Targeting ATM pathway for therapeutic intervention in cancer

The Ataxia Telangiectasia Mutated gene encodes the ATM protein, a key element in the DNA damage response (DDR) signalling pathway responsible for maintaining genomic integrity within the cell. The ATM protein belongs to a family of large protein kinases containing the phosphatidylinositol-3 catalytic domain, including ATM, ATR and PI3K. ATM provides the crucial link between DNA damage, cell cycle progression and cell death by first sensing double stranded DNA breaks and subsequently phosphorylating and activating other downstream proteins functioning in DNA damage repair, cell cycle arrest and apoptotic pathways,. Mammalian cells are constantly challenged by genotoxic agents from a variety of sources and therefore require a robust sensing and repair mechanism to maintain DNA integrity or activate alternative cell fate pathways. This review covers the role of ATM in DDR signalling and describes the interaction of the ATM kinase with other proteins in order to fulfil its various functions. Special emphasis is given to how the growing knowledge of the DDR can help identify drug targets for cancer therapy, thus providing a rationale for exploiting the ATM pathway in anticancer drug development. Moreover, we discuss how a network modelling approach can be used to identify and characterise ATM inhibitors and predict their therapeutic potential

Atrophy, oxidative switching and ultrastructural defects in skeletal muscle of the ataxia telangiectasia mouse model

Ataxia telangiectasia is a rare, multi system disease caused by ATM kinase deficiency. Atm-knockout mice recapitulate premature aging, immunodeficiency, cancer predisposition, growth retardation and motor defects, but not cerebellar neurodegeneration and ataxia. We explored whether Atm loss is responsible for skeletal muscle defects by investigating myofiber morphology, oxidative/glycolytic activity, myocyte ultrastructural architecture and neuromuscular junctions. Atm-knockout mice showed reduced muscle and fiber size. Atrophy, protein synthesis impairment and a switch from glycolytic to oxidative fibers were detected, along with an increase of in expression of slow and fast myosin types (Myh7, and Myh2 and Myh4, respectively) in tibialis anterior and solei muscles isolated from Atm-knockout mice. Transmission electron microscopy of tibialis anterior revealed misalignments of Z-lines and sarcomeres and mitochondria abnormalities that were associated with an increase in reactive oxygen species. Moreover, neuromuscular junctions appeared larger and more complex than those in Atm wild-type mice, but with preserved presynaptic terminals. In conclusion, we report for the first time that Atm-knockout mice have clear morphological skeletal muscle defects that will be relevant for the investigation of the oxidative stress response, motor alteration and the interplay with peripheral nervous system in ataxia telangiectasia

Survey of traffic control schemes and error control schemes for ATM networks

Among the techniques proposed for B-ISDN transfer mode, ATM concept is considered to be the most promising transfer technique because of its flexibility and efficiency. This paper surveys and reviews a number of topics related to ATM networks. Those topics cover congestion control, provision of multiple classes of traffic, and error control. Due to the nature of ATM networks, those issues are far more challenging than in conventional networks. Sorne of the more promising solutions to those issues are surveyed, and the corresponding results on performance are summarized. Future research problems in ATM protocol aspect are also presented

The ATM Reforms - New Evidence from Survey and Market Data

Following the introduction of direct charging in March 2009, ATM pricing has become more transparent and flexible. Cardholders continue to respond to the clearer price signals by changing their cash withdrawal behaviour to avoid paying direct charges, and newly available data indicate that behaviour varies across age groups and geographic locations. For the small proportion of transactions that do incur a direct charge, flexibility in ATM pricing has led to a distinct pattern in these charges across different types of ATM locations. Variations in business models between ATM owners mean that most consumers have access to a large number of ATMs on which they pay no direct charge, while it remains possible for ATMs to be profitably deployed in high-cost or low-volume locations.ATMs; ATM reforms; ATM fees; foreign fees; foreign ATMs; direct charging; ATM surcharging; interchange fees; ATM Access Regime; ATM Deployment; payments reform; consumer use study; payment patterns; consumer behaviour

ATM surcharges

The recent spread of ATM surcharges has sparked significant debate among consumers, policymakers, and ATM owners. Much of this debate has focused on the direct costs that surcharges impose on consumers. The use of ATM surcharges, however, also raises broader questions about ATM deployment, customer convenience, and the nature of banking competition.Automated tellers ; Banks and banking - Service charges

Design of a secure unified e-payment system in Nigeria: A case study

The automatic teller machine (ATM) is the most widely used e-Payment instrument in Nigeria. It is responsible for about 89% (in volume) of all e-Payment instruments since 2006 to 2008. Some customers have at least two ATM cards depending on the number of accounts operated by them and they represent the active users of the ATM cards. Furthermore, identity theft has been identified as one of the most prominent problems hindering the wider adoption of e-Business, particularly e-Banking, hence the need for a more secure platform of operation. Therefore, in this paper we propose a unified (single) smart card-based ATM card with biometric-based cash dispenser for all banking transactions. This is to reduce the number of ATM cards carried by an individual and the biometric facility is to introduce another level of security in addition to the PIN which is currently being used. A set of questionnaire was designed to evaluate the acceptability of this concept among users and the architecture of the proposed system is presented

Discriminatory fees, coordination and investment in shared ATM networks

This paper empirically examines the effects of discriminatory fees on ATM investment and welfare, and considers the role of coordination in ATM investment between banks. Our main findings are that foreign fees tend to reduce ATM availability and (consumer) welfare, whereas surcharges positively affect ATM availability and the different welfare components when the consumers' price elasticity is not too large. Second, an organization of the ATM market that contains some degree of coordination between the banks may be desirable from a welfare perspective. Finally, ATM availability is always higher when a social planner decides on discriminatory fees and ATM investment to maximize total welfare. This implies that there is underinvestment in ATMs, even in the presence of discriminatory feesinvestment, coordination, ATMs, network industries, empirical entry models, spatial discrete choice demand models

On the incentives to form strategic coalitions in ATM markets

This paper studies ATM coalitions in retail banking. We ask when it is profitable for banks to make agreements which ban direct ATM transaction fees. In the case of a coalition banks loose income from ATM transactions but relax competition in the banking market. We find that such agreements are profitable when the interchange fee is sufficiently high. When banks can collude on the interchange they always form a coalition. Coalitions may harm consumers but lead to higher total welfare. Moreover, we find that smaller banks have larger incentives to form ATM coalitions. Investment in ATM networks is typically higher with a coalition. --Banking competition,ATM networks,collusion

Survey of switching techniques in high-speed networks and their performance

One of the most promising approaches for high speed networks for integrated service applications is fast packet switching, or ATM (Asynchronous Transfer Mode). ATM can be characterized by very high speed transmission links and simple, hard wired protocols within a network. To match the transmission speed of the network links, and to minimize the overhead due to the processing of network protocols, the switching of cells is done in hardware switching fabrics in ATM networks.A number of designs has been proposed for implementing ATM switches. While many differences exist among the proposals, the vast majority of them is based on self-routing multi-stage interconnection networks. This is because of the desirable features of multi-stage interconnection networks such as self-routing capability and suitability for VLSI implementation.Existing ATM switch architectures can be classified into two major classes: blocking switches, where blockings of cells may occur within a switch when more than one cell contends for the same internal link, and non-blocking switches, where no internal blocking occurs. A large number of techniques has also been proposed to improve the performance of blocking and nonblocking switches. In this paper, we present an extensive survey of the existing proposals for ATM switch architectures, focusing on their performance issues