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Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
A novel common variant in DCST2 is associated with length in early life and height in adulthood
(2015)
Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 x 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; beta = 0.046, SE = 0.008, P = 2.46 x 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 x 10(-4)) and adult height (N = 127 513; P = 1.45 x 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
Saturn’s main ring system is associated with a set of small moons that either are embedded within it or interact with the rings to alter their shape and composition. Five close flybys of the moons Pan, Daphnis, Atlas, Pandora, and Epimetheus were performed between December 2016 and April 2017 during the ring-grazing orbits of the Cassini mission. Data on the moons’ morphology, structure, particle environment, and composition were returned, along with images in the ultraviolet and thermal infrared. We find that the optical properties of the moons’ surfaces are determined by two competing processes: contamination by a red material formed in Saturn’s main ring system and accretion of bright icy particles or water vapor from volcanic plumes originating on the moon Enceladus.
Giant planets helped to shape the conditions we see in the Solar System today and they account for more than 99% of the mass of the Sun's planetary system. They can be subdivided into the Ice Giants (Uranus and Neptune) and the Gas Giants (Jupiter and Saturn), which differ from each other in a number of fundamental ways. Uranus, in particular is the most challenging to our understanding of planetary formation and evolution, with its large obliquity, low self-luminosity, highly asymmetrical internal field, and puzzling internal structure. Uranus also has a rich planetary system consisting of a system of inner natural satellites and complex ring system, five major natural icy satellites, a system of irregular moons with varied dynamical histories, and a highly asymmetrical magnetosphere. Voyager 2 is the only spacecraft to have explored Uranus, with a flyby in 1986, and no mission is currently planned to this enigmatic system. However, a mission to the uranian system would open a new window on the origin and evolution of the Solar System and would provide crucial information on a wide variety of physicochemical processes in our Solar System. These have clear implications for understanding exoplanetary systems. In this paper we describe the science case for an orbital mission to Uranus with an atmospheric entry probe to sample the composition and atmospheric physics in Uranus' atmosphere. The characteristics of such an orbiter and a strawman scientific payload are described and we discuss the technical challenges for such a mission. This paper is based on a white paper submitted to the European Space Agency's call for science themes for its large-class mission programme in 2013.
The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using gamma-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant gamma-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section <sigma nu >. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach <sigma nu > values of 6 x 10(-26) cm(3) s(-1) in the W+W- channel for a DM particle mass of 1.5 TeV, and 2 x 10(-26) cm(3) s(-1) in the tau(+)tau(-) channel for a 1 TeV mass. For the first time, ground-based gamma-ray observations have reached sufficient sensitivity to probe <sigma nu > values expected from the thermal relic density for TeV DM particles.
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P< 5 x 10(-8). In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 Â 10 À8 . In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
Myriapods (e. g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.
The new sediment record from the deep Dead Sea basin (ICDP core 5017-1) provides a unique archive for hydroclimatic variability in the Levant. Here, we present high-resolution sediment facies analysis and elemental composition by micro-X-ray fluorescence (mu XRF) scanning of core 5017-1 to trace lake levels and responses of the regional hydroclimatology during the time interval from ca. 117 to 75 ka, i. e. the transition between the last interglacial and the onset of the last glaciation. We distinguished six major micro-facies types and interpreted these and their alterations in the core in terms of relative lake level changes. The two end-member facies for highest and lowest lake levels are (a) up to several metres thick, greenish sediments of alternating aragonite and detrital marl laminae (aad) and (b) thick halite facies, respectively. Intermediate lake levels are characterised by detrital marls with varying amounts of aragonite, gypsum or halite, reflecting lower-amplitude, shorter-term variability. Two intervals of pronounced lake level drops occurred at similar to 110-108 +/- 5 and similar to 93-87 +/- 7 ka. They likely coincide with stadial conditions in the central Mediterranean (Melisey I and II pollen zones in Monticchio) and low global sea levels during Marine Isotope Stage (MIS) 5d and 5b. However, our data do not support the current hypothesis of an almost complete desiccation of the Dead Sea during the earlier of these lake level low stands based on a recovered gravel layer. Based on new petrographic analyses, we propose that, although it was a low stand, this well-sorted gravel layer may be a vestige of a thick turbidite that has been washed out during drilling rather than an in situ beach deposit. Two intervals of higher lake stands at similar to 108-93 +/- 6 and similar to 87-75 +/- 7 ka correspond to interstadial conditions in the central Mediterranean, i. e. pollen zones St. Germain I and II in Monticchio, and Greenland interstadials (GI) 24+23 and 21 in Greenland, as well as to sapropels S4 and S3 in the Mediterranean Sea. These apparent correlations suggest a close link of the climate in the Levant to North Atlantic and Mediterranean climates during the time of the build-up of Northern Hemisphere ice shields in the early last glacial period.
