707 research outputs found

    Estimation of interdomain flexibility of N-terminus of factor H using residual dipolar couplings

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    Characterization of segmental flexibility is needed to understand the biological mechanisms of the very large category of functionally diverse proteins, exemplified by the regulators of complement activation, that consist of numerous compact modules or domains linked by short, potentially flexible, sequences of amino acid residues. The use of NMR-derived residual dipolar couplings (RDCs), in magnetically aligned media, to evaluate interdomain motion is established but only for two-domain proteins. We focused on the three N-terminal domains (called CCPs or SCRs) of the important complement regulator, human factor H (i.e. FH1-3). These domains cooperate to facilitate cleavage of the key complement activation-specific protein fragment, C3b, forming iC3b that no longer participates in the complement cascade. We refined a three-dimensional solution structure of recombinant FH1-3 based on nuclear Overhauser effects and RDCs. We then employed a rudimentary series of RDC datasets, collected in media containing magnetically aligned bicelles (disk-like particles formed from phospholipids) under three different conditions, to estimate interdomain motions. This circumvents a requirement of previous approaches for technically difficult collection of five independent RDC datasets. More than 80% of conformers of this predominantly extended three-domain molecule exhibit flexions of < 40 °. Such segmental flexibility (together with the local dynamics of the hypervariable loop within domain 3), could facilitate recognition of C3b via initial anchoring and eventual reorganization of modules to the conformation captured in the previously solved crystal structure of a C3b:FH1-4 complex

    SHREC 2011: robust feature detection and description benchmark

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    Feature-based approaches have recently become very popular in computer vision and image analysis applications, and are becoming a promising direction in shape retrieval. SHREC'11 robust feature detection and description benchmark simulates the feature detection and description stages of feature-based shape retrieval algorithms. The benchmark tests the performance of shape feature detectors and descriptors under a wide variety of transformations. The benchmark allows evaluating how algorithms cope with certain classes of transformations and strength of the transformations that can be dealt with. The present paper is a report of the SHREC'11 robust feature detection and description benchmark results.Comment: This is a full version of the SHREC'11 report published in 3DO

    Analyzing collaborative learning processes automatically

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    In this article we describe the emerging area of text classification research focused on the problem of collaborative learning process analysis both from a broad perspective and more specifically in terms of a publicly available tool set called TagHelper tools. Analyzing the variety of pedagogically valuable facets of learners’ interactions is a time consuming and effortful process. Improving automated analyses of such highly valued processes of collaborative learning by adapting and applying recent text classification technologies would make it a less arduous task to obtain insights from corpus data. This endeavor also holds the potential for enabling substantially improved on-line instruction both by providing teachers and facilitators with reports about the groups they are moderating and by triggering context sensitive collaborative learning support on an as-needed basis. In this article, we report on an interdisciplinary research project, which has been investigating the effectiveness of applying text classification technology to a large CSCL corpus that has been analyzed by human coders using a theory-based multidimensional coding scheme. We report promising results and include an in-depth discussion of important issues such as reliability, validity, and efficiency that should be considered when deciding on the appropriateness of adopting a new technology such as TagHelper tools. One major technical contribution of this work is a demonstration that an important piece of the work towards making text classification technology effective for this purpose is designing and building linguistic pattern detectors, otherwise known as features, that can be extracted reliably from texts and that have high predictive power for the categories of discourse actions that the CSCL community is interested in

    Directional Fano resonances in light scattering by a high refractive index dielectric sphere

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    We report the experimental evidence of directional Fano resonances at the scattering of a linearly polarized electromagnetic plane wave by a homogeneous dielectric sphere with a high refractive index and low losses. We observe a typical asymmetric Fano profile for the intensity scattered in practically any given direction, while the overall extinction cross section remains Lorentzian. The phenomenon originates in the interference of the selectively excited electric dipolar and quadrupolar modes. The selectivity of the excitation is achieved by the proper choice of the frequency of the incident wave. Owing to the scaling invariance of the Maxwell equations, in these experiments we mimic the scattering of the visible and near IR radiation by a nanoparticle made of common semiconductor materials (Si, Ge, GaAs, GaP) by the equivalent scattering of a spherical particle of 18 mm in diameter in the microwave range. The theory developed to explain the experiments extends the conventional Fano approach to the case when both interfering partitions are resonant. A perfect agreement between the experiment and the theory is demonstrated. © 2016 American Physical Society.Acknowledgments. This research has been supported by MICINN (Spanish Ministry of Science and Innovation, Project No. FIS2013-45854-P). We also acknowledge the opportunity provided by the Centre Commun de Ressources en Microondeto use its fully equipped anechoic chamber

    Defining authorship in user-generated content : copyright struggles in The Game of Thrones

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    The notion of authorship is a core element in antipiracy campaigns accompanying an emerging copyright regime, worldwide. These campaigns are built on discourses that aim to ‘problematize’ the issues of ‘legality’ of content downloading practices, ‘protection’ for content creators and the alleged damage caused to creators’ livelihood by piracy. Under these tensions, fandom both subverts such discourses, through sharing and production practices, and legitimizes industry’s mythology of an ‘original’ author. However, how is the notion of authorship constructed in the cooperative spaces of fandom? The article explores the most popular fandom sites of A Song of Ice and Fire, the book series that inspires the TV-show Game of Thrones and argues that the notion of authorship is not one-dimensional, but rather consists of attributes that develop across three processes: community building, the creative and the industrial/production process. Here, fandom constructs a figure of the ‘author’ which, although more complex than the one presented by the industry in its copyright/anti-piracy campaigns, maintains the status quo of regulatory frameworks based on the idea of a ‘primary’ creator

    Antineoplastic activity of idazoxan hydrochloride

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    Idazoxan hydrochloride (IDA) is a 241 molecular weight imidazoline and adrenoreceptor ligand. It binds to mitochondrial membranes and promotes apoptosis of pancreatic beta cells. Since IDA has not been tested against tumor cells, the purpose of our study was to determine if IDA has antineoplastic activity. We used the conversion of a soluble tetrazolium salt to an insoluble formazan precipitate and differential staining cytotoxicity assays to determine if IDA was cytotoxic to cell lines of murine lung cancer and human prostate cancer, as well as to a variety of fresh human tumor samples. We used flow cytometry to analyze cell death and calreticulin expression. IDA is cytotoxic to both cell lines and against aliquots of specimens of breast, gastric, lung, ovarian and prostate cancers as well as non-Hodgkin’s lymphoma. It produces apoptotic cell death and promotes calreticulin expression, suggesting that IDA might be immunomodulatory in vivo. We anticipate that IDA will be clinically useful in cancer treatment
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