julilili42/papers huggingface dataset:
X-ray flashes from the low-mass X-ray binary IGR J17407−2808
2023-04-21

IGR J17407−2808 is an enigmatic and poorly studied X-ray binary that was recently observed quasi-simultaneously with NuSTAR and XMM-Newton . In this paper we report the results of this observational campaign. During the first 60 ks of observation, the source was caught in a relatively low emission state characterised by a modest variability and an average flux of ∼8.3 × 10 −13 erg cm −2 s −1 (4−60 keV). Subsequently, IGR J17407−2808 entered a significantly more active emission state that persisted for the remaining ∼40 ks of the NuSTAR observation. During this state, IGR J17407−2808 displayed several fast X-ray flares of ∼1 − 100 s in duration and featuring profiles with either single or multiple peaks. The source flux in the flaring state reached values as high as ∼2 × 10 −9 erg cm −2 s −1 (4−60 keV), leading to a measured dynamic range during the NuSTAR and XMM-Newton campaign of ≳10 3 . We also analysed available archival photometric near-infrared data for IGR J17407−2808 in order to improve the constraints available so far on the nature of the donor star hosted in this system. Our analysis shows that the donor star can be either a rare K or M-type sub-subgiant, a K-type main sequence or subgiant star. Our findings support the classification of IGR J17407−2808 as a low-mass X-ray binary. We discuss the X-ray behaviour of the source as recorded by NuSTAR and XMM-Newton in view of this revised classification.
New insights into the autophagy-NAD axis in brain disease
2023-04-21

Sun et al. demonstrate that defects in autophagy cause nicotinamide adenine dinucleotide (NAD) depletion and neurotoxicity.<sup>1</sup> Restoring NAD levels rescues cytotoxicity in autophagy-deficient neurons, providing a potential therapy for neurodegenerative and lysosomal storage diseases associated with autophagy defects.
2-Layer k-Planar Graphs Density, Crossing Lemma, Relationships And Pathwidth
2023-04-21

Abstract The -layer drawing model is a well-established paradigm to visualize bipartite graphs where vertices of the two parts lie on two horizontal lines and edges lie between these lines. Several beyond-planar graph classes have been studied under this model. Surprisingly, however, the fundamental class of -planar graphs has been considered only for in this context. We provide several contributions that address this gap in the literature. First, we show tight density bounds for the classes of -layer -planar graphs with . Based on these results, we provide a Crossing Lemma for -layer -planar graphs, which then implies a general density bound for -layer -planar graphs. We prove this bound to be almost optimal with a corresponding lower bound construction. Finally, we study relationships between -planarity and -quasiplanarity in the -layer model and show that -layer -planar graphs have pathwidth at most while there are also -layer -planar graphs with pathwidth at least .
Ocular permeability, intraocular biodistribution of lipid nanocapsule formulation intended for retinal drug delivery
2023-04-22

Recently, cGMP analogues have been investigated for the treatment of inherited retinal degenerations (IRD) using intravitreal injections. However, higher vitreous elimination rates limit the possibility to treat the retina with small molecule drugs. Here, we investigated the potential of lipid nanocapsules (LNCs) as vehicles to reduce clearance and prolong the delivery of cGMP analogue, CN03 to the retinal photoreceptors. Initially LNCs were investigated for both topical/periocular and intravitreal administration routes. While LNC-mediated drug permeation through the cornea proved to be too low for clinical applications, intravitreal application showed significant promise. Intravitreally administered LNCs containing fluorescent tracer in ex vivo porcine eyes showed complete intravitreal dispersal within 24 h. Ocular bio-distribution on histological sections showed that around 10 % of the LNCs had reached the retina, and 40 % accumulated in the ciliary body. For comparison, we used fluorescently labeled liposomes and these showed a different intraocular distribution with 48 % accumulated in the retina, and almost none were in the ciliary body. LNCs were then tested in retinal explants prepared from wild-type (WT) and rd1 mouse. In WT retina LNCs showed no significant toxic effects up to a concentration of 5 mg/mL. In rd1 retina, the LNC/CN03 formulation protected rd1 photoreceptors with similar efficacy to that of free CN03, demonstrating the usefulness of LNC/CN03 formulation in the treatment of IRD. Overall, our results indicate the suitability of LNCs for intraocular administration and drug delivery to both the retina and the ciliary body.
A Supervised Machine Learning Approach to Classify Brain Morphology of Professional Visual Artists versus Non-Artists
2023-04-22

