The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

Place of death in patients with lung cancer: a retrospective cohort study from 2004-2013

Introduction: Many patients with cancer die in an acute hospital bed, which has been frequently identified as the least preferred location, with psychological and financial implications. This study looks at place and cause of death in patients with lung cancer and identifies which factors are associated with dying in an acute hospital bed versus at home. Methods and Findings: We used the National Lung Cancer Audit linked to Hospital Episode Statistics and Office for National Statistics data to determine cause and place of death in those with lung cancer; both overall and by cancer Network. We used multivariate logistic regression to compare features of those who died in an acute hospital versus those who died at home. Results: Of 143627 patients identified 40% (57678) died in an acute hospital, 29% (41957) died at home and 17% (24108) died in a hospice. Individual factors associated with death in an acute hospital bed compared to home were male sex, increasing age, poor performance status, social deprivation and diagnosis via an emergency route. There was marked variation between cancer Networks in place of death. The proportion of patients dying in an acute hospital ranged from 28% to 48%, with variation most notable in provision of hospice care (9% versus 33%). Cause of death in the majority was lung cancer (86%), with other malignancies, chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD) comprising 9% collectively. Conclusions: A substantial proportion of patients with lung cancer die in acute hospital beds and this is more likely with increasing age, male sex, social deprivation and in those with poor performance status. There is marked variation between Networks, suggesting a need to improve end-of-life planning in those at greatest risk, and to review the allocation of resources to provide more hospice beds, enhanced community support and ensure equal access

Algebraic conformal quantum field theory in perspective

Conformal quantum field theory is reviewed in the perspective of Axiomatic, notably Algebraic QFT. This theory is particularly developped in two spacetime dimensions, where many rigorous constructions are possible, as well as some complete classifications. The structural insights, analytical methods and constructive tools are expected to be useful also for four-dimensional QFT.Comment: Review paper, 40 pages. v2: minor changes and references added, so as to match published versio

B-L Cosmic Strings in Heterotic Standard Models

E_{8} X E_{8} heterotic string and M-theory, when compactified on smooth Calabi-Yau manifolds with SU(4) vector bundles, can give rise to softly broken N=1 supersymmetric theories with the exact matter spectrum of the MSSM, including three right-handed neutrinos and one Higgs-Higgs conjugate pair of supermultiplets. These vacua have the SU(3)_{C} X SU(2)_{L} X U(1)_{Y} gauge group of the standard model augmented by an additional gauged U(1)_{B-L}. Their minimal content requires that the B-L symmetry be spontaneously broken by a vacuum expectation value of at least one right-handed sneutrino. The soft supersymmetry breaking operators can induce radiative breaking of the B-L gauge symmetry with an acceptable B-L/electroweak hierarchy. In this paper, it is shown that U(1)_{B-L} cosmic strings occur in this context, potentially with both bosonic and fermionic superconductivity. We present a numerical analysis that demonstrates that boson condensates can, in principle, form for theories of this type. However, the weak Yukawa and gauge couplings of the right-handed sneutrino suggests that bosonic superconductivity will not occur in the simplest vacua in this context. The electroweak phase transition also disallows fermion superconductivity, although substantial bound state fermion currents can exist.Comment: 41 pages, 5 figure

Whole-Blood Flow-Cytometric Analysis of Antigen-Specific CD4 T-Cell Cytokine Profiles Distinguishes Active Tuberculosis from Non-Active States

T-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p = 0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB

Quantum Symmetries and Marginal Deformations

We study the symmetries of the N=1 exactly marginal deformations of N=4 Super Yang-Mills theory. For generic values of the parameters, these deformations are known to break the SU(3) part of the R-symmetry group down to a discrete subgroup. However, a closer look from the perspective of quantum groups reveals that the Lagrangian is in fact invariant under a certain Hopf algebra which is a non-standard quantum deformation of the algebra of functions on SU(3). Our discussion is motivated by the desire to better understand why these theories have significant differences from N=4 SYM regarding the planar integrability (or rather lack thereof) of the spin chains encoding their spectrum. However, our construction works at the level of the classical Lagrangian, without relying on the language of spin chains. Our approach might eventually provide a better understanding of the finiteness properties of these theories as well as help in the construction of their AdS/CFT duals.Comment: 1+40 pages. v2: minor clarifications and references added. v3: Added an appendix, fixed minor typo

Blocking TGF-β signaling pathway preserves mitochondrial proteostasis and reduces early activation of PDGFRβ+ pericytes in aristolochic acid induced acute kidney injury in wistar male rats

The platelet-derived growth factor receptor β (PDGFRβ)+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target.In this regard, we first confirmed the presence of PDGFRβ+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN) and thereafter we focused on the early fibrosis events of transforming growth factor β (TGFβ) inhibition in a rat model of AAN.Neutralizing anti-TGFβ antibody (1D11) and its control isotype (13C4) were administered (5 mg/kg, i.p.) at Days -1, 0, 2 and 4; AA (15 mg/kg, sc) was injected daily.At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema) in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR) pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro.The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRβ+ pericytes-derived myofibroblasts accumulation

Probiotics, prebiotics and immunomodulation of gut mucosal defences: homeostasis and immunopathology.

Probiotics are beneficial microbes that confer a realistic health benefit on the host, which in combination with prebiotics, (indigestible dietary fibre/carbohydrate), also confer a health benefit on the host via products resulting from anaerobic fermentation. There is a growing body of evidence documenting the immune-modulatory ability of probiotic bacteria, it is therefore reasonable to suggest that this is potentiated via a combination of prebiotics and probiotics as a symbiotic mix. The need for probiotic formulations has been appreciated for the health benefits in "topping up your good bacteria" or indeed in an attempt to normalise the dysbiotic microbiota associated with immunopathology. This review will focus on the immunomodulatory role of probiotics and prebiotics on the cells, molecules and immune responses in the gut mucosae, from epithelial barrier to priming of adaptive responses by antigen presenting cells: immune fate decision-tolerance or activation? Modulation of normal homeostatic mechanisms, coupled with findings from probiotic and prebiotic delivery in pathological studies, will highlight the role for these xenobiotics in dysbiosis associated with immunopathology in the context of inflammatory bowel disease, colorectal cancer and hypersensitivity

Precision measurement of the top quark mass from dilepton events at CDF II

We report a measurement of the top quark mass, M_t, in the dilepton decay channel of $t\bar{t}\to b\ell'^{+}\nu_{\ell'}\bar{b}\ell^{-}\bar{\nu}_{\ell}$ using an integrated luminosity of 1.0 fb^{-1} of p\bar{p} collisions collected with the CDF II detector. We apply a method that convolutes a leading-order matrix element with detector resolution functions to form event-by-event likelihoods; we have enhanced the leading-order description to describe the effects of initial-state radiation. The joint likelihood is the product of the likelihoods from 78 candidate events in this sample, which yields a measurement of M_{t} = 164.5 \pm 3.9(\textrm{stat.}) \pm 3.9(\textrm{syst.}) \mathrm{GeV}/c^2, the most precise measurement of M_t in the dilepton channel.Comment: 7 pages, 2 figures, version includes changes made prior to publication by journa