bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constraining Suprathermal Electron Evolution in a Parker Spiral Field With Cassini Observations
Authors: Graham G. A. , Bakrania M. R. , Rae I. J. , Owen C. J. , Walsh A. P. , Owens M. J. 
Published: April 2021

AbstractSuprathermal electrons in the solar wind consist of the “halo,” present at all pitch angles, and the “strahl” which is a field‐aligned, beam‐like population. Examining the heliospheric evolution of strahl beams is key to understanding the in‐transit processing of solar wind suprathermal electrons, in particular, to identify electron scattering mechanisms and to establish the origin of the halo population. Not only does this have significant implications with regard to the kinetic processes occurring within the solar wind but also its thermodynamic evolution, as the suprathermal electrons carry the majority of the solar wind heat flux. In this investigation, an established model for suprathermal electron evolution in a Parker spiral interplanetary magnetic field is adapted from its original use. The model is constrained using solar wind strahl observed by the Cassini mission on its interplanetary journey to Saturn. The effects of large scale IMF geometry due to different solar wind velocities and application of different electron scattering factors are examined. It is found that slow solar wind speeds provide the closest match to the strahl width observations, both in terms of radial distance and electron energy trends, and that predominantly slower solar wind speeds were therefore likely observed by the Cassini mission en‐route to Saturn. It is necessary to include a strahl scattering factor which increases with electron energy in order to match observations, indicating that the strahl scattering mechanism must have an inherent energy dependence.
An Evaluation of Spire Radio Occultation Data in Assimilative Ionospheric Model GPSII and Validation by Ionosonde Measurements
Authors: Kramer Kelsey K. , Fridman Sergey V. , Nickisch L. J. 
Published: April 2021

AbstractThis paper presents a comprehensive analysis of results obtained using NWRA’s assimilative ionospheric model GPSII when it is driven by Spire Global, Inc.’s global navigation satellite system ‐ radio occultation (GNSS‐RO) measurements. Results of the assimilative model are validated using the database of Digisonde and Dynasonde ionograms. A week’s worth of dual‐frequency phase data was collected from Spire’s constellation of low‐Earth orbiting micro‐satellites carrying GNSS receivers and assimilated into GPSII. A validation study of GNSS‐RO measurements was performed in four geographical regions. GPSII operation with the data was evaluated and the results were validated against independent ionospheric measurements. Ground‐based ionosondes were employed in diagnosing the accuracy of the derived models; we studied the differences between the F2 peak parameters (the F2 layer critical frequency, , and the peak height of the F2 layer, ) derived from ionograms and those computed with GPSII. For the 1,491 validation events used in this study, the magnitude of the deviation of the GPSII‐predicted at an ionosonde location from the corresponding ionosonde‐observed value was found on average to be 0.608 MHz (with a median of 0.461 MHz) and the magnitude of the deviation of the GPSII‐predicted at an ionosonde location from the corresponding ionosonde‐observed value was found to be on average 22.9 km (with a median value of 18.0 km). Median GPSII validation errors for are a factor of four smaller than corresponding errors for IRI, while GPSII errors are a factors of two smaller than those for IRI. The analysis showed that Spire’s TEC data was both compatible for ingestion into GPSII and that the assimilation of the data improved the comparison to ground‐based ionosondes.
Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages
Authors: Lv Jiadi , Wang Zhenfeng , Qu Yajin , Zhu Hua , Zhu Qiangqiang , Tong Wei , Bao Linlin , Lv Qi , Cong Ji , Li Dan , Deng Wei , Yu Pin , Song Jiangping , Tong Wei-Min , Liu Jiangning , Liu Yuying , Qin Chuan , Huang Bo 
Published: April 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the alveoli, where abundant alveolar macrophages (AMs) reside. How AMs respond to SARS-CoV-2 invasion remains elusive. Here, we show that classically activated M1 AMs facilitate viral spread; however, alternatively activated M2 AMs limit the spread. M1 AMs utilize cellular softness to efficiently take up SARS-CoV-2. Subsequently, the invaded viruses take over the endo-lysosomal system to escape. M1 AMs have a lower endosomal pH, favoring membrane fusion and allowing the entry of viral RNA from the endosomes into the cytoplasm, where the virus achieves replication and is packaged to be released. In contrast, M2 AMs have a higher endosomal pH but a lower lysosomal pH, thus delivering the virus to lysosomes for degradation. In hACE2 transgenic mouse model, M1 AMs are found to facilitate SARS-CoV-2 infection of the lungs. These findings provide insights into the complex roles of AMs during SARS-CoV-2 infection, along with potential therapeutic targets.
Genetic drift from the out-of-Africa bottleneck leads to biased estimation of genetic architecture and selection
Authors: Ashraf Bilal , Lawson Daniel John 
Published: April 2021

