Formal and Informal Methods for Multi-Core Design Space Exploration

We propose a tool-supported methodology for design-space exploration for embedded systems. It provides means to define high-level models of applications and multi-processor architectures and evaluate the performance of different deployment (mapping, scheduling) strategies while taking uncertainty into account. We argue that this extension of the scope of formal verification is important for the viability of the domain.Comment: In Proceedings QAPL 2014, arXiv:1406.156

A Model-Derivation Framework for Software Analysis

Model-based verification allows to express behavioral correctness conditions like the validity of execution states, boundaries of variables or timing at a high level of abstraction and affirm that they are satisfied by a software system. However, this requires expressive models which are difficult and cumbersome to create and maintain by hand. This paper presents a framework that automatically derives behavioral models from real-sized Java programs. Our framework builds on the EMF/ECore technology and provides a tool that creates an initial model from Java bytecode, as well as a series of transformations that simplify the model and eventually output a timed-automata model that can be processed by a model checker such as UPPAAL. The framework has the following properties: (1) consistency of models with software, (2) extensibility of the model derivation process, (3) scalability and (4) expressiveness of models. We report several case studies to validate how our framework satisfies these properties.Comment: In Proceedings MARS 2017, arXiv:1703.0581

A Model-Derivation Framework for Software Analysis

Model-based verification allows to express behavioral correctness conditions like the validity of execution states, boundaries of variables or timing at a high level of abstraction and affirm that they are satisfied by a software system. However, this requires expressive models which are difficult and cumbersome to create and maintain by hand. This paper presents a framework that automatically derives behavioral models from real-sized Java programs. Our framework builds on the EMF/ECore technology and provides a tool that creates an initial model from Java bytecode, as well as a series of transformations that simplify the model and eventually output a timed-automata model that can be processed by a model checker such as UPPAAL. The framework has the following properties: (1) consistency of models with software, (2) extensibility of the model derivation process, (3) scalability and (4) expressiveness of models. We report several case studies to validate how our framework satisfies these properties.Comment: In Proceedings MARS 2017, arXiv:1703.0581

Timed Automata Semantics for Analyzing Creol

We give a real-time semantics for the concurrent, object-oriented modeling language Creol, by mapping Creol processes to a network of timed automata. We can use our semantics to verify real time properties of Creol objects, in particular to see whether processes can be scheduled correctly and meet their end-to-end deadlines. Real-time Creol can be useful for analyzing, for instance, abstract models of multi-core embedded systems. We show how analysis can be done in Uppaal.Comment: In Proceedings FOCLASA 2010, arXiv:1007.499

Urinary MicroRNA Profiling in the Nephropathy of Type 1 Diabetes

Background: Patients with Type 1 Diabetes (T1D) are particularly vulnerable to development of Diabetic nephropathy (DN) leading to End Stage Renal Disease. Hence a better understanding of the factors affecting kidney disease progression in T1D is urgently needed. In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression in many different health conditions. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease. Methods and Findings: We studied urine microRNA profiles with qPCR in 40 T1D with >20 year follow up 10 who never developed renal disease (N) matched against 10 patients who went on to develop overt nephropathy (DN), 10 patients with intermittent microalbuminuria (IMA) matched against 10 patients with persistent (PMA) microalbuminuria. A Bayesian procedure was used to normalize and convert raw signals to expression ratios. We applied formal statistical techniques to translate fold changes to profiles of microRNA targets which were then used to make inferences about biological pathways in the Gene Ontology and REACTOME structured vocabularies. A total of 27 microRNAs were found to be present at significantly different levels in different stages of untreated nephropathy. These microRNAs mapped to overlapping pathways pertaining to growth factor signaling and renal fibrosis known to be targeted in diabetic kidney disease. Conclusions: Urinary microRNA profiles differ across the different stages of diabetic nephropathy. Previous work using experimental, clinical chemistry or biopsy samples has demonstrated differential expression of many of these microRNAs in a variety of chronic renal conditions and diabetes. Combining expression ratios of microRNAs with formal inferences about their predicted mRNA targets and associated biological pathways may yield useful markers for early diagnosis and risk stratification of DN in T1D by inferring the alteration of renal molecular processes. © 2013 Argyropoulos et al

Sprouty2 loss‐induced IL6 drives castration‐resistant prostate cancer through scavenger receptor B1

Metastatic castration‐resistant prostate cancer (mCRPC) is a lethal form of treatment‐resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre‐clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self‐sufficient form of CRPC. Mechanistically, HER2‐IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1‐mediated cholesterol uptake in SPRY2‐deficient tumours. Systemically, IL6 elevated the levels of circulating cholesterol by inducing host adipose lipolysis and hepatic cholesterol biosynthesis. SPRY2‐deficient CRPC is dependent on cholesterol bioavailability and SRB1‐mediated tumoral cholesterol uptake for androgen biosynthesis. Importantly, treatment with ITX5061, a clinically safe SRB1 antagonist, decreased treatment resistance. Our results indicate that cholesterol transport blockade may be effective against SPRY2‐deficient CRPC