Automated property verification for large scale B models with ProB

In this paper we describe the successful application of the ProB tool for data validation in several industrial applications. The initial case study centred on the San Juan metro system installed by Siemens. The control software was developed and formally proven with B. However, the development contains certain assumptions about the actual rail network topology which have to be validated separately in order to ensure safe operation. For this task, Siemens has developed custom proof rules for Atelier B. Atelier B, however, was unable to deal with about 80 properties of the deployment (running out of memory). These properties thus had to be validated by hand at great expense, and they need to be revalidated whenever the rail network infrastructure changes. In this paper we show how we were able to use ProB to validate all of the about 300 properties of the San Juan deployment, detecting exactly the same faults automatically in a few minutes that were manually uncovered in about one man-month. We have repeated this task for three ongoing projects at Siemens, notably the ongoing automatisation of the line 1 of the Paris Métro. Here again, about a man month of effort has been replaced by a few minutes of computation. This achievement required the extension of the ProB kernel for large sets as well as an improved constraint propagation algorithm. We also outline some of the effort and features that were required in moving from a tool capable of dealing with medium-sized examples towards a tool able to deal with actual industrial specifications. We also describe the issue of validating ProB, so that it can be integrated into the SIL4 development chain at Siemens.     

Lock-in amplifier error prediction and correction in frequency sweep measurements

This article proposes an analytical algorithm for predicting errors in lock-in amplifiers (LIAs) working with time-varying reference frequency. Furthermore, a simple method for correcting such errors is presented. The reference frequency can be swept in order to measure the frequency response of a system within a given spectrum. The continuous variation of the reference frequency produces a measurement error that depends on three factors: the sweep speed, the LIA low-pass filters, and the frequency response of the measured system. The proposed error prediction algorithm is based on the final value theorem of the Laplace transform. The correction method uses a double-sweep measurement. A mathematical analysis is presented and validated with computational simulations and experimental measurements.     

Zur semantischen Interoperabilität in der Energiebranche: CIM IEC 61970

This contribution provides an introduction to the Common Information Model CIM which is an international standard maintained by the International Electrotechnical Commission IEC. Today’s market requirements towards the model are discussed, furthermore, we give an introduction to the history of the CIM, its serializations and scope of application. The contribution concludes with an overview of future use of the CIM for both science and commerce. Briefly, we focus on:

Message-based loose coupling of information systems

Exchange of power grid topologies with minimal communication and data overhead

Data quality assurance using ontology-based meta annotations and

Integration of heterogeneous standards in the utility domain. The contribution presents solutions to the use cases providing a better information management for the utility utilizing the Common Information Model.

     

Geoadditive expectile regression

Quantile regression has emerged as one of the standard tools for regression analysis that enables a proper assessment of the complete conditional distribution of responses even in the presence of heteroscedastic errors. Quantile regression estimates are obtained by minimising an asymmetrically weighted sum of absolute deviations from the regression line, a decision theoretic formulation of the estimation problem that avoids a full specification of the error term distribution. Recent advances in mean regression have concentrated on making the regression structure more flexible by including nonlinear effects of continuous covariates, random effects or spatial effects. These extensions often rely on penalised least squares or penalised likelihood estimation with quadratic penalties and may therefore be difficult to combine with the linear programming approaches often considered in quantile regression. As a consequence, geoadditive expectile regression based on minimising an asymmetrically weighted sum of squared residuals is introduced. Different estimation procedures are presented including least asymmetrically weighted squares, boosting and restricted expectile regression. The properties of these procedures are investigated in a simulation study and an analysis on rental fees in Munich is provided where the geoadditive specification allows for an analysis of nonlinear effects of the size of flats or the year of construction and the spatial distribution of rents simultaneously.     

Capability and limitation of max- and sum-type construction of Lyapunov functions for networks of iISS systems

This paper addresses the problem of verifying stability of networks whose subsystems admit dissipation inequalities of integral input-to-state stability (iISS). We focus on two ways of constructing a Lyapunov function satisfying a dissipation inequality of a given network. Their difference from one another is elucidated from the viewpoint of formulation, relation, fundamental limitation and capability. One is referred to as the max-type construction resulting in a Lipschitz continuous Lyapunov function. The other is the sum-type construction resulting in a continuously differentiable Lyapunov function. This paper presents geometrical conditions under which the Lyapunov construction is possible for a network comprising $n\ge 2$ subsystems. Although the sum-type construction for general $n>2$ has not yet been reduced to a readily computable condition, we obtain a simple condition of iISS small gain in the case of $n=2$. It is demonstrated that the max-type construction fails to offer a Lyapunov function if the network contains subsystems which are not input-to-state stable (ISS).     

An automated Thixo‐Forging Plant for Steel Parts

The scope of the article is to describe the automated production of a thixoformed steel part. The production plant was set up within a prototype initiative at the Institute of Metal Forming in cooperation with the Institute of Automatic Control of RWTH Aachen University and industrial partners. Preliminary experiments showed that the quality of the formed parts varied to a great extent due to changing production conditions since the handling of the billet was carried out manually. To eliminate the possible disturbances introduced by the manual handling of the billet, an automation concept has been elaborated in order to guarantee a defined production environment. An industrial robot (KUKA) fulfils the handling tasks like the feeding of the induction coil with the feedstock material and the placing of the heated billet into the hydraulic press. The removal of the formed part from the press is realised by a simple mechanical device in order to be able to use only one gripper. The design of the gripper ensures a minimal heat loss during handling. The induction coil, the gripper system and the cavity are flooded with inert gas in order to prevent scaling. The sequence control for the production of a part is realised on the controller of the robot which provides sufficient PLC functionality and can be easily equipped with the required I/O components to trigger the different automation components.     

Autoimmune Neutropenia and Immune-Dysregulation in a Patient Carrying a TINF2 Variant

In recent years, the knowledge about the immune-mediated impairment of bone marrow precursors in immune-dysregulation and autoimmune disorders has increased. In addition, immune-dysregulation, secondary to marrow failure, has been reported as being, in some cases, the most evident and early sign of the disease and making the diagnosis of both groups of disorders challenging. Dyskeratosis congenita is a disorder characterized by premature telomere erosion, typically showing marrow failure, nail dystrophy and leukoplakia, although incomplete genetic penetrance and phenotypes with immune-dysregulation features have been described. We report on a previously healthy 17-year-old girl, with a cousin successfully treated for acute lymphoblastic leukemia, who presented with leukopenia and neutropenia. The diagnostic work-up showed positive anti-neutrophil antibodies, leading to the diagnosis of autoimmune neutropenia, a slightly low NK count and high TCR-αβ+-double-negative T-cells. A next-generation sequencing (NGS) analysis showed the 734C>A variant on exon 6 of the TINF2 gene, leading to the p.Ser245Tyr. The telomere length was short on the lymphocytes and granulocytes, suggesting the diagnosis of an atypical telomeropathy showing with immune-dysregulation. This case underlines the importance of an accurate diagnostic work-up of patients with immune-dysregulation, who should undergo NGS or whole exome sequencing to identify specific disorders that deserve targeted follow-up and treatment.     

Circulating miR-200 Family and CTCs in Metastatic Breast Cancer before,during, and after a New Line of Systemic Treatment

The extracellular circulating microRNA (miR)-200 regulates epithelial-mesenchymal transition and, thus, plays an essential role in the metastatic cascade and has shown itself to be a promising prognostic and predictive biomarker in metastatic breast cancer (MBC). Expression levels of the plasma miR-200 family were analyzed in relationship to systemic treatment, circulating tumor cells (CTC) count, progression-free survival (PFS), and overall survival (OS). Expression of miR-200a, miR-200b, miR-200c, miR-141, and miR-429, and CTC status (CTC-positive ≥ 5 CTC/7.5 mL) was assessed in 47 patients at baseline (BL), after the first completed cycle of a new line of systemic therapy (1C), and upon the progression of disease (PD). MiR-200a, miR-200b, and miR-141 expression was reduced at 1C compared to BL. Upon PD, all miR-200s were upregulated compared to 1C. At all timepoints, the levels of miR-200s were elevated in CTC-positive versus CTC-negative patients. Further, heightened miR-200s expression and positive CTC status were associated with poorer OS at BL and 1C. In MBC patients, circulating miR-200 family members decreased after one cycle of a new line of systemic therapy, were elevated during PD, and were indicative of CTC status. Notably, increased levels of miR-200s and elevated CTC count correlated with poorer OS and PFS. As such, both are promising biomarkers for optimizing the clinical management of MBC.     

Effects of Combining Biofactors on Bioenergetic Parameters,Aβ Levels and Survival in Alzheimer Model Organisms

Increased amyloid beta (Aβ) levels and mitochondrial dysfunction (MD) in the human brain characterize Alzheimer disease (AD). Folic acid, magnesium and vitamin B6 are essential micro-nutrients that may provide neuroprotection. Bioenergetic parameters and amyloid precursor protein (APP) processing products were investigated in vitro in human neuroblastoma SH-SY5Y-APP695 cells, expressing neuronal APP, and in vivo, in the invertebrate Caenorhabditis elegans (CL2006 & GMC101) expressing muscular APP. Model organisms were incubated with either folic acid and magnesium-orotate (ID63) or folic acid, magnesium-orotate and vitamin B6 (ID64) in different concentrations. ID63 and ID64 reduced Aβ, soluble alpha APP (sAPPα), and lactate levels in SH-SY5Y-APP695 cells. The latter might be explained by enhanced expression of lactate dehydrogenase (LDHA). Micronutrient combinations had no effects on mitochondrial parameters in SH-SY5Y-APP695 cells. ID64 showed a significant life-prolonging effect in C. elegans CL2006. Incubation of GMC101 with ID63 significantly lowered Aβ aggregation. Both combinations significantly reduced paralysis and thus improved the phenotype in GMC101. Thus, the combinations of the tested biofactors are effective in pre-clinical models of AD by interfering with Aβ related pathways and glycolysis.     

Development of gluten-free fresh egg pasta based on oat and teff flour

Due to increased awareness of consumers about the relationship between food and health as well as the requirements of people following a gluten-free diet, the production of cereal products from raw materials other than wheat is of interest. However, the elimination of the visco-elastic gluten protein represents a technological challenge. During this study, response surface methodology was applied to determine optimal formulations for the production of egg pasta from oat and teff flour. Wheat flour was used as a control. The resulting products were characterised regarding firmness and elasticity, stickiness and cooking loss. The results showed that the mechanical texture of oat and teff pasta was comparable to wheat pasta, however, elasticity was significantly reduced. Compositional analysis was carried out on flour raw materials as well as on the final pasta products, showing that regarding fibre and mineral content, oat and teff samples are nutritionally superior to wheat. In addition, the microstructure was investigated by means of scanning electron microscopy, allowing also the observation of structural changes occurring during cooking. Upon cooking, a distinct outer layer can be observed, resulting from protein denaturation and starch gelatinisation. This structural feature is clearly visible for cooked wheat pasta and but is less apparent for teff and oat pasta.