This study aimed to investigate whether there are structural differences in the brains of professional artists who received formal training in the visual arts and non-artists who did not have any formal training or professional experience in the visual arts, and whether these differences can be used to accurately classify individuals as being an artist or not. Previous research using functional MRI has suggested that general creativity involves a balance between the default mode network and the executive control network. However, it is not known whether there are structural differences between the brains of artists and non-artists. In this study, a machine learning method called Multi-Kernel Learning (MKL) was applied to gray matter images of 12 artists and 12 non-artists matched for age and gender. The results showed that the predictive model was able to correctly classify artists from non-artists with an accuracy of 79.17% (AUC 88%), and had the ability to predict new cases with an accuracy of 81.82%. The brain regions most important for this classification were the Heschl area, amygdala, cingulate, thalamus, and parts of the parietal and occipital lobes as well as the temporal pole. These regions may be related to the enhanced emotional and visuospatial abilities that professional artists possess compared to non-artists. Additionally, the reliability of this circuit was assessed using two different classifiers, which confirmed the findings. There was also a trend towards significance between the circuit and a measure of vividness of imagery, further supporting the idea that these brain regions may be related to the imagery abilities involved in the artistic process.
Late, but Not Early, Night Sleep Loss Compromises Neuroendocrine Appetite Regulation and the Desire for Food
2023-04-23

Objective: There is evidence that reduced sleep duration increases hunger, appetite, and food intake, leading to metabolic diseases, such as type 2 diabetes and obesity. However, the impact of sleep timing, irrespective of its duration and on the regulation of hunger and appetite, is less clear. We aimed to evaluate the impact of sleep loss during the late vs. early part of the night on the regulation of hunger, appetite, and desire for food. Methods: Fifteen normal-weight ([mean ± SEM] body-mass index: 23.3 ± 0.4 kg/m2) healthy men were studied in a randomized, balanced, crossover design, including two conditions of sleep loss, i.e., 4 h sleep during the first night-half (‘late-night sleep loss’), 4 h sleep during the second night-half (‘early-night sleep loss’), and a control condition with 8h sleep (‘regular sleep’), respectively. Feelings of hunger and appetite were assessed through visual analogue scales, and plasma ghrelin and leptin were measured from blood samples taken before, during, and after night-time sleep. Results: Ghrelin and feelings of hunger and appetite, as well as the desire for food, were increased after ‘late-night sleep loss’, but not ‘early-night sleep loss’, whereas leptin remained unaffected by the timing of sleep loss. Conclusions: Our data indicate that timing of sleep restriction modulates the effects of acute sleep loss on ghrelin and appetite regulation in healthy men. ‘Late-night sleep loss’ might be a risk factor for metabolic diseases, such as obesity and type 2 diabetes. Thereby, our findings highlight the metabolic relevance of chronobiological sleep timing.
Blood and cerebellar abundance ofATXN3splice variants in spinocerebellar ataxia type 3/Machado-Joseph disease
2023-04-23

