Untangling Fine-Grained Code Changes

After working for some time, developers commit their code changes to a version control system. When doing so, they often bundle unrelated changes (e.g., bug fix and refactoring) in a single commit, thus creating a so-called tangled commit. Sharing tangled commits is problematic because it makes review, reversion, and integration of these commits harder and historical analyses of the project less reliable. Researchers have worked at untangling existing commits, i.e., finding which part of a commit relates to which task. In this paper, we contribute to this line of work in two ways: (1) A publicly available dataset of untangled code changes, created with the help of two developers who accurately split their code changes into self contained tasks over a period of four months; (2) a novel approach, EpiceaUntangler, to help developers share untangled commits (aka. atomic commits) by using fine-grained code change information. EpiceaUntangler is based and tested on the publicly available dataset, and further evaluated by deploying it to 7 developers, who used it for 2 weeks. We recorded a median success rate of 91% and average one of 75%, in automatically creating clusters of untangled fine-grained code changes

On the Wilf-Stanley limit of 4231-avoiding permutations and a conjecture of Arratia

We construct a sequence of finite automata that accept subclasses of the class of 4231-avoiding permutations. We thereby show that the Wilf-Stanley limit for the class of 4231-avoiding permutations is bounded below by 9.35. This bound shows that this class has the largest such limit among all classes of permutations avoiding a single permutation of length 4 and refutes the conjecture that the Wilf-Stanley limit of a class of permutations avoiding a single permutation of length k cannot exceed (k-1)^2.Comment: Submitted to Advances in Applied Mathematic

Correlative Microscopy Of Bone In Implant Osteointegration Studies.

Routine morphological analyses usually include investigations by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Each of these techniques provides specific information on tissue morphology and all the obtained results are then combined to give an in-depth morphological overview of the examined sample. The limitations of this traditional comparative microscopy lie in the fact that each technique requires a different experimental sample, so that many specimens are necessary and the combined results come from different samples. The present study describes a technical procedure of correlative microscopy, which allows us to examine the same bone section first by LM and then, after appropriate processing, by SEM or TEM. Thanks to the possibility of analyzing the same undecalcified bone sections both by LM and SEM, the approach described in the present study allows us to make very accurate evaluations of old/new bone morphology at the bone-implant interface

A CTNNA3 compound heterozygous deletion implicates a role for \u3b1T-catenin in susceptibility to autism spectrum disorder.

Autism spectrum disorder (ASD) is a highly heritable, neurodevelopmental condition showing extreme genetic heterogeneity. While it is well established that rare genetic variation, both de novo and inherited, plays an important role in ASD risk, recent studies also support a rare recessive contribution. METHODS: We identified a compound heterozygous deletion intersecting the CTNNA3 gene, encoding \u3b1T-catenin, in a proband with ASD and moderate intellectual disability. The deletion breakpoints were mapped at base-pair resolution, and segregation analysis was performed. We compared the frequency of CTNNA3 exonic deletions in 2,147 ASD cases from the Autism Genome Project (AGP) study versus the frequency in 6,639 controls. Western blot analysis was performed to get a quantitative characterisation of Ctnna3 expression during early brain development in mouse. RESULTS: The CTNNA3 compound heterozygous deletion includes a coding exon, leading to a putative frameshift and premature stop codon. Segregation analysis in the family showed that the unaffected sister is heterozygote for the deletion, having only inherited the paternal deletion. While the frequency of CTNNA3 exonic deletions is not significantly different between ASD cases and controls, no homozygous or compound heterozygous exonic deletions were found in a sample of over 6,000 controls. Expression analysis of Ctnna3 in the mouse cortex and hippocampus (P0-P90) provided support for its role in the early stage of brain development. CONCLUSION: The finding of a rare compound heterozygous CTNNA3 exonic deletion segregating with ASD, the absence of CTNNA3 homozygous exonic deletions in controls and the high expression of Ctnna3 in both brain areas analysed implicate CTNNA3 in ASD susceptibility

