Explaining Web Technology Diffusion: An Institutional Theory Perspective

This article uses institutional theory as a basis to understand organizational processes that influence the extent to which web technologies that support the organization-customer relationship are adopted and subsequently diffused within an organization. The effect of coercive, mimetic, and normative processes that lead an organization to initially implement web technologies, referred to as adoption, differ from how those processes influence an organization to integrate evolving web technologies with business activities, referred to as diffusion. Adoption is presented as homogeneous across organizations and organizational populations, whereas diffusion is homogeneous within organizational populations. A theoretical model and related propositions are provided to guide future research

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Basal body stability and ciliogenesis requires the conserved component Poc1

Centrioles are the foundation for centrosome and cilia formation. The biogenesis of centrioles is initiated by an assembly mechanism that first synthesizes the ninefold symmetrical cartwheel and subsequently leads to a stable cylindrical microtubule scaffold that is capable of withstanding microtubule-based forces generated by centrosomes and cilia. We report that the conserved WD40 repeat domain–containing cartwheel protein Poc1 is required for the structural maintenance of centrioles in Tetrahymena thermophila. Furthermore, human Poc1B is required for primary ciliogenesis, and in zebrafish, DrPoc1B knockdown causes ciliary defects and morphological phenotypes consistent with human ciliopathies. T. thermophila Poc1 exhibits a protein incorporation profile commonly associated with structural centriole components in which the majority of Poc1 is stably incorporated during new centriole assembly. A second dynamic population assembles throughout the cell cycle. Our experiments identify novel roles for Poc1 in centriole stability and ciliogenesis

Sensitisation waves in a bidomain fire-diffuse-fire model of intracellular Ca²⁺ dynamics

We present a bidomain threshold model of intracellular calcium (Ca²⁺) dynamics in which, as suggested by recent experiments, the cytosolic threshold for Ca²⁺ liberation is modulated by the Ca²⁺ concentration in the releasing compartment. We explicitly construct stationary fronts and determine their stability using an Evans function approach. Our results show that a biologically motivated choice of a dynamic threshold, as opposed to a constant threshold, can pin stationary fronts that would otherwise be unstable. This illustrates a novel mechanism to stabilise pinned interfaces in continuous excitable systems. Our framework also allows us to compute travelling pulse solutions in closed form and systematically probe the wave speed as a function of physiologically important parameters. We find that the existence of travelling wave solutions depends on the time scale of the threshold dynamics, and that facilitating release by lowering the cytosolic threshold increases the wave speed. The construction of the Evans function for a travelling pulse shows that of the co-existing fast and slow solutions the slow one is always unstable

Invasion success of a global avian invader is explained by within-taxon niche structure and association with humans in the native range

Aim To mitigate the threat invasive species pose to ecosystem functioning, reli- able risk assessment is paramount. Spatially explicit predictions of invasion risk obtained through bioclimatic envelope models calibrated with native species distribution data can play a critical role in invasive species management. Fore- casts of invasion risk to novel environments, however, remain controversial. Here, we assess how species’ association with human-modified habitats in the native range and within-taxon niche structure shape the distribution of invasive populations at biogeographical scales and influence the reliability of predictions of invasion risk. Location Africa, Asia and Europe. Methods We use ~1200 native and invasive ring-necked parakeet (Psittacula krameri) occurrences and associated data on establishment success in combi- nation with mtDNA-based phylogeographic structure to assess niche dynam- ics during biological invasion and to generate predictions of invasion risk. Niche dynamics were quantified in a gridded environmental space while bioclimatic models were created using the biomod2 ensemble modelling framework. Results Ring-necked parakeets show considerable niche expansion into climates colder than their native range. Only when incorporating a measure of human modification of habitats within the native range do bioclimatic envelope mod- els yield credible predictions of invasion risk for parakeets across Europe. Inva- sion risk derived from models that account for differing niche requirements of phylogeographic lineages and those that do not achieve similar statistical accu- racy, but there are pronounced differences in areas predicted to be susceptible for invasion. Main conclusions Information on within-taxon niche structure and especially association with humans in the native range can substantially improve predic- tive models of invasion risk. To provide policymakers with robust predictions of invasion risk, including these factors into bioclimatic envelope models is recommended

Genomic editing of metformin efficacy-associated genetic variants in SLC47A1 does not alter SLC47A1 expression

