A novel splice variant of the DNA-PKcs gene is associated with clinical and cellular radiosensivity in a patient with xeroderma pigmentosum

Background: Radiotherapy-induced DNA double-strand breaks (DSBs) are critical cytotoxic lesions. Inherited defects in DNA DSB repair pathways lead to hypersensitivity to ionising radiation, immunodeficiency and increased cancer incidence. A patient with xeroderma pigmentosum complementation group C, with a scalp angiosarcoma, exhibited dramatic clinical radiosensitivity following radiotherapy, resulting in death. A fibroblast cell line from non-affected skin (XP14BRneo17) was hypersensitive to ionising radiation and defective in DNA DSB repair. Aim: To determine the genetic defect causing cellular radiation hypersensitivity in XP14BRneo17 cells. Methods: Functional genetic complementation whereby copies of human chromosomes containing genes involved in DNA DSB repair (chromosomes 2, 5, 8 10, 13 and 22) were individually transferred to XP14BRneo17 cells in an attempt to correct the radiation hypersensitivity. Clonogenic survival assays and g-H2AX immunofluorescence were conducted to measure radiation sensitivity and repair of DNA DSBs. DNA sequencing of defective DNA repair genes was performed. Results: Transfer of chromosome 8 (location of DNAPKcs gene) and transfection of a mammalian expression construct containing the DNA-PKcs cDNA restored normal ionising radiation sensitivity and repair of DNA DSBs in XP14BRneo17 cells. DNA sequencing of the DNA-PKcs coding region revealed a 249-bp deletion (between base pairs 3656 and 3904) encompassing exon 31 of the gene. Conclusion: We provide evidence of a novel splice variant of the DNA-PKcs gene associated with radiosensitivity in a patient with xeroderma pigmentosum and report the first double mutant in distinct DNA repair pathways being consistent with viability

Composable architecture for rack scale big data computing

The rapid growth of cloud computing, both in terms of the spectrum and volume of cloud workloads, necessitate re-visiting the traditional rack-mountable servers based datacenter design. Next generation datacenters need to offer enhanced support for: (i) fast changing system configuration requirements due to workload constraints, (ii) timely adoption of emerging hardware technologies, and (iii) maximal sharing of systems and subsystems in order to lower costs. Disaggregated datacenters, constructed as a collection of individual resources such as CPU, memory, disks etc., and composed into workload execution units on demand, are an interesting new trend that can address the above challenges. In this paper, we demonstrated the feasibility of composable systems through building a rack scale composable system prototype using PCIe switch. Through empirical approaches, we develop assessment of the opportunities and challenges for leveraging the composable architecture for rack scale cloud datacenters with a focus on big data and NoSQL workloads. In particular, we compare and contrast the programming models that can be used to access the composable resources, and developed the implications for the network and resource provisioning and management for rack scale architecture

Itinerant Agents for Mobile Computing

This paper describes an abstract framework for itinerant agents that can be used to implement secure, remote applications in large, public networks such as the Internet or the IBM Global Network. Itinerant agents are programs, dispatched from a source computer, that roam among a set of networked servers until they accomplish their task. This is an extension to the client / server model in which the client sends a portion of itself to the server for execution. An additional feature of itinerant agents is their ability to migrate from server to server, perhaps seeking one that can help with the user's task or perhaps collecting information from all of them. A major focus of the paper is the Agent Meeting Point, an abstraction that supports the interaction of agents with each other and server based resources. Why is this extended form of client-server computing desirable or valuable? There are many detailed motivations for using itinerant agents [6]. They fall broadly into two categories: 1) support for mobile computers or lightweight devices and 2) the emerging need in rapidly evolving networks for an asynchronous method of searching for information or transaction services. For example: 1. The reduction of overall communication traffic over the low-bandwidth, high-latency, high-cost access networks typically employed by mobile computers. 2. The ability of the agent to engage in high-bandwidth communication (with a server, for example) to search through large, free text databases. 3. The ability of lightweight mobile computers to interact with heavyweight applications without prior, detailed knowledge of the remote server's capabilities. 4. The ability of the agent to integrate knowledge from the client and server and perform inferencing at the server. 5. The ability of th..

