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In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.
In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.
Prospects for Cherenkov Telescope Array Observations of the Young Supernova Remnant RX J1713.7-3946
(2017)
We perform simulations for future Cherenkov Telescope Array (CTA) observations of RX J1713.7-3946, a young supernova remnant (SNR) and one of the brightest sources ever discovered in very high energy (VHE) gamma rays. Special attention is paid to exploring possible spatial (anti) correlations of gamma rays with emission at other wavelengths, in particular X-rays and CO/H I emission. We present a series of simulated images of RX J1713.7-3946 for CTA based on a set of observationally motivated models for the gamma-ray emission. In these models, VHE gamma rays produced by high-energy electrons are assumed to trace the nonthermal X-ray emission observed by XMM-Newton, whereas those originating from relativistic protons delineate the local gas distributions. The local atomic and molecular gas distributions are deduced by the NANTEN team from CO and H I observations. Our primary goal is to show how one can distinguish the emission mechanism(s) of the gamma rays (i.e., hadronic versus leptonic, or a mixture of the two) through information provided by their spatial distribution, spectra, and time variation. This work is the first attempt to quantitatively evaluate the capabilities of CTA to achieve various proposed scientific goals by observing this important cosmic particle accelerator.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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.
Coccolithophores have influenced the global climate for over 200 million years(1). These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems(2). They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering them visible from space(3). Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO2 production or uptake, sequestration and export to the deep ocean(4). Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate that E. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions.
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
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.
The thermal behavior of poly(methoxydiethylenglycol acrylate) (PMDEGA) is studied in thin hydrogel films on solid supports and is compared with the behavior in aqueous solution. The PMDEGA hydrogel film thickness is varied from 2 to 422 nm. Initially, these films are homogenous, as measured with optical microscopy, atomic force microscopy, X-ray reflectivity, and grazing-incidence small-angle X-ray scattering (GISAXS). However, they tend to de-wet when stored under ambient conditions. Along the surface normal, no long-ranged correlations between substrate and film surface are detected with GISAXS, due to the high mobility of the polymer at room temperature. The swelling of the hydrogel films as a function of the water vapor pressure and the temperature are probed for saturated water vapor pressures between 2,380 and 3,170 Pa. While the swelling capability is found to increase with water vapor pressure, swelling in dependence on the temperature revealed a collapse phase transition of a lower critical solution temperature type. The transition temperature decreases from 40.6 A degrees C to 36.6 A degrees C with increasing film thickness, but is independent of the thickness for very thin films below a thickness of 40 nm. The observed transition temperature range compares well with the cloud points observed in dilute (0.1 wt.%) and semi-dilute (5 wt.%) solution which decrease from 45 A degrees C to 39 A degrees C with increasing concentration.
Systematic review and meta-analysis of ex-post evaluations on the effectiveness of carbon pricing
(2024)
Today, more than 70 carbon pricing schemes have been implemented around the globe, but their contributions to emissions reductions remains a subject of heated debate in science and policy. Here we assess the effectiveness of carbon pricing in reducing emissions using a rigorous, machine-learning assisted systematic review and meta-analysis. Based on 483 effect sizes extracted from 80 causal ex-post evaluations across 21 carbon pricing schemes, we find that introducing a carbon price has yielded immediate and substantial emission reductions for at least 17 of these policies, despite the low level of prices in most instances. Statistically significant emissions reductions range between –5% to –21% across the schemes (–4% to –15% after correcting for publication bias). Our study highlights critical evidence gaps with regard to dozens of unevaluated carbon pricing schemes and the price elasticity of emissions reductions. More rigorous synthesis of carbon pricing and other climate policies is required across a range of outcomes to advance our understanding of “what works” and accelerate learning on climate solutions in science and policy.
We report the discovery of three stars that, along with the prototype LP 40-365, form a distinct class of chemically peculiar runaway stars that are the survivors of thermonuclear explosions. Spectroscopy of the four confirmed LP 40-365 stars finds ONe-dominated atmospheres enriched with remarkably similar amounts of nuclear ashes of partial O- and Si-burning. Kinematic evidence is consistent with ejection from a binary supernova progenitor; at least two stars have rest-frame velocities indicating they are unbound to the Galaxy. With masses and radii ranging between 0.20 and 0.28M(circle dot) and between 0.16 and 0.60 R-circle dot, respectively, we speculate these inflated white dwarfs are the partly burnt remnants of either peculiar Type Iax or electron-capture supernovae. Adopting supernova rates from the literature, we estimate that similar to 20 LP 40-365 stars brighter than 19 mag should be detectable within 2 kpc from the Sun at the end of the Gaia mission. We suggest that as they cool, these stars will evolve in their spectroscopic appearance, and eventually become peculiar O-rich white dwarfs. Finally, we stress that the discovery of new LP 40-365 stars will be useful to further constrain their evolution, supplying key boundary conditions to the modelling of explosion mechanisms, supernova rates, and nucleosynthetic yields of peculiar thermonuclear explosions.
