julilili42/papers huggingface dataset:
Empirical research: Challenges and impulses for Islamic religious education
2020-01-07

The following article describes how empirical research can give new impulses to Islamic religious education. These impulses could lead to a reconciliation of the Islamic religious heritage with the fast-changing reality of Muslims in non-Muslim countries and societies. Due to the presence of Muslim children in public schools and the urgent question of their religious education, as an academic discipline, Islamic religious pedagogy (Islamische Religionspädagogik) has acquired a pioneering role among the various Islamic theological disciplines. On a scientific level, it has already taken its first steps in the scientific landscape in Germany and Austria and has established diverse references to modern science. Islamic religious pedagogy, as a young scientific discipline, necessarily requires empirical research to provide sound foundations for the quality of Islamic religious education and for a better understanding of religious educational processes. This calls for a dialogue between empirical educational research and theology and cannot be achieved based on purely theoretical assumptions.
Blockage of NMDA- and GABA(A) Receptors Improves Working Memory Selectivity of Primate Prefrontal Neurons
2020-01-07

The ongoing activity of prefrontal neurons after a stimulus has disappeared is considered a neuronal correlate of working memory. It depends on the delicate but poorly understood interplay between excitatory glutamatergic and inhibitory GABAergic receptor effects. We administered the NMDA receptor antagonist MK-801 and the GABA(A) receptor antagonist bicuculline methiodide while recording cellular activity in PFC of male rhesus monkeys performing a delayed decision task requiring working memory. The blockade of GABA(A) receptors strongly improved the selectivity of the neurons' delay activity, causing an increase in signal-to-noise ratio during working memory periods as well as an enhancement of the neurons' coding selectivity. The blockade of NMDA receptors resulted in a slight enhancement of selectivity and encoding capacity of the neurons. Our findings emphasize the delicate and more complex than expected interplay of excitatory and inhibitory transmitter systems in modulating working memory coding in prefrontal circuits. SIGNIFICANCE STATEMENT Ongoing delay activity of prefrontal neurons constitutes a neuronal correlate of working memory. However, how this delay activity is generated by the delicate interplay of synaptic excitation and inhibition is unknown. We probed the effects of excitatory neurotransmitter glutamate and inhibitory neurotransmitter GABA in regulating delay activity in rhesus monkeys performing a delayed decision task requiring working memory. Surprisingly, the blockade of both glutamatergic NMDA and GABA(A) receptors improved neuronal selectivity of delay activity, causing an increase in neuronal signal-to-noise ratio. Moreover, individual neurons were similarly affected by blockade of both receptors. This emphasizes the delicate and more complex than expected interplay of excitatory and inhibitory transmitter systems in modulating working memory coding in prefrontal circuits.
Sildenafil triggers tumor lethality through altered expression of HSP90 and degradation of PKD2
2020-01-07

Abstract The repurposing of existing drugs has emerged as an attractive additional strategy to the development of novel compounds in the fight against cancerous diseases. Inhibition of phosphodiesterase 5 (PDE5) has been claimed as a potential approach to target various cancer subtypes in recent years. However, data on the treatment of tumors with PDE5 inhibitors as well as the underlying mechanisms are as yet very scarce. Here, we report that treatment of tumor cells with low concentrations of Sildenafil was associated with decreased cancer cell proliferation and augmented apoptosis in vitro and resulted in impaired tumor growth in vivo. Notably, incubation of cancer cells with Sildenafil was associated with altered expression of HSP90 chaperone followed by degradation of protein kinase D2, a client protein previously reported to be involved in tumor growth. Furthermore, the involvement of low doses of PU-H71, an HSP90 inhibitor currently under clinical evaluation, in combination with low concentrations of Sildenafil, synergistically and negatively impacted on the viability of cancer cells in vivo. Taken together, our study suggests that repurposing of already approved drugs, alone or in combination with oncology-dedicated compounds, may represent a novel cancer therapeutic strategy.
Formation of native arsenic in hydrothermal base metal deposits and related supergene U6+ enrichment: The Michael vein near Lahr, SW Germany
2020-01-07

