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    The M1 and pre-M1 segments contribute differently to ion selectivity in ASICs and ENaCs

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    The ability to discriminate between different ionic species, termed ion selectivity, is a key feature of ion channels and forms the basis for their physiological function. Members of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily of trimeric ion channels are typically sodium selective, but to a surprisingly variable degree. While acid-sensing ion channels (ASICs) are weakly sodium selective (sodium:potassium around 10:1), ENaCs show a remarkably high preference for sodium over potassium (>500:1). The most obvious explanation for this discrepancy may be expected to originate from differences in the pore-lining second transmembrane segment (M2). However, these show a relatively high degree of sequence conservation between ASICs and ENaCs and previous functional and structural studies could not unequivocally establish that differences in M2 alone can account for the disparate degrees of ion selectivity. By contrast, surprisingly little is known about the contributions of the first transmembrane segment (M1) and the preceding pre-M1 region. In this study, we use conventional and non-canonical amino acid-based mutagenesis in combination with a variety of electrophysiological approaches to show that the pre-M1 and M1 regions of mASIC1a channels are major determinants of ion selectivity. Mutational investigations of the corresponding regions in hENaC show that they contribute less to ion selectivity, despite affecting ion conductance. In conclusion, our work supports the notion that the remarkably different degrees of sodium selectivity in ASICs and ENaCs are achieved through different mechanisms. The results further highlight how M1 and pre-M1 are likely to differentially affect pore structure in these related channels

    Sammelrezension: Digitaler Journalismus

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    John V. Pavlik: Journalism in the Age of Virtual Reality: How Experiential Media are Transforming News New York: Columbia UP 2019, 284 S., ISBN 9780231184496, GBP 25,- Karen Fowler-Watt, Stephen Jukes (Hg.): New Journalisms: Rethinking Practice, Theory and Pedagogy London, New York: Routledge 2020, 198 S., ISBN 9781138596757, GBP 34,9

    Less is Often More: Header Whitelisting as Semantic Gap Mitigation in HTTP-Based Software Systems

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    The web is the most wide-spread digital system in the world and is used for many crucial applications. This makes web application security extremely important and, although there are already many security measures, new vulnerabilities are constantly being discovered. One reason for some of the recent discoveries lies in the presence of intermediate systems—e.g. caches, message routers, and load balancers—on the way between a client and a web application server. The implementations of such intermediaries may interpret HTTP messages differently, which leads to a semantically different understanding of the same message. This so-called semantic gap can cause weaknesses in the entire HTTP message processing chain. In this paper we introduce the header whitelisting (HWL) approach to address the semantic gap in HTTP message processing pipelines. The basic idea is to normalize and reduce an HTTP request header to the minimum required fields using a whitelist before processing it in an intermediary or on the server, and then restore the original request for the next hop. Our results show that HWL can avoid misinterpretations of HTTP messages in the different components and thus prevent many attacks rooted in a semantic gap including request smuggling, cache poisoning, and authentication bypass

    AdvWarp: A Transformation Algorithm for Advanced Modeling of Gas Compressors and Drives

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    Solving transport network problems can be complicated by non-linear effects. In the particular case of gas transport networks, the most complex non-linear elements are compressors and their drives. They are described by a system of equations, composed of a piecewise linear ‘free’ model for the control logic and a non-linear ‘advanced’ model for calibrated characteristics of the compressor. For all element equations, certain stability criteria must be fulfilled, providing the absence of folds in associated system mapping. In this paper, we consider a transformation (warping) of a system from the space of calibration parameters to the space of transport variables, satisfying these criteria. The algorithm drastically improves stability of the network solver. Numerous tests on realistic networks show that nearly 100% convergence rate of the solver is achieved with this approach

    Business Model Innovation: Strategic Expansion of German Small and Medium Wineries into Hospitality and Tourism

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    This article provides insights into the modalities of business-model change and innovation. On the basis of an analysis of empirical data of small and medium enterprises, a transition from wine production centrism to its expanded use in hospitality and tourism is explored. Previous research on wine tourism and hospitality predominantly focuses on a destination perspective, neglecting the organizational winery perspective. The article deploys a mixed methods approach, combining netnography and a content analysis for data collection with grounded research and clustering for theory building. The sample size included 885 German wineries. Data stemmed from two distinct sources (websites and a secondary publication in form of a wine guide) and has been analyzed through a two-step clustering algorithm as well as a Principal Component Analysis (PCA). The two-step clustering algorithm resulted in nine different business models while the PCA analysis grouped the variables into the following two categories: basic winery business model (BM) and BM extension into hospitality and tourism, thereby validating the difference between the two constructs. The results point to the diverse nature of business model extensions of wineries in tourism and hospitality, depending on their organizational type and size. This study offers a classification of small and medium sized enterprise’s strategic business model expansion, and explores the expansion of the wine industry through wine hospitality and tourism services, starting with the winery organizational perspective, which has not been done before

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