AbstractMost complex traits evolved in the ancestors of all modern humans and have been under negative or balancing selection to maintain the distribution of phenotypes observed today. Yet all large studies mapping genomes to complex traits occur in populations that have experienced the Out-of-Africa bottleneck. Does this bottleneck affect the way we characterise complex traits? We demonstrate using the 1000 Genomes dataset and hypothetical complex traits that genetic drift can strongly affect the joint distribution of effect size and SNP frequency, and that the bias can be positive or negative depending on subtle details. Characterisations that rely on this distribution therefore conflate genetic drift and selection. We provide a model to identify the underlying selection parameter in the presence of drift, and demonstrate that a simple sensitivity analysis may be enough to validate existing characterisations. We conclude that biobanks characterising more worldwide diversity would benefit studies of complex traits.
Association of visual motor processing and social cognition in schizophrenia
Authors: Lu Pin-Yen , Huang Yu-Lien , Huang Pai-Chuan , Liu Yi-Chia , Wei Shyh-Yuh , Hsu Wei-Yun , Chen Kao Chin , Chen Po See , Wu Wen-Chen , Yang Yen Kuang , Tseng Huai-Hsuan 
Published: April 2021

AbstractPatients with schizophrenia have difficulties in social cognitive domains including emotion recognition and mentalization, and in sensorimotor processing and learning. The relationship between social cognitive deficits and sensorimotor function in patients with schizophrenia remains largely unexplored. With the hypothesis that impaired visual motor processing may decelerate information processing and subsequently affects various domains of social cognition, we examined the association of nonverbal emotion recognition, mentalization, and visual motor processing in schizophrenia. The study examined mentalization using the verbal subset of the Chinese version of Theory of Mind (CToM) Task, an equivalent task of the Faux Pas Test; emotion recognition using the Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW), and visual motor processing using a joystick tracking task controlled for basic motor function in 34 individuals with chronic schizophrenia in the community and 42 healthy controls. Patients with schizophrenia had significantly worse performance than healthy controls in social cognition, including facial, prosodic emotion recognition, and mentalization. Visual motor processing was also significantly worse in patients with schizophrenia. Only in patients with schizophrenia, both emotion recognition (mainly in prosodic modality, happy, and sad emotions) and mentalization were positively associated with their learning capacity of visual motor processing. These findings suggest a prospective role of sensorimotor function in their social cognitive deficits. Despite that the underlying neural mechanism needs further research, our findings may provide a new direction for restoration of social cognitive function in schizophrenia by enhancing visual motor processing ability.
Database of Wannier tight-binding Hamiltonians using high-throughput density functional theory
Authors: Garrity Kevin F. , Choudhary Kamal 
Published: April 2021

AbstractWannier tight-binding Hamiltonians (WTBH) provide a computationally efficient way to predict electronic properties of materials. In this work, we develop a computational workflow for high-throughput Wannierization of density functional theory (DFT) based electronic band structure calculations. We apply this workflow to 1771 materials (1406 3D and 365 2D), and we create a database with the resulting WTBHs. We evaluate the accuracy of the WTBHs by comparing the Wannier band structures to directly calculated spin-orbit coupling DFT band structures. Our testing includes k-points outside the grid used in the Wannierization, providing an out-of-sample test of accuracy. We illustrate the use of WTBHs with a few example applications. We also develop a web-app that can be used to predict electronic properties on-the-fly using WTBH from our database. The tools to generate the Hamiltonian and the database of the WTB parameters are made publicly available through the websites https://github.com/usnistgov/jarvis and https://jarvis.nist.gov/jarviswtb.
Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)
Authors: Wang Yi-Jun , Monteagudo Alina , Downey Matthew A. , Ashton-Rickardt Philip G. , Elmaleh David R. 
Published: April 2021

