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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.
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.
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.
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 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.
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.
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 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.
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.
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.
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.
Despite more than half a century of hominin fossil discoveries in eastern Africa, the regional environmental context of hominin evolution and dispersal is not well established due to the lack of continuous palaeoenvironmental records from one of the proven habitats of early human populations, particularly for the Pleistocene epoch. Here we present a 620,000-year environmental record from Chew Bahir, southern Ethiopia, which is proximal to key fossil sites. Our record documents the potential influence of different episodes of climatic variability on hominin biological and cultural transformation. The appearance of high anatomical diversity in hominin groups coincides with long-lasting and relatively stable humid conditions from similar to 620,000 to 275,000 years bp (episodes 1-6), interrupted by several abrupt and extreme hydroclimate perturbations. A pattern of pronounced climatic cyclicity transformed habitats during episodes 7-9 (similar to 275,000-60,000 years bp), a crucial phase encompassing the gradual transition from Acheulean to Middle Stone Age technologies, the emergence of Homo sapiens in eastern Africa and key human social and cultural innovations. Those accumulative innovations plus the alignment of humid pulses between northeastern Africa and the eastern Mediterranean during high-frequency climate oscillations of episodes 10-12 (similar to 60,000-10,000 years bp) could have facilitated the global dispersal of H. sapiens.
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.
Prevalence of Achilles tendinopathy increases with age leading to a weaker tendon with predisposition to rupture. Conclusive evidence of the influence of age and pathology on Achilles tendon (AT) properties remains limited, as previous studies are based on standardized isometric conditions. The study investigates the influence of age and pathology on AT properties during single-leg vertical jump (SLVJ). 10 children (C), 10 asymptomatic adults (A), and 10 tendinopathic patients (T) were included. AT elongation [mm] from rest to maximal displacement during a SLVJ on a force-plate was sonographically assessed. AT compliance [mm/N]) and strain [%] was calculated by dividing elongation by peak ground reaction force [N] and length, respectively. One-way ANOVA followed by Bonferroni post-hoc correction (=0.05) were used to compare C with A and A with T. AT elongation (p=0.004), compliance (p=0.001), and strain were found to be statistically significant higher in C (27 +/- 3mm, 0.026 +/- 0.006[mm/N], 13 +/- 2%) compared to A (21 +/- 4mm, 0.017 +/- 0.005[mm/N], 10 +/- 2%). No statistically significant differences (p0.05) was found between A and T (25 +/- 5mm, 0.019 +/- 0.004[mm/N], 12 +/- 3%). During SLVJ, tendon responded differently in regards to age and pathology with children having the most compliant AT. Higher compliance found in healthy tendons might be considered as a protective factor against load-related injuries.
Understanding eastern African paleoclimate is critical for contextualizing early human evolution, adaptation, and dispersal, yet Pleistocene climate of this region and its governing mechanisms remain poorly understood due to the lack of long, orbitally-resolved, terrestrial paleoclimate records. Here we present leaf wax hydrogen isotope records of rainfall from paleolake sediment cores from key time windows that resolve long-term trends, variations, and high-latitude effects on tropical African precipitation. Eastern African rainfall was dominantly controlled by variations in low-latitude summer insolation during most of the early and middle Pleistocene, with little evidence that glacial-interglacial cycles impacted rainfall until the late Pleistocene. We observe the influence of high-latitude-driven climate processes emerging from the last interglacial (Marine Isotope Stage 5) to the present, an interval when glacial-interglacial cycles were strong and insolation forcing was weak. Our results demonstrate a variable response of eastern African rainfall to low-latitude insolation forcing and high-latitude-driven climate change, likely related to the relative strengths of these forcings through time and a threshold in monsoon sensitivity. We observe little difference in mean rainfall between the early, middle, and late Pleistocene, which suggests that orbitally-driven climate variations likely played a more significant role than gradual change in the relationship between early humans and their environment.
Saturn’s main rings are composed of >95% water ice, and the nature of the remaining few percent has remained unclear. The Cassini spacecraft’s traversals between Saturn and its innermost D ring allowed its cosmic dust analyzer (CDA) to collect material released from the main rings and to characterize the ring material infall into Saturn. We report the direct in situ detection of material from Saturn’s dense rings by the CDA impact mass spectrometer. Most detected grains are a few tens of nanometers in size and dynamically associated with the previously inferred “ring rain.” Silicate and water-ice grains were identified, in proportions that vary with latitude. Silicate grains constitute up to 30% of infalling grains, a higher percentage than the bulk silicate content of the rings.
Gilbert et al. conclude that evidence from the Open Science Collaboration’s Reproducibility Project: Psychology indicates high reproducibility, given the study methodology. Their very optimistic assessment is limited by statistical misconceptions and by causal inferences from selectively interpreted, correlational data. Using the Reproducibility Project: Psychology data, both optimistic and pessimistic conclusions about reproducibility are possible, and neither are yet warranted.
Femtosecond x-ray laser pulses are used to probe the carbon monoxide (CO) oxidation reaction on ruthenium (Ru) initiated by an optical laser pulse. On a time scale of a few hundred femtoseconds, the optical laser pulse excites motions of CO and oxygen (O) on the surface, allowing the reactants to collide, and, with a transient close to a picosecond (ps), new electronic states appear in the OK-edge x-ray absorption spectrum. Density functional theory calculations indicate that these result from changes in the adsorption site and bond formation between CO and O with a distribution of OC-O bond lengths close to the transition state (TS). After 1 ps, 10% of the CO populate the TS region, which is consistent with predictions based on a quantum oscillator model.
