Miracle-dz/UniFAR-FTUs huggingface dataset:
SPIDR: a highly multiplexed method for mapping RNA-protein interactions uncovers a potential mechanism for selective translational suppression upon cellular stress

RNA binding proteins (RBPs) play crucial roles in regulating every stage of the mRNA life cycle and mediating non-coding RNA functions. Despite their importance, the specific roles of most RBPs remain unexplored because we do not know what specific RNAs most RBPs bind. Current methods, such as crosslinking and immunoprecipitation followed by sequencing (CLIP-seq), have expanded our knowledge of RBP-RNA interactions but are generally limited by their ability to map only one RBP at a time. To address this limitation, we developed SPIDR (Split and Pool Identification of RBP targets), a massively multiplexed method to simultaneously profile global RNA binding sites of dozens to hundreds of RBPs in a single experiment. SPIDR employs split-pool barcoding coupled with antibody-bead barcoding to increase the throughput of current CLIP methods by two orders of magnitude. SPIDR reliably identifies precise, single-nucleotide RNA binding sites for diverse classes of RBPs simultaneously. Using SPIDR, we explored changes in RBP binding upon mTOR inhibition and identified that 4EBP1 acts as a dynamic RBP that selectively binds to 5’-untranslated regions of specific translationally repressed mRNAs only upon mTOR inhibition. This observation provides a potential mechanism to explain the specificity of translational regulation controlled by mTOR signaling. SPIDR has the potential to revolutionize our understanding of RNA biology and both transcriptional and post-transcriptional gene regulation by enabling rapid, de novo discovery of RNA-protein interactions at an unprecedented scale.
Pre-attentive representation of prediction certainty in autism: A mismatch negativity (MMN) study

According to predictive processing theories of perception, the brain generates predictions to prepare for sensory input, and calibrates certainty of predictions based on their likelihood. When an input doesn’t match the prediction, an error signal leads to updating of the predictive model. Prior research suggests altered prediction certainty in autism, but predictive processing occurs across the cortical hierarchy, and the stage(s) of processing where prediction certainty breaks down is unknown. We therefore tested the integrity of prediction certainty in autism at pre-attentive and relatively automatic processing stages using the pre-attentive Mismatch Negativity (MMN) brain response. The MMN occurs in response to a “deviant” presented in a stream of “standards” and is measured while the participant performs an orthogonal task. Most critically, MMN amplitude typically varies with the level of certainty associated with the prediction. We recorded high-density EEG while presenting adolescents and young adults with and without autism with repetitive tones every half second (the standard) interspersed with infrequent pitch and inter-stimulus-interval (ISI) deviants. Pitch and ISI deviant probabilities were manipulated at 4, 8, or 16% within a block of trials to test whether MMN amplitude varied in a typical manner with respect to probability. For both groups, Pitch-MMN amplitude increased as the probability of deviance decreased. Unexpectedly, ISI-MMN amplitude did not reliably vary by probability in either group. Our Pitch-MMN findings suggest intact neural representation of pre-attentive prediction certainty in autism, addressing a critical knowledge gap in autism research. The implications of these findings are considered. LAY SUMMARY Our brains are always trying to predict what will happen next. For example, when you open your utensil drawer, it would be surprising to see books because your brain expected to see utensils. In our study, we looked at whether the brains of autistic individuals automatically and accurately recognize when something unexpected happens. Results showed similar brain patterns in individuals with and without autism, suggesting that responses to prediction violations are generated in a typical manner during early cortical information processing.
When Neural Activity Fails to Reveal Causal Contributions

