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The germline-restricted chromosome (GRC) is likely present in all songbird species but differs widely in size and gene content. This extra chromosome has been described as either a microchromosome with only limited basic gene content or a macrochromosome with enriched gene functions related to female gonad and embryo development. Here, we assembled, annotated, and characterized the first micro-GRC in the blue tit (Cyanistes caeruleus) using high-fidelity long-read sequencing data. Although some genes on the blue tit GRC show signals of pseudogenization, others potentially have important functions, either currently or in the past. We highlight the GRC gene paralog BMP15, which is among the highest expressed GRC genes both in blue tits and in zebra finches (Taeniopygia guttata) and is known to play a role in oocyte and follicular maturation in other vertebrates. The GRC genes of the blue tit are further enriched for functions related to the synaptonemal complex. We found a similar functional enrichment when analyzing published data on GRC genes from two nightingale species (Luscinia spp.). We hypothesize that these genes play a role in maintaining standard maternal inheritance or in recombining maternal and paternal GRCs during potential episodes of biparental inheritance.

Dry cold fronts, with large temperature differences across them, are a feature of the Australian summertime climate, with an apparent connection between strong dry cold fronts and increased fire danger in south-eastern Australia. While objective front detection methods exist, these methods are only applicable to gridded data, and require changing smoothing and threshold parameters as spatial resolution changes in order to obtain well-behaved results. This prevents use of these methods to analyse historic point records (such as station data), and to compare frontal behaviour in datasets of differing resolution.We present a method using daily temperature differences as way of identifying strong, dry cold fronts across both point records and variable resolution gridded data. This method is applied to station data, ERA5 reanalysis and CMIP6 model runs in order to determine the trend and variability in extreme dry fronts over south-east Australia. Station data and reanalysis agree on the frequency of strong cold fronts across different regions of Australia, but the longer station data records suggest that some trends seen in the reanalysis are a result of a shorter period of data. The CMIP6 models generally underestimate the number of extreme fronts seen near the surface compared to reanalysis, but display a roughly comparable level of interannual variability. In the station and reanalysis data, an apparent connection between the frequency of extreme fronts and the phase of climate patterns is seen, particularly for ENSO, which seems to be linked to soil moisture in inland southern Australia., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Heavy rainfall frequently occurs in subtropical eastern Australia. Many of these events are associated with slow-moving, upper-level low-pressure weather systems. Combined with moisture-rich easterly winds associated with a surface area of high pressure, these systems can produce heavy rainfall leading to some of the largest flooding events observed in the region, including the devastating floods of 2022. We investigate the upper-level dynamics of heavy rainfall over eastern Australia from a potential vorticity perspective. It is shown that slow-moving coherent potential vorticity anomalies and moist surface easterlies are produced through anticyclonic Rossby wave breaking. Moreover, it is shown that Rossby wave breaking over eastern Australia is enhanced by the interaction between tropical convection over the Maritime continent and the surrounding oceans and the extratropical jet., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Nanoclusters are promising materials for catalysis and sensing due to their large surface areas and unique electronic structures which can be tailored through composition, geometry, and chemistry. However, relationships correlating synthesis parameters directly to outcomes are limited. While previous computational studies have mapped the potential energy surface of specific systems of bare nanoclusters by generating and calculating the energies of reasonable structures, it is known that environmental ions and ligands crucially impact the final shape and size. In this work, phosphine-stabilized gold is considered as a test system and DFT calculations are performed for clusters with and without ligands, producing a database containing10000 structures for Au

Optical applications of lanthanide-doped nanoparticles require materials with low phonon energies to minimize nonradiative relaxation and promote nonlinear processes like upconversion. Heavy halide hosts offer low phonon energies but are challenging to synthesize as nanocrystals. Here, we demonstrate the size-controlled synthesis of low-phonon-energy KPb2X5 (X = Cl, Br) nanoparticles and the ability to tune nanocrystal phonon energies as low as 128 cm-1. KPb2Cl5 nanoparticles are moisture resistant and can be efficiently doped with lighter lanthanides. The low phonon energies of KPb2X5 nanoparticles promote upconversion luminescence from higher lanthanide excited states and enable highly nonlinear, avalanche-like emission from KPb2Cl5:Nd3+ nanoparticles. The realization of nanoparticles with tunable, ultra-low phonon energies facilitates the discovery of nanomaterials with phonon-dependent properties, precisely engineered for applications in nanoscale imaging, sensing, luminescence thermometry and energy conversion.

