Miracle-dz/UniFAR-FTUs huggingface dataset:
ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization

The actin cytoskeleton is tightly controlled by RhoGTPases, actin binding-proteins and nucleation-promoting factors to perform fundamental cellular functions. We have previously shown that ERK3, an atypical MAPK, controls IL-8 production and chemotaxis (Bogueka et al., 2020). Here, we show in human cells that ERK3 directly acts as a guanine nucleotide exchange factor for CDC42 and phosphorylates the ARP3 subunit of the ARP2/3 complex at S418 to promote filopodia formation and actin polymerization, respectively. Consistently, depletion of ERK3 prevented both basal and EGF-dependent RAC1 and CDC42 activation, maintenance of F-actin content, filopodia formation, and epithelial cell migration. Further, ERK3 protein bound directly to the purified ARP2/3 complex and augmented polymerization of actin in vitro. ERK3 kinase activity was required for the formation of actin-rich protrusions in mammalian cells. These findings unveil a fundamentally unique pathway employed by cells to control actin-dependent cellular functions.
Single‐cell analysis of lymphatic endothelial cell fate specification and differentiation during zebrafish development

During development, the lymphatic vasculature forms as a second network derived chiefly from blood vessels. The transdifferentiation of embryonic venous endothelial cells (VECs) into lymphatic endothelial cells (LECs) is a key step in this process. Specification, differentiation and maintenance of LEC fate are all driven by the transcription factor Prox1, yet the downstream mechanisms remain to be elucidated. We here present a single‐cell transcriptomic atlas of lymphangiogenesis in zebrafish, revealing new markers and hallmarks of LEC differentiation over four developmental stages. We further profile single‐cell transcriptomic and chromatin accessibility changes in zygotic prox1a mutants that are undergoing a LEC‐VEC fate shift. Using maternal and zygotic prox1a/prox1b mutants, we determine the earliest transcriptomic changes directed by Prox1 during LEC specification. This work altogether reveals new downstream targets and regulatory regions of the genome controlled by Prox1 and presents evidence that Prox1 specifies LEC fate primarily by limiting blood vascular and haematopoietic fate. This extensive single‐cell resource provides new mechanistic insights into the enigmatic role of Prox1 and the control of LEC differentiation in development.
Critical mechanistic features of HIV-1 viral capsid assembly

The maturation of HIV-1 capsid protein (CA) into a cone-shaped lattice encasing the condensed RNA genome is critical for viral infectivity. During HIV-1 maturation, CA can self-assemble into a wide range of capsid morphologies made of ~175-250 hexamers and 12 pentamers. Most recently, the cellular polyanion inositol hexakisphosphate (IP6) has been demonstrated to facilitate conical capsid formation by coordinating a ring of arginine residues within the central cavity of capsid hexamers and pentamers. However, the precise kinetic interplay of events during IP6 and CA co-assembly is unclear. In this work, we use Coarse-grained Molecular Dynamics (CGMD) simulations to elucidate the underlying molecular mechanism of capsid formation, including the crucial role played by IP6. We show that IP6, in relatively small quantities at first, promotes curvature generation by trapping pentameric defects in the growing lattice and shifts assembly behavior towards kinetically favored outcomes. Our analysis also suggests that IP6 can stabilize metastable capsid intermediates and can induce structural pleomorphism in mature capsids. Teaser Computer simulations reveal that IP6 promotes fullerene-like capsid formation by stabilizing high curvature regions of the capsid.
Multiscale structural anisotropy in pulvinus motor organs of the sensitive plant Mimosa pudica

