918 research outputs found

    The effect of technology disruption on organisational health: mediating effect of competence adequacy and moderating effect of innovation capacity and competence building

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    As a world’s fastest growing telecommunication market, India is undergoing evolutionary changes in telecommunication technologies. Rapidly changing communication technology has been posing innumerable challenges to the telecommunication companies in India for adequate skill availability and at the same time significantly changing competence requirements. The recognition of competence adequacy as a key factor to sustain organizational health in an increasingly competitive telecommunication sector has opened up several possibilities of competence based research. The study examined the inverse effect of technology disruption on competence adequacy and subsequently on the organizational health. Further, the organization’s intervention to competence building and innovation capacity was also put through the moderating tests as balancing factors. Knowledge Evolution Theory underpins this study framework to highlight the competence issues caused by technology disruption. This quantitative study was conducted in India among four leading Telecommunication firms. An online questionnaire was administered to managers from the firms who were selected using stratified random sampling. The eight hypotheses of this study were tested with Structural Equation Modelling using AMOS software. The results of the study found significant positive effects of competence adequacy, innovation capacity and competence building on organisational health. Secondly, technology disruption was found to have significant negative relationship with both competence adequacy and organisational health. In addition, the interaction of competence building and innovation capacity on the path of technology disruption and competence adequacy significantly moderated the relationship and finally, competence adequacy was found to have a significant mediating effect on the relationship between technology disruption and organisational health. The study provides new directions to the practising human resource professionals to improve the competence adequacy in high technology industries especially among telecommunication companies. The results of the study also highlights the widening technology skill gap present in telecommunication industry in India. The findings of this study also have pointed out the importance of innovation capacity as balancing factor in technology firms in the wake of evolutionary changes in telecommunication technology

    Effect of different UCOE-promoter combinations in creation of engineered cell lines for the production of Factor VIII

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    <p>Abstract</p> <p>Background</p> <p>The most common approach used in generating cell lines for the production of therapetic proteins relies on gene amplification induced by a drug resistance gene e. g., DHFR and glutamine synthetase. Practically, this results in screening large number of clones for the one that expresses high levels of the biologic in a stable manner. The inefficiency of mammalian vector systems to express proteins in a stable manner typically involves silencing of the exogenous gene resulting from modifications such as methylation of CpG DNA sequences, histone deacetylation and chromatin condensation. The use of un-methylated CpG island fragments from housekeeping genes referred to as UCOE (ubiquitous chromatin opening elements) in plasmid vectors is now well established for increased stability of transgene expression. However, few UCOE-promoter combinations have been studied to date and in this report we have tested 14 different combinations.</p> <p>Findings</p> <p>In this report we describe studies with two different UCOEs (the 1.5 Kb human RNP fragment and the 3.2 Kb mouse RPS3 fragment) in combination with various promoters to express a large protein (B domain deleted factor VIII; BDD-FVIII) in a production cell line, BHK21. We show here that there are differences in expression of BDD-FVIII by the different UCOE-promoter combinations in both attached and serum free suspension adapted cells. In all cases, the 1.5 Kb human RNP UCOE performed better in expressing BDD-FVIII than their corresponding 3.2 Kb mouse RPS3 UCOE. Surprisingly, in certain scenarios described here, expression from a number of promoters was equivalent or higher than the commonly used and industry standard human CMV promoter.</p> <p>Conclusion</p> <p>This study indicates that certain UCOE-promoter combinations are better than others in expressing the BDD-FVIII protein in a stable manner in BHK21 cells. An empirical study such as this is required to determine the best combination of UCOE-promoter in a vector for a particular production cell line.</p

    Pharmacogenetics of TNFi Response in Rheumatoid Arthritis Utilising the Two-Component Disease Activity Score

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    Aim: TNF inhibitor drugs are a treatment option for rheumatoid arthritis, but response is not universal. Response is typically measured using the composite 4-component (4C) disease activity score 28 (DAS28) which contains more subjective measures. This study used a validated 2-component (2C) DAS28 score to determine whether SNPs associated with response were replicated in the UK population. Materials & methods: A literature review identified TNF inhibitor response SNPs. Linear regression was conducted to replicate associations with 4C or 2C-DAS28 response. Results: Eighteen independent SNPs were analyzed in 1828 patients. One and four associations with 4C and 2C-DAS28 response respectively were identified (p ≤ 0.05). Conclusion: Further genetic associations were replicated using the 2C-DAS28 which may reflect the objective nature of 2C-AS28

