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

Signal description by means of a local frequency spectrum

The description of a signal by means of a local frequency spec-trum resembles such things as the score in music, the phase space in mechanics, and the ray concept in geometrical optics. Two types of local frequency spectra are presented: the Wigner distribution function and the sliding-window spectrum, the latter having the form of a cross-ambiguity function. The Wigner distribution function in particular can provide a link between Fourier optics and geometrical optics; many properties of the Wigner distribution function, and the way in which it prop-agates through linear systems, can be interpreted in geometric-optical terms. The Wigner distribution function is linearly related to other signal representations like Woodward's ambiguity function, Rihaczek's complex energy density function, and Mark's physical spectrum. An advantage of the Wigner distribution function and its related signal representations is that they can be applied not only to deterministic signals but to stochastic signals as well, leading to such things as Walther's generalized radiance and Sudarshan's Wolf tensor. On the other hand, the sliding-window spectrum has the advantage that a sampling theorem can be formulated for it: the sliding-window spectrum is completely determined by its values at the points of a certain space-frequency lattice, which is exactly the lattice suggested by Gabor in 1946. The sliding-window spectrum thus leads naturally to Gabor's expansion of a signal into a discrete set of properly shifted and modulated versions of an elementary signal, which is again another space-frequency signal representation, and which is related to the degrees of freedom of the signal

Erbium-doped fiber laser tuning using two cascaded unbalanced Mach-Zehnder interferometers as intracavity filter: numerical analysis and experimental confirmation

We propose a new method for tuning an Er3+-doped continuous-wave fiber-ring laser. We present a novel numerical model and confirm the model with experimental results. The numerical model relies on the implementation of the analytical solution of signal propagation over small (elemental) segments of amplifier fiber rather than using the usual Runge-Kutta algorithm. The validity of the model is verified by the good agreement between computer results and experimental data. Experiments demonstrating a 11.2-nm wavelength tuning range have been conducted using an electrooptic intracavity filter composed of two cascaded unbalanced Mach-Zehnder interferometers (MZIs) integrated in lithium niobate, The numerical analysis shows that the tuning range obtained is limited by the combination of gain shape and filter characteristics. Increased tuning range can be obtained by decreasing losses or by using a more selective filter

Communicating with hyperchaos: The dynamics of a DNLF emitter and recovery of transmitted information

It is reported that signal encoding with high-dimensional chaos produced by delayed feedback systems with strong nonlinearity can be broken. The procedure is described and the method is illustrated with chaotic waveforms obtained from a strongly nonlinear optical system used by the authors previously to demonstrate signal encryption and decryption with wavelength chaos. The method can be extended to any systems ruled by nonlinear time-delayed differential equations

Cracking chaos-based encryption systems ruled by nonlinear time delay differential equations

We report that signal encoding with high-dimensional chaos produced by delayed feedback systems with a strong nonlinearity can be broken. We describe the procedure and illustrate the method with chaotic waveforms obtained from a strongly nonlinear optical system that we used previously to demonstrate signal encryption/decryption with chaos in wavelength. The method can be extended to any systems ruled by nonlinear time-delayed differential equations