Pulvini are joint-like motor organs that power active leaf movement in many plants. Multiple structural specializations spanning subcellular, cellular, and tissue scales of pulvinus organization have been described; however, the impacts of multiscale mechanics on pulvinus physiology remain poorly understood. To investigate the influence of multiscale morphology on turgor-induced deformation, we visualized Mimosa pudica pulvinus morphology at multiple hierarchical scales of organization and used osmotic perturbations to experimentally swell pulvini in incremental states of dissection. We observed directional cellulose microfibril reinforcement, oblong, spindle-shaped primary pit fields, and flattened, disk-like cell geometries in the parenchyma of M. pudica. Consistent with these observations, isolated parenchyma tissues displayed highly anisotropic swelling behaviors indicating a high degree of mechanical anisotropy. Swelling behaviors at higher scales of pulvinus organization were also influenced by the presence of the pulvinus epidermis, which displayed oblong epidermal cells oriented transverse to the pulvinus long axis. Our findings indicate that structural specializations spread across multiple hierarchical scales of organization guide hydraulic deformation of pulvini, suggesting that multiscale mechanics are crucial to the translation of cell-level turgor variations into organ-scale pulvinus motion in vivo.
Capturing Brain-Cognition Relationship: Integrating Task-Based fMRI Across Tasks Markedly Boosts Prediction and Reliability and Reveals the Role of Frontoparietal Areas

Capturing individual differences in cognition is central to human neuroscience. Yet our ability to estimate cognitive abilities via brain MRI is still poor in both prediction and reliability. Our study tested if this inability was partly due to the over-reliance on 1) non-task MRI modalities and 2) single, rather than multiple, modalities. We directly compared predictive models comprising different sets of MRI modalities (e.g., task vs. non-task). Using the Human Connectome Project (n=873, 473 females, after quality control), we integrated task-based functional MRI (tfMRI) across seven tasks along with other non-task MRI modalities (structural MRI, resting-state functional connectivity). We applied two approaches to integrate multimodal MRI, stacked vs. flat models, and implemented 16 combinations of machine-learning algorithms. The model integrating all modalities via stacking Elastic Net provided unprecedented prediction (r=.57) and excellent test-retest reliability (ICC>.75) in capturing general cognitive abilities. Importantly, compared to the model integrating across non-task modalities (r=.27), the model integrating tfMRI across tasks led to significantly higher prediction (r=.56) while still providing excellent test-retest reliability (ICC>.75). The model integrating tfMRI across tasks was driven by areas in the frontoparietal network and by tasks that are cognition-related (working-memory, relational processing, and language). This result is consistent with the parieto-frontal integration theory of intelligence. Accordingly, our results sharply contradict the recently popular notion that tfMRI is not appropriate for capturing individual differences in cognition. Instead, our study suggests that tfMRI, when used appropriately (i.e., by drawing information across the whole brain and across tasks and by integrating with other modalities), provides predictive and reliable sources of information for individual differences in cognitive abilities, more so than non-task modalities. Highlights Non-task MRI (sMRI, rs-fMRI) are often used for the brain-cognition relationship. Task-based fMRI has deemed non-suitable for predicting individual differences. Drawing task-based fMRI information across regions/tasks improve its performance. Our approach boosts prediction of task-based fMRI over non-task MRI. Our approach renders task-based fMRI reliable over time. Our approach shows the importance of the frontoparietal network in cognition.
Size-dependent surface energies of Au nanoparticles

Motivated by often contradictory literature reports on size dependence of surface energy of gold nanoparticles, we performed an atomistic study combining molecular dynamics and \textit{ab initio} calculations. We show that in the case of Au nanocubes, their surface energy converges to a value for $(0\,0\,1)$ facets of bulk crystals. A fast convergence to a single valued surface energy is predicted also for nanosheres. In this case, however, the value of the surface energy is larger than that of any low-index surface facet of bulk Au crystal. This fact can be explained by the complex structure of the surface with an extensive number of broken bonds due to edge and corner atoms. A similar trend was obtained also for the case of cuboctahedron-shaped nanoobjects. As the exact surface area of the nanoparticles is an ill-defined quantity, we introduced the surface-induced excess energy and discussed this quantity as a function of (i) number of atoms forming the nanoobject or (ii) the nanoobject characteristic size. In case (i), a universal power-law behaviour was obtained independent of the nanoparticle shape. Importantly, we show that the size-dependence of the surface is hugely reduced is the surface area correction due to the extend of electronic cloud is considered, a phenomenon specifically important for small nanoparticles.
Finite temperature QCD using 2+1 flavors of domain wall fermions at Nt=8

