julilili42/papers huggingface dataset:
Pathway-specific effects of ADSL deficiency on neurodevelopment
2022-02-08

Adenylosuccinate lyase (ADSL) functions in de novo purine synthesis (DNPS) and the purine nucleotide cycle. ADSL deficiency (ADSLD) causes numerous neurodevelopmental pathologies, including microcephaly and autism spectrum disorder. ADSLD patients have normal serum purine nucleotide levels but exhibit accumulation of dephosphorylated ADSL substrates, S-Ado, and SAICAr, the latter being implicated in neurotoxic effects through unknown mechanisms. We examined the phenotypic effects of ADSL depletion in human cells and their relation to phenotypic outcomes. Using specific interventions to compensate for reduced purine levels or modulate SAICAr accumulation, we found that diminished AMP levels resulted in increased DNA damage signaling and cell cycle delays, while primary ciliogenesis was impaired specifically by loss of ADSL or administration of SAICAr. ADSL-deficient chicken and zebrafish embryos displayed impaired neurogenesis and microcephaly. Neuroprogenitor attrition in zebrafish embryos was rescued by pharmacological inhibition of DNPS, but not increased nucleotide concentration. Zebrafish also displayed phenotypes commonly linked to ciliopathies. Our results suggest that both reduced purine levels and impaired DNPS contribute to neurodevelopmental pathology in ADSLD and that defective ciliogenesis may influence the ADSLD phenotypic spectrum.
Equilibrium sampling of suspended particulate matter as a universal proxy for fish and mussel monitoring
2022-02-08

Bioaccumulation of persistent and hydrophobic organic compounds in the aquatic environment puts secondary consumers, such as fish, at risk. To assess their exposure, monitoring programs with high numbers of individuals have been conducted worldwide over decades that require major efforts and raise ethical issues. This study aimed at testing suspended particulate matter (SPM) as an alternative and accessible abiotic matrix to estimate the internal exposure concentrations of such chemicals in fish and mussels. Muscle tissues of bream (Abramis brama), tissues of zebra mussels (Dreissena polymorpha) and SPM were collected from four major German rivers, Elbe, Danube, Saar and Saale, in 2018 within the national monitoring program of the German Environmental Specimen Bank. We used (i) total solvent extraction for biota samples to quantify the lipid-normalized concentrations of polychlorinated biphenyls, polycyclic aromatic hydrocarbons and hexachlorobenzene and (ii) passive equilibrium sampling of SPM to derive equilibrium partitioning concentrations in lipids and (iii) set these independent data sets into context. Since the ratio of lipid-normalized concentration / equilibrium partitioning concentration in lipids was in most cases < 1.0, SPM may serve as a conservative proxy for the internal concentration of bream and mussels, although bream of high age (i.e., older than 10 years) showed a tendency for this ratio to exceed 1.0. This observation indicates that age-dependent biomagnification can exceed the predictions based on thermodynamic equilibrium relative to SPM.
On the system of conversational thinking: an overview
2022-02-08

As more researchers are either discussing the approach of Conversational Thinking or deploying it in their work, one question persists; what is the nature of Conversational Thinking? In investigating this question, I will trace the roots of Conversational Thinking as a theory of meaning-making rather than a theory of meaning. I conceptualise meaning-making as an attempt, through the process of creative struggle, to create ‘presence’ from the ‘metaphysics of absence’ and to demonstrate their complementarity as equal binaries. I will show its affinity and divergence from theories of meaning such as analytic philosophy, deconstruction and hermeneutics. I will argue that the preceding three systems over-estimate the role of language in the production of meaning and that this was due to the influence and limitations of two-valued logic. To overcome these limitations, I will provide a general overview of the system of Conversational Thinking that encapsulates its foundation, architecture and doctrine, and indicate the logical underpinnings of conversational method to signal [the] methodological shift it represents in philosophy, the humanities and interdisciplinary studies.
Initial involvement into birding: triggers, gender, and decade effects—a mixed-methods study
2022-02-08

Abstract Birdwatching is an increasing nature-related activity, with an important influence on data collection of citizen science programs. Initial involvement into a leisure activity is an important life event, but also of interest for nature conservation and citizen science projects. Here, we assessed the initiation into birding by an open-ended question. Based on an online survey, mainly in Austria, Germany and Switzerland we recruited 2668 participants, with 2464 people reporting a specific reason for their initial involvement. Data were analyzed by a combination of qualitative and quantitative methods. Initiation age was 22.90 years (±15.27). The reasons for initial involvement were in descending order: social influence, nature experience, bird-centered triggers, education (formal/informal), cognitive-emotional aspects (interest, curiosity), other emotions, involvement via other hobbies/jobs, life-course events, ecological aspects, bird clubs/groups and opportunity. Men were more influenced by males and women more by females. Men experienced birding initiation more by club/group and the venue of other activities (job/hobby). Women were more influenced by nature experience, bird experience, emotions, and life-course events. Social initiation became less important during decades, while ecological aspect, education, other activities, and life-course events became more important. The study has implications on program developers and nature conservation organizations.
Delayed prediction of idiom constituent meaning points to weak holistic multi-word representation in children
2022-02-08

