julilili42/papers huggingface dataset:
Plasma membrane association and resistosome formation of plant helper immune receptors
2023-01-24

Abstract Intracellular plant immune receptors, termed NLRs, respond to pathogen effectors delivered into plant cells. Activation of NLRs typically confers immunity. Sensor NLRs, involved in effector recognition, are either TIR-NLRs (TNLs) or CC-NLRs (CNLs). Helper NLRs, required for sensor NLR signaling, include CC R -NLRs (RNLs) and a special class of CNLs known as NRCs. Activated TNLs produce small molecules that induce an association between the EDS1/SAG101 heterodimer and the NRG1s helper RNLs. Auto active NRG1s oligomerize and form calcium signaling channels largely localized at the plasma membrane (PM). The molecular mechanisms of helper NLR PM association and effector induced NRG1 oligomerization are not well characterized. We find that both RNLs and NRCs require positively charged residues in the second and fourth helices of their CC R or CC domain for phospholipid binding and PM association before and after activation, despite conformational changes that accompany activation. We demonstrate that effector activation of TNLs induces NRG1 oligomerization at the PM and that the cytoplasmic pool of EDS1/SAG101 is critical for cell death function. EDS1/SAG101 cannot be detected in the oligomerized NRG1 resistosome, suggesting that additional unknown triggers might be required to induce the dissociation of EDS1/SAG101 from the previously described NRG1/EDS1/SAG101 heterotrimer before subsequent NRG1 oligomerization, or that the conformational changes resulting from NRG1 oligomerization abrogate the interface for EDS1/SAG101 association. Our data provide new observations regarding dynamic PM association during helper NLR activation and underpin an updated model for effector induced NRG1 resistosome formation.
Endovascular thrombectomy for basilar artery occlusion stroke: Analysis of the German Stroke Registry‐Endovascular Treatment
2023-01-24

Abstract Background and purpose Acute ischemic stroke due to basilar artery occlusion (BAO) causes the most severe strokes and has a poor prognosis. Data regarding efficacy of endovascular thrombectomy in BAO are sparse. Therefore, in this study, we performed an analysis of the therapy of patients with BAO in routine clinical practice. Methods Patients enrolled between June 2015 and December 2019 in the German Stroke Registry‐Endovascular Treatment (GSR‐ET) were analyzed. Primary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b‐3), substantial neurological improvement (≥8‐point National Institute of Health Stroke Scale [NIHSS] score reduction from admission to discharge or NIHSS score at discharge ≤1), and good functional outcome at 3 months (modified Rankin Scale [mRS] score of 0–2). Results Out of 6635 GSR‐ET patients, 640 (9.6%) patients (age 72.2 ± 13.3, 43.3% female) experienced BAO (median [interquartile range] NIHSS score 17 [8, 27]). Successful reperfusion was achieved in 88.4%. Substantial neurological improvement at discharge was reached by 45.5%. At 3‐month follow‐up, good clinical outcome was observed in 31.1% of patients and the mortality rate was 39.2%. Analysis of mTICI3 versus mTICI2b groups showed considerable better outcome in those with mTICI3 (38.9% vs. 24.4%; p = 0.005). The strongest predictors of good functional outcome were intravenous thrombolysis (IVT) treatment (odds ratio [OR] 3.04, 95% confidence interval [CI] 1.76–5.23) and successful reperfusion (OR 4.92, 95% CI 1.15–21.11), while the effect of time between symptom onset and reperfusion seemed to be small. Conclusions Acute reperfusion strategies in BAO are common in daily practice and can achieve good rates of successful reperfusion, neurological improvement and good functional outcome. Our data suggest that, in addition to IVT treatment, successful and, in particular, complete reperfusion (mTICI3) strongly predicts good outcome, while time from symptom onset seemed to have a lower impact.
Cassava - Recent Updates on Food, Feed, and Industry
2023-01-24

