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

CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is a selective blocker of L-type calcium channels in mammalian neurons

The inhibitor cystine-knot motif identified in the structure of CSTX-1 from Cupiennius salei venom suggests that this toxin may act as a blocker of ion channels. Whole-cell patch-clamp experiments performed on cockroach neurons revealed that CSTX-1 produced a slow voltage-independent block of both mid/low- (M-LVA) and high-voltage-activated (HVA) insect Cav channels. Since C. salei venom affects both insect as well as rodent species, we investigated whether Cav channel currents of rat neurons are also inhibited by CSTX-1. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Cav channels, and failed to modulate LVA Cav channel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Cav channel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC50 values were at least 1000-fold lower than in GH3 cells. L-type Cav channel currents of skeletal muscle myoballs and other voltage-gated ion currents of rat neurons, such as INa(v) or IK(v) were not affected by CSTX-1. The high potency and selectivity of CSTX-1 for a subset of L-type channels in mammalian neurons may enable the toxin to be used as a molecular tool for the investigation of this family of Cav channels. © 2007 Elsevier Ltd. All rights reserved

Partial Covering Arrays: Algorithms and Asymptotics

A covering array $\mathsf{CA}(N;t,k,v)$ is an $N\times k$ array with entries in $\{1, 2, \ldots , v\}$, for which every $N\times t$ subarray contains each $t$-tuple of $\{1, 2, \ldots , v\}^t$ among its rows. Covering arrays find application in interaction testing, including software and hardware testing, advanced materials development, and biological systems. A central question is to determine or bound $\mathsf{CAN}(t,k,v)$, the minimum number $N$ of rows of a $\mathsf{CA}(N;t,k,v)$. The well known bound $\mathsf{CAN}(t,k,v)=O((t-1)v^t\log k)$ is not too far from being asymptotically optimal. Sensible relaxations of the covering requirement arise when (1) the set $\{1, 2, \ldots , v\}^t$ need only be contained among the rows of at least $(1-\epsilon)\binom{k}{t}$ of the $N\times t$ subarrays and (2) the rows of every $N\times t$ subarray need only contain a (large) subset of $\{1, 2, \ldots , v\}^t$. In this paper, using probabilistic methods, significant improvements on the covering array upper bound are established for both relaxations, and for the conjunction of the two. In each case, a randomized algorithm constructs such arrays in expected polynomial time

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

k is the Magic Number -- Inferring the Number of Clusters Through Nonparametric Concentration Inequalities

Most convex and nonconvex clustering algorithms come with one crucial parameter: the $k$ in $k$-means. To this day, there is not one generally accepted way to accurately determine this parameter. Popular methods are simple yet theoretically unfounded, such as searching for an elbow in the curve of a given cost measure. In contrast, statistically founded methods often make strict assumptions over the data distribution or come with their own optimization scheme for the clustering objective. This limits either the set of applicable datasets or clustering algorithms. In this paper, we strive to determine the number of clusters by answering a simple question: given two clusters, is it likely that they jointly stem from a single distribution? To this end, we propose a bound on the probability that two clusters originate from the distribution of the unified cluster, specified only by the sample mean and variance. Our method is applicable as a simple wrapper to the result of any clustering method minimizing the objective of $k$-means, which includes Gaussian mixtures and Spectral Clustering. We focus in our experimental evaluation on an application for nonconvex clustering and demonstrate the suitability of our theoretical results. Our \textsc{SpecialK} clustering algorithm automatically determines the appropriate value for $k$, without requiring any data transformation or projection, and without assumptions on the data distribution. Additionally, it is capable to decide that the data consists of only a single cluster, which many existing algorithms cannot

Exoplanets and SETI

The discovery of exoplanets has both focused and expanded the search for extraterrestrial intelligence. The consideration of Earth as an exoplanet, the knowledge of the orbital parameters of individual exoplanets, and our new understanding of the prevalence of exoplanets throughout the galaxy have all altered the search strategies of communication SETI efforts, by inspiring new "Schelling points" (i.e. optimal search strategies for beacons). Future efforts to characterize individual planets photometrically and spectroscopically, with imaging and via transit, will also allow for searches for a variety of technosignatures on their surfaces, in their atmospheres, and in orbit around them. In the near-term, searches for new planetary systems might even turn up free-floating megastructures.Comment: 9 page invited review. v2 adds some references and v3 has other minor additions and modification

Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds

Animals are frequently used as model systems for determination of safety and efficacy in pharmaceutical research and development. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this cross-species methodology by investigating species specific differences of the peroxisome proliferatoractivator receptor (PPAR) a response in rat and human

The Effect of Transposable Element Insertions on Gene Expression Evolution in Rodents

Background:Many genomes contain a substantial number of transposable elements (TEs), a few of which are known to be involved in regulating gene expression. However, recent observations suggest that TEs may have played a very important role in the evolution of gene expression because many conserved non-genic sequences, some of which are know to be involved in gene regulation, resemble TEs. Results:Here we investigate whether new TE insertions affect gene expression profiles by testing whether gene expression divergence between mouse and rat is correlated to the numbers of new transposable elements inserted near genes. We show that expression divergence is significantly correlated to the number of new LTR and SINE elements, but not to the numbers of LINEs. We also show that expression divergence is not significantly correlated to the numbers of ancestral TEs in most cases, which suggests that the correlations between expression divergence and the numbers of new TEs are causal in nature. We quantify the effect and estimate that TE insertion has accounted for ~20% (95% confidence interval: 12% to 26%) of all expression profile divergence in rodents. Conclusions:We conclude that TE insertions may have had a major impact on the evolution of gene expression levels in rodents

Atmospheric Evolution

Earth's atmosphere has evolved as volatile species cycle between the atmosphere, ocean, biomass and the solid Earth. The geochemical, biological and astrophysical processes that control atmospheric evolution are reviewed from an "Earth Systems" perspective, with a view not only to understanding the history of Earth, but also to generalizing to other solar system planets and exoplanets.Comment: 34 pages, 3 figures, 2 tables. Accepted as a chapter in "Encyclopaedia of Geochemistry", Editor Bill White, Springer-Nature, 201

Do Null-Type Mutation Operators Help Prevent Null-Type Faults?

The null-type is a major source of faults in Java programs, and its overuse has a severe impact on software maintenance. Unfortunately traditional mutation testing operators do not cover null-type faults by default, hence cannot be used as a preventive measure. We address this problem by designing four new mutation operators which model null-type faults explicitly. We show how these mutation operators are capable of revealing the missing tests, and we demonstrate that these mutation operators are useful in practice. For the latter, we analyze the test suites of 15 open-source projects to describe the trade-offs related to the adoption of these operators to strengthen the test suite