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    Erratum: The chemistry of transient molecular cloud cores

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    We assume that some, but not all, of the structure observed in molecular clouds is associated with transient features which are not bound by self-gravity. We investigate the chemistry of a transient density fluctuation, with properties similar to those of a core within a molecular cloud. We run a multipoint chemical code through a core's condensation from a diffuse medium to its eventual dispersion, over a period of ∼1 Myr. The dynamical description adopted for our study is based on an understanding of a particular mechanism, involving slow-mode wave excitation, for transient structure formation which so far has been studied in detail only with plane-parallel models in which self-gravity has not been included. We find a significant enhancement of the chemical composition of the core material on its return to diffuse conditions, whilst the expansion of the core as it disperses moves this material out to large distances from the core centre. This process transports molecular species formed in the high-density regions out into the diffuse medium. Chemical enrichment of the cloud as a whole also occurs, as other cores of various sizes, life-spans and separations evolve throughout. Enrichment is strongly affected by freeze-out on to dust grains, which takes place in high-density, high visual extinction regions. As the core disperses after reaching its peak density and the visual extinction drops below a critical value, grain mantles are evaporated back into the gas phase, initiating more chemistry. The influence of the sizes, masses and cycle periods of cores will be large both for the level of chemical enrichment of a dark cloud and ultimately for the low-mass star formation rate. The cores in which stars form are almost certainly bound by their self-gravity and are not transient in the sense that the cores on which most of our study is focused are transient. Obviously, enrichment of the chemistry of low-density material will not take place if self-gravity prevents the re-expansion of a core. We also consider the case of a self-gravitating core, by holding its peak density conditions for a further 0.4 Myr. We find that the differences near the peak densities between transient and gravitationally bound cores are generally small, and the resultant column densities for objects near the peak densities do not provide definitive criteria for discriminating between transient and bound cores. However, increases in fractional abundances due to reinjection of mantle-borne species may provide a criterion for detection of a non-bound core

    A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells

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    Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide–major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705–restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1–specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1–specific CD8+ T cells, the HLA-B2705–KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I–specific receptor expressed on myelomonocytic cells. Binding of the B2705–KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversificatio

    BILIARY HAPTOGLOBIN, A POTENT PROMOTER OF CHOLESTEROL CRYSTALLIZATION AT PHYSIOLOGICAL CONCENTRATIONS

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    Background/Aims: Several proteins present in human bile have been reported to promote cholesterol crystallization and thus are potentially important in the formation of cholesterol crystals as the initial stage in gallstone pathogenesis. To be physiologically relevant, such proteins must either be present in high concentration in bile or have a potent promoting activity. The current study explored several of the more abundant but unexamined biliary proteins based upon their also having sufficiently high serum concentrations that antibodies were available for both their isolation and quantitation. Methods: Protein purification was accomplished by immunoaffinity chromatography of bile followed by delipidation. Con A affinity chromatography of bile was used to obtain the bound fraction, a portion of which was delipidated. Crystallization-promoting activity of both the purified proteins and Con A-bound glycoprotein fractions (CABG) was measured by a photometric crystal growth assay. A competitive antibody-capture ELISA assay was developed to measure concentrations of alpha(1)-antitrypsin, transferrin, and haptoglobin in native bile. Results: At their relevant physiological concentrations, biliary haptoglobin (15 mu g/ml) had a crystallization-promoting activity twice that of the biliary IgM (75 mu g/ml) used as a reference standard (P < 0.05). Biliary transferrin (20 mu g/ml) had only modest promoting activity (P < 0.05). Biliary alpha(1)-antitrypsin (50 mu g/ml), by contrast, showed no promoting activity. Delipidation of the CABG fraction decreased its promoting activity by 75%. Biliary haptoglobin accounts for about 30% of delipidated total CABG-promoting activity. Conclusions: Biliary haptoglobin at its physiological concentration has a highly potent crystallization-promoting activity and thus becomes a candidate for major attention in understanding gallstone pathogenesis. Biliary lipids associated with CABG account for a major portion of the cholesterol-crystallization-promoting activity of this fraction

    The egiin davaa prehistoric rupture, central mongolia: A large magnitude normal faulting earthquake on a reactivated fault with little cumulative slip located in a slowly deforming intraplate setting

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    The prehistoric Egiin Davaa earthquake rupture is well-preserved in late Quaternary deposits within the Hangay Mountains of central Mongolia. The rupture is expressed by a semicontinuous 80 km-long topographic scarp. Geomorphological reconstructions reveal a relatively constant scarp height of 4-4.5 m and a NW-directed slip vector. Previous researchers have suggested that the scarp's exceptional geomorphological preservation indicates that it may correspond to an earthquake that occurred in the region c. 500 years ago. However, we constrain the last rupture to have been at least 4 ka ago from morphological dating and < 7.4 ka ago based on radiocarbon dating from one of two palaeoseismic trenches. Our study shows that discrete earthquake ruptures, along with details such as the locations of partially infilled fissures, can be preserved for periods well in excess of 1000 years in the interior of Asia, providing an archive of fault movements that can be directly read from the Earth's surface over a timescale appropriate for the study of slowly deforming continental interiors. The Egiin Davaa rupture involved c. 8 m of slip which, along with the observations that it is largely unsegmented along its length and that the ratio of cumulative slip (c. 250 m) to fault length (c. 80 km) is small, suggests relatively recent reactivation of a pre-existing geological structure

