922 research outputs found
Entropy production by resonance decays
We investigate entropy production for an expanding system of particles and
resonances with isospin symmetry -- in our case pions and mesons --
within the framework of relativistic kinetic theory. A cascade code to simulate
the kinetic equations is developed and results for entropy production and
particle spectra are presented.Comment: 17 pages, 10 ps-figures included, only change: preprint number adde
Driving current through single organic molecules
We investigate electronic transport through two types of conjugated
molecules. Mechanically controlled break-junctions are used to couple thiol
endgroups of single molecules to two gold electrodes. Current-voltage
characteristics (IVs) of the metal-molecule-metal system are observed. These
IVs reproduce the spatial symmetry of the molecules with respect to the
direction of current flow. We hereby unambigously detect an intrinsic property
of the molecule, and are able to distinguish the influence of both the molecule
and the contact to the metal electrodes on the transport properties of the
compound system.Comment: 4 pages, 5 figure
It is Hobbes, not Rousseau:an experiment on voting and redistribution
We perform an experiment which provides a laboratory replica of some
important features of the welfare state. In the experiment, all individuals in a group
decide whether to make a costly effort, which produces a random (independent) outcome
for each one of them. The group members then vote on whether to redistribute
the resulting and commonly known total sum of earnings equally amongst themselves.
This game has two equilibria, if played once. In one of them, all players make
effort and there is little redistribution. In the other one, there is no effort and nothingWe thank Iris Bohnet, Tim Cason, David Cooper, John Duffy, Maia Guell, John Van Huyck and Robin Mason for helpful conversations and encouragement. The comments of the Editor and two referees helped improve the paper. We gratefully acknowledge the financial support from Spain’s Ministry of Science and Innovation under grants CONSOLIDER INGENIO 2010 CSD2006-0016 (all authors), ECO2009-10531 (Cabrales), ECO2008-01768 (Nagel) and the Comunidad de Madrid under grant Excelecon (Cabrales), the Generalitat de Catalunya and the CREA program (Nagel), and project SEJ2007-64340 of Spain’s Ministerio de Educación y Ciencia (Rodríguez Mora).Publicad
Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent Apoptosis, but are insensitive to direct activation with exogenous fas ligand
Introduction
Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF) receptor family members; CD40 and Fas (CD95). Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma.
Aims
To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines.
Results
Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both.
Conclusions
1) Both primary and malignant cholangiocytes are relatively resistant to Fas–mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2) The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes
Epidermal growth factor receptor expression analysis in chemotherapy-naive patients with advanced non-small-cell lung cancer treated with gefitinib or placebo in combination with platinum-based chemotherapy
Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1.
Holographic phase diagram of quark-gluon plasma formed in heavy-ions collisions
The phase diagram of quark gluon plasma (QGP) formed at a very early stage
just after the heavy ion collision is obtained by using a holographic dual
model for the heavy ion collision. In this dual model colliding ions are
described by the charged shock gravitational waves. Points on the phase diagram
correspond to the QGP or hadronic matter with given temperatures and chemical
potentials. The phase of QGP in dual terms is related to the case when the
collision of shock waves leads to formation of trapped surface. Hadronic matter
and other confined states correspond to the absence of trapped surface after
collision.
Multiplicity of the ion collision process is estimated in the dual language
as area of the trapped surface. We show that a non-zero chemical potential
reduces the multiplicity. To plot the phase diagram we use two different dual
models of colliding ions, the point and the wall shock waves, and find
qualitative agreement of the results.Comment: 33 pages, 14 figures, typos correcte
Genetic inactivation of the Fanconi anemia gene FANCC identified in the hepatocellular carcinoma cell line HuH-7 confers sensitivity towards DNA-interstrand crosslinking agents
Background: Inactivation of the Fanconi anemia (FA) pathway through defects in one of 13 FA genes occurs at low frequency in various solid cancer entities among the general population. As FA pathway inactivation confers a distinct hypersensitivity towards DNA interstrand-crosslinking (ICL)-agents, FA defects represent rational targets for individualized therapeutic strategies. Except for pancreatic cancer, however, the prevalence of FA defects in gastrointestinal (GI) tumors has not yet been systematically explored. Results: A panel of GI cancer cell lines was screened for FA pathway inactivation applying FANCD2 monoubiquitination and FANCD2/RAD51 nuclear focus formation and a newly identified FA pathway-deficient cell line was functionally characterized. The hepatocellular carcinoma (HCC) line HuH-7 was defective in FANCD2 monoubiquitination and FANCD2 nuclear focus formation but proficient in RAD51 focus formation. Gene complementation studies revealed that this proximal FA pathway inactivation was attributable to defective FANCC function in HuH-7 cells. Accordingly, a homozygous inactivating FANCC nonsense mutation (c.553C > T, p.R185X) was identified in HuH-7, resulting in partial transcriptional skipping of exon 6 and leading to the classic cellular FA hypersensitivity phenotype; HuH-7 cells exhibited a strongly reduced proliferation rate and a pronounced G2 cell cycle arrest at distinctly lower concentrations of ICL-agents than a panel of non-isogenic, FA pathway-proficient HCC cell lines. Upon retroviral transduction of HuH-7 cells with FANCC cDNA, FA pathway functions were restored and ICL-hypersensitivity abrogated. Analyses of 18 surgical HCC specimens yielded no further examples for genetic or epigenetic inactivation of FANCC, FANCF, or FANCG in HCC, suggesting a low prevalence of proximal FA pathway inactivation in this tumor type. Conclusions: As the majority of HCC are chemoresistant, assessment of FA pathway function in HCC could identify small subpopulations of patients expected to predictably benefit from individualized treatment protocols using ICL-agents
‘Shared intelligibility’ and two reflexive strategies as methods of supporting ‘responsible decisions’ in a hermeneutic phenomenological study
Hermeneutic phenomenologists propose that researchers inescapably bring themselves into their research because interpretation must inevitably be influenced by their contexts and pre-understandings. They propose that interpretation is a dynamic and active part of the construction of a text’s meaning, and involvement in this construction process leads to deep empathic understanding of others’ experience, reappraisal of accepted social and cultural systems, and a level of self-enlightenment. The strengths of the hermeneutic methodological approach have led to its use in a number of disciplines, however, there remains concerns about interpretative validity. It is widely acknowledged that in order to support rigour and validity in hermeneutic studies, researchers are required to develop and integrate strategies within the research process to promote awareness of the interplay between their pre-understandings and interpretation. This paper discusses how episodic interviewing which capitalises on ‘shared intelligibility’, and the reflexive strategies of ‘oppositional arrangement of perspectives’ and ‘backgrounding’ were used to shed light on data from a study of the experiences and views of nursing home nurses regarding their occupational role and status, and work identity
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