Recent global warming is acting across marine, freshwater, and terrestrial ecosystems to favor species adapted to warmer conditions and/or reduce the abundance of cold-adapted organisms (i.e., "thermophilization" of communities). Lack of community responses to increased temperature, however, has also been reported for several taxa and regions, suggesting that "climatic lags" may be frequent. Here we show that microclimatic effects brought about by forest canopy closure can buffer biotic responses to macroclimate warming, thus explaining an apparent climatic lag. Using data from 1,409 vegetation plots in European and North American temperate forests, each surveyed at least twice over an interval of 12-67 y, we document significant thermophilization of ground-layer plant communities. These changes reflect concurrent declines in species adapted to cooler conditions and increases in species adapted to warmer conditions. However, thermophilization, particularly the increase of warm-adapted species, is attenuated in forests whose canopies have become denser, probably reflecting cooler growing-season ground temperatures via increased shading. As standing stocks of trees have increased in many temperate forests in recent decades, local microclimatic effects may commonly be moderating the impacts of macroclimate warming on forest understories. Conversely, increases in harvesting woody biomass-e.g., for bioenergy-may open forest canopies and accelerate thermophilization of temperate forest biodiversity.
ISMIP6 Antarctica
(2020)
Ice flow models of the Antarctic ice sheet are commonly used to simulate its future evolution in response to different climate scenarios and assess the mass loss that would contribute to future sea level rise. However, there is currently no consensus on estimates of the future mass balance of the ice sheet, primarily because of differences in the representation of physical processes, forcings employed and initial states of ice sheet models. This study presents results from ice flow model simulations from 13 international groups focusing on the evolution of the Antarctic ice sheet during the period 2015-2100 as part of the Ice Sheet Model Intercomparison for CMIP6 (ISMIP6). They are forced with outputs from a subset of models from the Coupled Model Intercomparison Project Phase 5 (CMIP5), representative of the spread in climate model results. Simulations of the Antarctic ice sheet contribution to sea level rise in response to increased warming during this period varies between 7:8 and 30.0 cm of sea level equivalent (SLE) under Representative Concentration Pathway (RCP) 8.5 scenario forcing. These numbers are relative to a control experiment with constant climate conditions and should therefore be added to the mass loss contribution under climate conditions similar to present-day conditions over the same period. The simulated evolution of the West Antarctic ice sheet varies widely among models, with an overall mass loss, up to 18.0 cm SLE, in response to changes in oceanic conditions. East Antarctica mass change varies between 6 :1 and 8.3 cm SLE in the simulations, with a significant increase in surface mass balance outweighing the increased ice discharge under most RCP 8.5 scenario forcings. The inclusion of ice shelf collapse, here assumed to be caused by large amounts of liquid water ponding at the surface of ice shelves, yields an additional simulated mass loss of 28mm compared to simulations without ice shelf collapse. The largest sources of uncertainty come from the climate forcing, the ocean-induced melt rates, the calibration of these melt rates based on oceanic conditions taken outside of ice shelf cavities and the ice sheet dynamic response to these oceanic changes. Results under RCP 2.6 scenario based on two CMIP5 climate models show an additional mass loss of 0 and 3 cm of SLE on average compared to simulations done under present-day conditions for the two CMIP5 forcings used and display limited mass gain in East Antarctica.
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.
The mechanisms underlying improved insulin sensitivity after surgically-induced weight loss are still unclear. We monitored skeletal muscle metabolism in obese individuals before and over 52 weeks after metabolic surgery. Initial weight loss occurs in parallel with a decrease in muscle oxidative capacity and respiratory control ratio. Persistent elevation of intramyocellular lipid intermediates, likely resulting from unrestrained adipose tissue lipolysis, accompanies the lack of rapid changes in insulin sensitivity. Simultaneously, alterations in skeletal muscle expression of genes involved in calcium/lipid metabolism and mitochondrial function associate with subsequent distinct DNA methylation patterns at 52 weeks after surgery. Thus, initial unfavorable metabolic changes including insulin resistance of adipose tissue and skeletal muscle precede epigenetic modifications of genes involved in muscle energy metabolism and the long-term improvement of insulin sensitivity.
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.
Background: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. Conclusion: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.
