501 research outputs found

    CoStricTor: Collaborative HTTP Strict Transport Security in Tor Browser

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    HTTP Strict Transport Security (HSTS) is a widely-deployed security feature in modern web browsing. It is also, however, a potential vector for user tracking and surveillance. Tor Browser, a web browser primarily concerned with online anonymity, disables HSTS as a result of this tracking potential. We present the CoStricTor protocol which crowdsources HSTS data among Tor Browser clients. It gives Tor Browser users increased resistance to man-in-the-middle attacks without exposing them to HSTS tracking. Our protocol adapts other privacy-preserving data aggregation algorithms to share data effectively among users with strong local differential privacy guarantees. The CoStricTor protocol resists denial of service attacks by design through our innovative use of Bloom filters to represent complementary data. Our simulations show our protocol can model up to 150,000 websites, providing 10,000 upgrades to HSTS for users

    Educating through Exemplars: Alternative Paths to Virtue

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    This paper confronts Zagzebski’s exemplarism with the intertwined debates over the conditions of exemplarity and the unity-disunity of the virtues, to show the advantages of a pluralistic exemplar-based approach to moral education (PEBAME). PEBAME is based on a prima facie disunitarist perspective in moral theory, which amounts to admitting both exemplarity in all respects and single-virtue exemplarity. First, we account for the advantages of PEBAME, and we show how two figures in recent Italian history (Giorgio Perlasca and Gino Bartali) satisfy Blum’s definitions of ‘moral hero’ and ‘moral saint’ (1988). Then, we offer a comparative analysis of the effectiveness of heroes and saints with respect to character education, according to four criteria derived from PEBAME: admirability, virtuousness, transparency, and imitability. Finally, we conclude that both unitarist and disunitarist exemplars are fundamental to character education; this is because of the hero's superiority to the saint with respect to imitability, a fundamental feature of the exemplar for character education

    Quantitative susceptibility mapping (QSM) and R2* of silent cerebral infarcts in sickle cell anemia

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    Silent cerebral infarction (SCI) is the most commonly reported radiological abnormality in patients with sickle cell anemia (SCA) and is associated with future clinical stroke risk. To date, there have been few histological and quantitative MRI studies of SCI and multiple radiological definitions exist. As a result, the tissue characteristics and composition of SCI remain elusive. The objective of this work was therefore to investigate the composition of segmented SCI lesions using quantitative MRI for R 2 * and quantitative magnetic susceptibility mapping (QSM). 211 SCI lesions were segmented from 32 participants with SCA and 6 controls. SCI were segmented according to two definitions (FLAIR+/-T1w-based threshold) using a semi-automated pipeline. Magnetic susceptibility (χ) and R 2 * maps were calculated from a multi-echo gradient echo sequence and mean SCI values were compared to an equivalent region of interest in normal appearing white matter (NAWM). SCI χ and R 2 * were investigated as a function of SCI definition, patient demographics, anatomical location, and cognition. Compared to NAWM, SCI were significantly less diamagnetic (χ = -0.0067 ppm vs. -0.0153 ppm, p < 0.001) and had significantly lower R 2 * (16.7 s-1 vs. 19.2 s-1, p < 0.001). SCI definition had a significant effect on the mean SCI χ and R 2 * , with lesions becoming significantly less diamagnetic and having significantly lower R 2 * after the application of a more stringent T1w-based threshold. SCI-NAWM R 2 * decrease was significantly greater in patients with SCA compared with controls (-2.84 s-1 vs. -0.64 s-1, p < 0.0001). No significant association was observed between mean SCI-NAWM χ or R2* differences and subject age, lesion anatomical location, or cognition. The increased χ and decreased R 2 * in SCI relative to NAWM observed in both patients and controls is indicative of lower myelin or increased water content within the segmented lesions. The significant SCI-NAWM R 2 * differences observed between SCI in patients with SCA and controls suggests there may be differences in tissue composition relative to NAWM in SCI in the two populations. Quantitative MRI techniques such as QSM and R 2 * mapping can be used to enhance our understanding of the pathophysiology and composition of SCI in patients with SCA as well as controls

