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

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

Multi-scale analysis of the European airspace using network community detection

We show that the European airspace can be represented as a multi-scale traffic network whose nodes are airports, sectors, or navigation points and links are defined and weighted according to the traffic of flights between the nodes. By using a unique database of the air traffic in the European airspace, we investigate the architecture of these networks with a special emphasis on their community structure. We propose that unsupervised network community detection algorithms can be used to monitor the current use of the airspaces and improve it by guiding the design of new ones. Specifically, we compare the performance of three community detection algorithms, also by using a null model which takes into account the spatial distance between nodes, and we discuss their ability to find communities that could be used to define new control units of the airspace.Comment: 22 pages, 14 figure

Dynamic structural and topological phase transitions on the Warsaw Stock Exchange: A phenomenological approach

We study the crash dynamics of the Warsaw Stock Exchange (WSE) by using the Minimal Spanning Tree (MST) networks. We find the transition of the complex network during its evolution from a (hierarchical) power law MST network, representing the stable state of WSE before the recent worldwide financial crash, to a superstar-like (or superhub) MST network of the market decorated by a hierarchy of trees (being, perhaps, an unstable, intermediate market state). Subsequently, we observed a transition from this complex tree to the topology of the (hierarchical) power law MST network decorated by several star-like trees or hubs. This structure and topology represent, perhaps, the WSE after the worldwide financial crash, and could be considered to be an aftershock. Our results can serve as an empirical foundation for a future theory of dynamic structural and topological phase transitions on financial markets

Delay propagation – new metrics, new insights

Network delay propagation is intimately linked with the challenges of managing passenger itineraries and corresponding connections. Airline decision-making governing these processes is driven by operational and regulatory factors. Using the first European network simulation model with explicit passenger itineraries and full delay cost estimations, we explore these factors through various flight and passenger prioritisation rules, assessing the performance impacts. Delay propagation is further characterised under the different prioritisation rules using complexity science techniques such as percolation theory and network attack. The relative effects of randomised and targeted disruption are compared

Network provider domain federation in TINA

Federation in TINA CMA (Connection Management Architecture) provides the mechanisms for cooperation between different interworking network domains possibly owned by different administrators. In order to be able to offer services to their users, these administrators must cooperate. We present an implemented and validated architecture including the federation techniques necessary. We illustrate the problem based on experience from a user trial, in which different operators, and suppliers with different equipment participate

A systematic analysis of equivalence in multistage networks

Many approaches to switching in optoelectronic and optical networks decompose the switching function across multiple stages or hops. This paper addresses the problem of determining whether two multistage or multihop networks are functionally equivalent. Various ad-hoc methods have been used in the past to establish such equivalences. A systematic method for determining equivalence is presented based on properties of the link permutations used to interconnect stages of the network. This method is useful in laying out multistage networks, in determining optimal channel assignments for multihop networks, and in establishing the routing required in such networks. A purely graphical variant of the method, requiring no mathematics or calculations, is also described

Analysis of topology aggregation techniques for QoS routing

We study and compare topology aggregation techniques used in QoS routing. Topology Aggregation (TA) is defined as a set of techniques that abstract or summarize the state information about the network topology to be exchanged, processed, and maintained by network nodes for routing purposes. Due to scalability, aggregation techniques have been an integral part of some routing protocols. However, TA has not been studied extensively except in a rather limited context. With the continuing growth of the Internet, scalability issues of QoS routing have been gaining importance. Therefore, we survey the current TA techniques, provide methodology to classify, evaluate, and compare their complexities and efficiencies. ©2007 ACM.postprin