10,640 research outputs found

    Applications of satellite technology to broadband ISDN networks

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    Two satellite architectures for delivering broadband integrated services digital network (B-ISDN) service are evaluated. The first is assumed integral to an existing terrestrial network, and provides complementary services such as interconnects to remote nodes as well as high-rate multicast and broadcast service. The interconnects are at a 155 Mbs rate and are shown as being met with a nonregenerative multibeam satellite having 10-1.5 degree spots. The second satellite architecture focuses on providing private B-ISDN networks as well as acting as a gateway to the public network. This is conceived as being provided by a regenerative multibeam satellite with on-board ATM (asynchronous transfer mode) processing payload. With up to 800 Mbs offered, higher satellite EIRP is required. This is accomplished with 12-0.4 degree hopping beams, covering a total of 110 dwell positions. It is estimated the space segment capital cost for architecture one would be about 190Mwhereasthesecondarchitecturewouldbeabout190M whereas the second architecture would be about 250M. The net user cost is given for a variety of scenarios, but the cost for 155 Mbs services is shown to be about $15-22/minute for 25 percent system utilization

    Autophagy in DNA Damage Response

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    DNA damage response (DDR) involves DNA repair, cell cycle regulation and apoptosis, but autophagy is also suggested to play a role in DDR. Autophagy can be activated in response to DNA-damaging agents, but the exact mechanism underlying this activation is not fully understood, although it is suggested that it involves the inhibition of mammalian target of rapamycin complex 1 (mTORC1). mTORC1 represses autophagy via phosphorylation of the ULK1/2–Atg13–FIP200 complex thus preventing maturation of pre-autophagosomal structures. When DNA damage occurs, it is recognized by some proteins or their complexes, such as poly(ADP)ribose polymerase 1 (PARP-1), Mre11–Rad50–Nbs1 (MRN) complex or FOXO3, which activate repressors of mTORC1. SQSTM1/p62 is one of the proteins whose levels are regulated via autophagic degradation. Inhibition of autophagy by knockout of FIP200 results in upregulation of SQSTM1/p62, enhanced DNA damage and less efficient damage repair. Mitophagy, one form of autophagy involved in the selective degradation of mitochondria, may also play role in DDR. It degrades abnormal mitochondria and can either repress or activate apoptosis, but the exact mechanism remains unknown. There is a need to clarify the role of autophagy in DDR, as this process may possess several important biomedical applications, involving also cancer therapy

    MIRAI Architecture for Heterogeneous Network

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    One of the keywords that describe next-generation wireless communications is "seamless." As part of the e-Japan Plan promoted by the Japanese Government, the Multimedia Integrated Network by Radio Access Innovation project has as its goal the development of new technologies to enable seamless integration of various wireless access systems for practical use by 2005. This article describes a heterogeneous network architecture including a common tool, a common platform, and a common access. In particular, software-defined radio technologies are used to develop a multiservice user terminal to access different wireless networks. The common platform for various wireless networks is based on a wireless-supporting IPv6 network. A basic access network, separated from other wireless access networks, is used as a means for wireless system discovery, signaling, and paging. A proof-of-concept experimental demonstration system is available

    Resource management in IP-based radio access networks

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    IP is being considered to be used in the Radio Access Network (RAN) of UMTS. It is of paramount importance to be able to provide good QoS guarantees to real time services in such an IP-based RAN. QoS in IP networks is most efficiently provided with Differentiated services (Diffserv). However, currently Diffserv mainly specifies Per Hop Behaviors (PHB). Proper mechanisms for admission control and resource reservation have not yet been defined. A new resource management concept in the IP-based RAN is needed to offer QoS guarantees to real time services. We investigate the current Diffserv mechanisms and contribute to development of a new resource management protocol. We focus on the load control algorithm [9], which is an attempt to solve the problem of admission control and resource reservation in IP-based networks. In this document we present some load control issues and propose to enhance the load control protocol with the Measurement Based Admission Control (MBAC) concept. With this enhancement the traffic load in the IP-based RAN can be estimated, since the ingress router in the network path can be notified by marking packets with the resource state information. With this knowledge, the ingress router can perform admission control to keep the IP-based RAN stable with a high utilization even in overload situations

    Reverse engineering of drug induced DNA damage response signalling pathway reveals dual outcomes of ATM kinase inhibition

