3,617 research outputs found

    Hepatitis C virus (HCV) infection may elicit neutralizing antibodies targeting epitopes conserved in all viral genotypes

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    Anti-hepatitis C virus (HCV) cross-neutralizing human monoclonal antibodies, directed against conserved epitopes on surface E2 glycoprotein, are central tools for understanding virus-host interplay, and for planning strategies for prevention and treatment of this infection. Recently, we developed a research aimed at identifying these antibody specificities. The characteristics of one of these antibodies (Fab e20) were addressed in this study. Firstly, using immunofluorescence and FACS analysis of cells expressing envelope HCV glycoproteins, Fab e20 was able to recognize all HCV genotypes. Secondly, competition assays with a panel of mouse and rat monoclonals, and alanine scanning mutagenesis analyses located the e20 epitope within the CD81 binding site, documenting that three highly conserved HCV/E2 residues (W529, G530 and D535) are critical for e20 binding. Finally, a strong neutralizing activity against HCV pseudoparticles (HCVpp) incorporating envelope glycoproteins of genotypes 1a, 1b, 2a, 2b and 4, and against the cell culture-grown (HCVcc) JFH1 strain, was observed. The data highlight that neutralizing antibodies against HCV epitopes present in all HCV genotypes are elicited during natural infection. Their availability may open new avenues to the understanding of HCV persistence and to the development of strategies for the immune control of this infection

    Kinetic distance and kinetic maps from molecular dynamics simulation

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    Characterizing macromolecular kinetics from molecular dynamics (MD) simulations requires a distance metric that can distinguish slowly-interconverting states. Here we build upon diffusion map theory and define a kinetic distance for irreducible Markov processes that quantifies how slowly molecular conformations interconvert. The kinetic distance can be computed given a model that approximates the eigenvalues and eigenvectors (reaction coordinates) of the MD Markov operator. Here we employ the time-lagged independent component analysis (TICA). The TICA components can be scaled to provide a kinetic map in which the Euclidean distance corresponds to the kinetic distance. As a result, the question of how many TICA dimensions should be kept in a dimensionality reduction approach becomes obsolete, and one parameter less needs to be specified in the kinetic model construction. We demonstrate the approach using TICA and Markov state model (MSM) analyses for illustrative models, protein conformation dynamics in bovine pancreatic trypsin inhibitor and protein-inhibitor association in trypsin and benzamidine

    Deterministic Digital Clustering of Wireless Ad Hoc Networks

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    We consider deterministic distributed communication in wireless ad hoc networks of identical weak devices under the SINR model without predefined infrastructure. Most algorithmic results in this model rely on various additional features or capabilities, e.g., randomization, access to geographic coordinates, power control, carrier sensing with various precision of measurements, and/or interference cancellation. We study a pure scenario, when no such properties are available. As a general tool, we develop a deterministic distributed clustering algorithm. Our solution relies on a new type of combinatorial structures (selectors), which might be of independent interest. Using the clustering, we develop a deterministic distributed local broadcast algorithm accomplishing this task in O(ΔlogNlogN)O(\Delta \log^*N \log N) rounds, where Δ\Delta is the density of the network. To the best of our knowledge, this is the first solution in pure scenario which is only polylog(n)(n) away from the universal lower bound Ω(Δ)\Omega(\Delta), valid also for scenarios with randomization and other features. Therefore, none of these features substantially helps in performing the local broadcast task. Using clustering, we also build a deterministic global broadcast algorithm that terminates within O(D(Δ+logN)logN)O(D(\Delta + \log^* N) \log N) rounds, where DD is the diameter of the network. This result is complemented by a lower bound Ω(DΔ11/α)\Omega(D \Delta^{1-1/\alpha}), where α>2\alpha > 2 is the path-loss parameter of the environment. This lower bound shows that randomization or knowledge of own location substantially help (by a factor polynomial in Δ\Delta) in the global broadcast. Therefore, unlike in the case of local broadcast, some additional model features may help in global broadcast

    OPEN NETWORK FOR LOCAL SELF SUSTAINABILITY, BOOSTING BIOREGIONAL DEVELOPMENT THROUGH AN OPEN DATA SHARING SYSTEM

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    Abstract. The paper presents an online geodatabase currently under development. Its name is Open NETwork for Local Self Sustainability and the website address is www.oloss.net.The goal of this platform is to publish and share information about production and consumption chain oriented towards the use of locally available resources. To this end, it provides an open standard of supply chains georeferenced representation, and the ability to georefer data generally used in the context of life cycle analysis of products and services. This standard has the purpose of representing production and consumption chains in the form of Impact Geographies (IGs). This database may provide public administration centers, research centers, NGOs, planners and designers with information useful to develop projects geared towards the optimal use of local resources, consistent with the bioregional development paradigm (Sale, 1985) (Scudo, 2016). The bioregional approach promotes trans-scalar regional supply and demand chains where food and energy are grown, produced, sold and consumed within a certain territorial unit.</p

    Parallel Load Balancing on constrained client-server topologies

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    We study parallel Load Balancing protocols for the client-server distributed model defined as follows. There is a set of n clients and a set of n servers where each client has (at most) a constant number of requests that must be assigned to some server. The client set and the server one are connected to each other via a fixed bipartite graph: the requests of client v can only be sent to the servers in its neighborhood. The goal is to assign every client request so as to minimize the maximum load of the servers. In this setting, efficient parallel protocols are available only for dense topologies. In particular, a simple protocol, named raes, has been recently introduced by Becchetti et al. [1] for regular dense bipartite graphs. They show that this symmetric, non-adaptive protocol achieves constant maximum load with parallel completion time and overall work, w.h.p. Motivated by proximity constraints arising in some client-server systems, we analyze raes over almost-regular bipartite graphs where nodes may have neighborhoods of small size. In detail, we prove that, w.h.p., the raes protocol keeps the same performances as above (in terms of maximum load, completion time, and work complexity, respectively) on any almost-regular bipartite graph with degree. Our analysis significantly departs from that in [1] since it requires to cope with non-trivial stochastic-dependence issues on the random choices of the algorithmic process which are due to the worst-case, sparse topology of the underlying graph

    Lower Bounds for Structuring Unreliable Radio Networks

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    In this paper, we study lower bounds for randomized solutions to the maximal independent set (MIS) and connected dominating set (CDS) problems in the dual graph model of radio networks---a generalization of the standard graph-based model that now includes unreliable links controlled by an adversary. We begin by proving that a natural geographic constraint on the network topology is required to solve these problems efficiently (i.e., in time polylogarthmic in the network size). We then prove the importance of the assumption that nodes are provided advance knowledge of their reliable neighbors (i.e, neighbors connected by reliable links). Combined, these results answer an open question by proving that the efficient MIS and CDS algorithms from [Censor-Hillel, PODC 2011] are optimal with respect to their dual graph model assumptions. They also provide insight into what properties of an unreliable network enable efficient local computation.Comment: An extended abstract of this work appears in the 2014 proceedings of the International Symposium on Distributed Computing (DISC

    The impact of stapling technique and surgeon specialism on anastomotic failure after right-sided colorectal resection. An international multi-centre, prospective audit

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    There is little evidence to support choice of technique and configuration for stapled anastomoses after right hemicolectomy and ileocaecal resection. This study aimed to determine the relationship between stapling technique and anastomotic failure
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