Cassava is a staple crop in many nations due to its adaptability to a wide range of climates. It has expanded across tropical Asia, sub-Saharan Africa, and Latin America. Cassava, noted for its high carbohydrate content, is third in carbohydrate content after rice and maize. <i>Cassava - Recent Updates on Food, Feed, and Industry</i> is the second edition of our previous book, <i>Cassava - Biology, Production</i>, and Use. This new edition has four sections. The first section discusses the perspectives of several countries on cassava, including food security and the circular economy. Due to the importance of cassava in many countries, the second section examines recent biotechnological advances as well as soil management and modifications in the improvement of cassava. The third section discusses disease management and control of cassava plants. Due to its widespread use and industrial importance, cassava has been subjected to biological and technological intervention for processing into food, feed, and other industrial matter, which is covered in the final section. We hope that this book will help readers gain advanced knowledge about cassava and learn from experts in the field with multiple perspectives.
Turbulence structures and entrainment length scales in large offshore wind farms
2023-01-24

Abstract. The flow inside and around large offshore wind farms can range from smaller structures associated with the mechanical turbulence generated by wind turbines to larger structures indicative of the mesoscale flow. In this study, we explore the variation in turbulence structures and dominant scales of vertical entrainment above large offshore wind farms located in the North Sea, using data obtained from a research aircraft. The aircraft was flown upstream, downstream, and above wind farm clusters. Under neutrally stratified conditions, there is high ambient turbulence in the atmosphere and an elevated energy dissipation rate compared to stable conditions. The intensity of small-scale turbulence structures is increased above and downstream of the wind farm, and it prevails over mesoscale fluctuations. But in stable stratification, mesoscale flow structures are not only dominant upstream of the wind farm but also downstream. We observed that the vertical flux of horizontal momentum is the main source of energy recovery in large offshore wind farms, and it strongly depends on the magnitude of the length scales of the vertical wind velocity component. The dominant length scales of entrainment range from 20 to ∼60 m above the wind farm in all stratification strengths, and in the wake flow these scales range from 10 to ∼100 m only under near-neutral stratification. For strongly stable conditions, negligible vertical entrainment of momentum was observed even just 2 km downstream of large wind farms. We also observed that there is a significant lateral momentum flux above the offshore wind farms, especially under strongly stable conditions, which suggests that these wind farms do not satisfy the conditions of an “infinite wind farm”.
Burial taphonomy and megalithic ritual practices in Iberia: the Panoría cemetery
2023-01-24

Abstract Our ability to build precise narratives regarding megalithic funerary rituals largely depends on an accurate understanding of bone assemblage formation. The cemetery of Panoría offers an excellent opportunity for exploring the ritual variability through the study of funerary taphonomy, as four of the nine recently excavated dolmens are remarkably well-preserved. Based on a multi-proxy approach that includes the contextual archaeological features, skeletal preservation and representation indexes, taphonomic processes, and radiocarbon chronology, three main ritual practices can be outlined: (i) primary sequential inhumations followed by the differential in situ decomposition of skeletal remains; (ii) the selective removal of crania and long bones; and (iii) the curation of subadult crania and probably long bones. The use-life of tombs, the intensity of mortuary depositions, and the intentional protection of specific bones appear as key aspects for understanding the variability in bone assemblage formation.
Cephalic anatomy highlights morphological adaptation to underground habitats in a minute lacewing larva of Dilar (Dilaridae) and conflicting phylogenetic signal in Neuroptera
2023-01-24

Abstract Dilaridae are a distinctive and phylogenetically ambiguous neuropteran family. So far, the anatomy of the immature stages remains largely unknown. We examined the 1st instar larvae of Dilar montanus in detail and present results of live observations for the first time. The minute, cryptic larvae display features correlated with their underground lifestyle: for instance, a strongly flattened head, stout antennae, eyelessness, and burrowing forelegs. In contrast to molecular data, several characters suggest a ‘dilarid clade’ combining Dilaridae with Mantispoidea, for instance a very thin and curved or reduced tentorial bridge, and an elongated postmentum. We found intrinsic antennal muscles and Johnston's organ, the first record of these structures in holometabolous larvae. This proves that the first 2 larval antennomeres are homologous with the scapus and pedicellus. The described characters are discussed and analyzed with an updated matrix of neuropteran larval characters. Alternative scenarios of character evolution are presented. Additionally, we show how the 1st‐instar larvae move and feed in the substrate, and also provide a high‐resolution video recording of the function of the elongate tubular ovipositor and the egg‐laying behavior in an adult female under natural conditions.
Stimulus-specific random effects inflate false-positive classification accuracy in multivariate-voxel-pattern-analysis: A solution with generalized mixed-effects modelling
2023-01-24

When conducting multivariate-voxel pattern analysis (MVPA), researchers typically compute the average accuracy for each subject and statistically test if the average accuracy is different from the chance level across subjects (by-subject analysis). We argue that this traditional by-subject analysis leads to inflated Type-1 error rates, regardless of the type of machine learning method used (e.g., support vector machine). This is because by-subject analysis does not consider the variance attributed to the idiosyncratic features of the stimuli that have a common influence on all subjects (i.e., the random stimulus effect). As a solution, we proposed the use of generalized linear mixed-effects modelling to evaluate average accuracy. This method only requires post-classification data (i.e., it does not consider the type of classification methods used) and is easily implemented in the analysis pipeline with common statistical software (SPSS, R, Python, etc.). Using both statistical simulation and real fMRI data analysis, we demonstrated that the traditional by-subject method indeed increases Type-1 error rates to a considerable degree, while generalized mixed-effects modelling that incorporates random stimulus effects can indeed maintain the nominal Type-1 error rates.
Falsifying the Insufficient Adjustment Model: No Evidence for Unidirectional Adjustment From Anchors
2023-01-24

After considering a more or less random number (i.e., an anchor), people’s subsequent estimates are biased toward that number. Such anchoring phenomena have been explained via an adjustment process that ends too early. We present a formalized version of the insufficient adjustment model, which captures the idea that decreasing the time that people have to adjust from anchors draws their estimates closer to the anchors. In four independent studies (N = 898), we could not confirm this effect of time on anchoring. Moreover, anchoring effects vanished in the two studies that deviated from classical paradigms by using a visual scale or a two-alternative forced-choice paradigm to allow faster responses. Although we propose that the current version of the insufficient adjustment model should be discarded, we believe that adjustment models hold the most potential for the future of anchoring research, and we make suggestions for what these might look like.
timsTOF mass spectrometry-based immunopeptidomics refines tumor antigen identification
2023-01-24

Abstract T cell recognition of human leukocyte antigen (HLA)-presented tumor-associated peptides is central for cancer immune surveillance. Mass spectrometry (MS)-based immunopeptidomics represents the only unbiased method for the direct identification and characterization of naturally presented tumor-associated peptides, a key prerequisite for the development of T cell-based immunotherapies. This study reports on the de novo implementation of ion mobility separation-based timsTOF MS for next-generation immunopeptidomics, enabling high-speed and sensitive detection of HLA-presented peptides. A direct comparison of timsTOF-based with state-of-the-art immunopeptidomics using orbitrap technology showed significantly increased HLA peptide identifications from benign and malignant primary samples of solid tissue and hematological origin. First application of timsTOF-based immunopeptidomics for tumor antigen discovery enabled (i) the expansion of benign reference immunopeptidome databases with &gt; 150,000 HLA-presented peptides from 94 primary benign tissue samples, (ii) the refinement of previously described tumor antigens, and (iii) the identification of a vast array of novel tumor antigens, comprising low abundant neoepitopes, that might serve as targets for future cancer immunotherapy development.
The evolution of African monsoons and its impacts on precipitation seasonality in the late Cenozoic and future climate change
2023-01-24

The West African Monsoon (WAM) strongly drives precipitation variability and seasonality across continental West Africa and the tropical Eastern Atlantic. However, the evolution of the WAM in the late Cenozoic, in response to changes in vegetation, atmospheric CO , orbital forcings, paleogeography, and orography as well as its teleconnections such as the mean location of the African Easterly Jet (AEJ), Tropical Easterly Jet (TEJ), SubTropical Jet (STJ), Inter-Tropical Discontinuity (ITD) and low-level westerly flow is not well constrained. We contribute to understanding past WAM dynamics by performing high-resolution, time-specific paleoclimate simulation using General Circulation Model ECHAM5. We focus our analysis on the migration and intensification of the WAM and its associated atmospheric thermodynamic structure which influence the rainfall seasonality and patterns across the Sahel, Guinea Coast, and Sahara regions.
Policy Experimentation under Pressure in Contemporary China
2023-01-25

Abstract Many studies put forward the argument that local policy experimentation, a key feature of China's policy process in the Hu Jintao era, has been paralysed by Xi Jinping's (re)centralization of political power – otherwise known as “top-level design.” This narrative suggests that local policymakers have become increasingly risk-averse owing to the anti-corruption campaign and are therefore unwilling to experiment. This article, however, argues that local governments are still expected to innovate with new policy solutions and now will be punished if they do not. By introducing the analytical framework of “experimentation under pressure” and drawing on an analysis of over 3,000 local government regulations and fieldwork data related to foreign investment attraction policies in two localities, Foshan and Ganzhou, the authors highlight new features developing within current experimental policy cycles. Local cadres now have no choice but to experiment as the political risk of shirking the direct command to experiment may be higher than the inherent risk of experimentation itself.
Real‐world data on cannabidiol treatment of various epilepsy subtypes: A retrospective, multicenter study
2023-01-25

Abstract Objective Cannabidiol (CBD) is approved for treatment of Dravet syndrome (DS), Lennox‐Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC). Several studies suggest antiseizure effects also beyond these three epilepsy syndromes. Methods In a retrospective multicenter study, we analyzed the efficacy and tolerability of CBD in patients with epilepsy at 16 epilepsy centers. Results The study cohort comprised 311 patients with epilepsy with a median age of 11.3 (0‐72) years (235 children and adolescents, 76 adults). Therapy with CBD was off‐label in 91.3% of cases due to age, epilepsy subtype, lack of adjunct therapy with clobazam, and/or higher dose applied. CBD titration regimens were slower than recommended, with good tolerability of higher doses particularly in children. Of all patients, 36.9% experienced a reduction in seizure frequency of &gt;50%, independent of their epilepsy subtype or clobazam co‐medication. The median observation period was 15.8 months. About one third of all patients discontinued therapy within the observation period due to adverse effects or lack of efficacy. Adverse effects were reported frequently (46.9%). Significance Our study highlights that CBD has an antiseizure effect comparable to other antiseizure medications with a positive safety profile independent of the epilepsy subtype. Comedication with clobazam was not associated with a better outcome. Higher doses to achieve seizure frequency reduction were safe, particularly in children. These findings call for further trials for an extended approval of CBD for other epilepsy subtypes and for children &lt;2 years of age.
Tobacco heating system has less impact on bone metabolism than cigarette smoke
2023-01-25

Cigarette smoking promotes osteoclast activity, thus increasing the risk of secondary osteoporosis, leading to osteoporosis-associated fracture and impaired fracture healing. Heated tobacco products (HTP) are considered potential reduced-risk alternatives to cigarettes. However, their impact on bone metabolism remains to be elucidated. We developed an in vitro model that mimics in vivo bone cell interactions to comparatively evaluate the effects of HTPs and cigarette smoke on bone cell functionality and viability. We generated an in vitro coculture system with SCP-1 and THP-1 cells (1:8 ratio) cultured on a decellularized Saos-2 matrix with an optimized coculture medium. We found that, following acute or chronic exposure, particulate matter extract from the aerosol of an HTP, the Tobacco Heating System (THS), was less harmful to the bone coculture system than reference cigarette (1R6F) smoke extract. In the fracture healing model, cultures exposed to the THS extract maintained similar osteoclast activity and calcium deposits as control cultures. Conversely, smoke extract exposure promoted osteoclast activity, resulting in an osteoporotic environment, whose formation could be prevented by bisphosphonate coadministration. Thus, THS is potentially less harmful than cigarette smoke to bone cell differentiation and bone mineralization - both being crucial aspects during the reparative phase of fracture healing.
Evolution of Clinical Outcome Measures and Biomarkers in Sporadic Adult‐Onset Degenerative Ataxia
2023-01-25

ABSTRACT Background Sporadic adult‐onset ataxias without known genetic or acquired cause are subdivided into multiple system atrophy of cerebellar type (MSA‐C) and sporadic adult‐onset ataxia of unknown etiology (SAOA). Objectives To study the differential evolution of both conditions including plasma neurofilament light chain (NfL) levels and magnetic resonance imaging (MRI) markers. Methods SPORTAX is a prospective registry of sporadic ataxia patients with an onset &gt;40 years. Scale for the Assessment and Rating of Ataxia was the primary outcome measure. In subgroups, blood samples were taken and MRIs performed. Plasma NfL was measured via a single molecule assay. Regional brain volumes were automatically measured. To assess signal changes, we defined the pons and middle cerebellar peduncle abnormality score (PMAS). Using mixed‐effects models, we analyzed changes on a time scale starting with ataxia onset. Results Of 404 patients without genetic diagnosis, 130 met criteria of probable MSA‐C at baseline and 26 during follow‐up suggesting clinical conversion to MSA‐C. The remaining 248 were classified as SAOA. At baseline, NfL, cerebellar white matter (CWM) and pons volume, and PMAS separated MSA‐C from SAOA. NfL decreased in MSA‐C and did not change in SAOA. CWM and pons volume decreased faster, whereas PMAS increased faster in MSA‐C. In MSA‐C, pons volume had highest sensitivity to change, and PMAS was a predictor of faster progression. Fulfillment of possible MSA criteria, NfL and PMAS were risk factors, CWM and pons volume protective factors for conversion to MSA‐C. Conclusions This study provides detailed information on differential evolution and prognostic relevance of biomarkers in MSA‐C and SAOA. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Resolving equivocal gain modulation of corticospinal excitability
2023-01-25

The ratio between the input and output of neuronal populations, usually referred to as gain modulation, is rhythmically modulated along the oscillatory cycle. Previous research on spinal neurons, however, revealed contradictory findings: both uni- and bimodal patterns of increased responsiveness for synaptic input have been proposed for the oscillatory beta rhythm. In this study, we compared previous approaches of phase estimation directly on simulated data and empirically tested the corresponding predictions in healthy males and females. We applied single-pulse transcranial magnetic stimulation over the primary motor cortex at rest, and assessed the spinal output generated by this input. Specifically, the peak-to-peak amplitude of the motor evoked potential in the contralateral forearm was estimated as a function of the EMG phase at which the stimulus was applied. The findings indicated that human spinal neurons adhere to a unimodal pattern of increased responsiveness, and suggest that the rising phase of the upper beta band maximizes gain modulation. Importantly, a bimodal pattern of increased responsiveness was shown to result in an artifact during data analysis and filtering. This observation of invalid preprocessing could be generalized to other frequency bands (i.e., delta, theta, alpha, and gamma), different task conditions (i.e., voluntary muscle contraction), and EEG-based phase estimations. Appropriate analysis algorithms, such as broad-band filtering, enable us to accurately determine gain modulation of neuronal populations and to avoid erroneous phase estimations. This may facilitate novel phase-specific interventions for targeted neuromodulation.