julilili42/papers huggingface dataset:
Addressing Covid-19 Vaccination Conspiracy Theories and Vaccination Intentions
2022-04-07

Conspiracy theories often involve topics of uncertainty and ambivalence. One of those topics during the Covid-19 pandemic was the vaccination based on the new method using messenger RNA. In a preregistered study with N = 382 participants, we tested an intervention addressing the uncertainty concerning this new vaccination at a time when conspiracy theories about the vaccination method were not yet widely spread. Participants either only read short facts about the new vaccination (no explanation condition), or read these facts in addition to an explanation about the function of messenger RNA vaccines (relevant explanation condition), or they read the facts after the explanation of an alternative issue (irrelevant explanation condition). Results showed that individuals reading the relevant explanations addressing uncertainties surrounding the new vaccination method were less likely to agree with a Covid-19 vaccination conspiracy theory and were more willing to get a Covid-19 vaccination compared to the other conditions. An exploratory analysis showed that agreement with the Covid-19 vaccination conspiracy theory mediated the effect of explanation type on vaccination intentions. Potential implications and limitations are discussed.
Binding Error-Induced Control States
2022-04-07

Binding and retrieval of stimulus features, response features, and their attentional weighting tune cognitive processing to situational demands. The two mechanisms promote successful actions, especially in situations in which such actions depend on controlled processing. Here we explored binding and retrieval of attentional control states that follow from erroneous actions. By definition, such errors are characterized by insufficient cognitive control but at the same time, error detection has been shown to trigger corresponding adjustments to prevent future failures. We reanalyzed existing datasets and conducted a novel experiment to investigate whether error-induced control states become bound to task-relevant stimuli. Results point towards a binding and retrieval of error-induced control states; however, the effect appears to be less reliable than for binding and retrieval of specific stimulus and response features. We discuss potential implications and alternative interpretations in terms of a mediating impact of error-induced control.
Development and Experimental Validation of Regularized Machine Learning Models Detecting New, Structurally Distinct Activators of PXR
2022-04-07

The pregnane X receptor (PXR) regulates the metabolism of many xenobiotic and endobiotic substances. In consequence, PXR decreases the efficacy of many small-molecule drugs and induces drug-drug interactions. The prediction of PXR activators with theoretical approaches such as machine learning (ML) proves challenging due to the ligand promiscuity of PXR, which is related to its large and flexible binding pocket. In this work we demonstrate, by the example of random forest models and support vector machines, that classifiers generated following classical training procedures often fail to predict PXR activity for compounds that are dissimilar from those in the training set. We present a novel regularization technique that penalizes the gap between a model’s training and validation performance. On a challenging test set, this technique led to improvements in Matthew correlation coefficients (MCCs) by up to 0.21. Using these regularized ML models, we selected 31 compounds that are structurally distinct from known PXR ligands for experimental validation. Twelve of them were confirmed as active in the cellular PXR ligand-binding domain assembly assay and more hits were identified during follow-up studies. Comprehensive analysis of key features of PXR biology conducted for three representative hits confirmed their ability to activate the PXR.
Anaphoric reference in descriptions of surprising events
2022-04-07

The choice of anaphoric reference is a complex process regulated by a combination of linguistic and cognitive constraints. This paper experimentally addresses the impact of world knowledge on the types of references speakers produce, focusing on the predictability of event progressions. In order to avoid confounding event predictability and the predictability of words in their descriptions, we created an artificial virtual world and trained participants to recognize typical event progressions within. Speakers then described novel scenes, which either conformed to their expectations or violated them, in a free production experiment. The data reveal that surprising event progressions lead to a more frequent production of definite noun phrases, in contrast to reduced linguistic expressions (pronouns and zero anaphors). We further introduce a Bayesian inference model, which offers an explanation of why a definite noun phrase and not a pronoun is used for the description of surprising events. We conclude that speakers choose more informative descriptions to talk about surprising events because this strategy allows them to avoids misunderstanding with higher likelihood.
A Conserved Cysteine Residue in Coxsackievirus B3 Protein 3A with Implication for Elevated Virulence
2022-04-07

