1,378 research outputs found

    Novel vasocontractile role of the P2Y14receptor: characterization of its signalling in porcine isolated pancreatic arteries

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    Background and Purpose: The P2Y14 receptor is the newest member of the P2Y receptor family; it is Gi/o protein-coupled and is activated by UDP and selectively by UDP-glucose and MRS2690 (2-thiouridine-5′-diphosphoglucose) (7–10-fold more potent than UDP-glucose). This study investigated whether P2Y14 receptors were functionally expressed in porcine isolated pancreatic arteries. Experimental Approach: Pancreatic arteries were prepared for isometric tension recording and UDP-glucose, UDP and MRS2690 were applied cumulatively after preconstriction with U46619, a TxA2 mimetic. Levels of phosphorylated myosin light chain 2 (MLC2) were assessed with Western blotting. cAMP concentrations were assessed using a competitive enzyme immunoassay kit. Key Results: Concentration-dependent contractions with a rank order of potency of MRS2690 (10-fold) > UDP-glucose ≥ UDP were recorded. These contractions were reduced by PPTN {4-[4-(piperidin-4-yl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthoic acid}, a selective antagonist of P2Y14 receptors, which did not affect responses to UTP. Contraction to UDP-glucose was not affected by MRS2578, a P2Y6 receptor selective antagonist. Raising cAMP levels and forskolin, in the presence of U46619, enhanced contractions to UDP-glucose. In addition, UDP-glucose and MRS2690 inhibited forskolin-stimulated cAMP levels. Removal of the endothelium and inhibition of endothelium-derived contractile agents (TxA2, PGF2α and endothelin-1) inhibited contractions to UDP glucose. Y-27632, nifedipine and thapsigargin also reduced contractions to the agonists. UDP-glucose and MRS2690 increased MLC2 phosphorylation, which was blocked by PPTN. Conclusions and Implications: P2Y14 receptors play a novel vasocontractile role in porcine pancreatic arteries, mediating contraction via cAMP-dependent mechanisms, elevation of intracellular Ca2+ levels, activation of RhoA/ROCK signalling and MLC2, along with release of TxA2, PGF2α and endothelin-1

    BEING AGILE TO THRIVE AMIDST DISRUPTIVE DIGITAL INNOVATIONS

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    Firms around the world have been experiencing disruptive digital innovation. Such disruptionsaffect their business operations and models over time and geography. In this paper, we adopt Lucas and Goh’s (2009) framework of disruption responseto examine how do firms achieve agility in responding to disruptive digital innovation. The framework draws on dynamic capability theory, disruptive innovation concept, organizational agility concept and organizational core rigidity concept. This research-in-progress paper aims to conduct an in-depth case studyto understand how firms can be agile in responding to disruptive digital innovation. As a case study, this study adds to the growing corpus of literature on disruptive digital innovation. Theoretically, this study extends Lucas and Goh’s (2009) framework of disruption response, underpinning the advancement of knowledge in this area. The managerialinsights gleaned from this study can also guide firmsin being agile and thrive amidst disruptive digital innovations

    Onset voltage shift due to non-zero Landau ground state level in coherent magnetotransport

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    Coherent electron transport in double-barrier heterostructures with parallel electric and magnetic fields is analyzed theoretically and with the aid of a quantum simulator accounting for 3-dimensional transport effects. The onset-voltage shift induced by the magnetic field in resonant tunneling diodes, which was previously attributed to the cyclotron frequency wcw_c inside the well is found to arise from an upward shift of the non-zero ground (lowest) Landau state energy in the entire quantum region where coherent transport takes place. The spatial dependence of the cyclotron frequency is accounted for and verified to have a negligible impact on resonant tunneling for the device and magnetic field strength considered. A correction term for the onset-voltage shift arising from the magnetic field dependence of the chemical potential is also derived. The Landau ground state with its nonvanishing finite harmonic oscillator energy wc/2 \hbar w_c /2 is verified however to be the principal contributor to the onset voltage shift at low temperatures.Comment: 13 pages, and 3 figures. Accepted for publication in Phys. Rev.

    Bringing Order to Special Cases of Klee's Measure Problem

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    Klee's Measure Problem (KMP) asks for the volume of the union of n axis-aligned boxes in d-space. Omitting logarithmic factors, the best algorithm has runtime O*(n^{d/2}) [Overmars,Yap'91]. There are faster algorithms known for several special cases: Cube-KMP (where all boxes are cubes), Unitcube-KMP (where all boxes are cubes of equal side length), Hypervolume (where all boxes share a vertex), and k-Grounded (where the projection onto the first k dimensions is a Hypervolume instance). In this paper we bring some order to these special cases by providing reductions among them. In addition to the trivial inclusions, we establish Hypervolume as the easiest of these special cases, and show that the runtimes of Unitcube-KMP and Cube-KMP are polynomially related. More importantly, we show that any algorithm for one of the special cases with runtime T(n,d) implies an algorithm for the general case with runtime T(n,2d), yielding the first non-trivial relation between KMP and its special cases. This allows to transfer W[1]-hardness of KMP to all special cases, proving that no n^{o(d)} algorithm exists for any of the special cases under reasonable complexity theoretic assumptions. Furthermore, assuming that there is no improved algorithm for the general case of KMP (no algorithm with runtime O(n^{d/2 - eps})) this reduction shows that there is no algorithm with runtime O(n^{floor(d/2)/2 - eps}) for any of the special cases. Under the same assumption we show a tight lower bound for a recent algorithm for 2-Grounded [Yildiz,Suri'12].Comment: 17 page

