Automatic instantiation of abstract tests to 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 statebased 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

The perplexity of targeting genetic alterations in hepatocellular carcinoma

Genetic heterogeneity is a well-recognized feature of hepatocellular carcinoma (HCC). The coexistence of multiple genetic alterations in the same HCC nodule contributes to explain why gene-targeted therapy has largely failed. Targeting of early genetic alterations could theoretically be a more effective therapeutic strategy preventing HCC. However, the failure of most targeted therapies has raised much perplexity regarding the role of genetic alterations in driving cancer as the main paradigm. Here, we discuss the methodological and conceptual limitations of targeting genetic alterations and their products that may explain the limited success of the novel mechanism-based drugs in the treatment of HCC. In light of these limitations and despite the era of the so-called “precision medicine,” prevention and early diagnosis of conditions predisposing to HCC remain the gold standard approach to prevent the development of this type of cancer. Finally, a paradigm shift to a more systemic approach to cancer is required to find optimal therapeutic solutions to treat this disease

Obesity, nonalcoholic fatty liver disease and adipocytokines network in promotion of cancer

Western populations are becoming increasingly sedentary and the incidence of nonalcoholic fatty liver disease (NAFLD) is increasing and becoming one of the most common causes of liver disease worldwide. Also, NAFLD is considered one the new emerging risk factors for development of tumors of the gastro-intestinal tract, particularly hepatocellular carcinoma (HCC). Visceral obesity is an important risk factor for the onset of NAFLD. An accumulation of ectopic fat, including visceral obesity and fatty liver leads to a dysfunction of the adipose tissue with impaired production of adipocytokines which, in turn, favor an increase in pro-inflammatory cytokines. In this review, we discuss how the obesity-related chronic state of low-grade inflammation and the presence of NAFLD lead to the emergence of a microenvironment favorable to the development of cancer

Toward automated threat modeling of edge computing systems

Edge computing brings processing and storage capabilities closer to the data sources, to reduce network latency, save bandwidth, and preserve data locality. Despite the clear benefits, this paradigm brings unprecedented cyber risks due to the combination of the security issues and challenges typical of cloud and Internet of Things (IoT) worlds. Notwithstanding an increasing interest in edge security by academic and industrial communities, there is still no discernible industry consensus on edge computing security best practices, and activities like threat analysis and countermeasure selection are still not well established and are completely left to security experts.In order to cope with the need for a simplified yet effective threat modeling process, which is affordable in presence of limited security skills and economic resources, and viable in modern development approaches, in this paper, we propose an automated threat modeling and countermeasure selection strategy targeting edge computing systems. Our approach leverages a comprehensive system model able to describe the main involved architectural elements and the associated data flow, with a focus on the specific properties that may actually impact on the applicability of threats and of associated countermeasures

autotaxin a possible new biological marker of endometrial cancer

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Recent advances in desmoid tumor therapy

The desmoid tumor is a locally aggressive proliferative disease within the family of soft-tissue sarcomas. Despite its relatively good prognosis, the clinical management of desmoid tumors requires constant multidisciplinary evaluation due to its highly variable clinical behavior. Recently, active surveillance has being regarded as the appropriate strategy at diagnosis, as indolent persistence or spontaneous regressions are not uncommon. Here, we review the most recent advances in desmoid tumor therapy, including low-dose chemotherapy and treatment with tyrosine kinase inhibitors. We also explore the recent improvements in our knowledge of the molecular biology of this disease, which are leading to clinical trials with targeted agents

DNA Damage Response Protein CHK2 Regulates Metabolism in Liver Cancer

Defective mitosis with chromosome missegregation can have a dramatic effect on genome integrity by causing DNA damage, activation of the DNA damage response (DDR), and chromosomal instability. Although this is an energy-dependent process, mechanisms linking DDR to cellular metabolism are unknown. Here we show that checkpoint kinase 2 (CHK2), a central effector of DDR, regulates cellular energy production by affecting glycolysis and mitochondrial functions. Patients with hepatocellular carcinoma (HCC) had increased CHK2 mRNA in blood, which was associated with elevated tricarboxylic acid cycle (TCA) metabolites. CHK2 controlled expression of succinate dehydrogenase (SDH) and intervened with mitochondrial functions. DNA damage and CHK2 promoted SDH activity marked by increased succinate oxidation through the TCA cycle; this was confirmed in a transgenic model of HCC with elevated DNA damage. Mitochondrial analysis identified CHK2-controlled expression of SDH as key in sustaining reactive oxygen species production. Cells with DNA damage and elevated CHK2 relied significantly on glycolysis for ATP production due to dysfunctional mitochondria, which was abolished by CHK2 knockdown. This represents a vulnerability created by the DNA damage response that could be exploited for development of new therapies