Enteroviruses (EV) are implicated in an extensive range of clinical manifestations, such as pancreatic failure, cardiovascular disease, hepatitis, and meningoencephalitis. We recently reported on the biochemical properties of the highly conserved cysteine residue at position 38 (C38) of enteroviral protein 3A and demonstrated a C38-mediated homodimerization of the Coxsackievirus B3 protein 3A (CVB3-3A) that resulted in its profound stabilization. Here, we show that residue C38 of protein 3A supports the replication of CVB3, a clinically relevant member of the enterovirus genus. The infection of HeLa cells with protein 3A cysteine 38 to alanine mutants (C38A) attenuates virus replication, resulting in comparably lower virus particle formation. Consistently, in a mouse infection model, the enhanced virus propagation of CVB3-3A wt in comparison to the CVB3-3A[C38A] mutant was confirmed and found to promote severe liver tissue damage. In contrast, infection with the CVB3-3A[C38A] mutant mitigated hepatic tissue injury and ameliorated the signs of systemic inflammatory responses, such as hypoglycemia and hypothermia. Based on these data and our previous report on the C38-mediated stabilization of the CVB3-3A protein, we conclude that the highly conserved amino acid C38 in protein 3A enhances the virulence of CVB3.
What Makes Domain Knowledge Difficult? Word Usage Frequency From SUBTLEX and dlexDB Explains Knowledge Item Difficulty
2022-04-07

The quality of tests in psychological and assessment educational is of great scholarly and public interest. Item difficulty models are vital to generating test result interpretations based on evidence. A major determining factor of item difficulty in knowledge tests is the opportunity to learn about the facts and concepts in question. Knowledge is mainly conveyed through language. Exposure to language associated with facts and concepts might be an indicator of the opportunity to learn. Thus, we hypothesize that item difficulty in knowledge tests should be related to the probability of exposure to the item content in everyday life and/or academic settings and therefore also to word frequency. Results from a study with 99 political knowledge test items administrated to N = 250 German 7th (age: 11 – 14 years) and 10th (age: 15 – 18 years) graders showed that word frequencies in everyday settings (SUBTLEX-DE) explain variance in item difficulty, while word frequencies in academic settings (dlexDB) alone do not. However, both types of word frequency combined explain a considerable amount of the variance in item difficulty. Items with words that are relatively more frequent in everyday life compared to academic settings are easier, and items with words that are relatively more frequent in academic settings are more difficult. Difficult items have content that is rarely present in everyday settings and is instead more cultivated academically. Examining word frequency from different language settings can help researchers investigate test score interpretations and is a useful tool for predicting item difficulty and refining knowledge test items.
Synergetic Antimicrobial Activity and Mechanism of Clotrimazole-Linked CO-Releasing Molecules
2022-04-08

Several metal-based carbon monoxide-releasing molecules (CORMs) are active CO donors with established antibacterial activity. Among them, CORM conjugates with azole antibiotics of type [Mn(CO)<sub>3</sub>(2,2'-bipyridyl)(azole)]<sup>+</sup> display important synergies against several microbes. We carried out a structure-activity relationship study based upon the lead structure of [Mn(CO)<sub>3</sub>(Bpy)(Ctz)]<sup>+</sup> by producing clotrimazole (Ctz) conjugates with varying metal and ligands. We concluded that the nature of the bidentate ligand strongly influences the bactericidal activity, with the substitution of bipyridyl by small bicyclic ligands leading to highly active clotrimazole conjugates. On the contrary, the metal did not influence the activity. We found that conjugate [Re(CO)<sub>3</sub>(Bpy)(Ctz)]<sup>+</sup> is more than the sum of its parts: while precursor [Re(CO)<sub>3</sub>(Bpy)Br] has no antibacterial activity and clotrimazole shows only moderate minimal inhibitory concentrations, the potency of [Re(CO)<sub>3</sub>(Bpy)(Ctz)]<sup>+</sup> is one order of magnitude higher than that of clotrimazole, and the spectrum of bacterial target species includes Gram-positive and Gram-negative bacteria. The addition of [Re(CO)<sub>3</sub>(Bpy)(Ctz)]<sup>+</sup> to <i>Staphylococcus aureus</i> causes a general impact on the membrane topology, has inhibitory effects on peptidoglycan biosynthesis, and affects energy functions. The mechanism of action of this kind of CORM conjugates involves a sequence of events initiated by membrane insertion, followed by membrane disorganization, inhibition of peptidoglycan synthesis, CO release, and break down of the membrane potential. These results suggest that conjugation of CORMs to known antibiotics may produce useful structures with synergistic effects that increase the conjugate's activity relative to that of the antibiotic alone.
Are many too much? Examining the effects of multiple influencer endorsements from a persuasion knowledge model perspective
2022-04-08

