julilili42/papers huggingface dataset:
Neutrophil Elastase and Proteinase 3 Cleavage Sites Are Adjacent to the Polybasic Sequence within the Proteolytic Sensitive Activation Loop of the SARS-CoV-2 Spike Protein
2021-03-05

Serine proteases neutrophil elastase (NE), protease 3 (PR3), cathepsin G (CatG), and neutrophil serine protease 4 (NSP4) are released by activated neutrophils swarming around the place of pathogen invasion to provoke an immune response. However, uncontrolled proteolytic activity of proteases results in various human diseases, including cardiovascular diseases, thrombosis, and autoimmunity. In addition, proteases can be hijacked by several viruses to prime virus-derived surface proteins and evade immune detection by entering into the host cell. Indeed, porcine elastase increases the suitability of host cells to be infected by SARS-CoV-1. We compared the cleavage sites of human NE, PR3, and CatG as well as porcine-derived trypsin within the amino acid sequence of the proteolytic sensitive activation loop at the interface of S1/S2 of the spike protein (S protein) of SARS-CoV-1 as well as SARS-CoV-2. As a result, NE and PR3, but not CatG, hydrolyze the scissile peptide bond adjacent to the polybasic amino acid sequence of the S1/S2 interface of SARS-CoV-2, which is distinctive from SARS-CoV-1. These findings suggest that neutrophil-derived NE and PR3 participate in priming of the S1/S2 interface during an immune response.
Malaria parasites differentially sense environmental elasticity during transmission
2021-03-05

Transmission of malaria-causing parasites to and by the mosquito relies on active parasite migration and constitutes bottlenecks in the Plasmodium life cycle. Parasite adaption to the biochemically and physically different environments must hence be a key evolutionary driver for transmission efficiency. To probe how subtle but physiologically relevant changes in environmental elasticity impact parasite migration, we introduce 2D and 3D polyacrylamide gels to study ookinetes, the parasite forms emigrating from the mosquito blood meal and sporozoites, the forms transmitted to the vertebrate host. We show that ookinetes adapt their migratory path but not their speed to environmental elasticity and are motile for over 24 h on soft substrates. In contrast, sporozoites evolved more short-lived rapid gliding motility for rapidly crossing the skin. Strikingly, sporozoites are highly sensitive to substrate elasticity possibly to avoid adhesion to soft endothelial cells on their long way to the liver. Hence, the two migratory stages of Plasmodium evolved different strategies to overcome the physical challenges posed by the respective environments and barriers they encounter.
Direct enantioselective gradient reversed‐phase ultra‐high performance liquid chromatography tandem mass spectrometry method for 3‐hydroxy alkanoic acids in lipopeptides on an immobilized 1.6 μm amylose‐based chiral stationary phase
2021-03-05

Abstract 3‐Hydroxy fatty acids are important chiral building blocks of lipopeptides and metabolic intermediates of fatty acid oxidation, respectively. The analysis of the stereochemistry of such biomolecules has significant practical impact to elucidate and assign the enzymatic specificity of the biosynthesis machinery. In this work, a new mass spectrometry compatible direct chiral ultra high performance liquid chromatography separation method for 3‐hydroxy fatty acids without derivatization is presented. The application of amylose tris(3,5‐dimethylphenyl carbamate) based polysaccharide chiral stationary phase immobilized on 1.6 μm silica particles (CHIRALPAK IA‐U) allows the enantioseparation of 3‐hydroxy fatty acids under generic electrospray ionization mass spectrometry friendly reversed phase gradient elution conditions. Adequate separation factors were achieved with both acetonitrile and methanol as organic modifiers, covering hydrocarbon chain lengths between C 6 and C 14 . Elution orders were derived from rhamnolipid (R‐95) of which enantiomerically pure or enriched ( R )‐3‐hydroxy fatty acids were recovered after ester hydrolysis. The S ‐configured acids consistently eluted before the respective R‐ enantiomers. The method was successfully applied for the elucidation of the absolute configuration of 3‐hydroxy fatty acids originating from a novel lipopeptide with unknown structure. The work furthermore demonstrates that gradient elution is a viable option also in enantioselective (ultra)high performance liquid chromatography, even for analytes with modest separation factors, although less commonly exploited.
Enhancement of Pentachlorophenol Removal in a Historically Contaminated Soil by Adding Ascorbic Acid to H2O2/Magnetite System
2021-03-05