An important task of seismic hazard assessment consists of estimating the rate of seismic moment release which is correlated to the rate of tectonic deformation and the seismic coupling. However, the estimations of deformation depend on the type of information utilized (e.g. geodetic, geological, seismic) and include large uncertainties. We therefore estimate the deformation rate in the Lower Rhine Embayment (LRE), Germany, using an integrated approach where the uncertainties have been systematically incorporated. On the basis of a new homogeneous earthquake catalogue we initially determine the frequency-magnitude distribution by statistical methods. In particular, we focus on an adequate estimation of the upper bound of the Gutenberg-Richter relation and demonstrate the importance of additional palaeoseis- mological information. The integration of seismological and geological information yields a probability distribution of the upper bound magnitude. Using this distribution together with the distribution of Gutenberg-Richter a and b values, we perform Monte Carlo simulations to derive the seismic moment release as a function of the observation time. The seismic moment release estimated from synthetic earthquake catalogues with short catalogue length is found to systematically underestimate the long-term moment rate which can be analytically determined. The moment release recorded in the LRE over the last 250 yr is found to be in good agreement with the probability distribution resulting from the Monte Carlo simulations. Furthermore, the long-term distribution is within its uncertainties consistent with the moment rate derived by geological measurements, indicating an almost complete seismic coupling in this region. By means of Kostrov's formula, we additionally calculate the full deformation rate tensor using the distribution of known focal mechanisms in LRE. Finally, we use the same approach to calculate the seismic moment and the deformation rate for two subsets of the catalogue corresponding to the east- and west-dipping faults, respectively
In the last decade, there has been an increasing interest in compensating thermally induced errors to improve the manufacturing accuracy of modular tool systems. These modular tool systems are interfaces between spindle and workpiece and consist of several complicatedly formed parts. Their thermal behavior is dominated by nonlinearities, delay and hysteresis effects even in tools with simpler geometry and it is difficult to describe it theoretically. Due to the dominant nonlinear nature of this behavior the so far used linear regression between the temperatures and the displacements is insufficient. Therefore, in this study we test the hypothesis whether we can reliably predict such thermal displacements via nonlinear temperature-displacement regression functions. These functions are estimated firstly from learning measurements using the alternating conditional expectation (ACE) algorithm and then tested on independent data sets. First, we analyze data that were generated by a finite element spindle model. We find that our approach is a powerful tool to describe the relation between temperatures and displacements for simulated data. Next, we analyze the temperature-displacement relationship in a silent real experimental setup, where the tool system is thermally forced. Again, the ACE-algorithm is powerful to estimate the deformation with high precision. The corresponding errors obtained by using the nonlinear regression approach are 10-fold lower in comparison to multiple linear regression analysis. Finally, we investigate the thermal behavior of a modular tool system in a working milling machine and get again promising results. The thermally inducedaccuracy using this nonlinear regression analysis. Therefore, this approach seems to be very useful for the development of new modular tool systems. errors can be estimated with 1-2 micrometer
In the last decade, there has been an increasing interest in compensating thermally induced errors to improve the manufacturing accuracy of modular tool systems. These modular tool systems are interfaces between spindle and workpiece and consist of several complicatedly formed parts. Their thermal behavior is dominated by nonlinearities, delay and hysteresis effects even in tools with simpler geometry and it is difficult to describe it theoretically. Due to the dominant nonlinear nature of this behavior the so far used linear regression between the temperatures and the displacements is insufficient. Therefore, in this study we test the hypothesis whether we can reliably predict such thermal displacements via nonlinear temperature-displacement regression functions. These functions are estimated firstly from learning measurements using the alternating conditional expectation (ACE) algorithm and then tested on independent data sets. First, we analyze data that were generated by a finite element spindle model. We find that our approach is a powerful tool to describe the relation between temperatures and displacements for simulated data. Next, we analyze the temperature-displacement relationship in a silent real experimental setup, where the tool system is thermally forced. Again, the ACE-algorithm is powerful to estimate the deformation with high precision. The corresponding errors obtained by using the nonlinear regression approach are 10-fold lower in comparison to multiple linear regression analysis. Finally, we investigate the thermal behavior of a modular tool system in a working milling machine and get again promising results. The thermally induced errors can be estimated with 1-2${mu m}$ accuracy using this nonlinear regression analysis. Therefore, this approach seems to be very useful for the development of new modular tool systems.
This study presents results of ambient noise measurements from temporary single station and small-scale array deployments in the northeast of Basle. H/V spectral ratios were determined along various profiles crossing the eastern masterfault of the Rhine Rift Valley and the adjacent sedimentary rift fills. The fundamental H/V peak frequencies are decreasing along the profile towards the eastern direction being consistent with the dip of the tertiary sediments within the rift. Using existing empirical relationships between H/V frequency peaks and the depth of the dominant seismic contrast, derived on basis of the lambda/4-resonance hypothesis and a power law depth dependence of the S-wave velocity, we obtain thicknesses of the rift fill from about 155 m in the west to 280 in in the east. This is in agreement with previous studies. The array analysis of the ambient noise wavefield yielded a stable dispersion relation consistent with Rayleigh wave propagation velocities. We conclude that a significant amount of surface waves is contained in the observed wavefield. The computed ellipticity for fundamental mode Rayleigh waves for the velocity depth models used for the estimation of the sediment thicknesses is in agreement with the observed H/V spectra over a large frequency band
The Cassini-Huygens Cosmic Dust Analyzer (CDA) is intended to provide direct observations of dust grains with masses between 10(-19) and 10(-9) kg in interplanetary space and in the jovian and saturnian systems, to investigate their physical, chemical and dynamical properties as functions of the distances to the Sun, to Jupiter and to Saturn and its satellites and rings, to study their interaction with the saturnian rings, satellites and magnetosphere. Chemical composition of interplanetary meteoroids will be compared with asteroidal and cometary dust, as well as with Saturn dust, ejecta from rings and satellites. Ring and satellites phenomena which might be effects of meteoroid impacts will be compared with the interplanetary dust environment. Electrical charges of particulate matter in the magnetosphere and its consequences will be studied, e.g. the effects of the ambient plasma and the magnetic held on the trajectories of dust particles as well as fragmentation of particles due to electrostatic disruption. The investigation will be performed with an instrument that measures the mass, composition, electric charge, speed, and flight direction of individual dust particles. It is a highly reliable and versatile instrument with a mass sensitivity 106 times higher than that of the Pioneer 10 and I I dust detectors which measured dust in the saturnian system. The Cosmic Dust Analyzer has significant inheritance from former space instrumentation developed for the VEGA, Giotto, Galileo, and Ulysses missions. It will reliably measure impacts from as low as I impact per month up to 104 impacts per second. The instrument weighs 17 kg and consumes 12 W, the integrated time-of-flight mass spectrometer has a mass resolution of up to 50. The nominal data transmission rate is 524 bits/s and varies between 50 and 4192 bps
While searching for prey, Molossus molossus broadcasts narrow-band calls of 11.42 ms organized in pairs of pulses that alternate in frequency. The first signal of the pair is at 34.5 kHz, the second at 39.6 kHz. Pairs of calls with changing frequencies were only emitted when the interpulse intervals were below 200 ms. Maximum duty cycles during search phase are close to 20%. Frequency alternation of search calls is interpreted as a mechanism for increasing duty cycle and thus the temporal continuity of scanning, as well as increasing the detection range. A neurophysiological correlate for the processing of search calls was found in the inferior colliculus. 64% of neurons respond to frequencies in the 30- to 40-kHz range and only in this frequency range were closed tuning curves found for levels below 40 dB SPL. In addition, 15% of the neurons have double-tuned frequency-threshold curves with best thresholds at 34 and 39 kHz. Differing from observations in other bats, approach calls of M. molossus are longer and of higher frequencies than search calls. Close to the roost, the call frequency is increased to 45.049.8 kHz and, in addition, extremely broadband signals are emitted. This demonstrates high plasticity of call design
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⊙.
