304 research outputs found

    Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis

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    <p>Abstract</p> <p>Background</p> <p>Clinical trials where cancer patients were treated with protease inhibitors have suggested that the serine protease, prostasin, may act as a tumour suppressor. Prostasin is proteolytically activated by the serine protease, matriptase, which has a very high oncogenic potential. Prostasin is inhibited by protease nexin-1 (PN-1) and the two isoforms encoded by the mRNA splice variants of <it>hepatocyte growth factor activator inhibitor-1 </it>(<it>HAI-1</it>), <it>HAI-1A</it>, and <it>HAI-1B</it>.</p> <p>Methods</p> <p>Using quantitative RT-PCR, we have determined the mRNA levels for <it>prostasin </it>and <it>PN-1 </it>in colorectal cancer tissue (n = 116), severe dysplasia (n = 13), mild/moderate dysplasia (n = 93), and in normal tissue from the same individuals. In addition, corresponding tissues were examined from healthy volunteers (n = 23). A part of the cohort was further analysed for the mRNA levels of the two variants of HAI-1, here denoted <it>HAI-1A </it>and <it>HAI-1B</it>. mRNA levels were normalised to <it>β-actin</it>. Immunohistochemical analysis of prostasin and HAI-1 was performed on normal and cancer tissue.</p> <p>Results</p> <p>The mRNA level of prostasin was slightly but significantly decreased in both mild/moderate dysplasia (p < 0.001) and severe dysplasia (p < 0.01) and in carcinomas (p < 0.05) compared to normal tissue from the same individual. The mRNA level of <it>PN-1 </it>was more that two-fold elevated in colorectal cancer tissue as compared to healthy individuals (p < 0.001) and elevated in both mild/moderate dysplasia (p < 0.01), severe dysplasia (p < 0.05) and in colorectal cancer tissue (p < 0.001) as compared to normal tissue from the same individual. The mRNA levels of <it>HAI-1A </it>and <it>HAI-1B </it>mRNAs showed the same patterns of expression. Immunohistochemistry showed that prostasin is located mainly on the apical plasma membrane in normal colorectal tissue. A large variation was found in the degree of polarization of prostasin in colorectal cancer tissue.</p> <p>Conclusion</p> <p>These results show that the mRNA level of <it>PN-1 </it>is significantly elevated in colorectal cancer tissue. Future studies are required to clarify whether down-regulation of prostasin activity via up regulation of PN-1 is causing the malignant progression or if it is a consequence of it.</p

    Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

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    One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

    Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

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    This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

    Search for stop and higgsino production using diphoton Higgs boson decays

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    Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

    Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

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    Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

    Search for anomalous production of events with three or more leptons in pp collisions at √s = 8TeV

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    Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.A search for physics beyond the standard model in events with at least three leptons is presented. The data sample, corresponding to an integrated luminosity of 19.5fb-1 of proton-proton collisions with center-of-mass energy s=8TeV, was collected by the CMS experiment at the LHC during 2012. The data are divided into exclusive categories based on the number of leptons and their flavor, the presence or absence of an opposite-sign, same-flavor lepton pair (OSSF), the invariant mass of the OSSF pair, the presence or absence of a tagged bottom-quark jet, the number of identified hadronically decaying τ leptons, and the magnitude of the missing transverse energy and of the scalar sum of jet transverse momenta. The numbers of observed events are found to be consistent with the expected numbers from standard model processes, and limits are placed on new-physics scenarios that yield multilepton final states. In particular, scenarios that predict Higgs boson production in the context of supersymmetric decay chains are examined. We also place a 95% confidence level upper limit of 1.3% on the branching fraction for the decay of a top quark to a charm quark and a Higgs boson (t→cH), which translates to a bound on the left- and right-handed top-charm flavor-violating Higgs Yukawa couplings, λtcH and λctH, respectively, of |λtcH|2+|λctH|2<0.21

    Studies of jet mass in dijet and W/Z plus jet events

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    This is the pre-print version of the final published paper that is available from the link below.Invariant mass spectra for jets reconstructed using the anti-kT and Cambridge-Aachen algorithms are studied for different jet “grooming” techniques in data corresponding to an integrated luminosity of 5 fb-1, recorded with the CMS detector in proton-proton collisions at the LHC at a center-of-mass energy of 7TeV. Leading-order QCD predictions for inclusive dijet and W/Z+jet production combined with parton-shower Monte Carlo models are found to agree overall with the data, and the agreement improves with the implementation of jet grooming methods used to distinguish merged jets of large transverse momentum from softer QCD gluon radiation
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