While generative accounts of language processing assume that children break down language into smaller components on which they apply computational operations, usage-based accounts assume that children acquire frequently co-occurring words as large chunks, which they decompose only later in development. We investigated the evidence for the multi-word representation of idioms like <i>to let the cat out of the bag</i> in 9- to 10-year-olds using eye-tracking and Event-Related Potentials. Both measures indicated that children rapidly predict idiom-final words (<i>bag</i>). However, although they are generally capable of rapidly predicting semantic associates for highly predictive endings of novel sentences (as demonstrated in a control experiment), within idioms they activate semantic associates (<i>basket</i>) only in a late processing stage. We conclude that children rapidly activate multi-word units for idioms and decompose these units only after a short delay during online processing. This effect might relate to unitary acquisition of idioms as assumed by usage-based accounts.
Opening up new avenues for research on social power
2022-02-08

Abstract Power shapes relations within social contexts—often with relevant consequences for those lower and higher in power. To inspire novel ideas and dialogue on this topic, this special issue presents a collection of articles that illustrates important aspects of power research that have often received little attention to date. Specifically, we present four aspects that, from our perspective, for now as well as in the future can contribute to understanding the effects of power even better: (1) Going beyond main effects and considering contextual moderators; (2) Studying the mechanisms that bring the effects of social power about; (3) Examining the way those high in power behave towards each other; and (4) Taking into account that lay persons’ perception of power might affect how they deal with power. To conclude, while we already know many answers to how power shapes social interactions within hierarchies, there are also open questions that remain to be addressed in future research. This special issue gives four examples that may contribute towards targeting these future avenues — in the hope that many more research on aspects like this will follow.
Looking through the windows: a study about the dependency of phase-coupling estimates on the data length
2022-02-08

Abstract Objective. Being able to characterize functional connectivity (FC) state dynamics in a real-time setting, such as in brain–computer interface, neurofeedback or closed-loop neurostimulation frameworks, requires the rapid detection of the statistical dependencies that quantify FC in short windows of data. The aim of this study is to characterize, through extensive realistic simulations, the reliability of FC estimation as a function of the data length. In particular, we focused on FC as measured by phase-coupling (PC) of neuronal oscillations, one of the most functionally relevant neural coupling modes. Approach. We generated synthetic data corresponding to different scenarios by varying the data length, the signal-to-noise ratio, the phase difference value, the spectral analysis approach (Hilbert or Fourier) and the fractional bandwidth. We compared seven PC metrics, i.e. imaginary part of phase locking value (PLV), PLV of orthogonalized signals, phase lag index (PLI), debiased weighted PLI, imaginary part of coherency, coherence of orthogonalized signals and lagged coherence. Main results. Our findings show that, for a signal-to-noise-ratio of at least 10 dB, a data window that contains 5 to 8 cycles of the oscillation of interest (e.g. a 500-800ms window at 10Hz) is generally required to achieve reliable PC estimates. In general, Hilbert-based approaches were associated with higher performance than Fourier-based approaches. Furthermore, the results suggest that, when the analysis is performed in a narrow frequency range, a larger window is required. Significance. The achieved results pave the way to the introduction of best-practice guidelines to be followed when a real-time frequency-specific PC assessment is at target.
Integrin activation enables rapid detection of functional Vδ1+ and Vδ2+ γδ T cells
2022-02-08

Abstract Conformational change of the β2 integrin lymphocyte function‐associated antigen 1 (LFA‐1) is an early marker of T cell activation. A protocol using the mAb clone m24 recognizing the active, extended high‐affinity conformation has been previously described for the assessment of functional CD4 + and CD8 + T cells in response to MHC‐peptide stimulation. We investigated the applicability of the m24 mAb to detect the activation of γδ T cells in response to different soluble and immobilized stimuli. m24 mAb staining was associated with the expression of cytokines and was detectable as early as 10 min after stimulation, but with different kinetics depending on the nature of the stimulus. Hence, we conclude that this assay is suitable for the detection of functional γδ T cells and allows the assessment of activation more rapidly than alternative methods such as cytokine detection. Intracellular staining, protein trafficking inhibitors, or prior knowledge of the stimulating moiety recognized are no longer required for monitoring γδ T cell activation.
Short-range organization and photophysical properties of CdSe quantum dots coupled with aryleneethynylenes
2022-02-08

