Marine04 marine radiocarbon age calibration, 0-26 cal kyr BP

New radiocarbon calibration curves, IntCal04 and Marine04, have been constructed and internationally ratified to replace the terrestrial and marine components of IntCal98. The new calibration data sets extend an additional 2000 yr, from 0-26 cal kyr BP (Before Present, 0 cal. BP = AD 1950), and provide much higher resolution, greater precision, and more detailed structure than IntCal98. For the Marine04 curve, dendrochronologically-dated tree-ring samples, converted with a box diffusion model to marine mixed-layer ages, cover the period from 0-10.5 call kyr BR Beyond 10.5 cal kyr BP, high-resolution marine data become available from foraminifera in varved sediments and U/Th-dated corals. The marine records are corrected with site-specific C-14 reservoir age information to provide a single global marine mixed-layer calibration from 10.5-26.0 cal kyr BR A substantial enhancement relative to IntCal98 is the introduction of a random walk model, which takes into account the uncertainty in both the calendar age and the C-14 age to calculate the underlying calibration curve (Buck and Blackwell, this issue). The marine data sets and calibration curve for marine samples from the surface mixed layer (Marine04) are discussed here. The tree-ring data sets, sources of uncertainty, and regional offsets are presented in detail in a companion paper by Reimer et al. (this issue).

IntCal04 terrestrial radiocarbon age calibration, 0-26 cal kyr BP

A new calibration curve for the conversion of radiocarbon ages to calibrated (cal) ages has been constructed and internationally ratified to replace ImCal98, which extended from 0-24 cal kyr BP (Before Present, 0 cal BP = AD 1950). The new calibration data set for terrestrial samples extends from 0-26 cal kyr BP, but with much higher resolution beyond 11.4 cal kyr BP than ImCal98. Dendrochronologically-dated tree-ring samples cover the period from 0-12.4 cal kyr BP. Beyond the end of the tree rings, data from marine records (corals and foraminifera) are converted to the atmospheric equivalent with a site-specific marine reservoir correction to provide terrestrial calibration from 12.4-26.0 cal kyr BP. A substantial enhancement relative to ImCal98 is the introduction of a coherent statistical approach based on a random walk model, which takes into account the uncertainty in both the calendar age and the C-14 age to calculate the underlying calibration curve (Buck and Blackwell, this issue). The tree-ring data sets, sources of uncertainty, and regional offsets are discussed here. The marine data sets and calibration curve for marine samples from the surface mixed layer (Marine 04) are discussed in brief, but details are presented in Hughen et al. (this issue a). We do not make a recommendation for calibration beyond 26 cal kyr BP at this time; however, potential calibration data sets are compared in another paper (van der Plicht et al., this issue).

Trapping of palindromic ligands within native transthyretin prevents amyloid formation

Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2’-(4,4’-(heptane 1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2’-(4,4’-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was confirmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis.

Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing

Age-related decline in the integrity of mitochondria is an important contributor to the human ageing process. In a number of ageing stem cell populations, this decline in mitochondrial function is due to clonal expansion of individual mitochondrial DNA (mtDNA) point mutations within single cells. However the dynamics of this process and when these mtDNA mutations occur initially are poorly understood. Using human colorectal epithelium as an exemplar tissue with a well-defined stem cell population, we analysed samples from 207 healthy participants aged 17-78 years using a combination of techniques (Random Mutation Capture, Next Generation Sequencing and mitochondrial enzyme histochemistry), and show that: 1) non-pathogenic mtDNA mutations are present from early embryogenesis or may be transmitted through the germline, whereas pathogenic mtDNA mutations are detected in the somatic cells, providing evidence for purifying selection in humans, 2) pathogenic mtDNA mutations are present from early adulthood (<20 years of age), at both low levels and as clonal expansions, 3) low level mtDNA mutation frequency does not change significantly with age, suggesting that mtDNA mutation rate does not increase significantly with age, and 4) clonally expanded mtDNA mutations increase dramatically with age. These data confirm that clonal expansion of mtDNA mutations, some of which are generated very early in life, is the major driving force behind the mitochondrial dysfunction associated with ageing of the human colorectal epithelium.

Mesomorphic behaviour in copoly(ester-imide)s of poly(butylene-2,6-naphthalate) (PBN)

Copolycondensation of N,N’-bis(4-hydroxybutyl)-biphenyl-3,4,3',4'-tetracarboxylic diimide at 20 and 25 mol% with bis(4-hydroxybutyl)-2,6-naphthalate produces PBN-based copoly(ester-imide)s that not only crystallise but also form a (smectic) mesophase upon cooling from the melt. Incorporation of 25 mol% imide in PBN causes the glass transition temperature (measured by DSC) to rise from 51 to 74 °C, a significant increase relative to PBN. Furthermore, increased storage- (G'), loss- (G'') and elastic (E) moduli are observed for both copoly(ester-imide)s when compared to PBN itself. Structural analysis of the 20 mol% copolymer by X-ray powder and fibre diffraction, interfaced to computational modelling, suggests a crystal structure related to that of α-PBN, in space group P-1, with cell dimensions a = 4.74, b = 6.38, c = 14.45 Å, α = 106.1, β = 122.1, γ = 97.3°, ρ = 1.37 g cm-3.

The COnvective Precipitation Experiment (COPE): investigating the origins of heavy precipitation in the southwestern UK

A recent field campaign in southwest England used numerical modeling integrated with aircraft and radar observations to investigate the dynamic and microphysical interactions that can result in heavy convective precipitation. The COnvective Precipitation Experiment (COPE) was a joint UK-US field campaign held during the summer of 2013 in the southwest peninsula of England, designed to study convective clouds that produce heavy rain leading to flash floods. The clouds form along convergence lines that develop regularly due to the topography. Major flash floods have occurred in the past, most famously at Boscastle in 2004. It has been suggested that much of the rain was produced by warm rain processes, similar to some flash floods that have occurred in the US. The overarching goal of COPE is to improve quantitative convective precipitation forecasting by understanding the interactions of the cloud microphysics and dynamics and thereby to improve NWP model skill for forecasts of flash floods. Two research aircraft, the University of Wyoming King Air and the UK BAe 146, obtained detailed in situ and remote sensing measurements in, around, and below storms on several days. A new fast-scanning X-band dual-polarization Doppler radar made 360-deg volume scans over 10 elevation angles approximately every 5 minutes, and was augmented by two UK Met Office C-band radars and the Chilbolton S-band radar. Detailed aerosol measurements were made on the aircraft and on the ground. This paper: (i) provides an overview of the COPE field campaign and the resulting dataset; (ii) presents examples of heavy convective rainfall in clouds containing ice and also in relatively shallow clouds through the warm rain process alone; and (iii) explains how COPE data will be used to improve high-resolution NWP models for operational use.