julilili42/papers huggingface dataset:
The IgG glycome of SARS-CoV-2 infected individuals reflects disease course and severity
2022-10-18

Immunoglobulin G (IgG) antibodies play an important role in the immune response against viruses such as SARS-CoV-2. As the effector functions of IgG are modulated by N -glycosylation of the Fc region, the structure and possible function of the IgG N -glycome has been under investigation in relation to divergent COVID-19 disease courses. Through LC-MS analysis we studied both total IgG1 and spike protein-specific IgG1 Fc glycosylation of 129 German and 163 Brazilian COVID-19 patients representing diverse patient populations. We found that hospitalized COVID-19 patients displayed decreased levels of total IgG1 bisection and galactosylation and lowered anti-S IgG1 fucosylation and bisection as compared to mild outpatients. Anti-S IgG1 glycosylation was dynamic over the disease course and both anti-S and total IgG1 glycosylation were correlated to inflammatory markers. Further research is needed to dissect the possible role of altered IgG glycosylation profiles in (dys)regulating the immune response in COVID-19.
Levels of soluble complement regulators predict severity of COVID-19 symptoms
2022-10-18

The SARS-CoV-2 virus continues to cause significant morbidity and mortality worldwide from COVID-19. One of the major challenges of patient management is the broad range of symptoms observed. While the majority of individuals experience relatively mild disease, a significant minority of patients require hospitalisation, with COVID-19 still proving fatal for some. As such, there remains a desperate need to better understand what drives this severe disease, both in terms of the underlying biology, but also to potentially predict at diagnosis which patients are likely to require further interventions, thus enabling better outcomes for both patients and healthcare systems. Several lines of evidence have pointed to dysregulation of the complement cascade as a major factor in severe COVID-19 outcomes. How this is underpinned mechanistically is not known. Here, we have focussed on the role of the soluble complement regulators Complement Factor H (FH), its splice variant Factor H-like 1 (FHL-1) and five Factor H-Related proteins (FHR1-5). Using a targeted mass spectrometry approach, we quantified these proteins in a cohort of 188 plasma samples from controls and SARS-CoV-2 patients taken at diagnosis. This analysis revealed significant elevations in all FHR proteins, but not FH, in patients with more severe disease, particularly FHR2 and FHR5 (FHR2: 1.97-fold, p&amp;lt;0.0001; FHR5: 2.4-fold, p&amp;lt;0.0001). Furthermore, for a subset of 77 SARS-CoV-2 +ve patients we also analysed time course samples taken approximately 28 days post-diagnosis. Here, we see complement regulator levels drop in all individuals with asymptomatic or mild disease, but regulators remain high in those with more severe outcomes, with elevations in FHR2 over baseline levels in this group. These data support the hypothesis that elevation of circulating levels of the FHR family of proteins could predict disease severity in COVID-19 patients, and that the duration of elevation (or lack of immune activation resolution) may be partly responsible for driving poor outcomes in COVID-19.
Tracking the behavioral and neural dynamics of semantic representations through negation
2022-10-18

Abstract Combinatoric linguistic operations underpin human language processes, but how meaning is composed and refined in the mind of the reader is not well understood. We address this puzzle by exploiting the ubiquitous function of negation. We track the online effects of negation (“not”) and intensifiers (“really”) on the representation of scalar adjectives (e.g., “good”) in parametrically designed behavioral and neurophysiological (MEG) experiments. The behavioral data show that participants first interpret negated adjectives as affirmative and later modify their interpretation towards, but never exactly as, the opposite meaning. Decoding analyses of neural activity further reveal significant above chance decoding accuracy for negated adjectives within 600 ms from adjective onset, suggesting that negation does not invert the representation of adjectives (i.e., “not bad” represented as “good”); furthermore, decoding accuracy for negated adjectives is found to be significantly lower than that for affirmative adjectives. Overall, these results suggest that negation mitigates rather than inverts the neural representations of adjectives. This putative suppression mechanism of negation is supported by increased synchronization of beta-band neural activity in sensorimotor areas. The analysis of negation provides a steppingstone to understand how the human brain represents changes of meaning over time.
Stratification effects without morphological strata, syllable counting effects without counts – modelling English stress assignment with Naive Discriminative Learning
2022-10-18

