Existential Types for Relaxed Noninterference

Information-flow security type systems ensure confidentiality by enforcing noninterference: a program cannot leak private data to public channels. However, in practice, programs need to selectively declassify information about private data. Several approaches have provided a notion of relaxed noninterference supporting selective and expressive declassification while retaining a formal security property. The labels-as-functions approach provides relaxed noninterference by means of declassification policies expressed as functions. The labels-as-types approach expresses declassification policies using type abstraction and faceted types, a pair of types representing the secret and public facets of values. The original proposal of labels-as-types is formulated in an object-oriented setting where type abstraction is realized by subtyping. The object-oriented approach however suffers from limitations due to its receiver-centric paradigm. In this work, we consider an alternative approach to labels-as-types, applicable in non-object-oriented languages, which allows us to express advanced declassification policies, such as extrinsic policies, based on a different form of type abstraction: existential types. An existential type exposes abstract types and operations on these; we leverage this abstraction mechanism to express secrets that can be declassified using the provided operations. We formalize the approach in a core functional calculus with existential types, define existential relaxed noninterference, and prove that well-typed programs satisfy this form of type-based relaxed noninterference

T2 and T2⁎ mapping and weighted imaging in cardiac MRI

Cardiac imaging is progressing from simple imaging of heart structure and function to techniques visualizing and measuring underlying tissue biological changes that can potentially define disease and therapeutic options. These techniques exploit underlying tissue magnetic relaxation times: T1, T2 and T2*. Initial weighting methods showed myocardial heterogeneity, detecting regional disease. Current methods are now fully quantitative generating intuitive color maps that do not only expose regionality, but also diffuse changes – meaning that between-scan comparisons can be made to define disease (compared to normal) and to monitor interval change (compared to old scans). T1 is now familiar and used clinically in multiple scenarios, yet some technical challenges remain. T2 is elevated with increased tissue water – edema. Should there also be blood troponin elevation, this edema likely reflects inflammation, a key biological process. T2* falls in the presence of magnetic/paramagnetic materials – practically, this means it measures tissue iron, either after myocardial hemorrhage or in myocardial iron overload. This review discusses how T2 and T2⁎ imaging work (underlying physics, innovations, dependencies, performance), current and emerging use cases, quality assurance processes for global delivery and future research directions

Cytonuclear introgressive swamping and species turnover of bass after an introduction

Species-specific RFLP markers from mitochondrial DNA (mtDNA) were identified and employed in conjunction with previously reported data for nuclear allozyme markers to examine the genetic consequences of an artificial introduction of spotted bass (Micropterus punctulatus) into a north Georgia reservoir originally occupied by native small mouth bass (M. dolomieui). The cytonuclear genetic data indicate that within 10-15 years following the unauthorized introduction, a reversal in these species' abundances has occurred and that more than 99% of the population sample analyzed here consists of spotted bass or products of interspecific hybridization. This demographic shift, perhaps ecologically or environmentally mediated, has been accompanied by introgressive swamping; more than 95% of the remaining small mouth bass nuclear and cytoplasmic alleles are present in individuals of hybrid ancestry. Dilocus cytonuclear disequilibria were significantly different from zero, with patterns indicative of an excess of homospecific genetic combinations (relative to expectations from single-locus allelic frequencies) and a disproportionate contribution of small mouth bass mothers to the hybrid gene pool. Results document dramatic genetic and demographic changes following the human-mediated introduction of a nonnative species

Aerosol size distribution and radiative forcing response to anthropogenically driven historical changes in biogenic secondary organic aerosol formation

Emissions of biogenic volatile organic compounds (BVOCs) have changed in the past millennium due to changes in land use, temperature, and CO2 concentrations. Recent reconstructions of BVOC emissions have predicted that global isoprene emissions have decreased, while monoterpene and sesquiterpene emissions have increased; however, all three show regional variability due to competition between the various influencing factors. In this work, we use two modeled estimates of BVOC emissions from the years 1000 to 2000 to test the effect of anthropogenic changes to BVOC emissions on secondary organic aerosol (SOA) formation, global aerosol size distributions, and radiative effects using the GEOS-Chem-TOMAS (Goddard Earth Observing System; TwO-Moment Aerosol Sectional) global aerosol microphysics model. With anthropogenic emissions (e.g., SO2, NOx, primary aerosols) turned off and BVOC emissions changed from year 1000 to year 2000 values, decreases in the number concentration of particles of size Dp > 80 nm (N80) of > 25% in year 2000 relative to year 1000 were predicted in regions with extensive land-use changes since year 1000 which led to regional increases in the combined aerosol radiative effect (direct and indirect) of > 0.5 W m−2 in these regions. We test the sensitivity of our results to BVOC emissions inventory, SOA yields, and the presence of anthropogenic emissions; however, the qualitative response of the model to historic BVOC changes remains the same in all cases. Accounting for these uncertainties, we estimate millennial changes in BVOC emissions cause a global mean direct effect of between +0.022 and +0.163 W m−2 and the global mean cloud-albedo aerosol indirect effect of between −0.008 and −0.056 W m−2. This change in aerosols, and the associated radiative forcing, could be a largely overlooked and important anthropogenic aerosol effect on regional climates

