Loss of Interleukin-13-Receptor-Alpha-1 Induces Apoptosis and Promotes EMT in Pancreatic Cancer

In search of new therapies for pancreatic cancer, cytokine pathways have attracted increasing interest in recent years. Cytokines play a vital role in the crosstalk between tumour cells and the tumour microenvironment. The related inflammatory cytokines IL-4 and IL-13 can regularly be detected at increased levels in the microenvironment of pancreatic cancer. They share a receptor heterodimer consisting of IL-4Rα and IL-13Rα1. While IL-4Rα induces a more oncogenic phenotype, the role of IL-13Rα1 was yet to be determined. ShRNA-based knockdown of IL-13Rα1 was performed in Capan-1 and MIA PaCa-2. We assessed cell growth and migratory capacities under the influence of IL-13Rα1. Pathway alterations were detected by immunoblot analysis. We now have demonstrated that the loss of IL-13Rα1 induces apoptosis in pancreatic cancer cells. This was associated with an epithelial-to-mesenchymal transition. Loss of IL-13Rα1 also abolished the effects of exogenous IL-4 and IL-13 stimulation. Interestingly, in wild type cells, cytokine stimulation caused a similar increase in migratory capacities as after IL-13Rα1 knockdown. Overall, our results indicate the vital role of IL-13Rα1 in the progression of pancreatic cancer. The differential expression of IL-4Rα and IL-13Rα1 has to be taken into account when considering a cytokine-targeted therapy in pancreatic cancer.     

Internalization and Accumulation in Dendritic Cells of a Small pH‐Activatable Glycomimetic Fluorescent Probe as Revealed by Spectral Detection

DC‐SIGN, an antigen‐uptake receptor in dendritic cells (DCs), has a clear role in the immune response but, conversely, can also facilitate infection by providing entry of pathogens into DCs. The key action in both processes is internalization into acidic endosomes and lysosomes. Molecular probes that bind to DC‐SIGN could thus provide a useful tool to study internalization and constitute potential antagonists against pathogens. So far, only large molecules have been used to directly observe DC‐SIGN‐mediated internalization into DCs by fluorescence visualization. We designed and synthesized an appropriate small glycomimetic probe. Two particular properties of the probe were exploited: activation in a low‐pH environment and an aggregation‐induced spectral shift. Our results indicate that small glycomimetic molecules could compete with antigen/pathogen for binding not only outside but also inside the DC, thus preventing the harmful action of pathogens that are able to intrude into DCs, for example, HIV‐1.     

Processing of the quench detection signals in W7-X

The Wendelstein 7-X (W7-X) project uses superconductive coils for generation of the magnetic field to keep the plasma. One of the important safety systems is the protection against quench events. The quench detection system of W7-X protects the superconducting coils, the superconducting bus bar sections and the high temperature superconductor of the current leads against the damage because of a quench and against the high stress by a fast discharge of the magnet system.Therefore, the present design of the quench detection system (QDS) uses a two-stage safety concept for discharging the magnetic system. This paper describes the present design of the system assembly from the quench detection unit (QDU) for the detection of the quench to the quench detection interface (QDI) to implement the two-stage safety concept.     

A method for rapid vulnerability assessment of structures loaded by outside blasts

The blast loads have in most cases not been assumed as design basis loads of nuclear power plant buildings and structures. Recent developments however stimulated a number of analyses quantifying the potential effects of such loads.An effort was therefore made by the authors to revisit simple and robust structural analysis methods and to propose their use in the vulnerability assessment of blast-loaded structures. The leading idea is to break the structure into a set of typical structural elements, for which the response is estimated by the use of slightly modified handbook formulas. The proposed method includes provisions to predict the inelastic response and failure. Simplicity and versatility of the method facilitate its use in structural reliability calculations.The most important aspects of the proposed method are presented along with illustrative sample applications demonstrating:

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results comparable to full scale dynamic simulations using explicit finite element codes and

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the performance of the method in screening the existing structures and providing the structural reliability information for the vulnerability analysis.

     

Critical Evaluation of Current Hypotheses for the Pathogenesis of Hypertrophic Cardiomyopathy

Hereditary hypertrophic cardiomyopathy (HCM), due to mutations in sarcomere proteins, occurs in more than 1/500 individuals and is the leading cause of sudden cardiac death in young people. The clinical course exhibits appreciable variability. However, typically, heart morphology and function are normal at birth, with pathological remodeling developing over years to decades, leading to a phenotype characterized by asymmetric ventricular hypertrophy, scattered fibrosis and myofibrillar/cellular disarray with ultimate mechanical heart failure and/or severe arrhythmias. The identity of the primary mutation-induced changes in sarcomere function and how they trigger debilitating remodeling are poorly understood. Support for the importance of mutation-induced hypercontractility, e.g., increased calcium sensitivity and/or increased power output, has been strengthened in recent years. However, other ideas that mutation-induced hypocontractility or non-uniformities with contractile instabilities, instead, constitute primary triggers cannot yet be discarded. Here, we review evidence for and criticism against the mentioned hypotheses. In this process, we find support for previous ideas that inefficient energy usage and a blunted Frank–Starling mechanism have central roles in pathogenesis, although presumably representing effects secondary to the primary mutation-induced changes. While first trying to reconcile apparently diverging evidence for the different hypotheses in one unified model, we also identify key remaining questions and suggest how experimental systems that are built around isolated primarily expressed proteins could be useful.     