Abstract Native arsenic is an occasional ore mineral in some hydrothermal base metal deposits. Its rarity (compared to pyrite, arsenopyrite, galena, sphalerite, or chalcopyrite, for example) is surprising, as arsenic is a common constituent of upper crustal fluids. Hence, the conditions of formation must be quite special to precipitate native arsenic. An ideal location to investigate the formation of native As and to explore the parameters constraining its crystallization is the Michael vein near Lahr, Schwarzwald, southwest (SW) Germany. Here, galena, sphalerite, and native arsenic are the most abundant ore minerals. The two important ore stages comprise (1) galena-barite and (2) sphalerite-native arsenic-quartz, the latter with a general mineral succession of pyrite → sphalerite ± jordanite-gratonite solid solution → galena → native As. The native arsenic-bearing mineralization formed by cooling of an at least 130 °C hot saline fluid accompanied by a reduction due to the admixing of a sulfide-bearing fluid. Thermodynamic calculations reveal that for the formation of native arsenic, reduced conditions in combination with very low concentrations of the transition metals Fe, Co, and Ni, as well as low sulfide concentrations, are essential. “Typical” hydrothermal fluids do not fulfill these criteria, as they typically can contain significant amounts of Fe and sulfide. This results in the formation of arsenides, sulfarsenides, or As-bearing sulfides instead of native arsenic. Very minor amounts of pyrite, sulfarsenides, and arsenides record the very low concentrations of Fe, Co, and Ni present in the ore-forming fluid. High concentrations of aqueous Zn and Pb lead to early saturation of sphalerite and galena that promoted native arsenic precipitation by decreasing the availability of sulfide and hence suppressing realgar formation. Interestingly, native arsenic in the Michael vein acted as a trap for uranium during supergene weathering processes. Infiltrating oxidizing, U+VI-bearing fluids from the host lithologies reacted under ambient conditions with galena and native arsenic, forming a variety of U+VI (±Pb)-bearing arsenates such as hügelite, hallimondite, zeunerite, heinrichite, or novacekite together with U-free minerals like mimetite or anglesite. Some parts of the vein were enriched to U concentrations of up to 1 wt% by this supergene process. Reduced (hypogene) uranium phases like uraninite were never observed.
Simulating phonological and semantic impairment of English tense inflection with linear discriminative learning
2020-01-07

This study applies the computational theory of the ‘discriminative lexicon’ (Baayen et al., 2019) to the modeling of the production of regular and irregular English verbs in aphasic speech. Under impairment, speakers with memory loss have been reported to have greater difficulties with irregular verbs, whereas speakers with phonological impairment are described as having greater problems with regulars. Joanisse and Seidenberg (1999) were able to model this dissociation, but only by selectively adding noise to the semantic units of their model. We report two simulation studies in which topographically coherent regions of phonological and semantic networks were selectively damaged. Our model replicated the main findings, including the high variability in the consequences of brain lesions for speech production. Importantly, our model generated these results without having to lesion the semantic system more than the phonological system. The model’s success turns out to hinge on the use of a corpus-based distributional vector space for representing verbs’ meanings. Joanisse and Seidenberg (1999) used one-hot encoding for their semantic representation, under the assumption that semantically regular and irregular verbs do not differ in ways relevant to impairment in aphasia. However, irregular verbs have denser semantic neighborhoods than do regular verbs (Baayen and Moscoso del Prado Martín, 2005), and we show that in our model this greater density renders irregular verbs more fragile under semantic impairment. These results provide further support for the central idea underlying the discriminative lexicon: that behavioral patterns can, to a considerable extent, be understood as emerging from the distributional properties of a language and basic principles of human learning.
Cover Feature: Design and Analysis of the 4‐Anilinoquin(az)oline Kinase Inhibition Profiles of GAK/SLK/STK10 Using Quantitative Structure‐Activity Relationships (ChemMedChem 1/2020)
2020-01-07

