julilili42/papers huggingface dataset:
EP4 agonist increases myeloid derived suppressor cells activity and reduces airway inflammatory events in a murine model of asthma
2020-09-07

<b>Background:</b> Previously, we showed that EP4 receptor agonist increases the number and suppressive activity of myeloid derived suppressor cells (MDSCs; both G-MDSCs and M-MDSCs) in the bone marrow culture <i>in vitro</i>. <b>Methods:</b> In the first part, mice were rendered asthmatic using HDM and then the role of intravenous adoptive transfer of MDSC<sub>EP4</sub> (MDSCs generated and activated using the EP4 agonist <i>in vitro</i>) was assessed. In the second part, the role of three different doses of intravenous EP4 receptor agonist L902,688 (0.1, 0.2 and 0.4 mg/kg) on <i>in vivo</i> generation of MDSCs and respectively their anti-inflammatory role in asthmatic mice was studied. <b>Results:</b> We found that adoptive transfer of MDSC<sub>EP4</sub> could ameliorate the immune response in a murine asthma model. Furthermore, EP4 agonist therapy increases the number of MDSCs in the spleen and lung of asthmatic mice, in a dose response manner, and reduces the inflammatory responses and histopathological changes. Furthermore, MDSCs isolated from EP4 agonist treated asthmatic mice could significantly reduce the proliferation of CD4<sup>+</sup> T cells mainly through arginase 1 and inducible nitric oxide synthase. <b>Conclusion:</b> Our results demonstrate that EP4 agonist generates and activates anti-inflammatory MDSCs to suppress the proliferation of T cells and airway inflammation, likely by upregulating arginase 1 and inducible nitric oxide synthase. EP4 agonist therapy seems to be a potential therapeutic target that would ultimately result in anti-inflammatory effects in asthmatic patients through generation and activation of MDSCs.
Exploring the Concepts of Concentration Addition and Independent Action Using a Linear Low-Effect Mixture Model
2020-09-08

Abstract Chemicals emitted into the environment are typically present at low concentrations but may act together in mixtures. Concentration–response curves of in vitro bioassays were often linear for effect levels &amp;lt;30%, and the predictions for concentration addition (CA) of similarly acting chemicals and for independent action (IA) of dissimilarly acting chemicals overlapped. We derived a joint CA/IA mixture model for the low-effect level portion of concentration–response curves. In a first case study, we evaluated the cytotoxicity of over 200 mixtures of up to 17 components that were mixed in concentration ratios as they occurred in river water. The predictions of the full IA model were indistinguishable from the predictions of the full CA model up to 10% effect, confirming the applicability of the joint CA/IA mixture model at low effect levels. In a second case study, we evaluated if environmental concentrations trigger effects at levels low enough for the joint CA/IA mixture model to apply. The detected concentrations were scaled by their toxic potencies to estimate the mixture effect of the detected chemicals in a complex mixture. In 86% of 156 samples the effects fell in the validity range of the joint CA/IA mixture model (&amp;lt;10% effect level), confirming the CA assumption for toxic unit summation. The joint CA/IA mixture model is not suitable for testing specific mixture hypotheses and interactions of chemicals in mixtures, where more refined models are required; but it is helpful for the interpretation of effects of complex (multicomponent) environmental mixtures, especially for water samples with relatively low effect level. Environ Toxicol Chem 2020;39:2552–2559. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Abstract Complex mixtures of organic chemicals that occur in water samples typically at low concentrations act together by a joint mixture model that integrates concentration addition and independent action.
Alpha Synuclein Connects the Gut-Brain Axis in Parkinson’s Disease Patients – A View on Clinical Aspects, Cellular Pathology and Analytical Methodology
2020-09-08

