GRO.publications
Not a member yet
137257 research outputs found
Sort by
How energy determines spatial localisation and copy number of molecules in neurons
No full textAbstract In neurons, the quantities of mRNAs and proteins are traditionally assumed to be determined by functional, electrical or genetic factors. Yet, there may also be global, currently unknown computational rules that are valid across different molecular species inside a cell. Surprisingly, our results show that the energy for molecular turnover is a significant cellular expense, en par with spiking cost, and which requires energy-saving strategies. We show that the drive to save energy determines transcript quantities and their location while acting differently on each molecular species depending on the length, longevity and other features of the respective molecule. We combined our own data and experimental reports from five other large-scale mRNA and proteomics screens, comprising more than ten thousand molecular species to reveal the underlying computational principles of molecular localisation. We found that energy minimisation principles explain experimentally-reported exponential rank distributions of mRNA and protein copy numbers. Our results further reveal robust energy benefits when certain mRNA classes are moved into dendrites, for example mRNAs of proteins with long amino acid chains or mRNAs with large non-coding regions and long half-lives proving surprising insights at the level of molecular populations
Paternity analysis reveals sexual selection on cognitive performance in mosquitofish
No full textDepartment of Education and Training | Australian Research Council https://doi.org/10.13039/501100000923Deutsches Primatenzentrum https://doi.org/10.13039/50110000493
Precisely controlled colloids: a playground for path-wise non-equilibrium physics
No full textWe investigate path-wise observables in experiments on driven colloids in a periodic light field to dissect selected intricate transport features, kinetics, and transition-path time statistics out of thermodynamic equilibrium.We investigate path-wise observables in experiments on driven colloids in a periodic light field to dissect selected intricate transport features, kinetics, and transition-path time statistics out of thermodynamic equilibrium. These observables directly reflect the properties of individual paths in contrast to the properties of an ensemble of particles, such as radial distribution functions or mean-squared displacements. In particular, we present two distinct albeit equivalent formulations of the underlying stochastic equation of motion, highlight their respective practical relevance, and show how to interchange between them. We discuss conceptually different notions of local velocities and interrogate one- and two-sided first-passage and transition-path time statistics in and out of equilibrium. Our results reiterate how path-wise observables may be employed to systematically assess the quality of experimental data and demonstrate that, given sufficient control and sampling, one may quantitatively verify subtle theoretical predictions.We investigate path-wise observables in experiments on driven colloids in a periodic light field to dissect selected intricate transport features, kinetics, and transition-path time statistics out of thermodynamic equilibrium.We investigate path-wise observables in experiments on driven colloids in a periodic light field to dissect selected intricate transport features, kinetics, and transition-path time statistics out of thermodynamic equilibrium. These observables directly reflect the properties of individual paths in contrast to the properties of an ensemble of particles, such as radial distribution functions or mean-squared displacements. In particular, we present two distinct albeit equivalent formulations of the underlying stochastic equation of motion, highlight their respective practical relevance, and show how to interchange between them. We discuss conceptually different notions of local velocities and interrogate one- and two-sided first-passage and transition-path time statistics in and out of equilibrium. Our results reiterate how path-wise observables may be employed to systematically assess the quality of experimental data and demonstrate that, given sufficient control and sampling, one may quantitatively verify subtle theoretical predictions.HORIZON EUROPE European Research Council https://doi.org/10.13039/100019180Deutsche Forschungsgemeinschaft https://doi.org/10.13039/50110000165
Precise and efficient modeling of stellar-activity-affected solar spectra using SOAP-GPU
No full textContext. One of the main obstacles in exoplanet detection when using the radial velocity (RV) technique is the presence of stellar activity signal induced by magnetic regions. As the most advanced techniques to mitigate this signal are reaching a level better than one meter per second, it is difficult to evaluate their performance: instrumental systematics start to be similar in magnitude, and therefore it is impossible to know the ground truth of the stellar activity signal. In this context, a realistic simulated dataset that can provide photometry and spectroscopic outputs is needed for method development. Aims. The goal of this paper is to describe two realistic simulations of solar activity obtained from SOAP-GPU and to compare them with real data obtained from the HARPS-N solar telescope. For this purpose, both simulated spectral time series cover the time window of HARPS-N solar observation, but nothing prevents SOAP-GPU from modeling the data over different time spans. Methods. We describe two different methods of