ABSTRACT Background Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease (MJD) is an autosomal dominant polyglutamine disease. SCA3/MJD causative gene, ATXN3 , is known to undergo alternative splicing (AS) and 54 transcripts are currently annotated. Differences in the toxicity of ataxin-3 protein isoforms, harbouring on its C-terminus two or three ubiquitin interacting motifs (UIMs), were previously uncovered, raising the hypothesis that specific ATXN3 splice variants play key roles in promoting the selective toxicity displayed in SCA3/MJD. Methods Using RNA-seq datasets we identified and determined the abundance of annotated ATXN3 transcripts in blood (n=60) and cerebellum (n=12) of SCA3/MJD subjects and controls. Results Globally, the number and the abundance of individual ATXN3 transcripts were higher in the cerebellum than in the blood. While the most abundant transcript in the cerebellum was a protein with a coding sequence not defined of unknown function ( ATXN3 -208), the transcript with the highest abundance in blood was the reference transcript ( ATXN3 -251) which translates into an ataxin-3 isoform harboring three UIMs. Noteworthy, the abundance of ATXN3 -251 and ATXN3 -214, two out of the four transcripts that encode full-length ataxin-3 protein isoforms but differ in the C-terminus were strongly related with tissue expression specificity: ATXN3-251 (3UIM) was expressed in blood 50-fold more than in cerebellum, whereas ATXN3 -214 (2UIM) was expressed in the cerebellum 20-fold more than in blood. Conclusions These findings provide new insights into the elucidation of ATXN3 AS in different tissues, contributing for a better understanding of SCA3/MJD pathogenesis and providing information for the development of future effective ATXN3 mRNA-lowering therapies.
A versatile workflow for linear modelling in R
2023-04-24

Linear models are applied widely to analyse empirical data. Modern software allows implementation of linear models with a few clicks or lines of code. While convenient, this increases the risk of ignoring essential assessment steps. Indeed, inappropriate application of linear models is an important source of inaccurate statistical inference. Despite extensive guidance and detailed demonstration of exemplary analyses, many users struggle to implement and assess their own models. To fill this gap, we present a versatile R-workflow template that facilitates (Generalized) Linear (Mixed) Model analyses. The script guides users from data exploration through model formulation, assessment and refinement to the graphical and numerical presentation of results. The workflow accommodates a variety of data types, distribution families, and dependency structures that arise from hierarchical sampling. To apply the routine, minimal coding skills are required for data preparation, naming of variables of interest, linear model formulation, and settings for summary graphs. Beyond that, default functions are provided for visual data exploration and model assessment. Focused on graphs, model assessment offers qualitative feedback and guidance on model refinement, pointing to more detailed or advanced literature where appropriate. With this workflow, we hope to contribute to research transparency, comparability, and reproducibility.
Tackling the Pangenome Dilemma Requires the Concerted Analysis of Multiple Population Genetic Processes
2023-04-24

Abstract The pangenome is the set of all genes present in a prokaryotic population. Most pangenomes contain many accessory genes of low and intermediate frequencies. Different population genetics processes contribute to the shape of these pangenomes, namely selection and fitness-independent processes such as gene transfer, gene loss, and migration. However, their relative importance is unknown and highly debated. Here, we argue that the debate around prokaryotic pangenomes arose due to the imprecise application of population genetics models. Most importantly, two different processes of horizontal gene transfer act on prokaryotic populations, which are frequently confused, despite their fundamentally different behavior. Genes acquired from distantly related organisms (termed here acquiring gene transfer) are most comparable to mutation in nucleotide sequences. In contrast, gene gain within the population (termed here spreading gene transfer) has an effect on gene frequencies that is identical to the effect of positive selection on single genes. We thus show that selection and fitness-independent population genetic processes affecting pangenomes are indistinguishable at the level of single gene dynamics. Nevertheless, population genetics processes are fundamentally different when considering the joint distribution of all accessory genes across individuals of a population. We propose that, to understand to which degree the different processes shaped pangenome diversity, the development of comprehensive models and simulation tools is mandatory. Furthermore, we need to identify summary statistics and measurable features that can distinguish between the processes, where considering the joint distribution of accessory genes across individuals of a population will be particularly relevant.
Efficient coding of natural scenes improves neural system identification
2023-04-24

