561 research outputs found

    The Farrell-Jones isomorphism conjecture for 3-manifold groups

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    We show that the Fibered Isomorphism Conjecture (FIC) of Farrell and Jones corresponding to the stable topological pseudoisotopy functor is true for the fundamental groups of a large class of 3-manifolds. We also prove that if the FIC is true for irreducible 3-manifold groups then it is true for all 3-manifold groups. In fact, this follows from a more general result we prove here, namely we show that if the FIC is true for each vertex group of a graph of groups with trivial edge groups then the FIC is true for the fundamental group of the graph of groups. This result is part of a program to prove FIC for the fundamental group of a graph of groups where all the vertex and edge groups satisfy FIC. A consequence of the first result gives a partial solution to a problem in the problem list of R. Kirby. We also deduce that the FIC is true for a class of virtually PD_3-groups. Another main aspect of this article is to prove the FIC for all Haken 3-manifold groups assuming that the FIC is true for B-groups. By definition a B-group contains a finite index subgroup isomorphic to the fundamental group of a compact irreducible 3-manifold with incompressible nonempty boundary so that each boundary component is of genus \geq 2. We also prove the FIC for a large class of B-groups and moreover, using a recent result of L.E. Jones we show that the surjective part of the FIC is true for any B-group.Comment: 35 pages, 1 figure (.eps file), AMS Latex file, final version. accepted for publication in K-theor

    Mechanism of activation of the BNLF2a immune evasion gene of Epstein-Barr virus by Zta

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    The human gamma herpes virus Epstein–Barr virus (EBV) exploits multiple routes to evade the cellular immune response. During the EBV lytic replication cycle, viral proteins are expressed that provide excellent targets for recognition by cytotoxic T cells. This is countered by the viral BNLF2a gene. In B cells during latency, where BNLF2a is not expressed, we show that its regulatory region is embedded in repressive chromatin. The expression of BNLF2a mirrors the expression of a viral lytic cycle transcriptional regulator, Zta (BZLF1, EB1, ZEBRA), in B cells and we propose that Zta plays a role in up-regulating BNLF2a. In cells undergoing EBV lytic replication, we identified two distinct regions of interaction of Zta with the chromatin-associated BNLF2a promoter. We identify five potential Zta-response elements (ZREs) in the promoter that are highly conserved between virus isolates. Zta binds to these elements in vitro and activates the expression of the BNLF2a promoter in both epithelial and B cells. We also found redundancy amongst the ZREs. The EBV genome undergoes a biphasic DNA methylation cycle during its infection cycle. One of the ZREs contains an integral CpG motif. We show that this can be DNA methylated during EBV latency and that both Zta binding and promoter activation are enhanced by its methylation. In summary, we find that the BNLF2a promoter is directly targeted by Zta and that DNA methylation within the proximal ZRE aids activation. The implications for regulation of this key viral gene during the reactivation of EBV from latency are discussed

    Aerobic exercise in adolescents with obesity: preliminary evaluation of a modular training program and the modified shuttle test

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    BACKGROUND: Increasing activity levels in adolescents with obesity requires the development of exercise programs that are both attractive to adolescents and easily reproducible. The aim of this study was to develop a modular aerobic training program for adolescents with severe obesity, with a focus on variety, individual targets and acquiring physical skills. We report here the effects on aerobic fitness from a pilot study. Furthermore, we examined the feasibility of the modified shuttle test (MST) as an outcome parameter for aerobic fitness in adolescents with severe obesity. METHODS: Fifteen adolescents from an inpatient body weight management program participated in the aerobic training study (age 14.7 ± 2.1 yrs, body mass index 37.4 ± 3.5). The subjects trained three days per week for 12 weeks, with each session lasting 30–60 minutes. The modular training program consisted of indoor, outdoor and swimming activities. Feasibility of the MST was studied by assessing construct validity, test-retest reliability and sensitivity to change. RESULTS: Comparing pretraining and end of training period showed large clinically relevant and significant improvements for all aerobic indices: e.g. VO(2 peak )17.5%, effect size (ES) 2.4; W(max )8%, ES 0.8. In addition, a significant improvement was found for the efficiency of the cardiovascular system as assessed by the oxygen pulse (15.8%, ES 1.6). Construct validity, test-retest reliability and sensitivity to change of the MST were very good. MST was significantly correlated with VO(2 peak )(r = 0.79) and W(max )(r = 0.84) but not with anthropometric measures. The MST walking distance improved significantly by 32.5%, ES 2.5. The attendance rate at the exercise sessions was excellent. CONCLUSION: This modular, varied aerobic training program has clinically relevant effects on aerobic performance in adolescents with severe obesity. The added value of our aerobic training program for body weight management programs for adolescents with severe obesity should be studied with a randomized trial. This study further demonstrated that the MST is a reliable, sensitive and easy to administer outcome measure for aerobic fitness in adolescent body weight management trials

    Distinct and Overlapping Brain Areas Engaged during Value-Based, Mathematical, and Emotional Decision Processing.