Advertisers report avoiding collaborations with influencers who endorse a large number of brands because they fear the negative outcomes of such over-endorsements. Yet many popular influencers endorse far more than one brand. Earlier research on multiple endorsements by celebrity testimonials and their effects on both brand and endorser evaluations produced mixed results. This article investigates the consequences of multiple endorsements in an influencer context. We conducted a between-subjects online experiment in which we varied the number of brand endorsements (one, three, seven endorsements) presented by an influencer. Results show that multiple influencer endorsements affect the performance of evaluative persuasion knowledge and subsequent coping behaviors, which in turn negatively affect brand attitude and perceived influencer authenticity. Coping with influencer endorsements is generally moderated by participants' parasocial relationships with the influencer. However, parasocial relationships appear not to be relevant in specifically processing multiple endorsements. Based on these findings, we discuss theoretical implications for researching influencer marketing from a persuasion knowledge model (PKM) perspective.
Genetics and Justice, Non-Ideal Theory and the Role of Patents: The Case of CRISPR-Cas9
2022-04-08

Abstract There are ongoing concerns of social justice regarding inequalities in the distribution of access to potential genome editing technologies. Working within non-ideal theory, Colin Farrelly advances a justification for the use of patents to speed up the arrival of safe and effective interventions for all, including the socially disadvantaged. This paper argues that such success is less assured when one considers the actual functioning of patents and the practical implications of the patent system in the context of biotechnological innovations. I suggest that non-ideal theoretical approaches risk reverting back to a form of ideal theory if they simply refer to such real-world constraints — e.g. patents — but do not critically assess and fully examine how such constraints manifest themselves in practice. I highlight some considerations that would be important in order to develop and foster a more robust non-ideal approach to justice in biotechnological developments.
Development of Personalized Non-Invasive Ventilation Interfaces for Neonatal and Pediatric Application Using Additive Manufacturing
2022-04-08

The objective of this study was to present a methodology and manufacturing workflow for non-invasive ventilation interfaces (NIV) for neonates and small infants. It aimed to procure a fast and feasible solution for personalized NIV produced in-house with the aim of improving fit and comfort for the patient. Three-dimensional scans were obtained by means of an intraoral (Trios 3) and a facial scanner (3dMd Flex System). Fusion 360 3D-modelling software was employed to automatize the design of the masks and their respective casting molds. These molds were additively manufactured by stereolithography (SLA) and fused filament fabrication (FFF) technologies. Silicone was poured into the molds to produce the medical device. In this way, patient individualized oronasal and nasal masks were produced. An automated design workflow and use of additive manufacturing enabled a fast and feasible procedure. Despite the cost for individualization likely being higher than for standard masks, a user-friendly workflow for in-house manufacturing of these medical appliances proved to have potential for improving NIV in neonates and infants, as well as increasing comfort.
Endometrial organoids derived from Mayer–Rokitansky–Küster–Hauser syndrome patients provide insights into disease-causing pathways
2022-04-08

