169,911 research outputs found

    The role of the lectin VIP36 in the early secretory pathway

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    Lectins are of emerging importance for quality control and intracellular transport of glycoproteins in mammalian cells. One of the most prominent lectins involved in intracellular transport is ERGIC-53, which belongs to the family of L-type lectins. ERGIC-53 mediates the ER export of several glycoproteins like cathepsin Z, α1-antitrypsin (α1-AT) or blood coagulation factors. VIP36 belongs to the same family as ERGIC-53, but its cellular function remains poorly understood. VIP36 is a type I membrane protein. It cycles within the early secretory pathway and binds high mannose glycans. In order to gain insight into the function of VIP36 we decided to search for a luminal interaction partner for VIP36. We used a YFP-protein fragmentation complementation (YFP-PCA) based FACS screen of a human adult liver library to unravel an interaction partner for VIP36. Complementation of YFP is irreversible. Therefore, the YFP-PCA is well suited to detect weak interactions, like those between mammalian lectins and glycoproteins. YFP2-VIP36 was used as the bait in our screen. The human liver library was tagged with YFP1. Our screen identified α1-AT as an interaction partner for VIP36. VIP36 recognized high mannose containing α1-AT, which is consistent with the previously obtained results about the glycan affinity of VIP36. This interaction was increased upon inhibition of complex glycosylation by kifunensine. The complex formed by α1-AT and VIP36 was localized to the Golgi and the ER. α1-AT was previously identified as a cargo for ERGIC-53. Knockdown of ERGIC-53 slowed down α1-AT transport, consistent with a role for ERGIC-53 in ER export of α1-AT. In contrast, knockdown of VIP36 accelerated transport of endogenous α1-AT in HepG2 cells. This effect was specific for α1-AT, as the non-glycosylated protein albumin showed no acceleration in transport. In addition, VIP36 knockdown did not affect general protein secretion. This finding makes it unlikely that VIP36 acts as an anterograde cargo receptor for α1-AT. Further studies on the dynamics of the complex formed by VIP36 and α1-AT revealed that VIP36 recycles α1-AT back to the ER, which argues for a role of VIP36 in post-ER quality control. This notion is further supported by the finding that the chaperone BiP co-immunoprecipitated with the complex of VIP36 and α1-AT. This chaperone was previously described as an interaction partner for VIP36. This argues for a complex consisting of VIP36 and BiP acting together in post-ER quality control to detect misfolded α1-antitrypsin in the Golgi and retrieve it back to the ER. Apart from searching for an interaction partner, I also determined the effect of depletion of VIP36 on the morphology of the secretory pathway. The rationale behind this is the observation that cargo receptors contribute to the structural integrity of organelles of the secretory pathway. Knockdown of VIP36 had no effect on ER exit sites or on the ERGIC. However, VIP36 knockdown resulted in fragmentation of the Golgi apparatus. The fragmented Golgi was not the consequence of disturbed bidirectional protein transport and not due to effects on microtubules. Knockdown of VIP36 reduced COPI staining on the Golgi. VIP36 is likely to provide COPI binding sites on the Golgi via its cytosolic tail and thereby contribute to Golgi structural integrity. Our results underscore the importance of cargo receptors, not only for intracellular transport within the secretory pathway, but also to maintain the integrity of the secretory pathway itself. In conclusion, my thesis provides a deeper insight into the function of VIP36 in the early secretory pathway

    Multivariate tests for the evaluation of high-dimensional EEG data

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    Hemmelmann C, Horn M, Reiterer S, Schack B, Süsse T, Weiss S. Multivariate tests for the evaluation of high-dimensional EEG data. Journal of Neuroscience Methods. 2004;139(1):111-120

