New limits on the ordered moments in alpha-Pu and Ga-stabilized delta-Pu

We present the first muon spin relaxation measurements ever performed on elemental Pu, and set the most stringent upper limits to date on the magnitude of the ordered moment in alpha-Pu and delta-stabilized Pu (alloyed with 4.3 at. % Ga). Assuming a nominal hyperfine coupling field of 1 kOe per Bohr magneton we set an upper limit of 0.001 Bohr magnetons for both materials at T = 4 K.Comment: 4 pages, 3 figures. Submitted to 10th International Conference on Muon Spin Rotation, Relaxation and Resonance, Oxford, UK, August 200

Supermassive Binaries and Extragalactic Jets

Some quasars show Doppler shifted broad emission line peaks. I give new statistics of the occurrence of these peaks and show that, while the most spectacular cases are in quasars with strong radio jets inclined to the line of sight, they are also almost as common in radio-quiet quasars. Theories of the origin of the peaks are reviewed and it is argued that the displaced peaks are most likely produced by the supermassive binary model. The separations of the peaks in the 3C 390.3-type objects are consistent with orientation-dependent "unified models" of quasar activity. If the supermassive binary model is correct, all members of "the jet set" (astrophysical objects showing jets) could be binaries.Comment: 31 pages, PostScript, missing figure is in ApJ 464, L105 (see http://www.aas.org/ApJ/v464n2/5736/5736.html

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

Mutational analysis of TARDP in neurodegenerative diseases

Neurodegenerative diseases are often characterized by the presence of aggregates of misfolded proteins. TDP-43 is a major component of these aggregates in amyotrophic lateral sclerosis (ALS), but has also been observed in Alzheimer's (AD) and Parkinson's Diseases (PD). In addition, mutations in the TARDBP gene, encoding TDP-43, have been found to be a significant cause of familial ALS (FALS). All mutations, except for one, have been found in exon 6. To confirm this observation in ALS and to investigate whether TARDBP may play a role in the pathogenesis of AD and PD, we screened for mutations in exon 6 of the TARDBP gene in three cohorts composed of 376 AD, 463 PD (18% familial PD) and 376 ALS patients (50% FALS). We found mutations in 3c7% of FALS and 3c0.5% of sporadic ALS (SALS) patients, including two novel mutations, p.N352T and p.G384R. In contrast, we did not find TARDBP mutations in our cohort of AD and PD patients. These results suggest that mutations in TARDBP are not a significant cause of AD and PD

Paraoxonase gene mutations in amyotrophic lateral sclerosis

Three clustered, homologous paraoxonase genes (PON1, PON2, and PON3) have roles in preventing lipid oxidation and detoxifying organophosphates. Recent reports describe a genetic association between the PON genes and sporadic amyotrophic lateral sclerosis (ALS). We now report that in genomic DNA from individuals with familial and sporadic ALS, we have identified at least 7 PON gene mutations that are predicted to alter PON function