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Background: The current ISO guidelines for minimal erythema dose (MED) determination require assessment of erythema area of UV‐irradiated skin sites. However, this parameter has not been adequately quantified in daily practice. The aims of this study were to investigate the dose response on the unprotected skin sites by quantifying the erythema area and intensity and to show the potential for improving the precision and consistency of MEDu determination by developing predictive models. Methods: Standard radiation tests were conducted on the back of 31 healthy Chinese volunteers and the MEDu site of each subject was clinically determined by dermatologists. Images of test sites were captured 24 h after radiation, and the erythema area (%EA) and intensity (∆a*) were measured by image analysis. The data were fitted to a logistic 3P function to obtain dose–response curves, and a set of logit (inverse‐logistic) models were then derived. An erythema area threshold of %EA = 52% was established to predict MEDu based on the clinical endpoints defined by ISO 24444:2019. Results: Analysis of the clinically determined MEDu sites revealed wide ranges of %EA (62.3 ± 15% SD) and ∆a* (2.96 ± 0.92 SD). The dose response fitted well to a logistic 3P model (mean R2 = 0.965 and 0.975 for %EA and ∆a*, respectively). Applying the area threshold, values of MEDu were determined by the logit model for the test population, which significantly improved the consistency of MEDu determination (52 ± 0% SD and 2.73 ± 0.61 SD for %EA and ∆a*, respectively). Conclusion: This study demonstrated that the dose response of UV‐induced erythema can be quantified and modeled once the erythema area and intensity are measured. The results of this study show the potential to improve the precision and consistency of MEDu determination in an SPF test. The similar potential in photodermatological, therapeutic, and diagnostic applications was also implied. [ABSTRACT FROM AUTHOR]

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.

A very important function of an issue tracking system is to assign labels to issue reports, such as bug, feature, enhancement, etc., in order to categorize issues to facilitate various development activities. In practice, it is very common that an issue has multiple labels. However, current works are mainly based on single-label prediction, which are not suitable for just-in-time multi-labeling services, due to the low efficiency. Therefore, in this paper, we propose MULA, a just-in-time MUlti-LAbeling system, which learns and automatically assigns multiple labels to issue reports. We have built a dataset with 81,601 entries and 11 labels, as the first benchmark for this task, and implemented a GitHub app. To the best of our knowledge, this is the first work and tool for online multi-labeling GitHub issues based on their categories. We conduct a comprehensive empirical study, including comparisons with five commonly adopted labeling models that show the superiority of MULA, as well as an evaluation that shows high consistency between MULA’s suggestions and developers’ opinions. [ABSTRACT FROM AUTHOR]

Abstract Background 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 misguide 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. Results 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. Conclusion 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.

In this paper, the effects of high carbon ferrochrome slag as coarse aggregate on workability, compressive strength, modulus of elasticity under static compression,electric flux, long-term shrinkage and content of extractable heavy metal of concrete were investigated. The results indicate that serious risk on technology will not arise when regarding the high carbon ferrochrome slag as coarse aggregate in concrete from the perspective of volume stability and extractable heavy metal. Under the appropriate mix ratio, the high carbon ferrochrome slag, if acting as coarse aggregate, will not bring obvious adverse effects into concrete. Hence, it will be feasible to consider the high carbon ferrochrome slag as coarse aggregate of concrete from the technical point of view. [ABSTRACT FROM AUTHOR]

Unsupervised machine learning is the training of an artificial intelligence system using information that is neither classified nor labeled, with a view to modeling the underlying structure or distribution in a dataset. Since unsupervised machine learning systems are widely used in many real-world applications, assessing the appropriateness of these systems and validating their implementations with respect to individual users’ requirements and specific application scenarios/contexts are indisputably two important tasks. Such assessments and validation tasks, however, are fairly challenging due to the absence of a priori knowledge of the data. In view of this challenge, in this article, we develop a METamorphic Testing approach to assessing and validating unsupervised machine LEarning systems, abbreviated as mettle. Our approach provides a new way to unveil the (possibly latent) characteristics of various machine learning systems, by explicitly considering the specific expectations and requirements of these systems from individual users’ perspectives. To support mettle, we have further formulated 11 generic metamorphic relations (MRs), covering users’ generally expected characteristics that should be possessed by machine learning systems. We have performed an experiment and a user evaluation study to evaluate the viability and effectiveness of mettle. Our experiment and user evaluation study have shown that, guided by user-defined MR-based adequacy criteria, end users are able to assess, validate, and select appropriate clustering systems in accordance with their own specific needs. Our investigation has also yielded insightful understanding and interpretation of the behavior of the machine learning systems from an end-user software engineering's perspective, rather than a designer's or implementor's perspective, who normally adopts a theoretical approach. [ABSTRACT FROM AUTHOR]

