1,689 research outputs found

    Resonant Leptogenesis

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    We study the scenario of thermal leptogenesis in which the leptonic asymmetries are resonantly enhanced through the mixing of nearly degenerate heavy Majorana neutrinos that have mass differences comparable to their decay widths. Field-theoretic issues arising from the proper subtraction of real intermediate states from the lepton-number-violating scattering processes are addressed in connection with an earlier developed resummation approach to unstable particle mixing in decay amplitudes. The pertinent Boltzmann equations are numerically solved after the enhanced heavy-neutrino self-energy effects on scatterings and the dominant gauge-mediated collision terms are included. We show that resonant leptogenesis can be realized with heavy Majorana neutrinos even as light as about 1 TeV, in complete accordance with the current solar and atmospheric neutrino data.Comment: 53 pages, LaTeX, 5 eps figures, improved Eq. (A.7) and clarifying comments adde

    On the Consistency of Perturbativity and Gauge Coupling Unification

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    We investigate constraints that the requirements of perturbativity and gauge coupling unification impose on extensions of the Standard Model and of the MSSM. In particular, we discuss the renormalization group running in several SUSY left-right symmetric and Pati-Salam models and show how the various scales appearing in these models have to be chosen in order to achieve unification. We find that unification in the considered models occurs typically at scales below M^{min}_{B violation} = 10^16 GeV, implying potential conflicts with the non-observation of proton decay. We emphasize that extending the particle content of a model in order to push the GUT scale higher or to achieve unification in the first place will very often lead to non-perturbative evolution. We generalize this observation to arbitrary extensions of the Standard Model and of the MSSM and show that the requirement of perturbativity up to M^{min}_{B violation}, if considered a valid guideline for model building, severely limits the particle content of any such model, especially in the supersymmetric case. However, we also discuss several mechanisms to circumvent perturbativity and proton decay issues, for example in certain classes of extra dimensional models.Comment: LaTeX, 20 pages, 8 figures, 1 tabl

    Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

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    Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two

    Chasing Brane Inflation in String-Theory

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    We investigate the embedding of brane anti-brane inflation into a concrete type IIB string theory compactification with all moduli fixed. Specifically, we are considering a D3-brane, whose position represents the inflaton ϕ\phi, in a warped conifold throat in the presence of supersymmetrically embedded D7-branes and an anti D3-brane localized at the tip of the warped conifold cone. After presenting the moduli stabilization analysis for a general D7-brane embedding, we concentrate on two explicit models, the Ouyang and the Kuperstein embeddings. We analyze whether the forces, induced by moduli stabilization and acting on the D3-brane, might cancel by fine-tuning such as to leave us with the original Coulomb attraction of the anti D3-brane as the driving force for inflation. For a large class of D7-brane embeddings we obtain a negative result. Cancelations are possible only for very small intervals of ϕ\phi around an inflection point but not globally. For the most part of its motion the inflaton then feels a steep, non slow-roll potential. We study the inflationary dynamics induced by this potential.Comment: 34 pages, 4 figures. Final version published in JCA

    Design considerations in a clinical trial of a cognitive behavioural intervention for the management of low back pain in primary care : Back Skills Training Trial

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    Background Low back pain (LBP) is a major public health problem. Risk factors for the development and persistence of LBP include physical and psychological factors. However, most research activity has focused on physical solutions including manipulation, exercise training and activity promotion. Methods/Design This randomised controlled trial will establish the clinical and cost-effectiveness of a group programme, based on cognitive behavioural principles, for the management of sub-acute and chronic LBP in primary care. Our primary outcomes are disease specific measures of pain and function. Secondary outcomes include back beliefs, generic health related quality of life and resource use. All outcomes are measured over 12 months. Participants randomised to the intervention arm are invited to attend up to six weekly sessions each of 90 minutes; each group has 6–8 participants. A parallel qualitative study will aid the evaluation of the intervention. Discussion In this paper we describe the rationale and design of a randomised evaluation of a group based cognitive behavioural intervention for low back pain

    The Minimal Phantom Sector of the Standard Model: Higgs Phenomenology and Dirac Leptogenesis

