Dynamical mechanism of atrial fibrillation: a topological approach

While spiral wave breakup has been implicated in the emergence of atrial fibrillation, its role in maintaining this complex type of cardiac arrhythmia is less clear. We used the Karma model of cardiac excitation to investigate the dynamical mechanisms that sustain atrial fibrillation once it has been established. The results of our numerical study show that spatiotemporally chaotic dynamics in this regime can be described as a dynamical equilibrium between topologically distinct types of transitions that increase or decrease the number of wavelets, in general agreement with the multiple wavelets hypothesis. Surprisingly, we found that the process of continuous excitation waves breaking up into discontinuous pieces plays no role whatsoever in maintaining spatiotemporal complexity. Instead this complexity is maintained as a dynamical balance between wave coalescence -- a unique, previously unidentified, topological process that increases the number of wavelets -- and wave collapse -- a different topological process that decreases their number.Comment: 15 pages, 14 figure

SATURN D6.5 - Final Report

The objective of the SATURN (Strategic Allocation of Traffic Using Redistribution in the Network) project is to make novel and credible use of market-based demand-management mechanisms to redistribute air traffic in the European airspace. This reduces congestion and saves the airspace users operational costs. The project is motivated by frequent demand and capacity imbalances in the European airspace network, which are forecast to continue in the near future. The present and foreseen ways of dealing with such imbalances mainly concern strategic and tactical capacity-side interventions, such as resectorisation and opening of more sectors to deal with excess demand. These are followed by tactical demand management measures, if needed. As a result, not only do substantial costs arise, but airspace users are also typically left with no choice but to comply with imposed air traffic flow management measures. The project shows how economic signals could be given to airspace users and air navigation service providers (ANSPs) to improve capacity-demand balancing, airspace design and usage, and what the benefits would be of a centralised planner compared with those of decentralised maximisation of self interests (by the ANSPs and/or airspace users)

Classification of protein interaction sentences via gaussian processes

The increase in the availability of protein interaction studies in textual format coupled with the demand for easier access to the key results has lead to a need for text mining solutions. In the text processing pipeline, classification is a key step for extraction of small sections of relevant text. Consequently, for the task of locating protein-protein interaction sentences, we examine the use of a classifier which has rarely been applied to text, the Gaussian processes (GPs). GPs are a non-parametric probabilistic analogue to the more popular support vector machines (SVMs). We find that GPs outperform the SVM and na\"ive Bayes classifiers on binary sentence data, whilst showing equivalent performance on abstract and multiclass sentence corpora. In addition, the lack of the margin parameter, which requires costly tuning, along with the principled multiclass extensions enabled by the probabilistic framework make GPs an appealing alternative worth of further adoption

A dynamic route choice model for public transport networks with boarding queues

The concepts of optimal strategy and hyperpath were born within the framework of static frequency-based public transport assignment, where it is assumed that travel times and frequencies do not change over time and no overcrowding occurs. However, the formation of queues at public transport stops can prevent passengers from boarding the first vehicle approaching and can thus lead to additional delays in their trip. Assuming that passengers know from previous experience that for certain stops/lines they will have to wait for the arrival of the 2nd, 3rd, …, k-th vehicle, they may alter their route choices, thus resulting in a different assignment of flows across the network. The aim of this paper is to investigate route choice behaviour changes as a result of the formation and dispersion of queues at stops within the framework of optimal travel strategies. A new model is developed, based on modifications of existing algorithms

Improving the Price of Anarchy for Selfish Routing via Coordination Mechanisms

We reconsider the well-studied Selfish Routing game with affine latency functions. The Price of Anarchy for this class of games takes maximum value 4/3; this maximum is attained already for a simple network of two parallel links, known as Pigou's network. We improve upon the value 4/3 by means of Coordination Mechanisms. We increase the latency functions of the edges in the network, i.e., if $\ell_e(x)$ is the latency function of an edge $e$, we replace it by $\hat{\ell}_e(x)$ with $\ell_e(x) \le \hat{\ell}_e(x)$ for all $x$. Then an adversary fixes a demand rate as input. The engineered Price of Anarchy of the mechanism is defined as the worst-case ratio of the Nash social cost in the modified network over the optimal social cost in the original network. Formally, if \CM(r) denotes the cost of the worst Nash flow in the modified network for rate $r$ and \Copt(r) denotes the cost of the optimal flow in the original network for the same rate then [\ePoA = \max_{r \ge 0} \frac{\CM(r)}{\Copt(r)}.] We first exhibit a simple coordination mechanism that achieves for any network of parallel links an engineered Price of Anarchy strictly less than 4/3. For the case of two parallel links our basic mechanism gives 5/4 = 1.25. Then, for the case of two parallel links, we describe an optimal mechanism; its engineered Price of Anarchy lies between 1.191 and 1.192.Comment: 17 pages, 2 figures, preliminary version appeared at ESA 201

