54 research outputs found

    Random Mass Dirac Fermions in Doped Spin-Peierls and Spin-Ladder systems: One-Particle Properties and Boundary Effects

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    Quasi-one-dimensional spin-Peierls and spin-ladder systems are characterized by a gap in the spin-excitation spectrum, which can be modeled at low energies by that of Dirac fermions with a mass. In the presence of disorder these systems can still be described by a Dirac fermion model, but with a random mass. Some peculiar properties, like the Dyson singularity in the density of states, are well known and attributed to creation of low-energy states due to the disorder. We take one step further and study single-particle correlations by means of Berezinskii's diagram technique. We find that, at low energy ϵ\epsilon, the single-particle Green function decays in real space like G(x,ϵ)(1/x)3/2G(x,\epsilon) \propto (1/x)^{3/2}. It follows that at these energies the correlations in the disordered system are strong -- even stronger than in the pure system without the gap. Additionally, we study the effects of boundaries on the local density of states. We find that the latter is logarithmically (in the energy) enhanced close to the boundary. This enhancement decays into the bulk as 1/x1/\sqrt{x} and the density of states saturates to its bulk value on the scale Lϵln2(1/ϵ)L_\epsilon \propto \ln^2 (1/\epsilon). This scale is different from the Thouless localization length λϵln(1/ϵ)\lambda_\epsilon\propto\ln (1/\epsilon). We also discuss some implications of these results for the spin systems and their relation to the investigations based on real-space renormalization group approach.Comment: 26 pages, LaTex, 9 PS figures include

    Identification of trans protein QTL for secreted airway mucins in mice and a causal role for Bpifb1

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    Mucus hyper-secretion is a hallmark feature of asthma and other muco-obstructive airway diseases. The mucin proteins MUC5AC and MUC5B are the major glycoprotein components of mucus and have critical roles in airway defense. Despite the biomedical importance of these two proteins, the loci that regulate them in the context of natural genetic variation have not been studied. To identify genes that underlie variation in airway mucin levels, we performed genetic analyses in founder strains and incipient lines of the Collaborative Cross (CC) in a house dust mite mouse model of asthma. CC founder strains exhibited significant differences in MUC5AC and MUC5B, providing evidence of heritability. Analysis of gene and protein expression of Muc5ac and Muc5b in incipient CC lines (n = 154) suggested that post-transcriptional events were important regulators of mucin protein content in the airways. Quantitative trait locus (QTL) mapping identified distinct, trans protein QTL for MUC5AC (chromosome 13) and MUC5B (chromosome 2). These two QTL explained 18 and 20% of phenotypic variance, respectively. Examination of the MUC5B QTL allele effects and subsequent phylogenetic analysis allowed us to narrow the MUC5B QTL and identify Bpifb1 as a candidate gene. Bpifb1 mRNA and protein expression were upregulated in parallel to MUC5B after allergen challenge, and Bpifb1 knockout mice exhibited higher MUC5B expression. Thus, BPIFB1 is a novel regulator of MUC5B

    Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome

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    Purpose: Variants in the DNA mismatch repair (MMR) gene MSH6, identified in individuals suspected of Lynch syndrome, are difficult to classify owing to the low cancer penetrance of defects in that gene. This not only obfuscates personalized health care but also the development of a rapid and reliable classification procedure that does not require clinical data. Methods: The complete in vitro MMR activity (CIMRA) assay was calibrated against clinically classified MSH6 variants and, employing Bayes’ rule, integrated with computational predictions of pathogenicity. To enable the validation of this two-component classification procedure we have employed a genetic screen to generate a large set of inactivating Msh6 variants, as proxies for pathogenic variants. Results: The genetic screen-derived variants established that the two-component classification procedure displays high sensitivities and specificities. Moreover, these inactivating variants enabled the direct reclassification of human variants of uncertain significance (VUS) as (likely) pathogenic. Conclusion: The two-component classification procedure and the genetic screens provide complementary approaches to rapidly and cost-effectively classify the large majority of human MSH6 variants. The approach followed here provides a template for the classification of variants in other disease-predisposing genes, facilitating the translation of personalized genomics into personalized health care

