julilili42/papers huggingface dataset:
Retigabine and gabapentin restore channel function and neuronal firing of an epilepsy-associated dominant-negativeKCNQ5variant
2023-03-25

Abstract Objective KCNQ5 encodes the voltage-gated potassium channel K V 7.5, a member of the K V 7 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 K V 7 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 K V 7.5-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 K V 7.5 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 K V 7.5-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 K V 7.5 leads to largely increased neuronal firing indicating a neuronal hyperexcitability. K V 7 channel openers, such as retigabine or gabapentin, could be treatment options for otherwise pharmacoresistant epilepsy patients carrying loss-of-function variants in KCNQ5 .
Chiral Stationary Phases Derived from Cinchona Alkaloids
2023-03-26

Cinchona alkaloids such as quinine, quinidine, cinchonidine, and cinchonine as well as their corresponding C 9 -epimers have shown great potential as chiral bases for fractionated crystallization, as building blocks for chiral catalysts, and, last but not least, as educts of chiral selectors for the synthesis of chiral stationary phases (CSPs). Their intrinsic ability for chiral recognition can be further enhanced by dedicated derivatizations. The introduction of a carbamate group turned out to be key for effective high-performance liquid chromatography (HPLC) enantiomer separation. Due to the basic quinuclidine group, which can be protonated under mobile phase conditions, such CSPs are also known as chiral anion-exchangers. This primary retention principle outlines the scope of application for enantiomer separation of chiral acids. The application range can be extended by the introduction of sulfonic acid residues which leads to zwitterionic CSPs with applicability to chiral acids, chiral bases, and zwitterionic analytes, such as underivatized amino acids and small peptides. In this chapter, the current knowledge and state of the art in selector chemistries, chiral recognition mechanisms, retention principles, and application ranges of cinchona alkaloid-based CSPs will be reviewed. The primary focus will be on liquid chromatography; however, few applications of supercritical fluid chromatography will be briefly mentioned as well. Recent trends in direction of ultra-high performance liquid chromatography (UHPLC) with use of small sub-2 μm particles and superficially porous particles will be covered also. The description of some selected applications will illustrate the potential and scope of these chiral separation materials.
Reframing dopamine: Controlling the controller at the limbic-motor interface
2023-03-26

Abstract Pavlovian influences notoriously interfere with operant behaviour; various such may be associated with the release of the neuromodulator dopamine in the nucleus accumbens. One role for cognitive control is suppressing these influences. Here, using the examples of active avoidance and omission behaviour, we examine the possibility that one instrument of control is direct manipulation of the dopamine signal itself.
Carbon–biodiversity relationships in a highly diverse subtropical forest
2023-03-27

Abstract Carbon‐focused climate mitigation strategies are becoming increasingly important in forests. However, with ongoing biodiversity declines we require better knowledge of how much such strategies account for biodiversity. We particularly lack information across multiple trophic levels and on established forests, where the interplay between carbon stocks, stand age, and tree diversity might influence carbon–biodiversity relationships. Using a large dataset (&gt;4600 heterotrophic species of 23 taxonomic groups) from secondary, subtropical forests, we tested how multitrophic diversity and diversity within trophic groups relate to aboveground, belowground, and total carbon stocks at different levels of tree species richness and stand age. Our study revealed that aboveground carbon, the key component of climate‐based management, was largely unrelated to multitrophic diversity. By contrast, total carbon stocks—that is, including belowground carbon—emerged as a significant predictor of multitrophic diversity. Relationships were nonlinear and strongest for lower trophic levels, but nonsignificant for higher trophic level diversity. Tree species richness and stand age moderated these relationships, suggesting long‐term regeneration of forests may be particularly effective in reconciling carbon and biodiversity targets. Our findings highlight that biodiversity benefits of climate‐oriented management need to be evaluated carefully, and only maximizing aboveground carbon may fail to account for biodiversity conservation requirements.
A systematic review of bilingual education teachers’ competences
2023-03-27

Ongoing globalisation processes call forth a need to foster students' intercultural competences and language skills. Simultaneously, teachers face an increasing diversity of students' first languages and cultures within classrooms, demanding responsive and integrative practices from them which address all students. Bilingual education is one possible format in which these challenges can be met; however, it requires a high level of teacher professionalism. This systematic literature review harvests international research on bilingual education teachers published between 1995 and 2020. It compares frameworks and research on bilingual education teachers' required competences for secondary education and generates a professional competence model for bilingual education teachers. This systematic review of 79 individual reports identifies a total of 16 converging competences, many focusing on language proficiency and pedagogical/psychological knowledge. Furthermore, it yields important implications for bilingual teacher training such as the fostering of (academic) language proficiency, cooperation skills and knowledge of bilingual education research.
Detection of circulating cell-free HPV DNA of 13 HPV types for patients with cervical cancer as potential biomarker to monitor therapy response and to detect relapse
2023-03-27