The contemporary state of functional traits and species richness in plant communities depends on legacy effects of past disturbances. Whether temporal responses of community properties to current environmental changes are altered by such legacies is, however, unknown. We expect global environmental changes to interact with land-use legacies given different community trajectories initiated by prior management, and subsequent responses to altered resources and conditions. We tested this expectation for species richness and functional traits using 1814 survey-resurvey plot pairs of understorey communities from 40 European temperate forest datasets, syntheses of management transitions since the year 1800, and a trait database. We also examined how plant community indicators of resources and conditions changed in response to management legacies and environmental change. Community trajectories were clearly influenced by interactions between management legacies from over 200 years ago and environmental change. Importantly, higher rates of nitrogen deposition led to increased species richness and plant height in forests managed less intensively in 1800 (i.e., high forests), and to decreases in forests with a more intensive historical management in 1800 (i.e., coppiced forests). There was evidence that these declines in community variables in formerly coppiced forests were ameliorated by increased rates of temperature change between surveys. Responses were generally apparent regardless of sites’ contemporary management classifications, although sometimes the management transition itself, rather than historic or contemporary management types, better explained understorey responses. Main effects of environmental change were rare, although higher rates of precipitation change increased plant height, accompanied by increases in fertility indicator values. Analysis of indicator values suggested the importance of directly characterising resources and conditions to better understand legacy and environmental change effects. Accounting for legacies of past disturbance can reconcile contradictory literature results and appears crucial to anticipating future responses to global environmental change.
Background and Purpose Recent studies suggested a role for PGE2 in the expression of the chemokine IL-8. PGE2 signals via four different GPCRs, EP1-EP4. The role of EP1 and EP4 receptors for IL-8 induction was studied in HEK293 cells, overexpressing EP1 (HEK-EP1), EP4 (HEK-EP4) or both receptors (HEK-EP1 + EP4). Experimental Approach IL-8 mRNA and protein induction and IL-8 promoter and NF-?B activation were assessed in EP expressing HEK cells. Key Results In HEK-EP1 and HEK-EP1 + EP4 but not HEK or HEK-EP4 cells, PGE2 activated the IL-8 promoter and induced IL-8 mRNA and protein synthesis. Stimulation of HEK-EP1 + EP4 cells with an EP1-specific agonist activated IL-8 promoter and induced IL-8 mRNA and protein, whereas a specific EP4 agonist neither activated the IL-8 promoter nor induced IL-8 mRNA and protein synthesis. Simultaneous stimulation of HEK- EP1 + EP4 cells with both agonists activated IL-8 promoter and induced IL-8 mRNA to the same extent as PGE2. In HEK-EP1 + EP4 cells, PGE2-mediated IL-8 promoter activation and IL-8 mRNA induction were blunted by inhibition of I?B kinase. PGE2 activated NF-?B in HEK-EP1, HEK-EP4 and HEK-EP1 + EP4 cells. In HEK-EP1 + EP4 cells, simultaneous activation of both receptors was needed for maximal PGE2-induced NF-?B activation. PGE2-stimulated NF-?B activation by EP1 was blocked by inhibitors of PLC, calcium-signalling and Src-kinase, whereas that induced by EP4 was only blunted by Src-kinase inhibition. Conclusions and Implications These findings suggest that PGE2-mediated NF-?B activation by simultaneous stimulation of EP1 and EP4 receptors induces maximal IL-8 promoter activation and IL-8 mRNA and protein induction.
Integration of titin into the sarcomeres of cultured differentiating human skeletal muscle cells
(1996)
We used single-molecule FRET in combination with other biophysical methods and molecular simulations to investigate the effect of temperature on the dimensions of unfolded proteins. With singlemolecule FRET, this question can be addressed even under nearnative conditions, where most molecules are folded, allowing us to probe a wide range of denaturant concentrations and temperatures. We find a compaction of the unfolded state of a small cold shock protein with increasing temperature in both the presence and the absence of denaturant, with good agreement between the results from single-molecule FRET and dynamic light scattering. Although dissociation of denaturant from the polypeptide chain with increasing temperature accounts for part of the compaction, the results indicate an important role for additional temperaturedependent interactions within the unfolded chain. The observation of a collapse of a similar extent in the extremely hydrophilic, intrinsically disordered protein prothymosin suggests that the hydrophobic effect is not the sole source of the underlying interactions. Circular dichroism spectroscopy and replica exchange molecular dynamics simulations in explicit water show changes in secondary structure content with increasing temperature and suggest a contribution of intramolecular hydrogen bonding to unfolded state collapse.
