46 research outputs found

    80 plus: Braucht es in 20 Jahren mehr oder weniger Pflegeplätze?

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    Die Nachkriegsgeneration wird in den nächsten 20 Jahren das Alter 80 plus erreichen: Bis ins Jahr 2035 nimmt die Zahl der pflegebedürftigen über 80-jährigen Menschen um 78 Prozent zu. Droht ein riesiger Kostenschub oder kommt alles anders, als wir heute denken? Zwei Studien versuchen, den künftigen Bedarf zu beziffern

    Proteolysis of SNAP-25 by types E and A botulinal neurotoxins

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    Clostridial neurotoxins, tetanus toxin (TeTx) and the seven related but serologically distinct botulinal neurotoxins (BoNT/A to BoNT/G), are potent inhibitors of synaptic vesicle exocytosis in nerve endings. Recently it was reported that the light chains of clostridial neurotoxins act as zinc-dependent metalloproteases which specifically cleave synaptic target proteins such as synaptobrevin/VAMPs, HPC-1/syntaxin (BoNT/C1), and SNAP-25 (BoNT/A). We show here that BoNT/E, like BoNT/A, cleaves SNAP-25, as generated by in vitro translation or by expression in Escherichia coli. BoNT/E cleaves the Arg180-Ile181 bond. This site is different from that of BoNT/A, which cleaves SNAP-25 between the amino acid residues Gln197 and Arg198. These findings further support the view that clostridial neurotoxins have evolved from an ancestral protease recognizing the exocytotic fusion machinery of synaptic vesicles whereby individual toxins target different members of the membrane fusion complex

    Association between physical activity, grip strength and sedentary behaviour with incidence of malignant melanoma: results from the UK Biobank

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    Background Physical activity has been positively related to malignant melanoma. However, that association may be confounded by ultraviolet radiation (UV), a variable closely related to both outdoor physical activity and malignant melanoma. We examined physical activity, grip strength and sedentary behaviour in relation to risk of malignant melanoma, accounting for relevant confounders using data from a prospective cohort study. Methods In 350,512 UK Biobank participants aged 38–73 years at baseline, physical activity was assessed with a modified version of the International Physical Activity Questionnaire Short Form, grip strength was measured with a hand dynamometer, and sedentary behaviour was recorded with three specific questions. Multivariable hazard ratios (HR) and corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Results During 7 years of follow-up, 1239 incident malignant melanoma diagnoses were recorded. Physical activity and sedentary behaviour were unrelated to malignant melanoma (HRs 1.01 (95% CI 0.95–1.07) and 1.04 (95% CI 0.97–1.12), respectively), and the initially positive association with grip strength in the basic model (HR 1.23, 95% CI 1.08–1.40) was attenuated after full adjustment (HR 1.10, 95% CI 0.96–1.26). Conclusion Physical activity, grip strength and sedentary behaviour are not associated with malignant melanoma risk

    Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles

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    B-Raf represents a critical physiological regulator of the Ras/RAF/MEK/ERK-pathway and a pharmacological target of growing clinical relevance, in particular in oncology. To understand how B-Raf itself is regulated, we combined mass spectrometry with genetic approaches to map its interactome in MCF-10A cells as well as in B-Raf deficient murine embryonic fibroblasts (MEFs) and B-Raf/Raf-1 double deficient DT40 lymphoma cells complemented with wildtype or mutant B-Raf expression vectors. Using a multi-protease digestion approach, we identified a novel ubiquitination site and provide a detailed B-Raf phospho-map. Importantly, we identify two evolutionary conserved phosphorylation clusters around T401 and S419 in the B-Raf hinge region. SILAC labelling and genetic/biochemical follow-up revealed that these clusters are phosphorylated in the contexts of oncogenic Ras, sorafenib induced Raf dimerization and in the background of the V600E mutation. We further show that the vemurafenib sensitive phosphorylation of the T401 cluster occurs in trans within a Raf dimer. Substitution of the Ser/Thr-residues of this cluster by alanine residues enhances the transforming potential of B-Raf, indicating that these phosphorylation sites suppress its signaling output. Moreover, several B-Raf phosphorylation sites, including T401 and S419, are somatically mutated in tumors, further illustrating the importance of phosphorylation for the regulation of this kinase

    Naivasha as a development hub : What are relevant problems related to ongoing developments in Naivasha?