Postural instability marks one of the most disabling features of Parkinson's disease (PD), but it only reveals itself after affected brain areas have already been significantly damaged. Thus there is a need to detect deviations in balance and postural control before visible symptoms occur. In this study, we visually perturbed balance in the anterior-posterior direction using sinusoidal oscillations of a moving room in virtual reality at different frequencies. We tested three groups: individuals with PD under dopaminergic medication, an age-matched control group, and a group of young healthy adults. We tracked their center of pressure and their full-body motion, from which we also extracted the center of mass. We investigated sway amplitudes and applied newly introduced phase-locking analyses to investigate responses across participants' bodies. Patients exhibited significantly higher sway amplitudes as compared with the control subjects. However, their sway was phase locked to the visual motion like that of age-matched and young healthy adults. Furthermore, all groups successfully compensated for the visual perturbation by phase locking their sway to the stimulus. As frequency of the perturbation increased, distribution of phase locking (PL) across the body revealed a shift of the highest PL values from the upper body toward the hip region for young healthy adults, which could not be observed in patients and elderly healthy adults. Our findings suggest an impaired motor control, but intact visuomotor processing in early stages of PD, while less flexibility to adapt postural strategy to different perturbations revealed to be an effect of age rather than disease.

Colloidal semiconductor nanocrystals (NCs) are used as bright chromatic fluorophores for energy-efficient displays. We focus here on the size-dependent Stokes shift for CsPbBr

To ensure validity and acceptance of NSQIP risk-adjusted benchmarking, it is important that adjustments adequately control for hospitals that vary in their proportions of lower- or higher-risk operations (combined risk for procedure and patient). This issue was addressed in separate empirical and simulation studies.For the empirical study, potential miscalibration bias favoring hospitals that do lower-risk operations or disfavoring hospitals that do higher-risk operations was evaluated for 14 modeled outcomes using NSQIP data. A determination was also made as to whether there was a relationship between mean hospital operation risk and benchmarking results (log odds ratio). In the simulation study of the same 14 outcomes, hospital benchmarked performance was evaluated when sampled cases were reconstituted to include either a larger proportion of lower-risk operations or a larger proportion of higher-risk operations.Miscalibration favoring either lower- or higher-risk operations was absent, as were important associations between operative risk and hospital log odds ratios (most model R 2 less than 0.01). In the simulation, there were no substantial changes in log odds ratios when greater percentages of either lower- or higher-risk operations were included in a hospital's sample (nonsignificant p values and effect sizes less than 0.1).These results should enhance NSQIP participants' confidence in the adequacy of NSQIP patient and procedure risk-adjustment methods. NSQIP participants may rely on benchmarking findings, and implement quality improvement efforts based on them, without concern that they are biased by a preponderance of lower or higher risk operations.

Purpose The facility decision-making process (FDMP), as described in this paper, is a framework based on decades of proven effectiveness in analogous military applications. The purpose of this paper is to evaluate key factors which justify the need for the FDMP before describing the FDMP. Design/methodology/approach This paper conducts a literature review as it relates to facilities specific decision-making, puts forward a new concept for those processes and provides an abridged case study of the concept in application. Findings Facilities management is a key function for nearly every type of business or enterprise. As part of facilities management, many decisions are made about physical assets that a business or enterprise owns or maintains. Currently, there is no uniform decision-making framework, in literature or in practice, which enables consistency, robustness and scalability for facility management decisions. Such a framework would enable facility managers to effectively justify decisions related to capital and operational expenses. Practical implications The FDMP provides a robust procedure for facilities managers and engineers that enables enhanced strength in the face of business enterprise scrutiny as compared with the often-intuitive decision-making processes currently used in practice. Originality/value This novel conceptual process articulates the opportunity to provide for a comprehensive facilities decision-making process that enables better decisions especially as it relates to what are often ill-defined problem sets in facilities management.

