LittleDarwin: a Feature-Rich and Extensible Mutation Testing Framework for Large and Complex Java Systems

Mutation testing is a well-studied method for increasing the quality of a test suite. We designed LittleDarwin as a mutation testing framework able to cope with large and complex Java software systems, while still being easily extensible with new experimental components. LittleDarwin addresses two existing problems in the domain of mutation testing: having a tool able to work within an industrial setting, and yet, be open to extension for cutting edge techniques provided by academia. LittleDarwin already offers higher-order mutation, null type mutants, mutant sampling, manual mutation, and mutant subsumption analysis. There is no tool today available with all these features that is able to work with typical industrial software systems.Comment: Pre-proceedings of the 7th IPM International Conference on Fundamentals of Software Engineerin

Calcium regulation of the human mitochondrial ATP-Mg/Pi carrier SLC25A24 uses a locking pin mechanism

Mitochondrial ATP-Mg/Pi carriers import adenine nucleotides into the mitochondrial matrix and export phosphate to the cytosol. They are calcium-regulated to control the size of the matrix adenine nucleotide pool in response to cellular energetic demands. They consist of three domains: an N-terminal regulatory domain containing four calcium-binding EF-hands, a linker loop domain with an amphipathic α-helix and a C-terminal mitochondrial carrier domain for the transport of substrates. Here, we use thermostability assays to demonstrate that the carrier is regulated by calcium via a locking pin mechanism involving the amphipathic α-helix. When calcium levels in the intermembrane space are high, the N-terminus of the amphipathic α-helix is bound to a cleft in the regulatory domain, leading to substrate transport by the carrier domain. When calcium levels drop, the cleft closes, and the amphipathic α-helix is released to bind to the carrier domain via its C-terminus, locking the carrier in an inhibited state

Investigation of glutathione S-transferase zeta and the development of sporadic breast cancer

BACKGROUND: Certain genes from the glutathione S-transferase superfamily have been associated with several cancer types. It was the objective of this study to determine whether alleles of the glutathione S-transferase zeta 1 (GSTZ1) gene are associated with the development of sporadic breast cancer. METHODS: DNA samples obtained from a Caucasian population affected by breast cancer and a control population, matched for age and ethnicity, were genotyped for a polymorphism of the GSTZ1 gene. After PCR, alleles were identified by restriction enzyme digestion and results analysed by chi-square and CLUMP analysis. RESULTS: Chi-squared analysis gave a χ(2) value of 4.77 (three degrees of freedom) with P = 0.19, and CLUMP analysis gave a T1 value of 9.02 with P = 0.45 for genotype frequencies and a T1 value of 4.77 with P = 0.19 for allele frequencies. CONCLUSION: Statistical analysis indicates that there is no association of the GSTZ1 variant and hence the gene does not appear to play a significant role in the development of sporadic breast cancer

Building SO(10) models from F-theory

We revisit local F-theory SO(10) and SU(5) GUTs and analyze their properties within the framework of the maximal underlying E_8 symmetry in the elliptic fibration. We consider the symmetry enhancements along the intersections of seven-branes with the GUT surface and study in detail the embedding of the abelian factors undergoing monodromies in the covering gauge groups. We combine flux data from the successive breaking of SO(10) to SU(5) gauge symmetry and subsequently to the Standard Model one, and further constrain the parameters determining the models' particle spectra. In order to eliminate dangerous baryon number violating operators we propose ways to construct matter parity like symmetries from intrinsic geometric origin. We study implementations of the resulting constrained scenario in specific examples obtained for a variety of monodromies.Comment: 53 page

Wavefunctions and the Point of E8 in F-theory

In F-theory GUTs interactions between fields are typically localised at points of enhanced symmetry in the internal dimensions implying that the coefficient of the associated operator can be studied using a local wavefunctions overlap calculation. Some F-theory SU(5) GUT theories may exhibit a maximum symmetry enhancement at a point to E8, and in this case all the operators of the theory can be associated to the same point. We take initial steps towards the study of operators in such theories. We calculate wavefunctions and their overlaps around a general point of enhancement and establish constraints on the local form of the fluxes. We then apply the general results to a simple model at a point of E8 enhancement and calculate some example operators such as Yukawa couplings and dimension-five couplings that can lead to proton decay.Comment: 46 page

