390 research outputs found

    The Effects of Book Choice in Small-Group Reading

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    This study investigated the effects choice has on student comprehension, motivation and overall satisfaction in a small-group setting within the reading classroom. The focus for this study was to determine if allowing students the opportunity to choose the book that is read in small-group is more beneficial than having the book chosen by the teacher. Data were collected through student comprehension scores, student surveys, and teacher observation sheets. Research took place within two 4th grade classrooms in a small school in central Minnesota. The results of this study indicated that allowing choice has positive effects on student learning

    Banknoten als sprachenpolitisches Instrument

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    For modern states, multilingualism is not an exception, but the norm. Most states explicitly deal with the status of their languages through their (often rather sparse) legislation, while implicitly reflecting their policy through language use on official documents. Banknotes provide a link between the official policy and its common application, as they are both a document of the state as well as an object of daily use. Here, the state is responsible for bridging the gap between legislature, national identity and the (sometimes conflicting) selfconceptions of its citizens. Thus, banknotes ideally provide evidence on a state’s factual (rather than nominal) language policy. In addition, the textual and pragmatic functions of banknotes are not prone to change over time, which qualifies them as excellent sources for diachronic questions. This article exemplarily illustrates the language policies of Norway, the Faroe Islands, Belgium and Luxembourg, as seen from a sociohistorical perspective, with their respective note emissions during their newer language history (19th and 20th centuries). It closes with a proposal for a typology of different language policies

    TIScover-A Tourism Information System based on Extranet and Intranet Technology

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    The tourism industry more and more intensifies the endeavors to take advantage of the World Wide Web. However, Web-based tourism information systems are required not to offer online brochures only, but rather to provide both, value and service. One system which has recognized this fact is TIScover. TIScover allows the tourist for convenient and powerful access to tourism information and products through the support of different information retrieval philosophies along with an online booking facility. In addition, TIScover employs an Extranet and an Intranet component allowing the decentralized maintenance and customization of the tourism database. With this, a high quality content in terms of comprehensiveness, accurateness and actuality can be achieved and the system can be easily adapted not only for different kinds of tourism information providers, but also for different regions and even different countries. This paper gives a brief overview of TIScover and describes its main functional components

    The Nod-Like Receptor (NLR) Family: A Tale of Similarities and Differences

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    Innate immunity represents an important system with a variety of vital processes at the core of many diseases. In recent years, the central role of the Nod-like receptor (NLR) protein family became increasingly appreciated in innate immune responses. NLRs are classified as part of the signal transduction ATPases with numerous domains (STAND) clade within the AAA+ ATPase family. They typically feature an N-terminal effector domain, a central nucleotide-binding domain (NACHT) and a C-terminal ligand-binding region that is composed of several leucine-rich repeats (LRRs). NLRs are believed to initiate or regulate host defense pathways through formation of signaling platforms that subsequently trigger the activation of inflammatory caspases and NF-kB. Despite their fundamental role in orchestrating key pathways in innate immunity, their mode of action in molecular terms remains largely unknown. Here we present the first comprehensive sequence and structure modeling analysis of NLR proteins, revealing that NLRs posses a domain architecture similar to the apoptotic initiator protein Apaf-1. Apaf-1 performs its cellular function by the formation of a heptameric platform, dubbed apoptosome, ultimately triggering the controlled demise of the affected cell. The mechanism of apoptosome formation by Apaf-1 potentially offers insight into the activation mechanisms of NLR proteins. Multiple sequence alignment analysis and homology modeling revealed Apaf-1-like structural features in most members of the NLR family, suggesting a similar biochemical behaviour in catalytic activity and oligomerization. Evolutionary tree comparisons substantiate the conservation of characteristic functional regions within the NLR family and are in good agreement with domain distributions found in distinct NLRs. Importantly, the analysis of LRR domains reveals surprisingly low conservation levels among putative ligand-binding motifs. The same is true for the effector domains exhibiting distinct interfaces ensuring specific interactions with downstream target proteins. All together these factors suggest specific biological functions for individual NLRs

    A highly efficient computational framework for fast scan-resolved simulations of metal additive manufacturing processes on the scale of real parts