We study the region of the QCD phase transition using 2+1 flavors of domain wall fermions and a 16{sup 3}x8 lattice volume with a fifth dimension of L{sub s}=32. The disconnected light quark chiral susceptibility, quark number susceptibility, and the Polyakov loop suggest a chiral and deconfining crossover transition lying between 155 and 185 MeV for our choice of quark mass and lattice spacing. In this region the lattice scale deduced from the Sommer parameter r{sub 0} is a{sup -1{approx_equal}}1.3 GeV, the pion mass is {approx_equal}300 MeV, and the kaon mass is approximately physical. The peak in the chiral susceptibility implies a pseudocritical temperature T{sub c}=171(10)(17) MeV where the first error is associated with determining the peak location and the second with our unphysical light quark mass and nonzero lattice spacing. The effects of residual chiral symmetry breaking on the chiral condensate and disconnected chiral susceptibility are studied using several values of the valence L{sub s}.
An explicit relaxation filtering framework based upon Perona-Malik anisotropic diffusion for shock capturing and subgrid scale modeling of Burgers turbulence

In this paper, we introduce a relaxation filtering closure approach to account for subgrid scale effects in explicitly filtered large eddy simulations using the concept of anisotropic diffusion. We utilize the Perona-Malik diffusion model and demonstrate its shock capturing ability and spectral performance for solving the Burgers turbulence problem, which is a simplified prototype for more realistic turbulent flows showing the same quadratic nonlinearity. Our numerical assessments present the behavior of various diffusivity functions in conjunction with a detailed sensitivity analysis with respect to the free modeling parameters. In comparison to direct numerical simulation (DNS) and under-resolved DNS results, we find that the proposed closure model is efficient in the prevention of energy accumulation at grid cut-off and is also adept at preventing any possible spurious numerical oscillations due to shock formation under the optimal parameter choices. In contrast to other relaxation filtering approaches, it is also shown that a larger inertial range can be obtained by the proposed anisotropic diffusion model using a compact stencil scheme in an efficient way.
Intuitive movement-based prosthesis control enables arm amputees to reach naturally in virtual reality

Impressive progresses are being made in bionic limbs design and control. Yet, controlling the numerous joints of a prosthetic arm necessary to place the hand at a correct position and orientation to grasp objects remains challenging. Here, we designed an intuitive, movement-based prosthesis control that leverages natural arm coordination to predict distal joints missing in arm amputees based on proximal stump motion and knowledge of the movement goal. This control was validated on 29 participants, including 7 above-elbow amputees, who picked and placed bottles in a wide range of locations in virtual reality, with median success rates over 99% and movement times identical to those of natural movements. Remarkably, this was achieved without any prior training, indicating that this control is intuitive and instantaneously usable. It could be used for phantom limb pain management in virtual reality, or to augment reaching capabilities of invasive neural interfaces usually more focused on hand and grasp control.
Development of an amplicon-based sequencing approach in response to the global emergence of human monkeypox virus