    The S-Matrix in Twistor Space

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    The simplicity and hidden symmetries of (Super) Yang-Mills and (Super)Gravity scattering amplitudes suggest the existence of a "weak-weak" dual formulation in which these structures are made manifest at the expense of manifest locality. We suggest that this dual description lives in (2,2) signature and is naturally formulated in twistor space. We recast the BCFW recursion relations in an on-shell form that begs to be transformed into twistor space. Our twistor transformation is inspired by Witten's, but differs in treating twistor and dual twistor variables more equally. In these variables the three and four-point amplitudes are amazingly simple; the BCFW relations are represented by diagrammatic rules that precisely define the "twistor diagrams" of Andrew Hodges. The "Hodges diagrams" for Yang-Mills theory are disks and not trees; they reveal striking connections between amplitudes and suggest a new form for them in momentum space. We also obtain a twistorial formulation of gravity. All tree amplitudes can be combined into an "S-Matrix" functional which is the natural holographic observable in asymptotically flat space; the BCFW formula turns into a quadratic equation for this "S-Matrix", providing a holographic description of N=4 SYM and N=8 Supergravity at tree level. We explore loop amplitudes in (2,2) signature and twistor space, beginning with a discussion of IR behavior. We find that the natural pole prescription renders the amplitudes well-defined and free of IR divergences. Loop amplitudes vanish for generic momenta, and in twistor space are even simpler than their tree-level counterparts! This further supports the idea that there exists a sharply defined object corresponding to the S-Matrix in (2,2) signature, computed by a dual theory naturally living in twistor space.Comment: V1: 46 pages + 23 figures. Less telegraphic abstract in the body of the paper. V2: 49 pages + 24 figures. Largely expanded set of references included. Some diagrammatic clarifications added, minor typo fixe

    Superconformal Yang-Mills quantum mechanics and Calogero model with OSp(N|2,R) symmetry

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    In spacetime dimension two, pure Yang-Mills possesses no physical degrees of freedom, and consequently it admits a supersymmetric extension to couple to an arbitrary number, N say, of Majorana-Weyl gauginos. This results in (N,0) super Yang-Mills. Further, its dimensional reduction to mechanics doubles the number of supersymmetries, from N to N+N, to include conformal supercharges, and leads to a superconformal Yang-Mills quantum mechanics with symmetry group OSp(N|2,R). We comment on its connection to AdS_2 \times S^{N-1} and reduction to a supersymmetric Calogero model.Comment: 1+28 pages, no figure; Refs added. To appear in JHE

    Assessment of coronary atherosclerosis by IVUS and IVUS-based imaging modalities: progression and regression studies, tissue composition and beyond

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    Cardiovascular disease remains the leading cause of mortality, morbidity and disability in the developed world, predominantly affecting the adult population. In the early 1990s coronary heart disease (CHD) was established as affecting one in two men and one in three women by the age of forty. Despite the dramatic progress in the field of cardiovascular medicine in terms of diagnosis and treatment of heart disease, modest improvements have only been achieved when the reduction of cardiovascular mortality and morbidity indices are assessed. To better understand coronary atherosclerosis, new imaging modalities have been introduced. These novel imaging modalities have been used in two ways: (1) for the characterization of plaque types; (2) for the assessment of the progression and regression of tissue types. These two aspects will be discussed in this review

    Alternatively Activated Mononuclear Phagocytes from the Skin Site of Infection and the Impact of IL-4Rα Signalling on CD4+T Cell Survival in Draining Lymph Nodes after Repeated Exposure to Schistosoma mansoni Cercariae

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    In a murine model of repeated exposure of the skin to infective Schistosoma mansoni cercariae, events leading to the priming of CD4 cells in the skin draining lymph nodes were examined. The dermal exudate cell (DEC) population recovered from repeatedly (4x) exposed skin contained an influx of mononuclear phagocytes comprising three distinct populations according to their differential expression of F4/80 and MHC-II. As determined by gene expression analysis, all three DEC populations (F4/80-MHC-IIhigh, F4/80+MHC-IIhigh, F4/80+MHC-IIint) exhibited major up-regulation of genes associated with alternative activation. The gene encoding RELMα (hallmark of alternatively activated cells) was highly up-regulated in all three DEC populations. However, in 4x infected mice deficient in RELMα, there was no change in the extent of inflammation at the skin infection site compared to 4x infected wild-type cohorts, nor was there a difference in the abundance of different mononuclear phagocyte DEC populations. The absence of RELMα resulted in greater numbers of CD4+ cells in the skin draining lymph nodes (sdLN) of 4x infected mice, although they remained hypo-responsive. Using mice deficient for IL-4Rα, in which alternative activation is compromised, we show that after repeated schistosome infection, levels of regulatory IL-10 in the skin were reduced, accompanied by increased numbers of MHC-IIhigh cells and CD4+ T cells in the skin. There were also increased numbers of CD4+ T cells in the sdLN in the absence of IL-4Rα compared to cells from singly infected mice. Although their ability to proliferate was still compromised, increased cellularity of sdLN from 4x IL-4RαKO mice correlated with reduced expression of Fas/FasL, resulting in decreased apoptosis and cell death but increased numbers of viable CD4+ T cells. This study highlights a mechanism through which IL-4Rα may regulate the immune system through the induction of IL-10 and regulation of Fas/FasL mediated cell death