modeling solar activity using SOAP-GPU. The first models the evolution of active regions based on the spot number as a function of time. Other physical parameters are either drawn from observed solar distributions or modeled with empirical relations. The second method relies on the extraction of active regions from the Solar Dynamics Observatory (SDO) data. The location of spots and faculae on the solar disk at each timestamp are derived from the magnetogram and intensity maps and are fed into SOAP-GPU to simulate the corresponding spectra. Results. The simulated spectral time series generated with the first method shows a long-term RV behavior similar to that seen in the HARPS-N solar observations. The effect of stellar activity induced by stellar rotation is also well modeled with prominent periodicities at the stellar rotation period and its first harmonic. The comparison between the simulated spectral time series generated using SDO images and the HARPS-N solar spectra shows that SOAP-GPU can precisely model the RV time series of the Sun to a precision better than 0.9 m/s. By studying the width and depth variations of each spectral line in the HARPS-N solar and SOAP-GPU data, we find a strong correlation between the observation and the simulation for strong spectral lines, therefore supporting the modeling of the stellar activity effect at the spectral level. The correlations are weaker for shallow lines, although it is likely that their lower signal-to-noise ratio does not allow a meaningful comparison. Conclusions. We introduce two methods for modeling solar activity using SOAP-GPU. With only sunspot numbers as input, we accurately capture the long-term magnetic cycle and rotational features. Additionally, we effectively model shift and depth variations at the spectral line level by using data from SDO. These simulated solar spectral time series serve as a useful test bed for evaluating spectral-level stellar activity mitigation techniques
Two planets likely residing in the sub-Neptune mass regime around a late K-dwarf
No full textContext . K-dwarf stars are promising targets in the exploration of potentially habitable planets. Their properties, falling between G and M dwarfs, provide an optimal trade-off between the prospect of habitability and ease of detection. The KOBE experiment is a blind-search survey exploiting this niche, monitoring the radial velocity of 50 late-type K-dwarf stars. It employs the CARMENES spectrograph, with an observational strategy designed to detect planets in the habitable zone of their system. Aims . In this work, we exploit the KOBE data set to characterize planetary signals in the K7 V star HIP 5957 (KOBE-1) and to constrain the planetary population within its habitable zone. Methods . We used 82 CARMENES spectra over a time span of three years. We employed a generalized Lomb–Scargle periodogram to search for significant periodic signals that would be compatible with Keplerian motion on KOBE-1. We carried out a model comparison within a Bayesian framework to ensure the significance of the planetary model over alternative configurations of lower complexity. We also inspected two available TESS sectors in search of planetary signals. Results . We identified two signals: at P b = 8.5 d and P c = 29.7 d. We confirmed their planetary nature through ruling out other non-planetary configurations. Their minimum masses are 8.80 ± 0.76 M ⊕ (KOBE-1 b), and 12.4 ± 1.1 M ⊕ (KOBE-1 c), corresponding to absolute masses within the planetary regime at a high certainty (>99.7%). By analyzing the sensitivity of the CARMENES time series to additional signals, we discarded planets above 8.5 M ⊕ within the habitable zone. We identified a single transit-like feature in TESS, whose origin is still uncertain, but still compatible within 1 σ with a transit from planet c. Conclusions . The KOBE-1 multi-planetary system, consisting of a relatively quiet K7-dwarf hosting two sub-Neptune-minimum- mass planets, establishes the first discovery from the KOBE experiment. We have explored future prospects for characterizing this system, concluding that Gaia DR4 will be insensitive to their astrometric signature. Meanwhile, nulling interferometry with the Large Interferometer For Exoplanets (LIFE) mission could be capable of directly imaging both planets and characterizing their atmospheres in future studies
Enhancing fire resistance in pine wood through DMDHEU resin and phosphate-nitrogen flame retardant synergies
No full textAbstract Wood modification with 1,3-dimethylol-4,5-dihydroxyethyleneurea (DMDHEU) has been widely demonstrated to enhance the biological durability and dimension stability of wood, thus it serves a predestined technology to equip wooden products for outdoor applications. However, such technology hardly affects the fire performance of wood, a parameter which gains increasing relevance in the construction sector. Recently, the combination of curing resins with flame retardants has been proposed as a potential approach to enhance the fire performance of wood in a permanent way, hence providing a durable fire protection system. Scots pine sapwood ( Pinus sylvestris L.) was impregnated with aqueous compositions of DMDHEU, a commercially available phosphate-nitrogen based fire retardant (adapted for wooden applications) and combinations thereof. The fixation of the flame retardant was assessed on the basis of a cold water leaching process according to EN 84 (2020). The fire performance of the treated wood was assessed through thermal gravimetry analysis (TGA), a Bunsen burner ignition test and mass loss calorimeter. Both wood treated with pure flame retardant and combination of a flame retardant and DMDHEU, demonstrated improvements in thermal stability, reduced flammability and decreased heat release after treatment. Notably, the THR 600s of wood treated with DMDHEU in combination with the flame retardant was reduced by 89.3% compared to wood treated solely with DMDHEU. However, after the leaching process, the flame retardant happened to leach out almost completely, which was assessed on the basis of a loss in its efficacy related to fire protection. On the contrary, DMDHEU seemed to partially fix the flame retardant inside the wood matrix, which was derived from a persistent enhancement in fire performance, even after wooden specimens passed a cold water leaching
