Hypothesis: ‘Vasocrine’ signalling from perivascular fat - a mechanism linking insulin resistance and vascular disease

Adipose tissue expresses cytokines which inhibit insulin signalling pathways in liver and muscle. Obesity also results in impairment of endothelium-dependent vasodilatation to insulin. We propose a vasoregulatory role for local deposits of fat around the origin of arterioles supplying skeletal muscle. Isolated first order arterioles from rat cremaster muscle are under dual regulation by insulin, which activates both endothelin-1 mediated vasoconstriction and nitric oxide mediated vasodilatation. In obese rat arterioles, insulin-stimulated nitric oxide synthesis is impaired, resulting in unopposed vasoconstriction. We propose this to be the consequence of production of the adipocytokine tumour necrosis factor-α from the cuff of fat seen surrounding the origin of the arteriole in obese rats – a depot to which we ascribe a specialist vasoregulatory role. We suggest that this cytokine accesses the nutritive vascular tree to inhibit insulin-mediated capillary recruitment – a mechanism we term ‘vasocrine’ signalling. We also suggest a homology between this vasoactive periarteriolar fat and both periarterial and visceral fat, which may explain relationships between visceral fat, insulin resistance and vascular disease

Corporate Ownership Structure and the Evolution of Bankruptcy Law in the US and UK

The past decade has seen intense academic debates over possible explanations for the different systems of corporate ownership and control that exist in developed economies. Yet the role of bankruptcy as a mechanism of corporate governance has received relatively little attention. Furthermore, many theories have failed to account successfully for events occurring in the UK, notwithstanding its similarity to the US. In response, this paper offers an account of the complementarities between bankruptcy law and ownership structure, which it is argued can explain developments in both the UK and the US. By identifying the effects of concentration or dispersion in firms' capital structure (across both equity and debt), and by analysing implications of these capital structure choices for bankruptcy, the paper develops a richer account of the corporate governance patterns we see in different nations.Bankruptcy, Law and Finance, Ownership Structure, Debt Concentration

Struggling to a monumental triumph : Re-assessing the final stages of the smallpox eradication program in India, 1960-1980

The global smallpox program is generally presented as the brainchild of a handful of actors from the WHO headquarters in Geneva and at the agency's regional offices. This article attempts to present a more complex description of the drive to eradicate smallpox. Based on the example of India, a major focus of the campaign, it is argued that historians and public health officials should recognize the varying roles played by a much wider range of participants. Highlighting the significance of both Indian and international field officials, the author shows how bureaucrats and politicians at different levels of administration and society managed to strengthen—yet sometimes weaken—important program components. Centrally dictated strategies developed at WHO offices in Geneva and New Delhi, often in association with Indian federal authorities, were reinterpreted by many actors and sometimes changed beyond recognition

Characterisation of galvanneal coatings on strip steel

Galvanneal is a form of zinc-coated sheet steel, where steel is dipped in molten zinc, and then heat treated in a furnace to produce a complex iron-zinc coating. Many industries, such as automotive, use galvanneal for components fabricated from sheet steel. The microstructural properties of galvanneal have a significant influence on how well the sheet metal changes shape on stamping. By means of optical microscopy, scanning electron microscopy, and glow-discharge optical emission spectrometry, we present a study of the microstructure of several galvanneal samples, both stamped and unformed, relating the phases and morphology of the coatings to performance in stamping operations. Samples of galvanneal were subjected to different heat-treatment temperatures. The frequency of defects in stamped components was found to be related to the average alloy content in the coatings, which varied with furnace temperature. An increased average iron content in the coatings was related to increased powdering defects in stamping operations that use galvanneal coated sheet steel.<br /

Reuse as heuristic : from transmission to nurture in learning activity design

In recent years a combination of ever more flexible and sophisticated Web technologies and an explosion in the quantity of online content has sparked learning technologists around the world to pursue the promise of the 'reusable learning object' or RLO with the idea that RLOs could be reused in different educational contexts, thereby providing greater overall flexibility and return on investment. In 2002 the ACETS Project undertook a three-year study in the UK to investigate whether RLOs worked in practice and how the pursuit of reuse affected the teacher and their teaching. Teachers working in healthcare-related subjects in Higher and Further Education were asked to create an original learning design or activity from third-party digital resources and to reflect both on the process and its outcomes. The expectation was that teachers would be the ones selecting and reusing third-party materials. This paper describes how one of the ACETS exemplifiers reinterpreted this remit, challenged the anticipated transmissive model of learning, and instead, gave their students an opportunity to create their own original learning designs and learning activities from third-party digital resources. By describing the educational enhancements, the resulting heightened levels of critical thinking, and sensitivity to patient needs, 'reuse' will be shown to be an effective heuristic for student self-direction and professional development