Application of glyph-based techniques for multivariate engineering visualization

This article presents a review of glyph-based techniques for engineering visualization as well as practical application for the multivariate visualization process. Two glyph techniques, Chernoff faces and star glyphs, uncommonly used in engineering practice, are described, applied to the selected data set, run through the chosen optimization methods and user evaluated. As an example of how these techniques function, a set of data for the optimization of a heat exchanger with a microchannel coil is adopted for visualization. The results acquired by the chosen visualization techniques are related to the results of optimization carried out by the response surface method and compared with the results of user evaluation. Based on the data set from engineering research and practice, the advantages and disadvantages of these techniques for engineering visualization are identified and discussed.     

Synthesis and characterization of crystalline hexagonal bipods of zinc oxide

The preparation of nano- and submicrometre-sized one-dimensional (1D) zinc oxides (ZnOs) from zinc nitrate was performed by precipitation with urea in two types of solvents (water and water/polyol mixtures). The influence of different polyols (ethylene glycol, diethylene glycol and tetraethylene glycol) on the size of the final particles (length and diameter) is presented for the first time. As well as the influence of the solvents used, the ratio of water/polyol, temperature, pH and time of synthesis was correlated with the size and morphology of the final particles. In all cases crystalline ZnO was synthesized in the form of hexagonal bipods. The morphological and crystalline properties of the samples obtained were characterized by SEM, IR, and XRD.     

Linking business and requirements engineering: is solution planning a missing activity in software product companies?

A strong link between strategy and product development is important, since companies need to select requirements for forthcoming releases. However, in practice, connecting requirements engineering (RE) and business planning is far from trivial. This paper describes the lessons learned from four software product companies that have recognized the need for more business-oriented long-term planning. The study was conducted using the action research approach. We identified five practices that seem to strengthen the link between business decisions and RE. These are (1) explicating the planning levels and time horizons; (2) separating the planning of products’ business goals from R&D resource allocation; (3) planning open-endedly with a pre-defined rhythm; (4) emphasizing whole-product thinking; and (5) making solution planning visible. To support whole-product thinking and solution planning, we suggest that companies create solution concepts. The purpose of the solution concept is to provide a big picture of the solution and guide RE activities.     

Evaluating the development of carbon capture and storage technologies in the United States

Carbon capture and storage (CCS) is seen as an important solution to solve the twin challenge of reducing GHG emissions, while utilizing fossil fuel reserves to meet future energy requirements. In this study an innovation systems perspective is applied to review the development of CCS technologies in the US between 2000 and 2009 and to come up with policy recommendations for technology managers that wish to accelerate the deployment of CCS. The analysis describes the successful built-up of an innovation system around CCS and pinpoints the key determinants for this achievement. However, the evaluation of the system's performance also indicates that America's leading role in the development of CCS should not be taken for granted. It shows that the large CCS R&D networks, as well as the extensive CCS knowledge base, which have been accumulated over the past decade, have not yet been valorized by entrepreneurs to explore the market for integrated CCS concepts linked to power generation. Therefore, it is argued that the build-up of the innovation system has entered a critical phase that is decisive for a further thriving development of CCS technologies in the US. This study provides a clear understanding of the current barriers to the technology's future deployment and outlines a policy strategy that (1) stimulates technological learning; (2) facilitates collaboration and coordination in CCS actor networks; (3) creates financial and market incentives for the technology; and (4) provides supportive regulation and sound communication on CCS.     

Influence of Whey Protein Addition and Feed Moisture Content on Chosen Physicochemical Properties of Directly Expanded Corn Extrudates

Production of extrudates from cereals is an often-used technological process in today’s world food industry. Extrudates from corn flour produced using the twin-screw extrusion process and enriched with whey protein concentrate represent high-quality source of proteins and fats. Whey protein concentrate (WPC) as a valuable source of proteins and minerals is one of the highest-quality components for possible extrudate enrichment. In this paper, the influence of various WPC addition and some extrusion process parameters such as feed moisture content ( Q_{\textH\text2 \textO} Q_{{{\text{H}}_{\text{2}} {\text{O}}}} ) on physicochemical properties of directly expanded corn flour extrudates manufactured in twin-screw co-rotating extruder was investigated. Whey protein concentrate was added in the following ratios 7.5%, 15% and 22.5% and water in 10.08, 12.18 and 14.28 L/h. Final composition of products is determined with measuring of protein, fat and water shares, water absorption index (WAI) and water solubility index (WSI). With added WPC and with increase of water volume flow, there was a significant rise in total protein, fat and water content in final products, as well as lowering of WSI and rising of WAI indexes. The statistical analysis of the obtained data shows that the lowest WSI and the highest WAI had samples with the largest share of WPC (22.5%) and water volume flow of 14.28 L/h. Colour is measured for each sample, and results were represented with hue angle (H), chroma (C) and lightness (L) values. Process parameters, WPC and Q_{\textH\text2 \textO} Q_{{{\text{H}}_{\text{2}} {\text{O}}}} influence the increase of saturation of C and lightness of L colour value, while H value stays unchanged. Mean value of H was 90.14 ± 1.06, which corresponds to dominance of yellow colour of samples.