57 research outputs found

    Online Library Package to Boost the Functionality and Usability of the Existing Libraries

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    The current computational era has given rise to the idea of the digital library. The essential purpose of digital libraries is to enable readers to more easily explore books for reading. The library is a fast-growing process. The prehistoric system of maintaining it is no longer efficient. Library staff handles tedious tasks which involve sorting, lending, returning, classification of books etc. In addition, library users encounter problems for searching, borrowing, renewing the book, queuing, and so on. To overcome these barriers, this paper proposes a smart E-library Application based on Android technology. It mainly focuses on the central operations in a Library like analyzing total books, calculating available books, updating information, searching books and a facility to request and return books. This Software package is an Android Application developed for android O.S based phones, intended to help users to maintain and organize Library Services. This software package is user-friendly. It will allow quick transactions and will make easy to handle the issue and return of books from the Library without much involvement of manual bookkeeping. This software has been developed to maintain all the daily work of the library. It has many features which are generally not available in normal library systems like facility of reader login and a facility of admin login. The admin can monitor the whole system

    Quantitative and Molecular Genetic Analyses of Mutations Increasing Drosophila Life Span

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    Understanding the genetic and environmental factors that affect variation in life span and senescence is of major interest for human health and evolutionary biology. Multiple mechanisms affect longevity, many of which are conserved across species, but the genetic networks underlying each mechanism and cross-talk between networks are unknown. We report the results of a screen for mutations affecting Drosophila life span. One third of the 1,332 homozygous P–element insertion lines assessed had quantitative effects on life span; mutations reducing life span were twice as common as mutations increasing life span. We confirmed 58 mutations with increased longevity, only one of which is in a gene previously associated with life span. The effects of the mutations increasing life span were highly sex-specific, with a trend towards opposite effects in males and females. Mutations in the same gene were associated with both increased and decreased life span, depending on the location and orientation of the P–element insertion, and genetic background. We observed substantial—and sex-specific—epistasis among a sample of ten mutations with increased life span. All mutations increasing life span had at least one deleterious pleiotropic effect on stress resistance or general health, with different patterns of pleiotropy for males and females. Whole-genome transcript profiles of seven of the mutant lines and the wild type revealed 4,488 differentially expressed transcripts, 553 of which were common to four or more of the mutant lines, which include genes previously associated with life span and novel genes implicated by this study. Therefore longevity has a large mutational target size; genes affecting life span have variable allelic effects; alleles affecting life span exhibit antagonistic pleiotropy and form epistatic networks; and sex-specific mutational effects are ubiquitous. Comparison of transcript profiles of long-lived mutations and the control line reveals a transcriptional signature of increased life span

    ROMK (Kir1.1) pharmacology comes of age

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    ML418: The First Selective, Sub-Micromolar Pore Blocker of Kir7.1 Potassium Channels

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    The inward rectifier potassium (Kir) channel Kir7.1 (<i>KCNJ13</i>) has recently emerged as a key regulator of melanocortin signaling in the brain, electrolyte homeostasis in the eye, and uterine muscle contractility during pregnancy. The pharmacological tools available for exploring the physiology and therapeutic potential of Kir7.1 have been limited to relatively weak and nonselective small-molecule inhibitors. Here, we report the discovery in a fluorescence-based high-throughput screen of a novel Kir7.1 channel inhibitor, VU714. Site-directed mutagenesis of pore-lining amino acid residues identified glutamate 149 and alanine 150 as essential determinants of VU714 activity. Lead optimization with medicinal chemistry generated ML418, which exhibits sub-micromolar activity (IC<sub>50</sub> = 310 nM) and superior selectivity over other Kir channels (at least 17-fold selective over Kir1.1, Kir2.1, Kir2.2, Kir2.3, Kir3.1/3.2, and Kir4.1) except for Kir6.2/SUR1 (equally potent). Evaluation in the EuroFins Lead Profiling panel of 64 GPCRs, ion-channels, and transporters for off-target activity of ML418 revealed a relatively clean ancillary pharmacology. While ML418 exhibited low CL<sub>HEP</sub> in human microsomes which could be modulated with lipophilicity adjustments, it showed high CL<sub>HEP</sub> in rat microsomes regardless of lipophilicity. A subsequent in vivo PK study of ML418 by intraperitoneal (IP) administration (30 mg/kg dosage) revealed a suitable PK profile (<i>C</i><sub>max</sub> = 0.20 μM and <i>T</i><sub>max</sub> = 3 h) and favorable CNS distribution (mouse brain/plasma <i>K</i><sub>p</sub> of 10.9 to support in vivo studies. ML418, which represents the current state-of-the-art in Kir7.1 inhibitors, should be useful for exploring the physiology of Kir7.1 in vitro and in vivo
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