Miracle-dz/UniFAR-FTUs huggingface dataset:
Stability of brain-behavior correlation patterns across measures of social support

The social environment has a critical influence on human development, cognition, and health. By using network approaches to map and analyze the connectivity between all pairs of brain regions simultaneously, we can clarify how relationships between brain regions (e.g. connectivity) change as a function of social relationships. Here we apply multilayer modeling and modularity maximization–both established tools in network neuroscience–to jointly cluster patterns of brain-behavior associations for seven social support measures. Our analyses build on both neuroecological findings and network neuroscientific approaches. In particular we find that subcortical and control systems are especially sensitive to different constructs of perceived social support. Network nodes in these systems are highly flexible; their community affiliations, which reflect groups of nodes with similar patterns of brain behavior associations, differ across social support measures. The multilayer approach used here enables direct comparison of the roles of all regions of the brain across all social support measures included. Additionally, our application of multilayer modeling to patterns of brainbehavior correlations, as opposed to just functional connectivity, represents an innovation in how multilayer models are used in. More than that, it offers a generalizable technique for studying the stability brain-behavior correlations.
Soliton solutions for a quasilinear Schrödinger equation with critical exponent

This paper is concerned with the existence of soliton solutions for a quasilinear Schrodinger equation in $R^N$ with critical exponent, which appears from modelling the self-channeling of a high-power ultrashort laser in matter. By working with a perturbation approach which was initially proposed in [26], we prove that the given problem has a positive ground state solution.
Retigabine and gabapentin restore channel function and neuronal firing of an epilepsy-associated dominant-negative KCNQ5 variant

Objective KCNQ5 encodes the voltage-gated potassium channel KV7.5, a member of the KV7 channel family, which conducts the M-current. This current was shown to be a potent regulator of neuronal excitability by mediating the medium and slow afterhyperpolarization. Recently, we have identified five loss-of-function variants in KCNQ5 in patients with genetic generalized epilepsy. Using the most severe dominant-negative variant p.(Arg359Cys) (R359C), we set out to investigate pharmacological therapeutic intervention by KV7 channel openers on channel function and neuronal firing. Methods Whole-cell patch clamp recordings were conducted in human embryonic kidney cells to investigate the immediate effect of retigabine, gabapentin and intracellular application of zinc on the R359C variant in absence and presence of KV7.5-WT subunits. Transfected primary hippocampal cultures were used to examine the effect of R359C on neuronal firing and whether this effect could be reversed by drug application. Results Retigabine and gabapentin both increased R359C-derived K+ current density and M-current amplitudes in both homomeric and heteromeric mutant KV7.5 channels. Retigabine was most effective in restoring K+ currents. Ten µM retigabine was sufficient to reach the level of WT currents without retigabine, whereas 100 µM of gabapentin showed less than half of this effect and application of 50 µM zinc only significantly increased M-current amplitude in heteromeric channels. Overexpression of KV7.5-WT potently inhibited neuronal firing by increasing the M-current, and medium afterhyperpolarization, whereas R359C overexpression had the opposite effect. All three aforementioned drugs reversed the effect of R359C reducing firing to nearly normal levels at high current injections. Significance Our study shows that a dominant-negative complete loss-of-function variant in KV7.5 leads to largely increased neuronal firing indicating a neuronal hyperexcitability. KV7 channel openers, such as retigabine or gabapentin, could be treatment options for otherwise pharmacoresistant epilepsy patients carrying loss-of-function variants in KCNQ5.
Visualization of translation reorganization upon persistent collision stress in mammalian cells

Aberrantly slow mRNA translation leads to ribosome stalling and subsequent collision with the trailing neighbor. Ribosome collisions have recently been shown to act as stress sensors in the cell, with the ability to trigger stress responses balancing survival and apoptotic cell-fate decisions depending on the stress level. However, we lack a molecular understanding of the reorganization of translation processes over time in mammalian cells exposed to an unresolved collision stress. Here we visualize the effect of a persistent collision stress on translation using in situ cryo electron tomography. We observe that low dose anisomycin collision stress leads to the stabilization of Z-site bound tRNA on elongating 80S ribosomes, as well as to the accumulation of an off-pathway 80S complex possibly resulting from collision splitting events. We visualize collided disomes in situ, occurring on compressed polysomes and revealing a stabilized geometry involving the Z-tRNA and L1 stalk on the stalled ribosome, and eEF2 bound to its collided rotated-2 neighbor. In addition, non-functional post-splitting 60S complexes accumulate in the stressed cells, indicating a limiting Ribosome associated Quality Control clearing rate. Finally, we observe the apparition of tRNA-bound aberrant 40S complexes shifting with the stress timepoint, suggesting a succession of different initiation inhibition mechanisms over time. Altogether, our work visualizes the changes of translation complexes under persistent collision stress in mammalian cells, indicating how perturbations in initiation, elongation and quality control processes contribute to an overall reduced protein synthesis. Summary Using in situ cryo electron tomography we visualized the reorganization of mammalian translation processes during a persistent collision stress.
Dynamics of vegetation cover and its driving factors in the Qinling-Daba Mountains on regional scale for 1986-2019

