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- Gruter, O, et al.
(författare)
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Lentiviral vector-mediated gene transfer in adult mouse photoreceptors is impaired by the presence of a physical barrier
- 2005
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Ingår i: Gene Therapy. - : Springer Science and Business Media LLC. - 0969-7128 .- 1476-5462. ; 12:11, s. 942-947
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Tidskriftsartikel (refereegranskat)abstract
- Gene transfer offers a substantial promise for the therapy of degenerative ocular diseases. Lentiviral vectors have the ability to efficiently transduce murine photoreceptors during the first days of life, but they are poorly effective on photoreceptors during adulthood. Here, we studied whether a physical barrier was responsible for this impairment. Previous studies have described the capacity of enzymes, such as chondroitinase ABC and neuraminidase X, to modify the structure of the interphotoreceptor matrix (IPM) when subretinally injected. Considering the IPM as a physical barrier that may decrease photoreceptor transduction, we injected different enzymes into the subretinal space of the adult mouse simultaneously with the lentiviral vector preparation, to increase viral transduction by fragilizing the IPM. Subretinal injection of neuraminidase X and chondroitinase ABC induces modifications in the IPM by, respectively, revealing or decreasing peanut agglutinin sites on photoreceptors. The simultaneous subretinal injection of neuraminidase X with a lentiviral vector driving the expression of a reporter gene in the photoreceptors increases the number of transduced cells significantly ( around five-fold). After the enzyme treatment, the diffusion of the vector between the pigmented epithelium and the photoreceptors appears to facilitate the lentiviral vector transduction. Such approach targeting the IPM may help to design new strategies to improve gene delivery into the adult photoreceptors.
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- Kostic, Dejan, et al.
(författare)
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High-bandwidth Data Dissemination for Large-scale Distributed Systems
- 2008
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Ingår i: ACM Transactions on Computer Systems. - : Association for Computing Machinery (ACM). - 0734-2071 .- 1557-7333. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- This article focuses on the multireceiver data dissemination problem. Initially, IP multicast formed the basis for efficiently supporting such distribution. More recently, overlay networks have emerged to support point-to-multipoint communication. Both techniques focus on constructing trees rooted at the source to distribute content among all interested receivers. We argue, however, that trees have two fundamental limitations for data dissemination. First, since all data comes from a single parent, participants must often continuously probe in search of a parent with an acceptable level of bandwidth. Second, due to packet losses and failures, available bandwidth is monotonically decreasing down the tree.To address these limitations, we present Bullet, a data dissemination mesh that takes advantage of the computational and storage capabilities of end hosts to create a distribution structure where a node receives data in parallel from multiple peers. For the mesh to deliver improved bandwidth and reliability, we need to solve several key problems: (i) disseminating disjoint data over the mesh, (ii) locating missing content, (iii) finding who to peer with (peering strategy), (iv) retrieving data at the right rate from all peers (flow control), and (v) recovering from failures and adapting to dynamically changing network conditions. Additionally, the system should be self-adjusting and should have few user-adjustable parameter settings. We describe our approach to addressing all of these problems in a working, deployed system across the Internet. Bullet outperforms state-of-the-art systems, including BitTorrent, by 25-70% and exhibits strong performance and reliability in a range of deployment settings. In addition, we find that, relative to tree-based solutions, Bullet reduces the need to perform expensive bandwidth probing.
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- Kostic, Dejan, et al.
(författare)
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Maintaining high bandwidth under dynamic network conditions
- 2005
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Ingår i: Proceedings of the USENIX Annual Technical Conference. - : USENIX - The Advanced Computing Systems Association.
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Konferensbidrag (refereegranskat)abstract
- The need to distribute large files across multiple wide-area sites is becoming increasingly common, for instance, in support of scientific computing, configuring distributed systems, distributing software updates such as open source ISOs or Windows patches, or disseminating multimedia content. Recently a number of techniques have been proposed for simultaneously retrieving portions of a file from multiple remote sites with the twin goals of filling the client’s pipe and overcoming any performance bottlenecks between the client and any individual server. While there are a number of interesting tradeoffs in locating appropriate download sites in the face of dynamically changing network conditions, to date there has been no systematic evaluation of the merits of different protocols. This paper explores the design space of file distribution protocols and conducts a detailed performance evaluation of a number of competing systems running in both controlled emulation environments and live across the Internet. Based on our experience with these systems under a variety of conditions, we propose, implement and evaluate Bullet’ (Bullet prime), a mesh based high bandwidth data dissemination system that outperforms previous techniques under both static and dynamic conditions
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