Eclipsing post-common-envelope binaries are highly important for resolving the poorly understood, very short-lived common-envelope phase of stellar evolution. Most hot subdwarfs (sdO/Bs) are the bare helium-burning cores of red giants that have lost almost all of their hydrogen envelope. This mass loss is often triggered by common-envelope interactions with close stellar or even substellar companions. Cool companions to hot subdwarf stars such as late-type stars and brown dwarfs are detectable from characteristic light-curve variations - reflection effects and often eclipses. In the recently published catalog of eclipsing binaries in the Galactic Bulge and in the Asteroid Terrestrial-impact Last Alert System (ATLAS) survey, we discovered 125 new eclipsing systems showing a reflection effect seen by visual inspection of the light curves and using a machine-learning algorithm, in addition to the 36 systems previously discovered by the Optical Gravitational Lesing Experiment (OGLE) team. The Eclipsing Reflection Effect Binaries from Optical Surveys (EREBOS) project aims at analyzing all newly discovered eclipsing binaries of the HW Vir type (hot subdwarf + close, cool companion) based on a spectroscopic and photometric follow up to derive the mass distribution of the companions, constrain the fraction of substellar companions, and determine the minimum mass needed to strip off the red-giant envelope. To constrain the nature of the primary we derived the absolute magnitude and the reduced proper motion of all our targets with the help of the parallaxes and proper motions measured by the Gaia mission and compared those to the Gaia white-dwarf candidate catalog. It was possible to derive the nature of a subset of our targets, for which observed spectra are available, by measuring the atmospheric parameter of the primary, confirming that less than 10% of our systems are not sdO/Bs with cool companions but are white dwarfs or central stars of planetary nebula. This large sample of eclipsing hot subdwarfs with cool companions allowed us to derive a significant period distribution for hot subdwarfs with cool companions for the first time showing that the period distribution is much broader than previously thought and is ideally suited to finding the lowest-mass companions to hot subdwarf stars. The comparison with related binary populations shows that the period distribution of HW Vir systems is very similar to WD+dM systems and central stars of planetary nebula with cool companions. In the future, several new photometric surveys will be carried out, which will further increase the sample of this project, providing the potential to test many aspects of common-envelope theory and binary evolution.
The presence of ultrahigh excitation (UHE) absorption lines (e.g. OVIII) in the optical spectra of several of the hottest white dwarfs poses a decades-long mystery and is something that has never been observed in any other astrophysical object. The occurrence of such features requires a dense environment with temperatures near 10(6) K, by far exceeding the stellar effective temperature. Here we report the discovery of a new hot wind white dwarf, GALEXJ014636.8+323615. Astonishingly, we found for the first time rapid changes of the equivalent widths of the UHE features, which are correlated to the rotational period of the star (P=0.242035 d). We explain this with the presence of a wind-fed circumstellar magnetosphere in which magnetically confined wind shocks heat up the material to the high temperatures required for the creation of the UHE lines. The photometric and spectroscopic variability of GALEXJ014636.8+323615 can then be understood as consequence of the obliquity of the magnetic axis with respect to the rotation axis of the white dwarf. This is the first time a wind-fed circumstellar magnetosphere around an apparently isolated white dwarf has been discovered and finally offers a plausible explanation of the ultrahot wind phenomenon.
In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
Nature-based solutions (NBS) are inspired and supported by nature but designed by humans. Historically, governmental stakeholders have aimed to control nature using a top-down approach; more recently, environmental governance has shifted to collaborative planning. Polycentric governance and co-creation procedures, which include a large spectrum of stakeholders, are assumed to be more effective in the management of public goods than traditional approaches. In this context, NBS projects should benefit from strong collaborative governance models, and the European Union is facilitating and encouraging such models. While some theoretical approaches exist, setting-up the NBS co-creation process (namely co-design and co-implementation) currently relies mostly on self-organized stakeholders rather than on strategic decisions. As such, systematic methods to identify relevant stakeholders seem to be crucial to enable higher planning efficiency, reduce bottlenecks and time needed for planning, designing, and implementing NBS. In this context, this contribution is based on the analysis of 16 NBS and 359 stakeholders. Real-life constellations are compared to theoretical typologies, and a systematic stakeholder mapping method to support co-creation is presented. Rather than making one-fit-all statements about the "right" stakeholders, the contribution provides insights for those "in charge" to strategically consider who might be involved at each stage of the NBS project.
Media coverage of the 2003 Iraq War frequently contained corrections and retractions of earlier information. For example, claims that Iraqi forces executed coalition prisoners of war after they surrendered were retracted the day after the claims were made. Similarly, tentative initial reports about the discovery of weapons of mass destruction were all later disconfirmed. We investigated the effects of these retractions and disconfirmations on people's memory for and beliefs about war-related events in two coalition countries (Australia and the United States) and one country that opposed the war (Germany). Participants were queried about (a) true events, (b) events initially presented as fact but subsequently retracted, and (c) fictional events. Participants in the United States did not show sensitivity to the correction of misinformation, whereas participants in Australia and Germany discounted corrected misinformation. Our results are consistent with previous findings in that the differences between samples reflect greater suspicion about the motives underlying the war among people in Australia and Germany than among people in the United States
Anthracyclines like daunorubicin (DRN) and doxorubicin (DOX) play an undisputed key role in cancer treatment, but their chronic administration can cause severe side effects. For precise anthracycline analytical systems, aptamers are preferable recognition elements. Here, we describe the detailed characterisation of a single-stranded DNA aptamer DRN-10 and its truncated versions for DOX and DRN detection. Binding affinities were determined from surface plasmon resonance (SPR) and microscale thermophoresis (MST) and combined with conformational data from circular dichroism (CD). Both aptamers displayed similar nanomolar binding affinities to DRN and DOX, even though their rate constants differed as shown by SPR recordings. SPR kinetic data unravelled a two-state reaction model including a 1 : 1 binding and a subsequent conformational change of the binding complex. This model was supported by CD spectra. In addition, the dissociation constants determined with MST were always lower than that from SPR, and especially for the truncated aptamer they differed by two orders of magnitude. This most probably reflects the methodological difference, namely labelling for MST vs. immobilisation for SPR. From CD recordings, we suggested a specific G-quadruplex as structural basis for anthracycline binding. We concluded that the aptamer DRN-10 is a promising recognition element for anthracycline detection systems and further selected aptamers can be also characterised with the combined methodological approach presented here.