Neuroscientists rely on distributed spatio-temporal patterns of neural activity to understand how neural units contribute to cognitive functions and behavior. However, the extent to which neural activity reliably indicates a unit’s causal contribution to the behavior is not well understood. To address this issue, we provide a systematic multi-site perturbation framework that captures time-varying causal contributions of elements to a collectively produced outcome. Applying our framework to intuitive toy examples and artificial neuronal networks revealed that recorded activity patterns of neural elements may not be generally informative of their causal contribution due to activity transformations within a network. Overall, our findings emphasize the limitations of inferring causal mechanisms from neural activities and offer a rigorous lesioning framework for elucidating causal neural contributions.
Scattered differentiation of unlinked loci across the genome underlines ecological divergence of the selfing grass Brachypodium stacei

Ecological divergence without geographic isolation, as an early speciation process that may lead finally to reproductive isolation through natural selection, remains one of the most interesting issues in evolutionary biology. However, the patterns of the underlying genetic divergences across the genome vary between different groups. Here we report that Brachypodium stacei, an inbreeding grass species, has been involved in sympatric ecological divergence without geographic isolation. Genomic, transcriptomic, and metabolomic analyses suggest that diploid B. stacei diverged sympatrically in two slopes with contrasting biomes at Evolution Canyon I (ECI), Mount Carmel, Israel, where gene flow has continued freely but reduced with the time. This ecological divergence involved the scattered divergence of many unlinked loci across the total genome that include both coding and non-coding regions. We also identified significantly differential expressions of ABA signaling pathway genes, and contrasting metabolome composition between the arid-vs forest-adapted B. stacei ECI populations. These results suggest that many small loci involved in environmental responses act additively to account for the ecological usages of this species in contrasted environments with gene flow. Significance Ecological divergence provides evidence for the origin of species through natural selection that has governed evolutionists’ attention since Darwin. In this study, we present multiple-omics analyses of two plant populations growing sympatrically in contrasted environments and revealed their distinct differentiation across all examined data. These two populations share the most recent ancestor compared with other populations and their divergence started in the early Holocene. We revealed that gene flow had continued but with a progressive reduction over time. The genetic divergences are scattered across the total genome involving many unlinked coding and non-coding regions. These findings highlight the significance of natural selection in the ecological divergence that may finally lead to species formation without geographic isolation.
Effects of sequence-dependent non-native interactions in equilibrium and kinetic folding properties of knotted proteins

Determining the role of non-native interactions in folding dynamics, kinetics and mechanisms is a classical problem in protein folding. More recently, this question has witnessed a renewed interest in light of the hypothesis that knotted proteins require the assistance of non-native interactions to fold efficiently. Here, we conducted extensive equilibrium and kinetic Monte Carlo simulations of a simple off-lattice C-alpha model to explore the role of non-native interactions in the thermodynamics and kinetics of three proteins embedding a trefoil knot in their native structure. We find that equilibrium knotted conformations are stabilized by non-native interactions that are non-local, and proximal to native ones, thus enhancing them. Additionally, non-native interactions increase the knotting frequency at high temperature, and in partially folded conformations below the transition temperature. While non-native interactions clearly enhance the efficiency of the transition from an unfolded conformation to a partially folded knotted one, they are not required to efficiently fold a knotted protein. Indeed, a native centric interaction potential drives the most efficient folding transition, provided that the simulation temperature is well below the transition temperature of the considered model system.
Effects of psychogenic stress on oxidative stress and antioxidant capacity at different growth stages

This study examined the psychogenic stress (PS) effects on changes in oxidative stress and the antioxidant capacity of an organism at different growth stages. The experimental animals were male Wistar rats of five different ages from growth periods (GPs) to old age. The growth stages were randomly classified into control (C) and experimental (PS) groups. PS was performed using restraint and water immersion once daily for 3 h for 4 weeks. Reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) were measured before and after the experiment. In addition, the liver and adrenal glands were removed, and the wet weight was measured. The d-ROM and BAP of all growth stages given PS increased significantly. The d-ROM in the C group without PS increased significantly in GPs while decreased significantly in old-aged. In addition, the BAP of the C group in GP and early adulthood were all significantly elevated. There were significant differences in organ weights between the C and PS groups at all growth stages. Oxidative stress and antioxidant capacity differed depending on the organism’s developmental status and growth stage, and PS also showed different effects. In particular, the variability in oxidative stress was remarkable, suggesting that the effect of PS was more significant in the organism’s immature organs.
A feasible memristive Chua's circuit via bridging a generalized memristor