The Qinling-Daba Mountains is the transitional zone of the north and south of China. The vegetation in this area, characterized by complexity, heterogeneity and transition, is particularly sensitive to global climate change and human activities. Based on the normalized vegetation index (NDVI) data of the growing season from 1986 to 2019, which was synthesized by Landsat series satellite data on Google Earth Engine, this paper uses the methods of spatial analysis and Geo-detectors to clarify dynamics of vegetation cover and its main driving factors in the Qinling-Daba Mountains. The results show that: (1) vegetation coverage in study area shows a U-shaped NDVI distribution pattern in latitude, anti-U-shaped patterns in longitude and with altitude ascending. (2) the dynamics of vegetation coverage can be divided into two periods according to the result of MK mutation test (the breakthrough increasing period around 2005) and the trend of NDVI change: the slow increasing period with an increasing rate of 0.25%/a from 1986 to 2004 (R2 0.74), and the rapid increasing period with an increasing rate of 0.30%/a from 2005 to 2019 (R2 0.92). (3) Soil type, landform, vegetation type, land use type and annual average temperature are the main driving factors of vegetation dynamics in the Qinling-Daba Mountains, while annual precipitation, population density and GDP are the secondary driving factors of vegetation dynamics. The land use type and land management policies in the Qinling-Daba Mountains have a strong impact on vegetation cover change, and the climate warming in recent decades plays more important role than precipitation on the vegetation dynamics. These results are of great significance to comprehensively understand the impact of global climate warming and human activities on the natural environment of the Qinling-Daba Mountains.
Shifting the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one inhibitors towards the salt-inducible kinase (SIK) subfamily

Salt-inducible kinases 1-3 (SIK1-3) are key regulators of the LKB1-AMPK pathway and play an important role in cellular homeostasis. Dysregulation of any of the three isoforms has been associated with tumorigenesis in liver, breast, and ovarian cancers. We have recently developed the dual pan-SIK/group I p21-activated kinase (PAK) chemical probe MRIA9. However, inhibition of p21-activated kinases has been associated with cardiotoxicity in vivo, which complicates the use of MRIA9 as a tool compound. Here, we present a structure-based approach involving the back-pocket and gatekeeper residues, for narrowing the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one-based inhibitors towards SIK kinases, eliminating PAK activity. Optimization was guided by high-resolution crystal structure analysis and computational methods, resulting in a pan-SIK inhibitor, MR22, which no longer exhibited activity on STE group kinases and displayed excellent selectivity in a representative kinase panel. MR22-dependent SIK inhibition led to centrosome dissociation and subsequent cell-cycle arrest in ovarian cancer cells, as observed with MRIA9, conclusively linking these phenotypic effects to SIK inhibition. Taken together, MR22 represents a valuable tool compound for studying SIK kinase function in cells.
Oligodendrocytes in human iPS cell-derived cortical grafts remyelinate adult rat and human cortical neurons

Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly warranted. Here we demonstrate the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem (iPS) cell-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin ensheathing human axons in the host tissue after grafting onto adult human cortical organotypic cultures. This lt-NES cell line is the first human stem cell source that after intracerebral delivery can repair both injured neural circuitries and demyelinated axons. Our findings provide supportive evidence for the potential future use of human iPS cell-derived cell lines to promote effective clinical recovery following brain injuries.
Active Dendrites Enable Robust Spiking Computations Despite Timing Jitter

Dendritic action potentials exhibit long plateaus of many tens of milliseconds, outliving axonal spikes by an order of magnitude. The computational role of these slow events seems at odds with any need to rapidly integrate and relay information throughout large nervous systems. We propose that the timescale of dendritic potentials allows reliable integration of asynchronous inputs. We develop a physiologically grounded model in which the extended duration of dendritic spikes equips each dendrite with a resettable memory of incoming signals. This provides a tractable model for capturing dendritic nonlinearities observed in experiments and in more complex, detailed models. Using this model, we show that long-lived, nonlinear dendritic plateau potentials allow reliable integration of asynchronous spikes. We demonstrate this model supports non-trivial computations in a network solving an arbitrary association/discrimination task using sparse spiking that is subject to timing jitter. This demonstrates a computational role for the specific timecourse of dendritic potentials in situations where decisions occur quickly, reliably, and with a low number of spikes. Our results provide empirically testable hypotheses for the role of dendritic action potentials in cortical function as well as a potential bio-inspired means of realising neuromorphic spiking computations in analog hardware.
Hearing what is being said: The distributed neural substrate for early speech interpretation