In July 2004 the Cassini–Huygens mission reached the Saturnian system and started its orbital tour. A total of 75 orbits will be carried out during the primary mission until August 2008. In these four years Cassini crosses the ring plane 150 times and spends approx. 400 h within Titan's orbit. The Cosmic Dust Analyser (CDA) onboard Cassini characterises the dust environment with its extended E ring and embedded moons. Here, we focus on the CDA results of the first year and we present the Dust Analyser (DA) data within Titan's orbit. This paper does investigate High Rate Detector data and dust composition measurements. The authors focus on the analysis of impact rates, which were strongly variable primarily due to changes of the spacecraft pointing. An overview is given about the ring plane crossings and the DA counter measurements. The DA dust impact rates are compared with the DA boresight configuration around all ring plane crossings between June 2004 and July 2005. Dust impacts were registered at altitudes as high as 100 000 km above the ring plane at distances from Saturn between 4 and 10 Saturn radii. In those regions the dust density of particles bigger than 0.5 can reach values of 0.001m-3.
The role that climate and environmental history may have played in influencing human evolution has been the focus of considerable interest and controversy among paleoanthropologists for decades. Prior attempts to understand the environmental history side of this equation have centered around the study of outcrop sediments and fossils adjacent to where fossil hominins (ancestors or close relatives of modern humans) are found, or from the study of deep sea drill cores. However, outcrop sediments are often highly weathered and thus are unsuitable for some types of paleoclimatic records, and deep sea core records come from long distances away from the actual fossil and stone tool remains. The Hominin Sites and Paleolakes Drilling Project (HSPDP) was developed to address these issues. The project has focused its efforts on the eastern African Rift Valley, where much of the evidence for early hominins has been recovered. We have collected about 2 km of sediment drill core from six basins in Kenya and Ethiopia, in lake deposits immediately adjacent to important fossil hominin and archaeological sites. Collectively these cores cover in time many of the key transitions and critical intervals in human evolutionary history over the last 4 Ma, such as the earliest stone tools, the origin of our own genus Homo, and the earliest anatomically modern Homo sapiens. Here we document the initial field, physical property, and core description results of the 2012-2014 HSPDP coring campaign.
The role that climate and environmental history may have played in influencing human evolution has been the focus of considerable interest and controversy among paleoanthropologists for decades. Prior attempts to understand the environmental history side of this equation have centered around the study of outcrop sediments and fossils adjacent to where fossil hominins (ancestors or close relatives of modern humans) are found, or from the study of deep sea drill cores. However, outcrop sediments are often highly weathered and thus are unsuitable for some types of paleoclimatic records, and deep sea core records come from long distances away from the actual fossil and stone tool remains. The Hominin Sites and Paleolakes Drilling Project (HSPDP) was developed to address these issues. The project has focused its efforts on the eastern African Rift Valley, where much of the evidence for early hominins has been recovered. We have collected about 2 km of sediment drill core from six basins in Kenya and Ethiopia, in lake deposits immediately adjacent to important fossil hominin and archaeological sites. Collectively these cores cover in time many of the key transitions and critical intervals in human evolutionary history over the last 4 Ma, such as the earliest stone tools, the origin of our own genus Homo, and the earliest anatomically modern Homo sapiens. Here we document the initial field, physical property, and core description results of the 2012-2014 HSPDP coring campaign.
