97 research outputs found

    Melting transition of an Ising glass driven by magnetic field

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    The quantum critical behavior of the Ising glass in a magnetic field is investigated. We focus on the spin glass to paramagnet transition of the transverse degrees of freedom in the presence of finite longitudinal field. We use two complementary techniques, the Landau theory close to the T=0 transition and the exact diagonalization method for finite systems. This allows us to estimate the size of the critical region and characterize various crossover regimes. An unexpectedly small energy scale on the disordered side of the critical line is found, and its possible relevance to experiments on metallic glasses is briefly discussed.Comment: 4 pages, 3 figure

    Structural and functional characterisation of a stable, broad-specificity multimeric sialidase from the oral pathogen Tannerella forsythia

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    Sialidases are glycosyl hydrolase enzymes targeting the glycosidic bond between terminal sialic acids and underlying sugars. The NanH sialidase of Tannerella forsythia, one of the bacteria associated with severe periodontal disease plays a role in virulence. Here, we show that this broad-specificity enzyme (but higher affinity for α2,3 over α2,6 linked sialic acids) digests complex glycans but not those containing Neu5,9Ac. Furthermore, we show it to be a highly stable dimeric enzyme and present a thorough structural analysis of the native enzyme in its apo-form and in complex with a sialic acid analogue/ inhibitor (Oseltamivir). We also use non-catalytic (D237A) variant to characterise molecular interactions while in complex with the natural substrates 3- and 6-siallylactose. This dataset also reveals the NanH carbohydrate-binding module (CBM, CAZy CBM 93) has a novel fold made of antiparallel beta-strands. The catalytic domain structure contains novel features that include a non-prolyl cis-peptide and an uncommon arginine sidechain rotamer (R306) proximal to the active site. Via a mutagenesis programme, we identified key active site residues (D237, R212 and Y518) and probed the effects of mutation of residues in proximity to the glycosidic linkage within 2,3 and 2,6-linked substrates. These data revealed that mutagenesis of R306 and residues S235 and V236 adjacent to the acid–base catalyst D237 influence the linkage specificity preference of this bacterial sialidase, opening up possibilities for enzyme engineering for glycotechology applications and providing key structural information that for in silico design of specific inhibitors of this enzyme for the treatment of periodontitis

    Cardiomyopathy in boxer dogs : a retrospective study of the clinical presentation, diagnostic findings and survival

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    Objectives: To retrospectively compare and contrast the clinical presentation, diagnostic findings and survival in Boxer dogs with cardiomyopathy, with or without left ventricular (LV) systolic failure. Animals, materials and methods: Medical records of Boxers referred between 1993 and 2008 in which a diagnosis of ventricular arrhythmias and/or cardiomyopathy was made, were reviewed. Dogs were divided into two groups according to their left ventricular (LV) systolic diameter, group A normal (20 dogs) or group B dilated (59 dogs). Results: Dogs in group A had a better outcome than dogs in group B (median survival time of 124 and 17 weeks respectively, p < 0.001). In group B, dogs with a history of collapse had a worse outcome (median survival time of 10 weeks) compared with dogs not showing collapse (median survival time 24 weeks) (p = 0.031). Conclusions: The majority of dogs, in this UK study, presented with the myocardial dysfunction form of the disease, with LV dilation and congestive heart failure signs. The prognosis was worse in dogs with LV dilation compared to dogs with a normal LV and ventricular arrhythmias. In the Boxers with LV dilation, dogs with collapse had a worse prognosis than those without

    Evidence for a novel Carbohydrate Binding Module (CBM) of Tannerella forsythia NanH sialidase, key to interactions at the host-pathogen interface

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    Bacterial sialidases cleave terminal sialic acid from a variety of host glycoproteins, and contribute to survival and growth of many human-dwelling bacterial species, including various pathogens.Tannerella forsythia, an oral, Gram-negative, fastidious anaerobe, is a key organism in periodontal disease, and possesses a dedicated sialic acid utilisation and scavenging (nan) operon, including NanH sialidase. Here, we describe biochemical characterisation of recombinant NanH, including its action on host-relevant sialoglycans such as sialyl Lewis A and sialyl Lewis X (SLeA/X), and on human cell-attached sialic acids directly, uncovering that it is a highly active broad specificity sialidase. Furthermore, theN-terminal domain of NanH was hypothesised and proven to be capable of binding to a range of sialoglycans and non-sialylated derivatives withKdin the micromolar range, as determined by steady-state tryptophan fluorescence spectroscopy, but it has no catalytic activity in isolation from the active site. We consider this domain to represent the founding member of a novel subfamily of Carbohydrate Binding Module (CBM), involved in glycosidase-ligand binding. In addition, we created a catalytically inactive version of the NanH enzyme (FRIP→YMAP) that retained its ability to bind sialic acid-containing ligands and revealed for the first time that binding activity of a CBM is enhanced by association with the catalytic domain. Finally, we investigated the importance of Lewis-type sialoglycans onT. forsythia-host interactions, showing that nanomolar amounts of SLeA/Xwere capable of reducing invasion of oral epithelial cells byT. forsythiasuggesting that these are key ligands for bacterial-cellular interactions during periodontal disease

    Finite-Temperature Transport in Finite-Size Hubbard Rings in the Strong-Coupling Limit