Bonding of the Ni2+(aq) complex is investigated with an unprecedented combination of resonant inelastic X-ray scattering (RIXS) measurements and ab initio calculations at the Ni L absorption edge. The spectra directly reflect the relative energies of the ligand-field and charge-transfer valence-excited states. They give element-specific access with atomic resolution to the ground-state electronic structure of the complex and allow quantification of ligand-field strength and 3d-3d electron correlation interactions in the Ni2+(aq) complex. The experimentally determined ligand-field strength is 10Dq = 1.1 eV. This and the Racah parameters characterizing 3d-3d Coulomb interactions B = 0.13 eV and C = 0.42 eV as readily derived from the measured energies match very well with the results from UV-vis spectroscopy. Our results demonstrate how L-edge RIXS can be used to complement existing spectroscopic tools for the investigation of bonding in 3d transition-metal coordination compounds in solution. The ab initio RASPT2 calculation is successfully used to simulate the L-edge RIXS spectra.
By traversing the plume erupting from high southern latitudes on Saturn's moon Enceladus, Cassini orbiter instruments can directly sample the material therein. Cassini Plasma Spectrometer, CAPS, data show that a major plume component comprises previously-undetected particles of nanometer scales and larger that bridge the mass gap between previously observed gaseous species and solid icy grains. This population is electrically charged both negative and positive, indicating that subsurface triboelectric charging, i.e., contact electrification of condensed plume material may occur through mutual collisions within vents. The electric field of Saturn's magnetosphere controls the jets' morphologies, separating particles according to mass and charge. Fine-scale structuring of these particles' spatial distribution correlates with discrete plume jets' sources, and reveals locations of other possible active regions. The observed plume population likely forms a major component of high velocity nanometer particle streams detected outside Saturn's magnetosphere.
Transition-metal complexes have long attracted interest for fundamental chemical reactivity studies and possible use in solar energy conversion(1,2). Electronic excitation, ligand loss from the metal centre, or a combination of both, creates changes in charge and spin density at the metal site(3-11) that need to be controlled to optimize complexes for photocatalytic hydrogen production(8) and selective carbon-hydrogen bond activation(9-11). An understanding at the molecular level of how transition-metal complexes catalyse reactions, and in particular of the role of the short-lived and reactive intermediate states involved, will be critical for such optimization. However, suitable methods for detailed characterization of electronic excited states have been lacking. Here we show, with the use of X-ray laser-based femtosecond-resolution spectroscopy and advanced quantum chemical theory to probe the reaction dynamics of the benchmark transition-metal complex Fe(CO)(5) in solution, that the photo-induced removal of CO generates the 16-electron Fe(CO)(4) species, a homogeneous catalyst(12,13) with an electron deficiency at the Fe centre(14,15), in a hitherto unreported excited singlet state that either converts to the triplet ground state or combines with a CO or solvent molecule to regenerate a penta-coordinated Fe species on a sub-picosecond timescale. This finding, which resolves the debate about the relative importance of different spin channels in the photochemistry of Fe(CO)(5) (refs 4, 16-20), was made possible by the ability of femtosecond X-ray spectroscopy to probe frontier-orbital interactions with atom specificity. We expect the method to be broadly applicable in the chemical sciences, and to complement approaches that probe structural dynamics in ultrafast processes.
First comparison of array-derived rotational ground motions with direct ring laser measurements
(2006)
Recently, ring laser technology has provided the first consistent observations of rotational ground motions around a vertical axis induced by earthquakes. "Consistent," in this context, implies that the observed waveforms and amplitudes are compatible with collocated recordings of translational ground motions. In particular, transverse accelerations should be in phase with rotation rate and their ratio proportional to local horizontal phase velocity assuming plane-wave propagation. The ring laser installed at the Fundamental station Wettzell in the Bavarian Forest, Southeast Germany, is recording the rotation rate around a vertical axis, theoretically a linear combination of the space derivatives of the horizontal components of motion. This suggests that, in principle, rotation can be derived from seismic-array experiments by "finite differencing." This has been attempted previously in several studies; however, the accuracy of these observations could never be tested in the absence of direct measurements. We installed a double cross-shaped array of nine stations from December 2003 to March 2004 around the ring laser instrument and observed several large earthquakes on both the ring laser and the seismic array. Here we present for the first time a comparison of array-derived rotations with direct measurements of rotations for ground motions induced by the M 6.3 Al Hoceima, Morocco, earthquake of 24 February 2004. With complete 3D synthetic seismograms calculated for this event we show that even low levels of noise may considerably influence the accuracy of the array-derived rotations when the minimum number of required stations (three) is used. Nevertheless, when using all nine stations, the overall fit between direct and array-derived measurements is surprisingly good (maximum correlation coefficient of 0.94).
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.
