130,498 research outputs found
The SM protein Sly1 accelerates assembly of the ER-Golgi SNARE complex
No full textSoluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) and Sec1/Munc18 (SM) proteins constitute the core of an ancient vesicle fusion machine that diversified into distinct sets that now function in different trafficking steps in eukaryotic cells. Deciphering their precise mode of action has proved challenging. SM proteins are thought to act primarily through one type of SNARE protein, the syntaxins. Despite high structural similarity, however, contrasting binding modes have been found for different SM proteins and syntaxins. Whereas the secretory SM protein Munc18 binds to the ‟closed conformation” of syntaxin 1, the ER–Golgi SM protein Sly1 interacts only with the N-peptide of Sed5. Recent findings, however, indicate that SM proteins might interact simultaneously with both syntaxin regions. In search for a common mechanism, we now reinvestigated the Sly1/Sed5 interaction. We found that individual Sed5 adopts a tight closed conformation. Sly1 binds to both the closed conformation and the N-peptide of Sed5, suggesting that this is the original binding mode of SM proteins and syntaxins. In contrast to Munc18, however, Sly1 facilitates SNARE complex formation by loosening the closed conformation of Sed5.Universität Göttingen. Graduate School for Neurosciences and Molecular Biosciences (Fellowship
At the Gates of Consciousness: Physicalism and Phenomenal Concepts
No full textIn this work, I have three related aims. First, I attempt to show that none of the popular responses to the Knowledge Argument works. The first chapter presents the Argument as it is originally proposed by Jackson and Nagel, clarifies the distinctions between two proposals, and identifies the core of the challenge it raises for physicalism. In the following two chapters, I show that "no-new-knowledge" and "new-knowledge/old-facts" responses to the Argument fail. My second aim is to develop an adequate account of phenomenal concepts. A widely held and influential idea is that phenomenal concepts, concepts under which we grasp the qualitative properties of our experiences, are epistemically and semantically special. In the fourth chapter, I provide an account that, I believe, captures the core of this special nature. On my account, phenomenal concepts are epistemically special in that our beliefs formed by the application of phenomenal concepts to our experiences are non-inferentially justified, and they are semantically special in that they are simple concepts that represent certain phenomenal properties without using any property other than those properties. In the fourth chapter, I also draw the logical implications of my account of phenomenal concepts with respect to the conceptual/non-conceptual distinctions, the "Myth of the Given", and the infallibility of phenomenal beliefs. My third aim, which is addressed in chapter five, is to provide a novel argument for property dualism on the basis of my account of phenomenal concepts. Instead of asking "how are phenomenal experiences possible in an entirely physical world?", I raise the question "how are phenomenal concepts possible in an entirely physical world?" This question accepts the invitation of our physicalist to ascend from the level of properties to the level of concepts but inquires whether such an ascent is of any help to the physicalist. I argue that ascending to higher levels only displaces the problem: phenomenal concepts are as problematic for physicalism as are phenomenal properties. I conclude that phenomenal concepts are not possible in an entirely physical world and, since we have phenomenal concepts, our world cannot be entirely physical
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
Scholarly Communication and Publishing Lunch and Learn Talk #11: The ULS Open Access Author Fee Fund
No full textAt the May 2014 talk, you will learn about the ULS Open Access Author Fee Fund--what it is, why we do it, how it works, and how the program is going so far
The R&D Tax Incentives
No full textThis article sets out some background information and reflections of the author on the R&D tax incentive schemes included in the Common Corporate Tax Base (CCTB) Proposal. In particular the author analyzes the stimulus to private R&D through ad hoc tax incentives included in the CCTB Proposal and dives into the actual provisions included in the Proposal highlighting the most relevant issues connected with their design and interpretation. Moreover, the author explores the interaction between the CCTB Proposal and the granting by Member States of domestic R&D tax incentives
The Association of Vitamin D Levels and the Frailty Phenotype Among Non-geriatric Dialysis Patients: A Cross-sectional Study
No full textOBJECTIVES: The aim of this study was to investigate the frequency of frailty and the association of vitamin D levels and the frailty phenotype among non-geriatric dialysis patients. METHOD: Seventy-four stable, chronic hemodialysis patients from the hemodialysis unit of the hospital were enrolled in the study. The patients’ medical histories and laboratory findings were obtained from the medical records of the dialysis unit. Serum parathyroid hormone and 25-hydroxy vitamin D levels were determined using chemiluminometric immunoassays. Frailty was defined by Fried et al. as a phenotype; shrinking, weakness, self-reported exhaustion, decreased activity and slowed walking speed were evaluated. RESULTS: Forty-one (55%) of the patients were males. The patients were divided into 3 groups according to frailty scores: 39 (53%) patients were frail, 6 (8%) patients were intermediately frail, and 28 (39%) patients were normal. Significant differences were found for 25-hydroxy vitamin D and hemoglobin levels among the groups; however, no differences were observed in body mass index, comorbidities, sex, marital status, education, disease and dialysis durations, or parathyroid hormone, creatinine, serum calcium, phosphorus, and potassium levels. CONCLUSIONS: Weakness and slowness are serious outcomes of both vitamin D deficiency and frailty, and vitamin D deficiency has been associated with increased risks of decreased physical activity, falls, fractures and death in postmenopausal women and older men. Although studies on frailty have focused on older adults, growing evidence indicates that the frailty phenotype is becoming a factor associated with poor health outcomes in non-geriatric populations with chronic disease
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