Promoting International Cybersecurity Cooperation: Lessons from the Proliferation Security Initiative (PSI)

Global efforts by states to cooperate through international rules in combating cyber threats have generated mixed results, at best. In this paper, we examine the architecture of the Proliferation Security Initiative (PSI) as a possible model for future cybersecurity cooperation among interested states. We identify several features of PSI\u27s architecture (rather than its substantive focus on non-proliferation) for further analysis, including PSI\u27s low entry costs, tiered structure, and flexibility, as well as its leveraging of both territorial jurisdiction and state consent. We conclude that, despite several hurdles visible in the scope of its membership and its legal framework, the PSI still offers worth-while parallels to draw upon, suggesting a new framework that could allow interested states to further cooperate in addressing current cyberthreats.

Concordance of copy number abnormality detection using SNP arrays and Multiplex Ligation-dependent Probe Amplification (MLPA) in acute lymphoblastic leukaemia

In acute lymphoblastic leukaemia, MLPA has been used in research studies to identify clinically relevant copy number abnormality (CNA) profiles. However, in diagnostic settings other techniques are often employed. We assess whether equivalent CNA profiles are called using SNP arrays, ensuring platform independence. We demonstrate concordance between SNP6.0 and MLPA CNA calling on 143 leukaemia samples from two UK trials; comparing 1,287 calls within eight genes and a region. The techniques are 99% concordant using manually augmented calling, and 98% concordant using an automated pipeline. We classify these discordant calls and examine reasons for discordance. In nine cases the circular binary segmentation (CBS) algorithm failed to detect focal abnormalities or those flanking gaps in IKZF1 probe coverage. Eight cases were discordant due to probe design differences, with focal abnormalities detectable using one technique not observable by the other. Risk classification using manually augmented array calling resulted in four out of 143 patients being assigned to a different CNA risk group and eight patients using the automated pipeline. We conclude that MLPA defined CNA profiles can be accurately mirrored by SNP6.0 or similar array platforms. Automated calling using the CBS algorithm proved successful, except for IKZF1 which should be manually inspected

MRI Sequence Influences Geometrical Information of Osseous Tissues

Although CT-scan data gives accurate geometrical information of bones, MRI data is commonly used instead due to its non-ionizing nature. The geometrical information has a number of applications, including image registration and computer simulations of the human joints, presurgical planning, prosthesis design, linking geometry with function and pain and kinematics. Hence, it is important to for the geometrical information extracted from the MRI data to be accurate. However, this information is influenced by the choice of the MRI sequence. Therefore, the aim of this study is to investigate the effect of different MRI sequences on the accuracy of geometrical information of bones

Turbulent Aeroheating Measurements on a 7-deg Half-Angle Sphere-Cone in a High-Enthalpy CO2 Expansion Tunnel

A database of heating and pressure measurements on a 7-deg half-angle cone in a highenthalpy expansion tunnel in CO2 has been generated to support development and validation of computational models to be employed in the design of future Mars missions. Laminar, transitional, and turbulent simulations were performed at the test conditions for comparisons with the data. Close agreement was obtained for both fully-laminar and fully turbulent conditions. For the remaining transitional/turbulent conditions, agreement to within, or slightly more than, the estimated experimental uncertainty was demonstrated. The influence of transition intermittency and transition length models on predicted heating levels was demonstrated, as were differences in turbulent heating predictions generated using various algebraic, one-equation, and two-equation turbulence models. These comparisons provide some measure of confidence in turbulent simulation capabilities; however, because the data were not obtained on a relevant entry vehicle geometry, it is not possible to fully quantify computational uncertainties for the definition of Mars mission aerothermodynamic environments at this tim

Searching for the Kuhnian moment : the Black-Scholes-Merton formula and the evolution of modern finance theory