Abstract Stress position in English words is well-known to correlate with both their morphological properties and their phonological organisation in terms of non-segmental, prosodic categories like syllable structure. While two generalisations capturing this correlation, directionality and stratification, are well established, the exact nature of the interaction of phonological and morphological factors in English stress assignment is a much debated issue in the literature. The present study investigates if and how directionality and stratification effects in English can be learned by means of Naive Discriminative Learning, a computational model that is trained using error-driven learning and that does not make any a-priori assumptions about the higher-level phonological organisation and morphological structure of words. Based on a series of simulation studies we show that neither directionality nor stratification need to be stipulated as a-priori properties of words or constraints in the lexicon. Stress can be learned solely on the basis of very flat word representations. Morphological stratification emerges as an effect of the model learning that informativity with regard to stress position is unevenly distributed across all trigrams constituting a word. Morphological affix classes like stress-preserving and stress-shifting affixes are, hence, not predefined classes but sets of trigrams that have similar informativity values with regard to stress position. Directionality, by contrast, emerges as spurious in our simulations; no syllable counting or recourse to abstract prosodic representations seems to be necessary to learn stress position in English.
Computational Exploration of the Intersystem Crossing from the X3A2 to the a1A1 State in Boryl Nitrenes upon Photoexcitation
2022-10-18

The boryl nitrene CatBN (Cat = catecholato) turns highly reactive toward small inert molecules upon irradiation of its triplet ground state <i>X</i>̃<sup>3</sup>A<sub>2</sub> with light of wavelength λ > 550 nm. A computational study of a model boryl nitrene using complete active space self-consistent field (CASSCF) theory provides evidence for the population of the highly reactive electronic state <i>a</i>̃<sup>1</sup>A<sub>1</sub> upon irradiation. Potential energy scans connecting different critical points (minima, minimum energy crossing points, and conical intersections) reveal two possible pathways that could relax photoexcited boryl nitrene from the Franck-Condon region of <i>A</i>̃<sup>3</sup>B<sub>1</sub> to the <i>a</i>̃<sup>1</sup>A<sub>1</sub> state minimum. Considering the energy barriers to relaxation from one electronic state to another and the magnitude of spin-orbit couplings, the energetically most favorable pathway involves photoexcitation to <i>A</i>̃<sup>3</sup>B<sub>2</sub>, followed by intersystem crossing to the open-shell singlet state (<i>b</i>̃<sup>1</sup>A<sub>2</sub>) and internal conversion to <i>a</i>̃<sup>1</sup>A<sub>1</sub>. The relevant minimum energy crossing point is about 7-8 kcal mol<sup>-1</sup> higher in energy than the Franck-Condon region.
Temporal aspects of two types of backward crosstalk in dual-tasks: An analysis of continuous mouse-tracking data
2022-10-18

A common explanation for processing limitations in dual-tasking is the existence of a bottleneck during response selection, meaning that the selection of responses can only occur serially for different tasks. However, a large body of data shows that features of a (secondary) Task 2 can already influence the processing of a (primary) Task 1. Such effects are referred to as backward crosstalk effects (BCEs). In the present study, two types of such BCEs were investigated: the compatibility-based BCE, which depends on the dimensional (often spatial) overlap between task features, and a BCE based on a go/no-go task in Task 2 (no-go BCE). Joining a line of research that suggests different mechanisms for these two types of BCEs, we investigated them using a mouse-tracking setup. Time continuous analyses revealed that the compatibility-based BCE triggered a spatial activation of the Task 2 response early during Task 1 processing, whereas the no-go BCE triggered an inhibitory effect in the case of a no-go Task 2, which spills over to Task 1 execution. This occurred, however, earlier in the time course than expected. The results are discussed with regard to recent models of dual-task processing.
Comment on egusphere-2022-492
2022-10-18