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    The DNA Damage Response (DDR) pathway represents a signalling mechanism that is activated in eukaryotic cells following DNA damage and comprises of proteins involved in DNA damage detection, DNA repair, cell cycle arrest and apoptosis. This pathway consists of an intricate network of signalling interactions driving the cellular ability to recognise DNA damage and recruit specialised proteins to take decisions between DNA repair or apoptosis. ATM and ATR are central components of the DDR pathway. The activities of these kinases are vital in DNA damage induced phosphorylational induction of DDR substrates. Here, firstly we have experimentally determined DDR signalling network surrounding the ATM/ATR pathway induced following double stranded DNA damage by monitoring and quantifying time dependent inductions of their phosphorylated forms and their key substrates. We next involved an automated inference of unsupervised predictive models of time series data to generate in silico (molecular) interaction maps. We characterized the complex signalling network through system analysis and gradual utilisation of small time series measurements of key substrates through a novel network inference algorithm. Furthermore, we demonstrate an application of an assumption-free reverse engineering of the intricate signalling network of the activated ATM/ATR pathway. We next studied the consequences of such drug induced inductions as well as of time dependent ATM kinase inhibition on cell survival through further biological experiments. Intermediate and temporal modelling outcomes revealed the distinct signaling profile associated with ATM kinase activity and inhibition and explained the underlying signalling mechanism for dual ATM functionality in cytotoxic and cytoprotective pathways

    ISDN at NASA Lewis Research Center

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    An expository investigation of the potential impact of the Integrated Services Digital Network (ISDN) at NASA Lewis Research Center is described. To properly frame the subject, the paper contains a detailed survey of the components of Narrowband ISDN. The principles and objectives are presented as decreed by the Consultative Committee for International Telephone and Telegraph (CCITT). The various channel types are delineated and their associated service combinations are described. The subscriber-access network functions are explained pictorially via the ISDN reference configuration. A section on switching techniques is presented to enable the reader to understand the emergence of the concept of fast packet switching. This new technology is designed to operate over the high bandwidth, low error rate transmission media that characterizes the LeRC environment. A brief introduction to the next generation of networks is covered with sections on Broadband ISDM (B-ISDN), Asynchronous Transfer Mode (ATM), and Synchronous Optical Networks (SONET). Applications at LeRC are presented, first in terms of targets of opportunity, then in light of compatibility constraints. In-place pilot projects and testing are described that demonstrate actual usage at LeRC

    Congenital microcephaly

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    The underlying etiologies of genetic congenital microcephaly are complex and multifactorial. Recently, with the exponential growth in the identification and characterization of novel genetic causes of congenital microcephaly, there has been a consolidation and emergence of certain themes concerning underlying pathomechanisms. These include abnormal mitotic microtubule spindle structure, numerical and structural abnormalities of the centrosome, altered cilia function, impaired DNA repair, DNA Damage Response signaling and DNA replication, along with attenuated cell cycle checkpoint proficiency. Many of these processes are highly interconnected. Interestingly, a defect in a gene whose encoded protein has a canonical function in one of these processes can often have multiple impacts at the cellular level involving several of these pathways. Here, we overview the key pathomechanistic themes underlying profound congenital microcephaly, and emphasize their interconnected nature

    Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions.

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    Life and death fate decisions allow cells to avoid massive apoptotic death in response to genotoxic stress. Although the regulatory mechanisms and signalling pathways controlling DNA repair and apoptosis are well characterized, the precise molecular strategies that determine the ultimate choice of DNA repair and survival or apoptotic cell death remain incompletely understood. Here we report that a protein tyrosine phosphatase, EYA, is involved in promoting efficient DNA repair rather than apoptosis in response to genotoxic stress in mammalian embryonic kidney cells by executing a damage-signal-dependent dephosphorylation of an H2AX carboxy-terminal tyrosine phosphate (Y142). This post-translational modification determines the relative recruitment of either DNA repair or pro-apoptotic factors to the tail of serine phosphorylated histone H2AX (gamma-H2AX) and allows it to function as an active determinant of repair/survival versus apoptotic responses to DNA damage, revealing an additional phosphorylation-dependent mechanism that modulates survival/apoptotic decisions during mammalian organogenesis
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