Development of new tools to improve the efficiency of iron minerals in promoting Fenton oxidation for environmental remediation is a highly promising field. Here, we examine for the first time the role of ascorbic acid (AA) in improving the magnetite (Fe3O4)-mediated Fenton oxidation to remove pentachlorophenol (PCP) in a historically contaminated soil. Experiments were performed in batch and flow-through conditions. In batch slurry experiments, the combination of Fe3O4/AA/H2O2 removed up to 95% of PCP as compared to the 43% removal by Fe3O4/H2O2. Dissolved Fe(II) measurements and Mössbauer spectroscopy highlight the role of AA in increasing the Fe(II) generation. Therefore, its presence enabled the Fe3O4 to maintain its structural Fe(II) content even after the oxidation reaction. Despite kinetic limitations in water-saturated columns, use of Fe3O4/AA/H2O2 removed about 70% of PCP contrary to the 20% PCP removal with Fe3O4/H2O2. This oxidation performance was affected by an injection flow rate or column residence time of AA and H2O2 in columns. Thus, the presence of AA significantly improved the ability of magnetite in promoting the Fenton reaction. Owing to the crucial role of AA in the Fe(II)/Fe(III) redox cycling, a mixed-valent character of magnetite makes it a potential catalyst for Fenton oxidation of organic pollutants.
3-Hydroxy-propanamidines, a New Class of Orally Active Antimalarials Targeting Plasmodium falciparum
2021-03-05

3-Hydroxypropanamidines are a new promising class of highly active antiplasmodial agents. The most active compound 22 exhibited excellent antiplasmodial in vitro activity with nanomolar inhibition of chloroquine-sensitive and multidrug-resistant parasite strains ofPlasmodium falciparum (with IC50 values of 5 and 12 nM against 3D7 and Dd2 strains, respectively) as well as low cytotoxicity in human cells. In addition, 22 showed strong in vivo activity in thePlasmodium berghei mouse model with a cure rate of 66% at 50 mg/kg and a cure rate of 33% at 30 mg/kg in the Peters test after once daily oral administration for 4 consecutive days. A quick onset of action was indicated by the fast drug absorption shown in mice. The new lead compound was also characterized by a high barrier to resistance and inhibited the heme detoxification machinery in P. falciparum.
Structure of Thin Films of [6] and [7]Phenacene and Impact of Potassium Deposition
2021-03-05

Abstract Organic semiconductors offer a flexibility in band gap tuning through different molecular lengths and have shown to be promising candidates for high‐performance electronic devices. While electronic properties have been extensively studied in many publications, the topic of thin film structure and molecular packing is still quite neglected. In this work, the thin film crystal structure of [6]phenacene (Fulminene) and [7]phenacene deposited on silicon substrates using the OMBD method as well as further studies with potassium deposition on [6]phenacene are investigated. Ex‐situ X‐ray and optical methods are employed to obtain an insight into the crystal structure and optical properties. The orientation of the molecules and the unit cell structure is calculated from the measured reciprocal space maps. Additionally, the influence of a possible interfacial doping mechanism by deposition of potassium on top of [6]phenacene is investigated. Thin films of [6]phenacene show a high crystallinity with a standing‐up configuration and a similar molecular structure and symmetry compared to [4]phenacene. [7]phenacene features two different apparently thickness‐dependent polymorphs (H and L) with a structure similar to [5]phenacene. These results reveal that odd/even parity, that is, even or odd number of benzene rings, directly influences the phenacene thin film structure.
Genotyping-by-sequencing-based identification ofArabidopsispattern recognition receptor RLP32 recognizing proteobacterial translation initiation factor IF1
2021-03-05

