Towards new metrics assessing air traffic network interactions

In ATM systems, the massive number of interactin entities makes it difficult to predict the system-wide effects that innovations might have. Here, we present the approach proposed by the project Domino to assess such effects and identify the impact that innovations might bring for the different stake-holders, based on agent-based modelling and complex network science. Domino will model scenarios mirroring different system innovations which change the agents’ actions and behaviour. Suitable network metrics are needed to evaluate the effect of innovations on the network functioning. We review existing centrality and causality metrics and show their limitations in characterising the network by applying them to a dataset of US flights. We finally suggest improvements that should be introduced to obtain new metrics answering to Domino’s needs

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

ATM in focus:a damage sensor and cancer target

The ability of a cell to conserve and maintain its native DNA sequence is fundamental for the survival and normal functioning of the whole organism and protection from cancer development. Here we review recently obtained results and current topics concerning the role of the ataxia-telangiectasia mutated (ATM) protein kinase as a damage sensor and its potential as therapeutic target for treating cancer. This monograph discusses DNA repair mechanisms activated after DNA double-strand breaks (DSBs), i.e. non-homologous end joining, homologous recombination and single strand annealing and the role of ATM in the above types of repair. In addition to DNA repair, ATM participates in a diverse set of physiological processes involving metabolic regulation, oxidative stress, transcriptional modulation, protein degradation and cell proliferation. Full understanding of the complexity of ATM functions and the design of therapeutics that modulate its activity to combat diseases such as cancer necessitates parallel theoretical and experimental efforts. This could be best addressed by employing a systems biology approach, involving mathematical modelling of cell signalling pathways

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

Using Computational Agents to Design Participatory Social Simulations

In social science, the role of stakeholders is increasing in the development and use of simulation models. Their participation in the design of agent-based models (ABMs) has widely been considered as an efficient solution to the validation of this particular type of model. Traditionally, "agents" (as basic model elements) have not been concerned with stakeholders directly but via designers or role-playing games (RPGs). In this paper, we intend to bridge this gap by introducing computational or software agents, implemented from an initial ABM, into a new kind of RPG, mediated by computers, so that these agents can interact with stakeholders. This interaction can help not only to elicit stakeholders' informal knowledge or unpredicted behaviours, but also to control stakeholders' focus during the games. We therefore formalize a general participatory design method using software agents, and illustrate it by describing our experience in a project aimed at developing agent-based social simulations in the field of air traffic management.Participatory Social Simulations, Agent-Based Social Simulations, Computational Agents, Role-Playing Games, Artificial Maieutics, User-Centered Design

Bibliographic Analysis on Research Publications using Authors, Categorical Labels and the Citation Network

Bibliographic analysis considers the author's research areas, the citation network and the paper content among other things. In this paper, we combine these three in a topic model that produces a bibliographic model of authors, topics and documents, using a nonparametric extension of a combination of the Poisson mixed-topic link model and the author-topic model. This gives rise to the Citation Network Topic Model (CNTM). We propose a novel and efficient inference algorithm for the CNTM to explore subsets of research publications from CiteSeerX. The publication datasets are organised into three corpora, totalling to about 168k publications with about 62k authors. The queried datasets are made available online. In three publicly available corpora in addition to the queried datasets, our proposed model demonstrates an improved performance in both model fitting and document clustering, compared to several baselines. Moreover, our model allows extraction of additional useful knowledge from the corpora, such as the visualisation of the author-topics network. Additionally, we propose a simple method to incorporate supervision into topic modelling to achieve further improvement on the clustering task.Comment: Preprint for Journal Machine Learnin

Did inflation really soar after the euro cash changeover? Indirect evidence from ATM withdrawals

The introduction of the euro notes and coins in the first two months of 2002 was followed by a lively debate on the alleged inflationary effects of the new currency. In Italy, as in the rest of the euro area, survey-based measures signaled a much sharper rise in inflation than measured by the official price indices, whose quality was called into question. In this paper we gather indirect evidence on the behavior of prices from the analysis of cash withdrawals from ATM and their determinants. Since these data do not rely on official inflation statistics, they provide an independent check for the latter. We present a model in which the relationship between aggregate ATM withdrawals and aggregate expenditure is not homogenous of degree one in the price level, a prediction which is strongly supported by the data. This feature allows us to test the hypothesis that, after the introduction of the euro notes and coins, consumer prices underwent an increase not recorded by official inflation statistics. We do not find evidence in support of this hypothesis.banknotes, currency, euro, inflation.

Complexity challenges in ATM

After more than 4 years of activity, the ComplexWorld Network, together with the projects and PhDs covered under the SESAR long-term research umbrella, have developed sound research material contributing to progress beyond the state of the art in fields such as resilience, uncertainty, multi-agent systems, metrics and data science. The achievements made by the ComplexWorld stakeholders have also led to the identification of new challenges that need to be addressed in the future. In order to pave the way for complexity science research in Air Traffic Management (ATM) in the coming years, ComplexWorld requested external assessments on how the challenges have been covered and where there are existing gaps. For that purpose, ComplexWorld, with the support of EUROCONTROL, established an expert panel to review selected documentation developed by the network and provide their assessment on their topic of expertise

Experiences in Integrated Multi-Domain Service Management

Increased competition, complex service provision chains and integrated service offerings require effective techniques for the rapid integration of telecommunications services and management systems over multiple organisational domains. This paper presents some of the results of practical development work in this area, detailing the technologies and standards used, the architectural approach taken and the application of this approach to specific services. This work covers the integration of multimedia services, broadband networks, service management and network management, though the detailed examples given focus specifically on the integration of services and service management