The cover feature shows the key 4-anilinoquinoline ligand (6,7-dimethoxy-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine) modelled in cyclin G associated kinase (GAK). The image shows a zoomed-in version of the 3D-QSAR model that Christopher R. M. Asquith et al. developed for GAK inhibition, as described in their Full Paper. In addition, they developed models for STE20-like serine/threonine protein kinase (SLK) and serine/threonine protein kinase 10 (STK10), all with the 4-anilinoquin(az)oline inhibitor scaffold. These models are a basis for further inhibitor development and understanding of wider kinase inhibitor design. More information can be found in the Full Paper by Asquith et al. on page 26 in Issue 1, 2020 (DOI: 10.1002/cmdc.201900521). Cover image by Tuomo Laitinen and Christopher Asquith.
Faculty Opinions recommendation of c-Jun overexpression in CAR T cells induces exhaustion resistance.
2020-01-07

CAR T cells mediate antitumor effects in a small subset of cancer patients 1-3 , but dysfunction due to T cell exhaustion is an important barrier to progress 4-6 .To investigate the biology of exhaustion in human T cells expressing CAR receptors, we used a model system employing a tonically signaling CAR, which induces hallmark features of exhaustion 6 .Exhaustion was associated with a profound defect in IL-2 production alongside increased chromatin accessibility of AP-1 Users may view, print, copy, and
Raw EEG-EOG data used in the publication "Auditory Electrooculogram-based Communication System for ALS Patients in Transition from Locked-in to Complete Locked-in State"
2020-01-07

The dataset includes raw EEG and EOG recordings during BCI experiments for three patients: p11, p13, p15, and p16. The structure of the dataset is the following: patient/visit/day. The experiment is described in detail in the publication "Auditory Electrooculogram-based Communication System for ALS Patients in Transition from Locked-in to Complete Locked-in State". The correspondence between raw file and BCI session is reported in the attached pdf file "Supplementary Table S5 Session to Raw File Recordings Correspondence". The datasets include EEG and EOG channels. The data are raw (i.e. non filtered and non processed). Data have been acquired with a sampling rate of 500Hz using active electrodes and the amplifier V-Amp DC (Brain Products, Germany). EOG channels are labeled EOGU, EOGD, EOGR, EOGL namely for EOG up, down, right, left; the location in the 10-20 system are respectively SO1, IO1, LO1, LO2. The data are marked with triggers: for each session two markers indicate start and end of the session; for each trial markers indicate start of baseline, start of presentation of question, start of response time, start of feedback. Each trial was marked in a different way if it was a yes trial belonging to a training or feedback session, a no trial belonging to a training or feedback session, or a trial belonging to a speller session. The markers that have been used are the following:<br> <strong>start</strong> 9<br> <em> yes no speller</em><br> <strong>baseline</strong> 10 11 12<br> <strong>presentation</strong> 5 6 7<br> <strong>response</strong> 4 8 13<br> <strong>feedback</strong> 1 2 3 <strong>end</strong><strong> </strong> 15
Raw EEG-EOG data used in the publication "Auditory Electrooculogram-based Communication System for ALS Patients in Transition from Locked-in to Complete Locked-in State"
2020-01-07

