Multivariate Nonparametric Estimation of the Pickands Dependence Function using Bernstein Polynomials

Many applications in risk analysis, especially in environmental sciences, require the estimation of the dependence among multivariate maxima. A way to do this is by inferring the Pickands dependence function of the underlying extreme-value copula. A nonparametric estimator is constructed as the sample equivalent of a multivariate extension of the madogram. Shape constraints on the family of Pickands dependence functions are taken into account by means of a representation in terms of a specific type of Bernstein polynomials. The large-sample theory of the estimator is developed and its finite-sample performance is evaluated with a simulation study. The approach is illustrated by analyzing clusters consisting of seven weather stations that have recorded weekly maxima of hourly rainfall in France from 1993 to 2011

Evolutionary Dynamics of Pathoadaptation Revealed by Three Independent Acquisitions of the VirB/D4 Type IV Secretion System in Bartonella.

The α-proteobacterial genus Bartonella comprises a group of ubiquitous mammalian pathogens that are studied as a model for the evolution of bacterial pathogenesis. Vast abundance of two particular phylogenetic lineages of Bartonella had been linked to enhanced host adaptability enabled by lineage-specific acquisition of a VirB/D4 type IV secretion system (T4SS) and parallel evolution of complex effector repertoires. However, the limited availability of genome sequences from one of those lineages as well as other, remote branches of Bartonella has so far hampered comprehensive understanding of how the VirB/D4 T4SS and its effectors called Beps have shaped Bartonella evolution. Here, we report the discovery of a third repertoire of Beps associated with the VirB/D4 T4SS of B. ancashensis, a novel human pathogen that lacks any signs of host adaptability and is only distantly related to the two species-rich lineages encoding a VirB/D4 T4SS. Furthermore, sequencing of ten new Bartonella isolates from under-sampled lineages enabled combined in silico analyses and wet lab experiments that suggest several parallel layers of functional diversification during evolution of the three Bep repertoires from a single ancestral effector. Our analyses show that the Beps of B. ancashensis share many features with the two other repertoires, but may represent a more ancestral state that has not yet unleashed the adaptive potential of such an effector set. We anticipate that the effectors of B. ancashensis will enable future studies to dissect the evolutionary history of Bartonella effectors and help unraveling the evolutionary forces underlying bacterial host adaptation

Fluid-structure interaction simulation of prosthetic aortic valves : comparison between immersed boundary and arbitrary Lagrangian-Eulerian techniques for the mesh representation

In recent years the role of FSI (fluid-structure interaction) simulations in the analysis of the fluid-mechanics of heart valves is becoming more and more important, being able to capture the interaction between the blood and both the surrounding biological tissues and the valve itself. When setting up an FSI simulation, several choices have to be made to select the most suitable approach for the case of interest: in particular, to simulate flexible leaflet cardiac valves, the type of discretization of the fluid domain is crucial, which can be described with an ALE (Arbitrary Lagrangian-Eulerian) or an Eulerian formulation. The majority of the reported 3D heart valve FSI simulations are performed with the Eulerian formulation, allowing for large deformations of the domains without compromising the quality of the fluid grid. Nevertheless, it is known that the ALE-FSI approach guarantees more accurate results at the interface between the solid and the fluid. The goal of this paper is to describe the same aortic valve model in the two cases, comparing the performances of an ALE-based FSI solution and an Eulerian-based FSI approach. After a first simplified 2D case, the aortic geometry was considered in a full 3D set-up. The model was kept as similar as possible in the two settings, to better compare the simulations' outcomes. Although for the 2D case the differences were unsubstantial, in our experience the performance of a full 3D ALE-FSI simulation was significantly limited by the technical problems and requirements inherent to the ALE formulation, mainly related to the mesh motion and deformation of the fluid domain. As a secondary outcome of this work, it is important to point out that the choice of the solver also influenced the reliability of the final results

Patient-specific image-based computer simulation for theprediction of valve morphology and calcium displacement after TAVI with the Medtronic CoreValve and the Edwards SAPIEN valve