    A new insight for monitoring ungulates : density surface modelling of roe deer in a Mediterranean habitat

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    We would like to thank the University of Aveiro (Department of Biology) and FCT/MEC for the financial support to CESAM RU (UID/AMB/50017) through national funds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement. TAM is partially funded by FCT, Fundação para a Ciência e a Tecnologia, Portugal, through the project UID/MAT/00006/2013.Ungulates are especially difficult to monitor, and population estimates are challenging to obtain; nevertheless, such information is fundamental for effective management. This is particularly important for expanding species such as roe deer (Capreolus capreolus), whose populations dramatically increased in number and geographic distribution over the last decades. In an attempt to follow population trends and assess species ecology, important methodological advances were recently achieved by combining line or point sampling with geographic information systems (GIS). In this study, we combined density surface modelling (DSM) with line transect survey to predict roe deer density in northeastern Portugal. This was based on modelling pellet group counts as a function of environmental factors while taking into account the probability of detecting pellets and conversion factors to relate pellet density to animal density. We estimated a global density of 3.01 animals/100 ha (95 % CI 0.37–3.51) with a 32.82 % CV. Roe deer densities increased with increasing distance to roads as well as with higher percentage of cover areas and decreased with increasing distance to human populations. This recently developed spatial method can be advantageous to predict density over space through the identification of key factors influencing species abundance. Furthermore, surface maps for subset areas will enable to visually depict abundance distribution of wild populations. This will enable the assessment of areas where ungulate impacts should be minimized, allowing an adaptive management through time.PostprintPeer reviewe

    Capturing and testing perceptual-cognitive expertise: A comparison of stationary and movement response methods

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    Numerous methods have been used to study expertise and performance. In the present article, we compare the cognitive thought processes of skilled soccer players when responding to film-based simulations of defensive situations involving two different experimental conditions. Participants either remained stationary in a seated position (n = 10) or were allowed to move (n = 10) in response to life-size film sequences of 11 versus 11 open-play soccer situations viewed from a player’s perspective. Response accuracy and retrospective verbal reports of thinking were collected across the two task conditions. In the movement-based response group, participants generated a greater number of verbal report statements, including a higher proportion of evaluation, prediction, and action planning statements, than did participants in the stationary group. Findings suggest that the processing strategies employed during performance differ depending on the nature of the response required of participants. Implications for behavioral methods and experimental design are discussed

    Economic evaluation alongside pragmatic randomised trials: developing a standard operating procedure for clinical trials units

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    <p>Abstract</p> <p>Background</p> <p>There is wide recognition that pragmatic randomised trials are the best vehicle for economic evaluation. This is because trials provide the best chance of ensuring internal validity, not least through the rigorous prospective collection of patient-specific data. Furthermore the marginal cost of collecting economic data alongside clinical data is typically modest. UK Clinical Research Collaboration (UKCRC) does not require a standard operating procedure (SOP) for economic evaluation as a prerequisite for trial unit registration. We judge that such a SOP facilitates the integration of health economics into trials.</p> <p>Methods</p> <p>A collaboration between health economists and trialists at Bangor University led to the development of a SOP for economic evaluation alongside pragmatic trials, in addition to the twenty SOPs required by UKCRC for registration, which include randomisation, data management and statistical analysis.</p> <p>Results</p> <p>Our recent telephone survey suggests that no other UKCRC-registered trials unit currently has an economic SOP.</p> <p>Conclusion</p> <p>We argue that UKCRC should require, from all Trials Units undertaking economic evaluation and seeking registration or re-registration, a SOP for economic evaluation as one of their portfolio of supporting SOPs.</p

    A weak characterization of slow variables in stochastic dynamical systems

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    We present a novel characterization of slow variables for continuous Markov processes that provably preserve the slow timescales. These slow variables are known as reaction coordinates in molecular dynamical applications, where they play a key role in system analysis and coarse graining. The defining characteristics of these slow variables is that they parametrize a so-called transition manifold, a low-dimensional manifold in a certain density function space that emerges with progressive equilibration of the system's fast variables. The existence of said manifold was previously predicted for certain classes of metastable and slow-fast systems. However, in the original work, the existence of the manifold hinges on the pointwise convergence of the system's transition density functions towards it. We show in this work that a convergence in average with respect to the system's stationary measure is sufficient to yield reaction coordinates with the same key qualities. This allows one to accurately predict the timescale preservation in systems where the old theory is not applicable or would give overly pessimistic results. Moreover, the new characterization is still constructive, in that it allows for the algorithmic identification of a good slow variable. The improved characterization, the error prediction and the variable construction are demonstrated by a small metastable system
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