Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid, automated and experimenter-free assessment of cognitive flexibility reveals learning impairments following recovery from activity-based anorexia in female rats

Anorexia nervosa (AN) has among the highest mortality rates of any psychiatric disorder and is characterised by cognitive inflexibility that persists after weight recovery and contributes to the low rates of recovery. What remains unknown is whether cognitive inflexibility predisposes individuals to AN, a question that is difficult to determine from human studies. Our previous work using the most well-established animal model of AN, known as activity-based anorexia (ABA) identified a neurobiological link between cognitive inflexibility and susceptibility to pathological weight loss in female rats. However, testing flexible learning prior to exposure to ABA in the same animals has been thus far impossible due to the length of training required and the necessity of daily handling, which can itself influence the development of ABA. Here we describe experiments that validate and optimise the first fully-automated and experimenter-free touchscreen cognitive testing system for rats (n=20) and use this novel system to examine the reciprocal links between reversal learning (an assay of cognitive flexibility) and weight loss in the ABA model (n=60). Firstly, we show substantially reduced testing time and increased throughput compared to conventional touchscreen testing methods because animals engage in test sessions at their own direction and can complete multiple sessions per day without experimenter involvement. We also show that, contrary to expectations, cognitive inflexibility does not predispose rats to pathological weight loss in ABA but instead that rats subsequently susceptible to weight loss performed better on the reversal learning task. Intriguingly, we show reciprocal links between ABA exposure and cognitive flexibility, with ABA exposed (but weight recovered) rats performing much worse that ABA naïve rats on the reversal learning task. On the other hand, animals that had been trained on reversal learning were better able to resist weight loss upon subsequent exposure to the ABA model. We also uncovered some stable behavioural differences between ABA susceptible versus resistant rats during touchscreen test sessions using machine learning tools that highlight possible predictors of anorectic phenotypes. These findings shed new light on the relationship between cognitive inflexibility and pathological weight loss and provide a robust target for future studies using the ABA model to investigate potential novel pharmacotherapies for AN.
KBPRNA: A novel method integrating bulk RNA-seq data and LINCS-L1000 gene signatures to predict kinase activity based on machine learning

Background Kinases are a type of enzymes which can transfer phosphate groups from high-energy and phosphate-donating molecules to specific substrates. Kinase activities could be utilized to be represented as specific biomarkers of specific cancer types. Nowadays novel algorithms have already been developed to compute kinase activities from phosphorylated proteomics data. However, phosphorylated proteomics sequencing could be costly expensive and need valuable samples. Moreover,not methods which could achieve kinase activities from bulk RNA-sequence data have been developed. Here we propose KBPRNA, a general computational framework for extracting specific kinase activities from bulk RNA-sequencing data in cancer samples. KBPRNA also achieves better performance in predicting kinase activities from bulk RNA-sequence data under cancer conditions benchmarking against other models. Results In this study, we used LINCS-L1000 dataset which was used to be reported as efficient gene signatures in defining bulk RNA-seq data as input dataset of KBPRNA. Also, we utilized eXtreme Gradient Boosting (XGboost) as the main algorithm to extract valuable information to predict kinase activities. This model outperforms other methods such as linear regression and random forest in predicting kinase activities from bulk RNA-seq data. KBPRNA integrated tissue samples coming from breast invasive carcinoma, hepatocellular carcinoma, lung squamous cell carcinoma, Glioblastoma multiforme and Uterine Corpus Endometrial Carcinoma. It was found that KBPRNA achieved good performance with an average R score above threshold of 0.5 in kinase activity prediction. Conclusions Model training and testing process showed that KBPRNA outperformed other machine learning methods in predicting kinase activities coming from various cancer types’ tissue samples. This model could be utilized to approximate basic kinase activities and link it with specific biological functions, which in further promoted the progress of cancer identification and prognosis.
Repulsive interaction and secondary structure of highly charged proteins in regulating biomolecular condensation

