382 research outputs found

    Spectral Parameters for Scattering Amplitudes in N=4 Super Yang-Mills Theory

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    49 pages, 20 figures; v2: typos fixedPlanar N=4 Super Yang-Mills theory appears to be a quantum integrable four-dimensional conformal theory. This has been used to find equations believed to describe its exact spectrum of anomalous dimensions. Integrability seemingly also extends to the planar space-time scattering amplitudes of the N=4 model, which show strong signs of Yangian invariance. However, in contradistinction to the spectral problem, this has not yet led to equations determining the exact amplitudes. We propose that the missing element is the spectral parameter, ubiquitous in integrable models. We show that it may indeed be included into recent on-shell approaches to scattering amplitude integrands, providing a natural deformation of the latter. Under some constraints, Yangian symmetry is preserved. Finally we speculate that the spectral parameter might also be the regulator of choice for controlling the infrared divergences appearing when integrating the integrands in exactly four dimensions.Peer reviewe

    Predictability of evolutionary trajectories in fitness landscapes

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    Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

    Revisiting the S-matrix approach to the open superstring low energy effective lagrangian

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    The conventional S-matrix approach to the (tree level) open string low energy effective lagrangian assumes that, in order to obtain all its bosonic αN{\alpha'}^N order terms, it is necessary to know the open string (tree level) (N+2)(N+2)-point amplitude of massless bosons, at least expanded at that order in α\alpha'. In this work we clarify that the previous claim is indeed valid for the bosonic open string, but for the supersymmetric one the situation is much more better than that: there are constraints in the kinematical bosonic terms of the amplitude (probably due to Spacetime Supersymmetry) such that a much lower open superstring nn-point amplitude is needed to find all the αN{\alpha'}^N order terms. In this `revisited' S-matrix approach we have checked that, at least up to α4{\alpha'}^4 order, using these kinematical constraints and only the known open superstring 4-point amplitude, it is possible to determine all the bosonic terms of the low energy effective lagrangian. The sort of results that we obtain seem to agree completely with the ones achieved by the method of BPS configurations, proposed about ten years ago. By means of the KLT relations, our results can be mapped to the NS-NS sector of the low energy effective lagrangian of the type II string theories implying that there one can also find kinematical constraints in the NN-point amplitudes and that important informations can be inferred, at least up to α4{\alpha'}^4 order, by only using the (tree level) 4-point amplitude.Comment: 34 pages, 3 figure, Submitted on Aug 4, 2012, Published on Oct 15, 201

    Effect of Correlated tRNA Abundances on Translation Errors and Evolution of Codon Usage Bias

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    Despite the fact that tRNA abundances are thought to play a major role in determining translation error rates, their distribution across the genetic code and the resulting implications have received little attention. In general, studies of codon usage bias (CUB) assume that codons with higher tRNA abundance have lower missense error rates. Using a model of protein translation based on tRNA competition and intra-ribosomal kinetics, we show that this assumption can be violated when tRNA abundances are positively correlated across the genetic code. Examining the distribution of tRNA abundances across 73 bacterial genomes from 20 different genera, we find a consistent positive correlation between tRNA abundances across the genetic code. This work challenges one of the fundamental assumptions made in over 30 years of research on CUB that codons with higher tRNA abundances have lower missense error rates and that missense errors are the primary selective force responsible for CUB

    Vitamin D3 Supplementation Reduces Subsequent Brain Injury and Inflammation Associated with Ischemic Stroke

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    Acute inflammation can exacerbate brain injury after ischemic stroke. Beyond its well-characterized role in calcium metabolism, it is becoming increasingly appreciated that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-VitD3), has potent immunomodulatory properties. Here, we aimed to determine whether 1,25-VitD3 supplementation could reduce subsequent brain injury and associated inflammation after ischemic stroke. Male C57Bl6 mice were randomly assigned to be administered either 1,25-VitD3 (100 ng/kg/day) or vehicle i.p. for 5 day prior to stroke. Stroke was induced via middle cerebral artery occlusion for 1 h followed by 23 h reperfusion. At 24 h post-stroke, we assessed infarct volume, functional deficit, expression of inflammatory mediators and numbers of infiltrating immune cells. Supplementation with 1,25-VitD3 reduced infarct volume by 50% compared to vehicle. Expression of pro-inflammatory mediators IL-6, IL-1β, IL-23a, TGF-β and NADPH oxidase-2 was reduced in brains of mice that received 1,25-VitD3 versus vehicle. Brain expression of the T regulatory cell marker, Foxp3, was higher in mice supplemented with 1,25-VitD3 versus vehicle, while expression of the transcription factor, ROR-γ, was decreased, suggestive of a reduced Th17/γδ T cell response. Immunohistochemistry indicated that similar numbers of neutrophils and T cells were present in the ischemic hemispheres of 1,25-VitD3- and vehicle-supplemented mice. At this early time point, there were also no differences in the impairment of motor function. These data indicate that prior administration of exogenous vitamin D, even to vitamin D-replete mice, can attenuate infarct development and exert acute anti-inflammatory actions in the ischemic and reperfused brain

