Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative Structure–Toxicity Relationship in Bioactive Molecules from a Conceptual DFT Perspective

The preclinical drug discovery stage often requires a large amount of costly and time-consuming experiments using huge sets of chemical compounds. In the last few decades, this process has undergone significant improvements by the introduction of quantitative structure-activity relationship (QSAR) modelling that uses a certain percentage of experimental data to predict the biological activity/property of compounds with similar structural skeleton and/or containing a particular functional group(s). The use of machine learning tools along with it has made life even easier for pharmaceutical researchers. Here, we discuss the toxicity of certain sets of bioactive compounds towards Pimephales promelas and Tetrahymena pyriformis in terms of the global conceptual density functional theory (CDFT)-based descriptor, electrophilicity index (ω). We have compared the results with those obtained by using the commonly used hydrophobicity parameter, logP (where P is the n-octanol/water partition coefficient), considering the greater ease of computing the ω descriptor. The Human African trypanosomiasis (HAT) curing activity of 32 pyridyl benzamide derivatives is also studied against Tryphanosoma brucei. In this review article, we summarize these multiple linear regression (MLR)-based QSAR studies in terms of electrophilicity (ω, ω2) and hydrophobicity (logP, (logP)2) parameters.
The Loss-of-Function Mutation aldA67 Leads to Enhanced α-L-Rhamnosidase Production by Aspergillus nidulans

In Aspergillus nidulans L-rhamnose is catabolised to pyruvate and L-lactaldehyde, and the latter ultimately to L-lactate, via the non-phosphorylated pathway (LRA) encoded by the genes lraA-D, and aldA that encodes a broad substrate range aldehyde dehydrogenase (ALDH) that also functions in ethanol utilisation. LRA pathway expression requires both the pathway-specific transcriptional activator RhaR (rhaR is expressed constitutively) and the presence of L-rhamnose. The deletion of lraA severely impairs growth when L-rhamnose is the sole source of carbon and in addition it abolishes the induction of genes that respond to L-rhamnose/RhaR, indicating that an intermediate of the LRA pathway is the physiological inducer likely required to activate RhaR. The loss-of-function mutation aldA67 also has a severe negative impact on growth on L-rhamnose but, in contrast to the deletion of lraA, the expression levels of L-rhamnose/RhaR-responsive genes under inducing conditions are substantially up-regulated and the production of α-L-rhamnosidase activity is greatly increased compared to the aldA+ control. These findings are consistent with accumulation of the physiological inducer as a consequence of the loss of ALDH activity. Our observations suggest that aldA loss-of-function mutants could be biotechnologically relevant candidates for the over-production of α-L-rhamnosidase activity or the expression of heterologous genes driven by RhaR-responsive promoters.
Effects of Plant-Derived Glycerol Monolaurate (GML) Additive on the Antioxidant Capacity, Anti-Inflammatory Ability, Muscle Nutritional Value, and Intestinal Flora of Hybrid Grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂)

In a context where the search for plant-derived additives is a hot topic, glycerol monolaurate (GML) was chosen as our subject to study its effect on grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂). Seven gradient levels of GML (0, 600, 1200, 1800, 2400, 3000, and 3600 mg/kg) were used for the experiment. Based on our experiments, 1800 mg/kg GML significantly increased the final body weight (FBW) and weight gain rate (WGR). GML increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased malondialdehyde (MDA). Adding 1800 mg/kg GML also significantly increased the levels of lauric acid (C12:0) (LA), n-3 polyunsaturated fatty acids (PFA), and the n-6 PFA-to-n-3/n-6 ratio, while significantly decreasing the levels of saturated fatty acids (SFA). Dietary supplementation with GML significantly inhibited the expression of pro-inflammatory factors and reduced the occurrence of inflammation. GML improved intestinal flora and the abundance of beneficial bacteria (Bacillus, Psychrobacter, Acinetobacter, Acinetobacter, Stenotrophomonas, and Glutamicibacter). It provides a theoretical basis for the application of GML in aquafeed and greatly enhances the possibility of using GML in aquafeed. Based on the above experimental results, the optimum level of GML in grouper feed is 1800 mg/kg.
3D hydrodynamic simulations of carbon burning in massive stars