ABSTRACT The uterus is responsible for the nourishment and mechanical protection of the developing embryo and fetus and is an essential part in mammalian reproduction. Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. Although heavily studied, the cause of the disease is still enigmatic. Current research in the field of MRKH mainly focuses on DNA-sequencing efforts and, so far, has been unable to decipher the nature and heterogeneity of the disease, thereby holding back scientific and clinical progress. Here, we developed long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically, they share great similarity with healthy control organoids and are surprisingly fully hormone responsive. Transcriptome analyses, however, identified an array of dysregulated genes that point to potentially disease-causing pathways altered during the development of the female reproductive tract. We consider the endometrial organoid cultures to be a powerful research tool that promise to enable an array of studies into the pathogenic origins of MRKH syndrome and possible treatment opportunities to improve patient quality of life.
Density Functional Investigation on α-MoO3 (100): Amines Adsorption and Surface Chemistry
2022-04-08

The (100) surface of α-MoO<sub>3</sub> should possess overwhelmingly more exposed Mo atoms than the (010), and the exposed Mo has been extensively considered as an active site for amine adsorption. However, α-MoO<sub>3</sub> (100) has drawn little attention concerning the amine sensing mechanism. In this research, adsorption of ammonia (NH<sub>3</sub>), monomethylamine (MMA), dimethylamine (DMA), and trimethylamine (TMA) is systematically investigated by density functional theory (DFT). All four of these molecules have high affinity to α-MoO<sub>3</sub> (100) through interaction between the N and the exposed Mo, and the affinity is mainly influenced by both the characteristics of the molecules and the geometric environment of the surface active site. Adsorption and dissociation of water and oxygen molecule on stoichiometric and defective α-MoO<sub>3</sub> (100) surfaces are then simulated to fully understand the surface chemistry of α-MoO<sub>3</sub> (100) in practical conditions. At low temperature, α-MoO<sub>3</sub> (100) must be covered with a large number of water molecules; the water can desorb or dissociate into hydroxyl groups at high temperature. Oxygen vacancy (V<sub>O</sub>) can be generated through the annealing process during sensor device fabrication; V<sub>O</sub> must be filled with an O<sub>2</sub> molecule, which can further interact with adsorbed water nearby to form hydroxyl groups. According to this research, α-MoO<sub>3</sub> (100) must be the active surface for amine sensing and its surface chemistry is well understood. In the near future, further reaction and interaction will be simulated at α-MoO<sub>3</sub> (100), and much more attention should be paid to α-MoO<sub>3</sub> (100) not only theoretically but also experimentally.
High-Throughput Assessment of the Abiotic Stability of Test Chemicals in In Vitro Bioassays
2022-04-08

Abiotic stability of chemicals is not routinely tested prior to performing <i>in vitro</i> bioassays, although abiotic degradation can reduce the concentration of test chemicals leading to the formation of active or inactive transformation products, which may lead to misinterpretation of bioassay results. A high-throughput workflow was developed to measure the abiotic stability of 22 test chemicals in protein-rich aqueous media under typical bioassay conditions at 37 °C for 48 h. These test chemicals were degradable in the environment according to a literature review. The chemicals were extracted from the exposure media at different time points using a novel 96-pin solid-phase microextraction. The conditions were varied to differentiate between various reaction mechanisms. For most hydrolyzable chemicals, pH-dependent degradation in phosphate-buffered saline indicated that acid-catalyzed hydrolysis was less important than reactions with hydroxide ions. Reactions with proteins were mainly responsible for the depletion of the test chemicals in the media, which was simulated by bovine serum albumin (BSA) and glutathione (GSH). 1,2-Benzisothiazol-3(2<i>H</i>)-one, 2-methyl-4-isothiazolinone, and l-sulforaphane reacted almost instantaneously with GSH but not with BSA, indicating that GSH is a good proxy for reactivity with electrophilic amino acids but may overestimate the actual reaction with three-dimensional proteins. Chemicals such as hydroquinones or polyunsaturated chemicals are prone to autoxidation, but this reaction is difficult to differentiate from hydrolysis and could not be simulated by the oxidant <i>N</i>-bromosuccinimide. Photodegradation played a minor role because cells are exposed in incubators in the dark and simulations with high light intensities did not yield realistic degradation. Stability predictions from various <i>in silico</i> prediction models for environmental conditions can give initial indications of the stability but were not always consistent with the experimental stability in bioassays. As the presented workflow can be performed in high throughput under realistic bioassay conditions, it can be used to provide an experimental database for developing bioassay-specific stability prediction models.
Lepton phenomenology of Stueckelberg portal to dark sector
2022-04-08