Background/Objective: The role of gene expression changes in acne patients treated by oral isotretinoin (ISO) and in influencing the ISO therapeutic effects is still unclear. In this study, we investigated the gene profiles of patients with severe acne who responded variously to ISO therapy. Methods: The peripheral blood of 113 acne vulgaris patients (Pillsbury IV grade) was collected before treatment. After 8 weeks of oral ISO, nine acne patients were selected and divided into the following groups. A: effectively treated by ISO, group B: ineffectively treated by ISO, group C: ISO-induced acne flare-up, and 3 healthy subjects were included as control group D. The peripheral blood of patients pre- and post-treatment was subjected to high-throughput RNA sequencing technology and bioinformatics analysis of the separate groups (n = 3). The candidate genes were validated by qRT-PCR. Results: Comparing pre- and post-oral ISO treatment, gene expression was changed as 39 genes in ISO-effective group, 345 genes in ISO-ineffective group, and 57 genes in ISO-induced acne flare-up group. Comparing the ISO-induced acne flare-up group with healthy control subjects revealed 34 upregulated genes and 23 downregulated genes, while comparing the ISO-induced acne flare-up group with ISO-ineffective patients identified 1835 changed genes. Expression of GATA2 (2.73 fold, P=0.024512), C4BPA (35.87 folds, P=0.038073), and CCR5 (2.48 folds, P=0.004681) increased in the ISO-induced acne flare-up patients. Meanwhile, the expression of DEFA3 (0.18 fold, P=0.041934), ELANE (0.14 fold, P=0.030767), MMP9 (0.41 fold, P=0.013383), and RPS4Y1 (0.00018 fold, P=0.000986) decreased when compared with ISO-ineffective patients. Conclusion: Oral ISO treatment could temporarily alter gene expression in acne patients. ISO therapeutic mechanisms were involved, not only in regulating the inflammatory reaction but also in the process of DNA repair. GATA2, C4BPA, CCR5, DEFA3, ELANE, MMP9, and RPS4Y1 might be susceptible to genes that could participate in the ISO-induced aggravation of acne. [ABSTRACT FROM AUTHOR]

Pyridine Nucleotide-Disulphide Oxidoreductase Domain 2 (PYROXD2), a Hepatitis B virus X protein (HBx)-interacting protein, is significantly down-regulated in hepatocellular carcinoma (HCC), however its exact biological function remains unclear. The aim of this study is to investigate the subcellular localization and biological function of PYROXD2 in hepatic cells. The results showed that PYROXD2 was imported to the mitochondrial inner membrane/matrix by Tom40 and Tim23, but not Mia40. PYROXD2 151-230aa might be the mitochondrial targeting sequence. PYROXD2 interacted with complex IV subunit COX5B. Knockout of PYROXD2 decreased MMP, intracellular ROS, complex IV activity, cell proliferation, ATP content and mtDNA copy number, but increased mtROS levels and the number of immature mitochondria. In summary, our data illustrated that PYROXD2 localizes to the mitochondrial inner membrane/matrix, and it plays important roles in regulating mitochondrial function. • PYROXD2 is a new protein located in the inner mitochondrial membrane/matrix fraction and interacted with COX5B. • The import of PYROXD2 to mitochondria is dependent on its mitochondrial targeting sequence 151-230 aa. • PYROXD2 plays important roles in the regulation of mitochondrial function. [ABSTRACT FROM AUTHOR]