A Resource Based Pricing Policy For Real-Time Channels In A Packet-Switching Network.

In the packet switching networks of the future the need for guaranteed performance on a wide variety of traffic characteristics will be of paramount importance. The generation of revenue, to recover costs and provide profit, and the multiple type of services offered will require that new pricing policies be implemented. This paper presents a resource based pricing policy for real-time channels ( ie., channels with guaranteed performance ) in a packet switching network. The policy is based on a set of specific criteria, and the charges for any channel are based on the resources reserved for use by the channel. This reservation charge is based on the type of service requested, the time of day during which the channel exists, and the lifetime of the channel. We argue that the traditional resources are not sufficient to determine a fair reservation charge for a channel offering guaranteed delay bounds, and we introduce the notion of a delay resource in our charging formula. The type of ser..

Transformation Proxy Support for Thin-Clients

The desire for ubiquitous connection to the Internet has fueled recent research into access for low-cost, resource limited, "thin-clients". We describe a proxy, the MetaServer, based on transforming structured documents dependent on the client's capabilities and environment. A key element is the MultiMedia Transformation Language, or MMTL. MMTL is an embedded scripting language specifically designed for transforming structured network documents. MMTL provides the MetaServer with a general solution for the problem of matching media to client capabilities. Our initial prototype and experiments indicate that a MetaServer has acceptable performance as an HTTP server that transforms HTML documents. Keywords: World Wide Web, Internet Clients, Proxy, Multi-Media Languages, Thin-Clients 1 Introduction Within the last three years there has been a growing dependency on instantly accessible, accurate information for both business and personal use. This is readily evidenced by the growth in mind..

Network Support for Lossless Digital Image Browsing

There are two main characteristics that distinguish ordinary video applications from lossless digital image browsing: first, digital images used in medical imaging and scientific visualization applications usually can not tolerate any compromise of image quality; second, unlike live or playback video, browsing implies different playback rates. With these differences, it is no longer possible to increase the browsing speed by dropping alternate frames or by increasing compression ratios as done in video applications. From a network's point of view, the image browsing applications send data at different rates during different periods of time. These type of applications require guaranteed performance service in terms of bandwidth, end-to-end delay and jitter, however, their performance requirements change during the lifetime of the application. Most of the existing solutions that support guaranteed performance services require resource reservation on a per-connection basis and the amount ..

The Dynamic Management of Guaranteed Performance Connections in Packet Switched Integrated Service Networks

The Dynamic Management of Guaranteed-Performance Connections in Packet Switched Integrated-Services Networks Colin James Parris Doctor of Philosophy in Engineering - Electrical Engineering and Computer Sciences University of California at Berkeley Professor Domenico Ferrari, Chair The communication infrastructure of the future must provide efficient support for applications with diverse traffic characteristics and performance requirements. Currently these applications are supported using several specialized networks that accommodate the different services (e.g., cable networks for video, phone networks for voice, and so on); however, technological advancements in the fields of microelectronics and optics have made it possible to integrate these services on a single network. These Integrated Services Networks support a wide range of qualities of services to the client and provide many advantages, which include large economies of scale, increased network management capabilities, improve..

Dynamic Management of Guaranteed Performance Multimedia Connections

Most of the solutions proposed to support real-time (i.e. guaranteed performance) communication services in packetswitching networks adopt a connection-oriented and reservation-oriented approach. In such an approach, resource allocation and route selection decisions are made before the start of the communication on the basis of resource availability and realtime network load at that time, and are usually kept for the duration of the communication. This rather static resource management approach has certain limitations: it does not take into account (a) the dynamics of the communicating clients; (b) the dynamics of the network state; and (c) the tradeoff between quality of service and network availability, thus affecting the availability and flexibility of the real-time network services. Availability is the ability of the network to accommodate as many real-time clients as possible, while flexibility is the ability to adapt the real-time services to changing network state and client dem..