Physics with the KLOE-2 experiment at the upgraded DAϕ\phiNE

Investigation at a $\phi$--factory can shed light on several debated issues in particle physics. We discuss: i) recent theoretical development and experimental progress in kaon physics relevant for the Standard Model tests in the flavor sector, ii) the sensitivity we can reach in probing CPT and Quantum Mechanics from time evolution of entangled kaon states, iii) the interest for improving on the present measurements of non-leptonic and radiative decays of kaons and eta/eta$^\prime$ mesons, iv) the contribution to understand the nature of light scalar mesons, and v) the opportunity to search for narrow di-lepton resonances suggested by recent models proposing a hidden dark-matter sector. We also report on the $e^+ e^-$ physics in the continuum with the measurements of (multi)hadronic cross sections and the study of gamma gamma processes.Comment: 60 pages, 41 figures; added affiliation for one of the authors; added reference to section

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

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

Biological production of liquid fuels from biomass. Annual report, September 1, 1978-August 31, 1979

The production of liquid fuels from renewable resources such as poplar wood and lignocellulosic wastes from a refuse hydropulper were studied. The particular scheme being studied involves the conversion of a cellulosic residue, resulting from a solvent delignified lignocellulosic feed, into either high concentration sugar syrups or into ethyl and/or butyl alcohol. The process is aimed at achieving total raw material utilization and maximization of high value by-product recovery. Specific goals of the investigation are the demonstration of the process technical feasibility and economic practicality and its optimization for maximum economic yield and efficiency. The construction of a pilot apparatus for solvent delignifying 150g samples of lignocellulosic feeds has been completed. Also, an analysis method for characterizing the delignified product has been selected and tested. Delignified samples are now being prepared and tested for their extent of delignification and susceptibility to enzyme hydrolysis

Biological production of organic solvents from cellulosic wastes. Progress report, September 15, 1976--September 14, 1977

The objectives of this project are to optimize a modular process to convert cellulosic wastes to butanol and other oil-sparing chemicals. Research to date has focused on developing analytical methods, establishing a good data base and improving cellulase yields. Reliable assay methods for the Thermoactinomyces cellulase complex have been developed, measuring glucose and reducing sugar from filter paper and Avicel for total cellulase activity, viscosity change with carboxymethyl cellulose for the endoglucanase activity, and fluorescence change with methylumbelliferyl-..beta..-D-glucopyranoside for ..beta..-glucosidase activity. Isoelectric focusing within the range pH 3.5 to 6.0 has proved to be a quick and useful means of determining effective cellulase complex composition. About 10 different proteins are present in the fermentation broth. Detailed procedures for uv and near uv plus 8-methoxy-psoralen mutagenesis have been developed, and four mutants having 50% greater activity than the parent YX strain have been isolated. Cellulase production by Thermoactinomyces is growth related and is maximum when growth stops at 12 to 16 hours with 1 to 5% Avicel at pH 7.0 to 7.2 and 55/sup 0/C. A multistage fermenter has been assembled for optimization of butanol versus acetone production by Cl. acetobutylicum. A preliminary economic assessment, currently indicating butanol at just above 30 cents/lb, is being continuously updated