Semi-supervised and Active Learning Models for Software Fault Prediction

As software continues to insinuate itself into nearly every aspect of our life, the quality of software has been an extremely important issue. Software Quality Assurance (SQA) is a process that ensures the development of high-quality software. It concerns the important problem of maintaining, monitoring, and developing quality software. Accurate detection of fault prone components in software projects is one of the most commonly practiced techniques that offer the path to high quality products without excessive assurance expenditures. This type of quality modeling requires the availability of software modules with known fault content developed in similar environment. However, collection of fault data at module level, particularly in new projects, is expensive and time-consuming. Semi-supervised learning and active learning offer solutions to this problem for learning from limited labeled data by utilizing inexpensive unlabeled data.;In this dissertation, we investigate semi-supervised learning and active learning approaches in the software fault prediction problem. The role of base learner in semi-supervised learning is discussed using several state-of-the-art supervised learners. Our results showed that semi-supervised learning with appropriate base learner leads to better performance in fault proneness prediction compared to supervised learning. In addition, incorporating pre-processing technique prior to semi-supervised learning provides a promising direction to further improving the prediction performance. Active learning, sharing the similar idea as semi-supervised learning in utilizing unlabeled data, requires human efforts for labeling fault proneness in its learning process. Empirical results showed that active learning supplemented by dimensionality reduction technique performs better than the supervised learning on release-based data sets

Abnormal Plasma Levels of Steroids and Their Ratios in Patients With Prurigo Nodularis: A Pilot Study

Background: It has been suggested that cortisol levels are abnormal in chronic urticaria and atopic dermatitis, but other steroids, such as dehydroepiandrosterone (DHEA) and testosterone, are still unknown, and whether these hormones affect the maintenance of skin homeostasis or the pathogenesis of skin diseases is not fully understood. Limited data are available on steroid levels in prurigo nodularis (PN)-related research, and no study has examined the association between pruritus severity and steroid levels in PN patients.Aims: This pilot study aimed to investigate the differences in the levels of five steroids combined with their ratios in plasma between PN patients and controls and to examine the associations between the biomarkers and pruritus severity.Methods: Plasma concentrations of five steroids, including cortisol, cortisone, testosterone, progesterone, and dehydroepiandrosterone (DHEA), in 36 patients with PN were compared with concentrations in thirty-six and matched healthy controls. The concentrations of steroids were quantitated using liquid chromatography-tandem mass spectrometry. The PN symptoms, including pruritus severity, pain, and life quality, were assessed with the use of the visual analog scale, prurigo score index, numerical rating scale, and verbal rating scale and dermatology life quality index scores.Results: In comparison with controls, PN patients had lower levels of plasma cortisol and cortisone, which negatively correlated with PN symptoms. PN patients had higher levels of cortisone and testosterone to cortisol, which positively correlated with pruritus severity. Additionally, there were no significant differences in plasma concentrations of DHEA and testosterone between the two groups. We found no correlation between plasma concentrations of DHEA and testosterone and pruritus severity.Conclusion: This pilot study suggests that there may be abnormalities in peripheral blood levels of cortisol, and cortisone and the ratios of cortisone and testosterone to cortisol in patients with PN, and they are related to pruritus severity. The plasma concentrations of testosterone and DHEA may be not abnormal in PN patients and may not be associated with pruritus severity

Expression of a Constitutively Active Nitrate Reductase Variant in Tobacco Reduces Tobacco-Specific Nitrosamine Accumulation in Cured Leaves and Cigarette Smoke

Burley tobaccos (Nicotiana tabacum) display a nitrogen-use-deficiency phenotype that is associated with the accumulation of high levels of nitrate within the leaf, a trait correlated with production of a class of compounds referred to as tobacco-specific nitrosamines (TSNAs). Two TSNA species, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), have been shown to be strong carcinogens in numerous animal studies. We investigated the potential of molecular genetic strategies to lower nitrate levels in burley tobaccos by overexpressing genes encoding key enzymes of the nitrogen-assimilation pathway. Of the various constructs tested, only the expression of a constitutively active nitrate reductase (NR) dramatically decreased free nitrate levels in the leaves. Field-grown tobacco plants expressing this NR variant exhibited greatly reduced levels of TSNAs in both cured leaves and mainstream smoke of cigarettes made from these materials. Decreasing leaf nitrate levels via expression of a constitutively active NR enzyme represents an exceptionally promising means for reducing the production of NNN and NNK, two of the most well-documented animal carcinogens found in tobacco products

