Mechanisms altering airway smooth muscle cell Ca(2+) homeostasis in two asthma models

Background: Asthma is characterized by airway remodeling, altered mucus production and airway smooth muscle cell (ASMC) contraction causing extensive airway narrowing. In particular, alterations of ASMC contractility seem to be of crucial importance. The elevation of the cytoplasmic Ca(2+) concentration is a key event leading to ASMC contraction and changes in the agonist- induced Ca(2+) increase in ASMC have been reported in asthma. Objective: The aim of this study was to investigate mechanisms underlying these changes. Methods: Murine tracheal smooth muscle cells (MTSMC) from T- bet KO mice and human bronchial smooth muscle cells (HBSMC) incubated with IL-13 and IL-4 served as asthma models. Acetylcholine- induced changes in the cytoplasmic Ca(2+) concentration were recorded using fluorescence microscopy and the expression of Ca(2+) homeostasis regulating proteins was investigated with Western blot analysis. Results: Acetylcholine- induced Ca(2+) transients were elevated in both asthma models. This correlated with an increased Ca(2+) content of the sarcoplasmic reticulum (SR). In MTSMC from T-bet KO mice, the expression of the SR Ca(2+) buffers calreticulin and calsequestrin was higher compared to wild- type mice. In HBSMC incubated with IL-13 or IL-4, the expression of ryanodine receptors, inositol-3-phosphate receptors and sarcoplasmic/ endoplasmic reticulum Ca 2+ ATPases 2 was increased compared to HBSMC without incubation with interleukins. The enlarged acetylcholine- induced Ca(2+) transients could be reversed by blocking inositol-3- phosphate receptors. Conclusions: We conclude that in the murine asthma model the SR Ca(2+) buffer capacity is increased, while in the human asthma model the expression of SR Ca(2+) channels is altered. The investigation of the Ca(2+) homeostasis of ASMC has the potential to provide new therapeutical options in asthma. Copyright (C) 2008 S. Karger AG, Basel

Design, Application and Evaluation of a Multi Agent System in the Logistics Domain

The increasing demand for flexibility of automated production systems also affects the automated material flow systems (aMFS) they contain and demands reconfigurable systems. However, the centralized control concept usually applied in aMFS hinders an easy adaptation, as the entire control software has to be re-tested, when manually changing sub-parts of the control. As adaption and subsequent testing are a time-consuming task, concepts for splitting the control from one centralized to multiple, decentralized control nodes are required. Therefore, this paper presents a holistic agent-based control concept for aMFS, whereby the system is divided into so-called automated material flow modules (aMFM), each being controlled by a dedicated module agent. The concept allows the reconfiguration of aMFS, consisting of heterogeneous, stationary aMFM, during runtime. Furthermore, it includes aspects such as uniform agent knowledge bases through metamodel-based development, a communication ontology considering different information types and properties, strategic route optimization in decentralized control architecture and a visualization concept to make decisions of the module agents comprehensible to operators and maintenance staff. The evaluation of the concept is performed by means of material flow simulations as well as a prototypical implementation on a lab-sized demonstrator.Comment: 13 pages, https://ieeexplore.ieee.org/abstract/document/9042827

Modularity and Architecture of PLC-based Software for Automated Production Systems: An analysis in industrial companies

Adaptive and flexible production systems require modular and reusable software especially considering their long term life cycle of up to 50 years. SWMAT4aPS, an approach to measure Software Maturity for automated Production Systems is introduced. The approach identifies weaknesses and strengths of various companie's solutions for modularity of software in the design of automated Production Systems (aPS). At first, a self assessed questionnaire is used to evaluate a large number of companies concerning their software maturity. Secondly, we analyze PLC code, architectural levels, workflows and abilities to configure code automatically out of engineering information in four selected companies. In this paper, the questionnaire results from 16 German world leading companies in machine and plant manufacturing and four case studies validating the results from the detailed analyses are introduced to prove the applicability of the approach and give a survey of the state of the art in industry

Transcript profiles uncover temporal and stress-induced changes of metabolic pathways in germinating sugar beet seeds

<p>Abstract</p> <p>Background</p> <p>With a cultivation area of 1.75 Mio ha and sugar yield of 16.7 Mio tons in 2006, sugar beet is a crop of great economic importance in Europe. The productivity of sugar beet is determined significantly by seed vigour and field emergence potential; however, little is known about the molecular mechanisms underlying these traits. Both traits exhibit large variations within sugar beet germplasm that have been difficult to ascribe to either environmental or genetic causes. Among potential targets for trait improvement, an enhancement of stress tolerance is considered because of the high negative influence of environmental stresses on trait parameters. Extending our knowledge of genetic and molecular determinants of sugar beet germination, stress response and adaptation mechanisms would facilitate the detection of new targets for breeding crop with an enhanced field emergence potential.</p> <p>Results</p> <p>To gain insight into the sugar beet germination we initiated an analysis of gene expression in a well emerging sugar beet hybrid showing high germination potential under various environmental conditions. A total of 2,784 ESTs representing 2,251 'unigenes' was generated from dry mature and germinating seeds. Analysis of the temporal expression of these genes during germination under non-stress conditions uncovered drastic transcriptional changes accompanying a shift from quiescent to metabolically active stages of the plant life cycle. Assay of germination under stressful conditions revealed 157 genes showing significantly different expression patterns in response to stress. As deduced from transcriptome data, stress adaptation mechanisms included an alteration in reserve mobilization pathways, an accumulation of the osmoprotectant glycine betaine, late embryogenesis abundant proteins and detoxification enzymes. The observed transcriptional changes are supposed to be regulated by ABA-dependent signal transduction pathway.</p> <p>Conclusion</p> <p>This study provides an important step toward the understanding of main events and metabolic pathways during germination in sugar beet. The reported alterations of gene expression in response to stress shed light on sugar beet stress adaptation mechanisms. Some of the identified stress-responsive genes provide a new potential source for improvement of sugar beet stress tolerance during germination and field emergence.</p

Measuring the Overall Complexity of Graphical and Textual IEC 61131-3 Control Software

Software implements a significant proportion of functionality in factory automation. Thus, efficient development and the reuse of software parts, so-called units, enhance competitiveness. Thereby, complex control software units are more difficult to understand, leading to increased development, testing and maintenance costs. However, measuring complexity is challenging due to many different, subjective views on the topic. This paper compares different complexity definitions from literature and considers with a qualitative questionnaire study the complexity perception of domain experts, who confirm the importance of objective measures to compare complexity. The paper proposes a set of metrics that measure various classes of software complexity to identify the most complex software units as a prerequisite for refactoring. The metrics include complexity caused by size, data structure, control flow, information flow and lexical structure. Unlike most literature approaches, the metrics are compliant with graphical and textual languages from the IEC 61131-3 standard. Further, a concept for interpreting the metric results is presented. A comprehensive evaluation with industrial software from two German plant manufacturers validates the metrics' suitability to measure complexity.Comment: 8 pages, https://ieeexplore.ieee.org/abstract/document/9444196

A PRÁTICA DO PROFESSOR DA EDUCAÇÃO INFANTIL

A Educação Infantil sofreu grandes transformações nos últimos tempos, nem sempre teve um lugar de destaque no desenvolvimento da criança.  Pensando nisso desenvolveu-se uma pesquisa através do componente de Prática e Investigação Educativa na Educação Infantil com os seguintes objetivos: I) Identificar boas práticas educativas;  II) Conhecer os desafios  da prática docente; III) Verificar as concepções sobre o educar, o cuidar e o brincar.  Após  o aprofundamento teórico sobre a Educação Infantil e suas concepções, elaborou-se o instrumento de coletas de dados.   Realizou-se uma entrevista com professora da Educação Infantil do município de Tangará- SC.  Relatou sobre suas dificuldades,  vivências,  rotina,  práticas pedagógicas e concepções.   Reconhece a educação infantil como a primeira etapa para o desenvolvimento integral da criança e por isso reitera da importância e necessidade do trabalho comprometido e responsável do professor. Constata-se que ao  experimentar diversas vivências, a criança terá uma aprendizagem capaz de contribuir para o desenvolvimento  social, cognitivo, emocional se mediado por professores qualificados e preparados. Sendo assim, o educador precisa conhecer como as crianças pensam e se apropriam dos conhecimentos para saber intervir, de maneira lúdica e dinâmica para que a criança possa avançar com êxito. Os resultados deste trabalho apontam a importância dos profissionais trabalharem com qualidade no contexto da educação infantil, sobre tudo pelo fato de contribuir com o desenvolvimento integral e pleno da criança

The liquid helix

From everyday experience, we all know that a solid edge can deflect a liquid flowing over it significantly, up to the point where the liquid completely sticks to the solid. Although important in pouring, printing and extrusion processes, there is no predictive model of this so-called "teapot effect". By grazing vertical cylinders with inclined capillary liquid jets, we here use the teapot effect to attach the jet to the solid and form a new structure: the liquid helix. Using mass and momentum conservation along the liquid stream, we first quantitatively predict the shape of the helix and then provide a parameter-free inertial-capillary adhesion model for the jet deflection and critical velocity for helix formation.Comment: Accepted in Physical Review Letters, author versio

Chlamydia Inhibit Host Cell Apoptosis by Degradation of Proapoptotic BH3-only Proteins

Chlamydia are obligate intracellular bacteria that replicate in a vacuole inside a host cell. Chlamydial infection has been shown to protect the host cell against apoptotic stimuli. This is likely important for the ability of Chlamydia to reproduce in human cells. Here we show that resistance to apoptosis is conveyed by the destruction of the proapoptotic BH3-only proteins Bim/Bod, Puma, and Bad during infection. Apoptotic stimuli were blocked upstream of the mitochondrial activation of Bax/Bak. During infection with both species, Chlamydia trachomatis and Chlamydia pneumoniae, Bim protein gradually disappeared without noticeable changes in Bim mRNA. The disappearance was blocked by inhibitors of the proteasome. Infected cells retained sensitivity to Bim expressed by transfection, indicating functional relevance of the Bim disappearance. Fusion to Bim targeted the green fluorescent protein for destruction during infection. Analysis of truncation mutants showed that a short region of Bim containing the BH3 domain was sufficient for destruction during chlamydial infection. Like Bim, Puma and Bad proteins disappeared during infection. These results reveal a novel way by which microbes can interfere with the host cell's apoptotic machinery, and provide a molecular explanation of the cellular resistance to apoptosis during infection with Chlamydia

Identification of rhabdoviral sequences in oropharyngeal swabs from German and Danish bats

BACKGROUND: In the frame of active lyssavirus surveillance in bats, oropharyngeal swabs from German (N = 2297) and Danish (N = 134) insectivorous bats were investigated using a newly developed generic pan-lyssavirus real-time reverse transcriptase PCR (RT-qPCR). FINDINGS: In total, 15 RT-qPCR positive swabs were detected. Remarkably, sequencing of positive samples did not confirm the presence of bat associated lyssaviruses but revealed nine distinct novel rhabdovirus-related sequences. CONCLUSIONS: Several novel rhabdovirus-related sequences were detected both in German and Danish insectivorous bats. The results also prove that the novel generic pan-lyssavirus RT-qPCR offers a very broad detection range that allows the collection of further valuable data concerning the broad and complex diversity within the family Rhabdoviridae