928 research outputs found

    Reflexivity of the translation-dilation algebras on L^2(R)

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    The hyperbolic algebra A_h, studied recently by Katavolos and Power, is the weak star closed operator algebra on L^2(R) generated by H^\infty(R), as multiplication operators, and by the dilation operators V_t, t \geq 0, given by V_t f(x) = e^{t/2} f(e^t x). We show that A_h is a reflexive operator algebra and that the four dimensional manifold Lat A_h (with the natural topology) is the reflexive hull of a natural two dimensional subspace.Comment: 10 pages, no figures To appear in the International Journal of Mathematic

    Quantification of Plasma and Urine Thymidine and 2'-Deoxyuridine by LC-MS/MS for the Pharmacodynamic Evaluation of Erythrocyte Encapsulated Thymidine Phosphorylase in Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy.

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    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disorder caused by mutations in TYMP, leading to a deficiency in thymidine phosphorylase and a subsequent systemic accumulation of thymidine and 2'-deoxyuridine. Erythrocyte-encapsulated thymidine phosphorylase (EE-TP) is under clinical development as an enzyme replacement therapy for MNGIE. Bioanalytical methods were developed according to regulatory guidelines for the quantification of thymidine and 2'-deoxyuridine in plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for supporting the pharmacodynamic evaluation of EE-TP. Samples were deproteinized with 5% perchloric acid (v/v) and the supernatants analyzed using a Hypercarb column (30 × 2.1 mm, 3 ”m), with mobile phases of 0.1% formic acid in methanol and 0.1% formic acid in deionized water. Detection was conducted using an ion-spray interface running in positive mode. Isotopically labelled thymidine and 2'-deoxyuridine were used as internal standards. Calibration curves for both metabolites showed linearity (r > 0.99) in the concentration ranges of 10-10,000 ng/mL for plasma, and 1-50 ”g/mL for urine, with method analytical performances within the acceptable criteria for quality control samples. The plasma method was successfully applied to the diagnosis of two patients with MNGIE and the quantification of plasma metabolites in three patients treated with EE-TP

    A Two-Player Game of Life

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    We present a new extension of Conway's game of life for two players, which we call p2life. P2life allows one of two types of token, black or white, to inhabit a cell, and adds competitive elements into the birth and survival rules of the original game. We solve the mean-field equation for p2life and determine by simulation that the asymptotic density of p2life approaches 0.0362.Comment: 7 pages, 3 figure

    Sampling properties of directed networks

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    For many real-world networks only a small "sampled" version of the original network may be investigated; those results are then used to draw conclusions about the actual system. Variants of breadth-first search (BFS) sampling, which are based on epidemic processes, are widely used. Although it is well established that BFS sampling fails, in most cases, to capture the IN-component(s) of directed networks, a description of the effects of BFS sampling on other topological properties are all but absent from the literature. To systematically study the effects of sampling biases on directed networks, we compare BFS sampling to random sampling on complete large-scale directed networks. We present new results and a thorough analysis of the topological properties of seven different complete directed networks (prior to sampling), including three versions of Wikipedia, three different sources of sampled World Wide Web data, and an Internet-based social network. We detail the differences that sampling method and coverage can make to the structural properties of sampled versions of these seven networks. Most notably, we find that sampling method and coverage affect both the bow-tie structure, as well as the number and structure of strongly connected components in sampled networks. In addition, at low sampling coverage (i.e. less than 40%), the values of average degree, variance of out-degree, degree auto-correlation, and link reciprocity are overestimated by 30% or more in BFS-sampled networks, and only attain values within 10% of the corresponding values in the complete networks when sampling coverage is in excess of 65%. These results may cause us to rethink what we know about the structure, function, and evolution of real-world directed networks.Comment: 21 pages, 11 figure

    Efficient Representation of Multidimensional Data over Hierarchical Domains

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    The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-46049-9_19[Abstract] We consider the problem of representing multidimensional data where the domain of each dimension is organized hierarchically, and the queries require summary information at a different node in the hierarchy of each dimension. This is the typical case of OLAP databases. A basic approach is to represent each hierarchy as a one-dimensional line and recast the queries as multidimensional range queries. This approach can be implemented compactly by generalizing to more dimensions the k2k2 -treap, a compact representation of two-dimensional points that allows for efficient summarization queries along generic ranges. Instead, we propose a more flexible generalization, which instead of a generic quadtree-like partition of the space, follows the domain hierarchies across each dimension to organize the partitioning. The resulting structure is much more efficient than a generic multidimensional structure, since queries are resolved by aggregating much fewer nodes of the tree.Ministerio de EconomĂ­a, Industria y Competitividad; TIN2013-46238-C4-3-RMinisterio de EconomĂ­a, Industria y Competitividad; IDI-20141259Ministerio de EconomĂ­a, Industria y Competitividad; ITC-20151305Ministerio de EconomĂ­a y Competitividad; ITC-20151247Xunta de Galicia; GRC2013/053Chile.Fondo Nacional de Desarrollo CientĂ­fico y TecnolĂłgico; 1-140796COST. IC130

