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

Wavelength dependence of switching contrast ratio of semiconductor optical amplifier-based nonlinear loop mirror

The authors report that the contrast ratio in a semiconductor optical amplifier-based nonlinear loop mirror may be improved by an appropriate choice of operating wavelength to minimise amplitude modulation. Contrast ratios as high as 21 dB for 1590 nm pulses are measured

All-optical clock division at 10 and 20 GHz in a semiconductor optical amplifier based nonlinear loop mirror

Spontaneous all-optical clock division at 10 and 20 GHz is reported. This is achieved using a semiconductor optical amplifier based nonlinear loop mirror arrangement in which the reflected pulses are fed back as switching pulses

Temporal evolution of amplitude restoration and thresholding in an all-optical regenerative memory

In this paper, we experimentally measure the temporal evolution of amplitude restoration and thresholding in an all-optical regenerative memory. The memory architecture comprises two coupled all-optical switching gates and different wavelength optical pulses are used for clock and data sources. The all-optical gates are nonlinear interferometers incorporating semiconductor optical amplifiers as the nonlinear optical material. The concatenated response of these nonlinear interferometers provides the required square top transmission function that allows the stored optical pulses to be equalized in amplitude. The edge of the transmission function forms the threshold for pulse storage in the memory. We input a variable amplitude data packet into the memory and record the temporal evolution of the pulses with a fast real-time digitizing oscilloscope. Complete amplitude restoration of the pulses occurs after ∼5 circulations of the optical fibre memory loop. This measurement is in good agreement with the theoretical prediction and indicates that the square top transmission response could also be achieved for data ‚on the fly' with a linear concatenation of only a few all-optical switching gates

Semiconductor optical amplifier based nonlinear optical loop mirror with feedback: two modes of operation at high switching rates

We describe the operating conditions under which a semiconductor optical amplifier based nonlinear loop mirror with optical feedback can have two stable modes of operation at switching rates faster than the gain recovery rate of the semiconductor optical amplifier. It can act either as an all-optical circulating shift register with inverter or as an all-optical clock divider, depending on the relative timing of the switching pulses

All-optical clock division at 40 GHz using semiconductor optical amplifier based nonlinear interferometer

All-optical clock division of a 40 GHz pulse train is demonstrated, using a semiconductor optical amplifier based nonlinear interferometer with feedback. The dynamical evolution of the clock divided train is also observed

Nonlinear optics for high-speed digital information processing

Recent advances in developing nonlinear optical techniques for processing serial digital information at high speed are reviewed. The field has been transformed by the advent of semiconductor nonlinear devices capable of operation at 100 gigabits per second and higher, well beyond the current speed limits of commercial electronics. These devices are expected to become important in future high-capacity communications networks by allowing digital regeneration and other processing functions to be performed on data signals “on the fly” in the optical domain

10 Gbit/s all-optical regenerative memory using single SOA-based logic gate

The authors report an all-optical regenerative memory operating at 10 Gbit/s using a semiconductor optical amplifier-based interferometer as a regenerator in an optical fibre loop. Error-free operation was measured after more than 30 000 circulations of the stored dat