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Hydrogen sulfide contributes to hypoxic inhibition of airway transepithelial sodium absorption
(2016)
We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1β from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1β is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1β release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing α9 and α10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of α9 subunits or heteromeric receptors containing α9 and α10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions.
Hydrogen sulfide (H2S) is a well-known environmental chemical threat with an unpleasant smell of rotten eggs. Aside from the established toxic effects of high-dose H2S, research over the past decade revealed that cells endogenously produce small amounts of H2S with physiological functions. H2S has therefore been classified as a gasotransmitter. A major challenge for cells and tissues is the maintenance of low physiological concentrations of H2S in order to prevent potential toxicity. Epithelia of the respiratory and gastrointestinal tract are especially faced with this problem, since these barriers are predominantly exposed to exogenous H2S from environmental sources or sulfur-metabolising microbiota. In this paper, we review the cellular mechanisms by which epithelial cells maintain physiological, endogenous H2S concentrations. Furthermore, we suggest a concept by which epithelia use their electrolyte and liquid transport machinery as defence mechanisms in order to eliminate exogenous sources for potentially harmful H2S concentrations.
An exploratory study: Analysis of Serbian tourism market and identification of major market segments
(2016)
Currently, there are a lot of research activities dealing with gamma titanium aluminide (γ-TiAl) alloys as new materials for low pressure turbine (LPT) blades. Even though the scatter in mechanical properties of such intermetallic alloys is more distinctive as in conventional metallic alloys, stochastic investigations on γ -TiAl alloys are very rare. For this reason, we analyzed the scatter in static and dynamic mechanical properties of the cast alloy Ti-48Al-2Cr-2Nb. It was found that this alloy shows a size effect in strength which is less pronounced than the size effect of brittle materials. A weakest-link approach is enhanced for describing a scalable size effect under multiaxial stress states and implemented in a post processing tool for reliability analysis of real components. The presented approach is a first applicable reliability model for semi-brittle materials. The developed reliability tool was integrated into a multidisciplinary optimization of the geometry of a LPT blade. Some processes of the optimization were distributed in a wide area network, so that specialized tools for each discipline could be employed. The optimization results show that it is possible to increase the aerodynamic efficiency and the structural mechanics reliability at the same time, while ensuring the blade can be manufactured in an investment casting process.
The aim of design science research (DSR) in information systems is the user-centred creation of IT-artifacts with regard to specific social environments. For culture research in the field, which is necessary for a proper localization of IT-artifacts, models and research approaches from social sciences usually are adopted. Descriptive dimension-based culture models most commonly are applied for this purpose, which assume culture being a national phenomenon and tend to reduce it to basic values. Such models are useful for investigations in behavioural culture research because it aims to isolate, describe and explain culture-specific attitudes and characteristics within a selected society. In contrast, with the necessity to deduce concrete decisions for artifact-design, research results from DSR need to go beyond this aim. As hypothesis, this contribution generally questions the applicability of such generic culture dimensions’ models for DSR and focuses on their theoretical foundation, which goes back to Hofstede’s conceptual Onion Model of Culture. The herein applied literature-based analysis confirms the hypothesis. Consequently, an alternative conceptual culture model is being introduced and discussed as theoretical foundation for culture research in DSR.
Background: Falls are common in older adults and can result in serious injuries. Due to demographic changes, falls and related healthcare costs are likely to increase over the next years. Participation and motivation of older adults in fall prevention measures remain a challenge. The iStoppFalls project developed an information and communication technology (ICT)-based system for older adults to use at home in order to reduce common fall risk factors such as impaired balance and muscle weakness. The system aims at increasing older adults’ motivation to participate in ICT-based fall prevention measures. This article reports on usability, user-experience and user-acceptance aspects affecting the use of the iStoppFalls system by older adults.
Methods: In the course of a 16-week international multicenter study, 153 community-dwelling older adults aged 65+ participated in the iStoppFalls randomized controlled trial, of which half used the system in their home to exercise and assess their risk of falling. During the study, 60 participants completed questionnaires regarding the usability, user experience and user acceptance of the iStoppFalls system. Usability was measured with the System Usability Scale (SUS). For user experience the Physical Activity Enjoyment Scale (PACES) was applied. User acceptance was assessed with the Dynamic Acceptance Model for the Re-evaluation of Technologies (DART). To collect more detailed data on usability, user experience and user acceptance, additional qualitative interviews and observations were conducted with participants.
Results: Participants evaluated the usability of the system with an overall score of 62 (Standard Deviation, SD 15.58) out of 100, which suggests good usability. Most users enjoyed the iStoppFalls games and assessments, as shown by the overall PACES score of 31 (SD 8.03). With a score of 0.87 (SD 0.26), user acceptance results showed that participants accepted the iStoppFalls system for use in their own home. Interview data suggested that certain factors such as motivation, complexity or graphical design were different for gender and age.
Conclusions: The results suggest that the iStoppFalls system has good usability, user experience and user acceptance. It will be important to take these along with factors such as motivation, gender and age into consideration when designing and further developing ICT-based fall prevention systems.