    Learning Through Competition

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    The USA has been foremost in developing and promoting sales competitions for university graduates. However, this dominance is quietly being challenged by the Europeans and universities across South East Asia. There are different factors at play across the world as well as alternative pedagogical approaches. This article discusses the challenges of organising a sales competition, recent research in the impact on students and observations about cultural differences.Sales competitions are business-to-business role-play events, where an experienced industry buyer is matched up with a sales education student in a ‘live’ interactive selling experience. Observing the interactions are judges from industry and academia. The ‘business case’ may be imaginary or, more often, based on a real case developed from a sponsoring company. Students may be selling anything from software, recruitment services or even aeroplanes.The success of the European Sales Competition (ESC) and South East Asian Sales competition (SEASAC) depends on cooperation between business and academia. This discussion is from just three seasoned stalwarts from the many hundreds involved in these events. They are: Dr Colin Mackenzie, previous head judge for the UK competition, a buyer and judge in the SEASAC and ESC. Johannes Reiterer, Competition Director for ESC 2020, and Dr Alexander Bauer, judge, buyer and co-researcher with Johannes Reiterer on the impact of sales competitions on sales students. All of these academic-practitioners have extensive sales backgrounds

    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

    Mitomycin C in highly myopic eyes - Author reply

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    Ophthalmology. 2005 Feb;112(2):208-18; discussion 219. Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes. Gambato C, Ghirlando A, Moretto E, Busato F, Midena E. SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy. Abstract PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes. DESIGN: Prospective, double-masked, randomized clinical trial. PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia. METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months). MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH. RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively). CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK. Comment in Ophthalmology. 2006 Feb;113(2):357; author reply 357-8

    Proceedings of Cross-Surface 2016: Workshop on Challenges and Opportunities for 'Bring-Your-Own-Device' (BYOD) in the Wild

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    In this workshop, we reviewed and discussed challenges and opportunities for Human-Computer Interaction in relation to cross-surface interaction in the wild based on the bring-your-own-device (BYOD) practice. We brought together researchers and practitioners working on technical infrastructures for cross-surface computing, studies of cross-surface computing in particular domains as well as interaction challenges for introducing cross-surface computing in the wild, all with a particular focus on BYOD. Examples of application domains are: cultural institutions, work places, public libraries, schools and education. Please find more details about the workshop, in the submitted proposal [1]. The workshop was held in conjunction with the 2016 ACM Conference on Human Factors in Computing Systems (CHI), that took place from May 7 to 12 in San Jose, USA. [1] Steven Houben, Nicolai Marquardt, Jo Vermeulen, Johannes Schöning, Clemens Klokmose, Harald Reiterer, Henrik Korsgaard, and Mario Schreiner. 2016. Cross-Surface: Challenges and Opportunities for 'bring your own device' in the wild

    Sehen, Fühlen, Erfahren: Rechtsmedizin mit mARBLE® erleben

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    Noll C, von Jan U, Schaft T, Matthies HK, Albrecht U-V. Sehen, Fühlen, Erfahren: Rechtsmedizin mit mARBLE® erleben. In: Reiterer H, Deussen O, eds. Mensch & Computer 2012 : interaktiv informiert - allgegenwärtig und allumfassend!? : 12. Fachübergreifende Konferenz für Interaktive und Kooperative Medien. München: Oldenbourg; 2012: 241-246

    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

    A Multi-Language Comparison of Influences on Author Verification using Character N-Grams

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    We create a new multi-language corpus for author verification based on Wikipedia talkpages, and evaluate the influence that differences in topic and time have on character n-gram author profiles. Topic alignment between two texts is found to increase author verification precision, and an authors writing style is found to change over time, but not more significantly after 3 years than after 1 year.Information ArchitectureWISElectrical Engineering, Mathematics and Computer Scienc

    A 0.12mm<sup>2</sup> Wien-Bridge Temperature Sensor with 0.1°C (3σ) Inaccuracy from -40°C to 180°C

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    Resistor-based temperature sensors can achieve much higher resolution and energy efficiency than conventional BJT-based sensors [1], but they typically occupy more area (&gt; 0.25 mm 2 ) and have lower operating temperatures (le 125 {circ} {C}) [2]-[4]. This work describes a 0.12mm 2 resistor-based sensor that uses a Wien-bridge (WB) filter to achieve 0.1 {circ} {C} (3 sigma) inaccuracy from - 40 {circ} {C} to 180 {circ} {C}. Compared to a state-of-the-art WB sensor [4], it occupies 6 × less area and achieves comparable relative accuracy over a 76% wider operating range. Session 10.3 Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic InstrumentationMicroelectronic
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