1,806 research outputs found

    Reverse Bisimulations on Stable Configuration Structures

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    The relationships between various equivalences on configuration structures, including interleaving bisimulation (IB), step bisimulation (SB) and hereditary history-preserving (HH) bisimulation, have been investigated by van Glabbeek and Goltz (and later Fecher). Since HH bisimulation may be characterised by the use of reverse as well as forward transitions, it is of interest to investigate forms of IB and SB where both forward and reverse transitions are allowed. We give various characterisations of reverse SB, showing that forward steps do not add extra power. We strengthen Bednarczyk's result that, in the absence of auto-concurrency, reverse IB is as strong as HH bisimulation, by showing that we need only exclude auto-concurrent events at the same depth in the configuration

    Packaging signals in single-stranded RNA viruses: nature’s alternative to a purely electrostatic assembly mechanism

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    The formation of a protective protein container is an essential step in the life-cycle of most viruses. In the case of single-stranded (ss)RNA viruses, this step occurs in parallel with genome packaging in a co-assembly process. Previously, it had been thought that this process can be explained entirely by electrostatics. Inspired by recent single-molecule fluorescence experiments that recapitulate the RNA packaging specificity seen in vivo for two model viruses, we present an alternative theory, which recognizes the important cooperative roles played by RNA–coat protein interactions, at sites we have termed packaging signals. The hypothesis is that multiple copies of packaging signals, repeated according to capsid symmetry, aid formation of the required capsid protein conformers at defined positions, resulting in significantly enhanced assembly efficiency. The precise mechanistic roles of packaging signal interactions may vary between viruses, as we have demonstrated for MS2 and STNV. We quantify the impact of packaging signals on capsid assembly efficiency using a dodecahedral model system, showing that heterogeneous affinity distributions of packaging signals for capsid protein out-compete those of homogeneous affinities. These insights pave the way to a new anti-viral therapy, reducing capsid assembly efficiency by targeting of the vital roles of the packaging signals, and opens up new avenues for the efficient construction of protein nanocontainers in bionanotechnology

    Genomic Risk Factors Driving Immune-Mediated Delayed Drug Hypersensitivity Reactions

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    Adverse drug reactions (ADRs) remain associated with significant mortality. Delayed hypersensitivity reactions (DHRs) that occur greater than 6 h following drug administration are T-cell mediated with many severe DHRs now associated with human leukocyte antigen (HLA) risk alleles, opening pathways for clinical prediction and prevention. However, incomplete negative predictive value (NPV), low positive predictive value (PPV), and a large number needed to test (NNT) to prevent one case have practically prevented large-scale and cost-effective screening implementation. Additional factors outside of HLA contributing to risk of severe T-cell-mediated DHRs include variation in drug metabolism, T-cell receptor (TCR) specificity, and, most recently, HLA-presented immunopeptidome-processing efficiencies via endoplasmic reticulum aminopeptidase (ERAP). Active research continues toward identification of other highly polymorphic factors likely to impose risk. These include those previously associated with T-cell-mediated HLA-associated infectious or auto-immune disease such as Killer cell immunoglobulin-like receptors (KIR), epistatically linked with HLA class I to regulate NK- and T-cell-mediated cytotoxic degranulation, and co-inhibitory signaling pathways for which therapeutic blockade in cancer immunotherapy is now associated with an increased incidence of DHRs. As such, the field now recognizes that susceptibility is not simply a static product of genetics but that individuals may experience dynamic risk, skewed toward immune activation through therapeutic interventions and epigenetic modifications driven by ecological exposures. This review provides an updated overview of current and proposed genetic factors thought to predispose risk for severe T-cell-mediated DHRs

    Signature of small rings in the Raman spectra of normal and compressed amorphous silica: A combined classical and ab initio study

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    We calculate the parallel (VV) and perpendicular (VH) polarized Raman spectra of amorphous silica. Model SiO2 glasses, uncompressed and compressed, were generated by a combination of classical and ab initio molecular-dynamics simulations and their dynamical matrices were computed within the framework of the density functional theory. The Raman scattering intensities were determined using the bond-polarizability model and a good agreement with experimental spectra was found. We confirm that the modes associated to the fourfold and threefold rings produce most of the Raman intensity of the D1 and D2 peaks, respectively, in the VV Raman spectra. Modifications of the Raman spectra upon compression are found to be in agreement with experimental data. We show that the modes associated to the fourfold rings still exist upon compression but do not produce a strong Raman intensity, whereas the ones associated to the threefold rings do. This result strongly suggests that the area under the D1 and D2 peaks is not directly proportional to the concentration of small rings in amorphous SiO2.Comment: 21 pages, 8 figures. Phys. Rev. B, in pres