Arctic lowlands are characterized by large numbers of small waterbodies, which are known to affect surface energy budgets and the global carbon cycle. Statistical analysis of their size distributions has been hindered by the shortage of observations at sufficiently high spatial resolutions. This situation has now changed with the high-resolution (<5 m) circum-Arctic Permafrost Region Pond and Lake (PeRL) database recently becoming available. We have used this database to make the first consistent, high-resolution estimation of Arctic waterbody size distributions, with surface areas ranging from 0.0001 km(2) (100 m(2)) to 1 km(2). We found that the size distributions varied greatly across the thirty study regions investigated and that there was no single universal size distribution function (including power-law distribution functions) appropriate across all of the study regions. We did, however, find close relationships between the statistical moments (mean, variance, and skewness) of the waterbody size distributions from different study regions. Specifically, we found that the spatial variance increased linearly with mean waterbody size (R-2 = 0.97, p < 2.2e-16) and that the skewness decreased approximately hyperbolically. We have demonstrated that these relationships (1) hold across the 30 Arctic study regions covering a variety of (bio)climatic and permafrost zones, (2) hold over time in two of these study regions for which multi-decadal satellite imagery is available, and (3) can be reproduced by simulating rising water levels in a high-resolution digital elevation model. The consistent spatial and temporal relationships between the statistical moments of the waterbody size distributions underscore the dominance of topographic controls in lowland permafrost areas. These results provide motivation for further analyses of the factors involved in waterbody development and spatial distribution and for investigations into the possibility of using statistical moments to predict future hydrologic dynamics in the Arctic.
A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others ('reinventing the wheel'). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available ('having tunnel vision'). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and traitbased models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its 'leading principle', there are many opportunities for combining approaches. We take the point of view that a single 'right' approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative view on the functioning of lake ecosystems. We end with a set of specific recommendations that may be of help in the further development of lake ecosystem models.
A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others ('reinventing the wheel'). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available ('having tunnel vision'). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and traitbased models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its 'leading principle', there are many opportunities for combining approaches. We take the point of view that a single 'right' approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative view on the functioning of lake ecosystems. We end with a set of specific recommendations that may be of help in the further development of lake ecosystem models.
Swelling and switching kinetics of gold coated end-capped poly(N-isopropylacrylamide) thin films
(2010)
Thin thermoresponsive hydrogel films of poly(N-isopropylacrylamide) end-capped with n-butyltrithiocarbonate(nbc- PNIPAM) oil si I icon supports with a gold layer on top, causing an asymmetric confinement, are investigated. For two different gold layer thicknesses (nominally 0.4 and 5 rim), the swelling and switching kinetics are probed with in situ neutron reflectivity. With a temperature jump from 23 to 40 degrees C the film is switched from a swollen into a collapsed state. For the thin gold layer this switching is faster as compared to the thick gold layer. The switching is a two-step process of water release and a subsequent structural relaxation. fit swelling and deswelling cycles, aging of the films is probed. After five cycles, the film exhibits enhanced water storage capacity. Grazing-incidence small-angle X-ray scattering (GISAXS) shows that these gold coated nbc-PNIPAM films do not age with respect to the inner structure but slightly roughen at the gold surface. As revealed by atomic force microscopy, the morphology of the gold layer is changed by the water uptake and release.
High resolution isotopic (delta O-18 and delta C-13) investigations on endogenic carbonates (calcite/aragonite) from Tso Moriri Lake, NW Himalaya show dramatic fluctuations during the late glacial and the early Holocene, and a persistent enrichment trend during the late Holocene. Changes in this lake are largely governed by the [input (meltwater + monsoon precipitation)/evaporationj (WE) ratio, also reflected in changes in the carbonate mineralogy with aragonite being formed during periods of lowest I/E. Using new isotopic data on endogenic carbonates in combination with the available data on geochemistry, mineralogy, and reconstructed mean annual precipitation, we demonstrate that the late glacial and early Holocene carbonate delta O-18 variability resulted from fluctuating Indian summer monsoon (ISM) precipitation in NW Himalaya. This region experienced increasing ISM precipitation between ca. 13.1 and 11.7 cal ka and highest ISM precipitation during the early Holocene (11.2-8.5 cal ka). However, during the late Holocene, evaporation was the dominant control on the carbonate delta O-18. Regional comparison of reconstructed hydrological changes from Tso Moriri Lake with other archives from the Asian summer monsoon and westerlies domain shows that the intensified westerly influence that resulted in higher lake levels (after 8 cal ka) in central Asia was not strongly felt in NW Himalaya. (C) 2015 Elsevier B.V. All rights reserved.
