Automatic instantiation of abstract tests on specific configurations for large critical control systems

Computer-based control systems have grown in size, complexity, distribution and criticality. In this paper a methodology is presented to perform an abstract testing of such large control systems in an efficient way: an abstract test is specified directly from system functional requirements and has to be instantiated in more test runs to cover a specific configuration, comprising any number of control entities (sensors, actuators and logic processes). Such a process is usually performed by hand for each installation of the control system, requiring a considerable time effort and being an error prone verification activity. To automate a safe passage from abstract tests, related to the so called generic software application, to any specific installation, an algorithm is provided, starting from a reference architecture and a state-based behavioural model of the control software. The presented approach has been applied to a railway interlocking system, demonstrating its feasibility and effectiveness in several years of testing experience

PI3K Functions in Cancer Progression, Anticancer Immunity and Immune Evasion by Tumors

The immunological surveillance of tumors relies on a specific recognition of cancer cells and their associate antigens by leucocytes of innate and adaptive immune responses. However, a dysregulated cytokine release can lead to, or be associated with, a failure in cell-cell recognition, thus, allowing cancer cells to evade the killing system. The phosphatidylinositol 3-kinase (PI3K) pathway regulates multiple cellular processes which underlie immune responses against pathogens or malignant cells. Conversely, there is accumulating evidence that the PI3K pathway is involved in the development of several malignant traits of cancer cells as well as their escape from immunity. Herein, we review the counteracting roles of PI3K not only in antitumor immune response but also in the mechanisms that cancer cells use to avoid leukocyte attack. In addition, we discuss, from antitumor immunological point of view, the potential benefits and disadvantages arising from use of anticancer pharmacological agents targeting the PI3K pathway

The Kakeya problem : a gap in the spectrum and classification of the smallest examples

Kakeya sets in the affine plane are point sets that are the union of lines, one through every point on the line at infinity. The finite field Kakeya problem asks for the size of the smallest Kakeya sets and the classification of these Kakeya sets. In this article we present a new example of a small Kakeya set and we give the classification of the smallest Kakeya sets up to weight q(q + 2)/2, q/4 , both in case q even

A Model Driven Approach to Water Resource Analysis based on Formal Methods and Model Transformation

AbstractSeveral frameworks have been proposed in literature in order to cope with critical infrastructure modelling issues, and almost all rely on simulation techniques. Anyway simulation is not enough for critical systems, where any problem may lead to consistent loss in money and even human lives. Formal methods are widely used in order to enact exhaustive analyses of these systems, but their complexity grows with system dimension and heterogeneity. In addition, experts in application domains could not be familiar with formal modelling techniques. A way to manage complexity of analysis is the use of Model Based Transformation techniques: analysts can express their models in the way they use to do and automatic algorithms translate original models into analysable ones, reducing analysis complexity in a completely transparent way.In this work we describe an automatic transformation algorithm generating hybrid automata for the analysis of a natural water supply system. We use real system located in the South of Italy as case study

1H-NMR metabolomics reveals a multitarget action of Crithmum maritimum ethyl acetate extract in inhibiting hepatocellular carcinoma cell growth

Hepatocellular carcinoma (HCC) is nowadays the sixth cause of tumour-related deceases worldwide, estimated to become the third in Western countries by 2030. New drugs for HCC treatment still have many adverse effects. Several lines of evidence indicate that plant metabolites offer concrete opportunities for developing new therapeutic strategies for many diseases, including cancer. We previously reported that ethyl acetate extract of a spontaneous edible plant harvested in Apulia, Crithmum maritimum, significantly inhibited cell growth in HCC cells. By 1H-NMR spectroscopy, here we show that Crithmum maritimum ethyl acetate extract counteracts the Warburg effect, by reducing intracellular lactate, inhibits protein anabolism, by decreasing amino acid level, and affects membrane biosynthesis by lowering choline and phosphocholine. Also, we observed an effect on lipid homeostasis, with a reduction in triglycerides, cholesterol, monounsaturated fatty acids (MUFA), and diunsaturated fatty acids (DUFA), and an increase in polyunsaturated fatty acids (PUFA). Taken together, these data demonstrate that Crithmum maritimum-induced cytostasis is exerted through a multi-effect action, targeting key metabolic processes in HCC cells. Overall, our findings highlight the role of Crithmum maritimum as a promising tool for the prevention and the improvement of the therapeutic options for HCC and other types of tumours

Differential inhibition of the TGF-b signaling pathway in HCC cells using the small molecule inhibitor LY2157299 and the D10 monoclonal antibody against TGF-β receptor Type II

We investigated blocking the TGF-b signaling pathway in HCC using two small molecule inhibitors (LY2157299, LY2109761) and a neutralizing humanized antibody (D10) against TGF-bRII. LY2157299 and LY2109761 inhibited HCC cell migration on Laminin-5, Fibronectin, Vitronectin, Fibrinogen and Collagen-I and de novo phosphorylation of pSMAD2. LY2157299 inhibited HCC migration and cell growth independently of the expression levels of TGF-bRII. In contrast to LY2157299, D10 showed a reduction in pSMAD2 only after a short exposure. This study supports the use of LY2157299 in clinical trials, and presents new insights into TGF-b receptor cycling in cancer cells