Neural system identification aims at learning the response function of neurons to arbitrary stimuli using experimentally recorded data, but typically does not leverage normative principles such as efficient coding of natural environments. Visual systems, however, have evolved to efficiently process input from the natural environment. Here, we present a normative network regularization for system identification models by incorporating, as a regularizer, the efficient coding hypothesis, which states that neural response properties of sensory representations are strongly shaped by the need to preserve most of the stimulus information with limited resources. Using this approach, we explored if a system identification model can be improved by sharing its convolutional filters with those of an autoencoder which aims to efficiently encode natural stimuli. To this end, we built a hybrid model to predict the responses of retinal neurons to noise stimuli. This approach did not only yield a higher performance than the “stand-alone” system identification model, it also produced more biologically plausible filters, meaning that they more closely resembled neural representation in early visual systems. We found these results applied to retinal responses to different artificial stimuli and across model architectures. Moreover, our normatively regularized model performed particularly well in predicting responses of direction-of-motion sensitive retinal neurons. The benefit of natural scene statistics became marginal, however, for predicting the responses to natural movies. In summary, our results indicate that efficiently encoding environmental inputs can improve system identification models, at least for noise stimuli, and point to the benefit of probing the visual system with naturalistic stimuli.
An alternative approach to the osmotic second virial coefficient of protein solutions and its application to liquid–liquid phase separation
2023-04-24

The osmotic second virial coefficient B2 is an important parameter to describe the interactions and phase behavior of protein solutions, including colloidal systems and macromolecular solutions. Another key parameter to describe the driving force of the nucleation of a new phase is the supersaturation, which is used in the classical nucleation theory framework and is connected with the favorable contribution in the Gibbs free energy in the bulk solution. In this article, we establish a connection between B2 calculated from small angle x-ray scattering (SAXS) data and the values of B2 obtained from supersaturation measurements using thermodynamics considerations. The values of the second virial coefficient calculated employing this method agree with those determined via SAXS in the region near the liquid–liquid phase separation border for human serum albumin and bovine serum albumin. The general relations adopted are shown to be useful for the estimation of the second virial coefficient B2 for globular proteins, in the proximity of the binodal biphasic coexistent region.
Depletion of Ly6G-Expressing Neutrophilic Cells Leads to Altered Peripheral T-Cell Homeostasis and Thymic Development in Neonatal Mice
2023-04-24

Newborns and especially preterm infants are much more susceptible to infections than adults. Due to immature adaptive immunity, especially innate immune cells play an important role in a newborn’s infection defense. Neonatal neutrophils exhibit profound differences in their functionality compared to neutrophils of adults. In particular, neonates possess a relevant population of suppressive neutrophils, which not only inhibit but also specifically modulate the function of T-cells. In this study, we investigated whether neonatal neutrophils are already involved in T-cell development in the thymus. For this purpose, we used a newly developed model of antibody-mediated immune cell depletion in which we administered a depleting antibody to pregnant and then lactating dams. Using this method, we were able to sufficiently deplete Ly6G-positive neutrophils in offspring. We demonstrated that the depletion of neutrophils in newborn mice resulted in altered peripheral T-cell homeostasis with a decreased CD4+/CD8+ T-cell ratio and decreased expression of CD62L. Neutrophil depletion even affected T-cell development in the thymus, with increased double positive thymocytes and a decreased CD4+/CD8+ single positive thymocyte ratio. Altogether, we demonstrated a previously unknown mechanism mediating neutrophils’ immunomodulatory effects in newborns.
Impairments in recognition of emotional facial expressions, affective prosody, and multisensory facilitation of response time in high-functioning autism
2023-04-24