Ice-rich yedoma-dominated landscapes store considerable amounts of organic carbon (C) and nitrogen (N) and are vulnerable to degradation under climate warming. We investigate the C and N pools in two thermokarst-affected yedoma landscapes - on Sobo-Sise Island and on Bykovsky Peninsula in the north of eastern Siberia. Soil cores up to 3m depth were collected along geomorphic gradients and analysed for organic C and N contents. A high vertical sampling density in the profiles allowed the calculation of C and N stocks for short soil column intervals and enhanced understanding of within-core parameter variability. Profile-level C and N stocks were scaled to the landscape level based on landform classifications from 5 m resolution, multispectral RapidEye satellite imagery. Mean landscape C and N storage in the first metre of soil for Sobo-Sise Island is estimated to be 20.2 kg C m(-2) and 1.8 kg N m(-2) and for Bykovsky Peninsula 25.9 kg C m(-2) and 2.2 kg N m(-2). Radiocarbon dating demonstrates the Holocene age of thermokarst basin deposits but also suggests the presence of thick Holoceneage cover layers which can reach up to 2 m on top of intact yedoma landforms. Reconstructed sedimentation rates of 0.10-0.57 mm yr(-1) suggest sustained mineral soil accumulation across all investigated landforms. Both yedoma and thermokarst landforms are characterized by limited accumulation of organic soil layers (peat). We further estimate that an active layer deepening of about 100 cm will increase organic C availability in a seasonally thawed state in the two study areas by similar to 5.8 Tg (13.2 kg C m(-2)). Our study demonstrates the importance of increasing the number of C and N storage inventories in ice-rich yedoma and thermokarst environments in order to account for high variability of permafrost and thermokarst environments in pan-permafrost soil C and N pool estimates.
Ice-rich yedoma-dominated landscapes store con-
siderable amounts of organic carbon (C) and nitrogen (N)
and are vulnerable to degradation under climate warming.
We investigate the C and N pools in two thermokarst-affected
yedoma landscapes – on Sobo-Sise Island and on Bykovsky
Peninsula in the north of eastern Siberia. Soil cores up to 3 m
depth were collected along geomorphic gradients and anal-
ysed for organic C and N contents. A high vertical sampling
density in the profiles allowed the calculation of C and N
stocks for short soil column intervals and enhanced under-
standing of within-core parameter variability. Profile-level C
and N stocks were scaled to the landscape level based on
landform classifications from 5 m resolution, multispectral
RapidEye satellite imagery. Mean landscape C and N storage
in the first metre of soil for Sobo-Sise Island is estimated to
be 20.2 kg C m −2 and 1.8 kg N m −2 and for Bykovsky Penin-
sula 25.9 kg C m −2 and 2.2 kg N m −2 . Radiocarbon dating
demonstrates the Holocene age of thermokarst basin de-
posits but also suggests the presence of thick Holocene-
age cover layers which can reach up to 2 m on top of in-
tact yedoma landforms. Reconstructed sedimentation rates
of 0.10–0.57 mm yr −1 suggest sustained mineral soil accu-
mulation across all investigated landforms. Both yedoma and
thermokarst landforms are characterized by limited accumu-
lation of organic soil layers (peat).
We further estimate that an active layer deepening of
about 100 cm will increase organic C availability in a sea-
sonally thawed state in the two study areas by ∼ 5.8 Tg
(13.2 kg C m −2 ). Our study demonstrates the importance of
increasing the number of C and N storage inventories in ice-
rich yedoma and thermokarst environments in order to ac-
count for high variability of permafrost and thermokarst en-
vironments in pan-permafrost soil C and N pool estimates.
Xanthohumol (XN) is the principal prenylated flavonoid of the hop plant and has recently gained considerable interest due to its potential cancer-chemopreventive effects. However, the metabolism of XN has not yet been investigated in detail. Therefore, we studied the in vitro phase 11 metabolism of XN using nine human recombinant UDP- glucuronosyltransferases (UGT) and five sulfotransferases (SULT). The identification of the metabolites formed was elucidated using HPLC with diode array detection as well as HPLC/API-ES MS. XN was efficiently glucuronidated by UGT 1A8, 1A9, and 1A10; further important UGTs were UGT 1A1, 1A7, and 2B7. With respect to the sulfation reaction, SULT 1A1*2, 1A2, and 1E1 were the most active SULT forms. UGT 1A3, 1A4, and 1A6 as well as SULT 1A3 and 2A1 were of minor importance for the conjugation of XN. Three mono-glucuronides as well as three mono-sulfates were identified. Considering the tissue distribution of the tested UGT and SULT enzyme forms, these findings suggest a prominent role for the glucuronidation and sulfation of XN in the liver as well as in the gastrointestinal tract
Context:
Massive binaries play a crucial role in the Universe. Knowing the distributions of their orbital parameters is important for a wide range of topics from stellar feedback to binary evolution channels and from the distribution of supernova types to gravitational wave progenitors, yet no direct measurements exist outside the Milky Way.