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    “It gives a feeling of security, when everyone is on board!” (Employee of NGO in Naivasha) Naivasha is known as an economic hub due to its flourish flower industry and divers landscape with the Lake Naivasha and several national parks in the area. Nevertheless, Naivasha struggles of socio-economic development and the fast population increase has reinforced it. A large number of international, regional and local non-governmental institutions (NGI) are working in Naivasha for a long time. Non-governmental institutions include all kinds of organizations who are working in the field of development, including non-governmental organizations (NGOs), FBIs, CBOs and many more. With this high density of NGIs in Naivasha, the question comes up, how these institutions coordinate their work to be efficient. Thereby, it is also important to take into consideration the cooperation with the sub-county of Naivasha, who is responsible for their coordination of government bodies. Therefore, the following main question will be asked: How is the cooperation of non-governmental institutions amongst themselves and the sub-county of Naivhasha’s administration? To get an overview of existing cooperations and also to get a better understanding of the meaning of cooperations with their benefits and challenges in Naivasha, the following four guiding questions will structure the research. 1. What cooperation and organization exist amongst non-governmental institutions and the sub-county? 2. What are the achievements of the cooperation amongst non-governmental institutions and the sub-county? 3. What are the challenges of these cooperations? 4. What are the expectations for existing and future cooperations? The research should give an idea, how the work of development cooperation is organized and structured in Naivasha. To answer these questions, several interviews with different non-governmental institutions and one interview with the Department of Social Development of the sub-county will be carried out

    Brain reserve contributes to distinguishing preclinical Alzheimer's stages 1 and 2

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    BackgroundIn preclinical Alzheimer's disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we examined the association of stage 1 vs. stage 2 with structural brain reserve in memory-related brain regions.MethodsWe tested whether the volumes of hippocampal subfields and parahippocampal regions were larger in individuals at stage 1 compared to asymptomatic amyloid-negative older adults (healthy controls, HCs). We also tested whether individuals with stage 2 would show the opposite pattern, namely smaller brain volumes than in amyloid-negative individuals with SCD. Participants with cerebrospinal fluid (CSF) biomarker data and bilateral volumetric MRI data from the observational, multi-centric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study were included. The sample comprised 95 amyloid-negative and 26 amyloid-positive asymptomatic participants as well as 104 amyloid-negative and 47 amyloid-positive individuals with SCD. Volumes were based on high-resolution T2-weighted images and automatic segmentation with manual correction according to a recently established high-resolution segmentation protocol.ResultsIn asymptomatic individuals, brain volumes of hippocampal subfields and of the parahippocampal cortex were numerically larger in stage 1 compared to HCs, whereas the opposite was the case in individuals with SCD. MANOVAs with volumes as dependent data and age, sex, years of education, and DELCODE site as covariates showed a significant interaction between diagnosis (asymptomatic versus SCD) and amyloid status (Ass42/40 negative versus positive) for hippocampal subfields. Post hoc paired comparisons taking into account the same covariates showed that dentate gyrus and CA1 volumes in SCD were significantly smaller in amyloid-positive than negative individuals. In contrast, CA1 volumes were significantly (p = 0.014) larger in stage 1 compared with HCs.ConclusionsThese data indicate that HCs and stages 1 and 2 do not correspond to linear brain volume reduction. Instead, stage 1 is associated with larger than expected volumes of hippocampal subfields in the face of amyloid pathology. This indicates a brain reserve mechanism in stage 1 that enables individuals with amyloid pathologic change to be cognitively normal and asymptomatic without subjective cognitive decline

