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Intermediate filament reorganization dynamically influences cancer cell alignment and migration
(2017)
The interactions between a cancer cell and its extracellular matrix (ECM) have been the focus of an increasing amount of investigation. The role of the intermediate filament keratin in cancer has also been coming into focus of late, but more research is needed to understand how this piece fits in the puzzle of cytoskeleton-mediated invasion and metastasis. In Panc-1 invasive pancreatic cancer cells, keratin phosphorylation in conjunction with actin inhibition was found to be sufficient to reduce cell area below either treatment alone. We then analyzed intersecting keratin and actin fibers in the cytoskeleton of cyclically stretched cells and found no directional correlation. The role of keratin organization in Panc-1 cellular morphological adaptation and directed migration was then analyzed by culturing cells on cyclically stretched polydimethylsiloxane (PDMS) substrates, nanoscale grates, and rigid pillars. In general, the reorganization of the keratin cytoskeleton allows the cell to become more ‘mobile’- exhibiting faster and more directed migration and orientation in response to external stimuli. By combining keratin network perturbation with a variety of physical ECM signals, we demonstrate the interconnected nature of the architecture inside the cell and the scaffolding outside of it, and highlight the key elements facilitating cancer cell-ECM interactions.
AUDI AG has historically focused on producing and selling premium vehicles but has begun to experiment with providing mobility services, built around car sharing. Its response to the so-called sharing economy addressed strategic and transformational challenges. Strategically, the company pursued additional sources of revenue from targeted, premium mobility services, rather than the less segmented services provided by competitors such as BMW and Zipcar. AUDI AG also transformed its organizational structure, processes and architecture to balance autonomy for innovation and integration for competitiveness.
Cell-cell and cell-extracellular matrix (ECM) adhesion regulates fundamental cellular functions and is crucial for cell-material contact. Adhesion is influenced by many factors like affinity and specificity of the receptor-ligand interaction or overall ligand concentration and density. To investigate molecular details of cell ECM and cadherins (cell-cell) interaction in vascular cells functional nanostructured surfaces were used Ligand-functionalized gold nanoparticles (AuNPs) with 6-8 nm diameter, are precisely immobilized on a surface and separated by non-adhesive regions so that individual integrins or cadherins can specifically interact with the ligands on the AuNPs. Using 40 nm and 90 nm distances between the AuNPs and functionalized either with peptide motifs of the extracellular matrix (RGD or REDV) or vascular endothelial cadherins (VEC), the influence of distance and ligand specificity on spreading and adhesion of endothelial cells (ECs) and smooth muscle cells (SMCs) was investigated. We demonstrate that RGD-dependent adhesion of vascular cells is similar to other cell types and that the distance dependence for integrin binding to ECM-peptides is also valid for the REDV motif. VEC-ligands decrease adhesion significantly on the tested ligand distances. These results may be helpful for future improvements in vascular tissue engineering and for development of implant surfaces.
The European Economic and Monetary Union (EMU) has been in turmoil for more than six years. The present governance rules do not seem to solve the problems neither permanently nor effectively. There is no vision about the future of Europe in the 21st century. This article describes a realignment of the economic governance, which does not necessarily lead to a transfer or political union. However, it solves the current and future challenges. In fact, the redesign of present rules is the most likely as well as legally and economically option today. The key ideais the detachment from the compulsive idea of an ever closer union. However, this vision requires boldness towards greater flexibility together with an exit clause or a state insolvency procedure for incompliant member states.
Saving energy and road safety became important in the last decades, hence several driving assistant systems were developed that help to improve the driving behaviour. However, these driving systems cover the area of either energy-efficiency or safety. Furthermore, they do not consider the reaction of the driver to a shown recommendation and the driver stress level. In this paper, the decision process of showing a recommendation to the driver in an energy-efficient and safety relevant driving system is presented. The decision process considers the driver's reaction to a shown recommendation and the driver stress in order to increase the user acceptance and the road safety. The results of the evaluation showed that the driving system was able to show recommendations when needed, while suppressing recommendations when the driver ignored a recommendation repeatedly or when the driver was in stress.
Introducing continuous experimentation in large software-intensive product and service organisations
(2017)
Software development in highly dynamic environments imposes high risks to development organizations. One such risk is that the developed software may be of only little or no value to customers, wasting the invested development efforts.Continuous experiment ation, as an experiment-driven development approach, may reduce such development risks by iteratively testing product and service assumptions that are critical to the success of the software. Although several experiment-driven development approaches are available, there is little guidance available on how to introduce continuous experimentation into an organization. This article presents a multiple-case study that aims at better understanding the process of introducing continuous experimentation into an organization with an already established development process. The results from the study show that companies are open to adopting such an approach and learning throughout the introduction process. Several benefits were obtained, such as reduced development efforts, deeper customer insights, and better support for development decisions. Challenges included complex stakeholder structures, difficulties in defining success criteria, and building experimen- tation skills. Our findings indicate that organizational factors may limit the benefits of experimentation. Moreover, introducing continuous experimentation requires fundamental changes in how companies operate, and a systematic introduction process can increase the chances of a successful start.
To evaluate the quality of sleep, it is important to determine how much time was spent in each sleep stage during the night. The gold standard in this domain is an overnight polysomnography (PSG). But the recording of the necessary electrophysiological signals is extensive and complex and the environment of the sleep laboratory, which is unfamiliar to the patient, might lead to distorted results. In this paper, a sleep stage detection algorithm is proposed that uses only the heart rate signal, derived from electrocardiogram (ECG), as a discriminator. This would make it possible for sleep analysis to be performed at home, saving a lot of effort and money. From the heart rate, using the fast Fourier transformation (FFT), three parameters were calculated in order to distinguish between the different sleep stages. ECG data along with a hypnogram scored by professionals was used from Physionet database, making it easy to compare the results. With an agreement rate of 41.3%, this approach is a good foundation for future research.
Zukünftige Montagearbeitsplätze müssen veränderten Herausforderungen, wie z. B. der zunehmenden Anzahl von Mensch Roboter-Kollaborationen, gerecht werden. Die Virtual Reality (VR)-Technik bietet im Rahmen der Arbeitsplatzgestaltung neue Möglichkeiten, diesen veränderten Planungsherausforderungen gerecht zu werden. Die Ausarbeitung stellt eine Methode zur Bewertung des sinnvollen Einsatzes der VR-Technik für einen spezifischen Arbeitsplatz vor. Außerdem wird aufgezeigt, wie die VR-Technik in den Prozess der Arbeitsplatzgestaltung integriert werden kann.
LDMOS transistors in integrated power technologies are often subject to thermo-mechanical stress, which degrades the on-chip metallization and eventually leads to a short. This paper investigates small sense lines embedded in the LDMOS metallization. It will be shown that their resistance depends strongly on the stress cycle number. Thus, they can be used as aging sensors and predict impending failures. Different test structures have been investigated to identify promising layout configurations. Such sensors are key components for resilient systems that adaptively reduce stress to allow aggressive LDMOS scaling without increasing the risk of failure.