Aims:
The Tarantula Massive Binary Monitoring project was designed to help fill this gap by obtaining multi-epoch radial velocity (RV) monitoring of 102 massive binaries in the 30 Doradus region.
Methods:
In this paper we analyze 32 FLAMES/GIRAFFE observations of 93 O- and 7 B-type binaries. We performed a Fourier analysis and obtained orbital solutions for 82 systems: 51 single-lined (SB1) and 31 double-lined (SB2) spectroscopic binaries.
Results:
Overall, the binary fraction and orbital properties across the 30 Doradus region are found to be similar to existing Galactic samples. This indicates that within these domains environmental effects are of second order in shaping the properties of massive binary systems. A small difference is found in the distribution of orbital periods, which is slightly flatter (in log space) in 30 Doradus than in the Galaxy, although this may be compatible within error estimates and differences in the fitting methodology. Also, orbital periods in 30 Doradus can be as short as 1.1 d, somewhat shorter than seen in Galactic samples. Equal mass binaries (q> 0.95) in 30 Doradus are all found outside NGC 2070, the central association that surrounds R136a, the very young and massive cluster at 30 Doradus’s core. Most of the differences, albeit small, are compatible with expectations from binary evolution. One outstanding exception, however, is the fact that earlier spectral types (O2–O7) tend to have shorter orbital periods than later spectral types (O9.2–O9.7).
Conclusions:
Our results point to a relative universality of the incidence rate of massive binaries and their orbital properties in the metallicity range from solar (Z⊙) to about half solar. This provides the first direct constraints on massive binary properties in massive star-forming galaxies at the Universe’s peak of star formation at redshifts z ~ 1 to 2 which are estimated to have Z ~ 0.5 Z⊙.
New aromatic poly(amide-ether)s (II) have been synthesized by solution polycondensation of various aromatic diamines having two ether bridges (I) with a diacid chloride containing silicon, namely bis(chlorocarbonylphenyl)- diphenyIsilane. These polymers are easy soluble in polar amidic solvents such as N-methylpyrrolidinone or dimethylformamide and can be cast into thin flexible films or coatings from such solutions. They show high thermal stability with initial decomposition temperature being above 400 °C. Their glass transition temperatures lie in the range of 220-250 °C, except for polymer He which did not show a clear Tg when heated in a differential scanning calorimetry experiment up to 300 °C. The large interval between the glass transition and decomposition temperatures of pnlymers Ia-Id could be advantageous for their processing via compression molding. The polymer coatings deposited by the spincoating, technique onto silicon wafers showed a very smooth, pinhole-free surface in atomic force microscopy investigations. The free-standing films of 20-30 mm thickness show low dielectric constant, in the range of 3.65-3.78, which is promising for future application as high performance dielectrics.
"Hastite", the orthorhombic dimorph of CoSe2, formerly considered as a valid mineral species occurring in the Trogtal quarries, Harz Mountains, Germany, is discredited as being identical with ferroselite, orthorhombic FeSe2. The discreditation has been unanimously approved by the IMA Commission on New Minerals, Nomenclature and Classification (CNMNC) (IMA No. 07-E). We also provide observations on the composition, homogeneity, and origin of trogtalite (cubic CoSe2) from its type locality.
The Stardust mission returned cometary, interplanetary and (probably) interstellar dust in 2006 to Earth that have been analysed in Earth laboratories worldwide. Results of this mission have changed our view and knowledge on the early solar nebula. The Rosetta mission is on its way to land on comet 67P/Churyumov-Gerasimenko and will investigate for the first time in great detail the comet nucleus and its environment starting in 2014. Additional astronomy and planetary space missions will further contribute to our understanding of dust generation, evolution and destruction in interstellar and interplanetary space and provide constraints on solar system formation and processes that led to the origin of life on Earth. One of these missions, SARIM-PLUS, will provide a unique perspective by measuring interplanetary and interstellar dust with high accuracy and sensitivity in our inner solar system between 1 and 2 AU. SARIM-PLUS employs latest in-situ techniques for a full characterisation of individual micrometeoroids (flux, mass, charge, trajectory, composition()) and collects and returns these samples to Earth for a detailed analysis. The opportunity to visit again the target comet of the Rosetta mission 67P/Churyumov-Gerasimeenternko, and to investigate its dusty environment six years after Rosetta with complementary methods is unique and strongly enhances and supports the scientific exploration of this target and the entire Rosetta mission. Launch opportunities are in 2020 with a backup window starting early 2026. The comet encounter occurs in September 2021 and the reentry takes place in early 2024. An encounter speed of 6 km/s ensures comparable results to the Stardust mission.