The 2022 multi-country monkeypox outbreak concurrent with the ongoing COVID-19 pandemic has further highlighted the need for genomic surveillance and pathogen whole genome sequencing. While metagenomic sequencing approaches have been used to sequence many of the early human monkeypox virus infections, these methods are resource intensive and require samples with high viral DNA concentrations. Given the atypical clinical presentation of cases associated with the current outbreak and uncertainty regarding viral load across both the course of infection and anatomical body sites, there is an urgent need for a more sensitive and broadly applicable sequencing approach. Amplicon-based sequencing (PrimalSeq) was initially developed for sequencing of Zika virus, and later adapted as the main sequencing approach for SARS-CoV-2. Here, we used PrimalScheme to develop a primer scheme for human monkeypox virus that can be used with many sequencing and bioinformatics pipelines implemented during the COVID-19 pandemic. We sequenced clinical samples that tested presumptive positive for monkeypox virus with amplicon-based and metagenomic sequencing approaches. Upon comparison, we found notably higher genome coverage across the virus genome, particularly in higher PCR cycle threshold (lower DNA titer) samples, with minimal amplicon drop-outs, in using the amplicon-based sequencing approach. By sending out primer pool aliquots to laboratories across the United States and internationally, we validated the primer scheme in 12 public health laboratories with their established Illumina or Oxford Nanopore Technologies sequencing workflows and with different sample types across a range of Ct values. Our findings suggest that amplicon-based sequencing increases the success rate across a wider range of viral DNA concentrations, with the PCR Ct value threshold at which laboratories were able to achieve 80% genome coverage at 10X ranging between Ct 25-33. Therefore, it increases the number of samples where near-complete genomes can be generated and it provides a cost-effective and widely applicable alternative to metagenomics for continued human monkeypox virus genomic surveillance. Importantly, we show that the human monkeypox virus primer scheme can be used with currently implemented amplicon-based SARS-CoV-2 sequencing workflows, with minimal change to the protocol.
SHOCK BREAKOUT AND EARLY LIGHT CURVES OF TYPE II-P SUPERNOVAE OBSERVED WITH KEPLER

We discovered two transient events in the Kepler field with light curves that strongly suggest they are type II-P supernovae (SNe II-P). Using the fast cadence of the Kepler observations we precisely estimate the rise time to maximum for KSN2011a and KSN2011d as 10.5 ± 0.4 and 13.3 ± 0.4 rest-frame days, respectively. Based on fits to idealized analytic models, we find the progenitor radius of KSN2011a (280 ± 20 R⊙) to be significantly smaller than that for KSN2011d (490 ± 20 R⊙), but both have similar explosion energies of 2.0 ± 0.3 × 1051 erg. The rising light curve of KSN2011d is an excellent match to that predicted by simple models of exploding red supergiants (RSG). However, the early rise of KSN2011a is faster than the models predict, possibly due to the supernova shock wave moving into pre-existing wind or mass-loss from the RSG. A mass-loss rate of 10−4M⊙ yr−1 from the RSG can explain the fast rise without impacting the optical flux at maximum light or the shape of the post-maximum light curve. No shock breakout emission is seen in KSN2011a, but this is likely due to the circumstellar interaction suspected in the fast rising light curve. The early light curve of KSN2011d does show excess emission consistent with model predictions of a shock breakout. This is the first optical detection of a shock breakout from a SNe II-P.
Metastability as a neuromechanistic biomarker of schizophrenia pathology

The disconnection hypothesis of schizophrenia proposes that symptoms of the disorder arise as a result of aberrant functional integration between segregated areas of the brain. The concept of metastability characterizes the coexistence of competing tendencies for functional integration and functional segregation in the brain and is therefore well suited for the study of schizophrenia. In this study we investigate metastability as a neuromechanistic biomarker of schizophrenia pathology, including a demonstration of reliability and face validity. Group-level discrimination, individual-level classification, and pathophysiological relevance were assessed using two independent case-control studies of schizophrenia, the Human Connectome Project Early Psychosis (HCPEP) study (controls n=82, non-affective psychosis n=53) and the Cobre study (controls n=71, cases n=59). In this work we introduce a new framework that uses Leading Eigenvector Dynamic Analysis (LEiDA) to capture specific features of dynamic functional connectivity and then implements a novel approach to estimate metastability. We used non-parametric testing to evaluate group-level differences and a naive Bayes classifier to discriminate cases from controls. Our results show that our new approach is capable of discriminating cases from controls with elevated effect sizes relative to published literature, reflected in an up to 76% area under the curve (AUC) in out-of-sample classification analyses. Furthermore, our analyses demonstrated that patients with early psychosis exhibit intermittent disconnectivity of subcortical regions with frontal cortex and cerebellar regions, introducing new insights about the mechanistic bases of these conditions. Overall, these findings demonstrate reliability and face validity of metastability as a neuromechanistic biomarker of schizophrenia pathology.
Dynamical phases and intermittency of the dissipative quantum Ising model