4MOST is a new high-multiplex, wide-field spectroscopic survey facility under construction for ESO's 4m-VISTA telescope at Paranal, Chile. Its key specifications are: a large field of view of 4.4 square degrees, a high multiplex fibre positioner based on the tilting spine principle that positions 2436 science fibres in the focal surface of which 1624 fibres go to two low-resolution optical spectrographs (R = lambda/Delta lambda similar to 6500) and 812 fibres transfer light to the high-resolution optical spectrograph (R similar to 20,000). Currently, almost all subsystems are completed and full testing in Europe will be finished in spring 2023, after which 4MOST will be shipped to Chile. An overview is given of instrument construction and capabilities, the planned science of the consortium and the recently selected community programmes, and the unique operational scheme of 4MOST.

Background It has been shown that humans adapt their postural sway to oscillatory, visually simulated self-motion. However, little is still known about the way individual body segments contribute to this adjustment of body sway and how this contribution varies with different environmental conditions. Research question How do the centre of pressure (COP) and individual body segments phase-lock to a sinusoidal visual drive depending on the frequency of stimulation? Methods In this study, we introduce phase coupling as a method for assessing full body motion in response to visual stimuli presented in virtual reality (VR). 12 participants (mean age: 31 ± 9 years) stood inside a virtual tunnel which oscillated sinusoidally in the anterior-posterior direction at a frequency of 0.2 Hz, 0.8 Hz or 1.2 Hz. Primary outcome measures were the trajectories of their COP as well as of 25 body segments obtained by a motion tracking system. Results Subjects significantly coupled the phase of their COP and body segments to the visual drive. Our analysis yielded significant phase coupling of the COP to the stimulus for all tested frequencies. The phase coupling of body segments revealed a shift in postural response as a function of frequency. At the low frequency of 0.2 Hz, we found strong and significant phase coupling homogeneously distributed across the body. At the higher frequencies of 0.8 Hz and 1.2 Hz, however, overall phase coupling became weaker and was centred around the lower torso and hip segments. Significance Information on how the visual percept of self-motion affects balance control is crucial for understanding visuomotor processing in health and disease. Our setup and methods constitute a reliable tool for assessing perturbed balance control, which can be utilized in future clinical trials.

The accurate processing of temporal information is of critical importance in everyday life. Yet, psychophysical studies in humans have shown that the perception of time is distorted around saccadic eye movements. The neural correlates of this misperception are still poorly understood. Behavioral and neural evidence suggest that it is tightly linked to other known perisaccadic modulations of visual perception. To further our understanding of how temporal processing is affected by saccades, we studied the representations of brief visual time intervals during fixation and saccades in area V4 of two awake macaques. We presented random sequences of vertical bar stimuli and extracted neural responses to double-pulse stimulation at varying interstimulus intervals. Our results show that temporal information about very brief intervals of as brief as 20 ms is reliably represented in the multiunit activity in area V4. Response latencies were not systematically modulated by the saccade. However, a general increase in perisaccadic activity altered the ratio of response amplitudes within stimulus pairs compared with fixation. In line with previous studies showing that the perception of brief time intervals is partly based on response levels, this may be seen as a possible correlate of the perisaccadic misperception of time.

Understanding the targets of selection associated with changes in behavioral traits represents an important challenge of current evolutionary research. Owls (Strigiformes) are a diverse group of birds, most of which are considered nocturnal raptors. However, a few owl species independently adopted a diurnal lifestyle in their recent evolutionary history. We searched for signals of accelerated rates of evolution associated with a diurnal lifestyle using a genome-wide comparative approach. We estimated substitution rates in coding and noncoding conserved regions of the genome of seven owl species, including three diurnal species. Substitution rates of the noncoding elements were more accelerated than those of protein-coding genes. We identified new, owl-specific conserved noncoding elements as candidates of parallel evolution during the emergence of diurnality in owls. Our results shed light on the molecular basis of adaptation to a new niche and highlight the importance of regulatory elements for evolutionary changes in behavior. These elements were often involved in the neuronal development of the brain.