Introduction Deficits in emotional perception are common in autistic people, but it remains unclear to which extent these perceptual impairments are linked to specific sensory modalities, specific emotions or multisensory facilitation. Methods This study aimed to investigate uni- and bimodal perception of emotional cues as well as multisensory facilitation in autistic ( n = 18, mean age: 36.72 years, SD: 11.36) compared to non-autistic ( n = 18, mean age: 36.41 years, SD: 12.18) people using auditory, visual and audiovisual stimuli. Results Lower identification accuracy and longer response time were revealed in high-functioning autistic people. These differences were independent of modality and emotion and showed large effect sizes (Cohen’s d 0.8–1.2). Furthermore, multisensory facilitation of response time was observed in non-autistic people that was absent in autistic people, whereas no differences were found in multisensory facilitation of accuracy between the two groups. Discussion These findings suggest that processing of auditory and visual components of audiovisual stimuli is carried out more separately in autistic individuals (with equivalent temporal demands required for processing of the respective unimodal cues), but still with similar relative improvement in accuracy, whereas earlier integrative multimodal merging of stimulus properties seems to occur in non-autistic individuals.
A new perspective on completeness and finitist consistency
2023-04-24

Abstract In this paper, we study the metamathematics of consistent arithmetical theories (containing ); we investigate numerical properties based on proof predicates that depend on numerations of the axioms. Numeral Completeness. For every true (in ) sentence , with a -formula, there is a numeration of the axioms of such that , where is the provability predicate for the numeration . Numeral Consistency. If is consistent, there is a -numeration of the axioms of such that , where denotes a -definition of ‘ is a -proof of ’. Finitist consistency is addressed by generalizing a result of Artemov: Partial finitism. If is consistent, there is a primitive recursive function such that, for all , is the code of an -proof of . These results are not in conflict with Gödel’s Incompleteness Theorems. Rather, they allow to extend their usual interpretation and show a deep connection to reflections in Hilbert’s last papers of 1931.
Microglia colonize the developing brain by clonal expansion of highly proliferative progenitors, following allometric scaling
2023-04-25

Microglia arise from the yolk sac and enter the brain during early embryogenesis. Upon entry, microglia undergo in situ proliferation and eventually colonize the entire brain by the third postnatal week in mice. However, the intricacies of their developmental expansion remain unclear. Here, we characterize the proliferative dynamics of microglia during embryonic and postnatal development using complementary fate-mapping techniques. We demonstrate that the developmental colonization of the brain is facilitated by clonal expansion of highly proliferative microglial progenitors that occupy spatial niches throughout the brain. Moreover, the spatial distribution of microglia switches from a clustered to a random pattern between embryonic and late postnatal development. Interestingly, the developmental increase in microglial numbers follows the proportional growth of the brain in an allometric manner until a mosaic distribution has been established. Overall, our findings offer insight into how the competition for space may drive microglial colonization by clonal expansion during development.
Transition for adolescents with a rare disease: results of a nationwide German project
2023-04-25

Abstract Purpose The transition process from paediatric/adolescent to adult medical care settings is of utmost importance for the future health of adolescents with chronic diseases and poses even more difficulties in the context of rare diseases (RDs). Paediatric care teams are challenged to deliver adolescent-appropriate information and structures. Here we present a structured transition pathway which is patient-focused and adoptable for different RDs. Methods The transition pathway for adolescents 16 years and older was developed and implemented as part of a multi-centre study in 10 university hospitals in Germany. Key elements of the pathway included: assessment of patients’ disease-related knowledge and needs, training/educational and counselling sessions, a structured epicrisis and a transfer appointment jointly with the paediatric and adult specialist. Specific care coordinators from the participating university hospitals were in charge of organization and coordination of the transition process. Results Of a total of 292 patients, 286 completed the pathway. Deficits in disease-specific knowledge were present in more than 90% of participants. A need for genetic or socio-legal counselling was indicated by &gt; 60%. A mean of 2.1 training sessions per patient were provided over a period of almost 1 year, followed by the transfer to adult care in 267 cases. Twelve patients remained in paediatric care as no adult health care specialist could be identified. Targeted training and counselling resulted in improved disease-specific knowledge and contributed to empowering of patients. Conclusion The described transition pathway succeeds to improve health literacy in adolescents with RDs and can be implemented by paediatric care teams in any RD specialty. Patient empowerment was mainly achieved by individualized training and counselling.