Background Exercise rehabilitation is highly recommended by current guidelines on prevention of cardiovascular disease, but its implementation is still poor. Many clinicians experience difficulties in prescribing exercise in the presence of different concomitant cardiovascular diseases and risk factors within the same patient. It was aimed to develop a digital training and decision support system for exercise prescription in cardiovascular disease patients in clinical practice: the European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool. Methods EXPERT working group members were requested to define (a) diagnostic criteria for specific cardiovascular diseases, cardiovascular disease risk factors, and other chronic non-cardiovascular conditions, (b) primary goals of exercise intervention, (c) disease-specific prescription of exercise training (intensity, frequency, volume, type, session and programme duration), and (d) exercise training safety advices. The impact of exercise tolerance, common cardiovascular medications and adverse events during exercise testing were further taken into account for optimized exercise prescription. Results Exercise training recommendations and safety advices were formulated for 10 cardiovascular diseases, five cardiovascular disease risk factors (type 1 and 2 diabetes, obesity, hypertension, hypercholesterolaemia), and three common chronic non-cardiovascular conditions (lung and renal failure and sarcopaenia), but also accounted for baseline exercise tolerance, common cardiovascular medications and occurrence of adverse events during exercise testing. An algorithm, supported by an interactive tool, was constructed based on these data. This training and decision support system automatically provides an exercise prescription according to the variables provided. Conclusion This digital training and decision support system may contribute in overcoming barriers in exercise implementation in common cardiovascular diseases.
L-edge spectroscopy of 3d transition metals provides important electronic structure information and has been used in many fields. However, the use of this method for studying dilute aqueous systems, such as metalloenzymes, has not been prevalent because of severe radiation damage and the lack of suitable detection systems. Here we present spectra from a dilute Mn aqueous solution using a high-transmission zone-plate spectrometer at the Linac Coherent Light Source (LCLS). The spectrometer has been optimized for discriminating the Mn L-edge signal from the overwhelming 0 K-edge background that arises from water and protein itself, and the ultrashort LCLS X-ray pulses can outrun X-ray induced damage. We show that the deviations of the partial-fluorescence yield-detected spectra from the true absorption can be well modeled using the state-dependence of the fluorescence yield, and discuss implications for the application of our concept to biological samples.
The Armutlu peninsula, located in the eastern Marmara Sea, coincides with the western end of the rupture of the 17 August 1999, Izmit M-W 7.6 earthquake which is the penultimate event of an apparently westward migrating series of strong and disastrous earthquakes along the NAFZ during the past century. We present new seismotectonic data of this key region in order to evaluate previous seismotectonic models and their implications for seismic hazard assessment in the eastern Marmara Sea. Long term kinematics were investigated by performing paleo strain reconstruction from geological field investigations by morphotectonic and kinematic analysis of exposed brittle faults. Short term kinematics were investigated by inverting for the moment tensor of 13 small to moderate recent earthquakes using surface wave amplitude spectra. Our results confirm previous models interpreting the eastern Marmara Sea Region as an active transtensional pull-apart environment associated with significant NNE-SSW extension and vertical displacement. At the northern peninsula, long term deformation pattern did not change significantly since Pliocene times contradicting regional tectonic models which postulate a newly formed single dextral strike slip fault in the Marmara Sea Region. This area is interpreted as a horsetail splay fault structure associated with a major normal fault segment that we call the Waterfall Fault. Apart from the Waterfall Fault, the stress strain relation appears complex associated with a complicated internal fault geometry, strain partitioning, and reactivation of pre-existing plane structures. At the southern peninsula, recent deformation indicates active pull-apart tectonics constituted by NE-SW trending dextral strike slip faults. Earthquakes generated by stress release along large rupture zones seem to be less probable at the northern, but more probable at the southern peninsula. Additionally, regional seismicity appears predominantly driven by plate boundary stresses as transtensional faulting is consistent with the southwest directed far field deformation of the Anatolian plate. (C) 2013 Elsevier B.V. All rights reserved.
To address one of the central questions of plate tectonics-How do large transform systems work and what are their typical features?-seismic investigations across the Dead Sea Transform (DST), the boundary between the African and Arabian plates in the Middle East, were conducted for the first time. A major component of these investigations was a combined reflection/ refraction survey across the territories of Palestine, Israel and Jordan. The main results of this study are: (1) The seismic basement is offset by 3-5 km under the DST, (2) The DST cuts through the entire crust, broadening in the lower crust, (3) Strong lower crustal reflectors are imaged only on one side of the DST, (4) The seismic velocity sections show a steady increase in the depth of the crust-mantle transition (Moho) from 26 km at the Mediterranean to 39 km under the Jordan highlands, with only a small but visible, asymmetric topography of the Moho under the DST. These observations can be linked to the left-lateral movement of 105 km of the two plates in the last 17 Myr, accompanied by strong deformation within a narrow zone cutting through the entire crust. Comparing the DST and the San Andreas Fault (SAF) system, a strong asymmetry in subhorizontal lower crustal reflectors and a deep reaching deformation zone both occur around the DST and the SAF. The fact that such lower crustal reflectors and deep deformation zones are observed in such different transform systems suggests that these structures are possibly fundamental features of large transform plate boundaries
Auxology has developed from mere describing child and adolescent growth into a vivid and interdisciplinary research area encompassing human biologists, physicians, social scientists, economists and biostatisticians. The meeting illustrated the diversity in auxology, with the various social, medical, biological and biostatistical aspects in studies on child growth and development.
Background: Development of eukaryotic organisms is controlled by transcription factors that trigger specific and global changes in gene expression programs. In plants, MADS-domain transcription factors act as master regulators of developmental switches and organ specification. However, the mechanisms by which these factors dynamically regulate the expression of their target genes at different developmental stages are still poorly understood.
