Lightweight coarse-grained coordination: a scalable system-level approach

In this paper, our solution to the problem of modelling functionally complex communication systems at the application level, based on lightweight coordination, is extended to seamlessly capture system-level testing as well. This extension could be realized simply by self-application: the bulk of the work for integrating system-level testing into our development environment, the ABC, concerned domain modelling, which can be done using the ABC. Therefore, the extension of the ABC to cover system-level testing was merely an application development on the basis of the ABC, illustrated here in the domain of Computer Telephony Integration. Here the adoption of a coarse-grained approach to test design, which is central to the scalability of the overall testing environment, is the enabling aspect for system-level test automation. Together with our lightweight coordination approach this induces an understandable modelling paradigm of system-wide test cases that is adequate for the needs and requirements of industrial test engineers. In particular, it enables test engineers to graphically design complex test cases that, in addition, can even be automatically checked for their intended purposes via model checking.     

Lipofilling in Breast Oncological Surgery: A Safe Opportunity or Risk for Cancer Recurrence?

Lipofilling (LF) is a largely employed technique in reconstructive and esthetic breast surgery. Over the years, it has demonstrated to be extremely useful for treatment of soft tissue defects after demolitive or conservative breast cancer surgery and different procedures have been developed to improve the survival of transplanted fat graft. The regenerative potential of LF is attributed to the multipotent stem cells found in large quantity in adipose tissue. However, a growing body of pre-clinical evidence shows that adipocytes and adipose-derived stromal cells may have pro-tumorigenic potential. Despite no clear indication from clinical studies has demonstrated an increased risk of cancer recurrence upon LF, these observations challenge the oncologic safety of the procedure. This review aims to provide an updated overview of both the clinical and the pre-clinical indications to the suitability and safety of LF in breast oncological surgery. Cellular and molecular players in the crosstalk between adipose tissue and cancer are described, and heterogeneous contradictory results are discussed, highlighting that important issues still remain to be solved to get a clear understanding of LF safety in breast cancer patients.     

Program verification and testing technologies

Program verification and testing techniques are crucial in fruitfully analyzing and validating complex software systems. This is an active research area and has produced various promising techniques in the last decade. However, many challenges lie ahead. We review the research area and summarize six papers selected from the Sixth International Symposium on Theoretical Aspects of Software Engineering (TASE 2012).     

Tool-supported enhancement of diagnosis in model-driven verification

We show on a case study from an autonomous aerospace context how to apply a game-based model-checking approach as a powerful technique for the verification, diagnosis, and adaptation of system behaviors based on temporal properties. This work is part of our contribution within the SHADOWS project, where we provide a number of enabling technologies for model-driven self-healing. We propose here to use GEAR, a game-based model checker, as a user-friendly tool that can offer automatic proofs of critical properties of such systems. Although it is a model checker for the full modal μ-calculus, it also supports derived, more user-oriented logics. With GEAR, designers and engineers can interactively investigate automatically generated winning strategies for the games, by this way exploring the connection between the property, the system, and the proof. This work has been partially supported by the European Union Specific Targeted Research Project SHADOWS (IST-2006-35157), exploring a Self-Healing Approach to Designing cOmplex softWare Systems. The project’s web page is at . This article is an extended version of Renner et al. [18] presented at ISoLA 2007, Poitiers, December 2007.     

Thymosin β4 is differentially expressed in the cerebrospinal fluid of Creutzfeldt‐Jakob disease patients: a MALDI‐TOF MS protein profiling study

MALDI‐TOF protein profiling analysis permits the detection of peptides and small proteins in complex protein mixtures with great accuracy. We applied this analysis to cerebrospinal fluid (CSF) from 15 patients affected by Creutzfeldt‐Jakob disease (CJD). We compared the levels of the normalized ion signals of 11 sporadic and 4 genetic CJD forms with those from ten healthy control subjects and eight non‐CJD relapsing‐remitting multiple sclerosis patients. In so doing, we detected 61 differentially expressed ion signals in CJD samples compared to controls. Among the 61 signals, 3 signals had significantly increased levels with high statistical significance (p <0.0001) and were located at 3238.3 m/z, 4963.7 m/z, and 8565.3 m/z. We characterized the 5.0 and 8.6 kDa proteins as thymosin β4 N‐acetylated and free ubiquitin, respectively, while the 3.2‐kDa peptide remained uncharacterized. Although elevated ubiquitin levels have previously been described in CJD, we have demonstrated for the first time the involvement of thymosin β4 in a neurodegenerative disease. To support the validity of thymosin β4 levels obtained by MALDI‐TOF analysis, an independent enzyme immunoassay analysis was performed. Moreover, a validation cohort consisting of CSF from three CJD patients, five healthy subjects, and six non‐CJD relapsing‐remitting multiple sclerosis patients was analyzed in a similar way, yielding superimposable results. We propose that thymosin β4 is a potential new candidate marker for the ante mortem diagnosis of CJD disease.     

Preface by the section editor

This special section is devoted to some of the novel approaches to hardware-like system verification that are currently being used in industry or the object of fielded research. The topics presented in this special section are based on a selection of the papers which appeared originally in the Proceedings of CHARME 2001, the Eleventh Advanced Research Working Conference on Correct Hardware Design and Verification Methods which took place in Livingston, Scotland, UK in September 2001. They are by no means a complete account of the numerous ways in which hardware and hardware-like systems are being subject to rigorous investigation, but they represent an interesting sample of today’s problems and of the techniques oriented around new uses of verification techniques. Published online: 10 April 2003     

Potential of the Stromal Matricellular Protein Periostin as a Biomarker to Improve Risk Assessment in Prostate Cancer

Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients.     

Downexpression of miR-200c-3p Contributes to Achalasia Disease by Targeting the PRKG1 Gene

Achalasia is an esophageal smooth muscle motility disorder with unknown pathogenesis. Taking into account our previous results on the downexpression of miR-200c-3p in tissues of patients with achalasia correlated with an increased expression of PRKG1, SULF1, and SYDE1 genes, our aim was to explore the unknown biological interaction between these genes and human miR-200c-3p and if this relation could unravel their functional role in the etiology of achalasia. To search for putative miR-200c-3p binding sites in the 3′-UTR of PRKG1, SULF1 and SYDE1, a bioinformatics tool was used. To test whether PRKG1, SULF1, and SYDE1 are targeted by miR-200c-3p, a dual-luciferase reporter assay and quantitative PCR on HEK293 and fibroblast cell lines were performed. To explore the biological correlation between PRKG1 and miR-200c-3p, an immunoblot analysis was carried out. The overexpression of miR-200c-3p reduced the luciferase activity in cells transfected with a luciferase reporter containing a fragment of the 3′-UTR regions of PRKG1, SULF1, and SYDE1 which included the miR-200c-3p seed sequence. The deletion of the miR-200c-3p seed sequence from the 3′-UTR fragments abrogated this reduction. A negative correlation between miR-200c-3p and PRKG1, SULF1, and SYDE1 expression levels was observed. Finally, a reduction of the endogenous level of PRKG1 in cells overexpressing miR-200c-3p was detected. Our study provides, for the first time, functional evidence about the PRKG1 gene as a direct target and SULF1 and SYDE1 as potential indirect substrates of miR-200c-3p and suggests the involvement of NO/cGMP/PKG signaling in the pathogenesis of achalasia.