SpMV Runtime Improvements with Program Optimization Techniques on Different Abstraction Levels
(2016)
The multiplication of a sparse matrix with a dense vector is a performance critical computational kernel in many applications, especially in natural and engineering sciences. To speed up this operation, many optimization techniques have been developed in the past, mainly focusing on the data layout for the sparse matrix. Strongly related to the data layout is the program code for the multiplication. But even for a fixed data layout with an accommodated kernel, there are several alternatives for program optimizations. This paper discusses a spectrum of program optimization techniques on different abstraction layers for six different sparse matrix data format and kernels. At the one end of the spectrum, compiler options can be used that hide from the programmer all optimizations done by the compiler internally. On the other end of the spectrum, a multiplication kernel can be programmed that use highly sophisticated intrinsics on an assembler level that ask for a programmer with a deep understanding of processor architectures. These special instructions can be used to efficiently utilize hardware features in processors like vector units that have the potential to speed up sparse matrix computations. The paper compares the programming effort and required knowledge level for certain program optimizations in relation to the gained runtime improvements.
With the rising interest in vehicular communication systems many proposals for secure vehicle-to-vehicle commu- nication were made in recent years. Also, several standard- ization activities concerning the security and privacy measures in these communication systems were initiated in Europe and in US. Here, we discuss some limitations for secure vehicle- to-infrastructure communication in the existing standards of the European Telecommunications Standards Institute. Next, a vulnerability analysis for roadside stations on one side and security and privacy requirements for roadside stations on the other side are given. Afterwards, a proposal for a multi-domain public key architecture for intelligent transport systems, which considers the necessities of road infrastructure authorities and vehicle manufacturers, is introduced. The domains of the public key infrastructure are cryptographically linked based on local trust lists. In addition, a crypto agility concept is suggested, which takes adaptation of key length and cryptographic algorithms during PKI operation into account.
The design of future materials for biotechnological applications via deposition of molecules on surfaces will require not only exquisite control of the deposition procedure, but of equal importance will be our ability to predict the shapes and stability of individual molecules on various surfaces. Furthermore, one will need to be able to predict the structure patterns generated during the self-organization of whole layers of (bio)molecules on the surface. In this review, we present an overview over the current state of the art regarding the prediction and clarification of structures of biomolecules on surfaces using theoretical and computational methods.
Beta-ketothiolase deficiency, also known as mitochondrial acetoacetyl-CoA thiolase (T2) deficiency, is an autosomal recessive disease caused by mutations in the acetylCoA acetyltransferase 1 (ACAT1) gene. A German T2deficient patient that developed a severe ketoacidotic episode at the age of 11 months, was revealed to be a compound heterozygote of a previously reported null mutation, c.472A>G (p.N158D) and a novel mutation, c.949G>A (p.D317N), in ACAT1. The c.949G>A mutation was suspected to cause aberrant splicing as it is located within an exonic splicing enhancer sequence (c. 947CTGACGC) that is a potential binding site for serine/argininerich splicing factor 1. A mutation in this sequence, c.951C>T, results in exon 10 skipping. A minigene construct was synthesized that included exon 9truncated intron 9exon 10truncated intron 10exon 11, and the splicing of this minigene revealed that the c.949G>A mutant construct caused exon 10 skipping in a proportion of the transcripts. Furthermore, additional substitution of G for C at the first nucleotide of exon 10 (c.941G>C) abolished the effect of the c.949G>A mutation. Transient expression analysis of the c.949G>A mutant cDNA revealed no residual T2 activity in the mutated D317N enzyme. Therefore, c.949G>A (D317N) is a pathogenic missense mutation, and diminishes the effect of an exonic splicing enhancer and causes exon 10 skipping. The present study demonstrates that a missense mutation, or even a synonymous substitution, may disrupt enzyme function by interference with splicing.
Companies often have difficulties determining which criteria to base their investment decisions in different countries on. When considering direct foreign investment several risk indices are available. The PCI (Peren-Clement-Index) in its original form was developed in 1998. Its further refinement improves the PCI in three major ways: First, it offers a dynamic adjustment of criteria and consideration of recent changes in the international environment. Second, it provides business specificities of a company or its industrial sector to be considered in addition to macroeconomic aspects by a two-dimensional presentation, which ensures a customized assessment. Third, the PCI allows for consolidating investment decisions by combining a resource-orientated with a market-oriented view. The PCI allows, unlike other indices, a customized and company-specific strategic planning process. Ultimately companies must take up both perspectives in the context of an international investment decision. The use of risk indices in corporate planning for assessing global investments decision creates a fundamentally new of risk assessment.
In this paper, a set of micro-benchmarks is proposed to determine basic performance parameters of single-node mainstream hardware architectures for High Performance Computing. Performance parameters of recent processors, including those of accelerators, are determined. The investigated systems are Intel server processor architectures and the two accelerator lines Intel Xeon Phi and Nvidia graphic processors. Additionally, the performance impact of thread mapping on multiprocessors and Intel Xeon Phi is shown. The results show similarities for some parameters between all architectures, but significant differences for others.