Abstract Hybrid organic–inorganic nanomaterials composed of organic semiconductors and inorganic quantum dots (QDs) are promising candidates for opto-electronic devices in a sustainable internet of things. Especially their ability to combine the advantages of both compounds in one material with new functionality, the energy-efficient production possibility and the applicability in thin films with little resource consumption are key benefits of these materials. However, a major challenge one is facing for these hybrid materials is the lack of a detailed understanding of the organic–inorganic interface which hampers the widespread application in devices. We advance the understanding of this interface by studying the short-range organization and binding motif of aryleneethynylenes coupled to CdSe QDs as an example system with various experimental methods. Clear evidence for an incorporation of the organic ligands in between the inorganic QDs is found, and polarization-modulation infrared reflection-absorption spectroscopy is shown to be a powerful technique to directly detect the binding in such hybrid thin-film systems. A monodentate binding and a connection of neighboring QDs by the aryleneethynylene molecules is identified. Using steady-state and time resolved spectroscopy, we further investigated the photophysics of these hybrid systems. Different passivation capabilities resulting in different decay dynamics of the QDs turned out to be the main influence of the ligands on the photophysics.
Physiological and Pathophysiological Roles of Metabolic Pathways for NET Formation and Other Neutrophil Functions
2022-02-09

Neutrophils are the most numerous cells in the leukocyte population and essential for innate immunity. To limit their effector functions, neutrophils are able to modulate glycolysis and other cellular metabolic pathways. These metabolic pathways are essential not only for energy usage, but also for specialized effector actions, such as the production of reactive oxygen species (ROS), chemotaxis, phagocytosis, degranulation, and the formation of neutrophil extracellular traps (NETs). It has been demonstrated that activated viable neutrophils can produce NETs, which consists of a DNA scaffold able to bind granule proteins and microorganisms. The formation of NETs requires the availability of increased amounts of adenosine triphosphate (ATP) as it is an active cellular and therefore energy-dependent process. In this article, we discuss the glycolytic and other metabolic routes in association with neutrophil functions focusing on their role for building up NETs in the extracellular space. A better understanding of the requirements of metabolic pathways for neutrophil functions may lead to the discovery of molecular targets suitable to develop novel anti-infectious and/or anti-inflammatory drugs.
Revealing vertical aquifer heterogeneity and hydraulic anisotropy by pumping partially penetrating wells
2022-02-09

Abstract The stratification of sedimentary aquifers introduces spatial variability in hydraulic conductivity, primarily between individual horizontal layers. On larger scales, the vertical heterogeneity enhances hydraulic anisotropy, with the horizontal conductivity typically exceeding the vertical one. In this study, the hydraulic anisotropy of a stratified aquifer is estimated from data of hydraulic tests in which water is sequentially extracted from well sections screened at different depths, and the hydraulic response is measured at various multilevel observation wells. The applicability of the method is demonstrated by field tests in a fluvial gravel aquifer in the Upper Rhine Valley, Germany. A homogeneous anisotropic model, and models with three and five anisotropic layers, are fitted to the measured drawdowns in the steady-shape regime, in which differences in hydraulic head between observation locations do not change over time even though the head values themselves change. The position of the five horizontal layers is based on the lithology of the drilling profile at the pumping-well location. The three-layer model is achieved by merging insensitive or similar layers with sensitive layers. The fits result in estimates of the radial and vertical hydraulic conductivities for all layers of the respective models, which are upscaled to effective parameters over the entire depth in the case of the multilayer models. The homogeneous model shows significantly higher errors than those of the heterogeneous models. The heterogeneous locally anisotropic models not only reveal vertical variability of hydraulic conductivity, but also lead to a three-times larger anisotropy ratio upon upscaling.
Plate corner subduction and rapid localized exhumation: Insights from3Dcoupled geodynamic and geomorphological modelling
2022-02-09

Abstract Rapid, localized exhumation has been reported at many plate corners between adjacent subduction/collision segments. Here we use a fully‐coupled geodynamic and geomorphological modelling approach to investigate overriding plate deformation and resulting rock uplift patterns in these narrow, cuspate regions. In this study, we focus on the effects of internal deformation within a subducting convex‐upward‐shaped indenter and the strength of the interface between the upper and downgoing plate. The strongest localization of high rock uplift rates in the region above the indenter apex is predicted in experiments with a deformable lower plate, a weak interface layer and lateral shortening accommodated only by subduction (i.e., without an upper plate advance component). Our results suggest that bull’s eye shaped structures characterized by young thermochronological ages can, in principle, be reproduced numerically when taking into account a non‐rigid subducting plate together with complex brittle‐ductile rheology and stratification of the overriding lithosphere and realistically implemented fluvial erosion at its surface.
E2 + norethisterone promotes the PI3K–AKT pathway via PGRMC1 to induce breast cancer cell proliferation
2022-02-09