Abstract Background HPV-related cervical cancer (CC) is the fourth most frequent cancer in women worldwide. Cell-free tumour DNA is a potent biomarker to detect treatment response, residual disease, and relapse. We investigated the potential use of cell-free circulating HPV-DNA (cfHPV-DNA) in plasma of patients with CC. Methods cfHPV-DNA levels were measured using a highly sensitive next-generation sequencing-based approach targeting a panel of 13 high-risk HPV types. Results Sequencing was performed in 69 blood samples collected from 35 patients, of which 26 were treatment-naive when the first liquid biopsy sample was retrieved. cfHPV-DNA was successfully detected in 22/26 (85%) cases. A significant correlation between tumour burden and cfHPV-DNA levels was observed: cfHPV-DNA was detectable in all treatment-naive patients with advanced-stage disease (17/17, FIGO IB3–IVB) and in 5/9 patients with early-stage disease (FIGO IA–IB2). Sequential samples revealed a decrease of cfHPV-DNA levels in 7 patients corresponding treatment response and an increase in a patient with relapse. Conclusions In this proof-of-concept study we demonstrated the potential of cfHPV-DNA as a biomarker for therapy monitoring in patients with primary and recurrent CC. Our findings facilitate the development of a sensitive and precise, non-invasive, inexpensive, and easily accessible tool in CC diagnosis, therapy monitoring and follow-up.
Robust deep learning object recognition models rely on low frequency information in natural images
2023-03-27

Machine learning models have difficulty generalizing to data outside of the distribution they were trained on. In particular, vision models are usually vulnerable to adversarial attacks or common corruptions, to which the human visual system is robust. Recent studies have found that regularizing machine learning models to favor brain-like representations can improve model robustness, but it is unclear why. We hypothesize that the increased model robustness is partly due to the low spatial frequency preference inherited from the neural representation. We tested this simple hypothesis with several frequency-oriented analyses, including the design and use of hybrid images to probe model frequency sensitivity directly. We also examined many other publicly available robust models that were trained on adversarial images or with data augmentation, and found that all these robust models showed a greater preference to low spatial frequency information. We show that preprocessing by blurring can serve as a defense mechanism against both adversarial attacks and common corruptions, further confirming our hypothesis and demonstrating the utility of low spatial frequency information in robust object recognition.
A frontoparietal network for volitional control of gaze following
2023-03-27

Abstract Gaze following is a major element of non‐verbal communication and important for successful social interactions. Human gaze following is a fast and almost reflex‐like behaviour, yet it can be volitionally controlled and suppressed to some extent if inappropriate or unnecessary, given the social context. In order to identify the neural basis of the cognitive control of gaze following, we carried out an event‐related fMRI experiment, in which human subjects' eye movements were tracked while they were exposed to gaze cues in two distinct contexts: A baseline gaze following condition in which subjects were instructed to use gaze cues to shift their attention to a gazed‐at spatial target and a control condition in which the subjects were required to ignore the gaze cue and instead to shift their attention to a distinct spatial target to be selected based on a colour mapping rule, requiring the suppression of gaze following. We could identify a suppression‐related blood‐oxygen‐level‐dependent (BOLD) response in a frontoparietal network comprising dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC), the anterior insula, precuneus, and posterior parietal cortex (PPC). These findings suggest that overexcitation of frontoparietal circuits in turn suppressing the gaze following patch might be a potential cause of gaze following deficits in clinical populations.
Weakly interacting massive particle cross section limits from LOFAR observations of dwarf spheroidal galaxies
2023-03-27

