MGHyper: Checking Satisfiability of HyperLTL Formulas Beyond the ∃∗∀∗\exists^*\forall^* Fragment

Hyperproperties are properties that refer to multiple computation traces. This includes many information-flow security policies, such as observational determinism, (generalized) noninterference, and noninference, and other system properties like symmetry or Hamming distances between in error-resistant codes. We introduce MGHyper, a tool for automatic satisfiability checking and model generation for hyperproperties expressed in HyperLTL. Unlike previous satisfiability checkers, MGHyper is not limited to the decidable $\exists^* \forall^*$ fragment of HyperLTL, but provides a semi-decisionprocedure for the full logic. An important application of MGHyper is to automatically check equivalences between different hyperproperties (and different formalizations of the same hyperproperty) and to build counterexamples that disprove a certain claimed implication. We describe the semi-decisionprocedure implemented in MGHyper and report on experimental results obtained both with typical hyperproperties from the literature and with randomly generated HyperLTL formulas

Neuromuscular, endocrine, and perceptual fatigue responses during different length between-match microcycles in professional rugby league players

The purpose of this study was to examine the changes in neuromuscular, perceptual and hormonal measures following professional rugby league matches during different length between-match microcycles. Methods: Twelve professional rugby league players from the same team were assessed for changes in countermovement jump (CMJ) performance (flight time and relative power), perceptual responses (fatigue, well-being and muscle soreness) and salivary hormone (testosterone [T] and cortisol [C]) levels during 5, 7 and 9 d between-match training microcycles. All training was prescribed by the club coaches and was monitored using the session-RPE method. Results: Lower mean daily training load was completed on the 5 d compared with the 7 and 9 d microcycles. CMJ flight time and relative power, perception of fatigue, overall well-being and muscle soreness were significantly reduced in the 48 h following the match in each microcycle (P < .05). Most CMJ variables returned to near baseline values following 4 d in each microcycle. Countermovement jump relative power was lower in the 7 d microcycle in comparison with the 9 d microcycle (P < .05). There was increased fatigue at 48 h in the 7 and 9 d microcycles (P < .05) but had returned to baseline in the 5 d microcycle. Salivary T and C did not change in response to the match. Discussion: Neuromuscular performance and perception of fatigue are reduced for at least 48 h following a rugby league match but can be recovered to baseline levels within 4 d. These findings show that with appropriate training, it is possible to recover neuromuscular and perceptual measures within 4 d after a rugby league match. © Human Kinetics, Inc

Constraint-Based Monitoring of Hyperproperties

Verifying hyperproperties at runtime is a challenging problem as hyperproperties, such as non-interference and observational determinism, relate multiple computation traces with each other. It is necessary to store previously seen traces, because every new incoming trace needs to be compatible with every run of the system observed so far. Furthermore, the new incoming trace poses requirements on future traces. In our monitoring approach, we focus on those requirements by rewriting a hyperproperty in the temporal logic HyperLTL to a Boolean constraint system. A hyperproperty is then violated by multiple runs of the system if the constraint system becomes unsatisfiable. We compare our implementation, which utilizes either BDDs or a SAT solver to store and evaluate constraints, to the automata-based monitoring tool RVHyper

Genetic Economy in Picornaviruses: Foot-and-Mouth Disease Virus Replication Exploits Alternative Precursor Cleavage Pathways

The RNA genomes of picornaviruses are translated into single polyproteins which are subsequently cleaved into structural and non-structural protein products. For genetic economy, proteins and processing intermediates have evolved to perform distinct functions. The picornavirus precursor protein, P3, is cleaved to produce membrane-associated 3A, primer peptide 3B, protease 3Cpro and polymerase 3Dpol. Uniquely, foot-and-mouth disease virus (FMDV) encodes three similar copies of 3B (3B1-3), thus providing a convenient natural system to explore the role(s) of 3B in the processing cascade. Using a replicon system, we confirmed by genetic deletion or functional inactivation that each copy of 3B appears to function independently to prime FMDV RNA replication. However, we also show that deletion of 3B3 prevents replication and that this could be reversed by introducing mutations at the C-terminus of 3B2 that restored the natural sequence at the 3B3-3C cleavage site. In vitro translation studies showed that precursors with 3B3 deleted were rapidly cleaved to produce 3CD but that no polymerase, 3Dpol, was detected. Complementation assays, using distinguishable replicons bearing different inactivating mutations, showed that replicons with mutations within 3Dpol could be recovered by 3Dpol derived from “helper” replicons (incorporating inactivation mutations in all three copies of 3B). However, complementation was not observed when the natural 3B-3C cleavage site was altered in the “helper” replicon, again suggesting that a processing abnormality at this position prevented the production of 3Dpol. When mutations affecting polyprotein processing were introduced into an infectious clone, viable viruses were recovered but these had acquired compensatory mutations in the 3B-3C cleavage site. These mutations were shown to restore the wild-type processing characteristics when analysed in an in vitro processing assay. Overall, this study demonstrates a dual functional role of the small primer peptide 3B3, further highlighting how picornaviruses increase genetic economy

Generation and quality control of lipidomics data for the alzheimers disease neuroimaging initiative cohort.