We employ the concept of a dynamical, activity order parameter to study the Ising model in a transverse magnetic field coupled to a Markovian bath. For a certain range of values of the spin-spin coupling, magnetic field and dissipation rate, we identify a first order dynamical phase transition between active and inactive {\em dynamical phases}. We demonstrate that dynamical phase-coexistence becomes manifest in an intermittent behavior of the bath quanta emission. Moreover, we establish the connection between the dynamical order parameter that quantifies the activity, and the longitudinal magnetization that serves as static order parameter. The system we consider can be implemented in current experiments with Rydberg atoms and trapped ions.
Generation of Large‐Area Highly‐Nonequlibrium Plasma in Pure Hydrogen at Atmospheric Pressure

Diffuse Coplanar Surface Barrier Discharge (DCSBD) is a novel type of atmospheric‐pressure plasma source developed for high‐speed large‐area surface plasma treatments. Basic characteristics of DCSBD operated in pure atmospheric‐pressure hydrogen were measured using optical and emission spectroscopy methods, and its potential for the surface treatment application was demonstrated by hydrogen plasma reduction of Cu2O thin layers. The discharge generates a thin layer of diffuse non‐equilibrium plasma with a high power density of 70 Wcm–3. The mean electron density and electron temperature derived from spectroscopic data were 1.3 x 1016cm–3 and 19 x 103K, and the surface Cu2O layers forming a weak boundary were reduced to metallic copper within several seconds. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Introduction to Business Statistics

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Sexualization of Children or Human Rights? Attitudes Toward Addressing Sexual-Orientation Diversity in School

ABSTRACT Lesbian, gay, and bisexual (LGB) adolescents are more likely to experience mental health problems than their heterosexual peers because they are victimized more often or fear discrimination. Governmental plans to improve this situation by addressing sexual diversity in German schools have been accompanied by public resistance and misinformation, e.g., that they aim to sexualize children. The present study assessed how widespread negative attitudes toward such plans really are and how they can be explained. A random sample of 2,013 German residents was surveyed by phone. Only 10% opposed promoting acceptance of LGB in school. Approval of such plans was predominantly predicted by respondents’ beliefs about sexual orientation and the plans’ aim, and only marginally by societal values. Respondents who knew that the plans’ aim was to promote acceptance of LGB and not to sexualize children and that children with same-sex parents are just as well off as those with heterosexual parents showed higher approval, whereas respondents who believed that homosexuality is affected by socialization showed higher opposition.
Influence of magnetoelectric coupling on electric field induced magnetization reversal in a composite unstrained multiferroic chain

We study theoretically the multiferroic dynamics in a composite one-dimensional system consisting of BaTiO${}_{3}$ multiferroically coupled to an iron chain. The method treats magnetization and polarization as thermodynamic quantities describable via a combination of the Landau-Lifshits-Gilbert and the Ginzburg-Landau dynamics coupled via an additional term in the total free energy density. This term stems from the multiferroic interaction at the interface. For a wide range of strengths of this coupling, we predict the possibility of obtaining a well-developed hysteresis in the ferromagnetic part of the system induced by an external electric field. The dependence of the reversal modes on the electric field frequency is also investigated and we predict a considerable stability of the magnetization reversal for frequencies in the range of 0.5--12 GHz.