An important research area of Spectrum-Based Fault Localization (SBFL) is the effectiveness of risk evaluation formulas. Most previous studies have adopted an empirical approach, which can hardly be ...considered as sufficiently comprehensive because of the huge number of combinations of various factors in SBFL. Though some studies aimed at overcoming the limitations of the empirical approach, none of them has provided a completely satisfactory solution. Therefore, we provide a theoretical investigation on the effectiveness of risk evaluation formulas. We define two types of relations between formulas, namely, equivalent and better. To identify the relations between formulas, we develop an innovative framework for the theoretical investigation. Our framework is based on the concept that the determinant for the effectiveness of a formula is the number of statements with risk values higher than the risk value of the faulty statement. We group all program statements into three disjoint sets with risk values higher than, equal to, and lower than the risk value of the faulty statement, respectively. For different formulas, the sizes of their sets are compared using the notion of subset. We use this framework to identify the maximal formulas which should be the only formulas to be used in SBFL.
Machine learning algorithms have provided core functionality to many application domains – such as bioinformatics, computational linguistics, etc. However, it is difficult to detect faults in such ...applications because often there is no “test oracle” to verify the correctness of the computed outputs. To help address the software quality, in this paper we present a technique for testing the implementations of machine learning classification algorithms which support such applications. Our approach is based on the technique “metamorphic testing”, which has been shown to be effective to alleviate the oracle problem. Also presented include a case study on a real-world machine learning application framework, and a discussion of how programmers implementing machine learning algorithms can avoid the common pitfalls discovered in our study. We also conduct mutation analysis and cross-validation, which reveal that our method has high effectiveness in killing mutants, and that observing expected cross-validation result alone is not sufficiently effective to detect faults in a supervised classification program. The effectiveness of metamorphic testing is further confirmed by the detection of real faults in a popular open-source classification program.
GitHub is a popular code platform that provides infrastructures to facilitate collaborative development. A Pull Request (PR) is one of the key ideas to support collaboration. Developers are ...encouraged to submit PRs to ask for the integration of their contributions. In practice, not all submitted PRs can be integrated into the codebase by project maintainers. Existing studies have investigated factors affecting PR integration. Nevertheless, the code style of PRs, which is largely considered by project maintainers, has not been deeply studied yet. In this paper, we performed an exploratory analysis on the effect of code style on PR integration in GitHub. We modeled the code style via the inconsistency between a submitted PR and the existing code in its target codebase. Such modeling makes our study not limited by a specific definition of code style. We conducted our experiments on 50,092 closed PRs in 117 Java projects. Our findings show that: (1) There indeed exists code style inconsistency between PRs and the codebase. (2) Several code style criteria on how to use spaces or indents, make comments, and write code lines with a suitable length, tend to show more inconsistency among PRs. (3) A PR that is consistent with the current code style tends to be merged into the codebase more easily. (4) A PR that violates the current code style is likely to take more time to get closed. Our study shows evidence to developers about how to deliver better contributions to facilitate efficient collaboration.
Recent advances in experimental and computational technologies have fueled the development of many sophisticated bioinformatics programs. The correctness of such programs is crucial as incorrectly ...computed results may lead to wrong biological conclusion or misguided downstream experimentation. Common software testing procedures involve executing the target program with a set of test inputs and then verifying the correctness of the test outputs. However, due to the complexity of many bioinformatics programs, it is often difficult to verify the correctness of the test outputs. Therefore our ability to perform systematic software testing is greatly hindered.
We propose to use a novel software testing technique, metamorphic testing (MT), to test a range of bioinformatics programs. Instead of requiring a mechanism to verify whether an individual test output is correct, the MT technique verifies whether a pair of test outputs conform to a set of domain specific properties, called metamorphic relations (MRs), thus greatly increases the number and variety of test cases that can be applied. To demonstrate how MT is used in practice, we applied MT to test two open-source bioinformatics programs, namely GNLab and SeqMap. In particular we show that MT is simple to implement, and is effective in detecting faults in a real-life program and some artificially fault-seeded programs. Further, we discuss how MT can be applied to test programs from various domains of bioinformatics.
This paper describes the application of a simple, effective and automated technique to systematically test a range of bioinformatics programs. We show how MT can be implemented in practice through two real-life case studies. Since many bioinformatics programs, particularly those for large scale simulation and data analysis, are hard to test systematically, their developers may benefit from using MT as part of the testing strategy. Therefore our work represents a significant step towards software reliability in bioinformatics.
The release of host mitochondrial cardiolipin is believed to be the main factor that contributes to the production of anti-cardiolipin antibodies in syphilis. However, the precise mechanism by which ...mitochondria release cardiolipin in this context remains elusive. This study aimed to elucidate the mechanisms underlying mitochondrial cardiolipin release in syphilis. We conducted a cardiolipin quantitative assay and immunofluorescence analysis to detect mitochondrial cardiolipin release in human microvascular endothelial cells (HMEC-1), with and without Treponema pallidum (Tp) infection. Furthermore, we explored apoptosis, a key mechanism for mitochondrial cardiolipin release. The potential mediator molecules were then analyzed through RNA-sequence and subsequently validated using in vitro knockout techniques mediated by CRISPR-Cas9 and pathway-specific inhibitors. Our findings confirm that live-Tp is capable of initiating the release of mitochondrial cardiolipin, whereas inactivated-Tp does not exhibit this capability. Additionally, apoptosis detection further supports the notion that the release of mitochondrial cardiolipin occurs independently of apoptosis. The RNA-sequencing results indicated that microtubule-associated protein2 (MAP2), an axonogenesis and dendrite development gene, was up-regulated in HMEC-1 treated with Tp, which was further confirmed in syphilitic lesions by immunofluorescence. Notably, genetic knockout of MAP2 inhibited Tp-induced mitochondrial cardiolipin release in HMEC-1. Mechanically, Tp-infection regulated MAP2 expression via the MEK-ERK-HES1 pathway, and MEK/ERK phosphorylation inhibitors effectively block Tp-induced mitochondrial cardiolipin release. This study demonstrated that the infection of live-Tp enhanced the expression of MAP2 via the MEK-ERK-HES1 pathway, thereby contributing to our understanding of the role of anti-cardiolipin antibodies in the diagnosis of syphilis.
