3,889 research outputs found

    Soils - the last frontier

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    Agile Software Development during the COVID-19 Pandemic: A Technology Company Survey

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    A common baseline is that Agile-based software development is conducted by co-located teams working in well-equipped office workspaces. The COVID-19 pandemic and subsequent lockdowns have cast new light on those assumptions. Suddenly, developers were no longer co-located with their teams and their well-equipped workspaces were vacant. How did the lockdowns, and the speed in which they were implemented, affect developers and development efforts? Did the lockdowns lead to diminished product quality? How was employee productivity impacted? A survey questionnaire was created to answer these questions

    The challenge of mainstreaming ICT design for all.

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    The education and training of ICT students and professionals with respect to Design for All is a vital part in the process of achieving eInclusion throughout Europe. This paper outlines the latest activity on the development of a curriculum in Design for All in ICT in higher education and professional development, and discusses some of the challenges of mainstreaming ICT Design for All. Concepts have been devised to introduce Design for All at bachelor-level of mainstream ICT education, to implement a masters degree in Design for All, and to provide training for professionals in ICT industry

    Predatory soil nematodes (Nematoda: Mononchida) in major land-use types across Ireland

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    The distribution of predatory soil nematodes (Mononchida) across Europe is well described. However, in Ireland knowledge of mononchids is limited to a single study. The CréBeo project was the first systematic survey of soil biodiversity in the major land-use types across the Republic of Ireland. Nematodes were sampled from 61 locations with an extensive geographical spread including arable, pasture, broadleaf forest, coniferous plantation, rough grazing and peatland sites. This study resulted in 11 first records of mononchid species from Ireland (of which 2 are new records for Britain and Ireland). We discuss the mononchid species found and aspects of their distribution across major land uses

    Conformationally selective multidimensional chemical shift ranges in proteins from a PACSY database purged using intrinsic quality criteria

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    We have determined refined multidimensional chemical shift ranges for intra-residue correlations ([superscript 13]C–[superscript 13]C, [superscript 15]N–[superscript 13]C, etc.) in proteins, which can be used to gain type-assignment and/or secondary-structure information from experimental NMR spectra. The chemical-shift ranges are the result of a statistical analysis of the PACSY database of >3000 proteins with 3D structures (1,200,207 [superscript 13]C chemical shifts and >3 million chemical shifts in total); these data were originally derived from the Biological Magnetic Resonance Data Bank. Using relatively simple non-parametric statistics to find peak maxima in the distributions of helix, sheet, coil and turn chemical shifts, and without the use of limited “hand-picked” data sets, we show that ~94 % of the [superscript 13]C NMR data and almost all [superscript 15]N data are quite accurately referenced and assigned, with smaller standard deviations (0.2 and 0.8 ppm, respectively) than recognized previously. On the other hand, approximately 6 % of the [superscript 13]C chemical shift data in the PACSY database are shown to be clearly misreferenced, mostly by ca. −2.4 ppm. The removal of the misreferenced data and other outliers by this purging by intrinsic quality criteria (PIQC) allows for reliable identification of secondary maxima in the two-dimensional chemical-shift distributions already pre-separated by secondary structure. We demonstrate that some of these correspond to specific regions in the Ramachandran plot, including left-handed helix dihedral angles, reflect unusual hydrogen bonding, or are due to the influence of a following proline residue. With appropriate smoothing, significantly more tightly defined chemical shift ranges are obtained for each amino acid type in the different secondary structures. These chemical shift ranges, which may be defined at any statistical threshold, can be used for amino-acid type assignment and secondary-structure analysis of chemical shifts from intra-residue cross peaks by inspection or by using a provided command-line Python script (PLUQin), which should be useful in protein structure determination. The refined chemical shift distributions are utilized in a simple quality test (SQAT) that should be applied to new protein NMR data before deposition in a databank, and they could benefit many other chemical-shift based tools.National Institutes of Health (U.S.) (Grant GM066976

    Bayesian Sensitivity Analysis of Flight Parameters in a Hard-Landing Analysis Process

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    A flight parameter sensor simulation model was developed to assess the conservatism of the landing gear component loads calculated using a typical hard-landing analysis process. Conservatism exists due to factors of safety that are incorporated into any hard-landing analysis process to account for uncertainty in the measurement of certain flight parameters. The flight parameter sensor simulation model consists of 1) an aircraft and landing gear dynamic model to determine the “actual” landing gear loads during a hard landing; 2) an aircraft sensor and data acquisition model to represent the aircraft sensors and flight data recorder systems to investigate the effect of signal processing on the flight parameters; and 3) an automated hard-landing analysis process, representative of that used by airframe and equipment manufacturers, to determine the “simulated” landing gear loads. Using a technique of Bayesian sensitivity analysis, a number of flight parameters are varied in the flight parameter sensor simulation model to gain an understanding of the sensitivity of the difference between actual and simulated loads to the individual flight parameters in symmetric and asymmetric two-point landings. This study shows that the error can be reduced by learning the true value of the following flight parameters: longitudinal tire–runway friction coefficient, aircraft vertical acceleration (related to vertical descent velocity), lateral acceleration (related to lateral velocity), Euler roll angle, mass, center of gravity position, and main landing gear tire type. It was also shown that, due to the modeling techniques used, shock absorber servicing state and tire pressure do not contribute significantly to the error

    The First Potent, Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 3 (PRMT3)

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    PRMT3 is a type I arginine methyltransferase that catalyzes mono- and asymmetric dimethylation of arginine residues of various proteins. The protein has demonstrated through in vitro studies functionality in the maturation of ribosomes, a possible role in lipogenesis, and has several implications in various diseases. The purpose of this project was to develop and characterize a chemical probe that potently and selectively inhibits PRMT3 for further use in cellular and animal studies. SGC707, formerly known as UNC3108, is the first chemical probe of PRMT3 and was developed via structure based optimization. This potent allosteric inhibitor has been thoroughly characterized in a number of biochemical, biophysical, and cellular assays. The methods highlighted in this thesis describe synthesis of this chemical probe and characterization of this probe by an isothermal titration calorimetry assay. In addition to its high potency (IC50 = 31 ± 2 nM, KD = 53 ± 2 nM), SGC707 is selective for PRMT3 over >250 protein targets. It engages PRMT3 and potently inhibits its methyltransferase activity in cells. Initial pharmacokinetic studies also demonstrated that SGC707 is bioavailable and suitable for animal studies. Therefore, SGC707 is an excellent tool to further study the role of PRMT3 in health and disease.Doctor of Pharmac

    A cyclic AMP response element mediates repression of tyrosine aminotransferase gene transcription by the tissue-specific extinguisher locus Tse-1

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    Tyrosine aminotransferase (TAT) gene expression is liver specific and inducible by glucocorticoids and via the cAMP signaling pathway. In fibroblasts and other nonliver cells the gene is subject to negative control by the trans-dominant tissue-specific extinguisher locus Tse-1. We identified a hepatocyte-specific enhancer that is repressed by Tse-1. Two distinct sequence motifs are absolutely essential for function of this enhancer: a cAMP response element (CRE), which is the target for repression by Tse-1, and a hepatocyte-specific element. The specificity of the enhancer is generated by the combination of these two essential elements, which are fully interdependent. In vivo footprinting indicates that Tse-1 acts by affecting protein binding at the CRE. A direct antagonism between Tse-1 and the cAMP signaling pathway suggests that Tse-1 plays a role in control of developmental activation of the TAT gene
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