Thermal correction to the Casimir force, radiative heat transfer, and an experiment

The low-temperature asymptotic expressions for the Casimir interaction between two real metals described by Leontovich surface impedance are obtained in the framework of thermal quantum field theory. It is shown that the Casimir entropy computed using the impedance of infrared optics vanishes in the limit of zero temperature. By contrast, the Casimir entropy computed using the impedance of the Drude model attains at zero temperature a positive value which depends on the parameters of a system, i.e., the Nernst heat theorem is violated. Thus, the impedance of infrared optics withstands the thermodynamic test, whereas the impedance of the Drude model does not. We also perform a phenomenological analysis of the thermal Casimir force and of the radiative heat transfer through a vacuum gap between real metal plates. The characterization of a metal by means of the Leontovich impedance of the Drude model is shown to be inconsistent with experiment at separations of a few hundred nanometers. A modification of the impedance of infrared optics is suggested taking into account relaxation processes. The power of radiative heat transfer predicted from this impedance is several times less than previous predictions due to different contributions from the transverse electric evanescent waves. The physical meaning of low frequencies in the Lifshitz formula is discussed. It is concluded that new measurements of radiative heat transfer are required to find out the adequate description of a metal in the theory of electromagnetic fluctuations.Comment: 19 pages, 4 figures. svjour.cls is used, to appear in Eur. Phys. J.

Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism

1,5-anhydroglucitol (1,5-AG) is a biomarker of hyperglycemic excursions associated with diabetic complications. Because of its structural similarity to glucose, genetic studies of 1,5-AG can deliver complementary insights into glucose metabolism. We conducted genome-wide association studies of serum 1,5-AG concentrations in 7,550 European ancestry (EA) and 2,030 African American participants (AA) free of diagnosed diabetes from the ARIC Study. Seven loci in/near EFNA1/SLC50A1, MCM6/LCT, SI, MGAM, MGAM2, SLC5A10, and SLC5A1 showed genome-wide significant associations (P < 5 × 10-8) among EA participants, five of which were novel. Six of the seven loci were successfully replicated in 8,790 independent EA individuals, and MCM6/LCT and SLC5A10 were also associated among AA. Most of 1,5-AG-associated index SNPs were not associated with the clinical glycemic markers fasting glucose or theHbA1c, and vice versa. Only the index variant in SLC5A1 showed a significant association with fasting glucose in the expected opposing direction. Products of genes in all 1,5-AG-associated loci have known roles in carbohydrate digestion and enteral or renal glucose transport, suggesting that genetic variants associated with 1,5-AG influence its concentration via effects on glucose metabolism and handling

Genome-wide association study of serum fructosamine and glycated albumin in adults without diagnosed diabetes: Results from the atherosclerosis risk in communities study

Fructosamine and glycated albumin are potentially useful alternatives to hemoglobin A1c (HbA1c) as diabetes biomarkers. The genetic determinants of fructosamine and glycated albumin, however, are unknown. We performed genome-wide association studies of fructosamine and glycated albumin among 2,104 black and 7,647 white participants without diabetes in the Atherosclerosis Risk in Communities (ARIC) Study and replicated findings in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Among whites, rs34459162, a novel missense single nucleotide polymorphism (SNP) in RCN3, was associated with fructosamine (P = 5.3 3 1029) and rs1260236, a known diabetes-related missense mutation in GCKR, was associated with percent glycated albumin (P = 5.9 3 1029) and replicated in CARDIA. We also found two novel associations among blacks: an intergenic SNP, rs2438321, associated with fructosamine (P = 6.2 3 1029), and an intronic variant in PRKCA, rs59443763, associated with percent glycated albumin (P = 4.1 3 1029), but these results did not replicate. Few established fasting glucose or HbA1c SNPs were also associated with fructosamine or glycated albumin. Overall, we found genetic variants associated with the glycemic information captured by fructosamine and glycated albumin as well as with their nonglycemic component. This highlights the importance of examining the genetics of hyperglycemia biomarkers to understand the information they capture, including potential glucose-independent factors

SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

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

Distributions of branched GDGTs in soils and lake sediments from western Uganda: Implications for a lacustrine paleothermometer