    A Logic with Reverse Modalities for History-preserving Bisimulations

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    We introduce event identifier logic (EIL) which extends Hennessy-Milner logic by the addition of (1) reverse as well as forward modalities, and (2) identifiers to keep track of events. We show that this logic corresponds to hereditary history-preserving (HH) bisimulation equivalence within a particular true-concurrency model, namely stable configuration structures. We furthermore show how natural sublogics of EIL correspond to coarser equivalences. In particular we provide logical characterisations of weak history-preserving (WH) and history-preserving (H) bisimulation. Logics corresponding to HH and H bisimulation have been given previously, but not to WH bisimulation (when autoconcurrency is allowed), as far as we are aware. We also present characteristic formulas which characterise individual structures with respect to history-preserving equivalences.Comment: In Proceedings EXPRESS 2011, arXiv:1108.407

    Identification of volatiles generated by potato tubers (Solanum tuberosum CV : Maris Piper) infected by erwinia carotovora, bacillus polymyxa and arthrobacter sp

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    Bacteria were isolated from internal tissues of surface sterilized healthy tubers of Solanum tuberosum cv. Maris Piper (8 different isolates) and from tubers inoculated with Erwinia carotovora ssp. carotovora showing soft-rot symptoms (3 different isolates), and identified by fatty acid profiling. Bacillus polymyxa and an Arthrobacter sp. were isolated from both sources, E. carotovora only from the soft-rotted tubers. The volatile organic compounds (VOCs) generated by tubers inoculated with E. carotovora, B. polymyxa and the Arthrobacter sp. were identified. Inoculated tubers of cv. Maris Piper were incubated under controlled humidity (95% relative humidity) and temperature (10°C) to simulate typical storage conditions. B. polymyxa and Arthrobacter sp. did not cause symptoms, whilst E. carotovora caused limited soft-rot infections after 4 weeks at the low temperatures typically associated with potatoes in storage. The VOCs released to the headspace around these tubers were collected using an adsorbent system and analysed by Gas Chromatography-Mass Spectrometry (GC-MS). Twenty-two volatiles unique to E. carotovora infection of potato tubers were found,) including 10 alkanes, four alkenes, two aldehydes, one sulphide, one ketone, one alcohol, one aromatic, one acid and one heterocyclic compound. B. polymyxa generated three unique volatiles: N,N-dimethylformamide, 1-pentadecene and 1-hexadecane. Only one volatile, 2,3-dihydrofuran, was unique to the Arthrobacter infection. Production of volatile nitrogen species from E. carotovora-infected tubers increased with time, whereas none were detected in the headspace above uninfected tubers. Further analysis using a modified GC-MS method established that ammonia, trimethylamine and several volatile sulphides were evolved from tubers infected by E. carotovora. No specific volatile was useful as a marker associated with any of the three bacterial species but in the case of E. carotovora-infected potato tubers a significant increase in the volume of compounds evolved was clearly observed. The results are discussed in relation to the use of sensors to detect VOCs evolved from infected tubers in order to provide an early warning system for the control of soft rot in potato store

    Determining Histories of Slip on Normal Faults With Bedrock Scarps Using Cosmogenic Nuclide Exposure Data

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    Cosmogenic exposure data can be used to calculate time-varying fault slip rates on normal faults with exposed bedrock scarps. The method relies on assumptions related to how the scarp is preserved, which should be consistent at multiple locations along the same fault. Previous work commonly relied on cosmogenic data from a single sample locality to determine the slip rate of a fault. Here we show that by applying strict sampling criteria and using geologically informed modeling parameters in a Bayesian-inference Markov chain Monte Carlo method, similar patterns of slip rate changes can be modeled at multiple sites on the same fault. Consequently, cosmogenic data can be used to resolve along-strike fault activity. We present cosmogenic 36Cl concentrations from seven sites on two faults in the Italian Apennines. The average slip rate varies between sites on the Campo Felice Fault (0.84 ± 0.23 to 1.61 ± 0.27 mm yr−1), and all sites experienced a period of higher than average slip rate between 0.5 and 2 ka and a period of lower than average slip rate before 3 ka. On the Roccapreturo fault, slip rate in the center of the fault is 0.55 ± 0.11 and 0.35 ± 0.05 mm yr−1 at the fault tip near a relay zone. The estimated time since the last earthquake is the same at each site along the same fault (631 ± 620 years at Campo Felice and 2,603 ± 1,355 years at Roccapreturo). These results highlight the potential for cosmogenic exposure data to reveal the detailed millennial history of earthquake slip on active normal faults
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