&lt;p&gt;The dataset includes raw EEG and EOG recordings during BCI experiments for three patients: p11, p13, p15, and p16. The structure of the dataset is the following: patient/visit/day.&lt;/p&gt;\\n\\n&lt;p&gt;The experiment is described in detail in the publication "Auditory Electrooculogram-based Communication System for ALS Patients in Transition from Locked-in to Complete Locked-in State". The correspondence between raw file and BCI session is reported in the attached pdf file "Supplementary Table S5 Session to Raw File Recordings Correspondence".&lt;/p&gt;\\n\\n&lt;p&gt;The datasets include EEG and EOG channels. The data are raw (i.e. non filtered and non processed). Data have been acquired with a sampling rate of 500Hz using active electrodes and the amplifier V-Amp DC (Brain Products, Germany). EOG channels are labeled EOGU, EOGD, EOGR, EOGL namely for EOG up, down, right, left; the location in the 10-20 system are respectively SO1, IO1, LO1, LO2.&lt;/p&gt;\\n\\n&lt;p&gt;The data are marked with triggers: for each session two markers indicate start and end of the session; for each trial markers indicate start of baseline, start of presentation of question, start of response time, start of feedback. Each trial was marked in a different way if it was a yes trial belonging to a training or feedback session, a no trial belonging to a training or feedback session, or a trial belonging to a speller session. The markers that have been used are the following:&lt;br&gt;\\n&lt;strong&gt;start&lt;/strong&gt; 9&lt;br&gt;\\n&lt;em&gt; yes no speller&lt;/em&gt;&lt;br&gt;\\n&lt;strong&gt;baseline&lt;/strong&gt; 10 11 12&lt;br&gt;\\n&lt;strong&gt;presentation&lt;/strong&gt; 5 6 7&lt;br&gt;\\n&lt;strong&gt;response&lt;/strong&gt; 4 8 13&lt;br&gt;\\n&lt;strong&gt;feedback&lt;/strong&gt; 1 2 3&lt;/p&gt;\\n\\n&lt;p&gt;&lt;strong&gt;end&lt;/strong&gt;&lt;strong&gt; &lt;/strong&gt; 15&lt;/p&gt;
Loss of Complement Factor H impairs antioxidant capacity and energy metabolism of human RPE cells
2020-01-08

Abstract Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. About 50% of AMD patients present polymorphisms in the Complement Factor H ( CFH ) gene, coding for Factor H protein (FH). AMD-associated CFH risk variants, Y402H in particular, impair FH function leading to complement overactivation. In AMD, retinal homeostasis is compromised due to dysfunction of retinal pigment epithelium (RPE) cells. Whether FH contributes to AMD pathogenesis only via complement system dysregulation remains unclear. To investigate the potential role of FH on energy metabolism and oxidative stress in RPE cells, we silenced CFH in human hTERT-RPE1 cells. FH-deprived RPE cells exposed to oxidative insult, showed altered metabolic homeostasis, including reduction of glycolysis and mitochondrial respiration, paralleled by an increase in lipid peroxidation. Our data suggest that FH protects RPE cells from oxidative stress and metabolic reprogramming, highlighting a novel function for FH in AMD pathogenesis. Graphical abstract
Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients
2020-01-08

CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.
Reproducible Colonization of Germ-Free Mice With the Oligo-Mouse-Microbiota in Different Animal Facilities
2020-01-09

The Oligo-Mouse-Microbiota (OMM<sup>12</sup>) is a recently developed synthetic bacterial community for functional microbiome research in mouse models (Brugiroux et al., 2016). To date, the OMM<sup>12</sup> model has been established in several germ-free mouse facilities world-wide and is employed to address a growing variety of research questions related to infection biology, mucosal immunology, microbial ecology and host-microbiome metabolic cross-talk. The OMM<sup>12</sup> consists of 12 sequenced and publically available strains isolated from mice, representing five bacterial phyla that are naturally abundant in the murine gastrointestinal tract (Lagkouvardos et al., 2016). Under germ-free conditions, the OMM<sup>12</sup> colonizes mice stably over multiple generations. Here, we investigated whether stably colonized OMM<sup>12</sup> mouse lines could be reproducibly established in different animal facilities. Germ-free C57Bl/6J mice were inoculated with a frozen mixture of the OMM<sup>12</sup> strains. Within 2 weeks after application, the OMM<sup>12</sup> community reached the same stable composition in all facilities, as determined by fecal microbiome analysis. We show that a second application of the OMM<sup>12</sup> strains after 72 h leads to a more stable community composition than a single application. The availability of such protocols for reliable <i>de novo</i> generation of gnotobiotic rodents will certainly contribute to increasing experimental reproducibility in biomedical research.
LC-MS screening of poly- and perfluoroalkyl substances in contaminated soil by Kendrick mass analysis
2020-01-09