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    This article proposes a novel high-performance computing approach for the prediction of the temperature field in powder bed fusion (PBF) additive manufacturing processes. In contrast to many existing approaches to part-scale simulations, the underlying computational model consistently resolves physical scan tracks without additional heat source scaling, agglomeration strategies or any other heuristic modeling assumptions. A growing, adaptively refined mesh accurately captures all details of the laser beam motion. Critically, the fine spatial resolution required for resolved scan tracks in combination with the high scan velocities underlying these processes mandates the use of comparatively small time steps to resolve the underlying physics. Explicit time integration schemes are well-suited for this setting, while unconditionally stable implicit time integration schemes are employed for the interlayer cool down phase governed by significantly larger time scales. These two schemes are combined and implemented in an efficient fast operator evaluation framework providing significant performance gains and optimization opportunities. The capabilities of the novel framework are demonstrated through realistic AM examples on the centimeter scale including the first scan-resolved simulation of the entire NIST AM Benchmark cantilever specimen, with a computation time of less than one day. Apart from physical insights gained through these simulation examples, also numerical aspects are thoroughly studied on basis of weak and strong parallel scaling tests. As potential applications, the proposed thermal PBF simulation framework can serve as a basis for microstructure and thermo-mechanical predictions on the part-scale, but also to assess the influence of scan pattern and part geometry on melt pool shape and temperature, which are important indicators for well-known process instabilities

    TGF-β dependent regulation of oxygen radicals during transdifferentiation of activated hepatic stellate cells to myofibroblastoid cells

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    BACKGROUND: The activation of hepatic stellate cells (HSCs) plays a pivotal role during liver injury because the resulting myofibroblasts (MFBs) are mainly responsible for connective tissue re-assembly. MFBs represent therefore cellular targets for anti-fibrotic therapy. In this study, we employed activated HSCs, termed M1-4HSCs, whose transdifferentiation to myofibroblastoid cells (named M-HTs) depends on transforming growth factor (TGF)-β. We analyzed the oxidative stress induced by TGF-β and examined cellular defense mechanisms upon transdifferentiation of HSCs to M-HTs. RESULTS: We found reactive oxygen species (ROS) significantly upregulated in M1-4HSCs within 72 hours of TGF-β administration. In contrast, M-HTs harbored lower intracellular ROS content than M1-4HSCs, despite of elevated NADPH oxidase activity. These observations indicated an upregulation of cellular defense mechanisms in order to protect cells from harmful consequences caused by oxidative stress. In line with this hypothesis, superoxide dismutase activation provided the resistance to augmented radical production in M-HTs, and glutathione rather than catalase was responsible for intracellular hydrogen peroxide removal. Finally, the TGF-β/NADPH oxidase mediated ROS production correlated with the upregulation of AP-1 as well as platelet-derived growth factor receptor subunits, which points to important contributions in establishing antioxidant defense. CONCLUSION: The data provide evidence that TGF-β induces NADPH oxidase activity which causes radical production upon the transdifferentiation of activated HSCs to M-HTs. Myofibroblastoid cells are equipped with high levels of superoxide dismutase activity as well as glutathione to counterbalance NADPH oxidase dependent oxidative stress and to avoid cellular damage

    TGF-β dependent regulation of oxygen radicals during transdifferentiation of activated hepatic stellate cells to myofibroblastoid cells

    Get PDF
    Background: The activation of hepatic stellate cells (HSCs) plays a pivotal role during liver injury because the resulting myofibroblasts (MFBs) are mainly responsible for connective tissue re-assembly. MFBs represent therefore cellular targets for anti-fibrotic therapy. In this study, we employed activated HSCs, termed M1-4HSCs, whose transdifferentiation to myofibroblastoid cells (named M-HTs) depends on transforming growth factor (TGF)-β. We analyzed the oxidative stress induced by TGF-β and examined cellular defense mechanisms upon transdifferentiation of HSCs to M-HTs. Results: We found reactive oxygen species (ROS) significantly upregulated in M1-4HSCs within 72 hours of TGF-β administration. In contrast, M-HTs harbored lower intracellular ROS content than M1-4HSCs, despite of elevated NADPH oxidase activity. These observations indicated an upregulation of cellular defense mechanisms in order to protect cells from harmful consequences caused by oxidative stress. In line with this hypothesis, superoxide dismutase activation provided the resistance to augmented radical production in M-HTs, and glutathione rather than catalase was responsible for intracellular hydrogen peroxide removal. Finally, the TGF-β/NADPH oxidase mediated ROS production correlated with the upregulation of AP-1 as well as platelet-derived growth factor receptor subunits, which points to important contributions in establishing antioxidant defense. Conclusion: The data provide evidence that TGF-β induces NADPH oxidase activity which causes radical production upon the transdifferentiation of activated HSCs to M-HTs. Myofibroblastoid cells are equipped with high levels of superoxide dismutase activity as well as glutathione to counterbalance NADPH oxidase dependent oxidative stress and to avoid cellular damage
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