetes was also undertaken. Antibodies were detected against glycoxidated histone in sera of type 1 diabetes patients by solid-phase enzyme immunoassay. The findings indicate that as a result of structural perturbation in histone by methylglyoxal, the modified histone may be involved in production of serum antibodies in the diabetes patients

Conformational change of L7/L12 stalk in the different functional states of 50S ribosomes

Conformational change of 50S ribosomes takes place during protein synthesis. The primary change is most likely in the secondary or tertiary structure of rRNA in the L7/L12 stalk region. In order to throw further light on this conformational change, the change in fluorescence of tight couple 50S ribosomes on conversion to loose couple 50S ribosomes containing 5-(iodoacetamido ethyl)-aminonaphthalene-l-sulphonic acid-labelled L7/L12, following the treatment with elongation factor-G and 5'-guanylyl methylene diphosphate was measured. It was enhanced in agreement with the results reported earlier. Further, the quenching of fluorescence of 50S ribosomes containing 5-(iodoacetamido ethyl)-aminonaphthalene-1-sulphonic acid-labelled L7/L12 by acrylamide was studied. The quenching is more in case of loose couples. On conversion of loose couple 50S ribosomes to tight couple ones the quenching becomes less whereas the reverse happens on conversion of tight couple 70S ribosomes to loose couples. These results indicate the conformational change of L7/L12 stalk in the different functional states of 50S ribosomes

Regulatory role of proteasome in determination of platelet life span

Limit of platelet life span (8-10 days) is determined by the activity of a putative "internal clock" composed of Bcl-2 family proteins, while role of other molecular players in this process remains obscure. Here, we sought to establish a central role of proteasome in platelet life span regulation. Administration of mice with inhibitors of proteasome peptidase activity induced significant thrombocytopenia. This was associated with enhanced clearance of biotin-labeled platelets from circulation and reduction in average platelet half life from 66 to 37 h. Cells pretreated in vitro with proteasome inhibitors exhibited augmented annexin V binding and drop in mitochondrial transmembrane potential indicative of apoptotic cell death and decreased platelet life span. These cells were preferentially phagocytosed by monocyte-derived macrophages, thus linking proteasome activity with platelet survival. Decisive role of proteasome in this process was underscored from enhanced expression of conformationally active Bax in platelets with attenuated proteasome activity, which was consistent with pro-apoptotic phenotype of these cells. The present study establishes a critical role of proteasome in delimiting platelet life span ostensibly through constitutive elimination of the conformationally active Bax. These findings bear potential implications in clinical settings where proteasome peptidase activities are therapeutically targeted

Effect of silver nanoparticles on growth of eukaryotic green algae

Silver nanoparticles, endowed with powerful antimicrobial property, are the most widely used nanomaterial in consumer products, with associated risk of their easy access to environment and freshwater ecosystems by surface runoff. Although toxic effects of nanosilver on bacterial, fungal and mammalian cells have been documented, its impact on algal growth remains unknown. Pithophora oedogonia and Chara vulgaris are predominant members of photosynthetic eukaryotic algae, which form major component of global aquatic ecosystem. Here we report for the first time that nanosilver has significant adverse effects on growth and morphology of these filamentous green algae in a dose-dependent manner. Exposure of algal thalli to increasing concentrations of silver nanoparticles resulted in progressive depletion in algal chlorophyll content, chromosome instability and mitotic disturbance, associated with morphological malformations in algal filaments. SEM micrographs revealed dramatic alterations in cell wall in nanoparticle-treated algae, characterized with cell wall rupture and degradation in Pithophora. Although these observations underscore severe deleterious effects of nanosilver on aquatic environment, the information can also be exploited as a bioengineering strategy to control unwanted and persistent growth of noxious algal weeds that clog the municipal water supply and water channels and produce fouling of water bodies

Understanding the expression of Toll-like receptors in Asian Indians predisposed to coronary artery disease

Introduction: Toll-like receptors (TLRs) are an important link between innate and adaptive immunity. Material and methods: Expression of TLR-2, TLR-4, and TLR-9 genes was assessed in 60 coronary artery disease (CAD) patients and 79 controls by SYBR Green 1 based real time PCR assay

