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Nitric oxide-dependent cytoskeletal changes and inhibition of endothelial cell migration contribute to the suppression of angiogenesis by RAD50 gene transfer

AbstractPrevious reports showed that human RAD50 (hRAD50) gene delivery induced regression of an experimental rat tumor and porcine neointimal hyperplasia. In this study, we examined the effects of hRAD50 on the morphological changes and migration of endothelial cells (EC) as possible mechanisms by which hRAD50 might block angiogenesis. Quantitative image analysis revealed significant inhibition of the number and total area of blood vessels in rat tumor tissues following hRAD50 gene delivery. hRAD50 distorted actin and tubulin arrangements, and significantly reduced the F/G-actin ratio and increased the nitric oxide (NO) production in the primary cultured human EC. These effects were blocked by pretreatment with L-NAME (NG-nitro-L-arginine-methyl ester), a NO synthase inhibitor. FACScan analysis showed that NO was involved in the necrosis and apoptosis of EC by hRAD50. hRAD50 also inhibited EC migration in an in vitro wound-healing model. These results indicate that NO-dependent cytoskeletal changes and inhibition of EC migration contribute to the suppression of angiogenesis by hRAD50 delivery in vivo

Wasm SpecTec: Engineering a Formal Language Standard

WebAssembly (Wasm) is a low-level bytecode language and virtual machine, intended as a compilation target for a wide range of programming languages, which is seeing increasing adoption across diverse ecosystems. As a young technology, Wasm continues to evolve -- it reached version 2.0 last year and another major update is expected soon. For a new feature to be standardised in Wasm, four key artefacts must be presented: a formal (mathematical) specification of the feature, an accompanying prose pseudocode description, an implementation in the official reference interpreter, and a suite of unit tests. This rigorous process helps to avoid errors in the design and implementation of new Wasm features, and Wasm's distinctive formal specification in particular has facilitated machine-checked proofs of various correctness properties for the language. However, manually crafting all of these artefacts requires expert knowledge combined with repetitive and tedious labor, which is a burden on the language's standardization process and authoring of the specification. This paper presents Wasm SpecTec, a technology to express the formal specification of Wasm through a domain-specific language. This DSL allows all of Wasm's currently handwritten specification artefacts to be error-checked and generated automatically from a single source of truth, and is designed to be easy to write, read, compare, and review. We believe that Wasm SpecTec's automation and meta-level error checking will significantly ease the current burden of the language's specification authors. We demonstrate the current capabilities of Wasm SpecTec by showcasing its proficiency in generating various artefacts, and describe our work towards replacing the manually written official Wasm specification document with specifications generated by Wasm SpecTec.Comment: 5 pages, 7 figure

Hypermethylation of p16INK4a in Korean Non-small Cell Lung Cancer Patients

Promoter hypermethylation of the p16INK4a gene was investigated in 81 sets of samples of tumor tissue and adjacent normal tissue from Korean patients with primary lung cancer, using the modified real-time polymerase chain reaction (PCR)/ SYBR Green detection method. The results showed hypermethylation of p16INK4a in 27.2% of tumor tissues, and in 11.1% of adjacent normal tissue. No significant association was found between the overall aberrant methylation in tumor and corresponding normal specimens (r=0.137, p=0.219). In 22 cases with p16INK4a hypermethylation in tumor tissues, only 4 (18.1%) cases were found to have a hypermethylated normal tissue specimen. The findings of this study show that smoking can influence the methylation level of the promoter region of p16INK4a, and that this occurs in tumor tissues more frequently than in normal tissues. Other clinicopathological characteristics, including age, sex, tumor stage, and histologic type were not found to be correlated with p16INK4a methylation

Characteristics and psychiatric symptoms of Internet Gaming Disorder among adults using self-reported DSM-5 criteria

Objective: The Section III of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) proposed nine diagnostic criteria and five cut-point criteria for Internet Gaming Disorder (IGD). We aimed to examine the efficacy of such criteria. Methods: Adults (n=3041, men: 1824, women: 1217) who engaged in internet gaming within last 6 months completed a self-report online survey using the suggested wordings of the criteria in DSM-5. Major characteristics, gaming behavior, and psychiatric symptoms of IGD were analyzed using ANOVA, chi-square, and correlation analyses. Results: The sociodemographic variables were not statistically significant between the healthy controls and the risk group. Among the participants, 419 (13.8%) were identified and labeled as the IGD risk group. The IGD risk group scored significantly higher on all motivation subscales (p<0.001). The IGD risk group showed significantly higher scores than healthy controls in all nine psychiatric symptom dimensions, i.e., somatization, obsession-compulsion, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism (p<0.001). Conclusion: The IGD risk group showed differential psychopathological manifestations according to DSM-5 IGD diagnostic criteria. Further studies are needed to evaluate the reliability and validity of the specific criteria, especially for developing screening instruments

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis