Mining metrics for buried treasure

The same but different: That might describe two metrics. On the surface CLASSI may show two metrics are locally equivalent, but buried beneath one may be a wealth of further structure. This was beautifully described in a paper by M.A.H. MacCallum in 1998. Here I will illustrate the effect with two flat metrics -- one describing ordinary Minkowski spacetime and the other describing a three-parameter family of Gal'tsov-Letelier-Tod spacetimes. I will dig out the beautiful hidden classical singularity structure of the latter (a structure first noticed by Tod in 1994) and then show how quantum considerations can illuminate the riches. I will then discuss how quantum structure can help us understand classical singularities and metric parameters in a variety of exact solutions mined from the Exact Solutions book.Comment: 16 pages, no figures, minor grammatical changes, submitted to Proceedings of the Malcolm@60 Conference (London, July 2004

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

Glycosylphosphatidylinositol-anchored proteases of Candida albicans target proteins necessary for both cellular processes and host-pathogen interactions.

Intracellular and secreted proteases fulfill multiple functions in microorganisms. In pathogenic microorganisms extracellular proteases may be adapted to interactions with host cells. Here we describe two cell surface-associated aspartic proteases, Sap9 and Sap10, which have structural similarities to yapsins of Saccharomyces cerevisiae and are produced by the human pathogenic yeast Candida albicans. Sap9 and Sap10 are glycosylphosphatidylinositol-anchored and located in the cell membrane or the cell wall. Both proteases are glycosylated, cleave at dibasic or basic processing sites similar to yapsins and Kex2-like proteases, and have functions in cell surface integrity and cell separation during budding. Overexpression of SAP9 in mutants lacking KEX2 or SAP10, or of SAP10 in mutants lacking KEX2 or SAP9, only partially restored these phenotypes, suggesting distinct target proteins of fungal origin for each of the three proteases. In addition, deletion of SAP9 and SAP10 modified the adhesion properties of C. albicans to epithelial cells and caused attenuated epithelial cell damage during experimental oral infection suggesting a unique role for these proteases in both cellular processes and host-pathogen interactions

Insight on polymer electrolytes for electrochemical devices applications

Polymer electrolytes (PEs) are of much attention as potential electrolytes of great technological relevance for solid-state electrochemistry, in particular for their possible practical application in devices such as batteries, supercapacitors, fuel cells, smart windows, sensors, and solar cells, among others. Generically, solid polymer electrolytes (SPEs) are mixtures of salts with basic polymers, such as poly(ethylene oxide) (PEO) or poly(ethylene imine) (PEI). However, there are also other polymers used as matrices for ionic conduction, like poly(vinyl alcohol) (PVA), poly(vinylidene fluoride) (PVDF), or natural macromolecules. A brief description of theoretical aspects of different PEs and past and recent trends in development of these materials are presented in this chapter. SPEs have many advantages including high energy density, no risk of leakage, no deleterious issues related to the presence of solvent, wide electrochemical stability window, simplified processability, and light weight. Some examples of prototypes of electrochromic device (ECD), batteries, supercapacitors, fuel cells, sensors, dye sensitized solar cells (DSSCs), and light emitting electrochemical cells are also presented and discussed in scope of this contribution.- (undefined