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The idea of the ‘digital natives’, a generation of tech‐savvy young people immersed in digital technologies for which current education systems cannot cater, has gained widespread popularity on the basis of claims rather than evidence. Recent research has shown flaws in the argument that there is an identifiable generation or even a single type of highly adept technology user. For educators, the diversity revealed by these studies provides valuable insights into students' experiences of technology inside and outside formal education. While this body of work provides a preliminary understanding, it also highlights subtleties and complexities that require further investigation. It suggests, for example, that we must go beyond simple dichotomies evident in the digital natives debate to develop a more sophisticated understanding of our students' experiences of technology. Using a review of recent research findings as a starting point, this paper identifies some key issues for educational researchers, offers new ways of conceptualizing key ideas using theoretical constructs from Castells, Bourdieu and Bernstein, and makes a case for how we need to develop the debate in order to advance our understanding.  相似文献   

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Pharmacophore modeling, including ligand- and structure-based approaches, has become an important tool in drug discovery. However, the ligand-based method often strongly depends on the training set selection, and the structure-based pharmacophore model is usually created based on apo structures or a single protein-ligand complex, which might miss some important information. In this study, multicomplex-based method has been suggested to generate a comprehensive pharmacophore map of cyclin-dependent kinase 2 (CDK2) based on a collection of 124 crystal structures of human CDK2-inhibitor complex. Our multicomplex-based comprehensive pharmacophore map contains almost all the chemical features important for CDK2-inhibitor interactions. A comparison with previously reported ligand-based pharmacophores has revealed that the ligand-based models are just a subset of our comprehensive map. Furthermore, one most-frequent-feature pharmacophore model consisting of the most frequent pharmacophore features was constructed based on the statistical frequency information provided by the comprehensive map. Validations to the most-frequent-feature model show that it can not only successfully discriminate between known CDK2 inhibitors and the molecules of focused inactive dataset, but also is capable of correctly predicting the activities of a wide variety of CDK2 inhibitors in an external active dataset. Obviously, this investigation provides some new ideas about how to develop a multicomplex-based pharmacophore model that can be used in virtual screening to discover novel potential lead compounds.  相似文献   

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Multimedia Tools and Applications - Medical imaging refers to several different technologies that are used to view the human body to diagnose, monitor, or treat medical conditions. It requires...  相似文献   

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Emerging disease modifying therapeutic strategies for Alzheimer's disease (AD) have generated a critical need for biomarkers of early stage disease. Here, we describe the identification and assessment of a number of candidate biomarkers in patients with mild to moderate probable AD. Plasma from 47 probable Alzheimer's patients and 47 matched controls were analysed by proteomics to define a significant number of proteins whose expression appeared to be associated with AD. These were compared to a similar proteomic comparison of a mouse transgenic model of amyloidosis, which showed encouraging overlap with the human data. From these studies a prioritised list of 31 proteins were then analysed by immunoassay and/or functional assay in the same human cohort to verify the changes observed. Eight proteins continued to show significance by either immunoassay or functional assay in the human plasma and these were tested in a further set of 100 probable AD patients and 100 controls from the original cohort. From our data it appeared that two proteins, serpin F1 (pigment epithelium-derived factor) and complement C1 inhibitor are down-regulated in plasma from AD patients.  相似文献   

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Urban land and rural land are typically represented as homogenous and mutually exclusive classes in land change analyses. As a result, differences in urban land use intensity, as well as mosaic landscapes combining urban and rural land uses are not represented. In this study we explore the distribution of urban land and urban land use intensity in Europe and the changes therein. Specifically, we analyze the distribution of built-up land within pixels of 1 km2. At that resolution we find that most built-up land is distributed over predominantly non-built-up pixels. Consistently, we find that most urban land use changes between 2000 and 2014 come in small incremental changes, rather than sudden large-scale conversions from rural to urban land. Using urban population densities, we find that urban land use intensity varies strongly across 1 km2 pixels in Europe, as illustrated by a coefficient of variation of 85%. We found a similarly high variation between urban population densities for most individual countries and within areas with the same share of built-up land. Population changes have led to different combinations of urban land expansion and urban intensity changes in different study periods (1975–1990, 1990–2000, and 2000–2015) and countries. These findings suggest that land use change models could be improved by more nuanced representations of urban land, including mosaic classes and different urban land use intensities.  相似文献   