Organosilanes are used routinely to functionalize various support materials for further modifications. Nevertheless, reliable quantitative information about surface functional group densities after layer formation is rarely available. Here, we present the analysis of thin organic nanolayers made from nitrogen containing silane molecules on naturally oxidized silicon wafers with reference-free total reflection X-ray fluorescence (TXR.F) and X-ray photoelectron spectroscopy (XPS). An areic density of 2-4 silane molecules per nm(2) was calculated from the layer's nitrogen mass deposition per area unit obtained by reference-free TXRF. Complementary energy and angle-resolved XPS (ER/AR-XPS) in the Si 2p core-level region was used to analyze the outermost surface region of the organic (silane layer)-inorganic (silicon wafer) interface. Different coexisting silicon species as silicon, native silicon oxide, and silane were identified and quantified. As a result of the presented proof-of-concept, absolute and traceable values for the areic density of silanes containing nitrogen as intrinsic marker are obtained by calibration of the XPS methods with reference-free TXRF. Furthermore, ER/AR-XPS is shown to facilitate the determination of areic densities in (mono)layers made from silanes having no heteroatomic marker other than silicon. After calibration with reference-free TXRF, these areic densities of silane molecules can be determined when using the XPS component intensity of the silane's silicon atom.
Successful aging (SA) has been conceptualized in a number of ways. Despite increasing research into how laypersons define SA, few studies capturing lay perspectives of SA in younger cohorts and in non-English speaking countries have been undertaken. The current study examines cross-cultural perspectives of SA in young (aged 18-35), lay adults from a variety of continental European countries and Turkey. Participants were recruited via snowball sampling from social network sites and invited to participate in an online survey. Persons between 18-35 years from Belgium, Estonia, Germany, Netherlands, Romania, Switzerland, or Turkey were included. Respondents (total: 390; Belgian: 32; Estonian: 96; German: 76; Romanian: 47; Swiss: 39; Dutch: 30; Turkish: 70), were primarily women (56.4%) and students (66.2%), with an average age of 24.1 years (SD 3.7). Personal resources, social and active engagement all emerged as dominant themes across countries, but were articulated in subtly different ways in the participant countries. Positive perspectives, desirable attributes and satisfaction themes were intertwined within themes of acceptance and engagement. The current study provides a first step in the inclusion of geographic and cultural diversity into the SA literature. These results suggest that layperson conceptualizations of SA have broad-sweeping similarities, but further research is required to articulate the nuance of cultural influences on SA.
Synchrotron-radiation XPS analysis of ultra-thin silane films: Specifying the organic silicon
(2016)
The analysis of chemical and elemental in-depth variations in ultra-thin organic layers with thicknesses below 5 nm is very challenging. Energy- and angle-resolved XPS (ER/AR-XPS) opens up the possibility for non-destructive chemical ultra-shallow depth profiling of the outermost surface layer of ultra-thin organic films due to its exceptional surface sensitivity. For common organic materials a reliable chemical in-depth analysis with a lower limit of the XPS information depth z(95) of about 1 nm can be performed. As a proof-of-principle example with relevance for industrial applications the ER/AR-XPS analysis of different organic monolayers made of amino- or benzamidosilane molecules on silicon oxide surfaces is presented. It is demonstrated how to use the Si 2p core-level region to non-destructively depth-profile the organic (silane monolayer) - inorganic (SiO2/Si) interface and how to quantify Si species, ranging from elemental silicon over native silicon oxide to the silane itself. The main advantage of the applied ER/AR-XPS method is the improved specification of organic from inorganic silicon components in Si 2p core-level spectra with exceptional low uncertainties compared to conventional laboratory XPS. (C) 2015 Elsevier B.V. All rights reserved.
Subduction and collision processes in the Central Andes constrained by converted seismic phases
(2000)
The Argentine-German Geodetic Observatory (AGGO) is one of the very few sites in the Southern Hemisphere equipped with comprehensive cutting-edge geodetic instrumentation. The employed observation techniques are used for a wide range of geophysical applications. The data set provides gravity time series and selected gravity models together with the hydrometeorological monitoring data of the observatory. These parameters are of great interest to the scientific community, e.g. for achieving accurate realization of terrestrial and celestial reference frames. Moreover, the availability of the hydrometeorological products is beneficial to inhabitants of the region as they allow for monitoring of environmental changes and natural hazards including extreme events. The hydrological data set is composed of time series of groundwater level, modelled and observed soil moisture content, soil temperature, and physical soil properties and aquifer properties. The meteorological time series include air temperature, humidity, pressure, wind speed, solar radiation, precipitation, and derived reference evapotranspiration. These data products are extended by gravity models of hydrological, oceanic, La Plata estuary, and atmospheric effects. The quality of the provided meteorological time series is tested via comparison to the two closest WMO (World Meteorological Organization) sites where data are available only in an inferior temporal resolution. The hydrological series are validated by comparing the respective forward-modelled gravity effects to independent gravity observations reduced up to a signal corresponding to local water storage variation. Most of the time series cover the time span between April 2016 and November 2018 with either no or only few missing data points. The data set is available at https://doi.org/10.588/GFZ.5.4.2018.001 (Mikolaj et al., 2018).