Context. Weakly interacting massive particles (WIMPs) can self-annihilate, thus providing us with a way to indirectly detect dark matter (DM). Dwarf spheroidal (dSph) galaxies are excellent places to search for annihilation signals because they are rich in DM and background emission is low. If O(0.1–10 μG) magnetic fields in dSph galaxies exist, the particles produced in DM annihilation emit synchrotron radiation in the radio band. Aims. We used the non-detection of 150 MHz radio continuum emission from dSph galaxies with the LOw Frequency ARray (LOFAR) to derive constraints on the annihilation cross section of WIMPs in electron–positron pairs. Our main underlying assumption is that the transport of the cosmic rays can be described by the diffusion approximation, which necessitates the existence of magnetic fields. Methods. We used observations of six dSph galaxies in the LOFAR Two-metre Sky Survey (LoTSS). The data were reimaged, and a radial profile was generated for each galaxy. We also used stacking to increase the sensitivity. In order to derive upper limits on the WIMP cross section, we injected fake Gaussian sources into the data, which were then detected with 2 σ significance in the radial profile. These sources represent the lowest emission we would have been able to detect. Results. We present limits from the observations of individual galaxies as well as from stacking. We explored the uncertainty due to the choice of diffusion and magnetic field parameters by constructing three different model scenarios: optimistic (OPT), intermediate (INT), and pessimistic (PES). Assuming monochromatic annihilation into electron–positron pairs, the limits from the INT scenario exclude thermal WIMPs (⟨ σv ⟩≈2.2 × 10 −26 cm 3 s −1 ) below 20 GeV, and the limits from the OPT scenario even exclude thermal WIMPs below 70 GeV. The INT limits can compete with limits set by Fermi -LAT using γ -ray observations of multiple dwarf galaxies, and they are especially strong for low WIMP masses.
[(thf)5Ln(Ge9{Si(SiMe3)3}2)] (Ln = Eu, Sm, Yb): Capping Metalloid Germanium Cluster with Lanthanides
2023-03-27

We report the synthesis of three neutral complexes with different coordination modes of a di-silylated metalloid germanium cluster to divalent lanthanides [(thf)<sub>5</sub>Ln(η<sup><i>n</i></sup>-Ge<sub>9</sub>(Hyp)<sub>2</sub>)] (Ln = Yb (<b>1</b>, <i>n</i> = 1); Eu (<b>2</b>, <i>n</i> = 2, 3), Sm (<b>3</b>, <i>n</i> = 2, 3); Hyp = Si(SiMe<sub>3</sub>)<sub>3</sub>) by the salt metathesis of LnI<sub>2</sub> with K<sub>2</sub>[Ge<sub>9</sub>(Hyp)<sub>2</sub>] in THF. The complexes were characterized by elemental analysis, nuclear magnetic resonance and UV-vis-NIR spectroscopy, and single-crystal X-ray diffraction. In thf solution, the formation of contact or solvate-separated ion pairs depending on the concentration is assumed. Compound <b>2</b> exhibits a blue luminescence typical for Eu<sup>2+</sup>. The solid-state magnetic measurements of compounds <b>2</b> and <b>3</b> confirm the presence of divalent europium and samarium, respectively.
Discrimination of finger movements by magnetomyography with optically pumped magnetometers
2023-03-27

Abstract Optically pumped magnetometers (OPM) are quantum sensors that offer new possibilities to measure biomagnetic signals. In magnetomyography (MMG), compared to the current standard surface electromyography (EMG), OPM sensors offer the advantage of contactless measurements of muscle activity. However, little is known about the relative performance of OPM-MMG and EMG, e.g. in their ability to detect and classify finger movements. To address this, we recorded simultaneous OPM-MMG and EMG of finger flexor muscles for the discrimination of individual finger movements. Using a deep learning model for movement classification, we found that both sensor modalities were able to discriminate finger movements with above 89% accuracy. Furthermore, model predictions for the two sensor modalities showed high agreement in movement detection (85% agreement; Cohen’s kappa: 0.45). Our findings show that OPM sensors can be employed for reliable, contactless discrimination of finger movements and incentivize future applications of OPM in magnetomyography.
Trusting Traumatic Memory: Considerations from Memory Science
2023-03-27

Abstract Court cases involving sexual assault and police violence rely heavily on victim testimony. We consider what we call the Traumatic Untrustworthiness Argument (TUA) according to which we should be skeptical about victim testimony because people are particularly liable to misremember traumatic events. The TUA is not obviously based in mere distrust of women, people of color, disabled people, poor people, and so forth. Rather, it seeks to justify skepticism on epistemic and empirical grounds. We consider how the TUA might appeal to the psychology and neuroscience of memory for empirical support. However, we argue that neither support the TUA.
Angle-dependent Magnetoresistance of an Ordered Bose Glass of Vortices in YBa2Cu3O7-δ Thin Films with a Periodic Pinning Lattice
2023-03-27