Zusammenfassung. Unsichere Berufsaussichten, Schwierigkeiten hinsichtlich der Work-Life-Balance und gesundheitliche Probleme werden ebenso wie eine mittlere bis hohe Arbeitszufriedenheit mit der Tätigkeit von Jungwissenschaftler_innen (JuWis) assoziiert. Da zur Situation von JuWis, die im Fach Psychologie in Österreich tätig sind, bisher keine systematischen Untersuchungen vorliegen, wurden ihre Arbeitssituation, Arbeitszufriedenheit und Beanspruchung in einer Online-Umfrage untersucht. Die Stichprobe ( N = 97) bestand aus 64 Praedocs (66 % Frauen, MAlter = 29.84 Jahre, SDAlter = 4.00 Jahre) und 33 Postdocs (55 % Frauen, MAlter = 33.39 Jahre, SDAlter = 3.41 Jahre). Die Ergebnisse zeigen eine durch verschiedene Belastungen (z. B. unsichere Karriereplanung durch befristete Verträge, eine hohe Anzahl an zusätzlichen Arbeitsstunden) gekennzeichnete Arbeitssituation von in der Psychologie tätigen JuWis. Die Arbeitszufriedenheit lag dabei im mittleren bis höheren Bereich, die Beanspruchung im mittleren bis niedrigeren Bereich. Es werden einige Bereiche mit Verbesserungspotenzial erkennbar. Aufgrund der geringen Stichprobengröße sind die Repräsentativität sowie die Generalisierbarkeit der Ergebnisse jedoch eingeschränkt. Auf Basis dieser Umfrage werden mögliche Ansatzpunkte zur Verbesserung der aktuellen Situation angeführt. Dieser Artikel soll angehenden JuWis als Orientierungshilfe dienen.

Owls (Strigiformes) evolved specific adaptations to their nocturnal predatory lifestyle, such as asymmetrical ears, a facial disk, and a feather structure allowing silent flight. Owls also share some traits with diurnal raptors and other nocturnal birds, such as cryptic plumage patterns, reversed sexual size dimorphism, and acute vision and hearing. The genetic basis of some of these adaptations to a nocturnal predatory lifestyle has been studied by candidate gene approaches but rarely with genome-wide scans. Here, we used a genome-wide comparative analysis to test for selection in the early history of the owls. We estimated the substitution rates in the coding regions of 20 bird genomes, including 11 owls of which five were newly sequenced. Then, we tested for functional overrepresentation across the genes that showed signals of selection. In the ancestral branch of the owls, we found traces of positive selection in the evolution of genes functionally related to visual perception, especially to phototransduction, and to chromosome packaging. Several genes that have been previously linked to acoustic perception, circadian rhythm, and feather structure also showed signals of an accelerated evolution in the origin of the owls. We discuss the functions of the genes under positive selection and their putative association with the adaptation to the nocturnal predatory lifestyle of the owls.

Temporal information is ubiquitous in natural vision and must be represented accurately in the brain to allow us to interact with a constantly changing world. Recent studies have employed a random stimulation paradigm to map the temporal response function (TRF) to luminance changes in the human EEG. This approach has revealed that the visual system, when presented with broadband visual input, actively selects distinct temporal frequencies, and retains their phase-information for prolonged periods of time. This non-linear response likely originates in primary visual cortex (V1), yet, so far it has not been investigated on a neural level. Here, we characterize the steady-state response to random broadband visual flicker in marmoset V1. In two experiments, we recorded from i) marmosets passively stimulated under general anesthesia, and ii) awake marmosets, under free viewing conditions. Our results show that LFP coupling to the stimulus was broadband and unselective under anesthesia, whereas in awake animals, it was restricted to two distinct frequency components, in the alpha and beta range. Within these frequency bands, coupling adhered to the receptive field (RF) boundaries of the local populations. The responses outside the RF did not provide evidence for a propagation of stimulus information across the cortex, contrary to results in human EEG studies. This result may be explained by short fixation durations, warranting further investigation. In summary, our findings show that during awake behavior V1 neural responses to broadband information are selective for distinct frequency bands, and that this selectivity is likely controlled actively by top-down mechanisms.