EU-FP7-ERC-St Grant [306901]; World Premier International Research Centre Initiative (WPI Initiative), Ministry of Education, Science and Culture (MEXT), Japan; COST (European Cooperation in Science and Technology); National Science Foundation grant [OCI-1053575]; NSF at the University of Arizona [1107445]; European Research Council [341157-COCO2CASA]; BIS National E-infrastructure capital grant [ST/K00042X/1]; STFC capital grants [ST/H008519/1, ST/K00087X/1]; STFC DiRAC Operations grant [ST/K003267/1]; Durham University
Longitudinal and transverse structure functions in high Reynolds-number magneto-hydrodynamic turbulence

We investigate the scaling behavior of longitudinal and transverse structure functions in homogeneous and isotropic magneto-hydrodynamic (MHD) turbulence by means of an exact hierarchy of structure function equations as well as by direct numerical simulations of two- and three-dimensional MHD turbulence. In particular, rescaling relations between longitudinal and transverse structure functions are derived and utilized in order to compare different scaling behavior in the inertial range. It is found that there are no substantial differences between longitudinal and transverse structure functions in MHD turbulence. This finding stands in contrast to the case of hydrodynamic turbulence which shows persistent differences even at high Reynolds numbers. We propose a physical picture that is based on an effective reduction of pressure contributions due to local regions of same magnitude and alignment of velocity and magnetic field fluctuations. Finally, our findings underline the importance of the pressure term for the actually observed scaling differences in hydrodynamic turbulence.
Human cortical amygdala dendrites and spines morphology under open‐source three‐dimensional reconstruction procedures

Visualizing nerve cells has been fundamental for the systematic description of brain structure and function in humans and other species. Different approaches aimed to unravel the morphological features of neuron types and diversity. The inherent complexity of the human nervous tissue and the need for proper histological processing have made studying human dendrites and spines challenging in postmortem samples. In this study, we used Golgi data and open‐source software for 3D image reconstruction of human neurons from the cortical amygdaloid nucleus to show different dendrites and pleomorphic spines at different angles. Procedures required minimal equipment and generated high‐quality images for differently shaped cells. We used the “single‐section” Golgi method adapted for the human brain to engender 3D reconstructed images of the neuronal cell body and the dendritic ramification by adopting a neuronal tracing procedure. In addition, we elaborated 3D reconstructions to visualize heterogeneous dendritic spines using a supervised machine learning‐based algorithm for image segmentation. These tools provided an additional upgrade and enhanced visual display of information related to the spatial orientation of dendritic branches and for dendritic spines of varied sizes and shapes in these human subcortical neurons. This same approach can be adapted for other techniques, areas of the central or peripheral nervous system, and comparative analysis between species.
Artificial Intelligence You Can Trust: What Matters Beyond Performance When Applying Artificial Intelligence to Renal Histopathology?

Although still in its infancy, artificial intelligence (AI) analysis of kidney biopsy images is anticipated to become an integral aspect of renal histopathology. As these systems are developed, the focus will understandably be on developing ever more accurate models, but successful translation to the clinic will also depend upon other characteristics of the system. In the extreme, deployment of highly performant but “black box” AI is fraught with risk, and high-profile errors could damage future trust in the technology. Furthermore, a major factor determining whether new systems are adopted in clinical settings is whether they are “trusted” by clinicians. Key to unlocking trust will be designing platforms optimized for intuitive human-AI interactions and ensuring that, where judgment is required to resolve ambiguous areas of assessment, the workings of the AI image classifier are understandable to the human observer. Therefore, determining the optimal design for AI systems depends on factors beyond performance, with considerations of goals, interpretability, and safety constraining many design and engineering choices. In this article, we explore challenges that arise in the application of AI to renal histopathology, and consider areas where choices around model architecture, training strategy, and workflow design may be influenced by factors beyond the final performance metrics of the system.
Abell 1758N from an optical point of view: new insights on a merging cluster with diffuse radio emission