AbstractCromolyn is a known mast cell stabilizer and is approved for treatment of asthma and for other allergic indications. Cromolyn, in a new redesigned dry powder formulation, is being tested in a pivotal clinical trial in combination with low dose ibuprofen to treat early Alzheimer’s Disease (AD) subjects. To better understand the mechanistic effect cromolyn has in slowing down or halting the neuroinflammatory response associated with AD progression, we tested the effect of cromolyn to dampen the inflammatory response in the human HMC3 microglia cell line. The direct effect of cromolyn on HMC3 microglia is on cytokines and chemokines production following their activation by the inflammatory cytokine TNF-α. Cromolyn and a new fluorinated analog dramatically reduced the secretion of a wide spectrum of inflammatory mediators, which included cytokines such as IL-1β, IL-6, IL-8 and IFN-γ, and chemokines such as CXCL10, CCL2, CCL3 and CCL4. These results bolster our understanding of how our cromolyn platform modulates toxic microglia behavior as a dynamic future treatment option for neurodegenerative disorders.
Digestive symptoms in daily life of chronic adrenal insufficiency patients are similar to irritable bowel syndrome symptoms
Authors: Quénéhervé L. , Drui D. , Blin J. , Péré M. , Coron E. , Barbara G. , Barbaro M. R. , Cariou B. , Neunlist M. , Masson D. , Bach-Ngohou K. 
Published: April 2021

AbstractGastrointestinal symptoms are frequent in acute adrenal insufficiency. Although digestive symptoms can significantly reduce quality of life, they are rarely described in patients with treated chronic adrenal insufficiency (CAI). We aimed to characterize digestive symptoms in CAI patients. We used the section pertaining functional bowel disorders of the Rome IV questionnaire. A questionnaire was published on the website of the non-profit patient association “Adrenals” (NPPA of CAI patients) for five months. Information on demographics, characteristics of adrenal insufficiency, digestive symptoms and quality of life was collected. The relatives of CAI patients served as a control group. We analyzed responses of 33 control subjects and 119 patients (68 primary adrenal insufficiency (PAI), 30 secondary adrenal insufficiency (SAI) and 21 congenital adrenal hyperplasia (CAH)). Abdominal pain at least once a week over the past 3 months was reported by 40%, 47% and 33% of patients with PAI, SAI and CAH respectively versus 15% for the controls (p = 0.01). Symptoms were consistent with the Rome IV criteria for irritable bowel syndrome in 27%, 33% and 33% of patients respectively versus 6% for the controls (p < 0.0001). Quality of life was described as poor or very poor in 35%, 57% and 24% of patients respectively versus 5% for the controls (p < 0.0001). In conclusion, digestive symptoms are frequent and incapacitating in CAI patients and similar to symptoms of irritable bowel syndrome in 30% of CAI patients. Assessment and management of digestive symptoms should be considered a priority for physicians treating patients with CAI.
In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer
Authors: Lin Z. Ping , Al Zouabi Nour N. , Xu Mark L. , Bowen Nicole E. , Wu Terence L. , Lavi Ethan S. , Huang Pamela H. , Zhu Yong-Lian , Kim Baek , Ratner Elena S. 
Published: April 2021

AbstractPoly ADP-ribose polymerase (PARP) inhibitors are promising targeted therapy for epithelial ovarian cancer (EOC) with BRCA mutations or defective homologous recombination (HR) repair. However, reversion of BRCA mutation and restoration of HR repair in EOC lead to PARP inhibitor resistance and reduced clinical efficacy of PARP inhibitors. We have previously shown that triapine, a small molecule inhibitor of ribonucleotide reductase (RNR), impaired HR repair and sensitized HR repair-proficient EOC to PARP inhibitors. In this study, we performed in silico screening of small molecule libraries to identify novel compounds that bind to the triapine-binding pocket on the R2 subunit of RNR and inhibit RNR in EOC cells. Following experimental validation of selected top-ranking in silico hits for inhibition of dNTP and DNA synthesis, we identified, DB4, a putative RNR pocket-binding inhibitor markedly abrogated HR repair and sensitized BRCA-wild-type EOC cells to the PARP inhibitor olaparib. Furthermore, we demonstrated that the combination of DB4 and olaparib deterred the progression of BRCA-wild type EOC xenografts and significantly prolonged the survival time of tumor-bearing mice. Herein we report the discovery of a putative small molecule inhibitor of RNR and HR repair for combination with PARP inhibitors to treat PARP inhibitor-resistant and HR repair-proficient EOC.
Optimizing hydroponic culture media and NO3−/NH4+ ratio for improving essential oil compositions of purple coneflower (Echinacea purpurea L.)
Authors: Ahmadi Fatemeh , Samadi Abbas , Sepehr Ebrahim , Rahimi Amir , Shabala Sergey 
Published: April 2021