AIMS: Our aim was to validate patient-specific software integrating baseline anatomy and biomechanical properties of both the aortic root and valve for the prediction of valve morphology and aortic leaflet calcium displacement after TAVI. METHODS AND RESULTS: Finite element computer modelling was performed in 39 patients treated with a Medtronic CoreValve System (MCS; n=33) or an Edwards SAPIEN XT (ESV; n=6). Quantitative axial frame morphology at inflow (MCS, ESV) and nadir, coaptation and commissures (MCS) was compared between multislice computed tomography (MSCT) post TAVI and a computer model as well as displacement of the aortic leaflet calcifications, quantified by the distance between the coronary ostium and the closest calcium nodule. Bland-Altman analysis revealed a strong correlation between the observed (MSCT) and predicted frame dimensions, although small differences were detected for, e.g., Dmin at the inflow (mean±SD MSCT vs. MODEL: 21.6±2.4 mm vs. 22.0±2.4 mm; difference±SD: -0.4±1.3 mm, p<0.05) and Dmax (25.6±2.7 mm vs. 26.2±2.7 mm; difference±SD: -0.6±1.0 mm, p<0.01). The observed and predicted calcium displacements were highly correlated for the left and right coronary ostia (R2=0.67 and R2=0.71, respectively p<0.001). CONCLUSIONS: Dedicated software allows accurate prediction of frame morphology and calcium displacement after valve implantation, which may help to improve outcome

Forces on a boiling bubble in a developing boundary layer, in microgravity with g-jitter and in terrestrial conditions

Terrestrial and microgravity flow boiling experiments were carried out with the same test rig, comprising a locally heated artificial cavity in the center of a channel near the frontal edge of an intrusive glass bubble generator. Bubble shapes were in microgravity generally not far from those of truncated spheres,which permitted the computation of inertial lift and drag from potential flow theory for truncated spheres approximating the actual shape. For these bubbles, inertial lift is counteracted by drag and both forces are of the same order of magnitude as g-jitter. A generalization of the Laplace equation is found which applies to a deforming bubble attached to a plane wall and yields the pressure difference between the hydrostatic pressures in the bubble and at the wall, p. A fully independent way to determine the overpressure p is given by a second Euler-Lagrange equation. Relative differences have been found to be about 5% for both terrestrial and microgravity bubbles. A way is found to determine the sum of the two counteracting major force contributions on a bubble in the direction normal to the wall from a single directly measurable quantity. Good agreement with expectation values for terrestrial bubbles was obtained with the difference in radii of curvature averaged over the liquid-vapor interface, (1/R2 − 1/R1), multiplied with the surface tension coefficient, σ. The new analysis methods of force components presented also permit the accounting for a surface tension gradient along the liquid-vapor interface. No such gradients were found for the present measurements

Global model simulations of air pollution during the 2003 European heat wave

Three global Chemistry Transport Models - MOZART, MOCAGE, and TM5 - as well as MOZART coupled to the IFS meteorological model including assimilation of ozone (O-3) and carbon monoxide (CO) satellite column retrievals, have been compared to surface measurements and MOZAIC vertical profiles in the troposphere over Western/Central Europe for summer 2003. The models reproduce the meteorological features and enhancement of pollution during the period 2-14 August, but not fully the ozone and CO mixing ratios measured during that episode. Modified normalised mean biases are around -25% (except similar to 5% for MOCAGE) in the case of ozone and from -80% to -30% for CO in the boundary layer above Frankfurt. The coupling and assimilation of CO columns from MOPITT overcomes some of the deficiencies in the treatment of transport, chemistry and emissions in MOZART, reducing the negative biases to around 20%. The high reactivity and small dry deposition velocities in MOCAGE seem to be responsible for the overestimation of O-3 in this model. Results from sensitivity simulations indicate that an increase of the horizontal resolution to around 1 degrees x1 degrees and potential uncertainties in European anthropogenic emissions or in long-range transport of pollution cannot completely account for the underestimation of CO and O-3 found for most models. A process-oriented TM5 sensitivity simulation where soil wetness was reduced results in a decrease in dry deposition fluxes and a subsequent ozone increase larger than the ozone changes due to the previous sensitivity runs. However this latest simulation still underestimates ozone during the heat wave and overestimates it outside that period. Most probably, a combination of the mentioned factors together with underrepresented biogenic emissions in the models, uncertainties in the modelling of vertical/horizontal transport processes in the proximity of the boundary layer as well as limitations of the chemistry schemes are responsible for the underestimation of ozone (overestimation in the case of MOCAGE) and CO found in the models during this extreme pollution event