    The development of a practical model for the editing of theses and dissertations

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    Thesis (MPhil)--Stellenbosch University, 2014.ENGLISH ABSTRACT: Theses and dissertations constitute a substantial platform for the documentation and dissemination of research findings, and the professional presentation of such findings is crucial for maintaining scientific integrity. Highly effective fact finders may lack writing skills and experience, or they may simply encounter barriers when expressing ideas, and thus perhaps inadequately present what they have so adequately found. In short, adequate editing of theses and dissertations is essential. Whereas a multitude of guidelines is available for thesis and dissertation writing, there is little guidance available on the editing of such works. Thus, with the latter objective in mind, this thesis is dedicated to developing a practical model to editing postgraduate research papers. Despite a notable lack of theory in the field of thesis editing, which became apparent while reviewing the respective literature, the most suitable sources of theory were selected to provide a basis for developing a model for thesis editing. These sources, combined with insights from a practical dissertation editing assignment, allowed for the design of a model for the practical editing process of postgraduate research texts. The editing model is based on a process-oriented approach, i.e. one which focuses on the learning process of the student. Moreover, the model promotes a level of editorial intervention that conforms to the current perception of ethical intervention in thesis editing. Ethical intervention is currently being negotiated against the backdrop of such standards as the purpose of thesis writing as well as the requirement of originality of theses and dissertations. In a testing phase the model was applied in a thesis editing assignment and emerged as a valuable guide in the process of editing. It also proved practicable in all its major aspects. Nevertheless, since a single testing assignment is not sufficient to prove the general practicality of any model, the model is still to be considered a prototype and may have to undergo further refinement after additional comprehensive testing.AFRIKAANSE OPSOMMING: Tesisse en verhandelinge is 'n belangrike basis vir die optekening en verspreiding van navorsingsbevindinge, en die professionele aanbieding van sodanige bevindinge is noodsaaklik vir die behoud van wetenskaplike integriteit. Tog is kom hoogs doeltreffende navorsers soms minder bedrewe of ervare skrywers, of hulle bloot voor hindernisse te staan wanneer hulle hul gedagtes moet verwoord, wat tot die ontoereikende aanbieding van bevredigende bevindinge lei. Kortom die toereikende redigering van tesisse en verhandelinge is van die allergrootste belang. Hoewel daar etlike riglyne vir die skryf van tesisse en verhandelinge bestaan, is daar weinig leiding beskikbaar vir die redigering daarvan. Gedagtig hieraan is hierdie tesis daarop toegespits om 'n praktiese model vir die redigering van nagraadse navorsingstekste te ontwikkel. Ondanks 'n merkbare gebrek aan teorie op die gebied van tesisredigering, wat baie duidelik uit 'n oorsig van die betrokke literatuur blyk, is die mees toepaslike teoretiese bronne as grondslag vir die ontwikkeling van 'n model vir tesisredigering gekies. Met behulp van hierdie bronne, tesame met die insigte verkry uit 'n praktiese redigeeropdrag, kon 'n praktiese model vir die redigering van nagraadse navorsingstekste ontwerp word. Die redigeermodel berus op 'n prosesgerigte benadering, dit wil sê 'n benadering wat op die student se leerproses konsentreer. Daarbenewens argumenteer die model ten gunste van redaksionele ingrepe wat met huidige opvattings oor etiese tesisredigering strook. Dit geskied teen die agtergrond van die huidige gesprek oor etiese intervensie, wat onder meer teen die agtergrond van standaarde soos die doel van die tesis sowel as die oorspronklikheidsvereiste vir tesisse en verhandelinge gevoer word. Die model is tydens 'n toetsfase in 'n tesisredigeringsopdrag toegepas en blyk nuttige riglyne vir die redigeerproses te bied. Ook het al die kernkomponente daarvan geblyk prakties bruikbaar te wees. Aangesien 'n enkele toetsopdrag nie voldoende is om die algemene bruikbaarheid van 'n model te bewys nie, word die model steeds as 'n prototipe beskou en dit sal waarskynlik ná bykomende omvattende toetsing verder verbeter word

    Multi-camera system for 3D forensic documentation

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    Three-dimensional (3D) surface documentation is well established in forensic documentation. The most common systems include laser scanners and surface scanners with optical 3D cameras. An additional documentation tool is photogrammetry. This article introduces the botscan© (botspot GmbH, Berlin, Germany) multi-camera system for the forensic markerless photogrammetric whole body 3D surface documentation of living persons in standing posture. We used the botscan© multi-camera system to document a person in 360°. The system has a modular design and works with 64 digital single-lens reflex (DSLR) cameras. The cameras were evenly distributed in a circular chamber. We generated 3D models from the photographs using the PhotoScan© (Agisoft LLC, St. Petersburg, Russia) software. Our results revealed that the botscan© and PhotoScan© produced 360° 3D models with detailed textures. The 3D models had very accurate geometries and could be scaled to full size with the help of scale bars. In conclusion, this multi-camera system provided a rapid and simple method for documenting the whole body of a person to generate 3D data with Photoscan
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