Abstract Pattern-triggered immunity (PTI) is a central component of plant immunity. Activation of PTI relies on the recognition of microbe-derived structures, termed patterns, through plant encoded surface-resident pattern recognition receptors (PRRs). We have identified proteobacterial translation initiation factor 1 (IF1) as an immunogenic pattern that triggers PTI in Arabidopsis thaliana and some related Brassicaceae species. Unlike most other immunogenic patterns identified, IF1 elicitor activity cannot be assigned to a small peptide epitope, suggesting that tertiary fold features are required for IF1 receptor activation. We have deployed natural variation in IF1 sensitivity to identify leucine-rich repeat (LRR) receptor-like protein 32 (RLP32) as the corresponding Arabidopsis receptor using a restriction site-associated DNA sequencing (RAD-seq) approach. Transgenic expression of RLP32 confers IF1 sensitivity to rlp32 mutants, IF1-insensitive Arabidopsis accessions and IF1-insensitive Nicotiana benthamiana . RLP32 binds IF1 specifically and forms complexes with LRR receptor kinases SOBIR1 and BAK1 to mediate signaling. Similar to previously identified PRRs RLP32 confers resistance to Pseudomonas syringae infection, highlighting an unexpectedly complex array of bacterial pattern sensors within a single plant species.
Salvage-Radiation Therapy and Regional Hyperthermia for Biochemically Recurrent Prostate Cancer after Radical Prostatectomy (Results of the Planned Interim Analysis)
2021-03-06

Efforts to improve the outcome of prostate cancer (PC) patients after radical prostatectomy (RP) include adjuvant or salvage radiation therapy (SRT), but still up to 50% of patients develop a disease progression after radiotherapy (RT). Regional hyperthermia (HT) is well-known to improve tumor sensitivity to RT in several entities. Here we report on a planned interim analysis of tolerability and feasibility after recruitment of the first 50 patients of a trial combining SRT and HT. We conducted a prospective multicenter non-randomized Phase-II-Trial (HTProstate-NCT04159051) investigating the implementation of combined moderate-dose escalated SRT (70 Gy in 35 fractions) and locoregional deep HT (7–10 HT sessions). The primary endpoints were the rate of acute genitourinary (GU), gastrointestinal (GI), and HT-related toxicities, completed HT sessions (≥7), and SRT applications per protocol (≥95% of patients). The two-step design included a planned interim analysis for acute GU-, GI- and HT-specific toxicities to ensure patients’ safety. Between November 2016 and December 2019, 52 patients entered into the trial. After 50 patients completed therapy and three months of follow-up, we performed the planned interim analysis. 10% of patients developed acute grade 2 GU and 4% grade 2 GI toxicities. No grade ≥3 GU or GI toxicities occurred. HT-specific symptoms grade 2 and 3 were observed in 4% and 2% of all patients. Thus, the pre-specified criteria for safety and continuation of recruitment were met. Moreover, ≥7 HT treatments were applicable, indicating the combination of SRT + HT to be feasible. Evaluation of early QoL showed no significant changes. With its observed low rate of GU and GI toxicities, moderate and manageable rates of HT-specific symptoms, and good feasibility, the combined SRT + HT seems to be a promising treatment approach for biochemical recurrence after RP in PC patients.
Distance from the magnification device contributes to differences in lower leg length measured in patients with TSF correction
2021-03-06