A statistical model of fragmentation of aggregates is proposed, based on the stochastic propagation of cracks through the body. The propagation rules are formulated on a lattice and mimic two important features of the process-a crack moves against the stress gradient while dissipating energy during its growth. We perform numerical simulations of the model for two-dimensional lattice and reveal that the mass distribution for small-and intermediate-size fragments obeys a power law, F(m) proportional to m(-3/2), in agreement with experimental observations. We develop an analytical theory which explains the detected power law and demonstrate that the overall fragment mass distribution in our model agrees qualitatively with that one observed in experiments.
Objective: Health-related quality of life (HRQoL) is an important outcome in individuals with a high risk for cardiovascular diseases. We investigated the association of HRQoL and body mass index (BMI) as an indicator for obesity.
Design: Secondary longitudinal analysis of the ORBITAL study, an intervention study which included high-risk cardiovascular primary care patients with hypercholesterolemia and an indication for statin therapy.
Methods: HRQoL was determined with the generic Short Form (SF)-12 health status instrument. Body weight and height were assessed at baseline and at months 6, 12, 18, 24, 30, and 36. We used a linear and a linear mixed-effects regression model to investigate the association between BMI and SF-12 summary scores at baseline as well as between change in BMI and SF-12 summary scores over 3 years. We adjusted for age, sex, smoking status, and in the longitudinal analysis also for the study arm and its interaction term with time.
Results: Of the 7640 participants who completed the baseline questionnaire, 6726 participants (mean age: 61 years) were analyzed. The baseline BMI was inversely associated with physical and mental SF-12 summary scores (beta [95% CI] per 1 kg/ m(2) : -0.36 [-0.41; -0.30] and -0.05 [-0.11; -0.00], respectively). A significant association between the change in BMI and physical SF-12 summary scores over time was only present in women (-0.18 [-0.27; -0.09]) and only in obese participants (-0.19 [-0.29; -0.10]). A change in BMI was directly associated with mental SF-12 summary scores (0.12 [0.06; 0.19]) in the total population.
Conclusion: Increases in BMI were associated with decreases in physical HRQoL, particularly in obese individuals and in women. In contrast, the mental HRQoL seemed to increase with increasing BMI over time. Thus, body weight management with respect to the HRQoL should be evaluated differentially by sex and body weight status.
The new sediment record from the deep Dead Sea basin (ICDP core 5017-1) provides a unique archive for hydroclimatic variability in the Levant. Here, we present high-resolution sediment facies analysis and elemental composition by micro-X-ray fluorescence (mu XRF) scanning of core 5017-1 to trace lake levels and responses of the regional hydroclimatology during the time interval from ca. 117 to 75 ka, i. e. the transition between the last interglacial and the onset of the last glaciation. We distinguished six major micro-facies types and interpreted these and their alterations in the core in terms of relative lake level changes. The two end-member facies for highest and lowest lake levels are (a) up to several metres thick, greenish sediments of alternating aragonite and detrital marl laminae (aad) and (b) thick halite facies, respectively. Intermediate lake levels are characterised by detrital marls with varying amounts of aragonite, gypsum or halite, reflecting lower-amplitude, shorter-term variability. Two intervals of pronounced lake level drops occurred at similar to 110-108 +/- 5 and similar to 93-87 +/- 7 ka. They likely coincide with stadial conditions in the central Mediterranean (Melisey I and II pollen zones in Monticchio) and low global sea levels during Marine Isotope Stage (MIS) 5d and 5b. However, our data do not support the current hypothesis of an almost complete desiccation of the Dead Sea during the earlier of these lake level low stands based on a recovered gravel layer. Based on new petrographic analyses, we propose that, although it was a low stand, this well-sorted gravel layer may be a vestige of a thick turbidite that has been washed out during drilling rather than an in situ beach deposit. Two intervals of higher lake stands at similar to 108-93 +/- 6 and similar to 87-75 +/- 7 ka correspond to interstadial conditions in the central Mediterranean, i. e. pollen zones St. Germain I and II in Monticchio, and Greenland interstadials (GI) 24+23 and 21 in Greenland, as well as to sapropels S4 and S3 in the Mediterranean Sea. These apparent correlations suggest a close link of the climate in the Levant to North Atlantic and Mediterranean climates during the time of the build-up of Northern Hemisphere ice shields in the early last glacial period.