Additional file 2: Supplemental Figure 1. Residual plasma correction. (a-c) Levels of a vascular marker (infliximab) in serum (a) and tissues (b) were used to infer residual plasma contamination and calculate correction factors (c). Also shown is the plasma volume fraction derived from the data in (Shah and Betts 2012). (d) Relative contribution of the residual plasma fraction to the total tissue AUC in tumor-bearing Balb/c nude mice.

Seit der Antike bringen die Gattungen der Bukolik und der Idylle sowie idyllische Elemente in Texten anderer Gattungen immer wieder verschiedene Möglichkeiten zum Ausdruck, den Beginn und den Anfang, das Erste und Einzige, sowie den Ursprung und das Originäre darzustellen. Dabei kann sich das ‚Erste‘ auf verschiedene diskursive Bereiche beziehen: Erstens auf das frühste dichterische Schaffen überhaupt, zweitens auf die bukolische Dichtung als eine erste Form dichterischen Schaffens, drittens auf den Beginn kultureller und zivilisatorischer Prozesse und viertens schließlich auf die Ursprünge des Menschlichen und Göttlichen überhaupt.

Additional file 4: Supplemental Figure 3. Schematic illustration of the principle of the centrifugation method to obtain interstitial fluid.

Additional file 1: Supplemental Table 1. Serum pharmacokinetic parameters in non-tumor bearing mice for charge-patch antibody variants as obtained by noncompartmental analysis.

Das in Idyllen dargestellte und geformte Verhältnis von Hirte und Herde ermöglicht historisch wie systematisch zahlreiche Verbindungslinien der Gattung zu politischen, ökonomischen und philosophischen Diskursen. Der Topos erscheint als beispielhaft für die in den Texten dargestellten „einfach-friedliche[n], meist ländliche[n] Lebensformen“.

Additional file 3: Supplemental Figure 2. Interstitial concentrations derived from total tissue levels in tumor-bearing Balb/c nude mice using the method of Chang et al. (Chang et al. 2020) suggest similar delivery to the tumor interstitium, while liver and muscle interstitial levels differ significantly.

Understanding the genomic landscape of adaptation is central to understanding microevolution in wild populations. Genomic targets of selection and the underlying genomic mechanisms of adaptation can be elucidated by genome-wide scans for past selective sweeps or by scans for direct fitness associations. We sequenced and assembled 150 haplotypes of 75 blue tits (Cyanistes caeruleus) of a single Central European population by a linked-read technology. We used these genome data in combination with coalescent simulations (i) to estimate an historical effective population size of ~250,000, which recently declined to ~10,000, and (ii) to identify genome-wide distributed selective sweeps of beneficial variants probably originating from standing genetic variation (soft sweeps). The genes linked to these soft sweeps, but also those linked to hard sweeps based on new beneficial mutants, showed a significant enrichment for functions associated with gene expression and transcription regulation. This emphasizes the importance of regulatory evolution in the population's adaptive history. Soft sweeps were further enriched for genes related to axon and synapse development, indicating the significance of neuronal connectivity changes in the brain potentially linked to behavioural adaptations. A previous scan of heterozygosity-fitness correlations revealed a consistent negative effect on arrival date at the breeding site for a single microsatellite in the MDGA2 gene. Here, we used the haplotype structure around this microsatellite to explain the effect as a local and direct outbreeding effect of a gene involved in synapse development.

It is critical to improve the resilience of military installations and their complex infrastructure systems to strengthen response to the uncertainty and threat driven by the increasing fre...

