43 research outputs found
Venus Atmosphere Profile from a Maximum Entropy Principle
The variational method with constraints recently developed by Verkley and
Gerkema to describe maximum-entropy atmospheric profiles is generalized to
ideal gases but with temperature-dependent specific heats. In so doing, an
extended and non standard potential temperature is introduced that is well
suited for tackling the problem under consideration. This new formalism is
successfully applied to the atmosphere of Venus. Three well defined regions
emerge in this atmosphere up to a height of from the surface: the
lowest one up to about is adiabatic, a transition layer located at the
height of the cloud deck and finally a third region which is practically
isothermal.Comment: 6 pages, 3 figure
Dynamics of Rumor Spreading in Complex Networks
We derive the mean-field equations characterizing the dynamics of a rumor
process that takes place on top of complex heterogeneous networks. These
equations are solved numerically by means of a stochastic approach. First, we
present analytical and Monte Carlo calculations for homogeneous networks and
compare the results with those obtained by the numerical method. Then, we study
the spreading process in detail for random scale-free networks. The time
profiles for several quantities are numerically computed, which allow us to
distinguish among different variants of rumor spreading algorithms. Our
conclusions are directed to possible applications in replicated database
maintenance, peer to peer communication networks and social spreading
phenomena.Comment: Final version to appear in PR
Metamodel-based model conformance and multiview consistency checking
Model-driven development, using languages such as UML and BON, often makes use of multiple diagrams (e.g., class and sequence diagrams) when modeling systems. These diagrams, presenting different views of a system of interest, may be inconsistent. A metamodel provides a unifying framework in which to ensure and check consistency, while at the same time providing the means to distinguish between valid and invalid models, that is, conformance. Two formal specifications of the metamodel for an object-oriented modeling language are presented, and it is shown how to use these specifications for model conformance and multiview consistency checking. Comparisons are made in terms of completeness and the level of automation each provide for checking multiview consistency and model conformance. The lessons learned from applying formal techniques to the problems of metamodeling, model conformance, and multiview consistency checking are summarized
Single-cell analysis identifies cellular markers of the HIV permissive cell.
Cellular permissiveness to HIV infection is highly heterogeneous across individuals. Heterogeneity is also found across CD4+ T cells from the same individual, where only a fraction of cells gets infected. To explore the basis of permissiveness, we performed single-cell RNA-seq analysis of non-infected CD4+ T cells from high and low permissive individuals. Transcriptional heterogeneity translated in a continuum of cell states, driven by T-cell receptor-mediated cell activation and was strongly linked to permissiveness. Proteins expressed at the cell surface and displaying the highest correlation with T cell activation were tested as biomarkers of cellular permissiveness to HIV. FACS sorting using antibodies against several biomarkers of permissiveness led to an increase of HIV cellular infection rates. Top candidate biomarkers included CD25, a canonical activation marker. The combination of CD25 high expression with other candidate biomarkers led to the identification of CD298, CD63 and CD317 as the best biomarkers for permissiveness. CD25highCD298highCD63highCD317high cell population showed an enrichment of HIV-infection of up to 28 fold as compared to the unsorted cell population. The purified hyper-permissive cell subpopulation was characterized by a downregulation of interferon-induced genes and several known restriction factors. Single-cell RNA-seq analysis coupled with functional characterization of cell biomarkers provides signatures of the "HIV-permissive cell"
Model Structure of Human APOBEC3G
BACKGROUND: APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) has antiretroviral activity associated with the hypermutation of viral DNA through cytosine deamination. APOBEC3G has two cytosine deaminase (CDA) domains; the catalytically inactive amino-terminal domain of APOBEC3G (N-CDA) carries the Vif interaction domain. There is no 3-D structure of APOBEC3G solved by X-ray or nuclear magnetic resonance. METHODOLOGY/PRINCIPAL FINDINGS: We predicted the structure of human APOBEC3G based on the crystal structure of APOBEC2. To assess the model structure, we evaluated 48 mutants of APOBEC3G N-CDA that identify novel variants altering ΔVif HIV-1 infectivity and packaging of APOBEC3G. Results indicated that the key residue D128 is exposed at the surface of the model, with a negative local electrostatic potential. Mutation D128K changes the sign of that local potential. In addition, two novel functionally relevant residues that result in defective APOBEC3G encapsidation, R122 and W127, cluster at the surface. CONCLUSIONS/SIGNIFICANCE: The structure model identifies a cluster of residues important for packaging of APOBEC3G into virions, and may serve to guide functional analysis of APOBEC3G
Formal Verification of Tokeneer Behaviours Modelled in fUML Using CSP
Much research work has been done on formalizing UML diagrams, but less has focused on using this formalization to analyze the dynamic behaviours between formalized components. In this paper we propose using a subset of fUML (Foundational Subset for Executable UML) as a semi-formal language, and formalizing it to the process algebraic specification language CSP, to make use of FDR as a model checker. Our formalization includes modelling the asynchronous communication framework used within fUML. This allows different interpretations of the communications model to be evaluated. To illustrate the approach, we use the modelling of the Tokeneer ID Station specifications into fUML, and formalize them in CSP to check if the model is deadlock free
Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1
Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection
Genomics meets HIV-1
Genomics is now a core element in the effort to develop a vaccine against HIV-1. Thanks to unprecedented progress in high-throughput genotyping and sequencing, in knowledge about genetic variation in humans, and in evolutionary genomics, it is finally possible to systematically search the genome for common genetic variants that influence the human response to HIV-1. The identification of such variants would help to determine which aspects of the response to the virus are the most promising targets for intervention. However, a key obstacle to progress remains the scarcity of appropriate human cohorts available for genomic research
Copy Number Variation of KIR Genes Influences HIV-1 Control
The authors that the number of activating and inhibitory KIR genes varies between individuals and plays a role in the regulation of immune mechanisms that determine HIV-1 control
Genetic Diversity of EBV-Encoded LMP1 in the Swiss HIV Cohort Study and Implication for NF-Κb Activation
Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1