Parkinson's disease (PD) is marked by different kinds of pathological features, one hallmark is the aggregation of α-synuclein (aSyn). The development of aSyn pathology in the substantia nigra is associated to the manifestation of motor deficits at the time of diagnosis. However, most of the patients suffer additionally from non-motor symptoms, which may occur already in the prodromal phase of the disease years before PD is diagnosed. Many of these symptoms manifest in the gastrointestinal system (GIT) and some data suggest a potential link to the occurrence of pathological aSyn forms within the GIT. These clinical and pathological findings lead to the idea of a gut-brain route of aSyn pathology in PD. The identification of pathological aSyn in the intestinal system, e.g., by GIT biopsies, is therefore of highest interest for early diagnosis and early intervention in the phase of formation and propagation of aSyn. However, reliable methods to discriminate between physiological and pathological forms of enteral aSyn on the cellular and biochemical level are still missing. Moreover, a better understanding of the physiological function of aSyn within the GIT as well as its structure and pathological aggregation pathways are crucial to understand its role within the enteric nervous system and its spreading from the gut to the brain. In this review, we summarize clinical manifestations of PD in the GIT, and discuss biochemical findings from enteral biopsies. The relevance of pathological aSyn forms, their connection to the gut-brain axis and new developments to identify pathologic forms of aSyn by structural features are critically reviewed.
Quantitative functional renormalization group description of the two-dimensional Hubbard model
2020-09-08

Using a leading algorithmic implementation of the functional renormalization\\ngroup (fRG) for interacting fermions on two-dimensional lattices, we provide a\\ndetailed analysis of its quantitative reliability for the Hubbard model. In\\nparticular, we show that the recently introduced multiloop extension of the fRG\\nflow equations for the self-energy and two-particle vertex allows for a precise\\nmatch with the parquet approximation also for two-dimensional lattice problems.\\nThe refinement with respect to previous fRG-based computation schemes relies on\\nan accurate treatment of the frequency and momentum dependences of the\\ntwo-particle vertex, which combines a proper inclusion of the high-frequency\\nasymptotics with the so-called truncated unity fRG for the momentum dependence.\\nThe adoption of the latter scheme requires, as an essential step, a consistent\\nmodification of the flow equation of the self-energy. We quantitatively compare\\nour fRG results for the self-energy and momentum-dependent susceptibilities and\\nthe corresponding solution of the parquet approximation to determinant quantum\\nMonte Carlo data, demonstrating that the fRG is remarkably accurate up to\\nmoderate interaction strengths. The presented methodological improvements\\nillustrate how fRG flows can be brought to a quantitative level for\\ntwo-dimensional problems, providing a solid basis for the application to more\\ngeneral systems.\\n
Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice
2020-09-08

Significance Vascular dysfunction, as it develops either during normal aging or vascular disease, remains a major medical problem. The amyloid Medin, which is derived from its precursor protein MFG-E8 (through unknown mechanisms), forms insoluble aggregates in the vasculature of virtually anybody over 50 years of age, and it has been hypothesized that Medin aggregation could contribute to age-associated vascular decline; however, mechanistic analyses have so far been lacking. Our data now demonstrate that reminiscent of humans, mice also develop Medin deposits in an age-dependent manner. Importantly, mice that genetically lack Medin show reduced vascular dysfunction in the aged brain. Therefore, the prevention of Medin accumulation should be investigated as a novel therapeutic approach to preserve vascular health in the aging population.
Top–Down Attentional Modulation in Human Frontal Cortex: Differential Engagement during External and Internal Attention
2020-09-08

Abstract Decades of electrophysiological research on top–down control converge on the role of the lateral frontal cortex in facilitating attention to behaviorally relevant external inputs. However, the involvement of frontal cortex in the top–down control of attention directed to the external versus internal environment remains poorly understood. To address this, we recorded intracranial electrocorticography while subjects directed their attention externally to tones and responded to infrequent target tones, or internally to their own thoughts while ignoring the tones. Our analyses focused on frontal and temporal cortices. We first computed the target effect, as indexed by the difference in high frequency activity (70–150 Hz) between target and standard tones. Importantly, we then compared the target effect between external and internal attention, reflecting a top–down attentional effect elicited by task demands, in each region of interest. Both frontal and temporal cortices showed target effects during external and internal attention, suggesting this effect is present irrespective of attention states. However, only the frontal cortex showed an enhanced target effect during external relative to internal attention. These findings provide electrophysiological evidence for top–down attentional modulation in the lateral frontal cortex, revealing preferential engagement with external attention.
Anticoagulants for Treatment of Alzheimer’s Disease
2020-09-08