    A Coxsackievirus B1-mediated nonlytic Extracellular Vesicle-to-cell mechanism of virus transmission and its possible control through modulation of EV release

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    Like most non-enveloped viruses, CVB1 mainly uses cell lysis to spread. Details of a nonlytic virus transmission remain unclear. Extracellular Vesicles (EVs) transfer biomolecules between cells. We show that CVB1 entry into HeLa cells results in apoptosis and release of CVB1-induced ‘medium-sized’ EVs (CVB1i-mEVs). These mEVs (100–300 nm) harbour CVB1 as shown by immunoblotting with anti-CVB1-antibody; viral capsids were detected by transmission electron microscopy and RT-PCR revealed CVB1 RNA. The percentage of mEVs released from CVB1-infected HeLa cells harbouring virus was estimated from TEM at 34 %. Inhibition of CVB1i-mEV production, with calpeptin or siRNA knockdown of CAPNS1 in HeLa cells limited spread of CVB1 suggesting these vesicles disseminate CVB1 virions to new host cells by a nonlytic EV-to-cell mechanism. This was confirmed by detecting CVB1 virions inside HeLa cells after co-culture with CVB1i-mEVs; EV release may also prevent apoptosis of infected cells whilst spreading apoptosis to secondary sites of infection

    Personalised trails and learner profiling in an e-learning environment

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    This deliverable focuses on personalisation and personalised trails. We begin by introducing and defining the concepts of personalisation and personalised trails. Personalisation requires that a user profile be stored, and so we assess currently available standard profile schemas and discuss the requirements for a profile to support personalised learning. We then review techniques for providing personalisation and some systems that implement these techniques, and discuss some of the issues around evaluating personalisation systems. We look especially at the use of learning and cognitive styles to support personalised learning, and also consider personalisation in the field of mobile learning, which has a slightly different take on the subject, and in commercially available systems, where personalisation support is found to currently be only at quite a low level. We conclude with a summary of the lessons to be learned from our review of personalisation and personalised trails

    Topological interactions in systems of mutually interlinked polymer rings

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    The topological interaction arising in interlinked polymeric rings such as DNA catenanes is considered. More specifically, the free energy for a pair of linked random walk rings is derived where the distance RR between two segments each of which is part of a different ring is kept constant. The topology conservation is imposed by the Gauss invariant. A previous approach (M.Otto, T.A. Vilgis, Phys.Rev.Lett. {\bf 80}, 881 (1998)) to the problem is refined in several ways. It is confirmed, that asymptotically, i.e. for large R≫RGR\gg R_G where RGR_G is average size of single random walk ring, the effective topological interaction (free energy) scales ∝R4\propto R^4.Comment: 16 pages, 3 figur

    A flexible and efficient template format for circular consensus sequencing and SNP detection

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    A novel template design for single-molecule sequencing is introduced, a structure we refer to as a SMRTbellℱ template. This structure consists of a double-stranded portion, containing the insert of interest, and a single-stranded hairpin loop on either end, which provides a site for primer binding. Structurally, this format resembles a linear double-stranded molecule, and yet it is topologically circular. When placed into a single-molecule sequencing reaction, the SMRTbell template format enables a consensus sequence to be obtained from multiple passes on a single molecule. Furthermore, this consensus sequence is obtained from both the sense and antisense strands of the insert region. In this article, we present a universal method for constructing these templates, as well as an application of their use. We demonstrate the generation of high-quality consensus accuracy from single molecules, as well as the use of SMRTbell templates in the identification of rare sequence variants

    A stochastic evolutionary model for capturing human dynamics

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    The recent interest in human dynamics has led researchers to investigate the stochastic processes that explain human behaviour in various contexts. Here we propose a generative model to capture the dynamics of survival analysis, traditionally employed in clinical trials and reliability analysis in engineering. We derive a general solution for the model in the form of a product, and then a continuous approximation to the solution via the renewal equation describing age-structured population dynamics. This enables us to model a wide range of survival distributions, according to the choice of the mortality distribution. We provide empirical evidence for the validity of the model from a longitudinal data set of popular search engine queries over 114 months, showing that the survival function of these queries is closely matched by the solution for our model with power-law mortality
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