Speech comprehension is remarkable for the immediacy with which the listener hears what is being said. Here, we focus on the neural underpinnings of this process in isolated spoken words. We analysed source-localised MEG data for nouns using Representational Similarity Analysis to probe the spatiotemporal coordinates of phonology, lexical form, and the semantics of emerging word candidates. Phonological model fit was detectable within 40-50 ms, engaging a bilateral network including superior and middle temporal cortex and extending into anterior temporal and inferior parietal regions. Lexical form emerged within 60-70 ms, and model fit to semantics from 100-110 ms. Strikingly, the majority of vertices in a central core showed model fit to all three dimensions, consistent with a distributed neural substrate for early speech analysis. The early interpretation of speech seems to be conducted in a unified integrative representational space, in conflict with conventional views of a linguistically stratified representational hierarchy.
Chromosome-Aware Phylogenomics of Assassin Bugs (Hemiptera: Reduvioidea) Elucidates Ancient Gene Conflict

Though the phylogenetic signal of loci on sex chromosomes can differ from those on autosomes, chromosomal-level genome assemblies for non-vertebrates are still relatively scarce and conservation of chromosomal gene content across deep phylogenetic scales has therefore remained largely unexplored. We here assemble a uniquely large and diverse set of samples (17 Anchored Hybrid Enrichment [AHE], 24 RNA-Seq, and 70 whole-genome sequencing [WGS] samples of variable depth) for the medically important assassin bugs (Reduvioidea). We assess the performance of genes based on multiple features (e.g., nucleotide vs. amino acid, nuclear vs. mitochondrial, and autosomal vs. X chromosomal) and employ different methods (concatenation and coalescence analyses) to reconstruct the unresolved phylogeny of this diverse (∼7,000 spp.) and old (>180 MYA) group. Our results show that genes on the X chromosome are more likely to have discordant phylogenies than those on autosomes. We find that the X chromosome conflict is driven by high gene substitution rates that impact accuracy of phylogenetic inference. However, gene tree clustering showed strong conflict even after discounting variable third codon positions. Alternative topologies were not particularly enriched for sex chromosome loci, but spread across the genome. We conclude that binning genes to autosomal or sex chromosomes may result in a more accurate picture of the complex evolutionary history of a clade.
Contribution and functional connectivity between cerebrum and cerebellum on sub-lexical and lexical-semantic processing of verbs

Language comprehension requires sub-lexical (e.g., phonological) and lexical-semantic processing. We designed a task to compare the sub-lexical and lexical-semantic processing of verbs during functional magnetic resonance imaging (fMRI). Likewise, we were interested in the dichotomous representation of concrete-motor versus abstract-non-motor concepts, so two semantic categories of verbs were included: motor and mental. The findings support the involvement of the left dorsal stream of the perisylvian network for sub-lexical processing during the reading of pseudo-verbs and the ventral stream for lexical-semantic representation during the reading of verbs. According to the embodied or grounded cognition approach, modality-specific mechanisms, i.e.,, sensory-motor systems, and the well-established multimodal left perisylvian network contribute to semantic representation for concrete and abstract verbs. The present study detected a preferential modality-specific system for abstract-mental verbs. The visual system was recruited by mental verbs and showed functional connectivity with the right crus I/lobule VI from the cerebellum, suggesting the existence of this network to support the semantic representation of abstract concepts. These results confirm the dissociation between sub-lexical and lexical-semantic processing and provide evidence about the neurobiological basis of semantic representations for abstract verbs.
Contrasting the form and strength of pre- and postcopulatory sexual selection in a transparent worm with fluorescent sperm

Sexual traits may be selected during multiple consecutive episodes of selection, occurring before, during, or after copulation. The overall strength and shape of selection acting on sexually selected traits may thus be determined by how selection (co-)varies along different episodes. However, it is challenging to measure pre- and postcopulatory phenotypic traits alongside variation in fitness components at each different episode. Here, we used a transgenic line of the transparent flatworm Macrostomum lignano expressing green fluorescent protein (GFP) in all cell types, including sperm cells, enabling in vivo sperm tracking. We exposed GFP(+) focal worms to three groups in which we assessed their mating success, sperm-transfer efficiency, and sperm fertilising efficiency. Moreover, we measured 13 morphological traits on the focal worms to study the fitness landscape in multivariate trait space. We found linear selection on sperm production rate arising from pre- and postcopulatory components, and on copulatory organ shape arising from sperm fertilising efficiency. We further found nonlinear (mostly concave) selection on combinations of copulatory organ and sperm morphology traits arising mostly from sperm-transfer efficiency and sperm fertilising efficiency. Our study shows that contrasting patterns of phenotypic selection are observed by measuring how sexual selection builds-up over consecutive episodes of selection.
Repeat transcranial Doppler ultrasound imaging in Kuwaiti children with sickle cell disease after a 10‐year interval: A prospective, cohort study