Genome-wide identification, expression and function analysis of the MTP gene family in tulip (Tulipa gesneriana)

Currently, soil heavy metal contamination is a severe issue, particularly with Cd pollution. The metal tolerance protein (MTP) proteins, as plant divalent cation transporters, play a crucial role in the transport and tolerance of heavy metals in plants. This study conducted comprehensive identification and characterization of the MTP gene family in the tulip. A total of 11 TgMTP genes were identified and phylogenetically classified into three subfamilies. Conserved motif and gene structure analyses unveiled commonalities and variations among subfamily members. Expression profiling demonstrated several TgMTPs were markedly upregulated under Cd exposure, including the TgMTP7.1. Heterologous expression in yeast validated that TgMTP7.1 could ameliorate Cd sensitivity and enhance its tolerance. These results provide primary insights into the MTP gene family in tulip. Phylogenetic relationships and functional analyses establish a framework for elucidating the transporters and molecular mechanisms governing Cd accumulation and distribution in tulip. Key TgMTPs identified, exemplified by TgMTP7.1, may illuminate molecular breeding efforts aimed at developing Cd-tolerant cultivars for the remediation of soil Cd contamination

PRIMA-1Met suppresses colorectal cancer independent of p53 by targeting MEK

This work was supported by Grant No. 81201779 (Hua Xiong) from the National Natural Science Youth Foundation; Grant No. 81502118 (Yanmei Zou) from the National Natural Science Youth Foundation; Grant No. 2014CFB250 (Yanmei Zou) from the Natural Science Foundation of Hubei Province; Grant No. 81372434 (Huihua Xiong) from the National Natural Science Foundation.PRIMA-1Met is the methylated PRIMA-1 (p53 reactivation and induction of massive apoptosis) and could restore tumor suppressor function of mutant p53 and induce p53 dependent apoptosis in cancer cells harboring mutant p53. However, p53 independent activity of PRIMA-1Met remains elusive. Here we reported that PRIMA-1Met attenuated colorectal cancer cell growth irrespective of p53 status. Kinase profiling revealed that mitogen-activated or extracellular signal-related protein kinase (MEK) might be a potential target of PRIMA-1Met. Pull-down binding and ATP competitive assay showed that PRIMA-1Met directly bound MEK in vitro and in cells. Furthermore, the direct binding sites of PRIMA-1Met were explored by using a computational docking model. Treatment of colorectal cancer cells with PRIMA-1Met inhibited p53-independent phosphorylation of MEK, which in turn impaired anchorage-independent cell growth in vitro. Moreover, PRIMA-1Met suppressed colorectal cancer growth in xenograft mouse model by inhibiting MEK1 activity. Taken together, our findings demonstrate a novel p53-independent activity of PRIMA-1Met to inhibit MEK and suppress colorectal cancer growth.Publisher PDFPeer reviewe

Stachydrine Ameliorates Cardiac Fibrosis Through Inhibition of Angiotensin II/Transformation Growth Factor β1 Fibrogenic Axis

