Optimised Realistic Test Input Generation Using Web Services

Abstract. We introduce a multi-objective formulation of service-oriented testing, focusing on the balance between service price and reliability. We experimented with NSGA2 for this problem, investigating the effect on performance and quality of composition size, topology and the number of services discovered. For topologies small enough for exhaustive search we found that NSGA2 finds a pareto front very near (the fronts are a Euclidean distance of ∼ 0.00024 price-reliability points apart) the true pareto front. Regarding performance, we find that composition size has the strongest effect, with smaller topologies consuming more machine time; a curious effect we believe is due to the influence of crowding dis-tance. Regarding result quality, our results reveal that size and topology have more effect on the front found than the number of service choices discovered. As expected the cost-reliability relationship (logarithmic, lin-ear, exponential) is replicated in the front discovered when correlation is high, but as the price-reliability correlation decreases, we find fewer solutions on the front and the front becomes less smooth.

Characterizing the morbid genome of ciliopathies

Background Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete. Results We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum. Likely causal mutations in previously described ciliopathy genes were identified in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a fully penetrant model for these genes, we found no significant difference in their “mutation load” beyond the causal variants between our ciliopathy cohort and a control non-ciliopathy cohort. Genomic analysis of our cohort further identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase, based on independent loss of function mutations in individuals with a consistent ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its deficiency on ciliary signaling. Our study also highlighted seven novel candidate genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of which have established links to ciliogenesis. Finally, we show that the morbid genome of ciliopathies encompasses many founder mutations, the combined carrier frequency of which accounts for a high disease burden in the study population. Conclusions Our study increases our understanding of the morbid genome of ciliopathies. We also provide the strongest evidence, to date, in support of the classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies

Hyperekplexia-like syndromes without mutations in the GLRA1 gene

Hyperekplexia (MIM: 149400): or startle disease, is an autosomal dominant neurological disorder characterized by an extreme generalized stiffness immediately after birth, normalizing during the first years of life. Other features of this disorder are excessive startle reactions to unexpected, particularly auditory, stimuli together with a short period of generalized stiffness during which voluntary movements are impossible. Linkage analysis mapped a gene for this disorder to chromosome 5q33-q35. Subsequently, mutations in the GLRA1 gene encoding the alpha 1-subunit of the glycine receptor proved to be causally related to the disease. In the present study, mutation analysis of all exon and nanking intron sequences of this gene was performed in sporadic patients and their parents. Moreover, a branch of the original Dutch hyperekplexia family with a very severely affected individual was screened for an additional mutation in the GLRA1 gene, Except for two polymorphisms, of which one results in an amino acid change, no potentially disease causing mutations were found in the alpha 1-subunit of the glycine receptor, Together with haplotype analysis these results exclude a recessive inheritance or new mutation etiology in these hyperekplexia-like syndromes and emphasize that hyperekplexia-like syndromes can be caused by other genetic factors. The involvement of other genes encoding subunits of the functional glycine receptor complex has not been excluded. (C) 1997 Elsevier Science B.V

Effective and Efficient API Misuse Detection via Exception Propagation and Search-Based Testing

Application Programming Interfaces (APIs) typically come with (implicit) usage constraints. The violations of these constraints (API misuses) can lead to software crashes. Even though there are several tools that can detect API misuses, most of them suffer from a very high rate of false positives. We introduce Catcher, a novel API misuse detection approach that combines static exception propagation analysis with automatic search-based test case generation to effectively and efficiently pinpoint crash-prone API misuses in client applications. We validate Catcher against 21 Java applications, targeting misuses of the Java platform’s API. Our results indicate that Catcher is able to generate test cases that uncover 243 (unique) API misuses that result in crashes. Our empirical evaluation shows that Catcher can detect a large number of misuses (77 cases) that would remain undetected by the traditional coverage-based test case generator EvoSuite. Additionally, on average, Catcher is eight times faster than EvoSuite in generating test cases for the identified misuses. Finally, we find that the majority of the exceptions triggered by Catcher are unexpected to developers, i.e., not only unhandled in the source code but also not listed in the documentation of the client applications.Software EngineeringSoftware Technolog

Exposure to Bisphenol A Substitutes, Bisphenol S and Bisphenol F, and Its Association with Developing Obesity and Diabetes Mellitus: A Narrative Review

Bisphenol A, a well-known endocrine-disrupting chemical, has been replaced with its analogs bisphenol S (BPS) and bisphenol F (BPF) over the last decade due to health concerns. BPS and BPF are present in relatively high concentrations in different products, such as food products, personal care products, and sales receipts. Both BPS and BPF have similar structural and chemical properties to BPA; therefore, considerable scientific efforts have investigated the safety of their exposure. In this review, we summarize the findings of relevant epidemiological studies investigating the association between urinary concentrations of BPS and/or BPF with the incidence of obesity or diabetes. The results showed that BPS and BPF were detected in many urinary samples at median concentrations ranging from 0.03 to 0.4 µg·L−1. At this exposure level, BPS median urinary concentrations (0.4 µg·L−1) were associated with the development of obesity. At a lower exposure level (0.1–0.03 µg·L−1), two studies showed an association with developing diabetes. For BPF exposure, only one study showed an association with obesity. However, most of the reported studies only assessed BPS exposure levels. Furthermore, we also summarize the findings of experimental studies in vivo and in vitro regarding our aim; results support the possible obesogenic effects/metabolic disorders mediated by BPS and/or BPF exposure. Unexpectedly, BPS may promote worse obesogenic effects than BPA. In addition, the possible mode of action underlying the obesogenic effects of BPS might be attributed to various pathophysiological mechanisms, including estrogenic or androgenic activities, alterations in the gene expression of critical adipogenesis-related markers, and induction of oxidative stress and an inflammatory state. Furthermore, susceptibility to the adverse effects of BPS may be altered by sex differences according to the results of both epidemiological and experimental studies. However, the possible mode of action underlying these sex differences is still unclear. In conclusion, exposure to BPS or BPF may promote the development of obesity and diabetes. Future approaches are highly needed to assess the safety of BPS and BPF regarding their potential effects in promoting metabolic disturbances. Other studies in different populations and settings are highly suggested