Definitiestudie afwegingskader : naar een klimaatbestendig Nederland : definitiestudie Fase 1, kaders voor afweging

Onzekerheid over (omvang en tempo van) de gevolgen van klimaatverandering vormt een essentieel punt bij beslissingen over de ruimtelijke inrichting. De mate waarin en de snelheid waarmee veranderingen optreden zijn niet precies bekend. Een afwegingskader geeft de overheid en de planontwikkelaar instrumenten in handen om de risico’s, de kansen, de kosten en de baten van klimaatadaptatie op verschillende onderscheiden thema’s inzichtelijk te maken. Afwegen: hoe doe je dat. Daarvoor wordt in drie stappen een kader voor gegeven

Predictive simulations identify potential neuromuscular contributors to idiopathic toe walking

Background: Most cases of toe walking in children are idiopathic. We used pathology-specific neuromusculoskeletal predictive simulations to identify potential underlying neural and muscular mechanisms contributing to idiopathic toe walking. Methods: A musculotendon contracture was added to the ankle plantarflexors of a generic musculoskeletal model to represent a pathology-specific contracture model, matching the reduced ankle dorsiflexion range-of-motion in a cohort of children with idiopathic toe walking. This model was employed in a forward dynamic simulation controlled by reflexes and supraspinal drive, governed by a multi-objective cost function to predict gait patterns with the contracture model. We validated the predicted gait using experimental gait data from children with idiopathic toe walking with ankle contracture, by calculating the root mean square errors averaged over all biomechanical variables. Findings:A predictive simulation with the pathology-specific model with contracture approached experimental ITW data (root mean square error = 1.37SD). Gastrocnemius activation was doubled from typical gait simulations, but lacked a peak in early stance as present in electromyography. This synthesised idiopathic toe walking was more costly for all cost function criteria than typical gait simulation. Also, it employed a different neural control strategy, with increased length- and velocity-based reflex gains to the plantarflexors in early stance and swing than typical gait simulations. Interpretation: The simulations provide insights into how a musculotendon contracture combined with altered neural control could contribute to idiopathic toe walking. Insights into these neuromuscular mechanisms could guide future computational and experimental studies to gain improved insight into the cause of idiopathic toe walking.</p

ATP Changes the Fluorescence Lifetime of Cyan Fluorescent Protein via an Interaction with His148

Recently, we described that ATP induces changes in YFP/CFP fluorescence intensities of Fluorescence Resonance Energy Transfer (FRET) sensors based on CFP-YFP. To get insight into this phenomenon, we employed fluorescence lifetime spectroscopy to analyze the influence of ATP on these fluorescent proteins in more detail. Using different donor and acceptor pairs we found that ATP only affected the CFP-YFP based versions. Subsequent analysis of purified monomers of the used proteins showed that ATP has a direct effect on the fluorescence lifetime properties of CFP. Since the fluorescence lifetime analysis of CFP is rather complicated by the existence of different lifetimes, we tested a variant of CFP, i.e. Cerulean, as a monomer and in our FRET constructs. Surprisingly, this CFP variant shows no ATP concentration dependent changes in the fluorescence lifetime. The most important difference between CFP and Cerulean is a histidine residue at position 148. Indeed, changing this histidine in CFP into an aspartic acid results in identical fluorescence properties as observed for the Cerulean fluorescent based FRET sensor. We therefore conclude that the changes in fluorescence lifetime of CFP are affected specifically by possible electrostatic interactions of the negative charge of ATP with the positively charged histidine at position 148. Clearly, further physicochemical characterization is needed to explain the sensitivity of CFP fluorescence properties to changes in environmental (i.e. ATP concentrations) conditions

VASP, zyxin and TES are tension-dependent members of Focal Adherens Junctions independent of the α-catenin-vinculin module