Context. The mechanisms producing the diffuse radio emission in galaxy clusters, and in particular their connection with cluster mergers, are still debated. Aims. We seek to explore the internal dynamics of the cluster Abell 1758N, which has been shown to host a radio halo and two relics, and is known to be a merging bimodal cluster. Methods. Our analysis is mainly based on new redshift data for 137 galaxies acquired at the Telescopio Nazionale Galileo, only four of which have redshifts previously listed in the literature. We also used photometric data from the Sloan Digital Sky Survey and from the Canada-France-Hawaii Telescope archive. We combined galaxy velocities and positions to select 92 cluster galaxies and analyzed the internal cluster dynamics.
Cold Tolerance of ScCBL6 Is Associated with Tonoplast Transporters and Photosynthesis in Arabidopsis

Plants that are adapted to harsh environments offer enormous opportunity to understand stress responses in ecological systems. Stipa capillacea is widely distributed in the frigid and arid region of the Tibetan Plateau, but its signal transduction system under cold stress has not been characterized. In this study, we isolated a cDNA encoding the signal transduction protein, ScCBL6, from S. capillacea, and evaluated its role in cold tolerance by ectopically expressing it in Arabidopsis. Full-length ScCBL6 encode 227 amino acids, and are clustered with CBL6 in Stipa purpurea and Oryza sativa in a phylogenetic analysis. Compared with tolerance in wild-type (WT) plants, ScCBL6-overexpressing plants (ScCBL6-OXP) were more tolerant to cold stress but not to drought stress, as confirmed by their high photosynthetic capacity (Fv/Fm) and survival rate under cold stress. We further compared their cold-responsive transcriptome profiles by RNA sequencing. In total, 3931 genes were differentially expressed by the introduction of ScCBL6. These gene products were involved in multiple processes such as the immune system, lipid catabolism, and secondary metabolism. A KEGG pathway analysis revealed that they were mainly enriched in plant hormone signal transduction and biomacromolecule metabolism. Proteins encoded by differentially expressed genes were predicted to be localized in chloroplasts, mitochondria, and vacuoles, suggesting that ScCBL6 exerts a wide range of functions. Based on its tonoplast subcellular location combined with integrated transcriptome and physiological analyses of ScCBL6-OXP, we inferred that ScCBL6 improves plant cold stress tolerance in Arabidopsis via the regulation of photosynthesis, redox status, and tonoplast metabolite transporters.
Perspectives on interpersonal touch are related to subjective sleep quality

Affective touch has been reported for its calming effects; however, it is less clear whether touch is associated with sleep. Here, the relationship between different touch variables and self‐reported sleep indicators was investigated. Data were extracted from the Touch Test, a cross‐sectional survey conducted in 2020. Data from a sample of 15,049 healthy adults from the UK (mean age = 56.13, SD = 13.8; 75.4% female) were analysed. Participants were asked to attribute positive, negative, or no effects on sleep to hugs, strokes, massages, intimate touch, and sleep onset with and without touch. The time since last intentional touch, touch amount satisfaction, and childhood bed routine with hugs and kisses were assessed. Sleep quality, duration, latency, wake after sleep onset and diurnal preference were measured. Data were analysed using chi‐square tests and logistic regressions. Affective touch before sleep was perceived to have positive effects on sleep. Touch recency emerged as a significant predictor for some sleep variables, with a longer timespan since the last intentional touch relating to improved sleep quality, longer sleep duration, and shorter and fewer instances of waking up after sleep onset in some participants. Experiencing too much touch was related to lower sleep quality and higher instances of waking up after sleep onset. These findings highlight the importance of interpersonal touch for subjective sleep quality.
Enrichment in r-process Elements from Multiple Distinct Events in the Early Draco Dwarf Spheroidal Galaxy