Surgery is an essential part of the curative plan for most patients affected with solid tumors. The outcome of such surgery, e.g., recurrence rates and ultimately patient survival, depends on several factors where the resection margin is of key importance. Presently the resection margin is assessed by classical histology, which is time-consuming (several days), destructive, and basically only gives two-dimensional information. Clearly it would be advantageous if immediate feedback on tumor extension in all three dimensions were available to the surgeon intra-operatively. In the present paper we investigate a laboratory propagation-based phase-contrast xray computed tomography (CT) system that provides the resolution, contrast, and, potentially, the speed for this purpose. The system relies on a liquid-metal jet micro-focus source and a scintillator-coated CMOS detector. The study is performed on paraffin-embedded non-stained samples of human pancreatic neuroendocrine tumors, liver intrahepatic cholangiocarcinoma, and pancreatic serous cystic neoplasm (benign). We observe tumors with distinct and sharp edges having cellular resolution (∼10 μm) as well as many assisting histological landmarks, allowing for resection margin assessment. All x-ray data is compared with classical histology. The agreement is excellent, and we conclude that the method has potential for intra-operative three-dimensional virtual histology.

Background: Tooth wear is a multifactorial process, leading to the loss of dental hard tissues. Therefore, it is important to detect the level of tooth wear at an early stage, so monitoring can be initiated. The Tooth Wear Evaluation System (TWES) enables such a multistage diagnosis of tooth wear. The further developed TWES 2.0 contains a complete taxonomy of tooth wear, but its reliability has not yet been validated. Objectives: The aim of the study was to examine in a randomised controlled trial (RCT) whether diagnoses made based on the TWES 2.0 are reproducible and whether this reproducibility is also achieved with computer-assisted diagnostics. Methods: 44 dental students received extensive training in TWES 2.0 assessment and taxonomy. The students each evaluated at least 10 (of the present 14) anonymised patient cases using gypsum models and high-resolution intra-oral photographs according to TWES 2.0. One half initially evaluated on paper; the other half used dedicated software (CMDfact / CMDbrux). After half of the patient cases (5), the evaluation methods were switched (AB/BA crossover design). The diagnoses were then evaluated for agreement with the predefined sample solution. Results: Evaluation of agreement with the sample solution according to Cohen's kappa indicated a value of 0.46 for manual (traditional) evaluation; and 0.44 for computer-assisted evaluation. Evaluation of agreement between examiners was 0.38 for manual and 0.48 for computer-assisted evaluation (Fleiss’ kappa). Conclusion: The results of this study proved that the taxonomy of the TWES 2.0 has acceptable reliability and can thus be used by dentists. Accordingly, the system can be learned quickly even by untrained practitioners. Comparable results are achieved with computer-assisted evaluation.

This study explores the impact of antibody surface charge on tissue distribution into various tissues including tumor. Tumor-bearing mice were dosed intravenously with a mixture comprising three antibodies engineered to carry negative charge patches, a balanced charge distribution, or positive patches, respectively (cassette dosing). Tissue levels were analyzed with a specific LC-MS/MS method. In addition, the antibody mix was administered to non-tumor bearing mice. Muscle and skin interstitial fluid were obtained by centrifugation and analyzed by LC-MS/MS. An in vitro endothelium model was explored for its feasibility to mimic the observed distribution differences.A balanced charge distribution was optimal in terms of total tumor exposure, while in other tissues, negatively charged and balanced charged antibodies gave similar results. In contrast, positive charge patches generally resulted in increased serum clearance but markedly enhanced tumor and organ uptake, leading to higher tissue-to-serum ratios. The uptake and availability in the interstitial space were confirmed by specific assessment of antibody levels in the interstitial fluid of the muscle and skin, with similar charge impact as in total tissue. The in vitro model was able to differentiate the transport propensity of this series of antibody variants. In summary, our results show the differential effects of charge patches on an antibody surface on biodistribution and tumor uptake. These insights may help in the design of molecules with biodistribution properties tailored to their purpose, and an optimized safety profile.