Mechanical forces are integrated at cadherin-based adhesion complexes to regulate morphology and strength of cell-cell junctions and organization of associated F-actin. A central mechanosensor at the cadherin complex is α-catenin, whose stretching recruits vinculin to regulate adhesion strength. The identity of the F-actin regulating signals that are also activated by mechanical forces at cadherin-based junctions has remained elusive. Here we identify the actin-regulators VASP, zyxin and TES as members of punctate, tensile cadherin-based junctions called Focal Adherens Junctions (FAJ) and show that they display mechanosensitive recruitment similar to that of vinculin. However, this recruitment is not altered by destroying or over-activating the α-catenin/vinculin module. Structured Illumination Microscopy (SIM) indicates that these tension sensitive proteins concentrate at locations within FAJs that are distinct from the core cadherin complex proteins. Furthermore, localization studies using mutated versions of VASP and zyxin indicate that these two proteins require binding to each other in order to localize to the FAJs. We conclude that there are multiple force sensitive modules present at the FAJ that are activated at distinct locations along the cadherin-F-actin axis and regulate specific aspects of junction dynamics

FMAP: Distributed Cooperative Multi-Agent Planning

This paper proposes FMAP (Forward Multi-Agent Planning), a fully-distributed multi-agent planning method that integrates planning and coordination. Although FMAP is specifically aimed at solving problems that require cooperation among agents, the flexibility of the domain-independent planning model allows FMAP to tackle multi-agent planning tasks of any type. In FMAP, agents jointly explore the plan space by building up refinement plans through a complete and flexible forward-chaining partial-order planner. The search is guided by h D T G , a novel heuristic function that is based on the concepts of Domain Transition Graph and frontier state and is optimized to evaluate plans in distributed environments. Agents in FMAP apply an advanced privacy model that allows them to adequately keep private information while communicating only the data of the refinement plans that is relevant to each of the participating agents. Experimental results show that FMAP is a general-purpose approach that efficiently solves tightly-coupled domains that have specialized agents and cooperative goals as well as loosely-coupled problems. Specifically, the empirical evaluation shows that FMAP outperforms current MAP systems at solving complex planning tasks that are adapted from the International Planning Competition benchmarks.This work has been partly supported by the Spanish MICINN under projects Consolider Ingenio 2010 CSD2007-00022 and TIN2011-27652-C03-01, the Valencian Prometeo project II/2013/019, and the FPI-UPV scholarship granted to the first author by the Universitat Politecnica de Valencia.Torreño Lerma, A.; Onaindia De La Rivaherrera, E.; Sapena Vercher, O. (2014). FMAP: Distributed Cooperative Multi-Agent Planning. Applied Intelligence. 41(2):606-626. https://doi.org/10.1007/s10489-014-0540-2S606626412Benton J, Coles A, Coles A (2012) Temporal planning with preferences and time-dependent continuous costs. 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The Frenchness of Marcel Lefebvre and the Society of St Pius X:a new reading

The case of Marcel Lefebvre and the Society of St Pius X (SSPX) deserves fresh perspectives. The current historiography is too franco-centric, focused on selective aspects of Lefebvre’s biography and the actions of isolated individuals, rather than with the life of the SSPX itself. After evaluating the current state of the historiography, this article proposes a new analysis of the SSPX’s political discourses in France and internationally and undertakes to reframe the relationship between Lefebvre’s life and his congregation by re-examining his African missionary experiences. Such new perspectives will be helpful as the SSPX moves towards regularisation under the pontificate of Pope Francis

Quantitative real-time imaging of intracellular FRET biosensor dynamics using rapid multi-beam confocal FLIM

Fluorescence lifetime imaging (FLIM) is a quantitative, intensity-independent microscopical method for measurement of diverse biochemical and physical properties in cell biology. It is a highly effective method for measurements of Förster resonance energy transfer (FRET), and for quantification of protein-protein interactions in cells. Time-domain FLIM-FRET measurements of these dynamic interactions are particularly challenging, since the technique requires excellent photon statistics to derive experimental parameters from the complex decay kinetics often observed from fluorophores in living cells. Here we present a new time-domain multi-confocal FLIM instrument with an array of 64 visible beamlets to achieve parallelised excitation and detection with average excitation powers of ~ 1–2 μW per beamlet. We exemplify this instrument with up to 0.5 frames per second time-lapse FLIM measurements of cAMP levels using an Epac-based fluorescent biosensor in live HeLa cells with nanometer spatial and picosecond temporal resolution. We demonstrate the use of time-dependent phasor plots to determine parameterisation for multi-exponential decay fitting to monitor the fractional contribution of the activated conformation of the biosensor. Our parallelised confocal approach avoids having to compromise on speed, noise, accuracy in lifetime measurements and provides powerful means to quantify biochemical dynamics in living cells