<strong class="journal-contentHeaderColor">Abstract.</strong> Numerical models have become an indispensable tool for understanding and predicting the flow of ice sheets and glaciers. Here we present the full-Stokes software package Underworld to the glaciological community. The code is already well established in simulating complex geodynamic systems. Advantages for glaciology are that it provides a full-Stokes solution for elasto-visco-plastic materials and includes mechanical anisotropy. Underworld uses a material point method to track the full history information of Lagrangian material points, of stratigraphic layers and of free surfaces. We show that Underworld successfully reproduces the results of other full-Stokes models for the benchmark experiments of the ISMIP-HOM project. Furthermore, we test FE meshes with different geometries and highlight the need to be able to adapt the finite-element grid to discontinuous interfaces between materials with strongly different properties, such as the ice-bedrock boundary.
Questions to consider when caring for patients with ulcerative colitis
2022-10-18

Abstract Although the management of patients with ulcerative colitis (UC) is well defined by national and international guidelines, there are many debates and open questions related to daily care of UC patients. Here, we aimed to review topics with high clinical relevance including therapy algorithms, potential biomarkers for disease prognosis and response to therapy, the role of interventions targeting the gut microbiota, insights from head-to-head trials, novel UC medications, exit strategies, the impact of COVID19 on UC, care of patients with acute severe disease, cancer screening, and the role of surgery.
Multi-view confounder detection for biomedical studies
2022-10-18

ABSTRACT In many biomedical studies an important first step is checking for confounding factors. For association studies, confounding can for example be caused by ethnic differences in the case and control groups. In many other settings there might be confounding factors like batch effects or founder effects that also need to be detected and controlled for 1 . Detecting confounding for data from one data source is well established (e.g., genomics data). Since more and more studies are now based on data from multiple data modalities (e.g., multi-omics), we evaluated whether multi-view confounder detection can benefit from state-of-the-art methods for multi-view data integration. Especially for clustering of multi-omics data, it has been shown that these methods can perform better than methods that treat the data modalities separately 2 . Our results show that multi-view confounder analysis is possible and that building on multi-view data integration methods is better than treating the different data modalities separately.
Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial
2022-10-19

Background: This study was conducted to determine the effect of hypothermic temperature control after in-hospital cardiac arrest (IHCA) on mortality and functional outcome as compared with normothermia. Methods: An investigator initiated, open-label, blinded-outcome-assessor, multicenter, randomized controlled trial comparing hypothermic temperature control (32-34°C) for 24 h with normothermia after IHCA in 11 hospitals in Germany. The primary endpoint was all-cause mortality after 180 days. Secondary end points included in-hospital mortality and favorable functional outcome using the Cerebral Performance Category scale after 180 days. A Cerebral Performance Category score of 1 or 2 was defined as a favorable functional outcome. Results: A total of 1055 patients were screened for eligibility and 249 patients were randomized: 126 were assigned to hypothermic temperature control and 123 to normothermia. The mean age of the cohort was 72.6±10.4 years, 64% (152 of 236) were male, 73% (166 of 227) of cardiac arrests were witnessed, 25% (57 of 231) had an initial shockable rhythm, and time to return of spontaneous circulation was 16.4±10.5 minutes. Target temperature was reached within 4.2±2.8 hours after randomization in the hypothermic group and temperature was controlled for 48 hours at 37.0°±0.9°C in the normothermia group. Mortality by day 180 was 72.5% (87 of 120) in hypothermic temperature control arm, compared with 71.2% (84 of 118) in the normothermia group (relative risk, 1.03 [95% CI, 0.79–1.40]; P =0.822). In-hospital mortality was 62.5% (75 of 120) in the hypothermic temperature control as compared with 57.6% (68 of 118) in the normothermia group (relative risk, 1.11 [95% CI, 0.86–1.46, P =0.443). Favorable functional outcome (Cerebral Performance Category 1 or 2) by day 180 was 22.5% (27 of 120) in the hypothermic temperature control, compared with 23.7% (28 of 118) in the normothermia group (relative risk, 1.04 [95% CI, 0.78–1.44]; P =0.822). The study was prematurely terminated because of futility. Conclusions: Hypothermic temperature control as compared with normothermia did not improve survival nor functional outcome at day 180 in patients presenting with coma after IHCA. The HACA in-hospital trial (Hypothermia After Cardiac Arrest in-hospital) was underpowered and may have failed to detect clinically important differences between hypothermic temperature control and normothermia. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT00457431.
Detailed Structural and Electrochemical Comparison between High Potential Layered P2-NaMnNi and Doped P2-NaMnNiMg Oxides
2022-10-19