The stellar record of elemental abundances in satellite galaxies is important to identify the origin of r-process because such a small stellar system could have hosted a single r-process event, which would distinguish member stars that are formed before and after the event through the evidence of a considerable difference in the abundances of r-process elements, as found in the ultra-faint dwarf galaxy Reticulum II (Ret II). However, the limited mass of these systems prevents us from collecting information from a sufficient number of stars in individual satellites. Hence, it remains unclear whether the discovery of a remarkable r-process enrichment event in Ret II explains the nature of r-process abundances or is an exception. We perform high-resolution spectroscopic measurements of r-process abundances for 12 metal-poor stars in the Draco dwarf galaxy in the metallicity range of . We found that these stars are separated into two groups with r-process abundances differing by one order of magnitude. A group of stars with high abundances of r-process elements was formed by a single r-process event that corresponds to the event evidenced in Ret II. On the other hand, the low r-process abundance group was formed by another sporadic enrichment channel producing far fewer r-process elements, which is clearly identified for the first time. Accordingly, we identified two populations of stars with different r-process abundances, which are built by two r-process events that enriched gases at levels that differ by more than one order of magnitude.
Ecotoxicological Assessment of “Glitter” Leachates in Aquatic Ecosystems: An Integrated Approach

The most worrisome fraction within plastic pollution is that of microplastics (MP). A category of MP almost completely ignored is that of glitter. The objective of this study is to test the toxicity of nine types of glitter leachate (3 soak times: 3, 90 and 180 days) on model organisms in freshwater (Allivibrio fischeri, Raphidocelis subcapitata, Daphnia magna) and saltwater (Allivibrio fischeri, Phaeodactylum tricornutum, Paracentrotus lividus). An integrated approach was applied to obtain the percentage of ecotoxicological risk. The results show that (i) photosynthesizing primary producers are the most sensitive trophic level; (ii) algae transitioned from growth inhibition to biostimulation; (iii) D. magna showed higher sensitivity after 48 h compared to 24 h; (iv) A. fischeri responded more strongly in saltwater than in freshwater. The integrated data show a greater risk associated with the marine environment, with the highest risk for glitters that are hexagonal and composed of poly-methyl-methacrylate. Our multivariate analysis shows that the toxicity of plastic leaching is a complex phenomenon that depends on the sensitivity of the species, in some cases on the soaking time and on the medium, and is not clearly linked to the polymer type, the contact area or the colors of the particles.
Insights from Quantum Information into Fundamental Physics

This thesis is split into two parts, which are united in the sense that they involve applying ideas from quantum information to fundamental physics. The first part is focused on examining discrete-time models in quantum computation (discrete-time quantum walks and quantum cellular automata) as discretized models of relativistic systems. One of the results here is a theorem demonstrating that a large class of discrete-time quantum walks have relativistic dynamics in the continuum limit. Additionally, the problem of fermion doubling for these models is investigated, and it is seen that the problem can be circumvented in two dimensional space. This was already known for one dimensional systems. Another result involves taking the limits of causal free field theories in discrete spacetime to recover continuum field theories, something that is not straightforward because of the nontrivial nature of the vacuum in quantum field theory. Additionally, it is shown that general systems of fermions evolving causally in discrete spacetime can be represented by quantum cellular automata, which makes them efficiently simulable by quantum computers. A related result is that quantum cellular automata composed of fermions are equivalent to regular quantum cellular automata. In the second part of this thesis, the focus is on the foundations of statistical physics. The main result of this part is a general bound on the time it takes a quantum system to effectively reach equilibrium. The discussion also includes a practical definition of equilibration that takes our measurement capabilities into account. Finally, the nature of the equilibrium state is also discussed, with a focus on initial state independence, which relates to the important question of when the equilibrium state is a Gibbs state.
Microglia and astrocyte activation is region‐dependent in the α‐synuclein mouse model of Parkinson's disease