    Dimensionless cosmology

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    Although it is well known that any consideration of the variations of fundamental constants should be restricted to their dimensionless combinations, the literature on variations of the gravitational constant GG is entirely dimensionful. To illustrate applications of this to cosmology, we explicitly give a dimensionless version of the parameters of the standard cosmological model, and describe the physics of Big Bang Neucleosynthesis and recombination in a dimensionless manner. The issue that appears to have been missed in many studies is that in cosmology the strength of gravity is bound up in the cosmological equations, and the epoch at which we live is a crucial part of the model. We argue that it is useful to consider the hypothetical situation of communicating with another civilization (with entirely different units), comparing only dimensionless constants, in order to decide if we live in a Universe governed by precisely the same physical laws. In this thought experiment, we would also have to compare epochs, which can be defined by giving the value of any {\it one} of the evolving cosmological parameters. By setting things up carefully in this way one can avoid inconsistent results when considering variable constants, caused by effectively fixing more than one parameter today. We show examples of this effect by considering microwave background anisotropies, being careful to maintain dimensionlessness throughout. We present Fisher matrix calculations to estimate how well the fine structure constants for electromagnetism and gravity can be determined with future microwave background experiments. We highlight how one can be misled by simply adding GG to the usual cosmological parameter set

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia

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    The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3′ end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence

    Dust Devil Sediment Transport: From Lab to Field to Global Impact

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    The impact of dust aerosols on the climate and environment of Earth and Mars is complex and forms a major area of research. A difficulty arises in estimating the contribution of small-scale dust devils to the total dust aerosol. This difficulty is due to uncertainties in the amount of dust lifted by individual dust devils, the frequency of dust devil occurrence, and the lack of statistical generality of individual experiments and observations. In this paper, we review results of observational, laboratory, and modeling studies and provide an overview of dust devil dust transport on various spatio-temporal scales as obtained with the different research approaches. Methods used for the investigation of dust devils on Earth and Mars vary. For example, while the use of imagery for the investigation of dust devil occurrence frequency is common practice for Mars, this is less so the case for Earth. Modeling approaches for Earth and Mars are similar in that they are based on the same underlying theory, but they are applied in different ways. Insights into the benefits and limitations of each approach suggest potential future research focuses, which can further reduce the uncertainty associated with dust devil dust entrainment. The potential impacts of dust devils on the climates of Earth and Mars are discussed on the basis of the presented research results

    A fully validated microbiological assay for daptomycin injection and comparison to HPLC method

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    abstract Daptomycin (DPT) was the first lipopeptide antibiotic available for commercialization. It is active against gram-positive bacteria, including resistant strains. This work aimed to develop and validate a turbidimetric microbiologic assay to determine daptomycin in an injectable form. A 3x3 design was employed, at concentrations of 1, 2 and 4.0 µg/mL. The microorganism test used was Staphylococcus aureus ATCC 6538p, and Antibiotic Medium 3 was used as the culture medium. Method validation demonstrated that the bioassay was linear (r=0.9995), precise (RSD=2.58%), accurate (recovery 100.48± 2.11%), and robust. Degradation kinetics was also performed in an alkaline medium, indicating that daptomycin degradation follows first order kinetics under these conditions. The analyses of degraded solutions showed that daptomycin degradation products do not possess bactericidal activity. The bioassay was compared to HPLC method that was previously developed and no significant difference was found between them (p>0.05). The method proved to be appropriate for daptomycin injection quality control

    Orbital Observations of Dust Lofted by Daytime Convective Turbulence

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    Over the past several decades, orbital observations of lofted dust have revealed the importance of mineral aerosols as a climate forcing mechanism on both Earth and Mars. Increasingly detailed and diverse data sets have provided an ever-improving understanding of dust sources, transport pathways, and sinks on both planets, but the role of dust in modulating atmospheric processes is complex and not always well understood. We present a review of orbital observations of entrained dust on Earth and Mars, particularly that produced by the dust-laden structures produced by daytime convective turbulence called “dust devils”. On Earth, dust devils are thought to contribute only a small fraction of the atmospheric dust budget; accordingly, there are not yet any published accounts of their occurrence from orbit. In contrast, dust devils on Mars are thought to account for several tens of percent of the planet’s atmospheric dust budget; the literature regarding martian dust devils is quite rich. Because terrestrial dust devils may temporarily contribute significantly to local dust loading and lowered air quality, we suggest that martian dust devil studies may inform future studies of convectively-lofted dust on Earth

    Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

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    notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations
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