144 research outputs found

    Corporate financing decisions: UK survey evidence

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    Despite theoretical developments in recent years, our understanding of corporate capital structure remains incomplete. Prior empirical research has been dominated by archival regression studies which are limited in their ability to fully reflect the diversity found in practice. The present paper reports on a comprehensive survey of corporate financing decision-making in UK listed companies. A key finding is that firms are heterogeneous in their capital structure policies. About half of the firms seek to maintain a target debt level, consistent with trade-off theory, but 60 per cent claim to follow a financing hierarchy, consistent with pecking order theory. These two theories are not viewed by respondents as either mutually exclusive or exhaustive. Many of the theoretical determinants of debt levels are widely accepted by respondents, in particular the importance of interest tax shield, financial distress, agency costs and also, at least implicitly, information asymmetry. Results also indicate that cross-country institutional differences have a significant impact on financial decisions

    Reorganization of the chick basilar papilla after acoustic trauma

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    The auditory epithelium in birds and mammals consists of a postmitotic population of hair cells and supporting cells. Unlike mammals, birds can regenerate their auditory epithelia after trauma. Recent evidence indicates that supporting cells undergo mitosis after acoustic trauma, suggesting that supporting cells may transdifferentiate into hair cells. The goals of this study were to (1) characterize the responses of hair cells and supporting cells to acoustic trauma, and (2) determine whether hair cell loss is a prerequisite for generation of new hair cells. Chicks were exposed to an octave-band noise and their inner ears assayed with fluorescence or scanning electron microscopy. In one area of the basilar papilla, defined as the center of the lesion, extensive hair cell degeneration occurred. Expanded supporting cells obliterated degenerating hair cells and invaded spaces normally occupied by hair cells. Aggregates of DNA were found within the basilar papilla, suggesting that hair cell death and disintegration may occur within the epithelium. The epithelial sheet appeared structurally confluent at all times examined. Supporting cells exhibited altered apical contour in distal regions of the basilar papilla, where hair cell damage was mild or inconspicuous. Four days after noise exposure, newly generated hair cells were found in the center of the lesion and in the distal areas, where no hair cell loss could be detected. The results suggest that supporting cells may play an important role in maintenance and repair of the traumatized basilar papilla and raise the possibility that production of new hair cells is not dependent on hair cell loss in the immediate vicinity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50055/1/903300408_ftp.pd

    Time-dependent mechanical behavior of human amnion: Macroscopic and microscopic characterization

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    Characterizing the mechanical response of the human amnion is essential to understand and to eventually prevent premature rupture of fetal membranes. In this study, a large set of macroscopic and microscopic mechanical tests have been carried out on fresh unfixed amnion to gain insight into the time-dependent material response and the underlying mechanisms. Creep and relaxation responses of amnion were characterized in macroscopic uniaxial tension, biaxial tension and inflation configurations. For the first time, these experiments were complemented by microstructural information from nonlinear laser scanning microscopy performed during in situ uniaxial relaxation tests. The amnion showed large tension reduction during relaxation and small inelastic strain accumulation in creep. The short-term relaxation response was related to a concomitant in-plane and out-of-plane contraction, and was dependent on the testing configuration. The microscopic investigation revealed a large volume reduction at the beginning, but no change of volume was measured long-term during relaxation. Tension–strain curves normalized with respect to the maximum strain were highly repeatable in all configurations and allowed the quantification of corresponding characteristic parameters. The present data indicate that dissipative behavior of human amnion is related to two mechanisms: (i) volume reduction due to water outflow (up to ∼20 s) and (ii) long-term dissipative behavior without macroscopic deformation and no systematic global reorientation of collagen fibers

    Activation of P2X7-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice

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    <p>Abstract</p> <p>Background</p> <p>The study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X<sub>7 </sub>receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X<sub>7 </sub>system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X<sub>7 </sub>action.</p> <p>Methods</p> <p>Skin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X<sub>7</sub>-null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide influx (P2X<sub>7 </sub>pore formation) were determined by confocal laser microscopy.</p> <p>Results</p> <p>(a) Co-application on the skin of the P2X<sub>7 </sub>specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28) the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In the normal skin BzATP affected mainly P2X<sub>7</sub>-receptor – expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d) Levels of P2X<sub>7 </sub>receptor, protein and mRNA were 4–5 fold lower in cancer tissues than in normal mouse tissues. (e) In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for BzATP. (g) Pore formation and the augmented calcium influx were depended on the expression of the P2X<sub>7 </sub>receptor, while the BzATP-induced apoptosis depended on calcium influx. (h) The BzATP-induced apoptosis could be blocked by co-treatment with inhibitors of caspase-9 and caspase-3, but not of caspase-8.</p> <p>Conclusion</p> <p>(a) P2X<sub>7</sub>-dependent apoptosis is an important mechanism that controls the development and progression of epidermal neoplasia in the mouse. (b) The P2X<sub>7</sub>-dependent apoptosis is mediated by calcium influx via P2X<sub>7 </sub>pores, and involves the caspase-9 (mitochondrial) pathway. (c) The diminished pro-apoptotic effect of BzATP in mouse cancer keratinocytes is possibly the result of low expression of the P2X<sub>7 </sub>receptor. (d) Activation of P2X<sub>7</sub>-dependent apoptosis, e.g. with BzATP could be a novel chemotherapeutic growth-preventive modality for papillomas and epithelial cancers in vivo.</p

    Function and failure of the fetal membrane : modelling the mechanics of the chorion and amnion

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    The fetal membrane surrounds the fetus during pregnancy and is a thin tissue composed of two layers, the chorion and the amnion. While rupture of this membrane normally occurs at term, preterm rupture can result in increased risk of fetal mortality and morbidity, as well as danger of infection in the mother. Although structural changes have been observed in the membrane in such cases, the mechanical behaviour of the human fetal membrane in vivo remains poorly understood and is challenging to investigate experimentally. Therefore, the objective of this study was to develop simplified finite element models to investigate the mechanical behaviour and rupture of the fetal membrane, particularly its constituent layers, under various physiological conditions. It was found that modelling the chorion and amnion as a single layer predicts remarkably different behaviour compared with a more anatomically-accurate bilayer, significantly underestimating stress in the amnion and under-predicting the risk of membrane rupture. Additionally, reductions in chorion-amnion interface lubrication and chorion thickness (reported in cases of preterm rupture) both resulted in increased membrane stress. Interestingly, the inclusion of a weak zone in the fetal membrane that has been observed to develop overlying the cervix would likely cause it to fail at term, during labour. Finally, these findings support the theory that the amnion is the dominant structural component of the fetal membrane and is required to maintain its integrity. The results provide a novel insight into the mechanical effect of structural changes in the chorion and amnion, in cases of both normal and preterm rupture

    Student politics, teaching politics, black politics: an interview with Ansel Wong

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    Ansel Wong is the quiet man of British black politics, rarely in the limelight and never seeking political office. And yet his ‘career’ here – from Black Power firebrand to managing a multimillion budget as head of the Greater London Council’s Ethnic Minority Unit in the 1980s – spells out some of the most important developments in black educational and cultural projects. In this interview, he discusses his identification with Pan-Africanism, his involvement in student politics, his role in the establishment of youth projects and supplementary schools in the late 1960s and 1970s, and his involvement in black radical politics in London in the same period, all of which took place against the background of revolutionary ferment in the Third World and the world of ideas, and were not without their own internal class and ethnic conflicts

    Inflammation: Basic Principles and Clinical Correlates

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