Results: We characterized the relationship of chromatin accessibility, gene expression, and DNA binding of two MADS-domain proteins at different stages of Arabidopsis flower development. Dynamic changes in APETALA1 and SEPALLATA3 DNA binding correlated with changes in gene expression, and many of the target genes could be associated with the developmental stage in which they are transcriptionally controlled. We also observe dynamic changes in chromatin accessibility during flower development. Remarkably, DNA binding of APETALA1 and SEPALLATA3 is largely independent of the accessibility status of their binding regions and it can precede increases in DNA accessibility. These results suggest that APETALA1 and SEPALLATA3 may modulate chromatin accessibility, thereby facilitating access of other transcriptional regulators to their target genes.
Conclusions: Our findings indicate that different homeotic factors regulate partly overlapping, yet also distinctive sets of target genes in a partly stage-specific fashion. By combining the information from DNA-binding and gene expression data, we are able to propose models of stage-specific regulatory interactions, thereby addressing dynamics of regulatory networks throughout flower development. Furthermore, MADS-domain TFs may regulate gene expression by alternative strategies, one of which is modulation of chromatin accessibility.
The potential of ecological models for supporting environmental decision making is increasingly acknowledged. However, it often remains unclear whether a model is realistic and reliable enough. Good practice for developing and testing ecological models has not yet been established. Therefore, TRACE, a general framework for documenting a model's rationale, design, and testing was recently suggested. Originally TRACE was aimed at documenting good modelling practice. However, the word 'documentation' does not convey TRACE's urgency. Therefore, we re-define TRACE as a tool for planning, performing, and documenting good modelling practice. TRACE documents should provide convincing evidence that a model was thoughtfully designed, correctly implemented, thoroughly tested, well understood, and appropriately used for its intended purpose. TRACE documents link the science underlying a model to its application, thereby also linking modellers and model users, for example stakeholders, decision makers, and developers of policies. We report on first experiences in producing TRACE documents. We found that the original idea underlying TRACE was valid, but to make its use more coherent and efficient, an update of its structure and more specific guidance for its use are needed. The updated TRACE format follows the recently developed framework of model 'evaludation': the entire process of establishing model quality and credibility throughout all stages of model development, analysis, and application. TRACE thus becomes a tool for planning, documenting, and assessing model evaludation, which includes understanding the rationale behind a model and its envisaged use. We introduce the new structure and revised terminology of TRACE and provide examples. (C) 2014 Elsevier B.V. All rights reserved.
Volcanic tremor extraction and earthquake detection using music information retrieval algorithms
(2021)
Volcanic tremor signals are usually observed before or during volcanic eruptions and must be monitored to evaluate the volcanic activity. A challenge in studying seismic signals of volcanic origin is the coexistence of transient signal swarms and long-lasting volcanic tremor signals. Separating transient events from volcanic tremors can, therefore, contrib-ute to improving upon our understanding of the underlying physical processes. Exploiting the idea of harmonic-percussive separation in musical signal processing, we develop a method to extract the harmonic volcanic tremor signals and to detect tran-sient events from seismic recordings. Based on the similarity properties of spectrogram frames in the time-frequency domain, we decompose the signal into two separate spec-trograms representing repeating (harmonic) and nonrepeating (transient) patterns, which correspond to volcanic tremor signals and earthquake signals, respectively. We reconstruct the harmonic tremor signal in the time domain from the complex spectrogram of the repeating pattern by only considering the phase components for the frequency range in which the tremor amplitude spectrum is significantly contribut-ing to the energy of the signal. The reconstructed signal is, therefore, clean tremor signal without transient events. Furthermore, we derive a characteristic function suitable for the detection of tran-sient events (e.g., earthquakes) by integrating amplitudes of the nonrepeating spectro-gram over frequency at each time frame. Considering transient events like earthquakes, 78% of the events are detected for signal-to-noise ratio = 0.1 in our semisynthetic tests. In addition, we compared the number of detected earthquakes using our method for one month of continuous data recorded during the Holuhraun 2014-2015 eruption in Iceland with the bulletin presented in Agustsdottir et al. (2019). Our single station event detection algorithm identified 84% of the bulletin events. Moreover, we detected a total of 12,619 events, which is more than twice the number of the bulletin events.
Dielectrophoretic functionalization of nanoelectrode arrays for the detection of influenza viruses
(2017)
“They Took to the Sea”
(2023)
The sea and maritime spaces have long been neglected in the field of Jewish studies despite their relevance in the context of Jewish religious texts and historical narratives. The images of Noah’s arche, king Salomon’s maritime activities or the miracle of the parting of the Red Sea immediately come into mind, however, only illustrate a few aspects of Jewish maritime activities. Consequently, the relations of Jews and the sea has to be seen in a much broader spatial and temporal framework in order to understand the overall importance of maritime spaces in Jewish history and culture.
Almost sixty years after Samuel Tolkowsky’s pivotal study on maritime Jewish history and culture and the publication of his book “They Took to the Sea” in 1964, this volume of PaRDeS seeks to follow these ideas, revisit Jewish history and culture from different maritime perspectives and shed new light on current research in the field, which brings together Jewish and maritime studies.
The articles in this volume therefore reflect a wide range of topics and illustrate how maritime perspectives can enrich our understanding of Jewish history and culture and its entanglement with the sea – especially in modern times. They study different spaces and examine their embedded narratives and functions. They follow in one way or another the discussions which evolved in the last decades, focused on the importance of spatial dimensions and opened up possibilities for studying the production and construction of spaces, their influences on cultural practices and ideas, as well as structures and changes of social processes. By taking these debates into account, the articles offer new insights into Jewish history and culture by taking us out to “sea” and inviting us to revisit Jewish history and culture from different maritime perspectives.
Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.