    Reproducibility of volumetric intravascular ultrasound radiofrequency-based analysis of coronary plaque composition in vivo

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    Intravascular ultrasound radiofrequency (RF-IVUS) data permit the analysis of coronary plaque composition in vivo and is used as an endpoint of ongoing pharmacological intervention trials. We assessed the reproducibility of volumetric RF-IVUS analyses in mild-to-moderately diseased atherosclerotic human coronary arteries in vivo. A total of 9,212 IVUS analyses on cross-sectional IVUS frames was performed to evaluate the reproducibility of volumetric RF-IVUS measurements in 33 coronary segments with a length of 27 ± 7 mm. For vessel, lumen, and plaque + media volume the relative measurement differences (P = NS for all) were (A = intraobserver comparison, same pullback) −0.40 ± 1.0%; −0.48 ± 1.4%; −0.35 ± 1.6%, (B = intraobserver comparison, repeated pullback) −0.42 ± 1.2%; −0.52 ± 1.8%; −0.43 ± 4.5% (C = interobserver comparison, same pullback) 0.71 ± 1.8%; 0.71 ± 2.2%, and 0.89 ± 5.0%, respectively. For fibrous, fibro-lipidic, calcium, and necrotic-core volumes the relative measurement differences (P = NS for all) were (A) 0.45 ± 2.1%; −1.12 ± 4.9%; −0.84 ± 2.1%; −0.22 ± 1.8%, (B) 1.40 ± 4.1%; 1.26 ± 6.7%; 2.66 ± 7.4%; 0.85 ± 4.4%, and (C) −1.60 ± 4.9%; 3.85 ± 8.2%; 1.66 ± 7.5%, and −1.58 ± 4.7%, respectively. Of note, necrotic-core volume showed on average the lowest measurement variability. Thus, in mild-to-moderate atherosclerotic coronary artery disease the reproducibility of volumetric compositional RF-IVUS measurements from the same pullback is relatively high, but lower than the reproducibility of geometrical IVUS measurements. Measurements from repeated pullbacks and by different observers show acceptable reproducibilities; the volumetric measurement of the necrotic-core shows on average the highest reproducibility of the compositional RF-IVUS measurement

    ADHM and the 4d quantum Hall effect

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    Yang-Mills instantons are solitonic particles in d=4+1 dimensional gauge theories. We construct and analyse the quantum Hall states that arise when these particles are restricted to the lowest Landau level. We describe the ground state wavefunctions for both Abelian and non-Abelian quantum Hall states. Although our model is purely bosonic, we show that the excitations of this 4d quantum Hall state are governed by the Nekrasov partition function of a certain five dimensional supersymmetric gauge theory with Chern-Simons term. The partition function can also be interpreted as a variant of the Hilbert series of the instanton moduli space, counting holomorphic sections rather than holomorphic functions. It is known that the Hilbert series of the instanton moduli space can be rewritten using mirror symmetry of 3d gauge theories in terms of Coulomb branch variables. We generalise this approach to include the effect of a five dimensional Chern-Simons term. We demonstrate that the resulting Coulomb branch formula coincides with the corresponding Higgs branch Molien integral which, in turn, reproduces the standard formula for the Nekrasov partition function

    Impact of analyzing less image frames per segment for radiofrequency-based volumetric intravascular ultrasound measurements in mild-to-moderate coronary atherosclerosis

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    Volumetric radiofrequency-based intravascular ultrasound (RF–IVUS) data of coronary segments are increasingly used as endpoints in serial trials of novel anti-atherosclerotic therapies. In a relatively time-consuming process, vessel and lumen contours are defined; these contours are first automatically detected, then visually checked, and finally (in most cases) manually edited to generate reliable volumetric data of vessel geometry and plaque composition. Reduction in number of cross-sectional images for volumetric analysis could save analysis time but may also increase measurement variability of volumetric data. To assess whether a 50% reduction in number of frames per segment (every second frame) alters the reproducibility of volumetric measurements, we performed repeated RF–IVUS analyses of 15 coronary segments with mild-to-moderate atherosclerosis (20.2 ± 0.2 mm-long segments with 46 ± 13% plaque burden). Volumes were calculated based on a total of 731 image frames. Reducing the number of cross-sectional image frames for volumetric measurements saved analysis time (38 ± 9 vs. 68 ± 17 min/segment; P < 0.0001) and resulted for only a few parameters in (borderline) significant but mild differences versus measurements based on all frames (fibrous volume, P < 0.05; necrotic-core volume, P = 0.07). Compared to the intra-observer variability, there was a mild increase in measurement variability for most geometrical and compositional volumetric RF–IVUS parameters. In RF–IVUS studies of mild-to-moderate coronary disease, analyzing less image frames saved analysis time, left most volumetric parameters greatly unaffected, and resulted in a no more than mild increase in measurement variability of volumetric data
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