Incremental Model Transformations with Triple Graph Grammars for Multi-version Models

Like conventional software projects, projects in model-driven software engineering require adequate management of multiple versions of development artifacts, importantly allowing living with temporary inconsistencies. In previous work, multi-version models for model-driven software engineering have been introduced, which allow checking well-formedness and finding merge conflicts for multiple versions of a model at once. However, also for multi-version models, situations where different artifacts, that is, different models, are linked via automatic model transformations have to be handled. In this paper, we propose a technique for jointly handling the transformation of multiple versions of a source model into corresponding versions of a target model, which enables the use of a more compact representation that may afford improved execution time of both the transformation and further analysis operations. Our approach is based on the well-known formalism of triple graph grammars and the aforementioned encoding of model version histories called multi-version models. In addition to batch transformation of an entire model version history, the technique also covers incremental synchronization of changes in the framework of multi-version models. We show the correctness of our approach with respect to the standard semantics of triple graph grammars and conduct an empirical evaluation to investigate the performance of our technique regarding execution time and memory consumption. Our results indicate that the proposed technique affords lower memory consumption and may improve execution time for batch transformation of large version histories, but can also come with computational overhead in unfavorable cases.Comment: arXiv admin note: substantial text overlap with arXiv:2301.0062

Attitude to Secondary Prevention and Concerns about Colonoscopy Are Independent Predictors of Acceptance of Screening Colonoscopy

Background: Colonoscopy in combination with endoscopic polypectomy has been shown to be an efficient measure for reducing colorectal cancer incidence. In Germany, a colorectal cancer screening program based on colonoscopy for individuals aged 55 and above was introduced in 2002. However, for largely unknown reasons, participation rates remain low. The purpose of this study was to identify factors influencing compliance with colorectal cancer screening. Methods: A structured survey of 239 individuals aged 55-79 years ;was performed. Statistical analysis included chi(2) test, t test, principal component analysis, and logistic regression. Results: 56% of previously screened, but only 26% of non-screened individuals had received a recommendation to undergo screening colonoscopy. 50% of the non-screened believed a screening colonoscopy should only be performed in case of complaints. Univariate analysis identified participation in any secondary prevention measures (p < 0.001), concerns about colonoscopy (p < 0.012), and knowledge about colorectal cancer (p < 0.001) as critical issues distinguishing between groups. Multivariate analysis revealed that secondary prevention (p < 0.001) and concerns about colonoscopy (p = 0.026) were independent predictors of compliance with screening recommendations. Conclusion: Our survey has identified critical factors deterring compliance with colorectal cancer screening recommendations. This will help to direct future campaigns in order to increase participation in colorectal cancer screening. Copyright (C) 2010 S. Karger AG, Base

Modeling many-particle mechanical effects of an interacting Rydberg gas

In a recent work [Phys. Rev. Lett. 98, 023004 (2007)] we have investigated the influence of attractive van der Waals interaction on the pair distribution and Penning ionization dynamics of ultracold Rydberg gases. Here we extend this description to atoms initially prepared in Rydberg states exhibiting repulsive interaction. We present calculations based on a Monte Carlo algorithm to simulate the dynamics of many atoms under the influence of both repulsive and attractive longrange interatomic forces. Redistribution to nearby states induced by black body radiation is taken into account, changing the effective interaction potentials. The model agrees with experimental observations, where the ionization rate is found to increase when the excitation laser is blue-detuned from the atomic resonance

The interface of gravity and quantum mechanics illuminated by Wigner phase space

We provide an introduction into the formulation of non-relativistic quantum mechanics using the Wigner phase-space distribution function and apply this concept to two physical situations at the interface of quantum theory and general relativity: (i) the motion of an ensemble of cold atoms relevant to tests of the weak equivalence principle, and (ii) the Kasevich-Chu interferometer. In order to lay the foundations for this analysis we first present a representation-free description of the Kasevich-Chu interferometer based on unitary operators.Comment: 69 pages, 6 figures, minor changes to match the published version. The original publication is available at http://en.sif.it/books/series/proceedings_fermi or http://ebooks.iospress.nl/volumearticle/3809

Epithelial-to-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma and Pancreatic Tumor Cell Lines: The Role of Neutrophils and Neutrophil-Derived Elastase

Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with fibrosis and a prominent inflammatory infiltrate in the desmoplastic stroma. Moreover, in PDAC, an epithelial-to-mesenchymal transition (EMT) is observed. To explore a possible connection between the infiltrating cells, particularly the polymorphonuclear neutrophils (PMN) and the tumor cell transition, biopsies of patients with PDAC (n=115) were analysed with regard to PMN infiltration and nuclear expression of β-catenin and of ZEB1, well-established indicators of EMT. In biopsies with a dense PMN infiltrate, a nuclear accumulation of β-catenin and of ZEB1 was observed. To address the question whether PMN could induce EMT, they were isolated from healthy donors and were cocultivated with pancreatic tumor cells grown as monolayers. Rapid dyshesion of the tumor cells was seen, most likely due to an elastase-mediated degradation of E-cadherin. In parallel, the transcription factor TWIST was upregulated, β-catenin translocated into the nucleus, ZEB1 appeared in the nucleus, and keratins were downregulated. EMT was also induced when the tumor cells were grown under conditions preventing attachment to the culture plates. Here, also in the absence of elastase, E-cadherin was downmodulated. PMN as well as prevention of adhesion induced EMT also in liver cancer cell line. In conclusion, PMN via elastase induce EMT in vitro, most likely due to the loss of cell-to-cell contact. Because in pancreatic cancers the transition to a mesenchymal phenotype coincides with the PMN infiltrate, a contribution of the inflammatory response to the induction of EMT and—by implication—to tumor progression is possible

