Hepatic fibrogenesis requires sympathetic neurotransmitters

Background and aims: Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear. Methods: We studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis. Results: HSC expressed adrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by α- and β-adrenoceptor antagonists. HSC from dopamine β-hydroxylase deficient (Dbh(−/−)) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh(−/−) mice, as evidenced by reduced hepatic accumulation of α-smooth muscle actin(+ve) HSC and decreased induction of transforming growth factor β1 (TGF-β1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and are resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-β1 and collagen, and increased liver fibrosis. Conclusions: HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis

Double Parton Scattering Singularity in One-Loop Integrals

We present a detailed study of the double parton scattering (DPS) singularity, which is a specific type of Landau singularity that can occur in certain one-loop graphs in theories with massless particles. A simple formula for the DPS singular part of a four-point diagram with arbitrary internal/external particles is derived in terms of the transverse momentum integral of a product of light cone wavefunctions with tree-level matrix elements. This is used to reproduce and explain some results for DPS singularities in box integrals that have been obtained using traditional loop integration techniques. The formula can be straightforwardly generalised to calculate the DPS singularity in loops with an arbitrary number of external particles. We use the generalised version to explain why the specific MHV and NMHV six-photon amplitudes often studied by the NLO multileg community are not divergent at the DPS singular point, and point out that whilst all NMHV amplitudes are always finite, certain MHV amplitudes do contain a DPS divergence. It is shown that our framework for calculating DPS divergences in loop diagrams is entirely consistent with the `two-parton GPD' framework of Diehl and Schafer for calculating proton-proton DPS cross sections, but is inconsistent with the `double PDF' framework of Snigirev.Comment: 29 pages, 8 figures. Minor corrections and clarifications added. Version accepted for publication in JHE

Quantum States and Phases in Driven Open Quantum Systems with Cold Atoms

An open quantum system, whose time evolution is governed by a master equation, can be driven into a given pure quantum state by an appropriate design of the system-reservoir coupling. This points out a route towards preparing many body states and non-equilibrium quantum phases by quantum reservoir engineering. Here we discuss in detail the example of a \emph{driven dissipative Bose Einstein Condensate} of bosons and of paired fermions, where atoms in an optical lattice are coupled to a bath of Bogoliubov excitations via the atomic current representing \emph{local dissipation}. In the absence of interactions the lattice gas is driven into a pure state with long range order. Weak interactions lead to a weakly mixed state, which in 3D can be understood as a depletion of the condensate, and in 1D and 2D exhibits properties reminiscent of a Luttinger liquid or a Kosterlitz-Thouless critical phase at finite temperature, with the role of the ``finite temperature'' played by the interactions.Comment: 9 pages, 2 figure

An Open-System Quantum Simulator with Trapped Ions

The control of quantum systems is of fundamental scientific interest and promises powerful applications and technologies. Impressive progress has been achieved in isolating the systems from the environment and coherently controlling their dynamics, as demonstrated by the creation and manipulation of entanglement in various physical systems. However, for open quantum systems, engineering the dynamics of many particles by a controlled coupling to an environment remains largely unexplored. Here we report the first realization of a toolbox for simulating an open quantum system with up to five qubits. Using a quantum computing architecture with trapped ions, we combine multi-qubit gates with optical pumping to implement coherent operations and dissipative processes. We illustrate this engineering by the dissipative preparation of entangled states, the simulation of coherent many-body spin interactions and the quantum non-demolition measurement of multi-qubit observables. By adding controlled dissipation to coherent operations, this work offers novel prospects for open-system quantum simulation and computation.Comment: Pre-review submission to Nature. For an updated and final version see publication. Manuscript + Supplementary Informatio

Conformal symmetry of the critical 3D Ising model inside a sphere

We perform Monte-Carlo simulations of the three-dimensional Ising model at the critical temperature and zero magnetic field. We simulate the system in a ball with free boundary conditions on the two dimensional spherical boundary. Our results for one and two point functions in this geometry are consistent with the predictions from the conjectured conformal symmetry of the critical Ising model.We are grateful to Slava Rychkov for useful discussions and for suggesting this work. The research leading to these results has received funding from the [European Union] Seventh Framework Programme [FP7-People-2010-IRSES] and [FP7/2007-2013] under grant agreements No 269217, 317089 and No 247252, and from the grant CERN/FP/123599/2011. Centro de Física do Porto is partially funded by the Foundation for Science and Technology of Portugal (FCT). J.V.P.L. acknowledges funding from projecto Operacional Regional do Norte, within Quadro de Referência Estratégico Nacional (QREN) and through Fundo Europeu de Desenvolvimento Regional (FEDER), Ref. NORTE-07-0124-FEDER- 00003

Double parton correlations and constituent quark models: a light front approach to the valence sector

An explicit evaluation of the double parton distribution functions (dPDFs), within a relativistic Light-Front approach to constituent quark models, is presented. dPDFs encode information on the correlations between two partons inside a target and represent the non-perturbative QCD ingredient for the description of double parton scattering in proton-proton collisions, a crucial issue in the search of new Physics at the LHC. Valence dPDFs are evaluated at the low scale of the model and the perturbative scale of the experiments is reached by means of QCD evolution. The present results show that the strong correlation effects present at the scale of the model are still sizable, in the valence region, at the experimental scale. At the low values of x presently studied at the LHC the correlations become less relevant, although they are still important for the spin-dependent contributions to unpolarized proton scattering