Thermal erosion is a major mechanism of permafrost degradation, resulting in characteristic landforms. We inventory thermo-erosional valleys in ice-rich coastal lowlands adjacent to the Siberian Laptev Sea based on remote sensing, Geographic Information System (GIS), and field investigations for a first regional assessment of their spatial distribution and characteristics. Three study areas with similar geological (Yedoma Ice Complex) but diverse geomorphological conditions vary in valley areal extent, incision depth, and branching geometry. The most extensive valley networks are incised deeply (up to 35 m) into the broad inclined lowland around Mamontov Klyk. The flat, low-lying plain forming the Buor Khaya Peninsula is more degraded by thermokarst and characterized by long valleys of lower depth with short tributaries. Small, isolated Yedoma Ice Complex remnants in the Lena River Delta predominantly exhibit shorter but deep valleys. Based on these hydrographical network and topography assessments, we discuss geomorphological and hydrological connections to erosion processes. Relative catchment size along with regional slope interact with other Holocene relief-forming processes such as thermokarst and neotectonics. Our findings suggest that thermo-erosional valleys are prominent, hitherto overlooked permafrost degradation landforms that add to impacts on biogeochemical cycling, sediment transport, and hydrology in the degrading Siberian Yedoma Ice Complex.
Past climate and continentality inferred from ice wedges at Batagay Highlands, interior Yakutia
(2019)
Ice wedges in the Yana Highlands of interior Yakutia - the most continental region of the Northern Hemisphere - were investigated to elucidate changes in winter climate and continentality that have taken place since the Middle Pleistocene. The Batagay megaslump exposes ice wedges and composite wedges that were sampled from three cryostratigraphic units: the lower ice complex of likely pre-Marine Isotope Stage (MIS) 6 age, the upper ice complex (Yedoma) and the upper sand unit (both MIS 3 to 2). A terrace of the nearby Adycha River provides a Late Holocene (MIS 1) ice wedge that serves as a modern reference for interpretation. The stable-isotope composition of ice wedges in the MIS 3 upper ice complex at Batagay is more depleted (mean delta O-18 about -35 parts per thousand) than those from 17 other ice-wedge study sites across coastal and central Yakutia. This observation points to lower winter temperatures and therefore higher continentality in the Yana Highlands during MIS 3. Likewise, more depleted isotope values are found in Holocene wedge ice (mean delta O-18 about -29 parts per thousand) compared to other sites in Yakutia. Ice-wedge isotopic signatures of the lower ice complex mean delta O-18 about -33 parts per thousand) and of the MIS 3-2 upper sand unit (mean delta O-18 from about -33 parts per thousand to -30 parts per thousand) are less distinctive regionally. The latter unit preserves traces of fast formation in rapidly accumulating sand sheets and of post-depositional isotopic fractionation.
The PEGASOS project was a major international seismic hazard study, one of the largest ever conducted anywhere in the world, to assess seismic hazard at four nuclear power plant sites in Switzerland. Before the report of this project has become publicly available, a paper attacking both methodology and results has appeared. Since the general scientific readership may have difficulty in assessing this attack in the absence of the report being attacked, we supply a response in the present paper. The bulk of the attack, besides some misconceived arguments about the role of uncertainties in seismic hazard analysis, is carried by some exercises that purport to be validation exercises. In practice, they are no such thing; they are merely independent sets of hazard calculations based on varying assumptions and procedures, often rather questionable, which come up with various different answers which have no particular significance. (C) 2005 Elsevier B.V. All rights reserved
Tendon adaptation due to mechanical loading is controversially discussed. However, data concerning the development of tendon thickness in adolescent athletes is sparse. The purpose of this study was to examine possible differences in Achilles (AT) and patellar tendon (PT) thickness in adolescent athletes while considering age, gender and sport-specific loading. In 500 adolescent competitive athletes of 16 different sports and 40 recreational controls both ATs and PTs were sonographically measured. Subjects were divided into 2 age groups (< 13; ≥ 13 years) and 6 sport type categories (ball, combat, and water sports, combined disciplines, cycling, controls). In addition, 3 risk groups (low, moderate, high) were created according to the athlete’s risk of developing tendinopathy. AT and PT thickness did not significantly differ between age groups (AT/PT:<13: 5.4±0.7 mm/3.6±0.5 mm;≥13: 5.3±0.7 mm/3.6±0.5 mm). In both age groups males presented higher tendon thickness than females (p<0.001). AT thickness was highest in ball sports/cyclists and lowest in controls (p≤0.002). PT thickness was greatest in water sports and lowest in controls (p=0.02). High risk athletes presented slightly higher AT thickness compared to the low risk group (p=0.03). Increased AT and PT thickness in certain sport types compared to controls supports the hypothesis of structural tendon adaptation due to sport-specific loading.