Rechargeable sodium-ion batteries are viable candidates as next-generation energy storage devices. Nonetheless, the development of high-potential and stable cathode materials is still one among the open tasks. Here, we propose a combined experimental/theoretical approach to shed light on the effect of magnesium doping on the layered P2-Na0.67Mn0.75Ni0.25O2 cathode material. The P2-Na0.67Mn0.75Ni0.25O2 baseline material and doped P2-Na0.67Mn0.75Ni0.20Mg0.05O2, synthesized via coprecipitation route followed by thermal treatment, have been physically and chemically characterized via X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), as well as electrochemically via galvanostatic cycling and galvanostatic intermittent titration technique (GITT). The Mg-doped material showed stabilization of the high potential plateau and improved cycle life. The analysis of the phase transition with synchrotron operando XRD (SXRD) shows multiple possible intermediate phases ("Z-phase") rather than a pure OP4-like structure. Based on our experimental data and periodic density functional theory (DFT) calculations, the stability of the O2, P2, and OP4 phases for the pristine and Mg-doped systems was investigated to elucidate the origin of the "Z"-phase formation in the Mg-doped material.
Calpain-mediated proteolysis as driver and modulator of polyglutamine toxicity
2022-10-19

Among posttranslational modifications, directed proteolytic processes have the strongest impact on protein integrity. They are executed by a variety of cellular machineries and lead to a wide range of molecular consequences. Compared to other forms of proteolytic enzymes, the class of calcium-activated calpains is considered as modulator proteases due to their limited proteolytic activity, which changes the structure and function of their target substrates. In the context of neurodegeneration and - in particular - polyglutamine disorders, proteolytic events have been linked to modulatory effects on the molecular pathogenesis by generating harmful breakdown products of disease proteins. These findings led to the formulation of the toxic fragment hypothesis , and calpains appeared to be one of the key players and auspicious therapeutic targets in Huntington disease and Machado Joseph disease. This review provides a current survey of the role of calpains in proteolytic processes found in polyglutamine disorders. Together with insights into general concepts behind toxic fragments and findings in polyglutamine disorders, this work aims to inspire researchers to broaden and deepen the knowledge in this field, which will help to evaluate calpain-mediated proteolysis as a unifying and therapeutically targetable posttranslational mechanism in neurodegeneration.
Dendritic Cells or Macrophages? The Microenvironment of Human Clear Cell Renal Cell Carcinoma Imprints a Mosaic Myeloid Subtype Associated with Patient Survival
2022-10-19

Since their initial description by Elie Metchnikoff, phagocytes have sparked interest in a variety of biologic disciplines. These important cells perform central functions in tissue repair and immune activation as well as tolerance. Myeloid cells can be immunoinhibitory, particularly in the tumor microenvironment, where their presence is generally associated with poor patient prognosis. These cells are highly adaptable and plastic, and can be modulated to perform desired functions such as antitumor activity, if key programming molecules can be identified. Human clear cell renal cell carcinoma (ccRCC) is considered immunogenic; yet checkpoint blockades that target T cell dysfunction have shown limited clinical efficacy, suggesting additional layers of immunoinhibition. We previously described “enriched-in-renal cell carcinoma” (erc) DCs that were often found in tight contact with dysfunctional T cells. Using transcriptional profiling and flow cytometry, we describe here that ercDCs represent a mosaic cell type within the macrophage continuum co-expressing M1 and M2 markers. The polarization state reflects tissue-specific signals that are characteristic of RCC and renal tissue homeostasis. ErcDCs are tissue-resident with increasing prevalence related to tumor grade. Accordingly, a high ercDC score predicted poor patient survival. Within the profile, therapeutic targets (VSIG4, NRP1, GPNMB) were identified with promise to improve immunotherapy.
Absorbing boundary condition as limiting case of imaginary potentials
2022-10-19