Summary: Background: Emergence of highly inflammatory genital dermatophyte infections has been reported from Southeast Asia. In view of this, knowledge of the non‐outbreak fungal flora of the genitals is required as a baseline study. Objectives: We present our 12‐year experience in a tertiary clinic with the diagnosis of scrotal fungal infections. Methods: A retrospective review was performed of patients with a diagnosis of scrotal fungal infections proven by direct microscopy and culture. Clinical, mycological and treatment data were collected. Results: In total, 35 male patients were identified, of which 27 concerned dermatophyte infections and eight were yeasts. Nannizzia gypsea was the most common agent (48.6%), presenting as thick pseudomembraneous lesions limited to the scrotum. Trichophyton rubrum (22.9%) and Epidermophyton floccosum (5.7%) mainly presented erythematous, dry and scaly lesions and involving more sites besides the scrotum. Candida albicans (n = 3), C. glabrata (n = 2), C. guilliermondii (n = 1) and Trichosporon asteroides (n = 1), presented various lesions. Sports, sweating and concurrent tineas are hypothesised as predisposing factors. Conclusions: The prevalent causative agent of scrotum infections is N. gypsea, but wide species diversity is observed. All infections show mild skin inflammation. It is suggested that this genital fungal flora represents the current situation prior to clonal dermatophyte outbreaks. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Although there have been some studies about changes of skin erythema and pigmentation following ultraviolet radiation in other races, the relevant data in Chinese have never been achieved. Thus, we evaluated the long-time course of skin erythema, pigmentation and hydration changes after different doses of solar-simulated ultraviolet ( SSUV) irradiation in 26 Chinese women for 168 days. The erythema index increased abruptly and peaked during 3 days of SSUV exposure, then slowly returned to the baseline level starting at day 7 and completely recovered during 168-day course of this study only in one minimal erythema doses ( MED) SSUV irradiation. The melanin index started to slowly increase at day 3 of SSUV exposure, peaking at day 14 and gradually returned to the baseline level thereafter, but did not return to the baseline level during 168-day course in all doses. Skin hydration slowly declined at day 3 of exposure, hitting the lowest point at day 7, then slowly recovered starting at day 14 and completely returned to the baseline level at day 28 only in 1.5 MED. These results will serve as baseline data on Chinese skin and provide useful references for the treatment of serious skin photodamage in Chinese. [ABSTRACT FROM AUTHOR]

Software testing is important and time-consuming. A test suite, i.e., a set of test cases, plays a key role in validating the expected program behavior. In modern test-driven development, a test suite pushes the development progress. Software evolves over time; its test suite is executed to detect whether a new code change adds bugs to the existing code. Executing all test cases after each code change is unnecessary and may be impossible due to the limited development cycle. On the one hand, multiple test cases may focus on an identical piece of code; then several test cases cannot detect extra bugs. On the other hand, even executing a test suite once in a large project takes around one hour [1]; frequent code changes require much time for conducting testing. For instance, in Hadoop, a framework of distributed computing, 2,847 version commits are accepted within one year from September 2014 with a peak of 135 commits in one week [2]. [ABSTRACT FROM PUBLISHER]

In a distributed, dynamic and volatile operating environment, runtime anomalies occurring in service-oriented systems (SOSs) must be located and fixed in a timely manner in order to guarantee successful delivery of outcomes in response to user requests. Monitoring all component services constantly and inspecting the entire SOS upon a runtime anomaly are impractical due to excessive resource and time consumption required, especially in large-scale scenarios. We present a spectrum-based approach that goes through a five-phase process to quickly localize runtime anomalies occurring in SOSs based on end-to-end system delays. Upon runtime anomalies, our approach calculates the similarity coefficient for each basic component (BC) of the SOS to evaluate their suspiciousness of being faulty. Our approach also calculates the delay coefficients to evaluate each BC's contribution to the severity of the end-to-end system delays. Finally, the BCs are ranked by their similarity coefficient scores and delay coefficient scores to determine the order of them being inspected. Extensive experiments are conducted to evaluate the effectiveness and efficiency of the proposed approach. The results indicate that our approach significantly outperforms random inspection and the popular Ochiai-based inspection in localizing single and multiple runtime anomalies effectively. Thus, our approach can help save time and effort for localizing runtime anomalies occuring in SOSs. [ABSTRACT FROM PUBLISHER]