Alzheimer’s disease (AD) is a multifactorial syndrome with a plethora of progressive, degenerative changes in the brain parenchyma, but also in the cerebrovascular and hemostatic system. A therapeutic approach for AD is reviewed, which is focused on the role of amyloid–β protein (Aβ) and fibrin in triggering intra-brain vascular dysfunction and connected, cognitive decline. It is proposed that direct oral anticoagulants (DOACs) counteract Aβ-induced pathological alterations in cerebral blood vessels early in AD, a condition, known as cerebral amyloid angiopathy (CAA). By inhibiting thrombin for fibrin formation, anticoagulants can prevent accumulations of proinflammatory thrombin and fibrin, and deposition of degradation-resistant, Aβ-containing fibrin clots. These fibrin–Aβ clots are found in brain parenchyma between neuron cells, and in and around cerebral blood vessels in areas of CAA, leading to decreased cerebral blood flow. Consequently, anticoagulant treatment could reduce hypoperfusion and restricted supply of brain tissue with oxygen and nutrients. Concomitantly, hypoperfusion-enhanced neurodegenerative processes, such as progressive Aβ accumulation via synthesis and reduced perivascular clearance, neuroinflammation, and synapse and neuron cell loss, could be mitigated. Given full cerebral perfusion and reduced Aβ- and fibrin-accumulating and inflammatory milieu, anticoagulants could be able to decrease vascular-driven progression in neurodegenerative and cognitive changes, present in AD, when treated early, therapeutically, or prophylactically.
Should I stay or should I go? Predictors and effects of studying abroad during high school
2020-09-08

In an increasingly globalized and culturally diverse world, extended stays abroad during high school are considered important opportunities for acquiring and improving a variety of skills, most importantly, language achievement. This study examines both predictors and effects of studying abroad in an English-speaking country during high school, using population data from the second largest city in Germany (N = 5361; 13% went abroad). In order to determine the most central predictors of studying abroad, we employed logistic regression models in which students' socioeconomic background emerged as the strongest predictor of studying abroad. To test the effects of studying abroad, we applied propensity score matching. Studying abroad had positive effects on standardized achievement, grades, and course choice in English, whereas it had hardly any effects on outcomes in math. Implications for studying abroad during high school and future research directions are discussed.
Explicit knowledge of task structure is the primary determinant of human model-based action
2020-09-08

Abstract Explicit information obtained through instruction profoundly shapes human choice behaviour. However, this has been studied in computationally simple tasks, and it is unknown how model-based and model-free systems, respectively generating goal-directed and habitual actions, are affected by the absence or presence of instructions. We assessed behaviour in a novel variant of a computationally more complex decision-making task, before and after providing information about task structure, both in healthy volunteers and individuals suffering from obsessive-compulsive (OCD) or other disorders. Initial behaviour was model-free, with rewards directly reinforcing preceding actions. Model-based control, employing predictions of states resulting from each action, emerged with experience in a minority of subjects, and less in OCD. Providing task structure information strongly increased model-based control, similarly across all groups. Thus, explicit task structural knowledge determines human use of model-based reinforcement learning, and is most readily acquired from instruction rather than experience.
Impact of fluorination on interface energetics and growth of pentacene on Ag(111)
2020-09-08

We studied the structural and electronic properties of 2,3,9,10-tetrafluoropentacene (F4PEN) on Ag(111) via X-ray standing waves (XSW), low-energy electron diffraction (LEED) as well as ultraviolet and X-ray photoelectron spectroscopy (UPS and XPS). XSW revealed that the adsorption distances of F4PEN in (sub)monolayers on Ag(111) were 3.00 Å for carbon atoms and 3.05 Å for fluorine atoms. The F4PEN monolayer was essentially lying on Ag(111), and multilayers adopted π-stacking. Our study shed light not only on the F4PEN–Ag(111) interface but also on the fundamental adsorption behavior of fluorinated pentacene derivatives on metals in the context of interface energetics and growth mode.
Data for "Magnetoencephalographic Signatures of Hierarchical Rule Learning in Newborns"
2020-09-08