    Approximability of Connected Factors

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    Finding a d-regular spanning subgraph (or d-factor) of a graph is easy by Tutte's reduction to the matching problem. By the same reduction, it is easy to find a minimal or maximal d-factor of a graph. However, if we require that the d-factor is connected, these problems become NP-hard - finding a minimal connected 2-factor is just the traveling salesman problem (TSP). Given a complete graph with edge weights that satisfy the triangle inequality, we consider the problem of finding a minimal connected dd-factor. We give a 3-approximation for all dd and improve this to an (r+1)-approximation for even d, where r is the approximation ratio of the TSP. This yields a 2.5-approximation for even d. The same algorithm yields an (r+1)-approximation for the directed version of the problem, where r is the approximation ratio of the asymmetric TSP. We also show that none of these minimization problems can be approximated better than the corresponding TSP. Finally, for the decision problem of deciding whether a given graph contains a connected d-factor, we extend known hardness results.Comment: To appear in the proceedings of WAOA 201

    Conflicts in Knowledge Management: Vistiting the Hidden Partner

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    As knowledge gains a reputation for being a critical resource in the information-intensive economy, organizations have doubled their efforts in trying to extract value from knowledge management policies. One particular aspect of knowledge management, which has gone unnoticed in academic research, is the presence of conflicts in knowledge activities. By adopting a conflict perspective of knowledge activities, this study arrives at a two-dimensional framework that defines knowledge conflicts in terms of its type and nature. Central to this paper is the fundamental idea that conflicts form an integral part of knowledge management and depending on how they are managed; conflicts may be formidable partners or dangerous adversaries in the corporate quest for knowledge-derived competitiveness

    Optimal Color Range Reporting in One Dimension

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    Color (or categorical) range reporting is a variant of the orthogonal range reporting problem in which every point in the input is assigned a \emph{color}. While the answer to an orthogonal point reporting query contains all points in the query range QQ, the answer to a color reporting query contains only distinct colors of points in QQ. In this paper we describe an O(N)-space data structure that answers one-dimensional color reporting queries in optimal O(k+1)O(k+1) time, where kk is the number of colors in the answer and NN is the number of points in the data structure. Our result can be also dynamized and extended to the external memory model

    String Indexing for Patterns with Wildcards

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    We consider the problem of indexing a string tt of length nn to report the occurrences of a query pattern pp containing mm characters and jj wildcards. Let occocc be the number of occurrences of pp in tt, and σ\sigma the size of the alphabet. We obtain the following results. - A linear space index with query time O(m+σjloglogn+occ)O(m+\sigma^j \log \log n + occ). This significantly improves the previously best known linear space index by Lam et al. [ISAAC 2007], which requires query time Θ(jn)\Theta(jn) in the worst case. - An index with query time O(m+j+occ)O(m+j+occ) using space O(σk2nlogklogn)O(\sigma^{k^2} n \log^k \log n), where kk is the maximum number of wildcards allowed in the pattern. This is the first non-trivial bound with this query time. - A time-space trade-off, generalizing the index by Cole et al. [STOC 2004]. We also show that these indexes can be generalized to allow variable length gaps in the pattern. Our results are obtained using a novel combination of well-known and new techniques, which could be of independent interest

    Perceived benefits of and barriers to Building Information Modelling (BIM) implementation in construction: The case of Hong Kong

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    BIM has experienced an increasing appeal in its adoption and implementation in the built environment worldwide in recent years. The current research study aims to identify and assess the perceived benefits of and barriers to BIM implementation in the Hong Kong construction industry. The study adopted a quantitative research design using a structured empirical questionnaire survey. Also, a comparative analysis of the perceptions of the respondents’ groupings was conducted. The major barriers to BIM adoption are related to the inherent resistance to change by construction stakeholders, inadequate organizational support and structure to execute BIM, and lack of BIM industry standards in Hong Kong. Meanwhile, the key benefits include better cost estimation and control, efficient construction planning and management, and improvement in design and project quality. Practical and insightful recommendations were suggested for policymakers, local authorities, construction firms, and other key stakeholders to increase the uptake of BIM in construction projects as well as to aid them in the quest for full adoption of BIM in the built environment. The practical implications of the research findings were also presented and discussed
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