Computing mean first exit times for stochastic processes using multi-level Monte Carlo

The multi-level approach developed by Giles (2008) can be used to estimate mean first exit times for stochastic differential equations, which are of interest in finance, physics and chemical kinetics. Multi-level improves the computational expense of standard Monte Carlo in this setting by an order of magnitude. More precisely, for a target accuracy of TOL, so that the root mean square error of the estimator is O(TOL), the O(TOL-4) cost of standard Monte Carlo can be reduced to O(TOL-3|log(TOL)|1/2) with a multi-level scheme. This result was established in Higham, Mao, Roj, Song, and Yin (2013), and illustrated on some scalar examples. Here, we briefly overview the algorithm and present some new computational results in higher dimensions

A flexible architecture for modeling and simulation of diffusional association

Up to now, it is not possible to obtain analytical solutions for complex molecular association processes (e.g. Molecule recognition in Signaling or catalysis). Instead Brownian Dynamics (BD) simulations are commonly used to estimate the rate of diffusional association, e.g. to be later used in mesoscopic simulations. Meanwhile a portfolio of diffusional association (DA) methods have been developed that exploit BD. However, DA methods do not clearly distinguish between modeling, simulation, and experiment settings. This hampers to classify and compare the existing methods with respect to, for instance model assumptions, simulation approximations or specific optimization strategies for steering the computation of trajectories. To address this deficiency we propose FADA (Flexible Architecture for Diffusional Association) - an architecture that allows the flexible definition of the experiment comprising a formal description of the model in SpacePi, different simulators, as well as validation and analysis methods. Based on the NAM (Northrup-Allison-McCammon) method, which forms the basis of many existing DA methods, we illustrate the structure and functioning of FADA. A discussion of future validation experiments illuminates how the FADA can be exploited in order to estimate reaction rates and how validation techniques may be applied to validate additional features of the model

#140ToWinIt

The Internet has transformed from being almost insubstantial in political campaigns to being essential in only ten years. The elections of 2008 and 2010 have revolutionized the way that campaigns reach out to voters, with a new benchmark set by President Barack Obama and his campaign team in 2008. In the 2010 midterm elections, Republicans in Congress were able to match Obama’s social media success, and voters turned out in their favor. By delving into the uses of social media in those campaigns, we can evaluate how Republicans in the upcoming 2012 campaign are sharing the same success.</jats:p

Rule-based multi-level modeling of cell biological systems

<p>Abstract</p> <p>Background</p> <p>Proteins, individual cells, and cell populations denote different levels of an organizational hierarchy, each of which with its own dynamics. Multi-level modeling is concerned with describing a system at these different levels and relating their dynamics. Rule-based modeling has increasingly attracted attention due to enabling a concise and compact description of biochemical systems. In addition, it allows different methods for model analysis, since more than one semantics can be defined for the same syntax.</p> <p>Results</p> <p>Multi-level modeling implies the hierarchical nesting of model entities and explicit support for downward and upward causation between different levels. Concepts to support multi-level modeling in a rule-based language are identified. To those belong rule schemata, hierarchical nesting of species, assigning attributes and solutions to species at each level and preserving content of nested species while applying rules. Further necessities are the ability to apply rules and flexibly define reaction rate kinetics and constraints on nested species as well as species that are nested within others. An example model is presented that analyses the interplay of an intracellular control circuit with states at cell level, its relation to cell division, and connections to intercellular communication within a population of cells. The example is described in ML-Rules - a rule-based multi-level approach that has been realized within the plug-in-based modeling and simulation framework JAMES II.</p> <p>Conclusions</p> <p>Rule-based languages are a suitable starting point for developing a concise and compact language for multi-level modeling of cell biological systems. The combination of nesting species, assigning attributes, and constraining reactions according to these attributes is crucial in achieving the desired expressiveness. Rule schemata allow a concise and compact description of complex models. As a result, the presented approach facilitates developing and maintaining multi-level models that, for instance, interrelate intracellular and intercellular dynamics.</p

Aesthetic, Spiritual, and Flow Experiences: Contrasts and Educational Implications

The purpose of this paper is to cross-examine Dewey’s ideas on religious and aesthetic experiences, and Csikszentmihalyi’s theory of flow experience. To achieve this end, we offer an analytic framework for evaluating experiences: triggers, characterizations, and import. In using this framework, we not only more deeply examine these ideas of experience, but we also discuss what educators may learn from the intersection of these three important theories of experience

Flow Cytometry and Polymerase Chain Reaction-Based Analyses of Minimal Residual Disease in Chronic Lymphocytic Leukemia