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    We propose the minimal, lepton-number conserving, SU(3)xSU(2)xU(1) gauge-singlet, or phantom, extension of the Standard Model. The extension is natural in the sense that all couplings are of O(1) or forbidden due to a phantom sector global U(1)_D symmetry, and basically imitates the standard Majorana see-saw mechanism. Spontaneous breaking of the U(1)_D symmetry triggers consistent electroweak gauge symmetry breaking only if it occurs at a scale compatible with small Dirac neutrino masses and baryogenesis through Dirac leptogenesis. Dirac leptogenesis proceeds through the usual out-of-equilibrium decay scenario, leading to left and right-handed neutrino asymmetries that do not fully equilibrate after they are produced. The model contains two physical Higgs bosons and a massless Goldstone boson. The existence of the Goldstone boson suppresses the Higgs to bb branching ratio and instead the Higgs bosons will mainly decay to invisible Goldstone and/or to visible vector boson pairs. In a representative scenario, we estimate that with 30 fb^-1 integrated luminosity, the LHC could discover this invisibly decaying Higgs, with mass ~120 GeV. At the same time a significantly heavier, partner Higgs boson with mass ~210 GeV could be found through its vector boson decays. Electroweak constraints as well as astrophysical and cosmological implications are analysed and discussed.Comment: 21 pages, 4 figures. Corrected typos and added references. To appear in JHE

    Recombination Rate Heterogeneity within Arabidopsis Disease Resistance Genes.

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    Meiotic crossover frequency varies extensively along chromosomes and is typically concentrated in hotspots. As recombination increases genetic diversity, hotspots are predicted to occur at immunity genes, where variation may be beneficial. A major component of plant immunity is recognition of pathogen Avirulence (Avr) effectors by resistance (R) genes that encode NBS-LRR domain proteins. Therefore, we sought to test whether NBS-LRR genes would overlap with meiotic crossover hotspots using experimental genetics in Arabidopsis thaliana. NBS-LRR genes tend to physically cluster in plant genomes; for example, in Arabidopsis most are located in large clusters on the south arms of chromosomes 1 and 5. We experimentally mapped 1,439 crossovers within these clusters and observed NBS-LRR gene associated hotspots, which were also detected as historical hotspots via analysis of linkage disequilibrium. However, we also observed NBS-LRR gene coldspots, which in some cases correlate with structural heterozygosity. To study recombination at the fine-scale we used high-throughput sequencing to analyze ~1,000 crossovers within the RESISTANCE TO ALBUGO CANDIDA1 (RAC1) R gene hotspot. This revealed elevated intragenic crossovers, overlapping nucleosome-occupied exons that encode the TIR, NBS and LRR domains. The highest RAC1 recombination frequency was promoter-proximal and overlapped CTT-repeat DNA sequence motifs, which have previously been associated with plant crossover hotspots. Additionally, we show a significant influence of natural genetic variation on NBS-LRR cluster recombination rates, using crosses between Arabidopsis ecotypes. In conclusion, we show that a subset of NBS-LRR genes are strong hotspots, whereas others are coldspots. This reveals a complex recombination landscape in Arabidopsis NBS-LRR genes, which we propose results from varying coevolutionary pressures exerted by host-pathogen relationships, and is influenced by structural heterozygosity.Research in the Henderson laboratory was supported by a Royal Society University Research Fellowship, Gatsby Charitable Foundation grant 2962, BBSRC grant BB/N007557/1 and National Natural Science Foundation of China grant 61403318. KC was funded by an EMBO long term postdoctoral fellowship ALTF 807-2009. PAZ was supported by a Polish Mobility Plus Fellowship 605/MOB/2011/0. GPC is funded by a National Science Foundation Grant (MCB-1121563). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It first appeared from PLOS at http://dx.doi.org/10.1371/journal.pgen.1006179

    Seminar on Evidence and Trial Practice

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    Outlines of speaker presentations offered during a series of one day seminars on evidence and trial practice offered by UK/CLE in late 1987-early 1988

    A subset of myofibroblastic cancer-associated fibroblasts regulate collagen fiber elongation, which is prognostic in multiple cancers

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    Collagen structure has been shown to influence tumor cell invasion, metastasis and clinical outcome in breast cancer. However, it remains unclear how it affects other solid cancers. Here we utilized multi-photon laser scanning microscopy and Second Harmonic Generation to identify alterations to collagen fiber structure within the tumor stroma of head & neck, esophageal and colorectal cancers. Image segmentation algorithms were then applied to quantitatively characterize these morphological changes, showing that elongated collagen fibers significantly correlated with poor clinical outcome (Log Rank p < 0.05). We used TGF-? treatment to model fibroblast conversion to smooth muscle actin SMA-positive cancer associated fibroblasts (CAFs) and found that these cells induce the formation of elongated collagen fibers in vivo. However, proteomic/transcriptomic analysis of SMA-positive CAFs cultured ex-vivo showed significant heterogeneity in the expression of genes with collagen fibril organizing gene ontology. Notably, stratifying patients according to stromal SMA-positivity and collagen fiber elongation was found to provide a highly significant correlation with poor survival in all 3 cancer types (Log Rank p ? 0.003). In summary, we show that increased collagen fiber length correlates with poor patient survival in multiple tumor types and that only a sub-set of SMA-positive CAFs can mediate the formation of this collagen structure
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