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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.
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.
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 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.
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.