5.26 Left Ventricular Hypertrophy Prevalence by Different Left Ventricular Mass Indexes

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An increased burden of rare exonic variants in NRXN1 microdeletion carriers is likely to enhance the penetrance for autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by a complex polygenic background, but with the unique feature of a subset of cases (~15%-30%) presenting a rare large-effect variant. However, clinical interpretation in these cases is often complicated by incomplete penetrance, variable expressivity and different neurodevelopmental trajectories. NRXN1 intragenic deletions represent the prototype of such ASD-associated susceptibility variants. From chromosomal microarrays analysis of 104 ASD individuals, we identified an inherited NRXN1 deletion in a trio family. We carried out whole-exome sequencing and deep sequencing of mitochondrial DNA (mtDNA) in this family, to evaluate the burden of rare variants which may contribute to the phenotypic outcome in NRXN1 deletion carriers. We identified an increased burden of exonic rare variants in the ASD child compared to the unaffected NRXN1 deletion-transmitting mother, which remains significant if we restrict the analysis to potentially deleterious rare variants only (P = 6.07 7 10-5 ). We also detected significant interaction enrichment among genes with damaging variants in the proband, suggesting that additional rare variants in interacting genes collectively contribute to cross the liability threshold for ASD. Finally, the proband's mtDNA presented five low-level heteroplasmic mtDNA variants that were absent in the mother, and two maternally inherited variants with increased heteroplasmic load. This study underlines the importance of a comprehensive assessment of the genomic background in carriers of large-effect variants, as penetrance modulation by additional interacting rare variants to might represent a widespread mechanism in neurodevelopmental disorders

An Empirical Study of Bots in Software Development -- Characteristics and Challenges from a Practitioner's Perspective

Software engineering bots - automated tools that handle tedious tasks - are increasingly used by industrial and open source projects to improve developer productivity. Current research in this area is held back by a lack of consensus of what software engineering bots (DevBots) actually are, what characteristics distinguish them from other tools, and what benefits and challenges are associated with DevBot usage. In this paper we report on a mixed-method empirical study of DevBot usage in industrial practice. We report on findings from interviewing 21 and surveying a total of 111 developers. We identify three different personas among DevBot users (focusing on autonomy, chat interfaces, and "smartness"), each with different definitions of what a DevBot is, why developers use them, and what they struggle with. We conclude that future DevBot research should situate their work within our framework, to clearly identify what type of bot the work targets, and what advantages practitioners can expect. Further, we find that there currently is a lack of general purpose "smart" bots that go beyond simple automation tools or chat interfaces. This is problematic, as we have seen that such bots, if available, can have a transformative effect on the projects that use them.Comment: To be published at the ACM Joint European Software Engineering Conference and Symposium on the Foundations of Software Engineering (ESEC/FSE

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Contribution of ultrarare variants in mTOR pathway genes to sporadic focal epilepsies

Objective: We investigated the contribution to sporadic focal epilepsies (FE) of ultrarare variants in genes coding for the components of complexes regulating mechanistic Target Of Rapamycin (mTOR)complex 1 (mTORC1). Methods: We collected genetic data of 121 Italian isolated FE cases and 512 controls by Whole Exome Sequencing (WES) and single-molecule Molecular Inversion Probes (smMIPs) targeting 10 genes of the GATOR1, GATOR2, and TSC complexes. We collapsed \u201cqualifying\u201d variants (ultrarare and predicted to be deleterious or loss of function) across the examined genes and sought to identify their enrichment in cases compared to controls. Results: We found eight qualifying variants in cases and nine in controls, demonstrating enrichment in FE patients (P&nbsp;=&nbsp;0.006; exact unconditional test, one-tailed). Pathogenic variants were identified in DEPDC5 and TSC2, both major genes for Mendelian FE syndromes. Interpretation: Our findings support the contribution of ultrarare variants in genes in the mTOR pathway complexes GATOR and TSC to the risk of sporadic FE and a shared genetic basis between rare and common epilepsies. The identification of a monogenic etiology in isolated cases, most typically encountered in clinical practice, may offer to a broader community of patients the perspective of precision therapies directed by the underlying genetic cause