Excessive sun exposure can cause sunburn, suntan, skin photoaging, and even skin cancer. Skin photoaging conflicts with the human pursuit of a young and beautiful appearance. Some research data indicate that the incidence of skin cancer in the Chinese has been increasing, although it remains lower than in whites. To estimate the prevalence of sun protection used on Chinese children aged 3-13 years and identify its predictors, a population-based cross-sectional questionnaire was given to 3684 parents/guardians of children in Guangzhou, China, of which 3083 questionnaires were returned. Of those returned, 35.5% of parents/guardians reported regularly using sun protection on their children and the primary reason cited was to prevent sunburn. Hats and handheld umbrellas were the most frequently used measures; sunscreen was less common, and when used, 48.8% of parents/guardians still reapplied sunscreen on their children every 2.0-3.0 h. Parental age, parents using sun protection measures themselves when outdoors, and the child's sex were factors associated with regular use of sun protection on children. These results suggest that sun protection campaigns targeted toward parents and children need to be conducted in Guangzhou, or throughout China, to strengthen awareness about sun protection and address any inadequate protocols of sun protection. [ABSTRACT FROM AUTHOR]

Objective To investigate genetic polymorphisms of HPRTB, DXS6803 and DXS6809 STR loci in Tianjin Han female population, and to provide experimental data in the prenatal diagnosis of aneuploidies accurately and rapidly. Methods A total of 150 blood samples were collected in Tianjin Han population. QF-PCR and capillary electrophoresis were used in this study. The relevant data were analyzed by ABI Prism GeneMapper v3.0 software. Two homozygotes were selected from each locus for sequencing. The frequencies of the genotypes were checked using Chi-square test to verify Hardy-Weinberg Equilibrium. Data of genetic polymorphisms were calculated by PowerStatsV 12 software. Results A total of 150 samples were successfully amplified in 24 hours. The 10, 6 and 10 alleles and 22, 12 and 29 genotypes were found respectively in HPRTB, DXS6803 and DXS6809 loci. The most common alleles were 14, 13 and 14. The higher frequencies of genotypes were 14- 14, 12- 13 and 13- 14. No significant deviations from the Hardy- Weinberg equilibrium were observed in these three STR loci (X2=10.554, 5.783 and 15.355, respectively, P > 0.05). Values of He were 0.748, 0.649 and 0.806 for these three STR loci respectively. Values of Ho were 0.607, 0.700 and 0.713 respectively. Values of PIC were 0.706, 0.599 and 0.775 respectively. Values of PD were 0.894, 0.814 and 0.931 respectively. And values of PE were 0.299, 0.428 and 0.449 respectively. Conclusion HPRTB, DXS6803 and DXS6809 STR loci were highly polymorphic, which are favorable genetic markers on chromosome X and can be used in rapid prenatal genetic diagnosis. [ABSTRACT FROM AUTHOR]

Minor ST-T abnormalities are common on the resting electrocardiogram of otherwise healthy persons, but the long-term importance of these findings has not been extensively evaluated, especially in women. In a prospective study, 7,985 women and 9,630 men (aged 40 to 64 years at baseline) without other electrocardiographic abnormalities and free of previous coronary heart disease (CHD) were studied using Cox regression for 22-years of follow-up. Primary outcomes were death from CHD and total cardiovascular disease (CVD); total mortality was a secondary outcome. Minnesota Code was employed to assess the presence or absence of electrocardiographic abnormalities. Analyses compared persons with minor Minnesota Code ST-segment (codes 4–3 or 4–4) or T-wave findings (codes 5–3 or 5–4) to those with normal electrocardiographic findings. In combined analyses of men and women adjusted for age, isolated minor T-wave abnormality, minor ST-segment depression, or a combination of minor ST-segment and T-wave abnormalities were each associated with increased mortality risks. For CHD mortality, hazard ratios (HRs) ranged from 1.60 to 2.10; for CVD mortality, HRs ranged from 1.50 to 1.95; and for total mortality, HRs ranged from 1.31 to 1.50 (p <0.05 for all HRs). In separate analyses by gender adjusted for age, increased risks were observed for combined ST-T-wave abnormalities in both genders for CHD and CVD mortality (HR 1.72 to 1.75 for men, p <0.05; HR 2.07 to 2.51 for women, p <0.001). These data indicate that nonspecific (minor) ST-segment depression and/or T-wave abnormalities have a long-term prognostic impact for CHD and CVD death in middle-aged women and men and can be considered markers of heightened CHD and CVD risk. [Copyright &y& Elsevier]