Managing scientific data

Data-oriented scientific processes depend on fast, accurate analysis of experimental data generated through empirical observation and simulation. However, scientists are increasingly overwhelmed by the volume of data produced by their own experiments. With improving instrument precision and the complexity of the simulated models, data overload promises to only get worse. The inefficiency of existing database management systems (DBMSs) for addressing the requirements of scientists has led to many application-specific systems. Unlike their general-purpose counterparts, these systems require more resources, hindering reuse of knowledge. Still, the data-management community aspires to general-purpose scientific data management. Here, we explore the most important requirements of such systems and the techniques being used to address them

An Economic Model for Self-tuned Cloud Caching

Cloud computing, the new trend for service infrastructures requires user multi-tenancy as well as minimal capital expenditure. In a cloud that services large amounts of data that are massively collected and queried, such as scientific data, users typically pay for query services. The cloud supports caching of data in order to provide quality query services. User payments cover query execution costs and maintenance of cloud infrastructure, and incur cloud profit. The challenge resides in providing efficient and resource-economic query services while maintaining a profitable cloud. In this work we propose an economic model for self-tuned cloud caching targeting the service of scientific data. The proposed economy is adapted to policies that encourage high-quality individual and overall query services but also brace the profit of the cloud. We propose a cost model that takes into account all possible query and infrastructure expenditure. The experimental study proves that the proposed solution is viable for a variety of workloads and data

Novel microfilaricidal activity of nanosilver

Sunil K Singh1, Kalyan Goswami2, Richa D Sharma2, Maryada VR Reddy2, Debabrata Dash11Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 2Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram, IndiaPurpose: The currently available drug repertoire against lymphatic filariasis, a major health hazard in the developing world, is inadequate and is fraught with serious limitations. Thus, the development of an effective antifilarial strategy has become a global research thrust mandated by the World Health Organization. Nanoparticles of silver endowed with antibacterial potency are known to induce apoptosis in eukaryotic cells. The present study was designed to investigate the possible microfilaricidal efficacy of silver nanoparticles and to establish the validity of apoptotic rationale in antifilarial drug designing.Methods: This report analyzed the effect of nanoparticles of silver as well as gold (size range: 10–15 nm) on the microfilariae of Brugia malayi obtained from the lavage of peritoneal cavities of infected jirds (Meriones unguiculatus). The study included a microfilarial motility assay, a trypan blue exclusion test, a poly(adenosine diphosphate-ribose) polymerase activity study, ethidium bromide/acridine orange differential staining, and transmission, as well as scanning electron microscopic evaluation of ultrastructural changes in microfilariae.Results: The study demonstrates that nanoparticles of silver, but not of gold, elicited significant loss in microfilarial motility. Differential staining of parasites with ethidium bromide and acridine orange, poly(adenosine diphosphate-ribose) polymerase activity in microfilarial lysate, and electron microscopic findings underscored apoptotic death of parasites attributable to nanosilver. In a trypan blue exclusion test, the 50% lethal dose of nanosilver was measured to be 101.2 µM, which was higher than the recorded complete inhibitory concentration value (50.6 µM), thus supporting nanosilver as a potential drug candidate against lymphatic filariasis.Conclusion: The present report provides the first ever conclusive proof in support of apoptosis as a novel stratagem in antifilarial drug designing and nanoscale silver as a valid lead in research on antifilarial therapeutics. The main embargo about the current drug diethylcarbamazine citrate is its empirical use without rationale. Effective microfilaricidal activity of nanosilver at relatively low concentrations as reported in this study, with evidence of the induction of apoptosis in microfilariae, projects nanosilver as a potential drug adjuvant against lymphatic filariasis. The much higher 50% lethal dose value of nanosilver compared to the complete inhibitory concentration value reported in this study argues in favor of a safe therapeutic window of this agent in its antifilarial efficacy.Keywords: silver nanoparticles, apoptosis, lymphatic filariasis, microfilaricidal agent, parasitic disease