Laboratory x-ray fluorescence (XRF) computed tomography (XFCT) with nanoparticles (NPs) as contrast agents now allows for in vivo preclinical imaging and longitudinal studies at low radiation dose. We present on developments of our XFCT arrangement capable of low-dose (

Postural instability marks one of the most disabling features of Parkinson’s disease (PD), but only reveals itself after affected brain areas have already been significantly damaged. Thus, there is a need to detect deviations in balance and postural control before visible symptoms occur. In this study, we visually perturbed balance in the anterior-posterior direction using sinusoidal oscillations of a moving room in virtual reality at different frequencies. We tested three groups: individuals with PD under dopaminergic medication, an age-matched control group, and a group of young healthy adults. We tracked their centre of pressure and their full-body motion. We investigated sway amplitudes and applied newly introduced phase-locking analyses to investigate responses across participants’ bodies. Patients exhibited significantly higher sway amplitudes as compared to the control subjects. However, their sway was phase-locked to the visual motion like that of age-matched and young healthy adults. Furthermore, all groups successfully compensated for the visual perturbation by – most likely reflexively - phase-locking their sway to the stimulus. As frequency of the perturbation increased, distribution of phase-locking (PL) across the body revealed a shift of the highest PL-values from the upper body towards the hip-region for young healthy adults, which could not be observed in patients and elderly healthy adults. Our findings suggest an impaired neuromuscular stability, but intact visuomotor processing in early stages of PD, while less flexibility to adapt postural strategy to different perturbations revealed to be an effect of age rather than disease.New & NoteworthyA better understanding of visuomotor control in Parkinson’s disease (PD) potentially serves as a tool for earlier diagnosis, which is crucial for improving patient’s quality of life. In our study, we assess body sway responses to visual perturbations of the balance control system in patients with early-to-mid stage PD, using motion tracking along with recently established phase-locking techniques. Our findings suggest patients at this stage to have an impaired muscular stability but intact visuomotor control.

The oculomotor system can initiate remarkably accurate saccades towards moving targets (interceptive saccades) the processing of which is still under debate. The generation of these saccades requires the oculomotor centers to have information about the motion parameters of the target that then must be extrapolated to bridge the inherent processing delays. We investigated to what degree the information about motion of a saccade target is available in the lateral intra-parietal area (area LIP) of macaque monkeys for generation of accurate interceptive saccades. When a multi-layer neural network was trained based on neural discharges from area LIP around the time of saccades towards stationary targets, it was also able to predict the end points of saccades directed towards moving targets. This prediction, however, lagged behind the actual post-saccadic position of the moving target by ~ 80 ms when the whole neuronal sample of 105 neurons was used. We further found that single neurons differentially code for the motion of the target. Selecting neurons with the strongest representation of target motion reduced this lag to ~ 30 ms which represents the position of the moving target approximately at the onset of the interceptive saccade. We conclude that—similarly to recent findings from the Superior Colliculus (Goffart et al. J Neurophysiol 118(5):2890–2901)—there is a continuum of contributions of individual LIP neurons to the accuracy of interceptive saccades. A contribution of other gaze control centers (like the cerebellum or the frontal eye field) that further increase the saccadic accuracy is, however, likely. Supplementary Information The online version contains supplementary material available at 10.1007/s00429-021-02365-x.

The receptor tyrosine kinase HER2 acts as oncogenic driver in numerous cancers. Usually, the gene is amplified, resulting in receptor overexpression, massively increased signaling and unchecked proliferation. However, tumors become frequently addicted to oncogenes and hence are druggable by targeted interventions. Here, we design an anti-HER2 biparatopic and tetravalent IgG fusion with a multimodal mechanism of action. The molecule first induces HER2 clustering into inactive complexes, evidenced by reduced mobility of surface HER2. However, in contrast to our earlier binders based on DARPins, clusters of HER2 are thereafter robustly internalized and quantitatively degraded. This multimodal mechanism of action is found only in few of the tetravalent constructs investigated, which must target specific epitopes on HER2 in a defined geometric arrangement. The inhibitory effect of our antibody as single agent surpasses the combination of trastuzumab and pertuzumab as well as its parental mAbs in vitro and it is effective in a xenograft model., HER2 acts an oncogenic driver in numerous cancers. Here, the authors design an anti-HER2 biparatopic and tetravalent IgG fusion with inhibitory effects in a xenograft model.

Lead toxicity has sparked interest into alternative halide nanomaterials with properties similar to CsPbX3 perovskites. A promising alternative suggested from bulk studies is the family of double p...