The competition between intrinsic disorder in superconducting YBa2Cu3O7−δ (YBCO) thin films and an ultradense triangular lattice of cylindrical pinning centers spaced at 30 nm intervals results in an ordered Bose glass phase of vortices. The samples were created by scanning the focused beam of a helium-ion microscope over the surface of the YBCO thin film to form columns of point defects where superconductivity was locally suppressed. The voltage–current isotherms reveal critical behavior and scale in the vicinity of the second-order glass transition. The latter exhibits a distinct peak in melting temperature (Tg) vs. applied magnetic field (Ba) at the magnetic commensurability field, along with a sharp rise in the lifetimes of glassy fluctuations. Angle-dependent magnetoresistance measurements in constant-Lorentz-force geometry unveil a strong increase in anisotropy compared to a pristine reference film where the density of vortices matches that of the columnar defects. The pinning is therefore, dominated by the magnetic-field component parallel to the columnar defects, exposing its one-dimensional character. These results support the idea of an ordered Bose glass phase.
Muscle preflex response to perturbations in locomotion: In vitro experiments and simulations with realistic boundary conditions
2023-03-27

This study focuses on understanding the muscle's intrinsic zero-delay response to ground perturbations during locomotion. In our study, we worked on the phase where the reflex-mediated response is not activated yet during the stance. This phase is known as preflex phase and muscle force by the intrinsic properties and feed-forward muscle activation during the preflex phase. The shared repository includes the experimental and simulation data, and code used for data analysis. Corresponding author: Matthew Araz, matthew.araz@uni-tuebingen.de
Vector-Boson Scattering at the LHC -- Recent Theory Developments
2023-03-27

Vector-boson scattering processes are at the heart of the physics program of the CERN Large Hadron Collider. This short contribution aims at giving a review on recent precision calculations for this important class of reactions. After a survey of fixed-order perturbative calculations the status of their matching to parton-shower programs is summarized. A brief outlook on new avenues in the exploration of vector-boson scattering completes the contribution.
How do Students' Cognitive and Motivational Characteristics Relate to Experimentation Skills and Conceptual Understanding during Scientific Inquiry
2023-03-27

Inquiry learning relies on students’ engagement, which is driven by their cognitive and motivational characteristics. The role of student characteristics for inquiry learning has been sparingly investigated and only from a variable-oriented perspective. In contrast, this study employed a person-centered approach to investigate the combined influence of students’ cognitive and motivational characteristics in relation to experimentation skills and conceptual understanding during guided inquiry learning. All students (N = 110, Mage = 12.07) attended a lesson about photosynthesis and worked on a structured inquiry task individually. Experimentation skills were measured by the proportion of controlled experiments that students conducted. Conceptual understanding comprised students’ written argumentation and conceptual knowledge posttest scores. We identified three distinct clusters, based on students’ prior knowledge, self-concept, and interest – Underestimating, Struggling, and Strong. Although Struggling students conducted a significantly higher proportion of controlled experiments than Strong students, Underestimating and Strong students outperformed them in the conceptual knowledge posttest. We found no differences in argumentation quality. These findings suggest that highly guided tasks might not be equally suitable for students with different levels of interest, prior knowledge, and self-concept and attest to the benefits of using person-oriented methods. Therefore, students’ motivation needs to be considered in addition to their prior knowledge when designing guidance for inquiry learning.
Revisiting Effects of Cognitive and Non-cognitive Teacher Characteristics on Stress: A Virtual Reality Study
2023-03-27

Identifying personal characteristics associated with teachers’ stress is a longstanding research goal with important implications for practice. The present work revisits the effects of cognitive (intelligence) and non-cognitive (neuroticism, classroom management self -efficacy) teacher characteristics on stress using virtual reality (VR). Relying on a sample of 56 German pre-service teachers (Mage = 22.73, SDage = 4.93; 50.9% females), we capitalized on a VR classroom environment that allowed the integration of experimental control and authentic teaching situations, where pre-service teachers responded to the disruptive behaviors of the student avatars. We focused on stress responses in terms of psychological stress (self reported stress) assessed after the VR session, and physiological stress (heart rate) assessed during the VR. Results from linear mixed effects models revealed that neuroticism positively predicted psychological and physiological stress responses in pre-service teachers. Classroom management self-efficacy and intelligence were not significantly related to stress responses. This study underlines the value of VR as a tool for psychological research. Our findings contribute to existing knowledge on teacher characteristics and stress, and support the adoption of a personality psychology perspective to better understand teachers’ stress in challenging situations.