AbstractMedicinal plants represent a valuable commodity due to beneficial effects of their natural products on human health, prompting a need for finding a way to optimize/increase their production. In this study, a novel growing media with various perlite particle size and its mixture with peat moss was tested for hydroponic-based production of Echinacea purpurea medicinal plant under greenhouse conditions. The plant growth parameters such as plant height, total fresh leave weight, fresh root weight, total biomass, total chlorophyll, leaf area, and essential oil compositions were assessed. Perlite particle size in the growing media was varied from very coarse (more than 2 mm) to very fine (less than 0.5 mm), and the ratio between perlite and peat moss varied from 50:50 v/v to 30:70 v/v. In addition, two nitrate (NO3−) to ammonium (NH4+) ratios (90:10 and 70:30) were tested for each growing media. The medium containing very fine-grade perlite and 50:50 v/v perlite to peat moss ratio was found to be most optimal and beneficial for E. purpurea performance, resulting in maximal plant height, fresh and dry weight, leaf surface area, and chlorophyll content. It was also found that an increase in NO3−/NH4+ ratio caused a significant increase in plant growth parameters and increase the plant essential oil content. The major terpene hydrocarbons found in extract of E. purpurea with the best growth parameters were germacrene D (51%), myrcene (15%), α-pinene (12%), β-caryophyllene (11%), and 1-Pentadecene (4.4%), respectively. The percentages of these terpene hydrocarbons were increased by increasing of NO3−/NH4+ ratio. It can be concluded that decreasing the perlite particle size and increasing the NO3−/NH4+ ratio increased the plant growth parameters and essential oil compositions in E. purpurea.
Low biological fluctuation of mitochondrial CpG and non-CpG methylation at the single-molecule level
Authors: Goldsmith Chloe , Rodríguez-Aguilera Jesús Rafael , El-Rifai Ines , Jarretier-Yuste Adrien , Hervieu Valérie , Raineteau Olivier , Saintigny Pierre , Chagoya de Sánchez Victoria , Dante Robert , Ichim Gabriel , Hernandez-Vargas Hector 
Published: April 2021

AbstractMammalian cytosine DNA methylation (5mC) is associated with the integrity of the genome and the transcriptional status of nuclear DNA. Due to technical limitations, it has been less clear if mitochondrial DNA (mtDNA) is methylated and whether 5mC has a regulatory role in this context. Here, we used bisulfite-independent single-molecule sequencing of native human and mouse DNA to study mitochondrial 5mC across different biological conditions. We first validated the ability of long-read nanopore sequencing to detect 5mC in CpG (5mCpG) and non-CpG (5mCpH) context in nuclear DNA at expected genomic locations (i.e. promoters, gene bodies, enhancers, and cell type-specific transcription factor binding sites). Next, using high coverage nanopore sequencing we found low levels of mtDNA CpG and CpH methylation (with several exceptions) and little variation across biological processes: differentiation, oxidative stress, and cancer. 5mCpG and 5mCpH were overall higher in tissues compared to cell lines, with small additional variation between cell lines of different origin. Despite general low levels, global and single-base differences were found in cancer tissues compared to their adjacent counterparts, in particular for 5mCpG. In conclusion, nanopore sequencing is a useful tool for the detection of modified DNA bases on mitochondria that avoid the biases introduced by bisulfite and PCR amplification. Enhanced nanopore basecalling models will provide further resolution on the small size effects detected here, as well as rule out the presence of other DNA modifications such as oxidized forms of 5mC.
Statistical analysis of comparative tumor growth repeated measures experiments in the ovarian cancer patient derived xenograft (PDX) setting
Authors: Oberg Ann L. , Heinzen Ethan P. , Hou Xiaonan , Al Hilli Mariam M. , Hurley Rachel M. , Wahner Hendrickson Andrea E. , Goergen Krista M. , Larson Melissa C. , Becker Marc A. , Eckel-Passow Jeanette E. , Maurer Matthew J. , Kaufmann Scott H. , Haluska Paul , Weroha S. John 
Published: April 2021