    Nominal Henkin Semantics: simply-typed lambda-calculus models in nominal sets

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    We investigate a class of nominal algebraic Henkin-style models for the simply typed lambda-calculus in which variables map to names in the denotation and lambda-abstraction maps to a (non-functional) name-abstraction operation. The resulting denotations are smaller and better-behaved, in ways we make precise, than functional valuation-based models. Using these new models, we then develop a generalisation of \lambda-term syntax enriching them with existential meta-variables, thus yielding a theory of incomplete functions. This incompleteness is orthogonal to the usual notion of incompleteness given by function abstraction and application, and corresponds to holes and incomplete objects.Comment: In Proceedings LFMTP 2011, arXiv:1110.668

    A Comparison of MRI Quantitative Susceptibility Mapping and TRUST-Based Measures of Brain Venous Oxygen Saturation in Sickle Cell Anaemia

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    In recent years, interest has grown in the potential for magnetic resonance imaging (MRI) measures of venous oxygen saturation (Yv) to improve neurological risk prediction. T2-relaxation-under-spin-tagging (TRUST) is an MRI technique which has revealed changes in Yv in patients with sickle cell anemia (SCA). However, prior studies comparing Yv in patients with SCA relative to healthy controls have reported opposing results depending on whether the calibration model, developed to convert blood T2 to Yv, is based on healthy human hemoglobin (HbA), bovine hemoglobin (HbBV) or sickle hemoglobin (HbS). MRI Quantitative Susceptibility Mapping (QSM) is an alternative technique that may hold promise for estimating Yv in SCA as blood magnetic susceptibility is linearly dependent upon Yv, and no significant difference has been found between the magnetic susceptibility of HbA and HbS. Therefore, the aim of this study was to compare estimates of Yv using QSM and TRUST with five published calibration models in healthy controls and patients with SCA. 17 patients with SCA and 13 healthy controls underwent MRI. Susceptibility maps were calculated from a multi-parametric mapping acquisition and Yv was calculated from the mean susceptibility in a region of interest in the superior sagittal sinus. TRUST estimates of T2, within a similar but much smaller region, were converted to Yv using five different calibration models. Correlation and Bland-Altman analyses were performed to compare estimates of Yv between TRUST and QSM methods. For each method, t-tests were also used to explore group-wise differences between patients with SCA and healthy controls. In healthy controls, significant correlations were observed between QSM and TRUST measures of Yv, while in SCA, there were no such correlations. The magnitude and direction of group-wise differences in Yv varied with method. The TRUST-HbBV and QSM methods suggested decreased Yv in SCA relative to healthy controls, while the TRUST-HbS (p < 0.01) and TRUST-HbA models suggested increased Yv in SCA as in previous studies. Further validation of all MRI measures of Yv, relative to ground truth measures such as O15 PET and jugular vein catheterization, is required in SCA before QSM or TRUST methods can be considered for neurological risk prediction

    One Health Aotearoa: a transdisciplinary initiative to improve human, animal and environmental health in New Zealand

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    The following article, Harrison, S., Baker, M.G., Benschop, J. et al. One Health Outlook 2, 4 (2020), was published online by BMC on31 January 2020 at: https://doi.org/10.1186/s42522-020-0011-0. It is © The Author(s) 2020, but is Open Access and is distributedunder the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), whichpermits unrestricted use, distribution, and reproduction in any medium, provided that appropriate credit is given to the originalauthor(s) and the source, a link is provided to the Creative Commons license, and any changes are indicated. Permission to republishthe paper here has been obtained from the authors, and no changes have been made to the text