Characterisation of local ICRF heat loads on the JET ILW

When using Ion Cyclotron Range of Frequency (ICRF) heating, enhanced heat-fluxes are commonly observed on some plasma facing components close to the antennas. Experiments have recently been carried out on JET with the new ITER-Like-Wall (ILW) to characterize the heat flux to the JET ICRF antennas. Using Infra-Red thermography and thermal models of the tiles, heat-fluxes were evaluated from the surface temperature increase during the RF phase of L-mode plasmas. The maximum observed heat-flux intensity was ~ 4.5 MW/m2 when operating with -{\pi}/2 current drive strap phasing at power level of 2MW per antenna and with a 4 cm distance between the plasma and the outer limiters. Heat-fluxes are reduced when using dipole strap phasing. The fraction of ICRF power deposited on the antenna limiters or septa was in the range 2-10% for dipole phasing and 10-20% with +/-{\pi}/2 phasing.Comment: 22 pages, 6 figure

Challenges of scaling up and of knowledge transfer in an action research project in Burkina Faso to exempt the worst-off from health care user fees

<p>Abstract</p> <p>Background</p> <p>Systems to exempt the indigent from user fees have been put in place to prevent the worst-off from being excluded from health care services for lack of funds. Yet the implementation of these mechanisms is as rare as the operational research on this topic. This article analyzes an action research project aimed at finding an appropriate solution to make health care accessible to the indigent in a rural district of Burkina Faso.</p> <p>Research</p> <p>This action research project was initiated in 2007 to study the feasibility and effectiveness of a community-based, participative and financially sustainable process for exempting the indigent from user fees. A interdisciplinary team of researchers from Burkina Faso and Canada was mobilized to document this action research project.</p> <p>Results and knowledge sharing</p> <p>The action process was very well received. Indigent selection was effective and strengthened local solidarity, but coverage was reduced by the lack of local financial resources. Furthermore, the indigent have many other needs that cannot be addressed by exemption from user fees. Several knowledge transfer strategies were implemented to share research findings with residents and with local and national decision-makers.</p> <p>Partnership achievements and difficulties</p> <p>Using a mixed and interdisciplinary research approach was critical to grasping the complexity of this community-based process. The adoption of the process and the partnership with local decision-makers were very effective. Therefore, at the instigation of an NGO, four other districts in Burkina Faso and Niger reproduced this experiment. However, national decision-makers showed no interest in this action and still seem unconcerned about finding solutions that promote access to health care for the indigent.</p> <p>Lessons learned</p> <p>The lessons learned with regard to knowledge transfer and partnerships between researchers and associated decision-makers are: i) involve potential users of the research results from the research planning stage; ii) establish an ongoing partnership between researchers and users; iii) ensure that users can participate in certain research activities; iv) use a variety of strategies to disseminate results; and v) involve users in dissemination activities.</p

Rational mutagenesis to support structure-based drug design: MAPKAP kinase 2 as a case study

<p>Abstract</p> <p>Background</p> <p>Structure-based drug design (SBDD) can provide valuable guidance to drug discovery programs. Robust construct design and expression, protein purification and characterization, protein crystallization, and high-resolution diffraction are all needed for rapid, iterative inhibitor design. We describe here robust methods to support SBDD on an oral anti-cytokine drug target, human MAPKAP kinase 2 (MK2). Our goal was to obtain useful diffraction data with a large number of chemically diverse lead compounds. Although MK2 structures and structural methods have been reported previously, reproducibility was low and improved methods were needed.</p> <p>Results</p> <p>Our construct design strategy had four tactics: <it>N</it>- and <it>C</it>-terminal variations; entropy-reducing surface mutations; activation loop deletions; and pseudoactivation mutations. Generic, high-throughput methods for cloning and expression were coupled with automated liquid dispensing for the rapid testing of crystallization conditions with minimal sample requirements. Initial results led to development of a novel, customized robotic crystallization screen that yielded MK2/inhibitor complex crystals under many conditions in seven crystal forms. In all, 44 MK2 constructs were generated, ~500 crystals were tested for diffraction, and ~30 structures were determined, delivering high-impact structural data to support our MK2 drug design effort.</p> <p>Conclusion</p> <p>Key lessons included setting reasonable criteria for construct performance and prioritization, a willingness to design and use customized crystallization screens, and, crucially, initiation of high-throughput construct exploration very early in the drug discovery process.</p