Semantic Mutation Analysis of Floating-Point Comparison

I Semantic Mutation Testing (SMT) for C I Semantic mutation operators for FPC I Experiment and result

Comparative transcriptomics uncovers alternative splicing changes and signatures of selection from maize improvement

Background: Alternative splicing (AS) is an important regulatory mechanism that greatly contributes to eukaryotic transcriptome diversity. A substantial amount of evidence has demonstrated that AS complexity is relevant to eukaryotic evolution, development, adaptation, and complexity. In this study, six teosinte and ten maize transcriptomes were sequenced to analyze AS changes and signatures of selection in maize domestication and improvement. Results In maize and teosinte, 13,593 highly conserved genes, including 12,030 multiexonic genes, were detected. By identifying AS isoforms from mutliexonic genes, we found that AS types were not significantly different between maize and teosinte. In addition, the two main AS types (intron retention and alternative acceptor) contributed to more than 60% of the AS events in the two species, but the average unique AS events per each alternatively spliced gene in maize (4.12) was higher than that in teosinte (2.26). Moreover, 94 genes generating 98 retained introns with transposable element (TE) sequences were detected in maize, which is far more than 9 retained introns with TEs detected in teosinte. This indicates that TE insertion might be an important mechanism for intron retention in maize. Additionally, the AS levels of 3864 genes were significantly different between maize and teosinte. Of these, 151 AS level-altered genes that are involved in transcriptional regulation and in stress responses are located in regions that have been targets of selection during maize improvement. These genes were inferred to be putatively improved genes. Conclusions We suggest that both maize and teosinte share similar AS mechanisms, but more genes have increased AS complexity during domestication from teosinte to maize. Importantly, a subset of AS level-increased genes that encode transcription factors and stress-responsive proteins may have been selected during maize improvement

A framework for pathologies of message sequence charts

This is the post-print version of the final paper published in Information Software and Technology. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2012 Elsevier B.V.Context - It is known that a Message Sequence Chart (MSC) specification can contain different types of pathology. However, definitions of different types of pathology and the problems caused by pathologies are unclear, let alone the relationships between them. In this circumstance, it can be problematic for software engineers to accurately predict the possible problems that may exist in implementations of MSC specifications and to trace back to the design problems in MSC specifications from the observed problems of an implementation. Objective - We focus on generating a clearer view on MSC pathologies and building formal relationships between pathologies and the problems that they may cause. Method - By concentrating on the problems caused by pathologies, a categorisation of problems that a distributed system may suffer is first introduced. We investigate the different types of problems and map them to categories of pathologies. Thus, existing concepts related to pathology are refined and necessary concepts in the pathology framework are identified. Finally, we formally prove the relationships between the concepts in the framework. Results - A pathology framework is established as desired based on a restriction that considers problematic scenarios with a single undesirable event. In this framework, we define disjoint categories of both pathologies and the problems caused; the identified types of pathology are successfully mapped to the problems that they may cause. Conclusion - The framework achieved in this paper introduces taxonomies into and clarifies relationships between concepts in research on MSC pathologies. The taxonomies and relationships in the framework can help software engineers to predict problems and verify MSC specifications. The single undesirable event restriction not only enables a categorisation of pathological scenarios, but also has the potential practical benefit that a software engineer can concentrate on key problematic scenarios. This may make it easier to either remove pathologies from an MSC specification MM or test an implementation developed from MM for potential problems resulting from such pathologies

Reducing the gap between streaming and non-streaming Transducer-based ASR by adaptive two-stage knowledge distillation

Transducer is one of the mainstream frameworks for streaming speech recognition. There is a performance gap between the streaming and non-streaming transducer models due to limited context. To reduce this gap, an effective way is to ensure that their hidden and output distributions are consistent, which can be achieved by hierarchical knowledge distillation. However, it is difficult to ensure the distribution consistency simultaneously because the learning of the output distribution depends on the hidden one. In this paper, we propose an adaptive two-stage knowledge distillation method consisting of hidden layer learning and output layer learning. In the former stage, we learn hidden representation with full context by applying mean square error loss function. In the latter stage, we design a power transformation based adaptive smoothness method to learn stable output distribution. It achieved 19\% relative reduction in word error rate, and a faster response for the first token compared with the original streaming model in LibriSpeech corpus

Self-crosslinkable chitosan-hyaluronic acid dialdehyde nanoparticles for CD44-targeted siRNA delivery to treat bladder cancer

Bladder cancer is one of the concerning malignancies worldwide, which is lacking effective targeted therapy. Gene therapy is a potential approach for bladder cancer treatment. While, a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo. In this study, we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs (siRNA) with high interfere to Bcl2 oncogene were designed and screened. Then hyaluronic acid dialdehyde (HAD) was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles (CS-HAD NPs) to achieve CD44 targeted siRNA delivery. The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs (siRNA@CS-HAD NPs) were approximately 100 nm in size, with improved stability, high siRNA encapsulation efficiency and low cytotoxicity. CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer. Overall, a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment, which could be more conducive to clinical application due to its simple preparation and high biological safety

Effects of Intranasal Oxytocin on Pup Deprivation-Evoked Aberrant Maternal Behavior and Hypogalactia in Rat Dams and the Underlying Mechanisms

Oxytocin (OT), a hypothalamic neuropeptide, applied through nasal approach (IAO), could improve maternal health during lactation that is disrupted by mother–baby separation; however, the regulation of IAO effects on maternal behaviors and lactation as well as the underlying mechanisms remain unclear. Using lactating rats, we observed effects of intermittent pup deprivation (PD) with and without IAO on maternal behaviors and lactation as well as the activity of OT neurons in the supraoptic nucleus (SON) and the activity of hypothalamic pituitary-adrenal axis, key factors determining the milk-letdown reflex during lactation and maternal behaviors. The results showed that PD reduced maternal behaviors and lactation efficiency of rat dams as indicated by significantly longer latency to retrieve their pups and low litter’s body weight gains during the observation, respectively. In addition, PD caused early involution of the mammary glands. IAO partially improved these changes in rat dams, which was not as significant as IAO effects on control dams. In the SON, PD decreased c-Fos and increased glial fibrillary acidic protein (GFAP) filaments significantly; IAO made PD-evoked c-Fos reduction insignificant while reduced GFAP filament significantly in PD dams. IAO tended to increase the levels of phosphorylated extracellular signal-regulated kinases (pERK) 1/2 in PD dams. Moreover, PD+IAO significantly increased plasma levels of dam adrenocorticotropic hormone and corticosterone but not OT levels. Lastly, PD+IAO tended to increase the level of corticotropin-releasing hormone in the SON. These results indicate that PD disrupts maternal behaviors and lactation by suppressing the activity of hypothalamic OT-secreting system through expansion of astrocytic processes, which are partially reversed by IAO through removing astrocytic inhibition of OT neuronal activity. However, the improving effect of IAO on the maternal health could be compromised by simultaneous activation of hypothalamic pituitary-adrenocortical axis

Genetic Markers of Toxicity From Capecitabine and Other Fluorouracil-Based Regimens: Investigation in the QUASAR2 Study, Systematic Review, and Meta-Analysis

Fluourouracil (FU) is a mainstay of chemotherapy, although toxicities are common. Genetic biomarkers have been used to predict these adverse events, but their utility is uncertain

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe