Ablaufgeregelte Entwicklung des hoch belasteten Klapparmes eines neuartigen Klappmechanismus für trailerbare Katamarane

Im Gegensatz zu Einrumpfbooten verfügen Katamarane in vielen Bereichen über bessere Segeleigenschaften und erfreuen sich daher einer wachsenden Beliebtheit. Auf Grund der großen Breite ergeben sich jedoch Schwierigkeiten in Bezug auf die Liegeplätze in Häfen und besonders für den Transport eines Bootes auf einem Anhänger (Trailer), da hier eine maximale Breite von 2,50 m nicht überschritten werden darf, wenn der Transport nicht als genehmigungspflichtiger Sondertransport erfolgen soll. Die vorliegende Arbeit greift dieses Problem auf und gestattet es durch die Entwicklung eines hoch belastbaren Klapparmes im Rahmen eines neuartigen Klappmechanismus, dass die beiden Rümpfe eines Katamarans auf einfache Art während der Liegezeit oder für den Transport zusammengeführt werden können, so dass eine Breite des Bootes erreicht wird, die den normalen Transport ermöglicht. Dazu wird eine ablaufgeregelte Produktentwicklung mit mehreren Optimierungsschritten angewendet, die ein Produktmodell benutzt, welches die in Dateien vorliegenden fach-spezifischen Datenmodelle der einzelnen IT-Systeme mittels einer verweisorientierten Zuordnung zu einem Modell zusammenfasst. Darüber hinaus wurden IT-Systeme zur konstruktiven Gestaltung, zur rechnergestützten Simluation, zur Erstellung eines Prototypen und zur Verwaltung der Produktdaten ausgewählt, die alle über eine hohe Integrationstiefe verfügen, so dass ein Datenabgleich zwischen diesen Systemen entfallen kann. Der Algorithmus für die Ablaufregelung orientiert sich an der Systemtechnik und ist so gestaltet, dass der Entwickler durch alle Detailprozesse zielgerichtet geführt wird, damit er sich in vollem Umfang auf die Umsetzung einer Produktidee in eine problemorientierte Lösung konzentrieren kann. Die am Beispiel eines Klapp-Mechanismus für einen trailerbaren Katamaran erzielten Ergebnisse haben deutlich gemacht, dass eine ablaufgeregelte Produktentwicklung zu einem ansprechenden Ergebnis führen kann. Die Richtigkeit der Vorgehensweise wird auch durch die Annahme eines von dem Verfasser dieser Arbeit eingereichten Patentes für den hier entwickelten Klappmechanismus unterstrichen

The Influence of Multimorbidity on Leading Causes of Death in Older Adults With Cognitive Impairment

Objective: The aim of this study is to evaluate the relationship of leading causes of death with gradients of cognitive impairment and multimorbidity. Method: This is a population-based study using data from the linked 1992- 2010 Health and Retirement Study and National Death Index (n = 9,691). Multimorbidity is defined as a combination of chronic conditions, functional limitations, and geriatric syndromes. Regression trees and Random Forest identified which combinations of multimorbidity associated with causes of death. Results: Multimorbidity is common in the study population. Heart disease is the leading cause in all groups, but with a larger percentage of deaths in the mild and moderate/severe cognitively impaired groups than among the noncognitively impaired. The different “paths” down the regression trees show that the distribution of causes of death changes with different combinations of multimorbidity. Discussion: Understanding the considerable heterogeneity in chronic conditions, functional limitations, geriatric syndromes, and causes of death among people with cognitive impairment can target care management and resource allocation

Towards self-explaining social robots. Verbal explanation strategies for a needs-based architecture

Stange S, Buschmeier H, Hassan T, Ritter C, Kopp S. Towards self-explaining social robots. Verbal explanation strategies for a needs-based architecture. Presented at the AAMAS 2019 Workshop on Cognitive Architectures for HRI: Embodied Models of Situated Natural Language Interactions (MM-Cog), Montréal, Canada.In order to establish long-term relationships with users, social companion robots and their behaviors need to be comprehensible. Purely reactive behavior such as answering questions or following commands can be readily interpreted by users. However, the robot's proactive behaviors, included in order to increase liveliness and improve the user experience, often raise a need for explanation. In this paper, we provide a concept to produce accessible “why-explanations” for the goal-directed behavior an autonomous, lively robot might produce. To this end we present an architecture that provides reasons for behaviors in terms of comprehensible needs and strategies of the robot, and we propose a model for generating different kinds of explanations

A phase II study for metabolic in vivo response monitoring with sequential 18FDG-PET-CT during treatment with the EGFR-monoclonal-antibody cetuximab in metastatic colorectal cancer: the Heidelberg REMOTUX trial

BACKGROUND: The epidermal growth factor receptor monoclonal antibody cetuximab has proven activity in metastatic colorectal cancer. To date, the mechanisms of action are not completely understood. Especially the impact on tumor glucose metabolism, or tumor vascularization remains largely unclear. The understanding of mechanisms such as early changes in tumor metabolism is of clinical importance since there may be a substantial influence on choice and sequence of drug combinations. Early signals of response to cetuximab may prove useful to identify patients having a relevant clinical treatment benefit. The objective of this trial is to evaluate the predictive relevance of the relative change in (18 )F-Fluorodeoxyglucose tumor uptake for early clinical response during short-term single agent treatment with cetuximab. Early clinical response will be routinely measured according to the response evaluation criteria in solid tumors. Accompanying research includes cytokine immune monitoring and analysis of tumor proteins and tumor genes. METHODS/DESIGN: The REMOTUX trial is an investigator-initiated, prospective, open-label, single-arm, single-center early exploratory predictive study. The first (18 )F-FDG PET-CT is conducted at baseline followed by the run-in phase with cetuximab at days 1 and 8. At day 14, the second (18 )F-FDG PET-CT is performed. Subsequently, patients are treated according to the Folfiri-cetuximab regimen as an active and approved first-line regimen for metastatic colorectal carcinoma. At day 56, clinical response is evaluated with a CT-scan compared to the baseline analysis. Tracer uptake is assessed using standardized uptake values (SUVs). The main hypothesis to be tested in the primary analysis is whether or not the relative change in the SUV from baseline to day 14 has any predictive relevance for early clinical response determined at day 56. Patients are followed until death from any cause or until 24 months after the last patient has ended trial treatment. DISCUSSION: The aim of this trial is to evaluate metabolic changes in metastatic colorectal cancer during short-term single agent treatment with cetuximab and to analyse their potential of predicting early clinical response. This could be helpful to answer the question if early identification of patients not responding to cetuximab is possible. TRIAL REGISTRATION: ClinicalTrials.gov NCT200811021020; EudraCT 20090132792

The allele distribution in next-generation sequencing data sets is accurately described as the result of a stochastic branching process

With the availability of next-generation sequencing (NGS) technology, it is expected that sequence variants may be called on a genomic scale. Here, we demonstrate that a deeper understanding of the distribution of the variant call frequencies at heterozygous loci in NGS data sets is a prerequisite for sensitive variant detection. We model the crucial steps in an NGS protocol as a stochastic branching process and derive a mathematical framework for the expected distribution of alleles at heterozygous loci before measurement that is sequencing. We confirm our theoretical results by analyzing technical replicates of human exome data and demonstrate that the variance of allele frequencies at heterozygous loci is higher than expected by a simple binomial distribution. Due to this high variance, mutation callers relying on binomial distributed priors are less sensitive for heterozygous variants that deviate strongly from the expected mean frequency. Our results also indicate that error rates can be reduced to a greater degree by technical replicates than by increasing sequencing depth

Validation of theory-based models for the control of plasma currents in W7-X divertor plasmas

A theory-based model for the control of plasma currents for steady-state operation in W7-X is proposed and intended for model-based plasma control. The conceptual outline implies the strength of physics-based models: it offer approaches applicable to future conditions of fusion devices or next-step machines. The application at extrapolated settings is related to the validity range of the theory model. Therefore, the predictive power of theory-based control models could be larger than for data-driven approaches and limitations can be predicted from the validity range for the prediction of bootstrap currents in W7-X. The model predicts the L/R response when density or heating power is changed. The model is based on neoclassical bootstrap current calculations and validated for different discharge conditions. While the model was found to be broadly applicable for conducted electron-cyclotron-heated discharges in W7-X, limits were found for cases when the polarization of the electron cyclotron heating was changed from X2 to O2-heating. The validity assessment attempts to quantify the potential of the derived model for model-based control in the operational space (density, heating power) of W7-X

Characterization of Changes in Serum Anti-Glycan Antibodies in Crohn's Disease – a Longitudinal Analysis

INTRODUCTION: Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohn's disease (CD). We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon. METHODS: 859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD) patients (207 CD, 46 ulcerative colitis (UC)) were tested for the presence of anti-laminarin (Anti-L), anti-chitin (Anti-C), anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-Saccharomyces cerevisiae (gASCA) antibodies by ELISA. All patients had at least two and up to eleven serum samples taken during the disease course. RESULTS: Median follow-up time for CD was 17.4 months (Interquartile range (IQR) 8.0, 31.6 months) and for UC 10.9 months (IQR 4.9, 21.0 months). In a subgroup of CD subjects marked changes in the overall immune response (quartile sum score) and levels of individual markers were observed over time. The marker status (positive versus negative) remained widely stable. Neither clinical phenotype nor NOD2 genotype was associated with the observed fluctuations. In a longitudinal analysis neither changes in disease activity nor CD behavior led to alterations in the levels of the glycan markers. The ability of the panel to discriminate CD from UC or its association with CD phenotypes remained stable during follow-up. In the serum of UC patients neither significant level nor status changes were observed. CONCLUSIONS: While the levels of anti-glycan antibodies fluctuate in a subgroup of CD patients the antibody status is widely stable over time

Simulation Modeling for Energy-Flexible Manufacturing: Pitfalls and How to Avoid Them

Due to the high share of industry in total electricity consumption, industrial demand-side management can make a relevant contribution to the stability of power systems. At the same time, companies get the opportunity to reduce their electricity procurement costs by taking advantage of increasingly fluctuating prices on short-term electricity markets, the provision of system services on balancing power markets, or by increasing the share of their own consumption from on-site generated renewable energy. Demand-side management requires the ability to react flexibly to the power supply situation without negatively affecting production targets. It also means that the management and operation of production must consider not only production-related parameters but also parameters of energy availability, which further increase the complexity of decision-making. Although simulation studies are a recognized tool for supporting decision-making processes in production and logistics, the simultaneous simulation of material and energy flows has so far been limited mainly to issues of energy efficiency as opposed to energy flexibility, where application-oriented experience is still limited. We assume that the consideration of energy flexibility in the simulation of manufacturing systems will amplify already known pitfalls in conducting simulation studies. Based on five representative industrial use cases, this article provides practitioners with application-oriented experiences of the coupling of energy and material flows in simulation modeling of energy-flexible manufacturing, identifies challenges in the simulation of energy-flexible production systems, and proposes approaches to face these challenges. Seven pitfalls that pose a particular challenge in simulating energy-flexible manufacturing have been identified, and possible solutions and measures for avoiding them are shown. It has been found that, among other things, consistent management of all parties involved, early clarification of energy-related, logistical, and resulting technical requirements for models and software, as well as the application of suitable methods for validation and verification are central to avoiding these pitfalls. The identification and characterization of challenges and the derivation of recommendations for coping with them can raise awareness of typical pitfalls. This paper thus helps to ensure that simulation studies of energy-flexible production systems can be carried out more efficiently in the future