We propose an extension of the Standard Model (SM) with a UA′(1) gauge-invariant dark sector connected to the SM via a new portal—the Stueckelberg portal, arising in the framework of dark photon A′ mass generation via the Stueckelberg mechanism. This portal opens through the effective dim=5 operators constructed from the covariant term of the auxiliary Stueckelberg scalar field σ providing flavor nondiagonal renormalizable couplings of both σ and A′ to the SM fermions ψ. The Stueckelberg scalar plays a role of Goldstone boson in the generation of mass of the dark photon. Contrary to the conventional kinetic mixing portal, in our scenario, flavor diagonal A′−ψ couplings are not proportional to the fermion charges and are, in general, flavor nondiagonal. These features drastically change the phenomenology of dark photon A′ relaxing or avoiding some previously established experimental constraints. We focus on the phenomenology of the described scenario of the Stueckelberg portal in the lepton sector and analyze the contribution of the dark sector fields A′ to the anomalous magnetic moment of muon (g−2)μ, lepton flavor–violating decays li→lkγ, and μ−e conversion in nuclei. We obtain limits on the model parameters from the existing data on the corresponding observables.
Distinguishing between Triplet-Pair State and Excimer Emission in Singlet Fission Chromophores Using Mixed Thin Films
2022-04-08

In the photoluminescence spectra of thin films made of singlet fission (SF) materials emission features that are red-shifted from the free exciton emission are of particular interest. They can be fingerprints of the correlated triplet-pair state and as such offer insights into the mechanisms of the multistep SF process. However, excimer formation or trap-state population can also cause such features and a clear disentanglement of the various contributions can be challenging. Here, we use blends of anthradithiophene (ADT) and weakly interacting organic semiconductors to control the polarizability of the molecular environment and, thus, to distinguish between excimer emission and emission from the correlated triplet-pair state. Using time-resolved photoluminescence spectroscopy measurements, we clarify the relation between excimer formation and SF in ADT and find that excimer formation constitutes a parallel relaxation channel for the exciton and neither mediates nor hinders SF.
Cerium Fluorenyl Complexes Including CC Coupling Reactions
2022-04-08

The first structurally characterized fluorenyl (Flu) complexes of cerium are reported, bearing one, two, and three fluorenyl ligands. The reaction of CeX3(THF)x (X = Cl and I) with KFlu led to the half-sandwich complexes FluCeX2(THF)3. The chloride derivative was utilized in salt metathesis reactions, affording complexes FluCeR2(THF)x with R = OtBu, OSiMe3, OC6H3iPr2-2,6, Me2Pz, and Cp (x = 1 or 2; Me2Pz = 3,5-dimethylpyrazolato, Cp = C5H5). The mono(fluorenyl) complexes FluCeR2(THF)x are prone to ligand redistribution at ambient temperature, leading to the respective sandwich complexes Flu2CeR(THF). Utilization of K(2,10-tBu2Flu) (KFlutBu) afforded tris(fluorenyl) complex FlutBu3Ce(THF) instead, showcasing two η5- and one η1-bound fluorenyl ligands. Treatment of FluCeCl2(THF)3 with halogenating oxidants such as C2Cl6, I2, or TeBr4 did not afford stable cerium(IV) species but mixtures of 9-halogenidofluorene and 1,1′-bifluorene. Selective fluorenyl coupling reactions could be achieved for C2Cl6. Respective investigations with lanthanum and neodymium complexes support σ-bond metathesis as the main reaction path for C–C-bond formation.