Towards Highly Scalable Runtime Models with History

Advanced systems such as IoT comprise many heterogeneous, interconnected, and autonomous entities operating in often highly dynamic environments. Due to their large scale and complexity, large volumes of monitoring data are generated and need to be stored, retrieved, and mined in a time- and resource-efficient manner. Architectural self-adaptation automates the control, orchestration, and operation of such systems. This can only be achieved via sophisticated decision-making schemes supported by monitoring data that fully captures the system behavior and its history. Employing model-driven engineering techniques we propose a highly scalable, history-aware approach to store and retrieve monitoring data in form of enriched runtime models. We take advantage of rule-based adaptation where change events in the system trigger adaptation rules. We first present a scheme to incrementally check model queries in the form of temporal logic formulas which represent the conditions of adaptation rules against a runtime model with history. Then we enhance the model to retain only information that is temporally relevant to the queries, therefore reducing the accumulation of information to a required minimum. Finally, we demonstrate the feasibility and scalability of our approach via experiments on a simulated smart healthcare system employing a real-world medical guideline.Comment: 8 pages, 4 figures, 15th International Symposium on Software Engineering for Adaptive and Self-Managing Systems (SEAMS2020

The Calcineurin Inhibitor-Sparing (CIS) Trial - individualised calcineurin-inhibitor treatment by immunomonitoring in renal allograft recipients: protocol for a randomised controlled trial

Background: Adequate monitoring tools are required to optimise the immunosuppressive therapy of an individual patient. Particularly, in calcineurin inhibitors, as critical dose drugs with a narrow therapeutic range, the optimal monitoring strategies are discussed in terms of safety and efficacy. Nevertheless, no pharmacokinetic monitoring markers reflect the biological activity of the drug. A new quantitative analysis of gene expression was employed to directly measure the functional effects of calcineurin inhibition: the transcriptional activities of the nuclear factor of activated T-cell (NFAT)-regulated genes in the peripheral blood. Methods/Design: The CIS study is a randomised prospective controlled trial, comparing a ciclosporin A (CsA)-based immunosuppressive regimen monitored by CsA trough levels to a CsA-based immunosuppressive regimen monitored by residual NFAT-regulated gene expression. Pulse wave velocity as an accepted surrogate marker of the cardiovascular risk is assessed in both study groups. Our hypothesis is that an individualised CsA therapy monitored by residual NFAT-regulated gene expression results in a significantly lower cardiovascular risk compared to CsA therapy monitored by CsA trough levels. Discussion: There is a lack of evidence in individualising standard immunosuppression in renal allograft recipients. The CIS study will consider the feasibility of individualised ciclosporin A immunosuppression by pharmacodynamic monitoring and evaluate the opportunity to reduce cardiovascular risk while maintaining sufficient immunosuppression. Trial registration: EudraCT identifier 2011-003547-21, registration date 18 July 201

Reduced spiral ganglion neuronal loss by adjunctive neurotrophin-3 in experimental pneumococcal meningitis

<p>Abstract</p> <p>Background</p> <p>Hearing loss is a frequent long-term complication of pneumococcal meningitis (PM). Its main pathological correlate is damage to the organ of Corti and loss of spiral ganglion neurons. The only current treatment option is cochlear implants which require surviving neurons. Here, we investigated the impact of systemically applied neurotrophin-3 (NT-3) on long-term hearing loss and the survival of neurons.</p> <p>Methods</p> <p>Eighteen hours after infection with <it>S. pneumoniae</it>, C57BL/6 mice were treated with a combination of ceftriaxone with NT-3 or dexamethasone or placebo. Hearing, cochlear damage, and brain damage were assessed by audiometry and histology.</p> <p>Results</p> <p>The main findings from immunohistochemical visualization of neurotrophins (NT-3, BDNF) and their receptors (TrkB, TrkC, and p75) in the cochlea were (i) enhanced staining for the cell survival-promoting receptor TrkB and (ii) increased NT-3 staining in NT-3 treated mice, showing that systemically applied NT-3 reaches the cochlea. The major effects of adjunctive NT-3 treatment were (i) a reduction of meningitis-induced hearing impairment and (ii) a reduction of spiral ganglion neuronal loss. The efficacy of NT-3 therapy was comparable to that of dexamethasone.</p> <p>Conclusion</p> <p>Systemically applied NT-3 might be an interesting candidate to improve hearing outcome after pneumococcal meningitis.</p

A Semi-Automated Approach for the Co-Refinement of Requirements and Architecture Models

Requirements and architecture specifications are strongly related as the second provides a solution to a problem stated by the first. This coupling is typically realized by traceability links and maintaining such links becomes extremely difficult as both requirements and architecture specifications frequently evolve, and in particular when the architecture is refined providing an increasing level of details. In such case, not only the traceability must evolve but the requirements must be refined as well. We present a novel semi-automated approach to evolve non-functional requirements and their traceability links following system's architecture refinement in the context of design space exploration and automated code generation. The approach has been prototyped for AADL models refined with the RAMSES tool and for model transformations implemented as Story Diagrams