New therapeutic strategies developed recently for chronic lymphocytic leukemia (CLL) have led to remarkable treatment response rates and complete hematological remissions. This means highly sensitive and specific techniques are increasingly needed to evaluate minimal residual disease (MRD) in CLL patients. Quantitative MRD levels can be used as prognostic markers, where total MRD eradication is associated with prolonged survival. Nowadays, PCR and flow cytometry techniques used to detect MRD in CLL patients can generate reliable and quantitative results with the highest sensitivity. MRD Flow is based on four-color flow cytometry using specific antibody combinations. For allele specific oligonucleotide real-time quantification (ASO RQ) PCR individual primers are designed to detect a specific immunoglobulin heavy chain (IgH) rearrangement in each patient clone. Five comprehensive studies investigated and compared the sensitivity and specificity of both methods. Groups of patients receiving different therapies were analyzed at different time points to generate quantitative MRD levels and MRD kinetics. All studies confirmed that both methods generate equivalent results with regard to sensitivity and MRD quantification, although each method has advantages and disadvantages in the daily routine of a standard hematological laboratory. Here, we review these investigations and compare their results in the light of modern therapies

Die Karte des luxemburgisch-kurtrierischen Grenzverlaufs aus dem Jahr 1776 – Ein Meisterwerk der Kartographie des späten Ancien Régime und eine faszinierende Quelle für die Landesgeschichte

Das Nationalarchiv hat drei außergewöhnliche Dokumente aus dem Jahr 1776 online gestellt. Hierbei handelt es sich um zwei sehr große Karten (7,1m x 2m ; 3,3m x 2,1m), die den Grenzverlauf zwischen Luxemburg und dem Kurfürstentum Trier zeigen. Sie wurden vom Ingenieur Bergé, Oberleutnant der österreichischen Armee, gezeichnet und mit Hilfe des Fotografen Tom Lucas und des Musée Dräi Eechelen digitalisiert. Hinzu kommt ein historisches Dokument von 325 Seiten in dem die auf den Karten abgebildete Grenze in Frage gestellt wird. Beide Karten sind aufgrund ihrer Größe nur schwer einsehbar, stellen aber eine wichtige Quelle für die Geschichte Luxemburgs dar und sind reich an Informationen, Details und Farben. Martin Uhrmacher, Dozent und Forscher an der Universität Luxemburg und Experte auf dem Gebiet der historischen Kartographie, hat beide Karten in diesem Beitrag ausführlich analysiert

Hunger and market dynamics in pre-modern communities: insights into the effects of market intervention from a multi-agent model

'Nahrungsmittelknappheit und Hungerkrisen waren ein wichtiger Faktor des Lebensstandards in vormodernen städtischen Gemeinwesen. Die Räte der Stadt versuchten üblicherweise, die sich bei solchen Ereignissen ergebende Marktdynamik durch Intervention unter Kontrolle zu halten. Unklar ist allerdings, ob damit der starke Anstieg von Nahrungsmittelpreisen und Löhnen tatsächlich langfristig gedämpft werden konnte. Mit einem Multi-Agenten-Modell, in dem in vereinfachter Form die wesentlichen ökonomischen Austauschbeziehungen einer vormodernen Stadt abgebildet sind, werden die Wirkungen von Markteingriffen der städtischen Obrigkeit bei Hungersnöten auf die langfristige wirtschaftliche und demographische Entwicklung simuliert. Marktintervention zeigt sich dabei grundsätzlich als eine Strategie, mit der die wohlfahrtsmindernde Wirkung einer Nahrungsmittelknappheit sehr wohl beschränkt werden konnte. Um allerdings zu verhindern, dass sich aus einer Nahrungsmittelknappheit eine Hungerkrise entwickelte, mussten Marktinterventionen zielgerichtet und in mehrere Märkte gleichzeitig erfolgen, ebenso wie sich ihr wohlfahrtserhaltender Effekt erst nach einiger Zeit entfaltete.' (Autorenreferat)'Food shortages and hunger had been a great threat to the standard of living in urban communities in the Middle Ages and in early modern times. In order to cope with this sort of critical events, local governments and municipal councils commonly tried to control market dynamics, but it is not clear, whether in cases like this the typical market reaction of rising prices of foodstuffs and wages could really be moderated in the long-run through an intervention in markets. In the present article, a simplified multi-agent-based model of the pre-modern urban economy is used which allows a simulation of effects that different strategies of crisis management had on the medium-term and long-range economic and demographic developments in an urban community experiencing a food shortage. Intervention in markets turns out to be a strategic choice of local authorities by which very likely wealth-destroying consequences of food shortages or even famines could be reduced to some extent. A successful intervention preventing a temporary food shortage turning into a substantial nutritional crisis nonetheless had to be goal-directed and of complex design, and showed its full wealth-keeping effects only after a considerably long period of time.' (author's abstract