CK2 is involved in phosphorylation of PGRMC1 at S181. The mechanism for the action of PGRMC1 for mediating proliferative progestogen effects obviously starts with promotion cell cycle regulation, and then activation of the PI3K-AKT pathway.
Visualizing the Unseen: Illustrating and Documenting Phantom Limb Sensations and Phantom Limb Pain With C.A.L.A.
2022-02-09

Currently, there is neither a standardized mode for the documentation of phantom sensations and phantom limb pain, nor for their visualization as perceived by patients. We have therefore created a tool that allows for both, as well as for the quantification of the patient's visible and invisible body image. A first version provides the principal functions: (1) Adapting a 3D avatar for self-identification of the patient; (2) modeling the shape of the phantom limb; (3) adjusting the position of the phantom limb; (4) drawing pain and cramps directly onto the avatar; and (5) quantifying their respective intensities. Our tool (C.A.L.A.) was evaluated with 33 occupational therapists, physiotherapists, and other medical staff. Participants were presented with two cases in which the appearance and the position of the phantom had to be modeled and pain and cramps had to be drawn. The usability of the software was evaluated using the System Usability Scale and its functional range was evaluated using a self-developed questionnaire and semi-structured interview. In addition, our tool was evaluated on 22 patients with limb amputations. For each patient, body image as well as phantom sensation and pain were modeled to evaluate the software's functional scope. The accuracy of the created body image was evaluated using a self-developed questionnaire and semi-structured interview. Additionally, pain sensation was assessed using the SF-McGill Pain Questionnaire. The System Usability Scale reached a level of 81%, indicating high usability. Observing the participants, though, identified several operational difficulties. While the provided functions were considered useful by most participants, the semi-structured interviews revealed the need for an improved pain documentation component. In conclusion, our tool allows for an accurate visualization of phantom limbs and phantom limb sensations. It can be used as both a descriptive and quantitative documentation tool for analyzing and monitoring phantom limbs. Thus, it can help to bridge the gap between the therapist's conception and the patient's perception. Based on the collected requirements, an improved version with extended functionality will be developed.
Leveraging Blood-Based Diagnostics to Predict Tumor Biology and Extend the Application and Personalization of Radiotherapy in Liver Cancers
2022-02-09

While the incidence of primary liver cancers has been increasing worldwide over the last few decades, the mortality has remained consistently high. Most patients present with underlying liver disease and have limited treatment options. In recent years, radiotherapy has emerged as a promising approach for some patients; however, the risk of radiation induced liver disease (RILD) remains a limiting factor for some patients. Thus, the discovery and validation of biomarkers to measure treatment response and toxicity is critical to make progress in personalizing radiotherapy for liver cancers. While tissue biomarkers are optimal, hepatocellular carcinoma (HCC) is typically diagnosed radiographically, making tumor tissue not readily available. Alternatively, blood-based diagnostics may be a more practical option as blood draws are minimally invasive, widely availability and may be performed serially during treatment. Possible blood-based diagnostics include indocyanine green test, plasma or serum levels of HGF or cytokines, circulating blood cells and genomic biomarkers. The albumin–bilirubin (ALBI) score incorporates albumin and bilirubin to subdivide patients with well-compensated underlying liver dysfunction (Child–Pugh score A) into two distinct groups. This review provides an overview of the current knowledge on circulating biomarkers and blood-based scores in patients with malignant liver disease undergoing radiotherapy and outlines potential future directions.
Eighteen trial-level parity judgment datasets (n = 1016) from five countries: benefits of sharing unified data of cognitive tasks
2022-02-09

Psychological science could greatly benefit from research synthesis, especially when it comes to overcoming limitations of too small samples tested in single studies. However, initiatives aimed at sharing large, curated trial-level data from cognitive tasks remain scarce. To address this problem, we initiated a collective effort allowing to assemble and report a collection of eighteen datasets of the speeded bimanual parity judgment of single-digit numbers with response-to-key assignment flipped mid-experiment (hereafter SNARC-B-PJ). SNARC-B-PJ is one of the most popular tasks in numerical cognition and is used to evaluate the Spatial-Numerical Association of Response Codes effect (SNARC), a hallmark effect for Spatial-Numerical Associations (SNAs) more generally. Datasets, related to both published and unpublished studies, were collected in eight labs across five countries, totaling 1016 healthy adult participants. We provide thorough documentation and a tentative outline of potential future analyses of these datasets. We also intend to expand this resource and encourage potentially interested colleagues to contribute to this database. At the same time, we generalize our approach by discussing potential benefits of building similar databases comprising data from other popular tasks used in cognitive psychology.