bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beam‐Driven Electron Cyclotron Harmonic and Electron Acoustic Waves as Seen in Particle‐In‐Cell Simulations
Authors: Zhang Xu , An Xin , Angelopoulos Vassilis , Artemyev Anton , Zhang Xiao‐Jia , Jia Ying‐Dong 
Published: May 2024

AbstractRecent study has demonstrated that electron cyclotron harmonic (ECH) waves can be excited by a low energy electron beam. Such waves propagate at moderately oblique wave normal angles (∼70°). The potential effects of beam‐driven ECH waves on electron dynamics in Earth's plasma sheet is not known. Using two‐dimensional Darwin particle‐in‐cell simulations with initial electron distributions that represent typical plasma conditions in the plasma sheet, we explore the excitation and saturation of such beam‐driven ECH waves. Both ECH and electron acoustic waves are excited in the simulation and propagate at oblique wave normal angles. Compared with the electron acoustic waves, ECH waves grow much faster and have more intense saturation amplitudes. Cold, stationary electrons are first accelerated by ECH waves through cyclotron resonance and then accelerated in the parallel direction by both the ECH and electron acoustic waves through Landau resonance. Beam electrons, on the other hand, are decelerated in the parallel direction and scattered to larger pitch angles. The relaxation of the electron beam and the continuous heating of the cold electrons contribute to ECH wave saturation and suppress the excitation of electron acoustic waves. When the ratio of plasma to electron cyclotron frequency ωpe/ωce increases, the ECH wave amplitude increases while the electron acoustic wave amplitude decreases. Our work reveals the importance of ECH and electron acoustic waves in reshaping sub‐thermal electron distributions and improves our understanding on the potential effects of wave‐particle interactions in trapping ionospheric electron outflows and forming anisotropic (field‐aligned) electron distributions in the plasma sheet.
Field Line Curvature (FLC) Scattering in the Dayside Off‐Equatorial Minima Regions
Authors: Cai Bin , Zhu Hui 
Published: May 2024

AbstractMagnetic field line curvature (FLC) scattering is an effective mechanism for collisionless particle scattering. In the terrestrial magnetosphere, the FLC scattering plays an essential role in shaping the outer boundary of protons radiation belt, the rapid decay of ring current, and the formation of proton isotropic boundary (IB). However, previous studies have yet to adequately investigate the influence of FLC scattering on charged particles in the Earth's dayside magnetosphere, particularly in the off‐equatorial magnetic minima regions. This study employs T89 magnetic field model to investigate the impacts of FLC scattering on ring current protons in the dayside magnetosphere, with a specific focus on the off‐equatorial minimum regions. We analyze the spatial distributions of single and dual magnetic minima regions, adiabatic parameter, and pitch angle diffusion coefficients due to FLC scattering as functions of Kp. The results show that the effects of FLC scattering are significant not only on the dusk and dawn sides but also in the off‐equatorial minima regions on the noon. Additionally, we investigate the role of dipole tilt angle in the hemispheric asymmetry of FLC scattering effects. The dipole tilt angle controls the overall displacement of the dayside magnetosphere, resulting in different FLC scattering effects in the two hemispheres. Our study holds significance for understanding the FLC scattering effects in the off‐equatorial region of Earth's dayside magnetosphere and for constructing a more accurate dynamic model of particles.
Estimation of the Contribution of the Ionospheric D Region to the TEC Value During a Series of Solar Flares in September 2017
Authors: Bekker S. Z. , Ryakhovsky I. A. 
Published: May 2024