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    We study the current, the curvature of levels, and the finite temperature charge stiffness, D(T,L), in the strongly correlated limit, U>>t, for Hubbard rings of L sites, with U the on-site Coulomb repulsion and t the hopping integral. Our study is done for finite-size systems and any band filling. Up to order t we derive our results following two independent approaches, namely, using the solution provided by the Bethe ansatz and the solution provided by an algebraic method, where the electronic operators are represented in a slave-fermion picture. We find that, in the U=\infty case, the finite-temperature charge stiffness is finite for electronic densities, n, smaller than one. These results are essencially those of spinless fermions in a lattice of size L, apart from small corrections coming from a statistical flux, due to the spin degrees of freedom. Up to order t, the Mott-Hubbard gap is \Delta_{MH}=U-4t, and we find that D(T) is finite for n<1, but is zero at half-filling. This result comes from the effective flux felt by the holon excitations, which, due to the presence of doubly occupied sites, is renormalized to \Phi^{eff}=\phi(N_h-N_d)/(N_d+N_h), and which is zero at half-filling, with N_d and N_h being the number of doubly occupied and empty lattice sites, respectively. Further, for half-filling, the current transported by any eigenstate of the system is zero and, therefore, D(T) is also zero.Comment: 15 pages and 6 figures; accepted for PR

    Characterization of Porphyromonas gingivalis sialidase and disruption of its role in host–pathogen interactions

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    Key to onset and progression of periodontitis is a complex relationship between oral bacteria and the host. The organisms most associated with severe periodontitis are the periodontal pathogens of the red complex: Tannerella forsythia , Treponema denticola and Porphyromonas gingivalis . These organisms express sialidases, which cleave sialic acid from host glycoproteins, and contribute to disease through various mechanisms. Here, we expressed and purified recombinant P. gingivalis sialidase SiaPG (PG_0352) and characterized its activity on a number of substrates, including host sialoglycoproteins and highlighting the inability to cleave diacetylated sialic acids – a phenomenon overcome by the NanS sialate-esterase from T. forsythia . Indeed SiaPG required NanS to maximize sialic acid harvesting from heavily O-acetylated substrates such as bovine salivary mucin, hinting at the possibility of interspecies cooperation in sialic acid release from host sources by these members of the oral microbiota. Activity of SiaPG and P. gingivalis was inhibited using the commercially available chemotherapeutic zanamivir, indicating its potential as a virulence inhibitor, which also inhibited sialic acid release from mucin, and was capable of inhibiting biofilm formation of P. gingivalis on oral glycoprotein sources. Zanamivir also inhibited attachment and invasion of oral epithelial cells by P. gingivalis and other periodontal pathogens, both in monospecies but also in multispecies infection experiments, indicating potential to suppress host–pathogen interactions of a mixed microbial community. This study broadens our understanding of the multifarious roles of bacterial sialidases in virulence, and indicates that their inhibition with chemotherapeutics could be a promising strategy for periodontitis therapy

    Cosmological Constraints from Measurements of Type Ia Supernovae Discovered during the First 1.5 yr of the Pan-STARRS1 Survey

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    We present griz P1 light curves of 146 spectroscopically confirmed Type Ia supernovae (SNe Ia; 0.03 < z < 0.65) discovered during the first 1.5 yr of the Pan-STARRS1 Medium Deep Survey. The Pan-STARRS1 natural photometric system is determined by a combination of on-site measurements of the instrument response function and observations of spectrophotometric standard stars. We find that the systematic uncertainties in the photometric system are currently 1.2% without accounting for the uncertainty in the Hubble Space Telescope Calspec definition of the AB system. A Hubble diagram is constructed with a subset of 113 out of 146 SNe Ia that pass our light curve quality cuts. The cosmological fit to 310 SNe Ia (113 PS1 SNe Ia + 222 light curves from 197 low-z SNe Ia), using only supernovae (SNe) and assuming a constant dark energy equation of state and flatness, yields w=−1.120−0.206+0.360(Stat)−0.291+0.269(Sys)w=-1.120^{+0.360}_{-0.206}\hbox{(Stat)} ^{+0.269}_{-0.291}\hbox{(Sys)}. When combined with BAO+CMB(Planck)+H 0, the analysis yields ΩM=0.280−0.012+0.013\Omega _{\rm M}=0.280^{+0.013}_{-0.012} and w=−1.166−0.069+0.072w=-1.166^{+0.072}_{-0.069} including all identified systematics. The value of w is inconsistent with the cosmological constant value of –1 at the 2.3σ level. Tension endures after removing either the baryon acoustic oscillation (BAO) or the H 0 constraint, though it is strongest when including the H 0 constraint. If we include WMAP9 cosmic microwave background (CMB) constraints instead of those from Planck, we find w=−1.124−0.065+0.083w=-1.124^{+0.083}_{-0.065}, which diminishes the discord to <2σ. We cannot conclude whether the tension with flat ΛCDM is a feature of dark energy, new physics, or a combination of chance and systematic errors. The full Pan-STARRS1 SN sample with ~three times as many SNe should provide more conclusive results

    The effect of autonomy, training opportunities, age and salaries on job satisfaction in the South East Asian retail petroleum industry

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    South East Asian petroleum retailers are under considerable pressure to improve service quality by reducing turnover. An empirical methodology from this industry determined the extent to which job characteristics, training opportunities, age and salary influenced the level of job satisfaction, an indicator of turnover. Responses are reported on a random sample of 165 site employees (a 68% response rate) of a Singaporean retail petroleum firm. A restricted multivariate regression model of autonomy and training opportunities explained the majority (35.4%) of the variability of job satisfaction. Age did not moderate these relationships, except for employees >21 years of age, who reported enhanced job satisfaction with additional salary. Human Capital theory, Life Cycle theory and Job Enrichment theory are invoked and explored in the context of these findings in the South East Asian retail petroleum industry. In the South East Asian retail petroleum industry, jobs providing employees with the opportunity to undertake a variety of tasks that enhanced the experienced meaningfulness of work are likely to promote job satisfaction, reduce turnover and increase the quality of service

    National identity predicts public health support during a global pandemic

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    Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio
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