Biomolecular condensation is involved in various cellular processes both functional and dysfunctional. Regulation of the condensation is thus crucial to avoid pathological protein aggregation and to maintain stable cellular environments. Recently, a class of highly charged intrinsically disordered proteins (IDPs), which are called the heat-resistant obscure (Hero) proteins, are shown to protect other client proteins from pathological aggregation. Besides the potential importance of this function, molecular mechanisms for how Hero proteins can protect other proteins from aggregation are not still known. Here we perform multiscale molecular dynamics (MD) simulations of Hero11, one of the Hero proteins, and the C-terminal region of TDP-43, as a target protein of Hero11, at various conditions to examine how they interact with each other. Based on the simulation results, three possible mechanisms have been proposed: (i) TDP-43 and Hero11 in dense phase reduces contacts with each other and shows faster diffusion due to the repulsive Hero11-Hero11 interactions, (ii) the amount of TDP-43 in dilute phase increases and their sizes become greater upon the attractive Hero11-TDP-43 interactions, and (iii) Hero-11 on the surface of small TDP-43 condensates avoids their fusions with the repulsive interactions. We also examine possible Hero-11 structures in atomistic and coarse-grained MD simulations and found disordered Hero-11 tend to assemble on the surface of the condensates, avoiding the droplet fusion effectively. The proposed mechanisms give us new insight into the regulation of biomolecular condensation in the cells and other conditions.
Epigenetic variation in the Lombardy poplar along climatic gradients is independent of genetic structure and persists across clonal reproduction

- Environmental changes can trigger phenotypic variation in plants through epigenetic mechanisms, but strong genetic influences make it difficult to isolate and study epigenetic effects. Clonal trees with low genetic variation, such as the Lombardy poplar (Populus nigra cv. ‘Italica’ Duroi), offer a unique system to study epigenetic variation associated with the environment. - We collected cuttings (ramets) of Lombardy poplar along a wide geographical range in Europe. We performed whole-genome-bisulfite sequencing of 164 ramets grown in a common garden and of a subset of 35 of the original parental individuals. Using historical bioclimatic data, we tested the relationship between DNA methylation and climatic gradients. - We found that average methylation levels in TEs and promoter regions correlate with biologically relevant climatic variables. Furthermore, we observed that DNA methylation was transmitted to the next clonal generation, but a fraction of the methylome changed relatively fast when comparing the parental individuals with the clonal offspring. - Our results suggest that the poplar methylome is a dynamic layer of information that can be transmitted to the clonal offspring and potentially affect how poplars acclimate to new environmental conditions.
Evidence for a Putative Isoprene Reductase in Acetobacterium wieringae

Isoprene was recently shown to act as an electron acceptor for a homoacetogenic bacterium. The focus of this study is the molecular basis for isoprene reduction. ABSTRACT Recent discoveries of isoprene-metabolizing microorganisms suggest they might play an important role in the global isoprene budget. Under anoxic conditions, isoprene can be used as an electron acceptor and is reduced to methylbutene. This study describes the proteogenomic profiling of an isoprene-reducing bacterial culture to identify organisms and genes responsible for the isoprene hydrogenation reaction. A metagenome-assembled genome (MAG) of the most abundant (89% relative abundance) lineage in the enrichment, Acetobacterium wieringae, was obtained. Comparative proteogenomics and reverse transcription-PCR (RT-PCR) identified a putative five-gene operon from the A. wieringae MAG upregulated during isoprene reduction. The operon encodes a putative oxidoreductase, three pleiotropic nickel chaperones (2 × HypA, HypB), and one 4Fe-4S ferredoxin. The oxidoreductase is proposed as the putative isoprene reductase with a binding site for NADH, flavin adenine dinucleotide (FAD), two pairs of canonical [4Fe-4S] clusters, and a putative iron-sulfur cluster site in a Cys6-bonding environment. Well-studied Acetobacterium strains, such as A. woodii DSM 1030, A. wieringae DSM 1911, or A. malicum DSM 4132, do not encode the isoprene-regulated operon but encode, like many other bacteria, a homolog of the putative isoprene reductase (~47 to 49% amino acid sequence identity). Uncharacterized homologs of the putative isoprene reductase are observed across the Firmicutes, Spirochaetes, Tenericutes, Actinobacteria, Chloroflexi, Bacteroidetes, and Proteobacteria, suggesting the ability of biohydrogenation of unfunctionalized conjugated doubled bonds in other unsaturated hydrocarbons. IMPORTANCE Isoprene was recently shown to act as an electron acceptor for a homoacetogenic bacterium. The focus of this study is the molecular basis for isoprene reduction. By comparing a genome from our isoprene-reducing enrichment culture, dominated by Acetobacterium wieringae, with genomes of other Acetobacterium lineages that do not reduce isoprene, we shortlisted candidate genes for isoprene reduction. Using comparative proteogenomics and reverse transcription-PCR we have identified a putative five-gene operon encoding an oxidoreductase referred to as putative isoprene reductase.
Schwarzschild and Birkhoff a la Weyl