Cardiovascular diseases, the leading cause of death worldwide, are tightly associated with the pathological myocardial fibrosis. Stachydrine (Sta), a major active compound in Chinese motherwort Leonurus heterophyllus, was reported to effectively attenuate cardiac fibrosis, but the cellular and molecular mechanism remains unclear. In this study, the anti-fibrotic effect of Sta and mechanism underlying were explored in a mouse model of pressure overload and AngII stimulated cardiac fibroblasts (CFs). Mice were randomly divided into sham, transverse aorta constriction with saline (TAC+Sal), TAC with telmisartan (TAC+Tel), and TAC with Sta (TAC+Sta) groups. Cardiac morphological and functional changes were evaluated by echocardiography and histological methods, and the molecular alterations were detected by western blotting. Primary cultured neonatal mouse CFs were treated with or without angiotensin II (AngII, 10−7 M), transformation growth factor β1 (TGFβ1, 10 ng/mL), and different dosage of Sta (10−6–10−4 M) for up to 96 h, and cell proliferation, cytotoxicity, morphology and related signals were also detected. The in vivo results revealed that TAC prominently induced cardiac dysfunction, left ventricular dilation, myocardial hypertrophy, and elevated myocardial collagen deposition, accompanied with increased fibrotic markers including α-smooth muscle actin (α-SMA) and periostin. However, Sta treatment partially reversed cardiac morphological and functional deteriorations, and significantly blunted cardiac fibrosis as well as Tel. Increments of myocardial angiotensinogen (AGT), angiotensin converting enzyme (ACE), AngII type 1 receptor (AT1R), and TGFβ1 transcripts, together with increased protein levels of ACE and AngII, after TAC were dramatically down-regulated by Sta treatment. Coincidently, in vitro experiments demonstrated that AngII stimulation in CFs led to up-regulation of AT1R and TGFβ1, and therefore promoted CFs trans-differentiating into hyper-activated myocardial fibroblasts (MFs) as evidenced by increased cell proliferation, collagen and fibrotic makers. On the contrary, Sta potently down-regulated but not directly inhibited AT1R, suppressed TGFβ1 production, and the pro-fibrotic effect of AngII in CFs. Moreover, activation of TGFβ1/Smads signal in the fibrotic process were observed both TAC model and in AngII stimulated CFs, which were also notably blunted by Sta. However, Sta failed to abolish the activation of CFs triggered by TGFβ1. Taken together, it was demonstrated in this study that Sta suppressed ACE/AngII/AT1R-TGFβ1 profibrotic axis, especially on the de novo production of AngII via down-regulating AGT/ACE and AT1R, and therefore inactivated CFs and blunted MFs transition, which ultimately prevented cardiac fibrosis

Analysis of chromosomal structural variations in patients with recurrent spontaneous abortion using optical genome mapping

Background and aims: Certain chromosomal structural variations (SVs) in biological parents can lead to recurrent spontaneous abortions (RSAs). Unequal crossing over during meiosis can result in the unbalanced rearrangement of gamete chromosomes such as duplication or deletion. Unfortunately, routine techniques such as karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and copy number variation sequencing (CNV-seq) cannot detect all types of SVs. In this study, we show that optical genome mapping (OGM) quickly and accurately detects SVs for RSA patients with a high resolution and provides more information about the breakpoint regions at gene level.Methods: Seven couples who had suffered RSA with unbalanced chromosomal rearrangements of aborted embryos were recruited, and ultra-high molecular weight (UHMW) DNA was isolated from their peripheral blood. The consensus genome map was created by de novo assembly on the Bionano Solve data analysis software. SVs and breakpoints were identified via alignments of the reference genome GRCh38/hg38. The exact breakpoint sequences were verified using either Oxford Nanopore sequencing or Sanger sequencing.Results: Various SVs in the recruited couples were successfully detected by OGM. Also, additional complex chromosomal rearrangement (CCRs) and four cryptic balanced reciprocal translocations (BRTs) were revealed, further refining the underlying genetic causes of RSA. Two of the disrupted genes identified in this study, FOXK2 [46,XY,t(7; 17)(q31.3; q25)] and PLXDC2 [46,XX,t(10; 16)(p12.31; q23.1)], had been previously shown to be associated with male fertility and embryo transit.Conclusion: OGM accurately detects chromosomal SVs, especially cryptic BRTs and CCRs. It is a useful complement to routine human genetic diagnostics, such as karyotyping, and detects cryptic BRTs and CCRs more accurately than routine genetic diagnostics