Abstract By bridging a generalized memristor between a passive LC oscillator and an active RC filter, a simple and feasible memristive Chua’s circuit is presented. The generalized memristor without grounded limitation is equivalently achieved by a full-wave rectifier cascaded with a first-order parallel RC filter. The dynamical characteristics of the proposed circuit are investigated both theoretically and numerically, from which it can be found that the circuit has three unstable equilibrium points and demonstrates complex nonlinear phenomena. The experimental circuit is easy to implement and the measurement results validate the results of theoretical analyses.
A Cloud-Resolving Simulation of Hurricane Bob, 1991: Storm Structure and Eyewall Buoyancy

Abstract A numerical simulation of Hurricane Bob (1991) is conducted using the Pennsylvania State University–National Center for Atmospheric Research fifth-generation Mesoscale Model (MM5) with a horizontal grid spacing of 1.3 km on the finest nested mesh. The model produces a realistic hurricane that intensifies slowly during the period of finescale simulation. The time-averaged structure is characterized by a wavenumber-1 asymmetry with maximum low-level vertical motions and near-surface inflow in the left-front quadrant relative to the nearly aligned storm motion and mean wind shear vectors and strong outflow just above the boundary layer collocated with the updrafts. Instantaneous distributions of radial flow, vertical motion, and precipitation are strongly modified by a wavenumber-2 asymmetry that rotates cyclonically around the center at about half the speed of the mean tangential winds, consistent with the theory for vortex Rossby waves. The time-mean asymmetric vertical motion is comprised of smal.
Dealing with Diverse Cultures and Needs: How Have Higher Education Institutions in Portugal Responded to COVID-19?

This article seeks to provide a comprehensive analysis of the strategies implemented by Portuguese higher education institutions in addressing cultural diversity and meeting the demands of international students, particularly in the context of the COVID-19 pandemic outbreak. In methodological terms, this is a qualitative study in which more than 40 in-depth interviews were conducted with degree mobility students from Brazil, Portuguese-speaking African Countries, China and Syria, who were already in Portugal when the pandemic was declared in the country in March 2020. Through the lens of multiculturalism, which understands that higher education should be inclusive and equal for all, we found that higher education institutions in Portugal did not provide adequate support to its international student body at a time of so many challenges and uncertainties. Our data indicate that higher education institutions in Portugal need to make more efforts towards fostering a diverse and inclusive environment, whilst taking into account the complex needs of international students.
The Prevalence and Risk Factors of Iron Deficiency Anemia among Rural School children in Kudat, Sabah

Introduction: Iron deficiency anaemia (IDA) is the most common nutritional anaemia in the world that affects individuals in both developed and developing countries including Malaysia. The prevalence of IDA among schoolchildren is crucial to know as IDA may contribute to poor mental and school academic performance. Hence, the objective of the study was to diagnose the present prevalence of IDA and to analyse the association with probable risk factors. Methods: This cross-sectional study was carried out from August 2017 to February 2018 among 261 school children, who aged between 8 to 10 years in Kudat, Sabah, were selected through simple random sampling. After getting informed consent from the parents or guardians of the participants self-administered validated questionnaire was used to gather information regarding socio-demographic data, knowledge, attitude and practice towards iron deficiency anaemia and Food Frequency Questionnaires. The blood sample was collected for confirmation of anaemia through serum haemoglobin (Hb) concentration and determination of iron status through serum ferritin, serum iron and serum TIBC and stool samples were collected for children identified with anaemia for soil-transmitted helminths analysis. Results: Out of 82 anaemic students, 36 were suffering from iron deficiency anaemia. The BMI status, the presence of soil-transmitted helminths and level of knowledge regarding IDA had highly significant (p<0.001) association with prevalence of IDA. Conclusion: By improving the household economy, education, sanitation, and personal hygiene status and promoting consistent nutritional education among the population may help to reduce the prevalence of IDA.
Comparative Effectiveness and Persistence of Antimicrobial Durability in Dry and Wet States of a Novel Antimicrobial Surface Disinfectant