Unlike traditional quality of service (QoS) value prediction, QoS ranking prediction examines the order of services under consideration for a particular user. To address this NP-Complete problem, ...greedy strategy-based solutions, such as CloudRank algorithm, have been widely adopted. However, they can only produce locally approximate solutions. In this paper, we propose a search-based prediction framework to address the QoS ranking problem. The traditional particle swarm optimization (PSO) algorithm has been adapted to optimize the order of services according to their QoS records. In real situations, QoS records for a given consumer are often incomplete, so the related data from close neighbour users is often used to determine preference relations among services. In order to filter the neighbours for a specific user, we present an improved method for measuring the similarity between two users by considering the occurrence probability of service pairs. Based on the similarity computation, the top-k neighbours are selected to provide QoS information support for evaluation of the service ranking. A fitness function for an ordered service sequence is defined to guide search algorithm to find high-quality ranking results, and some additional strategies, such as initial solution selection and trap escaping, are also presented. To validate the effectiveness of our proposed solution, experimental studies have been performed on real-world QoS data, the results from which show that our PSO-based approach has a better ranking for services than that computed by the existing CloudRank algorithm, and that the improvement is statistically significant, in most cases.
•An improved similarity measurement for two ranked sequences is proposed.•A new solution for predicting QoS ranking is proposed by adopting PSO algorithm.•The PSO-based QoS ranking prediction algorithm is better than CloudRank.
The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no ...method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES).
Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions.
Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.
The quality of Tungsten Inert Gas welding is dependent on human supervision, which can’t suitable for automation. This study designed a model for assessing the tungsten inert gas welding quality with ...the potential of application in real-time. The model used the K-Nearest Neighborhood (KNN) algorithm, paired with images in the visible spectrum formed by high dynamic range camera. Firstly, projecting the image of weld defects in the training set into a two-dimensional space using multidimensional scaling (MDS), so similar weld defects was aggregated into blocks and distributed in hash, and among different weld defects has overlap. Secondly, establishing models including the KNN, CNN, SVM, CART and NB classification, to classify and recognize the weld defect images. The results show that the KNN model is the best, which has the recognition accuracy of 98%, and the average time of recognizing a single image of 33ms, and suitable for common hardware devices. It can be applied to the image recognition system of automatic welding robot to improve the intelligent level of welding robot.
Fear generalization is an etiologically significant indicator of anxiety disorders, and understanding how to inhibit it is important in their treatment. Prior studies have found that reducing fear ...generalization using a generalization stimulus (GS) is ineffective in removing a conditioned fear that incorporates local features, and that topological properties appear to play a comparatively more significant role in the processes of perception and categorization. Our study utilized a conditioned-fear generalization design to examine whether the topological properties of stimuli influence the generalization and return of fear. Fear was indexed using online expectancy ratings and skin conductance responses (SCRs). The study's 52 participants were divided into three groups: Group 1, conditioned danger cue (CS+) extinction; Group 2, extinction of one GS; Group 3, extinction of three GSs. We found that the three groups acquired conditioned fear at the same level. In the generalization and extinction phase, fear was transferred to the GS with the same topological properties as CS+, and gradual decreases in both shock expectancy and SCRs over non-reinforced extinction trials were observed. In the test phase, participants' online expectancy ratings indicated that fear did not return in Group 1, but did return in Groups 2 and 3. All three groups demonstrated successful GS fear extinction, but only Group 1 did not show a return of fear for CS+. Regarding SCRs results, none of the groups demonstrated a return of fear, suggesting that utilization of topological properties successfully reduced the return of conditioned fear. Our results indicate that, in clinical settings, using GS with topological equivalence to CS+ might offer a potential method with which to extinct conditioned fear.
Summary
Introduction
Neck skin aging is of particular interest to skin scientists and dermatologists because of the increasing demand for neck wrinkle improvement. This study aimed to determine the ...neck aging features of Chinese women and to investigate the clinical alterations and mechanical, topographical, and biophysical properties of neck skin.
Methods
A total of 450 Chinese women (age range: 16‐66 years) were clinically examined and graded by the same dermatologist using standardized photographs. The skin properties were assessed by noninvasive skin measuring devices.
Results
The results showed that different neck aging signs, including the horizontal neck fold, neck sagging, hollowing of emaciated neck, platysmal bands, and neck texture, appeared in different ages, and all of them worsened age‐dependently since they manifested. The skin elasticity markedly changed before the onset of most of the aging signs and showed a negative correlation with both age and the severity of these signs. Transepidermal water loss (TEWL) was positively correlated with age, whereas hydration and pH were not significantly correlated with age. We also found that wrinkles (SEw) and average roughness (Ra) were significantly correlated with age. SEw, smoothness, the average depth of roughness (Rz), TEWL, and erythema index were significantly and positively correlated with the severity of the horizontal neck fold, neck sagging, hollowing of emaciated neck, and platysmal bands.
Conclusion
This is the first study to emphasize that age causes diverse changes in Chinese women's neck skin. The changes in skin elasticity may effectively predict neck aging before the onset of most of the neck aging signs.