We provide a simple derivation of the Schwarzschild solution in general relativity based on an approach by Weyl, but generalized to include Birkhoff’s theorem. This theorem states that the Schwarzschild mass must be constant in time. Our procedure is illustrated by a parallel derivation of the Coulomb field and the constancy of the electric charge in electrodynamics. We also explain the basis of Birkhoff’s theorem and note that even the original Weyl approach can be used to illuminate the special role played by the Schwarzschild coordinates.
Kinematics and Metallicity of M31 Red Giants: The Giant Southern Stream and Discovery of a Second Cold Component at R = 20 kpc

We present spectroscopic observations of red giant branch (RGB) stars in the Andromeda spiral galaxy (M31), acquired with the DEIMOS instrument on the Keck II 10 m telescope. The three fields targeted in this study are in the M31 spheroid, outer disk, and giant southern stream. In this paper, we focus on the kinematics and chemical composition of RGB stars in the stream field located at a projected distance of R = 20 kpc from M31's center. A mix of stellar populations is found in this field. M31 RGB stars are isolated from Milky Way dwarf star contaminants using a variety of spectral and photometric diagnostics. The radial velocity distribution of RGB stars displays a clear bimodality—a primary peak centered at 1 = -513 km s-1 and a secondary one at 2 = -417 km s-1—along with an underlying broad component that is presumably representative of the smooth spheroid of M31. Both peaks are found to be dynamically cold with intrinsic velocity dispersions of σ(v) ≈ 16 km s-1. The mean metallicity and metallicity dispersion of stars in the two peaks is also found to be similar: ⟨[Fe/H]⟩ ~ -0.45 and σ([Fe/H]) = 0.2. The observed velocity of the primary peak is consistent with that predicted by dynamical models for the stream, but there is no obvious explanation for the secondary peak. The nature of the secondary cold population is unclear: it may represent (1) tidal debris from a satellite merger event that is superimposed on, but unrelated to, the giant southern stream; (2) a wrapped around component of the giant southern stream; or (3) a warp or overdensity in M31's disk at Rdisk > 50 kpc (this component is well above the outward extrapolation of the smooth exponential disk brightness profile).
Galactic Chemical Evolution: Carbon through Zinc

We calculate the evolution of heavy-element abundances from C to Zn in the solar neighborhood, adopting our new nucleosynthesis yields. Our yields are calculated for wide ranges of metallicity (Z = 0-Z☉) and the explosion energy (normal supernovae and hypernovae), based on the light-curve and spectra fitting of individual supernovae. The elemental abundance ratios are in good agreement with observations. Among the α-elements, O, Mg, Si, S, and Ca show a plateau at [Fe/H] ≲ -1, while Ti is underabundant overall. The observed abundance of Zn ([Zn/Fe] ~ 0) can be explained only by the high-energy explosion models, as it requires a large contribution of hypernovae. The observed decrease in the odd-Z elements (Na, Al, and Cu) toward low [Fe/H] is reproduced by the metallicity effect on nucleosynthesis. The iron-peak elements (Cr, Mn, Co, and Ni) are consistent with the observed mean values at -2.5 ≲ [Fe/H] ≲ -1, and the observed trend at the lower metallicity can be explained by the energy effect. We also show the abundance ratios and the metallicity distribution functions of the Galactic bulge, halo, and thick disk. Our results suggest that the formation timescale of the thick disk is ~1-3 Gyr.
Numerical Predictions of Three Parallel Jets Interaction