Seasonlity of Kawasaki Disease: A global perspective

The authors are for the Kawasaki Disease Global Climate ConsortiumBACKGROUND: Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. METHODS: Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. RESULTS: A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. CONCLUSION: Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter months in the Northern Hemisphere extra-tropics.published_or_final_versio

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD

Involvement of a Nonstructural Protein in Poliovirus Capsid Assembly

Virus capsid proteins must perform a number of roles. These include the ability to self–assemble and to maintain stability under challenging environmental conditions, while retaining the conformational flexibility necessary to uncoat and deliver the viral genome into a host cell. Fulfilling these roles could place conflicting constraints on the innate abilities encoded within the protein sequences. In a previous study, we identified a number of mutations within the capsid coding sequence of poliovirus (PV) that were established in the population during selection for greater thermostability by sequential treatment at progressively higher temperatures. Two mutations in the VP1 protein acquired at an early stage were maintained throughout this selection procedure. One of these mutations prevented virion assembly when introduced into a wild type (wt) infectious clone. Here, we show by sequencing beyond the capsid coding region of the heat selected virions, that two mutations had arisen within the coding region for the 2A protease. Both mutations were maintained throughout the selection process. Introduction of these mutations into a wt infectious clone by site-directed mutagenesis considerably reduced replication. However, they permitted a low level of assembly of infectious virions containing the otherwise lethal mutation in VP1. The 2Apro mutations were further shown to slow the kinetics of viral polyprotein processing and we suggest that this delay improves the correct folding of the mutant capsid precursor protein to permit virion assembly

Comparison of embedded and added motor imagery training in patients after stroke: Results of a randomised controlled pilot trial

Copyright @ 2012 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Motor imagery (MI) when combined with physiotherapy can offer functional benefits after stroke. Two MI integration strategies exist: added and embedded MI. Both approaches were compared when learning a complex motor task (MT): ‘Going down, laying on the floor, and getting up again’. Methods: Outpatients after first stroke participated in a single-blinded, randomised controlled trial with MI embedded into physiotherapy (EG1), MI added to physiotherapy (EG2), and a control group (CG). All groups participated in six physiotherapy sessions. Primary study outcome was time (sec) to perform the motor task at pre and post-intervention. Secondary outcomes: level of help needed, stages of MT-completion, independence, balance, fear of falling (FOF), MI ability. Data were collected four times: twice during one week baseline phase (BL, T0), following the two week intervention (T1), after a two week follow-up (FU). Analysis of variance was performed. Results: Thirty nine outpatients were included (12 females, age: 63.4 ± 10 years; time since stroke: 3.5 ± 2 years; 29 with an ischemic event). All were able to complete the motor task using the standardised 7-step procedure and reduced FOF at T0, T1, and FU. Times to perform the MT at baseline were 44.2 ± 22s, 64.6 ± 50s, and 118.3 ± 93s for EG1 (N = 13), EG2 (N = 12), and CG (N = 14). All groups showed significant improvement in time to complete the MT (p < 0.001) and degree of help needed to perform the task: minimal assistance to supervision (CG) and independent performance (EG1+2). No between group differences were found. Only EG1 demonstrated changes in MI ability over time with the visual indicator increasing from T0 to T1 and decreasing from T1 to FU. The kinaesthetic indicator increased from T1 to FU. Patients indicated to value the MI training and continued using MI for other difficult-to-perform tasks. Conclusions: Embedded or added MI training combined with physiotherapy seem to be feasible and benefi-cial to learn the MT with emphasis on getting up independently. Based on their baseline level CG had the highest potential to improve outcomes. A patient study with 35 patients per group could give a conclusive answer of a superior MI integration strategy.The research project was partially funded by the Gottfried und Julia Bangerter-Rhyner Foundation

Reanalysis of cancer mortality in Japanese A-bomb survivors exposed to low doses of radiation: bootstrap and simulation methods

<p>Abstract</p> <p>Background</p> <p>The International Commission on Radiological Protection (ICRP) recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model.</p> <p>Methods</p> <p>Cancers with over 100 deaths in the 0 - 20 mSv subcohort of the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa) methods and simulation of the Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR) and tests against the linear model.</p> <p>Results</p> <p>The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 - 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years), liver (36.9), lung (13.6), leukaemia (23.66), and pancreas (11.86) and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose) are obtained from the 0 - 20 mSv and 5 - 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 - 500 mSv range.</p> <p>Conclusion</p> <p>Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response. A non-linear model is strongly superior for the stomach, liver, lung, pancreas and leukaemia. Bootstrap and Likelihood-based confidence intervals are broadly comparable and ERR is strictly positive by bootstrap methods for all 5 cancers. Except for the pancreas, similar estimates of latency and risk from 10 mSv are obtained from the 0 - 20 mSv and 5 - 500 mSv subcohorts. Large and significant cancer risks for Japanese survivors exposed to less than 20 mSv external radiation from the atomic bombs in 1945 cast doubt on the ICRP recommended annual occupational dose limit.</p