    All-mass n-gon integrals in n dimensions

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    We explore the correspondence between one-loop Feynman integrals and (hyperbolic) simplicial geometry to describe the "all-mass" case: integrals with generic external and internal masses. Specifically, we focus on nn-particle integrals in exactly nn space-time dimensions, as these integrals have particularly nice geometric properties and respect a dual conformal symmetry. In four dimensions, we leverage this geometric connection to give a concise dilogarithmic expression for the all-mass box in terms of the Murakami-Yano formula. In five dimensions, we use a generalized Gauss-Bonnet theorem to derive a similar dilogarithmic expression for the all-mass pentagon. We also use the Schl\"afli formula to write down the symbol of these integrals for all nn. Finally, we discuss how the geometry behind these formulas depends on space-time signature, and we gather together many results related to these integrals from the mathematics and physics literature.Comment: 49 pages, 8 figure

    Evolutionary History and Population Dynamics of Hepatitis E Virus

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    BACKGROUND: Hepatitis E virus (HEV) is an enterically transmitted hepatropic virus. It segregates as four genotypes. All genotypes infect humans while only genotypes 3 and 4 also infect several animal species. It has been suggested that hepatitis E is zoonotic, but no study has analyzed the evolutionary history of HEV. We present here an analysis of the evolutionary history of HEV. METHODS AND FINDINGS: The times to the most recent common ancestors for all four genotypes of HEV were calculated using BEAST to conduct a Bayesian analysis of HEV. The population dynamics for genotypes 1, 3 and 4 were analyzed using skyline plots. Bayesian analysis showed that the most recent common ancestor for modern HEV existed between 536 and 1344 years ago. The progenitor of HEV appears to have given rise to anthropotropic and enzootic forms of HEV, which evolved into genotypes 1 and 2 and genotypes 3 and 4, respectively. Population dynamics suggest that genotypes 1, 3 and 4 experienced a population expansion during the 20(th) century. Genotype 1 has increased in infected population size ∼30-35 years ago. Genotype 3 and 4 have experienced an increase in population size starting late in the 19(th) century until ca.1940-45, with genotype 3 having undergone additional rapid expansion until ca.1960. The effective population size for both genotype 3 and 4 rapidly declined to pre-expansion levels starting in ca.1990. Genotype 4 was further examined as Chinese and Japanese sequences, which exhibited different population dynamics, suggesting that this genotype experienced different evolutionary history in these two countries. CONCLUSIONS: HEV appears to have evolved through a series of steps, in which the ancestors of HEV may have adapted to a succession of animal hosts leading to humans. Analysis of the population dynamics of HEV suggests a substantial temporal variation in the rate of transmission among HEV genotypes in different geographic regions late in the 20(th) Century

    Utilization of the out of hours service in Poland: an observational study from Krakow

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    <p>Abstract</p> <p>Background</p> <p>In 2000 a new GP contract was introduced in Poland. It allowed GPs to subcontract out of hours care to specialized deputizing services. One such service in Kraków provides care to 61 GP practices with a population of 420 000 inhabitants. The aim of this study is to analyze seasonal and geographical variation in out of hours care use and to find the most important factors influencing it.</p> <p>Methods</p> <p>Routinely collected data for 24 months (2003–2004) containing type, date and time of the contacts were used.</p> <p>Results</p> <p>During the study period 238 072 contacts were recorded: 149 911 ambulatory doctor visits, 23 434 home visits and 64 727 nurse procedures. The mean rate of out of hours contacts was: for ambulatory visits 178 per 1000 inhabitants/year (varied between practices from 9 to 696), for home visits 28 (from 1 to 36) and for nurse procedures 77 (from 3 to 327). The highest rate of ambulatory visits was 739 in the age group 0–4, the lowest – 104 in the age group 45–49. The highest rate of home visits was 221 in the age group over 85. The rate of ambulatory GP visits and nurse procedures was negatively correlated with the distance between the location of GP practice and the nearest out of hours clinic. The rate of home visits was positively correlated with the age of the patient.</p> <p>Conclusion</p> <p>Significant differences between practices suggest that non medical factors may play an important role in the patient's decision to see a GP when the surgery is closed. Their influence should be limited to make the system more efficient.</p
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