Multi-proxy dating of Holocene maar lakes and Pleistocene dry maar sediments in the Eifel, Germany
(2013)
During the last twelve years the ELSA Project (Eifel Laminated Sediment Archive) at Mainz University has drilled a total of about 52 cores from 27 maar lakes and filled-in maar basins in the Eifel/Germany. Dating has been completed for the Holocene cores using 6 different methods (Pb-210 and Cs-137 activities, palynostratigraphy, event markers, varve counting, C-14) In general, the different methods consistently complement one another within error margins. Event correlation was used for relating typical lithological changes with historically known events such as the two major Holocene flood events at 1342 AD and ca 800 BC. Dating of MIS2-MIS3 core sections is based on greyscale tuning, radiocarbon and OSL dating, magnetostratigraphy and tephrochronology. The lithological changes in the sediment cores demonstrate a sequence of events similar to the North Atlantic rapid climate variability of the Last Glacial Cycle. The warmest of the MIS3 interstadials was GI14, when a forest with abundant spruce covered the Eifel area from 55 to 48 ka BP, i.e. during a time when also other climate archives in Europe suggested very warm conditions. The forest of this "Early Stage 3 warm phase" developed subsequently into a steppe with scattered birch and pine, and finally into a glacial desert at around 25 ka BP. Evidence for Mono Lake and Laschamp geomagnetic excursions is found in two long cores. Several large eruptions during Middle and Late Pleistocene (Ulmener Maar - 11,000 varve years BP, Laacher See - 12,900 varve years BP, Mosenberg volcanoes/Meerfelder Maar 41-45 cal ka BP, Dumpel Maar 116 ka BP, Glees Maar - 151 ka BP) produced distinct ash-layers crucial for inter-core and inter-site correlations. The oldest investigated maar of the Eifel is Ar-40/Ar-39 dated to the time older than 520 ka BP.
Tula virus (TULV) is a vole-associated hantavirus with low or no pathogenicity to humans. In the present study, 686 common voles (Microtus arvalis), 249 field voles (Microtus agrestis) and 30 water voles (Arvicola spec.) were collected at 79 sites in Germany, Luxembourg and France and screened by RT-PCR and TULV-IgG ELISA. TULV-specific RNA and/or antibodies were detected at 43 of the sites, demonstrating a geographically widespread distribution of the virus in the studied area. The TULV prevalence in common voles (16.7 %) was higher than that in field voles (9.2 %) and water voles (10.0 %). Time series data at ten trapping sites showed evidence of a lasting presence of TULV RNA within common vole populations for up to 34 months, although usually at low prevalence. Phylogenetic analysis demonstrated a strong genetic structuring of TULV sequences according to geography and independent of the rodent species, confirming the common vole as the preferential host, with spillover infections to co-occurring field and water voles. TULV phylogenetic clades showed a general association with evolutionary lineages in the common vole as assessed by mitochondrial DNA sequences on a large geographical scale, but with local-scale discrepancies in the contact areas.
Minimising Information Loss on Anonymised High Dimensional Data with Greedy In-Memory Processing
(2018)
Minimising information loss on anonymised high dimensional data is important for data utility. Syntactic data anonymisation algorithms address this issue by generating datasets that are neither use-case specific nor dependent on runtime specifications. This results in anonymised datasets that can be re-used in different scenarios which is performance efficient. However, syntactic data anonymisation algorithms incur high information loss on high dimensional data, making the data unusable for analytics. In this paper, we propose an optimised exact quasi-identifier identification scheme, based on the notion of k-anonymity, to generate anonymised high dimensional datasets efficiently, and with low information loss. The optimised exact quasi-identifier identification scheme works by identifying and eliminating maximal partial unique column combination (mpUCC) attributes that endanger anonymity. By using in-memory processing to handle the attribute selection procedure, we significantly reduce the processing time required. We evaluated the effectiveness of our proposed approach with an enriched dataset drawn from multiple real-world data sources, and augmented with synthetic values generated in close alignment with the real-world data distributions. Our results indicate that in-memory processing drops attribute selection time for the mpUCC candidates from 400s to 100s, while significantly reducing information loss. In addition, we achieve a time complexity speed-up of O(3(n/3)) approximate to O(1.4422(n)).
It has long been appreciated that material chemistry and topology profoundly affect cell adhesion and migration. Here, aqueous poly(N- isopropyl acrylamide) nanogels are designed, synthesized and printed in form of colloidal arrays on glass substrates using wrinkled polydimethylsiloxane templates. Using low-temperature plasma treatment, nanogels are chemically grafted onto glass supports thus leading to highly stable nanogel layers in cell culture media. Liquid cell atomic force microscopy investigations show that surface-grafted nanogels retain their swelling behavior in aqueous media and that extracellular matrix protein coating do not alter their stability and topography. It is demonstrated that surface-grafted nanogels could serve as novel substrates for the analysis of cell adhesion and migration. Nanogels influence size, speed, and dynamics of focal adhesions and cell motility forcing cells to move along highly directional trajectories. Moreover, modulation of nanogel state or spacing serves as an effective tool for regulation of cell motility. It is suggested that nanogel arrays deposited on solid surfaces could be used to provide a precise and tunable system to understand and control cell migration. Additionally, such nanogel arrays will contribute to the development of implantable systems aimed at supporting and enhancing cell migration during, for instance, wound healing and tissue regeneration.
Solute concentration variability is of fundamental importance for the chemical and ecological state of streams. It is often closely related to discharge variability and can be characterized in terms of a solute export regime. Previous studies, especially in lowland catchments, report that nitrate is often exported with an accretion pattern of increasing concentrations with increasing discharge. Several modeling approaches exist to predict the export regime of solutes from the spatial relationship of discharge generating zones with solute availability in the catchment. For a small agriculturally managed lowland catchment in central Germany, we show that this relationship is controlled by the depth to groundwater table and its temporal dynamics. Principal component analysis of groundwater level time series from wells distributed throughout the catchment allowed derivation of a representative groundwater level time series that explained most of the discharge variability. Groundwater sampling revealed consistently decreasing nitrate concentrations with an increasing thickness of the unsaturated zone. The relationships of depth to groundwater table to discharge and to nitrate concentration were parameterized and integrated to successfully model catchment discharge and nitrate export on the basis of groundwater level variations alone. This study shows that intensive and uniform agricultural land use likely results in a clear and consistent concentration-depth relationship of nitrate, which can be utilized in simple approaches to predict stream nitrate export dynamics at the catchment scale. (C) 2016 Elsevier Ltd. All rights reserved.