Inflammation is a common feature in neurodegenerative diseases that contributes to neuronal loss. Previously, we demonstrated that the basal inflammatory tone differed between brain regions and, consequently, the reaction generated to a pro‐inflammatory stimulus was different. In this study, we assessed the innate immune reaction in the midbrain and in the striatum using an experimental model of Parkinson's disease. An adeno‐associated virus serotype 9 expressing the α‐synuclein and mCherry genes or the mCherry gene was administered into the substantia nigra. Myeloid cells (CD11b+) and astrocytes (ACSA2+) were purified from the midbrain and striatum for bulk RNA sequencing. In the parkinsonian midbrain, CD11b+ cells presented a unique anti‐inflammatory transcriptomic profile that differed from degenerative microglia signatures described in experimental models for other neurodegenerative conditions. By contrast, striatal CD11b+ cells showed a pro‐inflammatory state and were similar to disease‐associated microglia. In the midbrain, a prominent increase of infiltrated monocytes/macrophages was observed and, together with microglia, participated actively in the phagocytosis of dopaminergic neuronal bodies. Although striatal microglia presented a phagocytic transcriptomic profile, morphology and cell density was preserved and no active phagocytosis was detected. Interestingly, astrocytes presented a pro‐inflammatory fingerprint in the midbrain and a low number of differentially displayed transcripts in the striatum. During α‐synuclein‐dependent degeneration, microglia and astrocytes experience context‐dependent activation states with a different contribution to the inflammatory reaction. Our results point towards the relevance of selecting appropriate cell targets to design neuroprotective strategies aimed to modulate the innate immune system during the active phase of dopaminergic degeneration.
Non-Mendelian inheritance patterns and extreme deviation rates of CGG repeats in autism

As expansions of CGG short tandem repeats (STRs) are established as the genetic etiology of many neurodevelopmental disorders, we aimed to elucidate the inheritance patterns and role of CGG STRs in autism-spectrum disorder (ASD). By genotyping 6063 CGG STR loci in a large cohort of trios and quads with an ASD-affected proband, we determined an unprecedented rate of CGG repeat length deviation across a single generation. Although the concept of repeat length being linked to deviation rate was solidified, we show how shorter STRs display greater degrees of size variation. We observed that CGG STRs did not segregate by Mendelian principles but with a bias against longer repeats, which appeared to magnify as repeat length increased. Through logistic regression, we identified 19 genes that displayed significantly higher rates and degrees of CGG STR expansion within the ASD-affected probands (P < 1 × 10−5). This study not only highlights novel repeat expansions that may play a role in ASD but also reinforces the hypothesis that CGG STRs are specifically linked to human cognition.
Swift J2218.4+1925: a new hard-X-ray-selected polar observed with XMM–Newton

Swift J2218.4+1925, a hard X-ray source detected by Swift BAT, has been proposed as a candidate magnetic cataclysmic variable of the polar type from optical spectroscopy. Using XMM-Newton we perform detailed timing and spectral analysis with simultaneous X-ray ($0.3-10$ keV) and optical B band data. We complement the spectral study with archival hard X-ray (14-70 keV) spectra collected by Swift BAT as well as with optical, near and mid-infrared photometry from $SDSS$, $2MASS$ and $WISE$ archive, respectively. A strong periodic X-ray signal at 2.16 h, consistent with the recently determined spectroscopic orbital period, adds Swift J2218.4+1925 to the small group of hard X-ray polars and locates it at the low edge of the orbital period gap. The X-ray pulse profile shows the typical bright and faint phases seen in polars ($\sim 70%$ and $\sim 30%$ of the orbit, respectively). A pronounced dip centred on the bright phase is also detected. It is stronger at lower energies and is mainly produced by photoelectric absorption. A binary inclination $i \sim 40^o - 50^o$ and a magnetic colatitude $\beta \sim 55^o - 64^o$ are estimated. The source appears to accrete over a large area $\sim 24^o$ wide. A multi-temperature optically thin emission with complex absorption well describes the broad-band ($0.3-70$ keV) spectrum, with no signs of a soft X-ray blackbody component. The spectral shape varies with the source rotation reaching plasma temperatures up to 55 keV, hardening at the dip and being softer during the faint phase ($\sim7$ keV). We find the first indication of an absorption edge due to a warm absorber in a polar. Indication of overabundance of neon is found in the RGS spectra. The UV to mid-IR spectral energy distribution reveals an excess in the near and mid-IR, likely due to low cyclotron harmonics. We estimate a WD mass of 0.97 M$_{\odot}$ and a distance of 230-250 pc.