MALDI-TOF-MS-based identification of monoclonal murine Anti-SARS-CoV-2 antibodies within one hour
(2022)
During the SARS-CoV-2 pandemic, many virus-binding monoclonal antibodies have been developed for clinical and diagnostic purposes. This underlines the importance of antibodies as universal bioanalytical reagents. However, little attention is given to the reproducibility crisis that scientific studies are still facing to date. In a recent study, not even half of all research antibodies mentioned in publications could be identified at all. This should spark more efforts in the search for practical solutions for the traceability of antibodies. For this purpose, we used 35 monoclonal antibodies against SARS-CoV-2 to demonstrate how sequence-independent antibody identification can be achieved by simple means applied to the protein. First, we examined the intact and light chain masses of the antibodies relative to the reference material NIST-mAb 8671. Already half of the antibodies could be identified based solely on these two parameters. In addition, we developed two complementary peptide mass fingerprinting methods with MALDI-TOF-MS that can be performed in 60 min and had a combined sequence coverage of over 80%. One method is based on the partial acidic hydrolysis of the protein by 5 mM of sulfuric acid at 99 degrees C. Furthermore, we established a fast way for a tryptic digest without an alkylation step. We were able to show that the distinction of clones is possible simply by a brief visual comparison of the mass spectra. In this work, two clones originating from the same immunization gave the same fingerprints. Later, a hybridoma sequencing confirmed the sequence identity of these sister clones. In order to automate the spectral comparison for larger libraries of antibodies, we developed the online software ABID 2.0. This open-source software determines the number of matching peptides in the fingerprint spectra. We propose that publications and other documents critically relying on monoclonal antibodies with unknown amino acid sequences should include at least one antibody fingerprint. By fingerprinting an antibody in question, its identity can be confirmed by comparison with a library spectrum at any time and context.
Intra- and interrater variability of sonographic investigations of patella and achilles tendons
(2012)
Background: Clinical examinations of tendon disorders routinely include ultrasound examinations, despite the fact that availability of data concerning validity criteria of these measurements are limited. The present study therefore aims to evaluate the reliability of measurements of Achilles- and Patella tendon diameter and in the detection of structural adaptations.
Materials and Methods: In 14 healthy, recreationally active subjects both asymptomatic Achilles (AT) and patella tendons (PT) were measured twice by two examiners in a test-retest design. Besides the detection of anteroposterior (a.p.-) and mediolateral (m.l.-) diameters, areas of hypoechogenicity and neovascularisation were registered. Data were analysed descriptively with calculation of test-retest variability (TRV), intraclass-correlation coefficient (ICC) and Bland and Altman's plots with bias and 95% limits of agreement (LOA).
Results: Intra- and interrater differences of AT- and PT-a.p.-diameter varied from 0.2 - 1.2 mm, those of AT- and PT-m.l-diameter from 0.7-5.1 mm. Areas of hypoechogenicity were visible in 24% of the tendons, while 15% showed neovascularisations. Intrarater AT-a.p.-diameters showed sparse deviations (TRV 4.5-7.4%; ICC 0.60-0.84; bias -0.05-0.07 mm; LOA-0.6-0.5 to -1.1 - 1.0 mm), while interrater AT- and PT-m.l.-diameters were highly variable (TRV 13.7-19.7%; ICC 0.11-0.20; bias -1.4-4.3 mm; LOA-5.5-2.7 to -10.5 - 1.9 mm).
Conclusion: Our results suggest that the measurement of AT- and PT-a.p.-diameters is a reliable parameter. In contrast, reproducibility of AT- and PT-m.l.-diameters is questionable. The study corroborates the presence of hypoechogenicity and neovascularisation in asymptomatic tendons.