While food deprivation has known effects on sympathovagal balance, little is known about hunger's influence on the perception of pain. Since autonomic activities influence many cognitive and emotional processes, this suggests that food deprivation should interact with the perception of pain. This study analyzed the possible effects of short-term food deprivation on pain sensitivity in healthy female participants. This study was comprised of 32 healthy female participants who underwent a 48-hr inpatient hospital investigation. Prior to testing, heart rate and heart rate variability were assessed. After a standardized breakfast, day 1 measurements were taken. Food intake was then not allowed again until the following evening for 22 participants (experimental group), while 12 participants were served standard meals (control group). Pain threshold and tolerance were assessed at 10:00 a. m. on both days using a pressure algometer. Additionally pain experience was examined. Food deprivation significantly reduced pain thresholds and tolerance scores in the experimental group. Additionally, the sympathovagal balance changed, characterized by a decrease in parasympathetic activation. Higher vagal withdrawal after food deprivation was associated with higher pain sensitivity in the experimental group. Furthermore, perceived unpleasantness and pain intensity increased for threshold and tolerance stimuli in the experimental group. We conclude that short-term food deprivation sensitized pain perception in healthy females. An imbalance in sympathovagal activation evoked by food deprivation accounted for this effect. Our results might be a pathogenic mechanism for the development of emotional difficulties associated with disturbed eating behavior.
The perception of internal bodily signals (interoception) plays a relevant role for emotion processing and feelings. This study investigated changes of interoceptive awareness and cardiac autonomic activity induced by short-term food deprivation and its relationship to hunger and affective experience. 20 healthy women were exposed to 24 h of food deprivation in a controlled setting. Interoceptive awareness was assessed by using a heartbeat tracking task. Felt hunger, cardiac autonomic activity, mood and subjective appraisal of interoceptive sensations were assessed before and after fasting. Results show that short-term fasting intensifies interoceptive awareness, not restricted to food cues, via changes of autonomic cardiac and/or cardiodynamic activity. The increase of interoceptive awareness was positively related to felt hunger. Additionally, the results demonstrate the role of cardiac vagal activity as a potential index of emotion related self-regulation, for hunger, mood and the affective appraisal of interoceptive signals during acute fasting.
The effect of chain architecture on the swelling and thermal response of thin films obtained from an amphiphilic three-arm star-shaped thermo-responsive block copolymer poly(methoxy diethylene glycol acrylate)-block-polystyrene ((PMDEGA-b-PS)(3)) is investigated by in situ neutron reflectivity (NR) measurements. The PMDEGA and PS blocks are micro-phase separated with randomly distributed PS nanodomains. The (PMDEGA-b-PS)(3) films show a transition temperature (TT) at 33 degrees C in white light interferometry. The swelling capability of the (PMDEGA-b-PS)(3) films in a D2O vapor atmosphere is better than that of films from linear PS-b-PMDEGA-b-PS triblock copolymers, which can be attributed to the hydrophilic end groups and limited size of the PS blocks in (PMDEGA-b-PS)(3). However, the swelling kinetics of the as-prepared (PMDEGA-b-PS)(3) films and the response of the swollen film to a temperature change above the TT are significantly slower than that in the PS-b-PMDEGA-b-PS films, which may be related to the conformation restriction by the star-shape. Unlike in the PS-b-PMDEGA-b-PS films, the amount of residual D2O in the collapsed (PMDEGA-b-PS)(3) films depends on the final temperature. It decreases from (9.7 +/- 0.3)% to (7.0 +/- 0.3)% or (6.0 +/- 0.3)% when the final temperatures are set to 35 degrees C, 45 degrees C and 50 degrees C, respectively. This temperature-dependent reduction of embedded D2O originates from the hindrance of chain conformation from the star-shaped chain architecture.
Water stable isotope signatures can provide valuable insights into the catchment internal runoff processes. However, the ability of the water isotope data to constrain the internal apportionments of runoff components in hydrological models for glacierized basins is not well understood. This study developed an approach to simultaneously model the water stable isotopic compositions and runoff processes in a glacierized basin in Central Asia. The fractionation and mixing processes of water stable isotopes in and from the various water sources were integrated into a glacio-hydrological model. The model parameters were calibrated on discharge, snow cover and glacier mass balance data, and additionally isotopic composition of streamflow. We investigated the value of water isotopic compositions for the calibration of model parameters, in comparison to calibration methods without using such measurements. Results indicate that: (1) The proposed isotope-hydrological integrated modeling approach was able to reproduce the isotopic composition of streamflow, and improved the model performance in the evaluation period; (2) Involving water isotopic composition for model calibration reduced the model parameter uncertainty, and helped to reduce the uncertainty in the quantification of runoff components; (3) The isotope-hydrological integrated modeling approach quantified the contributions of runoff components comparably to a three-component tracer-based end-member mixing analysis method for summer peak flows, and required less water tracer data. Our findings demonstrate the value of water isotopic compositions to improve the quantification of runoff components using hydrological models in glacierized basins.
