A Product Line Systems Engineering Process for Variability Identification and Reduction

Software Product Line Engineering has attracted attention in the last two decades due to its promising capabilities to reduce costs and time to market through reuse of requirements and components. In practice, developing system level product lines in a large-scale company is not an easy task as there may be thousands of variants and multiple disciplines involved. The manual reuse of legacy system models at domain engineering to build reusable system libraries and configurations of variants to derive target products can be infeasible. To tackle this challenge, a Product Line Systems Engineering process is proposed. Specifically, the process extends research in the System Orthogonal Variability Model to support hierarchical variability modeling with formal definitions; utilizes Systems Engineering concepts and legacy system models to build the hierarchy for the variability model and to identify essential relations between variants; and finally, analyzes the identified relations to reduce the number of variation points. The process, which is automated by computational algorithms, is demonstrated through an illustrative example on generalized Rolls-Royce aircraft engine control systems. To evaluate the effectiveness of the process in the reduction of variation points, it is further applied to case studies in different engineering domains at different levels of complexity. Subject to system model availability, reduction of 14% to 40% in the number of variation points are demonstrated in the case studies.Comment: 12 pages, 6 figures, 2 tables; submitted to the IEEE Systems Journal on 3rd June 201

Nuciferine downregulates Per-Arnt-Sim kinase expression during its alleviation of lipogenesis and inflammation on oleic acid-induced hepatic steatosis in HepG2 cells

Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disease associated with lipotoxicity, lipid peroxidation, oxidative stress and inflammation. Nuciferine, an active ingredient extracted from the natural lotus leaf, has been reported to be effective for the prevention and treatment of NAFLD. Per-Arnt-Sim kinase (PASK) is a nutrient responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration and gene expression. The aim of the present study was to investigate the protective effect of nuciferine against NAFLD and its inhibitory effect on PASK, exploring the possible underlying mechanism of nuciferine-mediated inhibition on NAFLD. Relevant biochemical parameters (lipid accumulation, extent of oxidative stress and release of inflammation cytokines) in oleic acid (OA)-induced HepG2 cells that mimicked steatosis in vitro were measured and compared with the control. It was found that nuciferine and silenced-PASK (siRNA PASK) both inhibited triglyceride (TG) accumulation and was effective in decreasing fatty acid (FFAs). The content of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) were increased respectively by nuciferine and siRNA PASK without increase in glutathione (GSH). Malondialdehyde (MDA) was decreased respectively by nuciferine and siRNA PASK. In addition, nuciferine decreased TNF-a, IL-6 and IL-8 as well as the siRNA PASK group. IL-10 was increased by nuciferine and siRNA PASK respectively. Further investigation revealed that nuciferine and siRNA PASK could respectively regulate the expression of target genes involved in lipogenesis and inflammation, suggesting that nuciferine may be a potential therapeutic treatment for NAFLD. Furthermore, the modulated effect of nuciferine on (OA)-induced HepG2 cells lipogenesis and inflammation, which was accompanied with PASK inhibition, was also consistent with siRNA PASK, implying that PASK might play a role in nuciferine-mediated regulation on NAFLD

Detection of a superconducting phase in a two-atom layer of hexagonal Ga film grown on semiconducting GaN(0001)

The recent observation of superconducting state at atomic scale has motivated the pursuit of exotic condensed phases in two-dimensional (2D) systems. Here we report on a superconducting phase in two-monolayer crystalline Ga films epitaxially grown on wide band-gap semiconductor GaN(0001). This phase exhibits a hexagonal structure and only 0.552 nm in thickness, nevertheless, brings about a superconducting transition temperature Tc as high as 5.4 K, confirmed by in situ scanning tunneling spectroscopy, and ex situ electrical magneto-transport and magnetization measurements. The anisotropy of critical magnetic field and Berezinski-Kosterlitz-Thouless-like transition are observed, typical for the 2D superconductivity. Our results demonstrate a novel platform for exploring atomic-scale 2D superconductor, with great potential for understanding of the interface superconductivity

A Wohlfahrtiimonas chitiniclastica with a novel type of blaVEB–1-carrying plasmid isolated from a zebra in China

BackgroundWohlfahrtiimonas chitiniclastica is an emerging fly-borne zoonotic pathogen, which causes infections in immunocompromised patients and some animals. Herein, we reported a W. chitiniclastica BM-Y from a dead zebra in China.MethodsThe complete genome sequencing of BM-Y showed that this isolate carried one chromosome and one novel type of blaVEB–1-carrying plasmid. Detailed genetic dissection was applied to this plasmid to display the genetic environment of blaVEB–1.ResultsThree novel insertion sequence (IS) elements, namely ISWoch1, ISWoch2, and ISWoch3, were found in this plasmid. aadB, aacA1, and gcuG were located downstream of blaVEB–1, composing a gene cassette array blaVEB–1–aadB–aacA1–gcuG bracketed by an intact ISWoch1 and a truncated one, which was named the blaVEB–1 region. The 5′-RACE experiments revealed that the transcription start site of the blaVEB–1 region was located in the intact ISWoch1 and this IS provided a strong promoter for the blaVEB–1 region.ConclusionThe spread of the blaVEB–1-carrying plasmid might enhance the ability of W. chitiniclastica to survive under drug selection pressure and aggravate the difficulty in treating infections caused by blaVEB–1-carrying W. chitiniclastica. To the best of our knowledge, this is the first report of the genetic characterization of a novel blaVEB–1-carrying plasmid with new ISs from W. chitiniclastica

Destabilization of Fatty Acid Synthase by Acetylation Inhibits De Novo Lipogenesis and Tumor Cell Growth

Fatty acid synthase (FASN) is the terminal enzyme in de novo lipogenesis and plays a key role in cell proliferation. Pharmacological inhibitors of FASN are being evaluated in clinical trials for treatment of cancer, obesity and other diseases. Here we report a previously unknown mechanism of FASN regulation involving its acetylation by KAT8 and its deacetylation by HDAC3. FASN acetylation promoted its degradation via the ubiquitin-proteasome pathway. FASN acetylation enhanced its association with the E3 ubiquitin-ligase TRIM21. Acetylation destabilized FASN and resulted in decreased de novo lipogenesis and tumor cell growth. FASN acetylation was frequently reduced in human hepatocellular carcinoma samples, which correlated with increased HDAC3 expression and FASN protein levels. Our results suggest opportunities to target FASN acetylation as an anticancer strategy