This work is about the interaction of three parallel non-ventilated turbulent slot jets. The central jet is set symmetrically between two identical lateral heated jets. There are so many applications of this flow configuration in engineering such as gas turbine airfoils, heating or cooling surfaces, combustion and mixing flow. Computations are achieved by finite volume method. The numerical predictions confirm the three types of flow patterns given by the available flow visualization. Furthermore, a fourth type of flow pattern is found in this paper. For a given distance between two neighboring jets of 11 times the nozzle thickness (D0 = 11a), the effects of the velocity ratio on the dynamical and thermal flow fields are examined. Therefore, the contours of the streamlines, vorticity, pressure, kenetic turbulence energy and isotherms for several velocity ratios (0.3 ≤ λ ≤ 15), are discussed in this paper. Several temperature gaps (10°C ≤ ΔT≤ 50°C) between the two neighboring jets are considered. Both cent.
Stochastic oscillations produce dragon king avalanches in self-organized quasi-critical systems

In the last decade, several models with network adaptive mechanisms (link deletion-creation, dynamic synapses, dynamic gains) have been proposed as examples of self-organized criticality (SOC) to explain neuronal avalanches. However, all these systems present stochastic oscillations hovering around the critical region that are incompatible with standard SOC. This phenomenology has been called self-organized quasi-criticality (SOqC). Here we make a linear stability analysis of the mean field fixed points of two SOqC systems: a fully connected network of discrete time stochastic spiking neurons with firing rate adaptation produced by dynamic neuronal gains and an excitable cellular automata with depressing synapses. We find that the fixed point corresponds to a stable focus that loses stability at criticality. We argue that when this focus is close to become indifferent, demographic noise can elicit stochastic oscillations that frequently fall into the absorbing state. This mechanism interrupts the oscillations, producing both power law avalanches and dragon king events, which appear as bands of synchronized firings in raster plots. Our approach differs from standard SOC models in that it predicts the coexistence of these different types of neuronal activity.
Loop quantum gravity and Planck-size black hole entropy

The Loop Quantum Gravity (LQG) program is briefly reviewed and one of its main applications, namely the counting of black hole entropy within the framework is considered. In particular, recent results for Planck size black holes are reviewed. These results are consistent with an asymptotic linear relation (that fixes uniquely a free parameter of the theory) and a logarithmic correction with a coefficient equal to −1/2. The account is tailored as an introduction to the subject for non-experts
New Advances in Pulsar Magnetosphere Modelling

The wealth of high-energy ( E & 50 MeV) and very-high-energy ( E > 100 GeV) data accumulated over the past few years have provided unprecedented opportu nities to probe pulsar emission models. TheFermi Large Area Telescope (LAT) has now detected over 200 γ-ray pulsars of vastly different ages, providing an extensive dataset of spectra a nd light curves compared to a mere decade ago. Ground-based Cherenkov telescopes deepened ou r appreciation of the mysterious richness of the pulsar mechanism by a surprise detection of p ulsed emission up to 1 TeV from the Crab pulsar. These discoveries position us to make real prog ress in pulsar theory. A number of studies have developed new and enhanced existing dissipati ve magnetohydrodynamical (MHD) and particle-in-cell (PIC) codes to solve the global electr odynamics and pursue fundamental questions about magnetospheric particle injection, accelerat ion, and radiation. While MHD models capture the global aspects of pulsar magnetospheres, the mi crophysics need to be probed selfconsistently by PIC simulations. Some dissipative MHD mode ls consider the current sheet (CS) as an important site for high-energy curvature radiation (C R), while early PIC results point to energy dissipation taking place in the CS, where particles a r accelerated by magnetic reconnection and may possibly emit γ rays via synchrotron radiation (SR). This is in marked contr ast to some older local emission models that studied CR γ rays produced in gaps nearer to the spinning neutron star. The universality of these results should beco m clearer as current computational restrictions are overcome and boundary conditions are refin ed. Continued and combined polarimetric, spectral, and temporal measurements should aid us i n scrutinising these new emission models in our persistent pursuit of a deeper understanding o f the pulsar marvel.
$β'_{IR}$ at an Infrared Fixed Point in Chiral Gauge Theories

