598 research outputs found

    Is every female equal? Caste biasing in tropical paper wasps

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    Item does not contain fulltextDiseases caused by nontuberculous mycobacteria are emerging in many settings. With an increased number of patients needing treatment, the role of drug susceptibility testing is again in the spotlight. This articles covers the history and methodology of drug susceptibility tests for nontuberculous mycobacteria, but focuses on the correlations between in vitro drug susceptibility, pharmacokinetics and in vivo outcomes of treatment. Among slow-growing nontuberculous mycobacteria, clear correlations have been established for macrolides and amikacin (Mycobacterium avium complex) and for rifampicin (Mycobacterium kansasii). Among rapid-growing mycobacteria, correlations have been established in extrapulmonary disease for aminoglycosides, cefoxitin and co-trimoxazole. In pulmonary disease, correlations are less clear and outcomes of treatment are generally poor, especially for Mycobacterium abscessus. The clinical significance of inducible resistance to macrolides among rapid growers is an important topic. The true role of drug susceptibility testing for nontuberculous mycobacteria still needs to be addressed, preferably within clinical trials

    Ab initio study of step formation and self-diffusion on Ag(100)

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    Using the plane wave pseudopotential method we performed density functional theory calculations on the stability of steps and self-diffusion processes on Ag(100). Our calculated step formation energies show that the {111}-faceted step is more stable than the {110}-faceted step. In accordance with experimental observations we find that the equilibrium island shape should be octagonal very close to a square with predominately {111}-faceted steps. For the (100) surface of fcc metals atomic migration proceeds by a hopping or an exchange process. For Ag(100) we find that adatoms diffuse across flat surfaces preferentially by hopping. Adatoms approaching the close-packed {111}-faceted step edges descend from the upper terrace to the lower level by an atomic exchange with an energy barrier almost identical to the diffusion barrier on flat surface regions. Thus, within our numerical accuracy (approx +- 0.05 eV) there is no additional step-edge barrier to descent. This provides a natural explanation for the experimental observations of the smooth two-dimensional growth in homoepitaxy of Ag(100). Inspection of experimental results of other fcc crystal surfaces indicates that our result holds quite generally.Comment: 10 pages, 9 figures. Submitted to Phys. Rev B (October 31, 1996

    Debris disk size distributions: steady state collisional evolution with P-R drag and other loss processes

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    We present a new scheme for determining the shape of the size distribution, and its evolution, for collisional cascades of planetesimals undergoing destructive collisions and loss processes like Poynting-Robertson drag. The scheme treats the steady state portion of the cascade by equating mass loss and gain in each size bin; the smallest particles are expected to reach steady state on their collision timescale, while larger particles retain their primordial distribution. For collision-dominated disks, steady state means that mass loss rates in logarithmic size bins are independent of size. This prescription reproduces the expected two phase size distribution, with ripples above the blow-out size, and above the transition to gravity-dominated planetesimal strength. The scheme also reproduces the expected evolution of disk mass, and of dust mass, but is computationally much faster than evolving distributions forward in time. For low-mass disks, P-R drag causes a turnover at small sizes to a size distribution that is set by the redistribution function (the mass distribution of fragments produced in collisions). Thus information about the redistribution function may be recovered by measuring the size distribution of particles undergoing loss by P-R drag, such as that traced by particles accreted onto Earth. Although cross-sectional area drops with 1/age^2 in the PR-dominated regime, dust mass falls as 1/age^2.8, underlining the importance of understanding which particle sizes contribute to an observation when considering how disk detectability evolves. Other loss processes are readily incorporated; we also discuss generalised power law loss rates, dynamical depletion, realistic radiation forces and stellar wind drag.Comment: Accepted for publication by Celestial Mechanics and Dynamical Astronomy (special issue on EXOPLANETS

    Factors affecting the outcome of surgically treated non-iatrogenic traumatic cervical esophageal perforation: 28 years experience at a single center

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    <p>Abstract</p> <p>Background</p> <p>We reviewed our experience with non-iatrogenic traumatic cervical esophageal perforations, paying particular attention to factors affecting the outcome of such cases.</p> <p>Methods</p> <p>In total, 30 patients treated surgically between 1980 and 2008 for non-iatrogenic traumatic cervical esophageal perforation in our clinic were reviewed.</p> <p>Results</p> <p>There were 25 male and 5 female patients with a median age of 27.5 years. The type of injury was external trauma in 21 (70%) patients and endoluminal injury in the remaining 9 (30%) patients. The mechanism of injury was gunshot in 16 patients, stabbing in 4, falling in 1 (extraluminal injury), and foreign body in 9 (endoluminal injuries). The overall mortality rate was 16.6% (5/30). The mortality rate for extraluminal injuries was 19%, and for endoluminal injuries was 11.1%. Mortality in patients treated within 24 h of sustaining injury was substantially less than in those for whom diagnosis and treatment were delayed (12.5 and 21.4%, respectively). The mortality rate was 33.3% (3/9) for patients with tracheal injuries and 9.5% (2/21) for those without tracheal injuries.</p> <p>Conclusions</p> <p>A treatment delay greater than 24 h, the presence of tracheal injury, or extraluminal perforation significantly affected the outcome of surgically treated non iatrogenic traumatic cervical esophageal perforation.</p

    Confab - Systematic generation of diverse low-energy conformers

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    <p>Abstract</p> <p>Background</p> <p>Many computational chemistry analyses require the generation of conformers, either on-the-fly, or in advance. We present Confab, an open source command-line application for the systematic generation of low-energy conformers according to a diversity criterion.</p> <p>Results</p> <p>Confab generates conformations using the 'torsion driving approach' which involves iterating systematically through a set of allowed torsion angles for each rotatable bond. Energy is assessed using the MMFF94 forcefield. Diversity is measured using the heavy-atom root-mean-square deviation (RMSD) relative to conformers already stored. We investigated the recovery of crystal structures for a dataset of 1000 ligands from the Protein Data Bank with fewer than 1 million conformations. Confab can recover 97% of the molecules to within 1.5 Å at a diversity level of 1.5 Å and an energy cutoff of 50 kcal/mol.</p> <p>Conclusions</p> <p>Confab is available from <url>http://confab.googlecode.com</url>.</p

    A trematode parasite derived growth factor binds and exerts influences on host immune functions via host cytokine receptor complexes

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    The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allow- ing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF) superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL)-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory recep- tor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is depen- dent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs) in their evasion of antibody- dependent cell cytotoxicity (ADCC) by reducing the NO response of macrophages—again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for damp- ened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow for a reduced effector response targetingjuvenile parasites which we demonstrate extends to an abrogation of the ADCC response. Thus suggesting that FhTLM is a stage specific evasion molecule that utilises host cytokine receptors. These findings are the first to clearly demonstrate the interaction of a helminth cytokine with a host receptor complex resulting in immune modifications that facilitate the non-protective chronic immune response which is characteristic of F. hepatica infection

    IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection

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    IL-21 is produced predominantly by activated CD4(+) T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (gamma(c)) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8(+) T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4(+) and CD8(+) T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R(-/-) mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R(-/-) T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis.This work was supported by National Institutes of Health Grants R21 AI100766, R01 AI106725, and P01 AI073748

    TRY plant trait database - enhanced coverage and open access

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    Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives
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