&amp;lt;p&amp;gt;Data uploaded here belongs to the manuscript "Magnetoencephalographic Signatures of Hierarchical Rule Learning in Newborns" (Moser, J., Schleger, F., Weiss, M., Sippel, K., Dehaene-Lambertz, G., &amp;amp; Preissl, H. (2020). Magnetoencephalographic signatures of hierarchical rule learning in newborns.&amp;nbsp;&amp;lt;em&amp;gt;Developmental cognitive neuroscience&amp;lt;/em&amp;gt;,&amp;nbsp;&amp;lt;em&amp;gt;46&amp;lt;/em&amp;gt;, 100871). It is processed MEG data and an R script, used for the analysis described in the manuscript. The content of the folder is further described in a README text file. For more information or additional data/code, please contact the authors. Additional code can be found on Github: https://github.com/moser297/fMEG_data_processing/tree/main/Code_DCN_2020_Neo.&amp;lt;/p&amp;gt;
Single and Multilayer Atomic Layer Deposition on and into Mesoporous Silicon Layers
2020-09-08

Electrochemically manufactured mesoporous silicon layers are widely used in the sensor or microfluidic technology especially for analysis of nano substances. Surface functionalization and pore filling of mesoporous layers are essential key aspects for successful application of complex porous matrices. Atomic layer deposition offers a possibility for the appropriate functionalization or pore filling with well-controlled process parameters at the nanoscale level. In these experiments mesoporous silicon layers with average pore size radius of 4.68 nm and porosity of 48% were fabricated and covered with different ALD single layers, such as thermal Al 2 O 3 , plasma TiO 2 , thermal ZnO, and layer combinations as multilayer ALD, such as plasma Al 2 O 3 /TiO 2 . This contribution gives an extensive investigation of single and multilayer depositions on and into mesoporous silicon layers and analyzes the material distribution and penetration profile of the corresponding atomic compositions.
Pyrrhonism and the Dialectical Methods
2020-09-08

Abstract The aim of this paper is to show how Outlines of Pyrrhonism II constitutes an original, ambitious, and unified skeptical inquiry into logic. My thesis is that Sextus’ argument in Book II is meant to accomplish both its stated goal (to investigate the topics typically grouped together by dogmatists under the heading of “logic”) and an unstated goal. The unstated goal is, in my view, interesting in itself and sheds new light on Sextus’ methodology. The goal is: to suspend judgement on the effectiveness of dogmatic methodologies.
Data for "Magnetoencephalographic Signatures of Hierarchical Rule Learning in Newborns"
2020-09-08

Data uploaded here belongs to the manuscript "Magnetoencephalographic Signatures of Hierarchical Rule Learning in Newborns" (Moser, J., Schleger, F., Weiss, M., Sippel, K., Dehaene-Lambertz, G., & Preissl, H. (2020). Magnetoencephalographic signatures of hierarchical rule learning in newborns. Developmental cognitive neuroscience, 46, 100871). It is processed MEG data and an R script, used for the analysis described in the manuscript. The content of the folder is further described in a README text file. For more information or additional data/code, please contact the authors. Additional code can be found on Github: https://github.com/moser297/fMEG_data_processing/tree/main/Code_DCN_2020_Neo.
Fast Rotating Relativistic Stars: Spectra and Stability without Approximation
2020-09-09

We study oscillations and instabilities of relativistic stars using perturbation theory in general relativity and take into account the contribution of a dynamic spacetime. We present the oscillation spectrum as well as the critical values for the onset of the secular CFS instability of neutron stars, and propose universal relations for gravitational wave asteroseismology, which may help constrain the neutron star radius and/or the nuclear equation of state. The results are relevant for all stages during a neutron star's life but especially to nascent or remnant objects following a binary merger.
Dynamics of fast rotating neutron stars: An approach in the Hilbert gauge
2020-09-09

We describe a set of time evolution equations and its numerical implementation for the investigation of non-axisymmetric oscillations of rapidly rotating compact objects in full General Relativity, taking into account the contribution of a dynamic spacetime. We derive the perturbation equations for the spacetime in the Hilbert gauge, while the hydrodynamical evolution is based on perturbations of the energy-momentum tensor. In our numerical implementation, we use Kreiss-Oliger dissipation in order to achieve a stable time evolution. Our code features high accuracy at comparably low computational expense and we are able to extract the frequencies of non-axisymmetric modes of compact objects with rotation rates up to the Kepler limit.
Validating CFD Predictions of Flow over an Escarpment Using Ground-Based and Airborne Measurement Devices
2020-09-09