The Black-Scholes-Merton formula has been put to widespread use by options traders because it provides a means of calculating the theoretically 'correct' price of stock options. Traders can therefore see whether the market price of stock options undervalues or overvalues them compared with their hypothetical Black-Scholes-Merton price, before choosing to buy or sell options accordingly. As a consequence of this close relationship between options pricing theory and options pricing practice, a strong performativity loop was activated, whereby market prices quickly converged on the hypothetical Black-Scholes-Merton prices following the dissemination of the formula. The theory has therefore had significant real-world effects, but how should we characterize the initial instinct to derive the theory from a philosophy of science perspective? The two books under review suggest that a Kuhnian reading of the advancement of scientific knowledge might well be the most appropriate. But, on closer inspection, it becomes clear that the publication of the Black-Scholes-Merton formula should not be seen as a Kuhnian moment with paradigm-shaping attributes. It is shown that, at most, the formula acts as an important exemplar which, via its use in the training of options pricing theorists and options pricing practitioners, reinforces the entrenchment of finance theory within the orthodox economics worldview

Sexual selection protects against extinction

Reproduction through sex carries substantial costs, mainly because only half of sexual adults produce offspring. It has been theorised that these costs could be countered if sex allows sexual selection to clear the universal fitness constraint of mutation load. Under sexual selection, competition between (usually) males, and mate choice by (usually) females create important intraspecific filters for reproductive success, so that only a subset of males gains paternity. If reproductive success under sexual selection is dependent on individual condition, which depends on mutation load, then sexually selected filtering through ‘genic capture’ could offset the costs of sex because it provides genetic benefits to populations. Here, we test this theory experimentally by comparing whether populations with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. After evolving replicate populations of the flour beetle Tribolium castaneum for ~7 years under conditions that differed solely in the strengths of sexual selection, we revealed mutation load using inbreeding. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness under inbreeding, with some families continuing to survive after 20 generations of sib × sib mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after generation 10. Multiple mutations across the genome with individually small effects can be difficult to clear, yet sum to a significant fitness load; our findings reveal that sexual selection reduces this load, improving population viability in the face of genetic stress

Acceptability of Aggression Among Children Who Reside With Substance-Abusing Parents: The Influence of Behavioral Dysregulation, Exposure to Neighborhood Violence, and Interparental Violence

The present study examined how interparental violence, neighborhood violence, behavioral regulation during parental conflict, and age predicted beliefs about the acceptability of aggression and the acceptance of retaliation against an aggressive peer among youths. Participants were 110 families (mothers, fathers, and children) in which one or both parents met criteria for substance use disorder. Results of a bootstrapped multivariate regression model revealed higher exposure to neighborhood violence predicted greater acceptability of general aggression, whereas higher father-to-mother violence perpetration predicted lower acceptability of general aggression. Higher exposure to neighborhood violence, behavioral dysregulation during parental conflict, and older child age predicted greater approval of retaliation toward an aggressive peer. Findings are interpreted as related to the cognitive-contextual framework

Benchmark Evaluation of True Single Molecular Sequencing to Determine Cystic Fibrosis Airway Microbiome Diversity

Cystic fibrosis (CF) is an autosomal recessive disease associated with recurrent lung infections that can lead to morbidity and mortality. The impact of antibiotics for treatment of acute pulmonary exacerbations on the CF airway microbiome remains unclear with prior studies giving conflicting results and being limited by their use of 16S ribosomal RNA sequencing. Our primary objective was to validate the use of true single molecular sequencing (tSMS) and PathoScope in the analysis of the CF airway microbiome. Three control samples were created with differing amounts of Burkholderia cepacia, Pseudomonas aeruginosa, and Prevotella melaninogenica, three common bacteria found in cystic fibrosis lungs. Paired sputa were also obtained from three study participants with CF before and \u3e6 days after initiation of antibiotics. Antibiotic resistant B. cepacia and P. aeruginosa were identified in concurrently obtained respiratory cultures. Direct sequencing was performed using tSMS, and filtered reads were aligned to reference genomes from NCBI using PathoScope and Kraken and unique clade-specific marker genes using MetaPhlAn. A total of 180-518K of 6-12 million filtered reads were aligned for each sample. Detection of known pathogens in control samples was most successful using PathoScope. In the CF sputa, alpha diversity measures varied based on the alignment method used, but similar trends were found between pre- and post-antibiotic samples. PathoScope outperformed Kraken and MetaPhlAn in our validation study of artificial bacterial community controls and also has advantages over Kraken and MetaPhlAn of being able to determine bacterial strains and the presence of fungal organisms. PathoScope can be confidently used when evaluating metagenomic data to determine CF airway microbiome diversity