Volcano-seismic signals such as long-period events and tremor are important indicators for volcanic activity and unrest. However, their wavefield is complex and characterization and location using traditional seismological instrumentation is often difficult.
In 2019 we recorded the full seismic wavefield using a newly developed 3C rotational sensor co-located with a 3C traditional seismometer on Etna, Italy. We compare the performance of the rotational sensor, the seismometer and the Istituto Nazionale di Geofisica e Vulcanologia-Osservatorio Etneo (INGV-OE) seismic network with respect to the analysis of complex volcano-seismic signals. We create event catalogs for volcano-tectonic (VT) and long-period (LP) events combining a STA/LTA algorithm and cross-correlations.
The event detection based on the rotational sensor is as reliable as the seismometer-based detection. The LP events are dominated by SH-type waves. Derived SH phase velocities range from 500 to 1,000 m/s for LP events and 300-400 m/s for volcanic tremor. SH-waves compose the tremor during weak volcanic activity and SH- and SV-waves during sustained strombolian activity.
We derive back azimuths using (a) horizontal rotational components and (b) vertical rotation rate and transverse acceleration. The estimated back azimuths are consistent with the INGV-OE event location for (a) VT events with an epicentral distance larger than 3 km and some closer events, (b) LP events and tremor in the main crater area. Measuring the full wavefield we can reliably analyze the back azimuths, phase velocities and wavefield composition for VT, LP events and tremor in regions that are difficult to access such as volcanoes.
On 21 April 2021, the European Commission presented its long-awaited proposal for a Regulation “laying down harmonized rules on Artificial Intelligence”, the so-called “Artificial Intelligence Act” (AIA). This article takes a critical look at the proposed regulation. After an introduction (1), the paper analyzes the unclear preemptive effect of the AIA and EU competences (2), the scope of application (3), the prohibited uses of Artificial Intelligence (AI) (4), the provisions on high-risk AI systems (5), the obligations of providers and users (6), the requirements for AI systems with limited risks (7), the enforcement system (8), the relationship of the AIA with the existing legal framework (9), and the regulatory gaps (10). The last section draws some final conclusions (11).
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.
initMIP-Antarctica
(2019)
Ice sheet numerical modeling is an important tool to estimate the dynamic contribution of the Antarctic ice sheet to sea level rise over the coming centuries. The influence of initial conditions on ice sheet model simulations, however, is still unclear. To better understand this influence, an initial state intercomparison exercise (initMIP) has been developed to compare, evaluate, and improve initialization procedures and estimate their impact on century-scale simulations. initMlP is the first set of experiments of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6), which is the primary Coupled Model Intercomparison Project Phase 6 (CMIP6) activity focusing on the Greenland and Antarctic ice sheets. Following initMlP-Greenland, initMlP-Antarctica has been designed to explore uncertainties associated with model initialization and spin-up and to evaluate the impact of changes in external forcings. Starting from the state of the Antarctic ice sheet at the end of the initialization procedure, three forward experiments are each run for 100 years: a control run, a run with a surface mass balance anomaly, and a run with a basal melting anomaly beneath floating ice. This study presents the results of initMlP-Antarctica from 25 simulations performed by 16 international modeling groups. The submitted results use different initial conditions and initialization methods, as well as ice flow model parameters and reference external forcings. We find a good agreement among model responses to the surface mass balance anomaly but large variations in responses to the basal melting anomaly. These variations can be attributed to differences in the extent of ice shelves and their upstream tributaries, the numerical treatment of grounding line, and the initial ocean conditions applied, suggesting that ongoing efforts to better represent ice shelves in continental-scale models should continue.
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.
The optical, structural, and electrical properties of thin layers made from poly(3-hexylthiophene) (P3HT) samples of different molecular weights are presented. As reported in a previous paper by Kline et al., Adv. Mater 2003, 15, 1519, the mobilities of these layers are a strong function of the molecular weight, with the largest mobility found for the largest molecular weight. Atomic force microscopy studies reveal a complex polycrystalline morphology which changes considerably upon annealing. X-ray studies show the occurrence of a layered phase for all P3HT fractions, especially after annealing at 1.50 degreesC . However, there is no clear correlation between the differences in the transport properties and the data from structural investigations. In order to reveal the processes limiting the mobility in these layers, the transistor properties were investigated as a function of temperature. The mobility decreases continuously with increasing temperatures; with the same trend pronounced thermochromic effects of the P3HT films occur. Apparently, the polymer chains adopt a more twisted, disordered conformation at higher temperatures, leading to interchain transport barriers. We conclude that the backbone conformation of the majority of the bulk material rather than the crystallinity of the layer is the most crucial parameter controlling the charge transport in these P3HT layers. This interpretation is supported by the significant blue-shift of the solid-state absorption spectra with decreasing molecular weight, which is indicative of a larger distortion of the P3HT backbone in the low-molecular weight P3HT layers
We report that the performances of blue polymer electrophosphorescent devices are crucially depending on the choice of the electron transporting material incorporated into the emissive layer. Devices with 1,3-bis[(4-tert- butylphenyl)-1,3,4-oxidiazolyl]phenylene (OXD-7) doped at similar to 40 wt% into a poly(vinylcarbazole) matrix exhibited significantly higher efficiencies than those with 2-(4-biphenylyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole (PBD), yielding maximum luminous and power efficiency values of 18.2 Cd/A and 8.8 lm/W, respectively. Time resolved photoluminescence measurements revealed a long lifetime phosphorescence component in layers with PBD, which we assign to significant triplet harvesting by this electron-transporting component. (c) 2006 American Institute of Physics