Pavlovian-to-instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high-risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18-year-old male adults. Participants (N = 191) were instructed to 'collect good shells' and 'leave bad shells' during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high-risk and low-risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high-risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high-risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High-risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom-up), decreased lPFC response (top-down), and their altered interplay may contribute to poor interference control in the high-risk drinkers.
Drunk decisions
(2018)
Background: Studies in humans and animals suggest a shift from goal-directed to habitual decision-making in addiction. We therefore tested whether acute alcohol administration reduces goal-directed and promotes habitual decision-making, and whether these effects are moderated by self-reported drinking problems. Methods: Fifty-three socially drinking males completed the two-step task in a randomised crossover design while receiving an intravenous infusion of ethanol (blood alcohol level=80 mg%), or placebo. To minimise potential bias by long-standing heavy drinking and subsequent neuropsychological impairment, we tested 18- to 19-year-old adolescents. Results: Alcohol administration consistently reduced habitual, model-free decisions, while its effects on goal-directed, model-based behaviour varied as a function of drinking problems measured with the Alcohol Use Disorders Identification Test. While adolescents with low risk for drinking problems (scoring <8) exhibited an alcohol-induced numerical reduction in goal-directed choices, intermediate-risk drinkers showed a shift away from habitual towards goal-directed decision-making, such that alcohol possibly even improved their performance. Conclusions: We assume that alcohol disrupted basic cognitive functions underlying habitual and goal-directed decisions in low-risk drinkers, thereby enhancing hasty choices. Further, we speculate that intermediate-risk drinkers benefited from alcohol as a negative reinforcer that reduced unpleasant emotional states, possibly displaying a novel risk factor for drinking in adolescence.
The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.
Behavioral choice can be characterized along two axes. One axis distinguishes reflexive, model-free systems that slowly accumulate values through experience and a model-based system that uses knowledge to reason prospectively. The second axis distinguishes Pavlovian valuation of stimuli from instrumental valuation of actions or stimulus–action pairs. This results in four values and many possible interactions between them, with important consequences for accounts of individual variation. We here explored whether individual variation along one axis was related to individual variation along the other. Specifically, we asked whether individuals' balance between model-based and model-free learning was related to their tendency to show Pavlovian interferences with instrumental decisions. In two independent samples with a total of 243 participants, Pavlovian–instrumental transfer effects were negatively correlated with the strength of model-based reasoning in a two-step task. This suggests a potential common underlying substrate predisposing individuals to both have strong Pavlovian interference and be less model-based and provides a framework within which to interpret the observation of both effects in addiction.
Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding. Acute stress reactivity is known to impair model-based but not model-free choice behavior, with higher working memory capacity protecting the model-based system from acute stress. However, it is not clear which impact accumulated real life stress has on model-free and model-based decision systems and how this influence interacts with cognitive abilities. Methods: We used a sequential decision-making task distinguishing relative contributions of both learning strategies to choice behavior, the Social Readjustment Rating Scale questionnaire to assess accumulated real life stress, and the Digit Symbol Substitution Test to test cognitive speed in 95 healthy subjects. Results: Individuals reporting high stress exposure who had low cognitive speed showed reduced model-based but increased model-free behavioral control. In contrast, subjects exposed to accumulated real life stress with high cognitive speed displayed increased model-based performance but reduced model-free control. Conclusion: These findings suggest that accumulated real life stress exposure can enhance reliance on cognitive speed for model-based computations, which may ultimately protect the model-based system from the detrimental influences of accumulated real life stress. The combination of accumulated real life stress exposure and slower information processing capacities, however, might favor model-free strategies. Thus, the valence and preference of either system strongly depends on stressful experiences and individual cognitive capacities.
No association of goal-directed and habitual control with alcohol consumption in young adults
(2017)
Alcohol dependence is a mental disorder that has been associated with an imbalance in behavioral control favoring model-free habitual over model-based goal-directed strategies. It is as yet unknown, however, whether such an imbalance reflects a predisposing vulnerability or results as a consequence of repeated and/or excessive alcohol exposure. We, therefore, examined the association of alcohol consumption with model-based goal-directed and model-free habitual control in 188 18-year-old social drinkers in a two-step sequential decision-making task while undergoing functional magnetic resonance imaging before prolonged alcohol misuse could have led to severe neurobiological adaptations. Behaviorally, participants showed a mixture of model-free and model-based decision-making as observed previously. Measures of impulsivity were positively related to alcohol consumption. In contrast, neither model-free nor model-based decision weights nor the trade-off between them were associated with alcohol consumption. There were also no significant associations between alcohol consumption and neural correlates of model-free or model-based decision quantities in either ventral striatum or ventromedial prefrontal cortex. Exploratory whole-brain functional magnetic resonance imaging analyses with a lenient threshold revealed early onset of drinking to be associated with an enhanced representation of model-free reward prediction errors in the posterior putamen. These results suggest that an imbalance between model-based goal-directed and model-free habitual control might rather not be a trait marker of alcohol intake per se.
Background:
Prejudices against minorities can be understood as habitually negative evaluations that are kept in spite of evidence to the contrary. Therefore, individuals with strong prejudices might be dominated by habitual or "automatic" reactions at the expense of more controlled reactions. Computational theories suggest individual differences in the balance between habitual/model-free and deliberative/model-based decision-making.
Methods:
127 subjects performed the two Step task and completed the blatant and subtle prejudice scale.
Results:
By using analyses of choices and reaction times in combination with computational modeling, subjects with stronger blatant prejudices showed a shift away from model-based control. There was no association between these decision-making processes and subtle prejudices.
