On defining the Hamiltonian beyond quantum theory

Energy is a crucial concept within classical and quantum physics. An essential tool to quantify energy is the Hamiltonian. Here, we consider how to define a Hamiltonian in general probabilistic theories, a framework in which quantum theory is a special case. We list desiderata which the definition should meet. For 3-dimensional systems, we provide a fully-defined recipe which satisfies these desiderata. We discuss the higher dimensional case where some freedom of choice is left remaining. We apply the definition to example toy theories, and discuss how the quantum notion of time evolution as a phase between energy eigenstates generalises to other theories.Comment: Authors' accepted manuscript for inclusion in the Foundations of Physics topical collection on Foundational Aspects of Quantum Informatio

POD for optimal control of the Cahn-Hilliard system using spatially adapted snapshots

The present work considers the optimal control of a convective Cahn-Hilliard system, where the control enters through the velocity in the transport term. We prove the existence of a solution to the considered optimal control problem. For an efficient numerical solution, the expensive high-dimensional PDE systems are replaced by reduced-order models utilizing proper orthogonal decomposition (POD-ROM). The POD modes are computed from snapshots which are solutions of the governing equations which are discretized utilizing adaptive finite elements. The numerical tests show that the use of POD-ROM combined with spatially adapted snapshots leads to large speedup factors compared with a high-fidelity finite element optimization

Mediating punitiveness: understanding public attitudes towards work-related fatality cases

This paper concerns an empirical investigation into public attitudes towards work-related fatality cases, where organizational offenders cause the death of workers or members of the public. This issue is particularly relevant following the introduction of the Corporate Manslaughter and Corporate Homicide Act 2007 into UK law. Here, as elsewhere, the use of criminal law against companies reflects governmental concerns over public confidence in the law’s ability to regulate risk. The empirical findings demonstrate that high levels of public concern over these cases do not translate into punitive attitudes. Such cases are viewed rationally and constructively, and lead to instrumental rather than purely expressive enforcement preferences

SoK: Making Sense of Censorship Resistance Systems

An increasing number of countries implement Internet censorship at different scales and for a variety of reasons. Several censorship resistance systems (CRSs) have emerged to help bypass such blocks. The diversity of the censor’s attack landscape has led to an arms race, leading to a dramatic speed of evolution of CRSs. The inherent complexity of CRSs and the breadth of work in this area makes it hard to contextualize the censor’s capabilities and censorship resistance strategies. To address these challenges, we conducted a comprehensive survey of CRSs-deployed tools as well as those discussed in academic literature-to systematize censorship resistance systems by their threat model and corresponding defenses. To this end, we first sketch a comprehensive attack model to set out the censor’s capabilities, coupled with discussion on the scope of censorship, and the dynamics that influence the censor’s decision. Next, we present an evaluation framework to systematize censorship resistance systems by their security, privacy, performance and deployability properties, and show how these systems map to the attack model. We do this for each of the functional phases that we identify for censorship resistance systems: communication establishment, which involves distribution and retrieval of information necessary for a client to join the censorship resistance system; and conversation, where actual exchange of information takes place. Our evaluation leads us to identify gaps in the literature, question the assumptions at play, and explore possible mitigations

Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases.

The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated α-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated α-synuclein in SNCA gene multiplication or aggregated β-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death. These 3 conceptual frameworks of protein aggregation (pathogenic, epiphenomenon, protective) are difficult to resolve because of the inability to probe brain tissue in real time. Whereas animal models, in which neither PD nor AD occur in natural states, consistently support a pathogenic role of protein aggregation, indirect evidence from human studies does not. We hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress. Future precision medicine efforts for molecular targeting of neurodegenerative diseases may require analyses not anchored on current clinicopathologic criteria but instead on biological signals generated from large deeply phenotyped aging populations or from smaller but well-defined genetic-molecular cohorts

Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population

Background Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry. Methods We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects. Results The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 – 1.56, p = 1.96 × 10-3). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p ≤ 1.04 × 10-7). Conclusion Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups

A runaway collision in a young star cluster as the origin of the brightest supernova

Supernova 2006gy in the galaxy NGC 1260 is the most luminous one recorded \cite{2006CBET..644....1Q, 2006CBET..647....1H, 2006CBET..648....1P, 2006CBET..695....1F}. Its progenitor might have been a very massive ($>100$ \msun) star \cite{2006astro.ph.12617S}, but that is incompatible with hydrogen in the spectrum of the supernova, because stars $>40$ \msun are believed to have shed their hydrogen envelopes several hundred thousand years before the explosion \cite{2005A&A...429..581M}. Alternatively, the progenitor might have arisen from the merger of two massive stars \cite{2007ApJ...659L..13O}. Here we show that the collision frequency of massive stars in a dense and young cluster (of the kind to be expected near the center of a galaxy) is sufficient to provide a reasonable chance that SN 2006gy resulted from such a bombardment. If this is the correct explanation, then we predict that when the supernova fades (in a year or so) a dense cluster of massive stars becomes visible at the site of the explosion

Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

The association between green space and cause-specific mortality in urban New Zealand: an ecological analysis of green space utility

<b>Background:</b> There is mounting international evidence that exposure to green environments is associated with health benefits, including lower mortality rates. Consequently, it has been suggested that the uneven distribution of such environments may contribute to health inequalities. Possible causative mechanisms behind the green space and health relationship include the provision of physical activity opportunities, facilitation of social contact and the restorative effects of nature. In the New Zealand context we investigated whether there was a socioeconomic gradient in green space exposure and whether green space exposure was associated with cause-specific mortality (cardiovascular disease and lung cancer). We subsequently asked what is the mechanism(s) by which green space availability may influence mortality outcomes, by contrasting health associations for different types of green space. <b>Methods:</b> This was an observational study on a population of 1,546,405 living in 1009 small urban areas in New Zealand. A neighbourhood-level classification was developed to distinguish between usable (i.e., visitable) and non-usable green space (i.e., visible but not visitable) in the urban areas. Negative binomial regression models were fitted to examine the association between quartiles of area-level green space availability and risk of mortality from cardiovascular disease (n = 9,484; 1996 - 2005) and from lung cancer (n = 2,603; 1996 - 2005), after control for age, sex, socio-economic deprivation, smoking, air pollution and population density. <b>Results:</b> Deprived neighbourhoods were relatively disadvantaged in total green space availability (11% less total green space for a one standard deviation increase in NZDep2001 deprivation score, p < 0.001), but had marginally more usable green space (2% more for a one standard deviation increase in deprivation score, p = 0.002). No significant associations between usable or total green space and mortality were observed after adjustment for confounders. <b>Conclusion</b> Contrary to expectations we found no evidence that green space influenced cardiovascular disease mortality in New Zealand, suggesting that green space and health relationships may vary according to national, societal or environmental context. Hence we were unable to infer the mechanism in the relationship. Our inability to adjust for individual-level factors with a significant influence on cardiovascular disease and lung cancer mortality risk (e.g., diet and alcohol consumption) will have limited the ability of the analyses to detect green space effects, if present. Additionally, green space variation may have lesser relevance for health in New Zealand because green space is generally more abundant and there is less social and spatial variation in its availability than found in other contexts

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts