julilili42/papers huggingface dataset:
Polyamine and Ethanolamine Metabolism in Bacteria as an Important Component of Nitrogen Assimilation for Survival and Pathogenicity
2022-07-29

Nitrogen is an essential element required for bacterial growth. It serves as a building block for the biosynthesis of macromolecules and provides precursors for secondary metabolites. Bacteria have developed the ability to use various nitrogen sources and possess two enzyme systems for nitrogen assimilation involving glutamine synthetase/glutamate synthase and glutamate dehydrogenase. Microorganisms living in habitats with changeable availability of nutrients have developed strategies to survive under nitrogen limitation. One adaptation is the ability to acquire nitrogen from alternative sources including the polyamines putrescine, cadaverine, spermidine and spermine, as well as the monoamine ethanolamine. Bacterial polyamine and monoamine metabolism is not only important under low nitrogen availability, but it is also required to survive under high concentrations of these compounds. Such conditions can occur in diverse habitats such as soil, plant tissues and human cells. Strategies of pathogenic and non-pathogenic bacteria to survive in the presence of poly- and monoamines offer the possibility to combat pathogens by using their capability to metabolize polyamines as an antibiotic drug target. This work aims to summarize the knowledge on poly- and monoamine metabolism in bacteria and its role in nitrogen metabolism.
Neurofilament light levels predict clinical progression and death in multiple system atrophy
2022-07-29

Abstract Disease-modifying treatments are currently being trialled in multiple system atrophy. Approaches based solely on clinical measures are challenged by heterogeneity of phenotype and pathogenic complexity. Neurofilament light chain protein has been explored as a reliable biomarker in several neurodegenerative disorders but data on multiple system atrophy have been limited. Therefore, neurofilament light chain is not yet routinely used as an outcome measure in multiple system atrophy. We aimed to comprehensively investigate the role and dynamics of neurofilament light chain in multiple system atrophy combined with cross-sectional and longitudinal clinical and imaging scales and for subject trial selection. In this cohort study, we recruited cross-sectional and longitudinal cases in a multicentre European set-up. Plasma and CSF neurofilament light chain concentrations were measured at baseline from 212 multiple system atrophy cases, annually for a mean period of 2 years in 44 multiple system atrophy patients in conjunction with clinical, neuropsychological and MRI brain assessments. Baseline neurofilament light chain characteristics were compared between groups. Cox regression was used to assess survival; receiver operating characteristic analysis to assess the ability of neurofilament light chain to distinguish between multiple system atrophy patients and healthy controls. Multivariate linear mixed-effects models were used to analyse longitudinal neurofilament light chain changes and correlated with clinical and imaging parameters. Polynomial models were used to determine the differential trajectories of neurofilament light chain in multiple system atrophy. We estimated sample sizes for trials aiming to decrease neurofilament light chain levels. We show that in multiple system atrophy, baseline plasma neurofilament light chain levels were better predictors of clinical progression, survival and degree of brain atrophy than the neurofilament light chain rate of change. Comparative analysis of multiple system atrophy progression over the course of disease, using plasma neurofilament light chain and clinical rating scales, indicated that neurofilament light chain levels rise as the motor symptoms progress, followed by deceleration in advanced stages. Sample size prediction suggested that significantly lower trial participant numbers would be needed to demonstrate treatment effects when incorporating plasma neurofilament light chain values into multiple system atrophy clinical trials in comparison to clinical measures alone. In conclusion, neurofilament light chain correlates with clinical disease severity, progression and prognosis in multiple system atrophy. Combined with clinical and imaging analysis, neurofilament light chain can inform patient stratification and serve as a reliable biomarker of treatment response in future multiple system atrophy trials of putative disease-modifying agents.
Neuroscience from the comfort of your home: Repeated, self-administered wireless dry EEG measures brain function with high fidelity
2022-07-29

Recent advances have enabled the creation of wireless, “dry” electroencephalography (EEG) recording systems, and easy-to-use engaging tasks, that can be operated repeatedly by naïve users, unsupervised in the home. Here, we evaluated the validity of dry-EEG, cognitive task gamification, and unsupervised home-based recordings used in combination. Two separate cohorts of participants—older and younger adults—collected data at home over several weeks using a wireless dry EEG system interfaced with a tablet for task presentation. Older adults ( n = 50; 25 females; mean age = 67.8 years) collected data over a 6-week period. Younger male adults ( n = 30; mean age = 25.6 years) collected data over a 4-week period. All participants were asked to complete gamified versions of a visual Oddball task and Flanker task 5–7 days per week. Usability of the EEG system was evaluated via participant adherence, percentage of sessions successfully completed, and quantitative feedback using the System Usability Scale. In total, 1,449 EEG sessions from older adults (mean = 28.9; SD = 6.64) and 684 sessions from younger adults (mean = 22.87; SD = 1.92) were collected. Older adults successfully completed 93% of sessions requested and reported a mean usability score of 84.5. Younger adults successfully completed 96% of sessions and reported a mean usability score of 88.3. Characteristic event-related potential (ERP) components—the P300 and error-related negativity—were observed in the Oddball and Flanker tasks, respectively. Using a conservative threshold for inclusion of artifact-free data, 50% of trials were rejected per at-home session. Aggregation of ERPs across sessions (2–4, depending on task) resulted in grand average signal quality with similar Standard Measurement Error values to those of single-session wet EEG data collected by experts in a laboratory setting from a young adult sample. Our results indicate that easy-to-use task-driven EEG can enable large-scale investigations in cognitive neuroscience. In future, this approach may be useful in clinical applications such as screening and tracking of treatment response.
FLASHIda enables intelligent data acquisition for top–down proteomics to boost proteoform identification counts
2022-07-29

Abstract The detailed analysis and structural characterization of proteoforms by top-down proteomics (TDP) has gained a lot of interest in biomedical research. Data-dependent acquisition (DDA) of intact proteins is non-trivial due to the diversity and complexity of proteoforms. Dedicated acquisition methods thus have the potential to greatly improve TDP. Here, we present FLASHIda, an intelligent online data acquisition algorithm for TDP that ensures the real-time selection of high-quality precursors of diverse proteoforms. FLASHIda combines fast charge deconvolution algorithms and machine learning-based quality assessment for optimal precursor selection. In an analysis of E. coli lysate, FLASHIda increases the number of unique proteoform level identifications from 800 to 1500 or generates a near-identical number of identifications in one third of the instrument time when compared to standard DDA mode. Furthermore, FLASHIda enables sensitive mapping of post-translational modifications and detection of chemical adducts. As a software extension module to the instrument, FLASHIda can be readily adopted for TDP studies of complex samples to enhance proteoform identification rates.
Contrast Sensitivity and Night Driving in Older People: Quantifying the Relationship Between Visual Acuity, Contrast Sensitivity, and Hazard Detection Distance in a Night-Time Driving Simulator
2022-07-29

Purpose (i) To assess how well contrast sensitivity (CS) predicts night-time hazard detection distance (a key component of night driving ability), in normally sighted older drivers, relative to a conventional measure of high contrast visual acuity (VA); (ii) To evaluate whether CS can be accurately quantified within a night driving simulator. Materials and Methods Participants were 15 (five female) ophthalmologically healthy adults, aged 55–81 years. CS was measured in a driving simulator using Landolt Cs, presented under static or dynamic driving conditions, and with or without glare. In the dynamic driving conditions, the participant was asked to simultaneously maintain a (virtual) speed of 60 km/h on a country road. In the with glare conditions, two calibrated LED arrays, moved by cable robots, simulated the trajectories and luminance characteristics of the (low beam) headlights of an approaching car. For comparison, CS was also measured clinically (with and without glare) using a Optovist I instrument (Vistec Inc., Olching, Germany). Visual acuity (VA) thresholds were also assessed at high and low contrast using the Freiburg Visual Acuity Test (FrACT) under photopic conditions. As a measure of driving performance, median hazard detection distance (MHDD) was computed, in meters, across three kinds of simulated obstacles of varying contrast. Results Contrast sensitivity and low contrast VA were both significantly associated with driving performance (both P &amp;lt; 0.01), whereas conventional high contrast acuity was not ( P = 0.10). There was good correlation ( P &amp;lt; 0.01) between CS measured in the driving simulator and a conventional clinical instrument (Optovist I). As expected, CS was shown to decrease in the presence of glare, in dynamic driving conditions, and as a function of age (all P &amp;lt; 0.01). Conclusion Contrast sensitivity and low contrast VA predict night-time hazard detection ability in a manner that conventional high contrast VA does not. Either may therefore provide a useful metric for assessing fitness to drive at night, particularly in older individuals. CS measurements can be made within a driving simulator, and the data are in good agreement with conventional clinical methods (Optovist I).
Differentiation between Wild-Type Group A Rotaviruses and Vaccine Strains in Cases of Suspected Horizontal Transmission and Adverse Events Following Vaccination
2022-07-29

Human group A rotaviruses (RVA) are important enteric pathogens, as they are a leading cause of acute gastroenteritis (AGE) in children worldwide. Since 2013, the German Standing Committee on vaccination recommended the routine rotavirus vaccination for infants in Germany. While vaccination has significantly decreased RVA cases and worldwide mortality, in some cases, infants can develop acute gastroenteritis as an adverse reaction after immunization with an attenuated live vaccine. Pediatricians, as well as clinicians and diagnostic laboratories, contacted the Consultant Laboratory for Rotaviruses and inquired whether cases of RVA-positive AGE after vaccination were associated with vaccine or with wild-type RVA strains. A testing algorithm based on distinguishing PCRs and confirmative sequencing was designed, tested, and applied. Diagnostic samples from 68 vaccinated children and six cases where horizontal transmission was suspected were investigated in this study. Using a combination of real-time PCR, fragment-length analysis of amplicons from multiplex PCRs and confirmative sequencing, vaccine-like virus was detected in 46 samples and wild-type RVA was detected in 6 samples. Three mixed infections of vaccine and wild-type RVA were detectable, no RVA genome was found in 19 samples. High viral loads (&gt;1.0 × 107 copies/g stool) were measured in most RVA-positive samples. Furthermore, information on co-infections with other AGE pathogens in the vaccinated study population was of interest. A commercial multiplex PCR and in-house PCRs revealed three co-infections of vaccinated infants with bacteria (two samples with Clostridioides difficile and one sample with enteropathogenic E. coli) and six co-infections with norovirus in a subset of the samples. Human astrovirus was detected in one sample, with suspected horizontal transmission. The cases of suspected horizontal transmission of vaccine RVA strains could not be confirmed, as they either involved wild-type RVA or were RVA negative. This study shows that RVA-positive AGE after vaccination is not necessarily associated with the vaccine strain and provides a reliable workflow to distinguish RVA vaccine strains from wild-type strains.
Stress Affects Central Compensation of Neural Responses to Cochlear Synaptopathy in a cGMP-Dependent Way
2022-07-29

In light of the increasing evidence supporting a link between hearing loss and dementia, it is critical to gain a better understanding of the nature of this relationship. We have previously observed that following cochlear synaptopathy, the temporal auditory processing (e.g., auditory steady state responses, ASSRs), is sustained when reduced auditory input is centrally compensated. This central compensation process was linked to elevated hippocampal long-term potentiation (LTP). We further observed that, independently of age, central responsiveness to cochlear synaptopathy can differ, resulting in either a low or high capacity to compensate for the reduced auditory input. Lower central compensation resulted in poorer temporal auditory processing, reduced hippocampal LTP, and decreased recruitment of activity-dependent brain-derived neurotrophic factor (BDNF) expression in hippocampal regions ( low compensators ). Higher central compensation capacity resulted in better temporal auditory processing, higher LTP responses, and increased activity-dependent BDNF expression in hippocampal regions. Here, we aimed to identify modifying factors that are potentially responsible for these different central responses. Strikingly, a poorer central compensation capacity was linked to lower corticosterone levels in comparison to those of high compensators . High compensators responded to repeated placebo injections with elevated blood corticosterone levels, reduced auditory brainstem response (ABR) wave I amplitude, reduced inner hair cell (IHC) ribbon number, diminished temporal processing, reduced LTP responses, and decreased activity-dependent hippocampal BDNF expression. In contrast, the same stress exposure through injection did not elevate blood corticosterone levels in low compensators , nor did it reduce IHC ribbons, ABR wave I amplitude, ASSR, LTP, or BDNF expression as seen in high compensators . Interestingly, in high compensators , the stress-induced responses, such as a decline in ABR wave I amplitude, ASSR, LTP, and BDNF could be restored through the “memory-enhancing” drug phosphodiesterase 9A inhibitor (PDE9i). In contrast, the same treatment did not improve these aspects in low compensators . Thus, central compensation of age-dependent cochlear synaptopathy is a glucocorticoid and cyclic guanosine-monophosphate (cGMP)-dependent neuronal mechanism that fails upon a blunted stress response.
A gas-flow funnel system to quantify advective gas emission rates from the subsurface
2022-07-29

Abstract The estimation of greenhouse gas emission rates from the subsurface into the atmosphere is an important part of climate-related research activities and associated efforts concerning the global carbon cycle. For the direct quantification of gas emission rates from the subsurface to the atmosphere a large variety of gas detection and flux quantification techniques exists. With the goal of measuring advective CO 2 gas exhalations circumventing limitations of available systems such as e.g. accumulation-chamber systems or eddy-flux covariance methods, we developed a simple, robust, and low-cost gas-flow funnel system. The device allows for the continuous measurement of mass flow rates with a free, unrestricted gas flow from advectively dominated gas exhalation spots. For the design of the gas-flow funnel we used custom-made, though easy-to-produce components, and sensors that are typically already available when working at such sites. Our general design can easily be applied at sites with focused, advectively driven gas exhalation like volcanic areas, shale-gas seeps, landfills, and open boreholes. For the proof-of-concept we tested the system during three field campaigns at a site with natural CO 2 -bound emissions associated with a geologic fault in southwestern Germany. The measurements showed to be comparable and repeatable throughout the three campaigns, and are consistent with findings from other field sites with comparable CO 2 exhalations.
Voluntary e-learning exercises support students in mastering statistics
2022-07-29

University students often learn statistics in large classes, and in such learning environments, students face an exceptionally high risk of failure. One reason for this is students' frequent statistics anxiety. This study shows how students can be supported using e-learning exercises with automated knowledge of correct response feedback, supplementing a face-to-face lecture. To this end, we surveyed 67 undergraduate social science students at a German university and observed their weekly e-learning exercises. We aggregated students’ exercise behavior throughout the semester to explain their exam performance. To control for participation bias, we included essential predictors of educational success, such as prior achievement, motivation, personality traits, time preferences, and goals. We applied a double selection procedure based on the machine learning method Elastic Net to include an optimal but sparse set of control variables. The e-learning exercises indirectly promoted the self-regulated learning techniques of self- testing and spacing and provided corrective feedback. Working on the e-learning exercises increased students’ performance on the final exam, even after controlling for the rich set of control variables. Two-thirds of students used our designed e-learning exercises; however, only a fraction of students spaced out the exercises, although students who completed the exercises during the semester and were not cramming at the end benefited additionally. Finally, we discuss how the results of our study inform the literature on self-testing, spacing, feedback, and e-learning in higher education.
Nova Quantum Gravity (NQG): Theory of the initial generation of only one particle in the Big Bang with decoupling of the electrical charge and gravitational constant at the neutron and proton level in the young universe
2022-07-29

&lt;p&gt;In contrary to the Standard Model, we present a theory and modality by which in the Big Bang&lt;/p&gt; &lt;p&gt;not all elemental particles and antiparticles that exist today were produced in the same amount,&lt;/p&gt; &lt;p&gt;but very probably initially only one type of particle, the down-quarks, which were emitted by&lt;/p&gt; &lt;p&gt;an extreme thermal radiation during Big Bang. This is a much more realistic scenario compared&lt;/p&gt; &lt;p&gt;to the Standard Model. The theory can be proofed impressively by the anomalous magnetic&lt;/p&gt; &lt;p&gt;moment of the muon. In the further we describe the generation mode of all other common&lt;/p&gt; &lt;p&gt;particles starting from the down-quarks as well as the decoupling of the electrical&lt;/p&gt; &lt;p&gt;charge and gravitational constant at the neutron and proton level during the expansion phase of&lt;/p&gt; &lt;p&gt;the young universe.&lt;/p&gt;
Middle Miocene climate and stable oxygen isotopes in Europe
2022-07-29

v1. Three ECHAM5-wiso model experiments for European region. For the first experiment (Europe_PI.nc), boundary conditions are set as pre-industrial and are identical to those in Botsyun et al., 2020. We also conducted two experiments with Middle Miocene boundary conditions reflecting two <em>p</em>CO<sub>2 </sub>settings (278 ppm and 450 ppm; Europe_Mio_278.nc and Europe_Mio_450.nc experiments) within current estimates of the Middle Miocene <em>p</em>CO<sub>2.</sub> v2. Global ECHAM5-wiso model experiments. geosp_simulations.nc contains surface geopotential for PI and Miocene experiments with modified Alpine topography and paleogeography.<br>
The spatial distribution of rhizosphere microbial activities under drought: water availability is more important than root‐hair‐controlled exudation
2022-07-30

Summary Root hairs and soil water content are crucial in controlling the release and diffusion of root exudates and shaping profiles of biochemical properties in the rhizosphere. But whether root hairs can offset the negative impacts of drought on microbial activity remains unknown. Soil zymography, 14 C imaging and neutron radiography were combined to identify how root hairs and soil moisture affect rhizosphere biochemical properties. To achieve this, we cultivated two maize genotypes (wild‐type and root‐hair‐defective rth3 mutant) under ambient and drought conditions. Root hairs and optimal soil moisture increased hotspot area, rhizosphere extent and kinetic parameters ( V max and K m ) of β‐glucosidase activities. Drought enlarged the rhizosphere extent of root exudates and water content. Colocalization analysis showed that enzymatic hotspots were more colocalized with root exudate hotspots under optimal moisture, whereas they showed higher dependency on water hotspots when soil water and carbon were scarce. We conclude that root hairs are essential in adapting rhizosphere properties under drought to maintain plant nutrition when a continuous mass flow of water transporting nutrients to the root is interrupted. In the rhizosphere, soil water was more important than root exudates for hydrolytic enzyme activities under water and carbon colimitation.
Real world data on IO-based therapy for metastatic renal cell carcinoma
2022-07-30

Abstract Purpose Immune-based (IO)-combinations are the backbone in the systemic therapy of metastatic renal cell carcinoma (mRCC). Despite phase III clinical trial data, real world data are of special importance to reflect clinical practice. Methods This retrospective study included 201 mRCC patients receiving first-line systemic therapy from January 2006. Clinicopathological and treatment-related data were recorded. Progression-free (PFS) and overall survival (OS) were analyzed using descriptive statistics and Kaplan–Meier analysis. Results Over the years, IO-based therapies have increased significantly. The collective comprises 76 patients with first-line IO-based therapy (IO-IO:55, TKI-IO:21) and 125 patients with TKI-monotherapy. PFS was significantly improved with TKI-IO combinations if compared to both TKI-monotherapy (23.9 vs. 10.3 months, HR 0.48, p = 0.034) and IO-IO combination (23.9 vs. 6.1 months, HR 0.37, p = 0.012). OS for TKI-IO treated patients was longer compared to TKI-monotherapy (HR 0.37, p = 0.050) at median follow-up of 24.1 versus 29.9 months. In a subanalysis of nivolumab treated patients, starting from second-line ( n = 40), PFS was 5.5 months. The addition of nivolumab either in second-or later lines improved OS compared to repeated TKI- or mTOR-therapies alone (6.13 vs. 2.61 years, HR 0.46, p = 0.003). Conclusion Both first-line IO-based combinations and nivolumab after first-line TKI-monotherapy prolong OS in a real-world setting.
An MCTAG with Tuples for Coherent Constructions in German
2022-07-30

&lt;p&gt;This paper introduces the notion of tree tuples to MCTAG, an extension of Tree Adjoining Grammar (TAG). Using tuples and node sharing we can provide an empirically broad and linguistically sound analysis of coherent constructions and scrambling in German, without the compulsive use of traces or the additional descriptive means in former MCTAG approaches.&lt;/p&gt;