Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Influence of wind conditions on wind turbine loads and measurement of turbulence using lidars

Variations in wind conditions influence the loads on wind turbines significantly. In order to determine these loads it is important that the external conditions are well understood. Wind lidars are well developed nowadays to measure wind profiles upwards from the surface. But how turbulence can be measured using lidars has not yet been investigated. This PhD thesis deals with the influence of variations in wind conditions on the wind turbine loads as well as with the determination of wind conditions using wind lidars. Part I of the thesis focuses on analysis of diabatic wind profiles, turbulence, and their influence on wind turbine loads. The diabatic wind profiles are analyzed using the measurements from two offshore sites, one in the Dutch North Sea, and the other in the Danish North Sea. Two wind profile models are compared, one that is strictly valid in the atmospheric surface layer, and the other that is valid for the entire boundary layer. The second model is much more complicated in comparison to the first. It is demonstrated that at heights more than 50 m above the surface, where modern wind turbines usually operate, it is advisable to use a wind profile model that is valid in the entire boundary layer. The influence of diabatic wind profiles under steady winds on the fatigue damage at the blade root is also demonstrated using the aero-elastic simulation tool Bladed. Furthermore, detailed analysis of the combined influence of diabatic wind profile and turbulence on the blade root flap-wise and edge-wise moments, tower base fore-aft moment, and the rotor bending moments at the hub is carried out using the aero-elastic simulation tool HAWC2. It is found that the tower base fore-aft moment is influenced by diabatic turbulence and a rotor bending moment at the hub is influenced by diabatic wind profiles. The blade root loads are influenced by diabatic wind profiles and turbulence, which results in averaging of the loads, i.e. the calculated blade loads using diabatic wind conditions and those calculated using neutral wind conditions are approximately the same. The importance of obtaining a site-specific wind speed and stability distribution is also emphasized since it has a direct influence on wind turbine loads. In comparison with the IEC standards, which generalize the wind conditions according to certain classes of wind speeds, the site-specific wind conditions are demonstrated to give significantly lower fatigue loads. There is thus a potential in reducing wind turbine costs if site-specific wind conditions are obtained. In this regard we then are faced with measurement challenges. The current industry standard for the measurement of wind speed is either the cup or the sonic anemometer. Both instruments require a meteorological mast to be mounted at the measurement site. For measuring the wind profile the instruments need to be mounted at several heights on the mast. To install a mast and set up these instruments is quite expensive, especially at offshore sites, where the cost of foundation increases significantly. Besides, there are problems with the flow distortion that have to be taken care of. In order to overcome these problems it would be ideal to have a remote sensing instrument that measures wind speed. Wind lidars are capable of doing that albeit with a price. Part II of the thesis deals with detailed investigations of the ability of wind lidars to perform turulence measurements. Modelling of the systematic errors in turbulence measurements is carried out using basic principles. Two mechanisms are identified that cause these systematic errors. One is the averaging effect due to the large sample volume in which lidars measure wind speeds, and the other is the contribution of all components of the Reynolds stress tensor. Modelling of turbulence spectra as measured by a scanning pulsed wind lidar is also carried out. We now understand in detail the distribution of turbulent energy at various wavenumbers, when a pulsed wind lidar measures turbulence. The lidar turbulence models have been verified with the measurements at different heights and under different atmospheric stabilities. Finally, a new method is investigated that in principle makes turbulence measurements by lidars possible. The so-called six beam method uses six lidar beams to avoid the contamination by all components of the Reynolds stress tensor. The theoretical calculations carried out demonstrates the potential of this method. In order to avoid averaging due to volume sampling, a different analysis method is required, which has not been investigated in this thesis. To summarize the entire thesis, it can be said that more work is required to ascertain the influence of atmospheric stability on wind turbine loads. In particular, comparing with the load measurements will go a long way in consolidating the understanding gained from the analysis in this thesis. If lidars are able to measure turbulence, there is a tremendous potential for performing site-specific wind turbine design and making the class based design of the IEC standards obsolete.Wind EnergyAerospace Engineerin

On the possibility of using site data for offshore wind turbine design

Aerospace Engineerin

Atmospheric stability and wind profile climatology over the North Sea: Case study at Egmond aan Zee

The statistics of atmospheric stability and non-dimensional wind profiles are studied using the standard surface-layer theory at Egmond aan Zee in the North Sea. Measurements at 21, 70 and 116 m are used to validate the theoretical profiles. Charnock’s relation is used to estimate the sea surface roughness. Bulk Richardson number is used to estimate the Obukhov length. The measured sea water temperature has a positive bias of 0.82?C resulting in the dominance of unstable conditions and a poor agreement of the theoretical wind profiles with the measurements. The conditions at Egmond aan Zee are dominated by unstable and neutral stabilities. The theoretical wind profiles agree very well with the measurements in the unstable and neutral conditions. In stable conditions, the wind profiles are over-predicted significantly as the height increases. The scaling of the wind profile with respect to the boundary layer height is necessary under stable conditions and the addition of another length scale parameter is preferred.Aerodynamics, Wind Energy & PropulsionAerospace Engineerin

Offshore wind turbine design using site data

Aerospace Engineerin

ON A NEW SPECIES OF THE GENUS HEROGLYPHUS KRAUSS (ORTHOPTERA : ACRIDIIDAE) FROM INDIA

A new species Hieroglyphus kolhapurensis is reported and described for the first time from India. Female : 48 mm long, tegmina 32 mm long, 6 mm wide; hind wing 34 mm long, 10 mm wide; antenna brownish with yellow bands; ovipositor 9 mm long, upper lamellae 5 mm long and lower lamellae 4 pm long, anal cerci 4 mm long. Male ; 41.3 mm long, tegmina 26 mm long, 4 mm wide; hind wing 26.5 mm long; antenna 23 mm long, brownish with yellow bands

Nuclear transport of paxillin depends on focal adhesion dynamics and FAT domains

10.1242/jcs.172643Journal of Cell Science129101981-198

How good are remote sensors at measuring extreme winds?

This article describes some preliminary efforts within the SafeWind project, aimed to identify the possible added value of using wind lidars to detect extreme wind events. Exceptionally good performance is now regularly reported in the measurement of the mean wind speed with some wind lidars in flat terrain. For turbulence measurements, recent theoretical work has revealed that the components of the Reynolds stress tensor are subjected to significant spatial attenuation and contamination by the cross-components of the horizontal and vertical wind speed. Thus, with the conical scanning of the lidar and velocity azimuth display technique of processing data, precision turbulence measurements are not possible. But how faithfully do wind lidars measure extreme wind events? Our study uses mast and wind lidar data from a flat terrain site. The ZephIR is used as a continuous wave lidar and the WindCube as a pulsed lidar. The data analysis consists of cup-lidar comparisons of the mean wind speed, the maximum wind speed, probability distributions of the time difference of the maximum wind speed, and variation of the gust factors with mean wind speed and atmospheric stability. We examine to what degree each of the different instruments are able to detect extreme events, and attempt to identify the differences in the measurements of the extreme events between cups and lidars. The data analysis showed that both lidars are capable of measuring the maximum wind speed within a 10-min period up to an underestimation of about 10% with respect to the cup anemometer. The Windcube is capable of measuring the gust factor that is comparable to that of the cup anemometer, whereas the ZephIR always underestimates it. The conclusion is still speculative and more theoretical work is required to deduce firm conclusions.Wind EnergyAerospace Engineerin