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N. Bonnardel   《Knowledge》2000,13(7-8):505-513
In order to show that the emergence of new ideas takes place in a “constrained cognitive environment”, we conducted two experimental studies in a creative professional area: non-routine design. The first study is focused on the role of analogical reasoning in creativity and, especially, on the nature of potential “sources” of inspiration, which facilitate the evocation process. The second study aims at understanding on which ground designers of different levels of expertise construct their own constrained cognitive environment. Based on the obtained results, we suggest ways to facilitate creative acts from designers.  相似文献   

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Numerous studies have shown that neuronal lipids are highly susceptible to oxidative stress including in those brain areas directly involved in the neurodegenerative process of Alzheimer's disease (AD). Lipid peroxidation directly damages membranes and also generates a number of secondary biologically active products (toxic aldehydes)that are capable of easily attacking lipids, proteins, and DNA. Accumulating evidence has demonstrated regionally increased brain lipid peroxidation in patients with AD; however, extensive studies on specific targets of lipid peroxidation‐induced damage are still missing. The present study represents a further step in understanding the relationship between oxidative modification of protein and neuronal death associated with AD. We used a proteomics approach to determine specific targets of lipid peroxidation in AD brain, both in hippocampus and inferior parietal lobule, by coupling immunochemical detection of 4‐hydroxynonenal‐bound proteins with 2‐D polyacrylamide gel electrophoresis and MS analysis. We identified 4‐hydroxynonenal‐bound proteins in the hippocampus and inferior parietal lobule brain regions of subjects with AD. The identified proteins play different biological functions including energy metabolism, antioxidant system, and structural proteins, thus impairing multiple molecular pathways. Our results provide further evidence for the role of lipid peroxidation in the pathogenesis of AD.  相似文献   

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Virtual worlds are increasing in importance as more multi-national firms are investing heavily in these emerging communities. Although much excitement has surrounded the idea of virtual worlds, a gap exists between those who register and those who engage in virtual worlds. Our analysis of the gap between those who merely register to join a virtual world and those who ultimately engage the community on a regular basis derives from a lack of assimilation. We present the 3C approach, a high-level theoretical framework delineating the relationship between three classes of factors (namely the technology class of factors; the community class of factors; and the user class of factors) that we posit explain virtual world assimilation and employ theories to represent these classes of factors and the interaction between them. After discussing and integrating these three classes of factors, we test our model through a study of 223 new users of Second Life. The results provide empirical support for the 3C framework; specifically, our analysis indicates that the technology and community classes of factors in exert a direct influence upon a user's attitude towards the virtual world, and this relationship is moderated by the user class of factors.  相似文献   

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This review summarises and discusses the degree to which proteomics is contributing to medical care, providing examples and signspots for future directions. Why do genomic approaches provide a limited view of gene expression? Because of the multifactorial nature of many diseases, proteomics enables us to understand the molecular basis of disease, not only at the organism, whole-cell or tissue levels, but also in subcellular structures, protein complexes and biological fluids. The application of proteomics in medicine is expected to have a major impact by providing an integrated view of individual disease processes. This review describes several proteomic platforms and examines the role of proteomics as a tool for clinical biomarker discovery, the identification of prognostic and earlier diagnostic markers, their use in monitoring the effects of drug treatments and eventually find more efficient and safer therapeutics for a wide range of pathologies.  相似文献   

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The aim of this study has been designed to identify the tuberculosis (TB)-related proteins in pericardial effusion by proteomic approaches. TB is one of the major infectious diseases causing pericardial effusion. This study details protein profiles in pericardial effusion from three TB patients and three heart failure patients. Pericardial effusions were analyzed using 2-DE combined with the nano-HPLC-ESI-MS/MS. Eleven protein spots with differential expression in pericardial effusion were identified between the two groups of TB and heart failure patients (the control group). Seven protein spots were upregulated and four were downregulated. The composition of the pericardial effusion proteome may reflect the pathophysiological conditions affecting the progression of tuberculous pericarditis. The proteins in the tuberculous pericardial effusion with differential expression may serve as new and direct indicators of drug treatment. A possible conclusion is indicated that fibrinogen may play an important role for fibrin assembly in tuberculous pericardial effusion.  相似文献   