Aims: We evaluated a novel disinfectant (VR) and seven comparators (disinfectants A–G) against resistant pathogens common in healthcare settings. Methods and Results: VR at different dilutions, along with commercial disinfectants A–G, was tested against surrogate viruses, and resistant bacterial and fungal pathogens. Surrogate viruses had an initial concentration of ~1 × 108 mL−1, and bacterial and fungal isolates had an initial concentration of ~1 × 106 mL−1 on Siliconee surfaces. After the application of VR or a comparator disinfectant, surfaces were tested for the reduction in microbial loads after 30 s and 5 min wet exposures, and after a 24 h dry residue exposure. Sterile deionized water was used as a control. The VR at a concentration of 4.68% was superior to all comparator disinfectants against most pathogens in wet and dry testing. The VR at 7.8% concentration showed the highest pathogen-reduction rate among all comparator disinfectants when tested against all pathogens. Conclusions: Overall, the novel VR disinfectant was the most effective disinfectant in both wet and dry residue states against the range of tested pathogens. Significance and Impact of the Study: VR is a broadly effective disinfectant combination for use in high-risk settings, particularly those in which intervals between applications of disinfectant can be lengthy or inconsistent.
Ultra-Scaled Si Nanowire Biosensors for Single DNA Molecule Detection

In this study, we use NEGF quantum transport simulations to study the fundamental detection limit of ultra-scaled Si nanowire FET (NWT) biosensors. A N-doped NWT is found to be more sensitive for negatively charged analytes as explained by the nature of the detection mechanism. Our results predict threshold voltage shifts due to a single-charge analyte of tens to hundreds of mV in air or low-ionic solutions. However, with typical ionic solutions and SAM conditions, the sensitivity rapidly drops to the mV/q range. Our results are then extended to the detection of a single 20-base-long DNA molecule in solution. The impact of front- and/or back-gate biasing on the sensitivity and limit of detection is studied and a signal-to-noise ratio of 10 is predicted. Opportunities and challenges to reach down to single-analyte detection in such systems are also discussed, including the ionic and oxide-solution interface-charge screening and ways to recover unscreened sensitivities.
Measuring maternal autonomy and its effect on child nutrition in rural India

This paper examines the link between a mother's autonomy—the freedom and ability to think, express, make decisions and act independently—and the nutritional status of her children. We treat ‘autonomy’ as a latent variable, and design a novel statistical framework to measure this. This method allows us to separate the direct associations of maternal and family characteristics in our model for nutrition, from their indirect associations that work through maternal autonomy. Using data from India, we explore the sensitivity of our estimates to endogeneity caused by sample selection in the presence of son preference. We find: (i) a one standard deviation (SD) higher autonomy score is associated with a 0.16 SD higher height‐for‐age z‐score (HAZ score); and (ii) a 10% lower prevalence of stunting (HAZ < −2 SD). The latter is equivalent to the prevention of approximately 300,000 children stunting, indicating the important role of maternal autonomy.
Nutation Damper Undergoing a Coupled Motion

