105,588 research outputs found

    Wnt/ -Catenin and MAPK Signaling: Allies and Enemies in Different Battlefields

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    Two papers published in Science Signaling reveal extensive crosstalk between Wnt/-catenin and mitogen-activated protein kinase (MAPK) signaling in cancer. Although both studies describe previously unknown links between these two signaling pathways, the relationship between Wnt/-catenin and MAPK signaling depends on the specific cellular context. Indeed, in melanoma, hyperactivated MAPK signaling down-regulates the Wnt/-catenin signal transduction cascade, thereby establishing a negative crosstalk between the two signaling pathways. In contrast, in colorectal cancer, stimulation of the Wnt/-catenin pathway leads to activation of the MAPK pathway through Ras stabilization, representing an example of positive crosstalk. Moreover, activation of Wnt/-catenin signaling has context-dependent functions that trigger opposing effects on tumor growth. In melanoma, aberrant activation of Wnt/-catenin signaling may have anti- oncogenic functions by promoting programmed cell death; by contrast, in the intestine, Wnt/-catenin signaling drives malignant transformation. Thus, there is no single correct way to target the Wnt/-catenin pathway for all cancers

    "De keuze van Hans Clevers"

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    Hans Clevers blijft met één been in de wetenschap staan

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    Slide preparation for single-cell-resolution imaging of fluorescent proteins in their three-dimensional near-native environment

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    In recent years, many mouse models have been developed to mark and trace the fate of adult cell populations using fluorescent proteins. High-resolution visualization of such fluorescent markers in their physiological setting is thus an important aspect of adult stem cell research. Here we describe a protocol to produce sections (150-200 mum) of near-native tissue with optimal tissue and cellular morphology by avoiding artifacts inherent in standard freezing or embedding procedures. The activity of genetically expressed fluorescent proteins is maintained, thereby enabling high-resolution three-dimensional (3D) reconstructions of fluorescent structures in virtually all types of tissues. The procedure allows immunofluorescence labeling of proteins to depths up to 50 mum, as well as a chemical 'Click-iT' reaction to detect DNA-intercalating analogs such as ethynyl deoxyuridine (EdU). Generation of near-native sections ready for imaging analysis takes approximately 2-3 h. Postsectioning processes, such as antibody labeling or EdU detection, take up to 10 h. [KEYWORDS: Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Luminescent Proteins/ analysis, Microscopy, Fluorescence/methods, Microtomy, Single-Cell Analysis/ methods

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Symptom patterns in irritable bowel syndrome

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    Who has never had them: symptoms in the abdominal region, such as pain, bloating, constipation, and diarrhoea? These are common symptoms of irritable bowel syndrome (IBS). IBS affects 5-10% of the population, especially females between the age of 16 and 40. The good news is that IBS is a benign disorder: IBS does not increase the risk of cancer, and symptoms are not progressive. The bad news is that impact on quality of life is high due to symptoms in the abdomen as well as elsewhere (e.g. joint pain) and psychological symptoms (e.g. anxiety) or even psychiatric disorders (e.g. anxiety disorders). Specifically, symptom-related anxiety is a predictor of more severe symptoms and worsening quality of life. Why exactly do people have symptoms? In part, symptoms can be explained by lifestyle factors, mainly food and stress. Common food triggers have been described for diarrhoea (confectionery, coffee, spices), flatulence (onions, fruits, bread), bloating (late eating), and pain (late eating, rice, bread). Before we start dieting, however, two important remarks must be made: - Intolerances to food and stress are very person-specific. Person-specific food-symptom and stress-symptom relations may be identified when a patient keeps a diary of food intake, stress, and symptoms. The computer analyses the diary for possible symptom triggers. Exclusion of personal triggers may lead to symptom improvement for a group of patients. - There are many non-lifestyle factors that drive symptoms in IBS. These include the gut bacteria and immune system. Therefore, it is possible that a patient does not benefit from any dietary or psychological therapy. This thesis leads to two research suggestions, both aiming for personalised management of IBS: - Personal symptom triggers. Although we know that the food/symptom diary concept can generate personalised lifestyle advice, we still lack evidence that it actually improves symptoms. Patients who keep a diary and receive personalised lifestyle advice should be followed up to monitor symptom evolution. A great opportunity would be to combine it with smart devices that measure physiologic variables, as these may explain how a trigger leads to symptoms. - Predictors of treatment response. For the patient, finding a good treatment is currently a process of trial and error. There is a need for an evidence-based treatment algorithm, as this makes IBS management more efficient and teaches us about the underlying mechanisms

    The construction of Karen Karnak: The multi-author-function

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    This thesis is situated within the comparatively recent developments of Web 2.0 and the emergence of interactive WikiMedia, and explores the mode of authorship within a Read/Write culture compared to that of a Read/Only tradition. The hypothesis of this study is that the role of the audience has become merged with the author, and as such, represents new functions and attributes, distinct from a more conventional concept of authorship, in which the roles of audience and author are more separate. Read/Write and participatory culture, as defined by this study, is focused on collaboration, and includes the influences of D.I.Y. culture, Open-Source practices and the production of text by multiple authors. Multi-authorship presents a re-thinking of several concepts which support the notion of the individual author, since the focus of multi-authorship is not on attribution and ownership of a finished text, but on the continued malleability of a text. Modes of multi-authorship, demonstrated in the use of the pseudonyms Alan Smithee and Karen Eliot, represent declarative authors whose names signify multiple origins, whilst concurrently indicating a distinct body of work. The function of these names form an important context to this study, since primary research involves the construction of an experimental mode of multi-authorship utilising WikiMedia technology and the interaction of thirty nine participants, who are invited to create a body of work under the collective pseudonym Karen Karnak. The data generated by this experiment is analysed using aspects of Michel Foucault's author-function to identify and determine power structures inherent in the WikiMedia context. The interplay of power structures, including concepts such as identity, ownership and the body of work, affect the resulting mode of authorship and contribute to the construction of Karen Karnak, suggesting further areas of research into the emerging multi-author

    Contribution of Information and Communication Technology (ICT) in Country’S H-Index

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    The aim of this study is to examine the effect of Information and Communication Technology (ICT) development on country’s scientific ranking as measured by H-index. Moreover, this study applies ICT development sub-indices including ICT Use, ICT Access and ICT skill to find the distinct effect of these sub-indices on country’s H-index. To this purpose, required data for the panel of 14 Middle East countries over the period 1995 to 2009 is collected. Findings of the current study show that ICT development increases the H-index of the sample countries. The results also indicate that ICT Use and ICT Skill sub-indices positively contribute to higher H-index but the effect of ICT access on country’s H-index is not clear
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