Abstract Introduction In absence of deformity or injury of the contralateral leg, the contralateral leg length is used to plan limb lengthening. Length variability on long-leg weight-bearing radiographs (LLR) can lead to inaccurate deformity correction. The aim of the study was to (1) examine the variability of the measured limb length on LLR and (2) to examine the influence of the position of the magnification device. Materials and methods The limb lengths of 38 patients during deformity correction with a taylor-spatial-frame were measured retrospectively on 7.3 ± 2.6 (4–13) LLR per patient. The measured length of the untreated limb between LLR were used to determine length variability between LLR in each patient. To answer the secondary aim, we took LLR from a 90 cm validation distance. A magnification device was placed in different positions: at the middle of the 90 cm distance ( z -position), 5 cm anterior and 5 cm posterior from the z -position, at the bottom and top of the validation distance as well as 5 cm medial and 15 cm lateral from the z -position. Results The measured length variability ranged within a patient from 10 to 50 mm. 76% of patients had a measured limb length difference of ≥ 2 cm between taken LLR. Compared to length measurement of the 90 cm test object with the magnification device in the z -position (90.1 cm), positioning the device 5 cm anterior led to smaller (88.6 cm) and 5 cm posterior led to larger measurements (91.7 cm). The measured length with the magnification device at the bottom, top, medial or lateral (90.4; 89.9; 90.2; 89.8 cm) to the object differed not relevantly. Conclusions High variability of limb length between different LLR within one patient was observed. This can result from different positions of the magnification device in the sagittal plane. These small changes in positioning the device should be avoided to achieve accurate deformity correction and bone lengthening. This should be considered for all length and size measurements on radiographs.
Exponentially accelerated approach to stationarity in Markovian open quantum systems through the Mpemba effect
2021-03-08

Ergodicity-breaking and slow relaxation are intriguing aspects of nonequilibrium dynamics both in classical and in quantum settings. These phenomena are typically associated with phase transitions, e.g. the emergence of metastable regimes near a first-order transition or scaling dynamics in the vicinity of critical points. Despite being of fundamental interest the associated divergent time scales are a hindrance when trying to explore steady-state properties. Here we show that the relaxation dynamics of Markovian open quantum systems can be accelerated exponentially by devising an optimal unitary transformation that is applied to the quantum system immediately before the actual dynamics. This initial "rotation" is engineered in such a way that the state of the quantum system becomes orthogonal to the slowest decaying dynamical mode. We illustrate our idea -- which is inspired by the so-called Mpemba effect, i.e., water freezing faster when initially heated up -- by showing how to achieve an exponential speed-up in the convergence to stationarity in Dicke models, and how to avoid metastable regimes in an all-to-all interacting spin system.
Technical Challenges of Real-Time Adaptive MR-Guided Radiotherapy
2021-03-08

In the past few years, radiotherapy (RT) has experienced a major technological innovation with the development of hybrid machines combining magnetic resonance (MR) imaging and linear accelerators. This new technology for MR-guided cancer treatment has the potential to revolutionize the field of adaptive RT due to the opportunity to provide high-resolution, real-time MR imaging before and during treatment application. However, from a technical point of view, several challenges remain which need to be tackled to ensure safe and robust real-time adaptive MR-guided RT delivery. In this manuscript, several technical challenges to MR-guided RT are discussed. Starting with magnetic field strength tradeoffs, the potential and limitations for purely MR-based RT workflows are discussed. Furthermore, the current status of real-time 3D MR imaging and its potential for real-time RT are summarized. Finally, the potential of quantitative MR imaging for future biological RT adaptation is highlighted.
Bio-Inspired Hybridization of Artificial Neural Networks: An Application for Mapping the Spatial Distribution of Soil Texture Fractions
2021-03-08

Soil texture and particle size fractions (PSFs) are a critical characteristic of soil that influences most physical, chemical, and biological properties of soil; furthermore, reliable spatial predictions of PSFs are crucial for agro-ecological modeling. Here, series of hybridized artificial neural network (ANN) models with bio-inspired metaheuristic optimization algorithms such as a genetic algorithm (GA-ANN), particle swarm optimization (PSO-ANN), bat (BAT-ANN), and monarch butterfly optimization (MBO-ANN) algorithms, were built for predicting PSFs for the Mazandaran Province of northern Iran. In total, 1595 composite surficial soil samples were collected, and 64 environmental covariates derived from terrain, climatic, remotely sensed, and categorical datasets were used as predictors. Models were tested using a repeated 10-fold nested cross-validation approach. The results indicate that the hybridized ANN methods were far superior to the reference approach using ANN with a backpropagation training algorithm (BP-ANN). Furthermore, the MBO-ANN approach was consistently determined to be the best approach and yielded the lowest error and uncertainty. The MBO-ANN model improved the predictions in terms of RMSE by 20% for clay, 10% for silt, and 24% for sand when compared to BP-ANN. The physiographical units, soil types, geology maps, rainfall, and temperature were the most important predictors of PSFs, followed by the terrain and remotely sensed data. This study demonstrates the effectiveness of bio-inspired algorithms for improving ANN models. The outputs of this study will support and inform sustainable soil management practices, agro-ecological modeling, and hydrological modeling for the Mazandaran Province of Iran.
Playing the Blame Game with Robots
2021-03-08