Abstract The application of contaminated paper sludge on arable land in southwest Germany caused the occurrence of a broad range of poly- and perfluoroalkyl substances (PFASs) on soil. Recently, the dead-end transformation products (TPs) perfluorooctanoic acid and perfluorooctanesulfonic acid were detected in groundwater and drinking water. The precursors and other transformation products mostly remained unknown. Therefore, HRMS screening by Kendrick mass analysis and assignment of homologous series in combination with suspect screening were applied to identify original PFASs and their TPs in four different soil samples from sites where contaminated paper sludge was applied. In total, twelve compound classes comprising more than 61 PFASs could be fully or tentatively identified. The data reveal that contamination mainly originates from polyfluorinated dialkylated phosphate esters (from 4:2/6:2 to 12:2/14:2), N -ethyl perfluorooctane sulfonamide ethanol–based phosphate diesters (only C 8 /C 8 ) and transformation products of these precursors. Contamination patterns can be attributed to PFASs used for paper impregnation and can vary slightly from site to site.
Effective and Reversible Carbon Dioxide Insertion into Cerium Pyrazolates
2020-01-09

Abstract The homoleptic pyrazolate complexes [Ce III 4 (Me 2 pz) 12 ] and [Ce IV (Me 2 pz) 4 ] 2 quantitatively insert CO 2 to give [Ce III 4 (Me 2 pz⋅CO 2 ) 12 ] and [Ce IV (Me 2 pz⋅CO 2 ) 4 ], respectively (Me 2 pz=3,5‐dimethylpyrazolato). This process is reversible for both complexes, as observed by in situ IR and NMR spectroscopy in solution and by TGA in the solid state. By adjusting the molar ratio, one molecule of CO 2 per [Ce IV (Me 2 pz) 4 ] complex could be inserted to give trimetallic [Ce 3 (Me 2 pz) 9 (Me 2 pz⋅CO 2 ) 3 (thf)]. Both the cerous and ceric insertion products catalyze the formation of cyclic carbonates from epoxides and CO 2 under mild conditions. In the absence of epoxide, the ceric catalyst is prone to reduction by the co‐catalyst tetra‐ n ‐butylammonium bromide (TBAB).
Bayesian inference for biophysical neuron models enables stimulus optimization for retinal neuroprosthetics
2020-01-09

ABSTRACT Multicompartment models have long been used to study the biophysical mechanisms underlying neural information processing. However, it has been challenging to infer the parameters of such models from data. Here, we build on recent advances in Bayesian simulation-based inference to estimate the parameters of detailed models of retinal neurons whose anatomical structure was based on electron microscopy data. We demonstrate how parameters of a cone, an OFF- and an ON-cone bipolar cell model can be inferred from standard two-photon glutamate imaging with simple light stimuli. The inference method starts with a prior distribution informed by literature knowledge and yields a posterior distribution over parameters highlighting parameters consistent with the data. This posterior allows determining how well parameters are constrained by the data and to what extent changes in one parameter can be compensated for by changes in another. To demonstrate the potential of such data-driven mechanistic neuron models, we created a simulation environment for external electrical stimulation of the retina as used in retinal neuroprosthetic devices. We used the framework to optimize the stimulus waveform to selectively target OFF- and ON-cone bipolar cells, a current major problem of retinal neuroprothetics. Taken together, this study demonstrates how a data-driven Bayesian simulation-based inference approach can be used to estimate parameters of complex mechanistic models with high-throughput imaging data.
An interaction network of RNA-binding proteins involved inDrosophilaoogenesis
2020-01-09

Abstract During Drosophila oogenesis, the localization and translational regulation of maternal transcripts relies on RNA-binding proteins (RBPs). Many of these RBPs localize several mRNAs and may have additional direct interaction partners to regulate their functions. Using immunoprecipitation from whole Drosophila ovaries coupled to mass spectrometry, we examined protein-protein associations of 6 GFP-tagged RBPs expressed at physiological levels. Analysis of the interaction network and further validation in human cells allowed us to identify 26 previously unknown associations, besides recovering several well characterized interactions. We identified interactions between RBPs and several splicing factors, providing links between nuclear and cytoplasmic events of mRNA regulation. Additionally, components of the translational and RNA decay machineries were selectively co-purified with some baits, suggesting a mechanism for how RBPs may regulate maternal transcripts. Given the evolutionary conservation of the studied RBPs, the interaction network presented here provides the foundation for future functional and structural studies of mRNA localization across metazoans.