Several pharmacogenetics studies have identified an association between a greater metformin-dependent reduction in HbA1c levels and the minor A allele at rs2289669 in intron 10 of SLC47A1, encoding multidrug and toxin extrusion 1 (MATE1), a presumed metformin transporter. It is currently unknown if the rs2289669 locus is a cis-eQTL, which would validate its role as predictor of metformin efficacy. We looked at association between common genetic variants in the SLC47A1 gene region and HbA1c reduction after metformin treatment using locus-wise meta-analysis from the MetGen consortium. CRISPR-Cas9 was applied to perform allele editing of, or genomic deletion around, rs2289669 and of the closely linked rs8065082 in HepG2 cells. The genome-edited cells were evaluated for SLC47A1 expression and splicing. None of the common variants including rs2289669 showed significant association with metformin response. Genomic editing of either rs2289669 or rs8065082 did not alter SLC47A1 expression or splicing. Experimental and in silico analyses show that the rs2289669-containing haploblock does not appear to carry genetic variants that could explain its previously reported association with metformin efficacy.Peer reviewe

Temperature-dependent release of ATP from human erythrocytes: Mechanism for the control of local tissue perfusion

Copyright @ 2012 The AuthorsThis article has been made available through the Brunel Open Access Publishing Fund.Human limb muscle and skin blood flow increases significantly with elevations in temperature, possibly through physiological processes that involve temperature-sensitive regulatory mechanisms. Here we tested the hypothesis that the release of the vasodilator ATP from human erythrocytes is sensitive to physiological increases in temperature both in vitro and in vivo, and examined potential channel/transporters involved. To investigate the source of ATP release, whole blood, red blood cells (RBCs), plasma and serum were heated in vitro to 33, 36, 39 and 42°C. In vitro heating augmented plasma or ‘bathing solution’ ATP in whole blood and RBC samples, but not in either isolated plasma or serum samples. Heat-induced ATP release was blocked by niflumic acid and glibenclamide, but was not affected by inhibitors of nucleoside transport or anion exchange. Heating blood to 42°C enhanced (P < 0.05) membrane protein abundance of cystic fibrosis transmembrane conductance regulator (CFTR) in RBCs. In a parallel in vivo study in humans exposed to whole-body heating at rest and during exercise, increases in muscle temperature from 35 to 40°C correlated strongly with elevations in arterial plasma ATP (r2 = 0.91; P = 0.0001), but not with femoral venous plasma ATP (r2 = 0.61; P = 0.14). In vitro, however, the increase in ATP release from RBCs was similar in arterial and venous samples heated to 39°C. Our findings demonstrate that erythrocyte ATP release is sensitive to physiological increases in temperature, possibly via activation of CFTR-like channels, and suggest that temperature-dependent release of ATP from erythrocytes might be an important mechanism regulating human limb muscle and skin perfusion in conditions that alter blood and tissue temperature.This article is made available through the Brunel Open Access Publishing Fund

Pseudospin, supersymmetry and the shell structure of atomic nuclei

The evolution of single-particle energies with varying isospin asymmetry in the shell model is an important issue when predicting changes in the shell structure for exotic nuclei. In many cases pseudospin partner levels, that are almost degenerate in energy for stable nuclei, are relevant in extracting the size of the shell gaps. A breaking of the pseudospin symmetry can affect the size of these gaps and change the magic numbers accordingly. The strength of the pseudospin splitting is expected to depend in particular on isovector-dependent and tensor contributions to the effective nuclear interaction. A description employing supersymmetric quantum mechanics allows to derive a pseudospin symmetry breaking potential that is regular in contrast to the pseudospin-orbit potential in the conventional relativistic treatment. The derived perturbation potential provides a measure to quantify the symmetry breaking and it can be employed to improve mean-field calculations in order to better reproduce the experimentally observed shell evolution. General potentials with exact pseudospin symmetry are obtained that can be used in relativistic mean-field Hamiltonians.Comment: 33 pages, 1 table, 6 figures, additional references, minor corrections, note added in proof, accepted for publication in Nuclear Physics

Beyond the Gene

This paper is a response to the increasing difficulty biologists find in agreeing upon a definition of the gene, and indeed, the increasing disarray in which that concept finds itself. After briefly reviewing these problems, we propose an alternative to both the concept and the word gene—an alternative that, like the gene, is intended to capture the essence of inheritance, but which is both richer and more expressive. It is also clearer in its separation of what the organism statically is (what it tangibly inherits) and what it dynamically does (its functionality and behavior). Our proposal of a genetic functor, or genitor, is a sweeping extension of the classical genotype/phenotype paradigm, yet it appears to be faithful to the findings of contemporary biology, encompassing many of the recently emerging—and surprisingly complex—links between structure and functionality