Prevalence and factors associated with the presence of non alcoholic fatty liver disease in an apparently healthy adult population in primary care units

<p>Abstract</p> <p>Background</p> <p>Fatty liver disease is characterized by the accumulation of fat vacuoles inside of the hepatocytes. Non alcoholic fatty liver is associated with obesity, type 2 diabetes, dyslipemia, the intake of certain drugs and with the so-called metabolic syndrome. However, there is little information on the clinical relevance of this disorder as a healthcare problem in the general population, since the studies published generally include a limited number of patients and the diagnosis is established on the basis of clear biochemical alterations and liver biopsy.</p> <p>Methods/Design</p> <p>The aim of the study is the prevalence of non-alcoholic fatty liver disease in a general adult population by hepatic ultrasonography.</p> <p>A population-based, descriptive, transversal, multicentre study. Eighteen primary care centres of the north of Barcelona and the Maresme Areas of Healthcare Management attending an urban and semi-urban population of 360.000 inhabitants.</p> <p>A randomized sample of 786 subjects of 15 years or older were selected from the population and assigned to the participating centres according to the Primary Care Information System (SIAP): This population is practically the same as the general population of the area.</p> <p>The following determinations will be carried out in all the participants: hepatic ultrasonography to detect fatty liver, a questionnaire concerning liver diseases, alcohol intake, smoking and drug use, physical examination including abdominal perimeter and body mass index and biochemical analysis including liver function tests and parameters related to the metabolic syndrome and the HAIR score.</p> <p>Ultrasonographic diagnosis of fatty liver will be made according to established criteria (American Gastroenterology Association) and diagnosis of metabolic syndrome according to the criteria of the European Group for the Study of Insulin Resistance.</p> <p>Discussion</p> <p>This study will attempt to determine the prevalence of non alcoholic fatty liver disease, as well as, the factors most frequently associated with the presence of this disease to thereby achieve the most appropriate treatment and avoid the evolution of the disease.</p

Logical Development of the Cell Ontology

<p>Abstract</p> <p>Background</p> <p>The Cell Ontology (CL) is an ontology for the representation of <it>in vivo </it>cell types. As biological ontologies such as the CL grow in complexity, they become increasingly difficult to use and maintain. By making the information in the ontology computable, we can use automated reasoners to detect errors and assist with classification. Here we report on the generation of computable definitions for the hematopoietic cell types in the CL.</p> <p>Results</p> <p>Computable definitions for over 340 CL classes have been created using a genus-differentia approach. These define cell types according to multiple axes of classification such as the protein complexes found on the surface of a cell type, the biological processes participated in by a cell type, or the phenotypic characteristics associated with a cell type. We employed automated reasoners to verify the ontology and to reveal mistakes in manual curation. The implementation of this process exposed areas in the ontology where new cell type classes were needed to accommodate species-specific expression of cellular markers. Our use of reasoners also inferred new relationships within the CL, and between the CL and the contributing ontologies. This restructured ontology can be used to identify immune cells by flow cytometry, supports sophisticated biological queries involving cells, and helps generate new hypotheses about cell function based on similarities to other cell types.</p> <p>Conclusion</p> <p>Use of computable definitions enhances the development of the CL and supports the interoperability of OBO ontologies.</p

Factors affecting seizure outcome after epilepsy surgery: an observational series

IMPORTANCE: Surgical treatment can bring seizure remission in people with focal epilepsy, but requires careful selection of candidates. OBJECTIVES: To determine which preoperative factors are associated with post-operative seizure outcome. DESIGN: We audited seizure outcome of 693 adults who had resective epilepsy surgery between 1990 and 2010 and used survival analysis to detect preoperatively identifiable risk factors of poor seizure outcome. RESULTS: Seven factors were significantly associated with increased probability of recurrence of seizures with impaired awareness post-surgery: MRI findings (eg hazard ratio adjusted for other variables in the model 2.5; 95% CI 1.6 to 3.8 for normal MRI compared with hippocampal sclerosis (HS)), a history of secondarily generalised convulsive seizures (2.3; 95% CI 1.7 to 3.0 for these seizures in the previous year vs never), psychiatric history (1.3; 95% CI 1.1 to 1.7), learning disability (1.8; 95% CI 1.2 to 2.6), and extratemporal (vs temporal) surgery (1.4; 95% CI 1.02, 2.04). People with an older onset of epilepsy had a higher probability of seizure recurrence (1.01; 95% CI 1.00, 1.02) as did those who had used more anti-epileptic drugs (1.05; 95% CI 1.01, 1.09). Combinations of variables associated with seizure recurrence gave overall low probabilities of 5-year seizure freedom (eg a normal MRI and convulsive seizures in the previous year has a probability of seizure freedom at five years of approximately 0.19). CONCLUSIONS AND RELEVANCE: Readily identified clinical features and investigations are associated with reduced probability of good outcome and need consideration when planning presurgical evaluation