AbstractThe paper presents the results of a numerical assessment of the contribution of the ionospheric D region to the total electron content during six powerful X‐ray flares that occurred in September 2017. The calculation of the electron concentration in the lower ionosphere was carried out using a plasma‐chemical model of the ionospheric D region. This model was verified using the data of ground‐based radiophysical measurements in the VLF (very low frequency) range and data of the incoherent scattering radar. To calculate the ionization rate at the D region heights, we used real data on the radiation flux measured by the GOES and SDO satellites during the considered flares. The total electron content was estimated using GNSS data. As a result of the analysis, it was found that the contribution of the lower ionosphere to the TEC change varied from 7% to 23% for flares with different spectra. A functional dependency has been obtained that can be used to estimate the contribution of the D region to the TEC increment depending on the spectrum of the flare.
Local and global effects of sedation in resting-state fMRI: a randomized, placebo-controlled comparison between etifoxine and alprazolam
Authors: Wein Simon , Riebel Marco , Seidel Philipp , Brunner Lisa-Marie , Wagner Viola , Nothdurfter Caroline , Rupprecht Rainer , Schwarzbach Jens V. 
Published: May 2024

AbstractTSPO ligands are promising alternatives to benzodiazepines in the treatment of anxiety, as they display less pronounced side effects such as sedation, cognitive impairment, tolerance development and abuse potential. In a randomized double-blind repeated-measures study we compare a benzodiazepine (alprazolam) to a TSPO ligand (etifoxine) by assessing side effects and acquiring resting-state fMRI data from 34 healthy participants after 5 days of taking alprazolam, etifoxine or a placebo. To study the effects of the pharmacological interventions in fMRI in detail and across different scales, we combine in our study complementary analysis strategies related to whole-brain functional network connectivity, local connectivity analysis expressed in regional homogeneity, fluctuations in low-frequency BOLD amplitudes and coherency of independent resting-state networks. Participants reported considerable adverse effects such as fatigue, sleepiness and concentration impairments, related to the administration of alprazolam compared to placebo. In resting-state fMRI we found a significant decrease in functional connection density, network efficiency and a decrease in the networks rich-club coefficient related to alprazolam. While observing a general decrease in regional homogeneity in high-level brain networks in the alprazolam condition, we simultaneously could detect an increase in regional homogeneity and resting-state network coherence in low-level sensory regions. Further we found a general increase in the low-frequency compartment of the BOLD signal. In the etifoxine condition, participants did not report any significant side effects compared to the placebo, and we did not observe any corresponding modulations in our fMRI metrics. Our results are consistent with the idea that sedation globally disconnects low-level functional networks, but simultaneously increases their within-connectivity. Further, our results point towards the potential of TSPO ligands in the treatment of anxiety and depression.
Novel biomarkers of preterm brain injury from blood transcriptome in sheep model of intrauterine asphyxia
Authors: Ek C. Joakim , Alkmark Mårten , Baburamani Ana A. , Supramaniam Veena G. , Sood Sanjana , Melchiotti Rossella , de Rinaldis Emanuele , Hagberg Henrik , Mallard Carina 
Published: May 2024

Abstract

Background
Infants born preterm have a higher incidence of neurological deficits. A key step in finding effective treatments is to identify biomarkers that reliably predict outcome.

Methods
Following umbilical cord occlusion (UCO) in pregnant sheep, whole fetal blood RNA was sequenced pre- and post-UCO, brain injury outcome was determined by battery of neuropathology scoring and the transcriptome signature correlated to the degree of brain injury. Additionally, we developed a novel analytical procedure to deduce cell blood composition over time.

Results
Sixty-one genes were identified with significant altered expression after UCO. In pre-UCO blood, the level of three mRNAs (Trex2, Znf280b, novel miRNA) and in post-UCO, four mRNAs (Fam184a, Angptl2, novel lincRNA and an unknown protein-coding gene) were associated to brain injury (FDR < 0.01). Several of these mRNAs are related to inflammation and angiogenesis. Pathway analysis highlighted genes playing a role in perinatal death and growth failure. Results also indicate that several leukocyte populations undergo significant changes after UCO.

Conclusion
We have used a whole transcriptomic approach to uncover novel biomarkers in fetal blood that correlate to neuropathology in the preterm sheep brain. The current data forms a basis for future studies to investigate mechanisms of these mRNAs in the injury progression.

Impact

Trend analysis of genes following asphyxia reveal a group of genes associated with perinatal death and growth failure.