    Simulating regoliths in microgravity

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    Despite their very low surface gravities, the surfaces of asteroids and comets are covered by granular materials – regolith – that can range from a fine dust to a gravel-like structure of varying depths. Understanding the dynamics of granular materials is, therefore, vital for the interpretation of the surface geology of these small bodies and is also critical for the design and/or operations of any device planned to interact with their surfaces. We present the first measurements of transient weakening of granular material after shear reversal in microgravity as well as a summary of experimental results recently published in other journals, which may have important implications for small-body surfaces. Our results suggest that the force contact network within a granular material may be weaker in microgravity, although the influence of any change in the contact network is felt by the granular material over much larger distances. This could mean that small-body surfaces are even more unstable than previously imagined. However, our results also indicate that the consequences of, e.g., a meteorite impact or a spacecraft landing, may be very different depending on the impact angle and location, and depending on the prior history of the small-body surface

    Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective

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    BACKGROUND AND OBJECTIVES: Cognitive difficulties in people with sickle cell anemia (SCA) are related to lower processing speed index (PSI) and working memory index (WMI). However, risk factors are poorly understood so preventative strategies have not been explored. Brain volumes, specifically white matter volumes (WMV) which increases through early adulthood, have been associated with better cognition in healthy typically developing individuals. In patients with SCA, the reduced WMV and total subcortical volumes noted could explain cognitive deficits. We therefore examined developmental trajectories for regional brain volumes and cognitive endpoints in patients with SCA. METHODS: Data from two cohorts, the Sleep and Asthma Cohort and Prevention of Morbidity in SCA, were available. MRI data included T1-weighted axial images, pre-processed before regional volumes were extracted using Free-surfer. PSI and WMI from the Weschler scales of intelligence were used to test neurocognitive performance. Hemoglobin, oxygen saturation, hydroxyurea treatment and socioeconomic status from education deciles were available. RESULTS: One hundred and twenty nine patients (66 male) and 50 controls (21 male) aged 8-64 years were included. Brain volumes did not significantly differ between patients and controls. Compared with controls, PSI and WMI were significantly lower in patients with SCA, predicted by increasing age and male sex, with lower hemoglobin in the model for PSI but no effect of hydroxyurea treatment. In male patients with SCA only, WMV, age and socioeconomic status predicted PSI, while total subcortical volumes predicted WMI. Age positively and significantly predicted WMV in the whole group (patients + controls). There was a trend for age to negatively predict PSI in the whole group. For total subcortical volume and WMI, age predicted decrease only in the patient group. Developmental trajectory analysis revealed that PSI only was significantly delayed in patients at 8 years of age; the rate of development for the cognitive and brain volume data did not differ significantly from controls. DISCUSSION: Increasing age and male sex negatively impact cognition in SCA, with processing speed, also predicted by hemoglobin, delayed by mid childhood. Associations with brain volumes were seen in males with SCA. Brain endpoints, calibrated against large control datasets, should be considered for randomized treatment trials

    Biochemical analysis of TssK, a core component of the bacterial Type VI secretion system, reveals distinct oligomeric states of TssK and identifies a TssK–TssFG subcomplex

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    Gram-negative bacteria use the Type VI secretion system (T6SS) to inject toxic proteins into rival bacteria or eukaryotic cells. However, the mechanism of the T6SS is incompletely understood. In the present study, we investigated a conserved component of the T6SS, TssK, using the antibacterial T6SS of Serratia marcescens as a model system. TssK was confirmed to be essential for effector secretion by the T6SS. The native protein, although not an integral membrane protein, appeared to localize to the inner membrane, consistent with its presence within a membrane-anchored assembly. Recombinant TssK purified from S. marcescens was found to exist in several stable oligomeric forms, namely trimer, hexamer and higher-order species. Native-level purification of TssK identified TssF and TssG as interacting proteins. TssF and TssG, conserved T6SS components of unknown function, were required for T6SS activity, but not for correct localization of TssK. A complex containing TssK, TssF and TssG was subsequently purified in vitro, confirming that these three proteins form a new subcomplex within the T6SS. Our findings provide new insight into the T6SS assembly, allowing us to propose a model whereby TssK recruits TssFG into the membrane-associated T6SS complex and different oligomeric states of TssK may contribute to the dynamic mechanism of the system
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