Episodes of environmental stability and instability may be equally important for African hominin speciation, dispersal, and cultural innovation. Three examples of a change from stable to unstable environmental conditions are presented on three different time scales: (1) the Mid Holocene (MH) wet dry transition in the Chew Bahir basin (Southern Ethiopian Rift; between 11 ka and 4 ka), (2) the MIS 5-4 transition in the Naivasha basin (Central Kenya Rift; between 160 ka and 50 ka), and (3) the Early Mid Pleistocene Transition (EMPT) in the Olorgesailie basin (Southern Kenya Rift; between 1.25 Ma and 0.4 Ma). A probabilistic age modeling technique is used to determine the timing of these transitions, taking into account possible abrupt changes in the sedimentation rate including episodes of no deposition (hiatuses). Interestingly, the stable-unstable conditions identified in the three records are always associated with an orbitally-induced decrease of insolation: the descending portion of the 800 kyr cycle during the EMPT, declining eccentricity after the 115 ka maximum at the MIS 5-4 transition, and after similar to 10 ka. This observation contributes to an evidence-based discussion of the possible mechanisms causing the switching between environmental stability and instability in Eastern Africa at three different orbital time scales (10,000 to 1,000,000 years) during the Cenozoic. This in turn may lead to great insights into the environmental changes occurring at the same time as hominin speciation, brain expansion, dispersal out of Africa, and cultural innovations and may provide key evidence to build new hypotheses regarding the causes of early human evolution. (C) 2015 Elsevier Ltd. All rights reserved.
BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies.
River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth’s biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented “next-generation biomonitoring” by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
We present the first SB2 orbital solution and disentanglement of the massive Wolf-Rayet binary R145 (P = 159 d) located in the Large Magellanic Cloud. The primary was claimed to have a stellar mass greater than 300 M-circle dot, making it a candidate for being the most massive star known to date. While the primary is a known late-type, H-rich Wolf-Rayet star (WN6h), the secondary has so far not been unambiguously detected. Using moderate-resolution spectra, we are able to derive accurate radial velocities for both components. By performing simultaneous orbital and polarimetric analyses, we derive the complete set of orbital parameters, including the inclination. The spectra are disentangled and spectroscopically analyzed, and an analysis of the wind-wind collision zone is conducted. The disentangled spectra and our models are consistent with a WN6h type for the primary and suggest that the secondary is an O3.5 If*/WN7 type star. We derive a high eccentricity of e = 0 : 78 and minimum masses of M-1 sin(3) i approximate to M-2 sin(3) i = 13 +/- 2 M-circle dot, with q = M-2/M-1 = 1.01 +/- 0.07. An analysis of emission excess stemming from a wind-wind collision yields an inclination similar to that obtained from polarimetry (i = 39 +/- 6 degrees). Our analysis thus implies M-1 = 53(-20)(+40) and M2 = 54(-20)(+40) M-circle dot, excluding M-1 > 300 M-circle dot. A detailed comparison with evolution tracks calculated for single and binary stars together with the high eccentricity suggests that the components of the system underwent quasi-homogeneous evolution and avoided mass-transfer. This scenario would suggest current masses of approximate to 80 M-circle dot and initial masses of M-i,M-1 approximate to 10(5) and M-i,M-2 approximate to 90 M-circle dot, consistent with the upper limits of our derived orbital masses, and would imply an age of approximate to 2.2 Myr.
The majority of cases of community-acquired pneumonia are caused by Streptococcus pneumoniae and most studies on pneumococcal host interaction are based on cell culture or animal experiments. Thus, little is known about infections in human lung tissue.
Cyclooxygenase-2 and its metabolites play an important regulatory role in lung inflammation. Therefore, we established a pneumococcal infection model on human lung tissue demonstrating mitogen-activated protein kinase (MAPK)-dependent induction of cyclooxygenase-2 and its related metabolites.
In addition to alveolar macrophages and the vascular endothelium, cyclooxygenase-2 was upregulated in alveolar type II but not type I epithelial cells, which was confirmed in lungs of patients suffering from acute pneumonia. Moreover, we demonstrated the expression profile of all four E prostanoid receptors at the mRNA level and showed functionality of the E prostanoid(4) receptor by cyclic adenosine monophosphate production. Additionally, in comparison to previous studies, cyclooxygenase-2/prostaglandin E-2 related pro- and anti-inflammatory mediator regulation was partly confirmed in human lung tissue after pneumococcal infection.
Overall, cell type-specific and MAPK-dependent cyclooxygenase-2 expression and prostaglandin E-2 formation in human lung tissue may play an important role in the early phase of pneumococcal infections.