Conclusion:
These results support the idea that blatant prejudices toward minorities are related to a relative dominance of habitual decision-making. This finding has important implications for developing interventions that target to change prejudices across societies.
Context. The TESS satellite was launched in 2018 to perform high-precision photometry from space over almost the whole sky in a search for exoplanets orbiting bright stars. This instrument has opened new opportunities to study variable hot subdwarfs, white dwarfs, and related compact objects. Targets of interest include white dwarf and hot subdwarf pulsators, both carrying high potential for asteroseismology. Aims. We present the discovery and detailed asteroseismic analysis of a new g-mode hot B subdwarf (sdB) pulsator, EC 21494-7018 (TIC 278659026), monitored in TESS first sector using 120-s cadence. Methods. The TESS light curve was analyzed with standard prewhitening techniques, followed by forward modeling using our latest generation of sdB models developed for asteroseismic investigations. By simultaneously best-matching all the observed frequencies with those computed from models, we identified the pulsation modes detected and, more importantly, we determined the global parameters and structural configuration of the star. Results. The light curve analysis reveals that EC 21494-7018 is a sdB pulsator counting up to 20 frequencies associated with independent g-modes. The seismic analysis singles out an optimal model solution in full agreement with independent measurements provided by spectroscopy (atmospheric parameters derived from model atmospheres) and astrometry (distance evaluated from Gaia DR2 trigonometric parallax). Several key parameters of the star are derived. Its mass (0.391 +/- 0.009x2006;M-circle dot) is significantly lower than the typical mass of sdB stars and suggests that its progenitor has not undergone the He-core flash; therefore this progenitor could originate from a massive (greater than or similar to 2;M-circle dot) red giant, which is an alternative channel for the formation of sdBs. Other derived parameters include the H-rich envelope mass (0.0037 +/- 0.0010;M-circle dot), radius (0.1694 +/- 0.0081;R-circle dot), and luminosity (8.2 +/- 1.1;L-circle dot). The optimal model fit has a double-layered He+H composition profile, which we interpret as an incomplete but ongoing process of gravitational settling of helium at the bottom of a thick H-rich envelope. Moreover, the derived properties of the core indicate that EC 21494-7018 has burnt similar to 43% (in mass) of its central helium and possesses a relatively large mixed core (M-core;=;0.198 +/- 0.010;M-circle dot), in line with trends already uncovered from other g-mode sdB pulsators analyzed with asteroseismology. Finally, we obtain for the first time an estimate of the amount of oxygen (in mass; X(O)(core) = 0.16(-0.05)(+0.13)X(O)core=0.16-0.05+0.13$ X(mathrm{O})_{mathrm{core}}=0.16_{-0.05}<^>{+0.13} $) produced at this stage of evolution by an helium-burning core. This result, along with the core-size estimate, is an interesting constraint that may help to narrow down the still uncertain C-12(alpha,;gamma)O-16 nuclear reaction rate.
EVR-CB-001: An Evolving, Progenitor, White Dwarf Compact Binary Discovered with the Evryscope
(2019)
We present EVR-CB-001, the discovery of a compact binary with an extremely low-mass (0.21 +/- 0.05M(circle dot)) helium core white dwarf progenitor (pre-He WD) and an unseen low-mass (0.32 +/- 0.06M(circle dot)) helium white dwarf (He WD) companion. He WDs are thought to evolve from the remnant helium-rich core of a main-sequence star stripped during the giant phase by a close companion. Low-mass He WDs are exotic objects (only about 0.2% of WDs are thought to be less than 0.3 M-circle dot), and are expected to be found in compact binaries. Pre-He WDs are even rarer, and occupy the intermediate phase after the core is stripped, but before the star becomes a fully degenerate WD and with a larger radius (approximate to 0.2R(circle dot)) than a typical WD. The primary component of EVR-CB-001 (the pre-He WD) was originally thought to be a hot subdwarf (sdB) star from its blue color and under-luminous magnitude, characteristic of sdBs. The mass, temperature (T-eff = 18,500 +/- 500 K), and surface gravity (log(g) = 4.96 +/- 0.04) solutions from this work are lower than values for typical hot subdwarfs. The primary is likely to be a post-red-giant branch, pre-He WD contracting into a He WD, and at a stage that places it nearest to sdBs on color-magnitude and T-eff-log(g) diagrams. EVR-CB-001 is expected to evolve into a fully double degenerate, compact system that should spin down and potentially evolve into a single hot subdwarf star. Single hot subdwarfs are observed, but progenitor systems have been elusive.
Short period double degenerate white dwarf (WD) binaries with periods of less than similar to 1 day are considered to be one of the likely progenitors of type Ia supernovae. These binaries have undergone a period of common envelope evolution. If the core ignites helium before the envelope is ejected, then a hot subdwarf remains prior to contracting into a WD. Here we present a comparison of two very rare systems that contain two hot subdwarfs in short period orbits. We provide a quantitative spectroscopic analysis of the systems using synthetic spectra from state-of-the-art non-LTE models to constrain the atmospheric parameters of the stars. We also use these models to determine the radial velocities, and thus calculate dynamical masses for the stars in each system.
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.
Pavlovian-to-instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high-risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18-year-old male adults. Participants (N = 191) were instructed to 'collect good shells' and 'leave bad shells' during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high-risk and low-risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high-risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high-risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High-risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom-up), decreased lPFC response (top-down), and their altered interplay may contribute to poor interference control in the high-risk drinkers.