Transcranial Doppler imaging (TCDI) of the cerebral arteries is the method of choice to predict patients with sickle cell disease (SCD) at risk for stroke. This study reports TCDI follow‐up of cerebral blood flow in a cohort of Kuwaiti children with SCD after a 10‐year interval.
Series in locally convex spaces and inclusions between FK spaces

Singer [10] defined a series Σxk in a Banach space X to be weakly p-unconditionally Cauchy if and only if Σλkxk converges in X for all λ∊lp, where 1 < p < ∞. For Banach spaces containing no subspace isomorphic to c0 Singer characterized such series as those for which where 1/p + 1/q = 1 and X′ is the dual space of X.
A consistent grayscale‐free topology optimization method using the level‐set method and zero‐level boundary tracking mesh

This paper proposes a level‐set based topology optimization method incorporating a boundary tracking mesh generating method and nonlinear programming. Because the boundary tracking mesh is always conformed to the structural boundary, good approximation to the boundary is maintained during optimization; therefore, structural design problems are solved completely without grayscale material. Previously, we introduced the boundary tracking mesh generating method into level‐set based topology optimization and updated the design variables by solving the level‐set equation. In order to adapt our previous method to general structural optimization frameworks, the incorporation of the method with nonlinear programming is investigated in this paper. To successfully incorporate nonlinear programming, the optimization problem is regularized using a double‐well potential. Furthermore, the sensitivities with respect to the design variables are strictly derived to maintain consistency in mathematical programming. We expect the investigation to open up a new class of grayscale‐free topology optimization. The usefulness of the proposed method is demonstrated using several numerical examples targeting two‐dimensional compliant mechanism and metallic waveguide design problems. Copyright © 2014 John Wiley & Sons, Ltd.
Common features of particle beams and x-rays generated in a low energy dense plasma focus device

Features of energetic charged particle beams and x-ray emission in a low energy (1–2 kJ) plasma focus (DPF) device are described and the possible mechanism are explained based on circuit analyses and energy balance in the DPF system. In particular, the resistance and the voltage across the plasma column are estimated to explain the mechanisms of the generation of particle beams and hard x-ray. The analysis shows that the total inductance of a DPF might have played a role for enhancement of the particle beams and x-ray emissions during the phase of anomalous resistance.
Influence of the idle region on the dynamic properties of window Josephson tunnel junctions

The processes developed in the last years for the fabrication of high quality, reliable all‐refractory Josephson tunnel junctions open a window in an insulating region, called the idle region, which provides the passivation of the base electrode all around the junction itself. We report experimental data showing that the phase velocity of electromagnetic waves in the junction barrier can be considerably modified by the presence of the insulating region surrounding the window Josephson tunnel junctions. We have investigated this phenomenon in unidimensional junctions, measuring the asymptotic voltage of the Fiske resonances in the presence of an externally applied magnetic field. We have considered the effect of an idle region: (i) along the long junction dimension and (ii) at the extremities of the junction. When comparing the behavior to that of a bare junction, in the first case the phase velocity has been found to increase and to be affected by dispersion, while in the latter case it decreased and was .
The effect of base flow variation on flow stability

The Orr–Sommerfeld operator's eigenvalues determine the stability of exponentially growing disturbances in parallel and quasi-parallel flows. This work assesses the sensitivity of these eigenvalues to modifications of the base flow, which need not be infinitesimally small. Such base flow variations may represent differences between the laboratory flow and its ideal, theoretical counterpart. The worst case, i.e. the change in base flow with the most destabilizing effect on the eigenvalues, is found using variational techniques for the plane Couette flow. Relatively small changes in the base flow are shown to be destabilizing, although the ideal flow is unconditionally stable according to linear theory. These observations inspire a velocity-based definition of pseudospectra in the hydrodynamic stability context.
Numeraire-invariant option pricing and american, bermudan, trigger stream rollover

Part I proposes a numeraire-invariant option pricing framework. It defines an option, its price process, and such notions as option indistinguishability and equivalence, domination, payoff process, trigger option, and semipositive option. It develops some of their basic properties, including price transitivity law, indistinguishability results, convergence results, and, in relation to nonnegative arbitrage, characterizations of semipositivity and consequences thereof. These are applied in Part II to study the Snell envelop and american options. The measurability and right-continuity of the former is established in general. The american option is then defined, and its pricing formula (for all times) is presented. Applying a concept of a domineering numeraire for superclaims derived from (the additive) Doob-Meyer decomposition, minimax duality formulae are given which resemble though differ from those in [R] and [H-K]. Multiplicative Doob-Meyer decomposition is discussed last. A part III is also envisaged.