A novel numerical model is proposed to simulate liquid sloshing in a rectangular nutation damper (i.e. a tuned liquid damper) undergoing a coupled horizontal and rotational motion. Shallow water theory is used consistently to derive the governing equations of motion so that the model is applicable to large sloshing involving a hydraulic jump. It can also accommodate exposure of part of the damper’s floor to air by using a somewhat improved boundary shear approximation. A simple finite difference approach – the Lax scheme – is found to solve the equations of motion surprisingly well. Numerical predictions are checked against limited experimental data for a purely horizontal motion. Good agreement is generally observed. Furthermore, to demonstrate the model’s broader scope, the effect of a rotation is also considered in conjunction with a horizontal motion. The rotation is shown to significantly enhance the damper’s energy dissipation and, hence, its attenuation capability. For convenient practical application, an equivalent singledegree-of-freedom oscillator model is presented to characterize a nutation damper’s behavior for a coupled motion. The equivalent parameters of the model are determined so that the dissipated energy “best” fits a numerical counterpart. Their effect is investigated for different lengths, depths, and vibration levels of the damper. While the motivation of this investigation is to control the wind-induced galloping of overhead power lines, the proposed approach is applicable more generally to any excitation that induces low frequency vibrations.
Second-order sensitivity and optimal spanwise-periodic flow modifications

We perform a second-order sensitivity analysis of the linear temporal stability of a parallel mixing layer $U_0(y)$ subject to small spanwise-periodic modification $\epsilon U_1(y)\cos(\beta z)$. It is known that spanwise-periodic flow modifications have a quadratic effect on the stability properties of parallel flows (i.e. the first-order eigenvalue variation is zero), hence the need for a second-order analysis. From a simple one-dimensional (1D) calculation we compute the second-order sensitivity operator, which allows us to predict the effect on stability of any $U_1(y)$ without computing the eigenmode correction. Comparisons with two-dimensional (2D) stability calculations of modified flows show excellent agreement. From the second-order sensitivity operator we optimise the growth rate variation and compute the most stabilising and most destabilising $U_1$, together with lower and upper bounds for the growth rate variation induced by any spanwise-periodic modification of given amplitude $\epsilon$. These bounds show a local maximum for a spanwise wavenumber of order unity $\beta \simeq 1$, while they diverge like $\beta^{-2}$ as $\beta$ goes to zero (long-wavelength limit). The most stabilising (destabilising) $U_1$ determined for the most unstable streamwise wavenumber $\alpha_{max}$ is efficient in stabilising (destabilising) the flow for other values of $\alpha$ too. We also find that optimal 2D spanwise-periodic flow modifications are more efficient in stabilising (destabilising) than the optimal 1D spanwise-invariant modification provided the amplitude $\epsilon$ and wavelength $2\pi/\beta$ are large enough.
Differences in cooperation between social dilemmas of gain and loss

In social interactions, people frequently encounter gain (i.e., all outcomes are gains from the status-quo) or loss (all outcomes are losses from the status-quo) social dilemmas, where their personal interests conflict with social interests. We ask whether there are any behavioral differences in social interactions when it comes to gains and losses. Using the Prisoner’s Dilemma games, in three studies we observed that participants were less cooperative in the loss domain than in the gain domain. This effect was robust, not moderated by payoff amount (Study 1), cooperation index (Study 1), domain comparison (Studies 1 and 2), and personal loss aversion (Study 3). Social motive and belief explained this effect: compared to the gain domain, participants in the loss domain aroused more pro-self motive and less prosocial motive, and showed stronger beliefs that their partner would defect, which led them to cooperate less. These findings suggest that gain and loss domains affect individual motivation and belief, subsequently affecting strategic choices in social dilemmas.
Graph Convolutional Networks from the Perspective of Sheaves and the Neural Tangent Kernel

Graph convolutional networks are a popular class of deep neural network algorithms which have shown success in a number of relational learning tasks. Despite their success, graph convolutional networks exhibit a number of peculiar features, including a bias towards learning oversmoothed and homophilic functions, which are not easily diagnosed due to the complex nature of these algorithms. We propose to bridge this gap in understanding by studying the neural tangent kernel of sheaf convolutional networks--a topological generalization of graph convolutional networks. To this end, we derive a parameterization of the neural tangent kernel for sheaf convolutional networks which separates the function into two parts: one driven by a forward diffusion process determined by the graph, and the other determined by the composite effect of nodes' activations on the output layer. This geometrically-focused derivation produces a number of immediate insights which we discuss in detail.