Micrometeorological observations from a tower, an eddy-covariance (EC) station and an unmanned aircraft system (UAS) at the WINSENT test-site are used to validate a computational fluid dynamics (CFD) model, driven by a mesoscale model. The observation site is characterised by a forested escarpment in a complex terrain. A two-day measurement campaign with a flow almost perpendicular to the escarpment is analysed. The first day is dominated by high wind speeds, while, on the second one, calm wind conditions are present. Despite some minor differences, the flow structure, analysed in terms of horizontal wind speeds, wind direction and inclination angles shows similarities for both days. A real-time strategy is used for the CFD validation with the UAS measurement, where the model follows spatially and temporally the aircraft. This strategy has proved to be successful. Stability indices such as the potential temperature and the bulk Richardson number are calculated to diagnose atmospheric boundary layer (ABL) characteristics up to the highest flight level. The calculated bulk Richardson values indicate a dynamically unstable region behind the escarpment and near the ground for both days. At higher altitudes, the ABL is returning to a near neutral state. The same characteristics are found in the model but only for the first day. The second day, where shear instabilities are more dominant, is not well simulated. UAS proves its great value for sensing the flow over complex terrains at high altitudes and we demonstrate the usefulness of UAS for validating and improving models.
Unusual Nitrene Oxidation Product Formation by Metathesis Involving the Dioxygen O−O and Borylnitrene B−N Bonds
2020-09-09

Abstract The reaction of dioxygen with nitrenes can have significant energy barriers, although both reactants are triplet diradicals and the formation of nitroso‐ O ‐oxides is spin‐allowed. By means of matrix‐isolation infrared spectroscopy in solid argon, nitrogen, and neon, and through high‐level computational quantum chemistry, it is shown herein that a 3‐nitreno‐1,3,2‐benzodioxaborole CatBN (Cat=catecholato) reacts with dioxygen under cryogenic conditions thermally at temperatures as low as 7 K to produce two distinct products, an anti ‐nitroso‐ O ‐oxide and a nitritoborane CatBONO. The computed barriers for the formation of nitroso‐ O ‐oxide isomers are very low. Whereas anti ‐nitroso‐ O ‐oxide is kinetically trapped, its bisected isomer has a very low barrier for metathesis, yielding the CatBO+NO radicals in a strongly exothermic reaction; these radicals can combine under matrix‐isolation conditions to give nitritoborane CatBONO. The trapped isomer, anti ‐nitroso‐ O ‐oxide, can form the nitritoborane CatBONO only after photoexcitation, possibly involving isomerization to the bisected isomer of anti ‐nitroso‐ O ‐oxide.
Development of a Multiplex Bead Assay for the Detection of IgG Antibody Responses to Guinea Worm
2020-09-09

The success of the Guinea Worm (GW) Eradication Program over the past three decades has been tempered by the persistence of GW disease in a few African nations and the potential for a future resurgence in cases. Domestic dogs are now a major concern as a disease reservoir as large numbers of cases of canine GW disease are now reported each year, mainly along the Chari River in Chad. As a first step toward the development of a serologic assay for dogs, archived human plasma samples from dracunculiasis-positive donors from Togo were used to select adult female GW antigens for peptide sequencing and cloning. Eight protein sequences of interest were expressed as recombinant glutathione-<i>S</i>-transferase (GST) fusion proteins, and the most promising proteins were coupled to carboxylated microspheres for use in multiplex assays. A thioredoxin-like protein (TRXL1) and a domain of unknown function (DUF148) were assessed for total IgG and IgG<sub>4</sub> reactivities using a panel of specimens from GW cases, uninfected donors, and individuals infected with various nematode worms, including <i>Onchocerca volvulus</i>. Both the DUF148-GST and the TRXL1-GST assays cross-reacted with <i>O. volvulus</i> sera, but the latter assay was always the more specific. The IgG<sub>4</sub> and total IgG TRXL1-GST assays both had sensitivities > 87% and specificities > 90%. Maximum specificity (> 96%) was obtained with the total IgG assay when reactivity to both antigens was used to define a positive case. Given the good performance of the human assay, we are now working to modify the assay for dog assessments.