169,708 research outputs found

    UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in C. elegans

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    Small GTPases of the Rab family regulate intracellular vesicular trafficking. In C. elegans, two dominant alleles of unc-108/rab-2 have been isolated based on their movement defects. Using a combination of pharmacological assays and electron microscopy, we show that the locomotion defects of rab-2 mutant animals are cause by a reduced facilitation of synaptic vesicle (SV) release from pre-synaptic sites due to lower levels of diacylglycerol (DAG). DAG levels at release sites can be regulated by neuro-peptides secreted from dense core vesicles (DCV). We show that while their number and distribution is not affected, DCVs in dominant rab-2 mutants are enlarged and contain less neuropeptides. This implicates RAB-2 in the biogenesis of DCVs at the Golgi complex. In rab-2 mutants DCV cargo inappropriately enters late endosomal compartments. Finally we show that RIC-19, the C. elegans ortholog of the human diabetes autoantigen ICA69, is recruited to Golgi membranes by RAB-2 for proper DCV biogenesis.sponsorship: We thank Francis Barr for the hRab2 cDNA, Shweta Aggarwal, Reinhard Jahn, and Gottfried Mieskes for support, Marc Pilon for RIC-19 antibodies, Ken Miller and Josh Kaplan for strains, and Ken Miller for sharing unpublished results and discussions. We specially thank Virginie Lecaudey, Nikhil Sasidharan, and Reinhard Jahn for their comments on the manuscript. Some strains were provided by the Caenorhabditis Genetics Center, which is supported by the National Institutes of Health National Center for Research Resources. We gratefully acknowledge funding by the European Union (EU) Sixth Framework Programme coordination action program European Network of Neuroscience Institutes, Neuroscience Early Stage Research Training fellowships of the EU to L. Luo and M. Sumakovic, and a postdoctoral fellowship from the Research Foundation Flanders (FWO) to S.J. Husson. L. Schoofs is supported by the FWO, and S. Eimer is supported by the German Research Foundation Research Center for Molecular Physiology of the Brain. (National Institutes of Health National Center for Research Resources, European Union (EU), Research Foundation Flanders (FWO), German Research Foundation Research Center for Molecular Physiology of the Brain)status: Publishe

    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

    Phase-contrast x-ray imaging and tomography of the nematode Caenorhabditis elegans

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    We have analyzed the model organism Caenorhabditis elegans with the help of phase-contrast x-ray tomography. This work combines techniques from x-ray imaging studies of single biological cells by in-line holography with three-dimensional reconstruction and furthermore extends these studies to the multicellular level. To preserve the sub-cellular ultrastructure of the nematodes, we used the near-native sample preparation of high-pressure freezing as commonly used in the field of electron microscopy. For the presented samples, a standard, non-magnifying parallel-beam setting, as well as a magnifying, divergent-beam setting using nanofocusing optics is evaluated based on their tomographic reconstruction potential. In this paper, we address difficulties in sample preparation and issues of image processing. By experimental refinement and through optimized reconstruction procedures, we were able to perform x-ray imaging studies on a living specimen

    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

    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

    A ±25A Versatile Shunt-Based Current Sensor with 10kHz Bandwidth and ±0.25% Gain Error from -40°C to 85°C Using 2-Current Calibration

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    Accurate current sensing is critical in many industrial applications, such as battery management and motor control. Precise shunt-based current sensors have been reported with gain errors of less than 1% over the industrial temperature range (-40°C to 85°C) [1]–[4]. However, since they are intended for coulomb counting, their bandwidth is limited to a few tens of Hz, making them unsuitable for battery impedance or motor-current sensing. This paper presents a current sensor with a wide (10kHz) bandwidth and a tunable temperature compensation scheme (TCS), which allows it to be flexibly used with different types of shunts while maintaining high accuracy. A low-cost room-temperature calibration scheme is proposed to optimize gain flatness over temperature by exploiting the shunt's self-heating at large currents. Over the industrial temperature range and a ±25A current range, it achieves state-of-the-art gain error (±0.25%) with both low-cost PCB and stable metal-alloy shunts.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

    An Article About Albertus C. Van Raalte, Author Unknown, Except for Parts Taken from an Article by Anna C. Post

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    An article about Albertus C. Van Raalte, author unknown, except for parts taken from an article by Anna C. Post. The author knew first generation persons in the Holland settlement and therefore, the article has some value.https://digitalcommons.hope.edu/vrp_1890s/1012/thumbnail.jp

    Archivist, Archaeologist, Author and the Tactile Window

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    The idea that the predominant way of engaging with architecture is through vision is not uncommon but also not always the most appropriate given that buildings are also experienced through tactile interventions. This consequence that emphasises visual aesthetics in order to appreciate and understand architecture probably has much to do with the assumed but rather vaguely defined role of the architect as designer in the practice of architectural design. A resulting misapprehension is that architects designing for visual appreciation think that they are actually designing physical space for embodied tactile engagement. This prioritisation of vision in the way architects think about and approach design is questioned through the design project of the Tactile Window in which the position of the architect is redefined through inhabiting the roles of archivist, archaeologist and author during the design process. A 16th century portrait of Queen Elizabeth I known as the Ditchley portrait, currently on display at the National Portrait Gallery is used as the source from which the design of the Tactile Window is derived from and refers back to. Questioning the validity of vision as the sole means of engaging with the work, information about the portrait and working methods gathered from the three carefully chosen positions mentioned above are drawn on and applied to the making of this Tactile Window that becomes an alternative Ditchley portrait. Through exploring the hidden historical and current narratives of and in the existing portrait, the presence of the portrait is alluded to on an alternative physical site. Key to this are the working methods of an invented archival system of design reasoning, the unearthing of archaeological texts and assuming of authorship within the individual frameworks of the roles of archivist, archaeologist and author. The redefined role of the architect as archaeologist takes onboard the unearthing of associated drawings and writings as well as the methods of organising and applying the recovered information to the system set up by the archivist. This analysis of the graphic and text based information is used to formulate historical narratives that are woven into the design project. Whereas traditional archaeology stresses on the study of a site from a site with quantifiable limits to the physical context, the notion of archaeological sites in this instance refers to the places where the stored information is unearthed. Through the careful process of archiving and analysing this information, a new site that is located within both the physical and historical contexts of interest is discovered. The author then draws upon the elements in the archival system that includes the findings of the archaeologist to construct the alternative Ditchley portrait in this new site of the Echoing Cedar, the result of which bears no visual resemblance to the existing work. The Tactile Window is a reading of the Ditchley portrait in which information about and in the painting is transformed into a design proposal for an inhabited structure. The intended method of interaction with this alternative portrait is not merely restricted to vision but relies on engagement with the other senses. This experience is enhanced by the interplay with certain site conditions such as wind and rain in order to allude to specific aspects of the Ditchley portrait that are not visually apparent in the existing work. In the processes of excavating, finding and revealing the hidden information to create this alternative portrait, the effects of the visuals afforded by the existing portrait inadvertently begin to fade as the validity of a single means of visual expression is questioned
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