We present scheme-independent calculations of the derivative of the beta function, denoted $\beta'_{IR}$, at a conformally invariant infrared (IR) fixed point, in several asymptotically free chiral gauge theories, namely SO($4k+2$) with $2 \le k \le 4$ with respective numbers $N_f$ of fermions in the spinor representation, and E$_6$ with fermions in the fundamental representation.
On the Dynamics of Pebbles in Protoplanetary Disks with Magnetically Driven Winds

We present an analytical model to investigate the production of pebbles and their radial transport through a protoplanetary disk (PPD) with magnetically driven winds. While most of the previous analytical studies in this context assumed that the radial turbulent coefficient is equal to the vertical dust diffusion coefficient, in the light of the results of recent numerical simulations, we relax this assumption by adopting effective parameterizations of the turbulent coefficients involved, in terms of the strength of the magnetic fields driving the wind. Theoretical studies have already pointed out that even in the absence of winds, these coefficients are not necessarily equal, though how this absence affects pebble production has not been explored. In this paper, we investigate the evolution of the pebble production line, the radial mass flux of the pebbles, and their corresponding surface density as a function of the plasma parameter at the disk midplane. Our analysis explicitly demonstrates that the presence of magnetically driven winds in a PPD leads to considerable reduction of the rate and duration of the pebble delivery. We show that when the wind is strong, the core growth in mass due to the pebble accretion is so slow that it is unlikely that a core could reach a pebble isolation mass during a PPD lifetime. When the mass of a core reaches this critical value, pebble accretion is halted due to core-driven perturbations in the gas. With decreasing wind strength, however, pebble accretion may, in a shorter time, increase the mass of a core to the pebble isolation mass.
Magnetic phase diagram of antiferroquadrupole ordering in Ho B 2 C 2

The magnetic phase diagram for antiferroquadrupole (AFQ) ordering in tetragonal $\mathrm{Ho}{\mathrm{B}}_{2}{\mathrm{C}}_{2}$ has been investigated by measurements of elastic constants ${C}_{11}$, ${C}_{44}$, and ${C}_{66}$ in fields along the basal $x\text{\ensuremath{-}}y$ plane as well as the principal [001]-axis. The hybrid magnet (GAMA) in Tsukuba Magnetic Laboratory was employed for high field measurements up to $30\phantom{\rule{0.3em}{0ex}}\mathrm{T}$. The AFQ phase is no longer observed above $26.3\phantom{\rule{0.3em}{0ex}}\mathrm{T}$ along the principal [001]-axis in contrast to the relatively small critical field of $3.9\phantom{\rule{0.3em}{0ex}}\mathrm{T}$ in fields applied along the basal [110]-axis. The quadrupolar intersite interaction of ${O}_{xy}$ and/or ${O}_{2}^{2}$ is consistent with the anisotropy in the magnetic phase diagram of the AFQ phase in $\mathrm{Ho}{\mathrm{B}}_{2}{\mathrm{C}}_{2}$.
A Fast Approximate Approach to Microlensing Survey Analysis

Microlensing can be used to discover exoplanets of a wide range of masses with orbits beyond ∼1 au, and even free-floating planets. The Wide Field Infrared Survey Telescope (WFIRST) mission will use microlensing to discover approximately 1600 planets by monitoring ∼100 million stars to find ∼50,000 microlensing events. Modeling each microlensing event, especially the ones involving two or more lenses, is typically complicated and time consuming, and analyzing thousands of WFIRST microlensing events is possibly infeasible using current methods. Here, we present an algorithm that is able to rapidly evaluate thousands of simulated WFIRST binary-lens microlensing light curves, returning an estimate for the physical parameters of the lens systems. We find that this algorithm can recover projected separations between the planet and the star very well for low-mass-ratio events, and can also estimate mass ratios within an order of magnitude for events with wide and close caustic topologies.