Ischemia-reperfusion (IR) injury is a main cause to and the mechanism of necrosis after flap transplantation. Researches were hardly conducted on the role and possible mechanism of keratinocyte growth factor (KGF) in association with IR flap injury. A CoCl 2 -stimulated hypoxia cell model was established to investigate the effects of KGF on cell viability, apoptosis, cell cycle, and reactive oxygen species level. The experiments were performed by cell counting kit-8 and flow cytometry as required. Meanwhile, the expressions of cell cycle-related and nuclear factor E2–related factor 2 (Nrf2) signaling–related genes were determined using quantitative real-time PCR and Western blot. The right dorsolateral areas of Institute of Cancer Research mice were marked as flaps, the pedicle of which formed an IR process through clamping and loosening. Tissue morphologies were observed using hematoxylin and eosin staining 24 h after the surgery. The effects of KGF on cell apoptosis and associated genes expressions were studied by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, immunohistochemistry, and Western blot. HaCAT cells treated with 40 μM CoCl 2 could not only reduce cell viability, promote cell apoptosis, arrest G1 phase of cell cycle and increase the activity of reactive oxygen species but also downregulate the expressions of c-myc, c-fos, transforming growth factor-α, Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase. Additional recombinant human KGF, on one hand, could protect the cells from hypoxia injury. On the other hand, recombinant human KGF could significantly inhibit cell apoptosis, increase KGF activity, and increase the Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase proteins levels in IR flap tissues. KGF played an important role in protecting mice flaps from IR injury, and the possible mechanism was involved in activating the Nrf2 signaling. [ABSTRACT FROM AUTHOR]

Background and Objectives: The application of adipose derived stem cells (ADSCs) in skin repair has attracted much attention nowadays. Epidermal growth factor (EGF) participates in the progress of skin proliferation, differentiation and so forth. We aimed to explore the role of EGF in the proliferation, invasion, migration and transdifferentiation into epidermal cell phenotypes of ADSCs., Methods and Results: ADSCs were extracted from adipose tissues from patient. Immunophenotyping was determined by flow cytometry. Overexpressed EGF or siEGF was transfected by lentiviruses. EGF was determined by enzyme linked immunosorbent assay (ELISA) or western blot. ADSCs and HaCaT cells were co-cultured by Transwell chambers. Conditioned medium (CM) was obtained from cultured HaCaT cells and used for the culturing of ADSCs. Cell viability was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Invasion rate was measured by Transwell invasion assay and migration rate by wound healing test. mRNA and protein levels were measured by qPCR and western blot respectively. The extracted cells from adipose tissues were identified as ADSCs by morphology and immunophenotyping. The expression of EGF was up or down regulated constantly in HaCaT cell line after transfection. EGF overexpression upregulated the proliferation, migration and invasion rates of ADSCs, and EGF expression regulated the expression of cytokeratin-19 (CK19) and integrin- β as well., Conclusions: EGF could be served as a stimulus to promote the proliferation, migration, and invasion as well as the transdifferentiation into epidermal stem cell immunophenotyping of ADSCs. The results showed that EGF had a promising effect on the repair of skin wound.

Adipose-derived stem cells (ADSCs) and vascular endothelial growth factor (VEGF) contribute to the healing of wound. The purpose of the present study was to investigate the role of VEGF produced by ADSCs in the protection of fibroblasts and skin of mice from ultraviolet (UV) radiation. ADSCs and fibroblasts were extracted from adipose and skin on the abdomen of mice by enzyme digestion methods. ADSCs surface markers were detected using flow cytometry, and immunofluorescence was used to identify fibroblasts. The expression of VEGF in modified ADSCs with lentivirus was determined. Fibroblasts were injured by UV radiation and co-cultured with ADSCs carrying overexpressed VEGF or normal VEGF. Cell cycle was assessed by flow cytometry. Mice were treated with UV radiation dorsally and injected with ADSCs containing overexpressed VEGF or normal VEGF. mRNA and protein levels of cell senescence-related genes were measured by qPCR and western blot. It was found that ADSCs with overexpressed VEGF not only promoted the effect of ADSCs on down-regulating senescence-associated (SA)-β-Gal, p21 and matrix metalloproteinase (MMP)-1, the healing of wound injured by UV radiation and up-regulating collagen I expression in fibroblasts and wound, but also on inhibiting cell cycle arrest in fibroblasts injured by UV radiation and preventing the skin from photoaging caused by UV radiation. VEGF expression in ADSCs played a key role in protecting skin fibroblasts from ageing, which further allowed the skin to resist photoaging, thereby promoting the recovery of wound injured by UV radiation., (© 2019 The Author(s).)