Recent research shows -- somewhat astonishingly -- that people are willing to ascribe moral blame to AI-driven systems when they cause harm [1]-[4]. In this paper, we explore the moral-psychological underpinnings of these findings. Our hypothesis was that the reason why people ascribe moral blame to AI systems is that they consider them capable of entertaining inculpating mental states (what is called mens rea in the law). To explore this hypothesis, we created a scenario in which an AI system runs a risk of poisoning people by using a novel type of fertilizer. Manipulating the computational (or quasi-cognitive) abilities of the AI system in a between-subjects design, we tested whether people's willingness to ascribe knowledge of a substantial risk of harm (i.e., recklessness) and blame to the AI system. Furthermore, we investigated whether the ascription of recklessness and blame to the AI system would influence the perceived blameworthiness of the system's user (or owner). In an experiment with 347 participants, we found (i) that people are willing to ascribe blame to AI systems in contexts of recklessness, (ii) that blame ascriptions depend strongly on the willingness to attribute recklessness and (iii) that the latter, in turn, depends on the perceived "cognitive" capacities of the system. Furthermore, our results suggest (iv) that the higher the computational sophistication of the AI system, the more blame is shifted from the human user to the AI system.
A Proof of Concept for Machine Learning-Based Virtual Knapping Using Neural Networks
2021-03-08

Prehistoric stone tools are an important source of evidence for the study of human behavioural and cognitive evolution. Archaeologists use insights from the experimental replication of stone tools to understand things such as the behaviours and cognitive capacities required to manufacture them. However, such experiments can require large amounts of time and raw materials, and achieving sufficient control of key knapping variables can be difficult. A computer program able to accurately simulate stone tool production would make lithic experimentation faster and more accessible, and may lead to reliable insights into the factors that structure the archaeological record. We present here a proof of concept for a machine learning-based virtual knapping framework capable of quickly and accurately predicting flake removals from 3D cores using a conditional adversarial neural network (CGAN). We programmatically generated a testing dataset of standardised 3D cores with flakes knapped from them. After training, the CGAN accurately predicted the length, volume, width, and shape of these flake removals using the core surface information alone. This demonstrates the feasibility of machine learning for investigating stone tool production virtually. With an increased training sample and validation against archaeological data, virtual knapping could enable fast, cheap, and highly-repeatable virtual lithic experimentation.
Embryonic staging of bats with special reference to Vespertilio sinensis and its cochlear development
2021-03-08

Abstract Background How bats deviate heterochronically from other mammals remains largely unresolved, reflecting the lack of a quantitative staging framework allowing comparison among species. The standard event system (SES) is an embryonic staging system allowing quantitative detection of interspecific developmental variations. Here, the first SES‐based staging system for bats, using Asian parti‐colored bat ( Vespertilio sinensis ) is introduced. General aspects of normal embryonic development and the three‐dimensional development of the bat cochlea were described for the first time. Recoding the embryonic staging tables of 18 previously reported bat species and Mus musculus into the SES system, quantitative developmental comparisons were performed. Results It was found that limb bud development of V. sinensis is relatively late among 19 bat species and late limb development is a shared trait of vespertilionid bats. The inner ear cochlear canal forms before the semicircular canal in V. sinensis while the cochlear canal forms after the semicircular canal in non‐volant mammals. Conclusions The present approach using the SES system provides a powerful framework to detect the peculiarities of bat development. Incorporating the timing of gene expression patterns into the SES framework will further contribute to the understanding of the evolution of specialized features in bats.