I learn what I like: children’s preferences but not maternal IDS influence word learning from IDS and ADS
No full textGerman Research Foundation 50110000165
CSF biomarkers are differentially linked to brain areas high and low in noradrenaline, dopamine and serotonin across the Alzheimer’s disease spectrum
No full textAbstract Neurotransmitter systems of noradrenaline, dopamine, serotonin and acetylcholine are implicated in cognitive functions such as memory, learning and attention and are known to be altered in neurodegenerative diseases like Alzheimer’s disease. Specific brain structures involved in these systems, e.g. the locus coeruleus, the main source of noradrenaline in the cortex, are in fact affected earliest by Alzheimer’s disease tau pathology. Preserved volumetric neurotransmitter specific brain areas could therefore be an important neural resource for cognitive reserve in aging. The aim of this study was to determine whether volumes of brain areas known to be high in neurotransmitter receptors are relatively preserved in individuals with lower levels of Alzheimer’s disease pathology. Based on the Human Protein Atlas for neurotransmitter receptor distribution, we distinguished between ‘areas high and low’ in noradrenaline, dopamine, serotonin and acetylcholine and assessed associations of atrophy in those areas with CSF amyloid-ß 42/40, CSF phosphorylated tau protein and cognitive function across healthy controls (n = 122), individuals with subjective cognitive decline (n = 156), mild cognitive impairment or mild Alzheimer’s disease dementia (n = 126) using structural equation modelling. CSF pathology markers were inversely correlated and showed a stronger association with disease severity, suggesting distinguishable interrelatedness of these biomarkers depending on the stage of Alzheimer’s disease dementia. Across groups, amyloid pathology was linked to atrophy in areas high as well as low in neurotransmitter receptor densities, while tau pathology did not show any significant link to brain area volumes for any of the neurotransmitters. Within disease severity groups, individuals with more amyloid pathology showed more atrophy only in ‘areas high in noradrenaline’, whereas for dopamine tau pathology was linked to higher volumes in areas low in receptor density possibly indicating compensatory mechanisms. Furthermore, individuals with more tau pathology showed a selective decrease in memory function while amyloid pathology was related to a decline in executive function and language capacity as well as memory function. In summary, our analyses highlight the benefits of investigating disease-relevant factors in Alzheimer’s disease using a multivariate multigroup approach. Assessing multivariate dependencies in different disease stages and across individuals revealed selective links of pathologies, cognitive decline and atrophy in particular for areas modulated by noradrenaline, dopamine and serotonin
How to Determine a Therapeutic Reference Range for a Psychotropic Drug Systematically? Recommendations of the TDM Task Force of the AGNP
No full textBackground: Therapeutic drug monitoring (TDM) is essential for controlling pharmacogenetic and pharmacokinetic variations and for optimizing pharmacotherapy. However, its value is often underestimated because of nonsystematic recommendations for target ranges in the literature. The purpose of this study was to emphasize transparency and systematization in the forthcoming Updates to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP)-TDM Consensus Guidelines. Methods: Here, a stepwise method for determining therapeutic reference ranges (TRRs) in psychiatry is introduced. By using various data types, a multidimensional approach for establishing a range is presented. The data types were classified based on how effectively they supported the target ranges. This method was demonstrated for 3 drugs commonly used in psychiatry (aripiprazole, olanzapine, and escitalopram). Results: Despite the methodological shortcomings in published concentration-effect studies, the approach used here enabled the determination of reference ranges by combining multiple types of data. The lower limit of the TRR is ideally derived from studies that link blood drug concentrations to clinical effectiveness, particularly symptom-specific responses, after fixed-dose treatment. The upper limit depends on the concentrations associated with adverse reactions or maximal response. Thresholds can be estimated using receiver operating characteristic analyses. Preliminary thresholds were derived from responder concentration data or from expected drug concentrations under approved doses. Positron emission tomography studies were used to further validate these ranges. Conclusions: This study proposed a new standard for determining the TRR of psychotropic drugs, thereby enhancing their clinical utility and validity. Adjusting blood levels to these ranges should improve response rates and medication tolerance