Several pre-asphyxia transcripts were associated to brain injury severity suggesting genomic susceptibility to injury.

Several post-asphyxia transcripts were correlated to brain injury severity, thus, serve as potential novel biomarkers of injury outcome.

Successfully adaptation of cell profiling algorithms suggests significant changes in blood cell composition following asphyxia.
TRIM33 plays a critical role in regulating dendritic cell differentiation and homeostasis by modulating Irf8 and Bcl2l11 transcription
Authors: Shen Xiangyi , Li Xiaoguang , Wu Tao , Guo Tingting , Lv Jiaoyan , He Zhimin , Luo Maocai , Zhu Xinyi , Tian Yujie , Lai Wenlong , Dong Chen , Hu Xiaoyu , Wu Li 
Published: May 2024

AbstractThe development of distinct dendritic cell (DC) subsets, namely, plasmacytoid DCs (pDCs) and conventional DC subsets (cDC1s and cDC2s), is controlled by specific transcription factors. IRF8 is essential for the fate specification of cDC1s. However, how the expression of Irf8 is regulated is not fully understood. In this study, we identified TRIM33 as a critical regulator of DC differentiation and maintenance. TRIM33 deletion in Trim33fl/fl Cre-ERT2 mice significantly impaired DC differentiation from hematopoietic progenitors at different developmental stages. TRIM33 deficiency downregulated the expression of multiple genes associated with DC differentiation in these progenitors. TRIM33 promoted the transcription of Irf8 to facilitate the differentiation of cDC1s by maintaining adequate CDK9 and Ser2 phosphorylated RNA polymerase II (S2 Pol II) levels at Irf8 gene sites. Moreover, TRIM33 prevented the apoptosis of DCs and progenitors by directly suppressing the PU.1-mediated transcription of Bcl2l11, thereby maintaining DC homeostasis. Taken together, our findings identified TRIM33 as a novel and crucial regulator of DC differentiation and maintenance through the modulation of Irf8 and Bcl2l11 expression. The finding that TRIM33 functions as a critical regulator of both DC differentiation and survival provides potential benefits for devising DC-based immune interventions and therapies.
Universal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein
Authors: Langedijk Johannes P. M. , Cox Freek , Johnson Nicole V. , van Overveld Daan , Le Lam , van den Hoogen Ward , Voorzaat Richard , Zahn Roland , van der Fits Leslie , Juraszek Jarek , McLellan Jason S. , Bakkers Mark J. G. 
Published: May 2024

AbstractThe Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), and zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. The RV3 fusion (F) protein is inherently metastable and will likely require prefusion (preF) stabilization for vaccine effectiveness. Here we used structure-based design to stabilize regions involved in structural transformation to generate a preF protein vaccine antigen with high expression and stability, and which, by stabilizing the coiled-coil stem region, does not require a heterologous trimerization domain. The preF candidate induces strong neutralizing antibody responses in both female naïve and pre-exposed mice and provides protection in a cotton rat challenge model (female). Despite the evolutionary distance of paramyxovirus F proteins, their structural transformation and local regions of instability are conserved, which allows successful transfer of stabilizing substitutions to the distant preF proteins of RV1 and NiV. This work presents a successful vaccine antigen design for RV3 and provides a toolbox for future paramyxovirus vaccine design and pandemic preparedness.
The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity
Authors: Prasad Chandra Bhushan , Oo Adrian , Liu Yujie , Qiu Zhaojun , Zhong Yaogang , Li Na , Singh Deepika , Xin Xiwen , Cho Young-Jae , Li Zaibo , Zhang Xiaoli , Yan Chunhong , Zheng Qingfei , Wang Qi-En , Guo Deliang , Kim Baek , Zhang Junran 
Published: May 2024

AbstractCheckpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i’s) in combination with chemotherapy have shown promising results in preclinical studies but have displayed minimal efficacy with substantial toxicity in clinical trials. To explore combinatorial strategies that can overcome these limitations, we perform an unbiased high-throughput screen in a non-small cell lung cancer (NSCLC) cell line and identify thioredoxin1 (Trx1), a major component of the mammalian antioxidant-system, as a determinant of CHK1i sensitivity. We establish a role for redox recycling of RRM1, the larger subunit of ribonucleotide reductase (RNR), and a depletion of the deoxynucleotide pool in this Trx1-mediated CHK1i sensitivity. Further, the TrxR inhibitor auranofin, an approved anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, we show a pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity.
Azoles activate type I and type II programmed cell death pathways in crop pathogenic fungi
Authors: Schuster Martin , Kilaru Sreedhar , Steinberg Gero 
Published: May 2024

AbstractTriazoles are widely used to control pathogenic fungi. They inhibit the ergosterol biosynthetic pathway, but the precise mechanisms leading to fungicidal activities in many fungal pathogens are poorly understood. Here, we elucidate the mode of action of epoxiconazole and metconazole in the wheat pathogen Zymoseptoria tritici and the rice blast fungus Magnaporthe oryzae. We show that both azoles have fungicidal activity and reduce fluidity, but not integrity, of the plasma membrane. This impairs localisation of Cdc15-like F-BAR proteins, resulting in defective actin ring assembly and incomplete septation. However, mutant studies and pharmacological experiments in vitro and in planta show that azole lethality is due to a combination of reactive oxygen species-induced apoptosis and macroautophagy. Simultaneous inhibition of both programmed cell death pathways abolishes azole-induced cell death. Other classes of ergosterol biosynthesis inhibitors also induce apoptosis and macroautophagy, suggesting that activation of these two cell death pathways is a hallmark of ergosterol synthesis-targeting fungicides. This knowledge will inform future crop protection strategies.
Non-linear relationships between daily temperature extremes and US agricultural yields uncovered by global gridded meteorological datasets
Authors: Hogan Dylan , Schlenker Wolfram 
Published: May 2024

AbstractGlobal agricultural commodity markets are highly integrated among major producers. Prices are driven by aggregate supply rather than what happens in individual countries in isolation. Estimating the effects of weather-induced shocks on production, trade patterns and prices hence requires a globally representative weather data set. Recently, two data sets that provide daily or hourly records, GMFD and ERA5-Land, became available. Starting with the US, a data rich region, we formally test whether these global data sets are as good as more fine-scaled country-specific data in explaining yields and whether they estimate similar response functions. While GMFD and ERA5-Land have lower predictive skill for US corn and soybeans yields than the fine-scaled PRISM data, they still correctly uncover the underlying non-linear temperature relationship. All specifications using daily temperature extremes under any of the weather data sets outperform models that use a quadratic in average temperature. Correctly capturing the effect of daily extremes has a larger effect than the choice of weather data. In a second step, focusing on Sub Saharan Africa, a data sparse region, we confirm that GMFD and ERA5-Land have superior predictive power to CRU, a global weather data set previously employed for modeling climate effects in the region.
Broadband near-infrared emission in silicon waveguides
Authors: Pruessner Marcel W. , Tyndall Nathan F. , Khurgin Jacob B. , Rabinovich William S. , Goetz Peter G. , Stievater Todd H. 
Published: May 2024

AbstractSilicon photonic integrated circuit foundries enable wafer-level fabrication of entire electro-optic systems-on-a-chip for applications ranging from datacommunication to lidar to chemical sensing. However, silicon’s indirect bandgap has so far prevented its use as an on-chip optical source for these systems. Here, we describe a fullyintegrated broadband silicon waveguide light source fabricated in a state-of-the-art 300-mm foundry. A reverse-biased p-i-n diode in a silicon waveguide emits broadband near-infrared optical radiation directly into the waveguide mode, resulting in nanowatts of guided optical power from a few milliamps of electrical current. We develop a one-dimensional Planck radiation model for intraband emission from hot carriers to theoretically describe the emission. The brightness of this radiation is demonstrated by using it for broadband characterization of photonic components including Mach-Zehnder interferometers and lattice filters, and for waveguide infrared absorption spectroscopy of liquid-phase analytes. This broadband silicon-based source can be directly integrated with waveguides and photodetectors with no change to existing foundry processes and is expected to find immediate application in optical systems-on-a-chip for metrology, spectroscopy, and sensing.
Why •CF2H is nucleophilic but •CF3 is electrophilic in reactions with heterocycles
Authors: Duan Meng , Shao Qianzhen , Zhou Qingyang , Baran Phil S. , Houk K. N. 
Published: May 2024