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    When comparing between the values of different choices, human beings can rely on either more cognitive processes, such as using mathematical computation, or more affective processes, such as using emotion. However, the neural correlates of how these two types of processes operate during value-based decision-making remain unclear. In this study, we investigated the extent to which neural regions engaged during value-based decision-making overlap with those engaged during mathematical and emotional processing in a within-subject manner. In a functional magnetic resonance imaging experiment, participants viewed stimuli that always consisted of numbers and emotional faces that depicted two choices. Across tasks, participants decided between the two choices based on the expected value of the numbers, a mathematical result of the numbers, or the emotional face stimuli. We found that all three tasks commonly involved various cortical areas including frontal, parietal, motor, somatosensory, and visual regions. Critically, the mathematical task shared common areas with the value but not emotion task in bilateral striatum. Although the emotion task overlapped with the value task in parietal, motor, and sensory areas, the mathematical task also evoked responses in other areas within these same cortical structures. Minimal areas were uniquely engaged for the value task apart from the other two tasks. The emotion task elicited a more expansive area of neural activity whereas value and mathematical task responses were in more focal regions. Whole-brain spatial correlation analysis showed that valuative processing engaged functional brain responses more similarly to mathematical processing than emotional processing. While decisions on expected value entail both mathematical and emotional processing regions, mathematical processes have a more prominent contribution particularly in subcortical processes

    Manifesto of computational social science

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    The increasing integration of technology into our lives has created unprecedented volumes of data on society's everyday behaviour. Such data opens up exciting new opportunities to work towards a quantitative understanding of our complex social systems, within the realms of a new discipline known as Computational Social Science. Against a background of financial crises, riots and international epidemics, the urgent need for a greater comprehension of the complexity of our interconnected global society and an ability to apply such insights in policy decisions is clear. This manifesto outlines the objectives of this new scientific direction, considering the challenges involved in it, and the extensive impact on science, technology and society that the success of this endeavour is likely to bring about.The publication of this work was partially supported by the European Union’s Seventh Framework Programme (FP7/2007–2013) under grant agreement No. 284709, a Coordination and Support Action in the Information and Communication Technologies activity area (‘FuturICT’ FET Flagship Pilot Project). We are grateful to the anonymous reviewers for the insightful comments.Publicad

    Risk factors for Epstein Barr virus-associated cancers: a systematic review, critical appraisal, and mapping of the epidemiological evidence

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    Background Epstein Barr Virus (EBV) infects 90%-95% of all adults globally and causes~1% of all cancers. Differing proportions of Burkitt’s lymphoma (BL), gastric carcinoma (GC), Hodgkin’s lymphoma (HL) and nasopharyngeal carcinoma (NPC) are associated with EBV. We sought to systematically review the global epidemiological evidence for risk factors that (in addition to EBV) contribute to the development of the EBV-associated forms of these cancers, assess the quality of the evidence, and compare and contrast the cancers. Methods MEDLINE, Embase and Web of Science were searched for studies of risk factors for EBV-associated BL, GC, HL and NPC without language or temporal restrictions. Studies were excluded if there was no cancer-free comparator group or where analyses of risk factors were inadequately documented. After screening and reference list searching, data were extracted into standardised spreadsheets and quality assessed. Due to heterogeneity, a narrative synthesis was undertaken. Results 9916 hits were retrieved. 271 papers were retained: two BL, 24 HL, one GC and 244 NPC. The majority of studies were from China, North America and Western Europe. Risk factors were categorised as dietary, environmental/non-dietary, human genetic, and infection and clinical. Anti-EBV antibody load was associated with EBV-associated GC and BL. Although the evidence could be inconsistent, HLA-A alleles, smoking, infectious mononucleosis and potentially other infections were risk factors for EBV-associated HL. Rancid dairy products; anti-EBV antibody and EBV DNA load; history of chronic ear, nose and/or throat conditions; herbal medicine use; family history; and human genetics were risk factors for NPC. Fresh fruit and vegetable and tea consumption may be protective against NPC. Conclusions Many epidemiological studies of risk factors in addition to EBV for the EBV-associated forms of BL, GC, HL and NPC have been undertaken, but there is a dearth of evidence for GC and BL. Available evidence is of variable quality. The aetiology of EBV-associated cancers likely results from a complex intersection of genetic, clinical, environmental and dietary factors, which is difficult to assess with observational studies. Large, carefully designed, studies need to be strategically undertaken to harmonise and clarify the evidence. Registration PROSPERO CRD4201705980

    A tree-parenchyma coupled model for lung ventilation simulation

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    International audienceIn this article we develop a lung-ventilation model. The parenchyma is described as an elastic homogenized media. It is irrigated by a space-filling dyadic resistive pipe network, which represents the tracheo-bronchial tree. In this model the tree and the parenchyma are strongly coupled. The tree induces an extra viscous term in the system constitutive relation, which leads, in the finite element framework, to a full matrix. We consider an efficient algorithm that takes advantage of the tree dyadic structure to enable a fast matrix-vector product computation. This framework can be used to model both free and mechanically induced respiration, in health and disease. Patient-specific lung geometries acquired from CT scans are considered. Realistic Dirichlet boundary conditions can be deduced from surface registration on CT images. The model is compared to a more classical exit-compartment approach. Results illustrate the coupling between the tree and the parenchyma, at global and regional levels, and how conditions for the purely 0D model can be inferred. Different types of boundary conditions are tested, including a nonlinear Robin model of the surrounding lung structures

    Party rules, party resources, and the politics of parliamentary democracies: how parties organize in the 21st Century

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    This article introduces the first findings of the Political Party Database (PPDB) project, a major survey of party organizations in parliamentary and semi-presidential democracies. The project’s first round of data covers 122 parties in 19 countries. In this paper we describe the scope of the database, then investigate what it tells us about contemporary party organization in these countries, focussing on parties’ resources, structures and internal decision-making. We examine organizational patterns by country and party family, and where possible we make temporal comparisons with older datasets. Our analyses suggest a remarkable coexistence of uniformity and diversity. In terms of the major organizational resources on which parties can draw, such as members, staff and finance, the new evidence largely confirms the continuation of trends identified in previous research: i.e., declining membership, but enhanced financial resources and more paid staff. We also find remarkable uniformity regarding the core architecture of party organizations. At the same time, however, we find substantial variation between countries and party families in terms of their internal processes, with particular regard to how internally democratic they are, and in the forms that this democratization takes
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