Abstract Imaginary potentials such as V ( x ) = −i σ 1 Ω ( x ) (with σ &gt; 0 a constant, Ω a subset of 3-space, and 1 Ω its characteristic function) have been used in quantum mechanics as models of a detector. They represent the effect of a ‘soft’ detector that takes a while to notice a particle in the detector volume Ω. In order to model a ‘hard’ detector (i.e. one that registers a particle as soon as it enters Ω), one may think of taking the limit σ → ∞ of increasing detector strength σ . However, as pointed out by Allcock, in this limit the particle never enters Ω; its wave function gets reflected at the boundary ∂Ω of Ω in the same way as by a Dirichlet boundary condition on ∂Ω. This phenomenon, a cousin of the ‘quantum Zeno effect,’ might suggest that a hard detector is mathematically impossible. Nevertheless, a mathematical description of a hard detector has recently been put forward in the form of the ‘absorbing boundary rule’ involving an absorbing boundary condition on the detecting surface ∂Ω. We show here that in a suitable (non-obvious) limit, the imaginary potential V yields a non-trivial distribution of detection time and place in agreement with the absorbing boundary rule. That is, a hard detector can be obtained as a limit, but it is a different limit than Allcock considered.
A GIS-based simulation and visualization tool for the assessment of gully erosion processes
2022-10-19

Formulae display:?Mathematical formulae have been encoded as MathML and are displayed in this HTML version using MathJax in order to improve their display. Uncheck the box to turn MathJax off. This feature requires Javascript. Click on a formula to zoom.
UmetaFlow: An untargeted metabolomics workflow for high-throughput data processing and analysis
2022-10-19

Metabolomics experiments generate highly complex datasets, which are time and work-intensive, sometimes even error-prone if inspected manually. Therefore, new methods for automated, fast, reproducible, and accurate data processing and dereplication are required. Here, we present UmetaFlow, a computational workflow for untargeted metabolomics that combines algorithms for data pre-processing, spectral matching, molecular formula and structural predictions, and an integration to the GNPS workflows Feature-Based Molecular Networking and Ion Identity Molecular Networking for downstream analysis. UmetaFlow is implemented as a Snakemake workflow, making it easy to use, scalable, and reproducible. For more interactive computing, visualization, as well as development, the workflow is also implemented in Jupyter notebooks using the Python programming language and a set of Python bindings to the OpenMS algorithms (pyOpenMS). UmetaFlow was validated with in-house LC-MS/MS datasets of actinomycetes producing known secondary metabolites, as well as commercial standards, and it detected all expected features and accurately annotated 76% of the molecular formulas and 65% of the structures. As a more generic validation, the publicly available MTBLS733 dataset was used for benchmarking, and UmetaFlow detected 797 out of the 836 (~95.3%) ground truth features and accurately quantified 94.9% of these. We anticipate that UmetaFlow will provide a universal platform for the interpretation of large metabolomics datasets.
First detection of the He i 10 830 Å emission in spectra of classical Cepheid X Cyg
2022-10-19

ABSTRACT For the first time, we describe a detection of the emission in the infrared (IR) He i triplet at 10 830 Å in the classical Cepheid X Cyg. Emissions are clearly seen at phases approximately from 0.25 to 0.85. The IR redshifted He i emission is excited by shock wave in the uppermost layers of the star’s envelope, in its falling layers. This is a first detection of the helium IR emission in the classical Cepheids.