AbstractRadical substitution is a useful method to functionalize heterocycles, as in the venerable Minisci reaction. Empirically observed regiochemistries indicate that the CF2H radical has a nucleophilic character similar to alkyl radicals, but the CF3 radical is electrophilic. While the difference between •CH3 and •CF3 is well understood, the reason that one and two Fs make little difference but the third has a large effect is puzzling. DFT calculations with M06-2X both reproduce experimental selectivities and also lead to an explanation of this difference. Theoretical methods reveal how the F inductive withdrawal and conjugative donation alter radical properties, but only CF3 becomes decidedly electrophilic toward heterocycles. Here, we show a simple model to explain the radical orbital energy trends and resulting nucleophilicity or electrophilicity of fluorinated radicals.
Nanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles
Authors: Andronov Leonid , Han Mengting , Zhu Yanyu , Balaji Ashwin , Roy Anish R. , Barentine Andrew E. S. , Patel Puja , Garhyan Jaishree , Qi Lei S. , Moerner W. E. 
Published: May 2024

AbstractThe SARS-CoV-2 viral infection transforms host cells and produces special organelles in many ways, and we focus on the replication organelles, the sites of replication of viral genomic RNA (vgRNA). To date, the precise cellular localization of key RNA molecules and replication intermediates has been elusive in electron microscopy studies. We use super-resolution fluorescence microscopy and specific labeling to reveal the nanoscopic organization of replication organelles that contain numerous vgRNA molecules along with the replication enzymes and clusters of viral double-stranded RNA (dsRNA). We show that the replication organelles are organized differently at early and late stages of infection. Surprisingly, vgRNA accumulates into distinct globular clusters in the cytoplasmic perinuclear region, which grow and accommodate more vgRNA molecules as infection time increases. The localization of endoplasmic reticulum (ER) markers and nsp3 (a component of the double-membrane vesicle, DMV) at the periphery of the vgRNA clusters suggests that replication organelles are encapsulated into DMVs, which have membranes derived from the host ER. These organelles merge into larger vesicle packets as infection advances. Precise co-imaging of the nanoscale cellular organization of vgRNA, dsRNA, and viral proteins in replication organelles of SARS-CoV-2 may inform therapeutic approaches that target viral replication and associated processes.
Atomically dispersed MoNi alloy catalyst for partial oxidation of methane
Authors: Ding Zheyuan , Chen Sai , Yang Tingting , Sheng Zunrong , Zhang Xianhua , Pei Chunlei , Fu Donglong , Zhao Zhi-Jian , Gong Jinlong 
Published: May 2024

AbstractThe catalytic partial oxidation of methane (POM) presents a promising technology for synthesizing syngas. However, it faces severe over-oxidation over catalyst surface. Attempts to modify metal surfaces by incorporating a secondary metal towards C–H bond activation of CH4 with moderate O* adsorption have remained the subject of intense research yet challenging. Herein, we report that high catalytic performance for POM can be achieved by the regulation of O* occupation in the atomically dispersed (AD) MoNi alloy, with over 95% CH4 conversion and 97% syngas selectivity at 800 °C. The combination of ex-situ/in-situ characterizations, kinetic analysis and DFT (density functional theory) calculations reveal that Mo-Ni dual sites in AD MoNi alloy afford the declined O2 poisoning on Ni sites with rarely weaken CH4 activation for partial oxidation pathway following the combustion reforming reaction (CRR) mechanism. These results underscore the effectiveness of CH4 turnovers by the design of atomically dispersed alloys with tunable O* adsorption.