Blends of nanoparticles, polymers, and small molecules can self-assemble into optical, magnetic, and electronic devices with structure-dependent properties. However, the relationship between a multicomponent nanocomposite's formulation and its assembled structure is complex and cannot be predicted by theory. The blends can be strongly influenced by processing conditions, which can introduce non-equilibrium states. Currently, nanocomposite devices are designed through cycles of experimental trial and error. Machine learning (ML) methods are a compelling alternative because they can use existing datasets to map high-dimensional spaces. These methods do not rely on known relationships between parameters, so they are suited to complex systems without a solid theoretical foundation. Here, a dataset of 595 microscopy images of nanocomposite thin films is used to train a series of ML models. Correlations between the input and output parameters are examined, providing new insights into the system. Finally, the most successful ML model is used to predict the structures of new nanocomposite compositions. The results confirm that ML techniques can be used to improve the efficiency of nanocomposite device design. More broadly, the current study suggests some of the advantages and challenges associated with applying ML to complex systems.

X-ray fluorescence computed tomography (XFCT) with nanoparticles (NPs) as contrast agents has reached technical maturity allowing for in vivo preclinical imaging in the laboratory setting. We present the first in vivo longitudinal study with XFCT where mice were 5 times each during an 8-week period. Imaging is performed with low radiation dose (

This paper presents the results of an experimental program conducted to evaluate the local damage behavior of steel-plate composite (SC) walls subjected to missile impact. There is signific...

All songbirds have one special accessory chromosome1–4, the so-called germline-restricted chromosome (GRC)4–7, which is only present in germline cells and absent from all somatic tissues. Earlier work on the zebra finch (Taeniopygia guttata castanotis) showed that the GRC is inherited only through the female line4,6,8,9 – like mitochondrial DNA7,9–12 – and is eliminated from the sperm during spermatogenesis5,7,9–11. Here we show that the GRC can also be paternally inherited. Confocal microscopy using GRC-specific FISH probes indicated that a considerable fraction of sperm heads (1-19%) in zebra finch ejaculates still contained the GRC. In line with these cytogenetic data, sequencing of ejaculates revealed that individual males from two families differed strongly and consistently in the number of GRCs in their ejaculates. Examining a captive-bred population of hybrids of the two zebra finch subspecies (T. g. guttata and T. g. castanotis) revealed that the descendants inherited their mitochondria from a castanotis mother but their GRC from a guttata father. Moreover, GRC haplotypes across nine different castanotis matrilines showed at best a weak tendency to be co-inherited with mtDNA haplotypes. Within castanotis, the GRC showed little variability, while the mtDNA of matrilines was highly divergent. This suggests that a single GRC haplotype has recently spread across the entire castanotis population, crossing the matriline boundaries via paternal spillover. Our findings raise the possibility that certain GRC haplotypes could selfishly spread through the population, via additional paternal transmission, thereby outcompeting other GRC haplotypes that were limited to strict maternal inheritance, even if this was partly detrimental to organismal fitness.

In dieser Untersuchung werden Lehramtsstudierende hinsichtlich ausgewahlter Personlichkeitseigenschaften – berufliche Interessen, berufliche Werthaltungen und Leistungsmotivation – beschrieben und im Anschluss daran Untergruppen (Cluster) identifiziert, die sich in Bezug auf diese Personlichkeitseigenschaften voneinander unterscheiden. Die Untersuchungsgruppe bilden 2289 Lehramtsstudierende (72 % weiblich), die in den Jahren 2007 bis 2012 an einem Beratungsprojekt teilgenommen haben.

This paper presents the development of normalized total force-total impulse (P-I) diagrams for analyzing and designing steel-plate composite (SC) walls to resist far-field blast loads. The ...

The reduced bending stiffness method is used in the framework of computational models for stringer stiffened panels. Here, the stringer foot is often stacked on top of the skin of the panel and leads to a stacked laminate with extensional bending stiffness coupling. The validity of the reduced bending stiffness method for the mentioned laminate type is investigated and assessed, as only unsymmetrical laminates without eccentricity have been considered in existing literature. In exemplary studies, the influence of the coupling effects is shown, which allows drawing conclusions on the error that is introduced in, e. g. closed-form analytical approximate solutions for the buckling of stringer stiffened panels.