239 research outputs found

    Einselection and Decoherence from an Information Theory Perspective

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    We introduce and investigate a simple model of conditional quantum dynamics. It allows for a discussion of the information-theoretic aspects of quantum measurements, decoherence, and environment-induced superselection (einselection).Comment: Proceedings of the Planck constant centenary meeting. Uses annalen.cls and fleqn.st

    Recombination rate and selection strength in HIV intra-patient evolution

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    The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Here, we estimate the rate of recombination and the distribution of selection coefficients from time-resolved sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be r=1.4e-5 recombinations per site and generation. Furthermore, we provide evidence that selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible, as soon as data with higher time resolution and greater sample sizes is available.Comment: to appear in PLoS Computational Biolog

    Classical kinetic energy, quantum fluctuation terms and kinetic-energy functionals

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    We employ a recently formulated dequantization procedure to obtain an exact expression for the kinetic energy which is applicable to all kinetic-energy functionals. We express the kinetic energy of an N-electron system as the sum of an N-electron classical kinetic energy and an N-electron purely quantum kinetic energy arising from the quantum fluctuations that turn the classical momentum into the quantum momentum. This leads to an interesting analogy with Nelson's stochastic approach to quantum mechanics, which we use to conceptually clarify the physical nature of part of the kinetic-energy functional in terms of statistical fluctuations and in direct correspondence with Fisher Information Theory. We show that the N-electron purely quantum kinetic energy can be written as the sum of the (one-electron) Weizsacker term and an (N-1)-electron kinetic correlation term. We further show that the Weizsacker term results from local fluctuations while the kinetic correlation term results from the nonlocal fluctuations. For one-electron orbitals (where kinetic correlation is neglected) we obtain an exact (albeit impractical) expression for the noninteracting kinetic energy as the sum of the classical kinetic energy and the Weizsacker term. The classical kinetic energy is seen to be explicitly dependent on the electron phase and this has implications for the development of accurate orbital-free kinetic-energy functionals. Also, there is a direct connection between the classical kinetic energy and the angular momentum and, across a row of the periodic table, the classical kinetic energy component of the noninteracting kinetic energy generally increases as Z increases.Comment: 10 pages, 1 figure. To appear in Theor Chem Ac

    Factors associated with the presence and prevalence of contagious ovine digital dermatitis: a 2013 study of 1136 random English sheep flocks

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    In 2013, a questionnaire was used to gather data on risks for introduction, and factors associated with prevalence, of contagious ovine digital dermatitis (CODD). There were 1136 (28.4%) usable responses from 4000 randomly selected sheep farmers in England. CODD was present in 58% (662) of flocks, with a reported prevalence of CODD lesions of 2.3%. The geometric mean period prevalence of all lameness was 4.2% and 2.8% in CODD positive and negative flocks respectively. Factors associated with a greater risk of presence of CODD were purchasing replacement ewes, not always checking the feet of sheep before purchase, not isolating purchased sheep, foot bathing returning ewes, foot trimming the flock more than twice in the year all compared with not doing these activities and increasing log10 flock size. Farmers who vaccinated sheep with Footvax™ were less likely to report presence of CODD. Factors associated with increasing prevalence of CODD lesions were not always checking the feet of purchased sheep, flocks that mixed with other flocks and sheep that left the farm for summer grazing and later returned. In addition, flocks where farmers followed the current recommended managements for control of footrot, had a lower prevalence of CODD whilst those who used foot bathing and where feet bled during routine foot trimming had a higher prevalence of CODD. The prevalence of CODD decreased with each log10 increase in flock size. We conclude that CODD is an infectious cause of lameness in sheep of increasing importance in GB. Introduction is linked to poor biosecurity with one likely source of the pathogen being introduction of or mixing with infected sheep. As with footrot, prevalence of CODD was lower in flocks where farmers focused on individual treatment to manage lameness and avoided foot bathing and trimming feet. We conclude that most of the currently recommended biosecurity and treatment approaches to control footrot in GB are also effective for control of CODD

    Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin

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    Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell- and mammalian cell-derived DENV was primarily dependent on the lectin pathway. Human MBL also bound to DENV and neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Experiments with human serum from naïve individuals with inherent variation in the levels of MBL in blood showed a direct correlation between the concentration of MBL and neutralization of DENV; samples with high levels of MBL in blood neutralized DENV more efficiently than those with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis

    Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

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    Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base
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