Irreducible pseudo 2-factor isomorphic cubic bipartite graphs

A bipartite graph is {\em pseudo 2--factor isomorphic} if all its 2--factors have the same parity of number of circuits. In \cite{ADJLS} we proved that the only essentially 4--edge-connected pseudo 2--factor isomorphic cubic bipartite graph of girth 4 is $K_{3,3}$, and conjectured \cite[Conjecture 3.6]{ADJLS} that the only essentially 4--edge-connected cubic bipartite graphs are $K_{3,3}$, the Heawood graph and the Pappus graph. There exists a characterization of symmetric configurations $n_3$ %{\bf decide notation and how to use it in the rest of the paper} due to Martinetti (1886) in which all symmetric configurations $n_3$ can be obtained from an infinite set of so called {\em irreducible} configurations \cite{VM}. The list of irreducible configurations has been completed by Boben \cite{B} in terms of their {\em irreducible Levi graphs}. In this paper we characterize irreducible pseudo 2--factor isomorphic cubic bipartite graphs proving that the only pseudo 2--factor isomorphic irreducible Levi graphs are the Heawood and Pappus graphs. Moreover, the obtained characterization allows us to partially prove the above Conjecture

Intermolecular O-H...O and C-H...π(C5H5), and intramolecular C-H...O interactions in 2-(ferrocenyl)thiophene-3-carboxylic acid

The title compound, [Fe(C₅H₅)(C₁₀H₇O₂S)], an important precursor en route to organometallic donor-π-acceptor systems, forms dimers in the solid state through cyclic intermolecular carboxylic acid O-H...O hydrogen bonds, graph set R²₂(8) [O...O 2.661 (2) Å and O-H...O 175°]. Intermolecular Ccp-H...πcp interactions between the unsubstituted cyclopentadienyl (Cp) rings and Cthiazole-H...πcp interactions link neighbouring molecules into a three-dimensional network [C...Cg 3.753 (7) Å and C-H...Cg 156°, and C...Cg 3.687 (3) Å and C-H...Cg 129°; Cg is the ring centroid]. Intramolecular C-H...O interactions are present, graph set S(7) [C...O 2.925 (3) Å and C-H...O 120°, and the closest C-H...Sthienyl contact has a C...S distance of 3.058 (2) Å]

Knowledge practices in design: The role of visual representations as 'epistemic objects'

We use a detailed study of the knowledge work around visual representations to draw attention to the multidimensional nature of `objects'. Objects are variously described in the literatures as relatively stable or in flux; as abstract or concrete; and as used within or across practices. We clarify these dimensions, drawing on and extending the literature on boundary objects, and connecting it with work on epistemic and technical objects. In particular, we highlight the epistemic role of objects, using our observations of knowledge work on an architectural design project to show how, in this setting, visual representations are characterized by a `lack' or incompleteness that precipitates unfolding. The conceptual design of a building involves a wide range of technical, social and aesthetic forms of knowledge that need to be developed and aligned. We explore how visual representations are used, and how these are meaningful to different stakeholders, eliciting their distinct contributions. As the project evolves and the drawings change, new issues and needs for knowledge work arise. These objects have an `unfolding ontology' and are constantly in flux, rather than fully formed. We discuss the implications for wider understandings of objects in organizations and for how knowledge work is achieved in practice

Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is unresponsive to current therapies and characterized by excessive collagen deposition and subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)-6, are elevated in IPF, the molecular mechanisms that underlie this disease are incompletely understood, although the development of fibrosis is believed to depend on canonical transforming growth factor (TGF)-β signalling. We examined bleomycin-induced inflammation and fibrosis in mice carrying a mutation in the shared IL-6 family receptor gp130. Using genetic complementation, we directly correlate the extent of IL-6-mediated, excessive Stat3 activity with inflammatory infiltrates in the lung and the severity of fibrosis in corresponding gp130757F mice. The extent of fibrosis was attenuated in B lymphocyte-deficient gp130757F;µMT−/− compound mutant mice, but fibrosis still occurred in their Smad3−/− counterparts consistent with the capacity of excessive Stat3 activity to induce collagen 1α1 gene transcription independently of canonical TGF-β/Smad3 signalling. These findings are of therapeutic relevance, since we confirmed abundant STAT3 activation in fibrotic lungs from IPF patients and showed that genetic reduction of Stat3 protected mice from bleomycin-induced lung fibrosis