Cornetto: A Combinatorial Lexical Semantic Database for Dutch

One of the goals of the STEVIN programme is the realisation of a digital infrastructure that will enforce the position of the Dutch language in the modern information and communication technology.A semantic database makes it possible to go from words to concepts and consequently, to develop technologies that access and use knowledge rather than textual representations

Absence of cardiovascular manifestations in a haploinsufficient Tgfbr1 mouse model

Loeys-Dietz syndrome (LDS) is an autosomal dominant arterial aneurysm disease belonging to the spectrum of transforming growth factor β (TGFβ)-associated vasculopathies. In its most typical form it is characterized by the presence of hypertelorism, bifid uvula/cleft palate and aortic aneurysm and/or arterial tortuosity. LDS is caused by heterozygous loss of function mutations in the genes encoding TGFβ receptor 1 and 2 (TGFBR1 and -2), which lead to a paradoxical increase in TGFβ signaling. To address this apparent paradox and to gain more insight into the pathophysiology of aneurysmal disease, we characterized a new Tgfbr1 mouse model carrying a p.Y378*nonsense mutation. Study of the natural history in this model showed that homozygous mutant mice die during embryonic development due to defective vascularization. Heterozygous mutant mice aged 6 and 12 months were morphologically and (immuno)histochemically indistinguishable from wild-type mice. We show that the mutant allele is degraded by nonsense mediated mRNA decay, expected to result in haploinsufficiency of the mutant allele. Since this haploinsufficiency model does not result in cardiovascular malformations, it does not allow further study of the process of aneurysm formation. In addition to providing a comprehensive method for cardiovascular phenotyping in mice, the results of this study confirm that haploinsuffciency is not the underlying genetic mechanism in human LDS

Validation of non-invasive central blood pressure devices: ARTERY Society task force consensus statement on protocol standardization

The original Riva-Rocci method to measure blood pressure (BP) using a cuff at the upper arm assumed the pressure obtained by this technique was a good proxy for central aortic BP.1,2 The clinical (prognostic) importance of brachial cuff BP is undeniable for both the assessment of cardiovascular risk associated with elevated BP and the benefits of treatment-induced BP reduction.3 However, it is also generally appreciated that peripheral artery systolic BP (SBP; brachial or radial artery) may be an inaccurate substitute for central SBP.4 This has been reported in human studies using intra-arterial catheterization of peripheral and central arteries.5–8 There may also be a discrepancy between peripheral and central BP responses to vasoactive drugs.9 These findings are corroborated in larger studies using non-invasive central aortic BP methods,10–13 and, while yet to be fully adopted in clinical practice, an independent prognostic value of central BP has been demonstrated.14–16 Altogether, there is a growing interest among clinicians towards improving risk estimates by using devices that provide more accurate measures of central aortic BP than those provided by current brachial cuff BP methods. Many non-invasive devices have been developed that purport to estimate central BP from different peripheral artery sites (e.g. radial, brachial, carotid arteries) using different principles of recording the pressure or surrogate signals (e.g. applanation tonometry, oscillometry, ultrasound, or magnetic resonance imaging) and different calibration methods to derive central BP. Since upper arm cuff-based devices to estimate central BP are more clinically appealing, in recent years several companies have developed such devices using a variety of techniques (e.g. oscillometric sub-diastolic or supra-systolic waveform analysis with generalized transfer functions), which employ a variety of signal processing steps to estimate central BP from peripheral signals.17,18 Yet, with no standardized guidelines,17 the accuracy testing of these new devices (as well as the preceding devices) has not been undertaken in a uniform fashion with comparable protocols, emphasizing the need for guidance in this field.19–22 An international task force was convened to address this situation