Alzheimers disease (AD) is a major public health priority with a large socioeconomic burden and complex etiology. The Alzheimer Disease Metabolomics Consortium (ADMC) and the Alzheimer Disease Neuroimaging Initiative (ADNI) aim to gain new biological insights in the disease etiology. We report here an untargeted lipidomics of serum specimens of 806 subjects within the ADNI1 cohort (188 AD, 392 mild cognitive impairment and 226 cognitively normal subjects) along with 83 quality control samples. Lipids were detected and measured using an ultra-high-performance liquid chromatography quadruple/time-of-flight mass spectrometry (UHPLC-QTOF MS) instrument operated in both negative and positive electrospray ionization modes. The dataset includes a total 513 unique lipid species out of which 341 are known lipids. For over 95% of the detected lipids, a relative standard deviation of better than 20% was achieved in the quality control samples, indicating high technical reproducibility. Association modeling of this dataset and available clinical, metabolomics and drug-use data will provide novel insights into the AD etiology. These datasets are available at the ADNI repository at http://adni.loni.usc.edu/

Acculturation and risk of traffic crashes in young Asian-born Australian drivers

The study examines changes over time in crash risk differences between young Australian drivers born in Asia and those born in Australia. Data from the 2003 baseline survey of the DRIVE cohort of 20 806 young drivers aged 17-24 years were linked to police, hospital and death data up until 2016. The association between country of birth and crash was investigated using flexible parametric survival models adjusted for confounders. Six months after baseline, the crash risk in Asian-born drivers was less than half that of their Australian-born counterparts (mean HR, MHR 0.41; 95% CI 0.29 to 0.57), only to increase steadily over time to resemble that of Australian-born drivers 13 years later (MHR 0.94; 95% CI 0.66 to 1.36). This is likely to be associated with acculturation and the adoption by young Asian-born Australian drivers of driving behaviour patterns akin to those born locally. This needs to be considered in future road safety campaigns

The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

Transformation of the rodent malaria parasite Plasmodium chabaudi and generation of a stable fluorescent line PcGFPCON

<p>Abstract</p> <p>Background</p> <p>The rodent malaria parasite <it>Plasmodium chabaudi </it>has proven of great value in the analysis of fundamental aspects of host-parasite-vector interactions implicated in disease pathology and parasite evolutionary ecology. However, the lack of gene modification technologies for this model has precluded more direct functional studies.</p> <p>Methods</p> <p>The development of <it>in vitro </it>culture methods to yield <it>P. chabaudi </it>schizonts for transfection and conditions for genetic modification of this rodent malaria model are reported.</p> <p>Results</p> <p>Independent <it>P. chabaudi </it>gene-integrant lines that constitutively express high levels of green fluorescent protein throughout their life cycle have been generated.</p> <p>Conclusion</p> <p>Genetic modification of <it>P. chabaudi </it>is now possible. The production of genetically distinct reference lines offers substantial advances to our understanding of malaria parasite biology, especially interactions with the immune system during chronic infection.</p

Five-Brane Superpotentials, Blow-Up Geometries and SU(3) Structure Manifolds

We investigate the dynamics of space-time filling five-branes wrapped on curves in heterotic and orientifold Calabi-Yau compactifications. We first study the leading N=1 scalar potential on the infinite deformation space of the brane-curve around a supersymmetric configuration. The higher order potential is also determined by a brane superpotential which we compute for a subset of light deformations. We argue that these deformations map to new complex structure deformations of a non-Calabi-Yau manifold which is obtained by blowing up the brane-curve into a four-cycle and by replacing the brane by background fluxes. This translates the original brane-bulk system into a unifying geometrical formulation. Using this blow-up geometry we compute the complete set of open-closed Picard-Fuchs differential equations and identify the brane superpotential at special points in the field space for five-branes in toric Calabi-Yau hypersurfaces. This has an interpretation in open mirror symmetry and enables us to list compact disk instanton invariants. As a first step towards promoting the blow-up geometry to a supersymmetric heterotic background we propose a non-Kaehler SU(3) structure and an identification of the three-form flux.Comment: 95 pages, 4 figures; v2: Minor corrections, references update

Sodium and Health: Old Myths and a Controversy Based on Denial

Purpose of Review The scientific consensus on which global health organizations base public health policies is that high sodium intake increases blood pressure (BP) in a linear fashion contributing to cardiovascular disease (CVD). A moderate reduction in sodium intake to 2000 mg per day helps ensure that BP remains at a healthy level to reduce the burden of CVD. Recent Findings Yet, since as long ago as 1988, and more recently in eight articles published in the European Heart Journal in 2020 and 2021, some researchers have propagated a myth that reducing sodium does not consistently reduce CVD but rather that lower sodium might increase the risk of CVD. These claims are not well-founded and support some food and beverage industry’s vested interests in the use of excessive amounts of salt to preserve food, enhance taste, and increase thirst. Nevertheless, some researchers, often with funding from the food industry, continue to publish such claims without addressing the numerous objections. This article analyzes the eight articles as a case study, summarizes misleading claims, their objections, and it offers possible reasons for such claims. Summary Our study calls upon journal editors to ensure that unfounded claims about sodium intake be rigorously challenged by independent reviewers before publication; to avoid editorial writers who have been co-authors with the subject paper’s authors; to require statements of conflict of interest; and to ensure that their pages are used only by those who seek to advance knowledge by engaging in the scientific method and its collegial pursuit. The public interest in the prevention and treatment of disease requires no less