Previous studies revealed that PYROXD2 was more highly expressed in normal liver tissue and liver cell lines than in cancer tissue and cancer cell lines, which indicated that decreased PYROXD2 expression may be involved in hepatocarcinogenesis. To identify the mechanisms which regulate PYROXD2 gene transcription, we constructed a series of luciferase reporter plasmids and used them to perform luciferase‑based reporter assays with HepG2, Sk-hep1, L02 and 293T cells with the purpose of characterizing the PYROXD2 reporter region. Our results revealed that the transcription factor myeloid zinc finger 1 (MZF1) is necessary for PYROXD2 gene transcription and that it functions as a trans-activator. DNA binding assays revealed that the MZF1 protein binds to the cis-element TGGGGA located in the -320/-312 region of the PYROXD2 promoter. This promoter had a significantly enhanced activity when the MZF1 protein was overexpressed and a significantly decreased activity when the MZF1 protein expression was silenced. However, MZF1 gene expression was not significantly correlated with PYROXD2 protein expression in the samples of resected tumor tissues, which revealed that the PYROXD2 promoter transcription activity was determined by the aggregated effect of numerous transcription factors. This finding may be helpful in understanding the underlying mechanism which regulates the PYROXD2 expression.

The emergence of ceftriaxone-resistantNeisseria gonorrhoeaeis currently a global public health concern. However, the mechanism of ceftriaxone resistance is not yet fully understood. To investigate the potential genes related to ceftriaxone resistance inNeisseria gonorrhoeae, we subcultured six gonococcal strains with increasing concentrations of ceftriaxone and isolated the strains that became resistant. After analyzing several frequently reported genes involved in ceftriaxone resistance, we found only a single mutation inpenA(A501V). However, differential analysis of the genomes and transcriptomes between pre- and postselection strains revealed many other mutated genes as well as up- and downregulated genes. Transformation of the mutatedpenAgene into nonresistant strains increased the MIC between 2.0- and 5.3-fold, and transformation of mutatedftsXincreased the MIC between 3.3- and 13.3-fold. Genes encoding the ABC transporters FarB, Tfq, Hfq, and ExbB were overexpressed, whilepilM,pilN, andpilQwere downregulated. Furthermore, the resistant strain developed cross-resistance to penicillin and cefuroxime, had an increased biochemical metabolic rate, and presented fitness defects such as prolonged growth time and downregulated PilMNQ. In conclusion, antimicrobial pressure could result in the emergence of ceftriaxone resistance, and the evolution of resistance ofNeisseria gonorrhoeaeto ceftriaxone is a complicated process at both the pretranscriptional and posttranscriptional levels, involving several resistance mechanisms of increased efflux and decreased entry., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

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.

Many applications in the field of scientific computing - such as computational biology, computational linguistics, and others - depend on Machine Learning algorithms to provide important core functionality to support solutions in the particular problem domains. However, it is difficult to test such applications because often there is no "test oracle" to indicate what the correct output should be for arbitrary input. To help address the quality of such software, in this paper we present a technique for testing the implementations of supervised machine learning classification algorithms on which such scientific computing software depends. Our technique is based on an approach called "metamorphic testing", which has been shown to be effective in such cases. More importantly, we demonstrate that our technique not only serves the purpose of verification, but also can be applied in validation. In addition to presenting our technique, we describe a case study we performed on a real-world machine learning application framework, and discuss how programmers implementing machine learning algorithms can avoid the common pitfalls discovered in our study. We also discuss how our findings can be of use to other areas outside scientific computing, as well.

Background: 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., Results: 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., Conclusion: 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.