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An approach to the design of a database system, the multilingual database system (MLDS), has been proposed and implemented. MLDS is a single database system that can execute may transactions written respectively in different data languages and support many databases structured correspondingly in various data models, i.e. DL/I transactions on hierarchical databases, CODASYL-DML transactions on network databases, SQL transactions on relational databases, and Daplex transactions on functional databases. The authors describe MLDS, focusing on its motivation and structure. It is shown how MLDS, by providing an integrated environment for experimenting with data models and data languages, also serves as a testbed that provides insight to data models and data-model semantics, using qualitative and quantitative techniques. Related work on data-language comparison and analysis is indicated  相似文献   

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Context

An optimal software development process is regarded as being dependent on the situational characteristics of individual software development settings. Such characteristics include the nature of the application(s) under development, team size, requirements volatility and personnel experience. However, no comprehensive reference framework of the situational factors affecting the software development process is presently available.

Objective

The absence of such a comprehensive reference framework of the situational factors affecting the software development process is problematic not just because it inhibits our ability to optimise the software development process, but perhaps more importantly, because it potentially undermines our capacity to ascertain the key constraints and characteristics of a software development setting.

Method

To address this deficiency, we have consolidated a substantial body of related research into an initial reference framework of the situational factors affecting the software development process. To support the data consolidation, we have applied rigorous data coding techniques from Grounded Theory and we believe that the resulting framework represents an important contribution to the software engineering field of knowledge.

Results

The resulting reference framework of situational factors consists of eight classifications and 44 factors that inform the software process. We believe that the situational factor reference framework presented herein represents a sound initial reference framework for the key situational elements affecting the software process definition.

Conclusion

In addition to providing a useful reference listing for the research community and for committees engaged in the development of standards, the reference framework also provides support for practitioners who are challenged with defining and maintaining software development processes. Furthermore, this framework can be used to develop a profile of the situational characteristics of a software development setting, which in turn provides a sound foundation for software development process definition and optimisation.  相似文献   

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This study seeks to validate a comprehensive model of consumer acceptance in the context of mobile payment. It uses the unified theory of acceptance and use of technology (UTAUT) model with constructs of security, trust, social influence, and self-efficacy. Structural equation modeling is used to construct a predictive model of attitudes toward the mobile wallet. Individuals’ responses to questions about attitude and intention to adopt/use a mobile wallet were collected and analyzed with various factors modified from UTAUT. While the model confirms the classical role of technology acceptance factors (i.e., perceived usefulness and ease of use are key antecedents to users’ attitude), the results also show that users’ attitudes and intentions are influenced by perceived security and trust. In the extended model, the moderating effects of demographics on the relations among the variables were found to be significant. The proposed model brings together extant research on mobile payment and provides an important cluster of antecedents to eventual technology acceptance via constructs of behavioral intention to use and actual system usage.  相似文献   

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Membrane microdomains (MM) are membrane rafts within the cell membrane enriched in cholesterol and glycosphingolipids that have been implicated in the trafficking and sorting of membrane proteins, secretory and endocytotic pathways, and signal transduction. To date, MM have not been characterised in the human brain. We reason that by identifying MM in the normal human cortex, we may better understand the molecular mechanisms of human brain dysfunction. To characterize the protein composition of MM in the human brain, we have carried out a comprehensive proteomic analysis of detergent resistant membranes (DRMs) associated proteins derived from human postmortem insular cortex using 1-DE separation prior to LC coupled to MS/MS or GeLC-MS/MS. Eighty five proteins were identified including 57 unique to human brain cortex DRMs (by comparison with DRM proteins reported in other cell types). High levels of signal transduction, cell adhesion, cell transport and cell trafficking proteins were identified including synaptic proteins such as synapsin II and synaptic vesicle membrane protein, mitochondrial proteins such as ATPase subunits and metabolic enzymes such as malate dehydrogenase. This data will facilitate our understanding of protein expression changes within membranes in candidate brain regions in human brain diseases such as schizophrenia, bipolar disorder and other psychiatric and neurodegenerative disorders.  相似文献   

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