Bacterially produced branched glycerol dialkyl glycerol tetraethers (GDGTs) are ubiquitous in soils and lake sediments and can potentially be used to reconstruct past temperatures. In lakes, however, it is still unclear if these compounds are derived from eroded soils or if they are produced in situ. To better understand environmental controls on the distributions of these compounds and the sources of branched GDGTs to lake sediments, we compare branched GDGT distributions and concentrations in lake sediments and catchment soils within a 3600 m altitudinal transect in western Uganda. Reconstructed mean annual air temperature (MAAT), determined from the degree of methylation (MBT) and cyclisation (CBT) of branched GDGTs in soils, decreases with increasing altitude, as is expected from the air temperature gradient in our transect. However, we observe significant offsets between observed and reconstructed temperatures in soils from wet, high elevation soils but not in most dry, low elevation soils. Branched GDGT distributions differ significantly between lake sediments and soils at all elevations, with greater differences at low elevations than at high elevations. These data support previous hypotheses that branched GDGTs are produced in situ in lakes and suggest that the abundance of water in soil environments may play a role in controlling the distribution of branched GDGTs. While branched GDGTs in lacustrine sediments can be used to reconstruct temporal temperature variations in lakes, we urge caution in utilizing this proxy in lacustrine systems with high soil loadings, especially if there is evidence of changing clastic fluxes through time

Seasonal variability of branched glycerol dialkyl glycerol tetraethers (brGDGTs) in a temperate lake system

Quantitative climate reconstructions are crucial for understanding the magnitude of and mechanisms behind natural and anthropogenic climate change, yet there are few proxies that can reliably reconstruct terrestrial temperature. Branched glycerol dialkyl glycerol tetraethers (brGDGTs) are bacterial membrane lipids that are increasingly used to reconstruct paleotemperature from lake sediments, but despite their potential, we have a poor understanding of (1) autochthonous vs. allochthonous sources of brGDGTs in lakes and (2) the seasonality of and environmental controls on brGDGT production within lakes. To investigate these factors, we examined water column suspended particulate matter (SPM) and settling particles from a sediment trap collected on a biweekly to monthly basis over a period of three years at Lower King Pond, a small kettle lake in northern Vermont, USA. We also compared the concentration and fractional abundances of brGDGTs in SPM and settling particles with those of catchment soils, river sediments, and lake surface sediments to constrain the relative importance of brGDGTs derived from the landscape versus brGDGTs produced within the lake itself. We find significant differences in concentrations and fractional abundances of brGDGTs between soil and river sediment samples from the catchment and lake sediments, indicating a mostly autochthonous source for lacustrine brGDGTs. BrGDGT concentrations, fluxes, and fractional abundances in SPM vary over the annual cycle, indicating that brGDGTs are produced throughout the year and respond to changes within the water column. The total annual flux of brGDGTs settling through the water column is comparable to the brGDGT accumulation rates in surface sediments, indicating that in this lake brGDGTs are mostly produced within the water column, not in the sediment itself. While brGDGTs are produced in all seasons within the water column, the flux to the sediments is highest during periods of spring and fall isothermal mixing, potentially biasing paleotemperature reconstructions towards mixing season temperature. Because the seasonal timing and frequency of lake mixing varies as a function of regional climate, lacustrine brGDGT calibrations should be regional in nature and comprise lakes with similar mixing regimes

Distributions of 5- and 6-methyl branched glycerol dialkyl glycerol tetraethers (brGDGTs) in East African lake sediment: Effects of temperature, pH, and new lacustrine paleotemperature calibrations

The distribution of branched glycerol dialkyl glycerol tetraethers (brGDGTs) in soils, peats, and lake sedimentshas been shown to correlate with mean annual air temperature (MAAT) and has provided valuablenew climate reconstructions. Here we use an improved chromatographic method to quantify the fractionalabundances of 5- and 6-methyl isomers in surface sediments from 65 East African lakes spanningtemperatures 1.6–26.8 °C, and investigate the relationships between these fractional abundances andtemperature, lake pH, and other environmental variables. We find that temperature exerts a strong controlon brGDGT distributions, including the relative abundances of 5- and 6-methyl isomers, whereasother environmental variables, including lake pH, are weakly correlated to the fractional abundancesof the brGDGTs. The distributions of brGDGTs in our lake sediments differ from those of soils and peats,leading to temperature offsets if soil- and peat-based brGDGT temperature calibrations are applied. Wedevelop new calibrations for MAAT for use in lake sediment based upon the MBT05Me and Index 1 ratios,as well as a multivariate regression of brGDGT fractional abundances on temperature using stepwiseforward selection. We obtain root mean square errors (RMSE) between ? 2.1 and 2.5 °C for these calibrations,highlighting the potential for brGDGTs to provide precise temperature reconstructions using lakesediment cores. Calibrations for lake pH perform more poorly, likely due to weak correlations betweenpH and brGDGT distributions in East African lakes. These results indicate that quantification of 5- and6-methyl isomers separately in lake sediment can improve paleoclimatic reconstructions