AbstractRepeated measures studies are frequently performed in patient-derived xenograft (PDX) models to evaluate drug activity or compare effectiveness of cancer treatment regimens. Linear mixed effects regression models were used to perform statistical modeling of tumor growth data. Biologically plausible structures for the covariation between repeated tumor burden measurements are explained. Graphical, tabular, and information criteria tools useful for choosing the mean model functional form and covariation structure are demonstrated in a Case Study of five PDX models comparing cancer treatments. Power calculations were performed via simulation. Linear mixed effects regression models applied to the natural log scale were shown to describe the observed data well. A straight growth function fit well for two PDX models. Three PDX models required quadratic or cubic polynomial (time squared or cubed) terms to describe delayed tumor regression or initial tumor growth followed by regression. Spatial(power), spatial(power) + RE, and RE covariance structures were found to be reasonable. Statistical power is shown as a function of sample size for different levels of variation. Linear mixed effects regression models provide a unified and flexible framework for analysis of PDX repeated measures data, use all available data, and allow estimation of tumor doubling time.
Differences in survival and phenotypic traits of curly birch preserved by heterovegetative propagation: a case study from Central-East Europe
Authors: Sarvašová Ivana , Sedmák Róbert , Sedmáková Denisa , Lukáčik Ivan 
Published: April 2021

AbstractCurly birch (Betula pendula Roth. var. carelica [Merklin] Hämet-Ahti) is a disappearing representative of the Betula genus facing a regeneration failure in a large part of its natural distribution in Europe. The unique long-term study of clonal replications originating in heterogeneous environments enabled the evaluation of long-term survival and phenotypic stability of progenies in seed orchard to assess the conservation and commercial potential of heterovegetative propagation. Seventy-eight geographic sources (95 clone origins) representing the south distribution edge in East-Central Europe were analysed for species variation in survival, growth form, bark colour, and stem quality of parent trees and their vegetative progeny, and the effects of four parental site origin characteristics. The survival rate was 73% after 28–33 years of growth. Retention of curly-grained wood was high, the curly-grained wood structure is heritable and thus clonally efficiently achievable (only 3.5% of grafted individuals showed no occurrence of figured wood structure). The phenotypic expression of curliness manifested on the trunks as bulges, stem growth forms (tree/shrub) and stem technical quality showed a lower degree of stability (coincidence) between the parent trees and heterovegatively propagated progenies. Despite this, the conservation potential of seed orchard is very high, especially when stabilization of the stem growth forms affecting the survival and commercial value of progenies can be probably achieved by a more careful selection of scions. Overall, heterovegetative orchards seem to be a very promising method for the long-term conservation of curly birch populations, which, in addition to their great biological and ecological value, have considerable commercial potential.
A neoclerodane orthoester and other new neoclerodane diterpenoids from Teucrium yemense chemistry and effect on secretion of insulin
Authors: Nur-e-Alam Mohammad , Parveen Ifat , Wilkinson Barrie , Ahmed Sarfaraz , Hafizur Rahman M. , Bari Ahmed , Woodman Timothy J. , Threadgill Michael D. , Al-Rehaily Adnan J. 
Published: April 2021

AbstractTeucrium yemense, a medicinal plant commonly grown in Saudi Arabia and Yemen, is traditionally used to treat infections, kidney diseases, rheumatism, and diabetes. Extraction of the dried aerial parts of the plant with methanol, followed by further extraction with butanol and chromatography, gave twenty novel neoclerodanes. Their structures, relative configurations and some conformations were determined by MS and 1-D and 2-D NMR techniques. Most were fairly conventional but one contained an unusual stable orthoester, one had its (C-16)–(C-13)–(C-14)–(C-15) (tetrahydro)furan unit present as a succinic anhydride and one had a rearranged carbon skeleton resulting from ring-contraction to give a central octahydroindene bicyclic core, rather than the usual decalin. Mechanisms are proposed for the biosynthetic formation of the orthoester and for the ring-contraction. Four novel neoclerodanes increased the glucose-triggered release of insulin from isolated murine pancreatic islets by more than the standard drug tolbutamide, showing that they are potential leads for the development of new anti-diabetic drugs.