Pollutant dispersion in a developing valley cold-air pool

Pollutants are trapped and accumulate within cold-air pools, thereby affecting air quality. A numerical model is used to quantify the role of cold-air-pooling processes in the dispersion of air pollution in a developing cold-air pool within an alpine valley under decoupled stable conditions. Results indicate that the negatively buoyant downslope flows transport and mix pollutants into the valley to depths that depend on the temperature deficit of the flow and the ambient temperature structure inside the valley. Along the slopes, pollutants are generally entrained above the cold-air pool and detrained within the cold-air pool, largely above the ground-based inversion layer. The ability of the cold-air pool to dilute pollutants is quantified. The analysis shows that the downslope flows fill the valley with air from above, which is then largely trapped within the cold-air pool, and that dilution depends on where the pollutants are emitted with respect to the positions of the top of the ground-based inversion layer and cold-air pool, and on the slope wind speeds. Over the lower part of the slopes, the cold-air-pool-averaged concentrations are proportional to the slope wind speeds where the pollutants are emitted, and diminish as the cold-air pool deepens. Pollutants emitted within the ground-based inversion layer are largely trapped there. Pollutants emitted farther up the slopes detrain within the cold-air pool above the ground-based inversion layer, although some fraction, increasing with distance from the top of the slopes, penetrates into the ground-based inversion layer.Peer reviewe

Fundamental Strings, Holography, and Nonlinear Superconformal Algebras

We discuss aspects of holography in the AdS_3 \times S^p near string geometry of a collection of straight fundamental heterotic strings. We use anomalies and symmetries to determine general features of the dual CFT. The symmetries suggest the appearance of nonlinear superconformal algebras, and we show how these arise in the framework of holographic renormalization methods. The nonlinear algebras imply intricate formulas for the central charge, and we show that in the bulk these correspond to an infinite series of quantum gravity corrections. We also makes some comments on the worldsheet sigma-model for strings on AdS_3\times S^2, which is the holographic dual geometry of parallel heterotic strings in five dimensions.Comment: 25 page

Randomised trials comparing different healthcare settings : an exploratory review of the impact of pre-trial preferences on participation, and discussion of other methodological challenges

BACKGROUND: We recently published a systematic review of different healthcare settings (such as outpatient, community or home) for administering intravenous chemotherapy, and concluded that performing conventionally designed randomised trials was difficult. The main problems were achieving adequate trial accrual rates and recruiting a study population which adequately represented the target population of interest. These issues stemmed from the fact that potential participants may have had pre-trial perceptions about the trial settings they may be allocated; such preferences will sometimes be strong enough for patients to decline an invitation to participate in a trial. A patient preference trial design (in which patients can choose, or be randomised to, an intervention) may have obviated these recruitment issues, although none of the trials used such a design. METHODS: In order to gain a better understanding of the broader prevalence and extent of these preference issues (and any other methodological challenges), we undertook an exploratory review of settings trials in any area of healthcare treatment research. We searched The Cochrane Library and Google Scholar and used snowballing methods to identify trials comparing different healthcare settings. RESULTS: Trial accrual was affected by patient preferences for a setting in 15 of the 16 identified studies; birth setting trials were the most markedly affected, with between 68 % and 85 % of eligible women declining to participate specifically because of preference for a particular healthcare setting. Recruitment into substance abuse and chemotherapy setting studies was also notably affected by preferences. Only four trials used a preference design: the proportion of eligible patients choosing to participate via a preference group ranged from between 33 % and 67 %. CONCLUSIONS: In trials of healthcare settings, accrual may be seriously affected by patient preferences. The use of trial designs which incorporate a preference component should therefore strongly be considered. When designing such trials, investigators should consider settings to be complex interventions, which are likely to have linked components which may be difficult to control for. Careful thought is also needed regarding the choice of comparator settings and the most appropriate outcome measures to be used

Threshold effect of foreign direct investment on environmental degradation

The aim of this paper is to investigate the threshold effect of foreign direct investment (FDI) on environmental degradation. In empirical analysis, FDI and environmental degradation are jointly determined under the given threshold variable and other exogenous variables. Using carbon dioxide (CO2) emissions per capita as a proxy for environmental degradation, the results show that increasing FDI worsens CO2 emissions after a threshold level of corruption has been reached. Our results demonstrate that increasing FDI will increase CO2 emissions when the degree of corruptibility is relatively high. The study suggests that further FDI and improved environmental quality are competing rather than compatible objectives in high-corruption countries and are compatible rather than competing objectives in low-corruption countries. Higher trade liberalization in low-corruption countries could contribute to negative environmental consequences because of the increased output or economic activity which results from increased trade. The robustness estimation confirms the evidence that pollution and economic development increase together up to a certain income level, after which the trend reverses.info:eu-repo/semantics/publishedVersio

Nontypeable haemophilus influenzae induces sustained lung oxidative stress and protease expression

© 2015 King et al. Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps