bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Energy Conserving Vlasov Solver That Tolerates Coarse Velocity Space Resolutions: Simulation of MMS Reconnection Events
Authors: Allmann‐Rahn F. , Lautenbach S. , Grauer R. 
Published: February 2022

AbstractVlasov solvers that operate on a phase‐space grid are highly accurate but also numerically demanding. Coarse velocity space resolutions, which are largely unproblematic in particle‐in‐cell (PIC) simulations, can lead to numerical heating or oscillations in continuum Vlasov methods. To address this issue, we present a new dual Vlasov solver which is based on an established positivity preserving advection scheme for the update of the distribution function and an energy conserving partial differential equation solver for the kinetic update of mean velocity and temperature. The solvers work together via moment fitting during which the maximum entropy part of the distribution function is replaced by the solution from the partial differential equation solver. This numerical scheme makes continuum Vlasov methods competitive with PIC methods concerning computational cost and enables us to model large scale reconnection in Earth's magnetosphere with a fully kinetic continuum method. The simulation results agree well with measurements by the MMS spacecraft.
Structure and Variability of the Kuroshio and Luzon Undercurrent Observed by a Mooring Array
Authors: Ma Jie , Hu Shijian , Hu Dunxin , Villanoy Cesar , Wang Qingye , Lu Xi , Yuan Xin 
Published: February 2022

AbstractThe spatial structure and variability of the western boundary currents east of Luzon Island at 18°N are investigated using measurements collected by acoustic Doppler current profilers (ADCPs) from three moorings between January 2018 and May 2020. During the observation period, the southward velocity of Luzon Undercurrent (LUC) has a maximum greater than 0.04 m at about 800 m on average and instantaneously reaches a maximum speed of about 0.47 m . Observations indicate that the LUC and Kuroshio have significant intraseasonal variability and the LUC is reversed occasionally. We find that the strong upper‐layer anticyclonic eddy plays a key role in the weakening and reversal of LUC and that the LUC is a permanent mean undercurrent. A vertical mode decomposition analysis is employed and results show that the first two baroclinic modes explain the main vertical features of the LUC and Kuroshio at its origin. No reversal of the southward undercurrent occurs in the second baroclinic mode velocity. We conclude that the LUC variability is generally a result of the second baroclinic mode but the observed reversal of the LUC is mainly caused by the first mode.
The Short‐Time Prediction of the Energetic Electron Flux in the Planetary Radiation Belt Based on Stacking Ensemble‐Learning Algorithm
Authors: Tang Rongxin , Tao Yuhao , Li Jiahao , Chen Zhou , Deng Xiaohua , Li Haimeng 
Published: February 2022

AbstractHigh energy electrons in planetary radiation belts are a major threat to satellites and communications in deep space applications. In order to predict the variations of energetic electron fluxes for different energy channels, we proposed a new ensemble machine leaning model for differential electron flux from 30 keV to 4 MeV in the Earth's radiation belts based on the RBSP‐A observation data from March 2013 to December 2017. The deep neural network (DNN), the convolutional neural network (CNN), the combination of CNN and DNN (CNN&DNN), the linear regression (LR), and the light gradient boosting machine (LightGBM) are among the machine learning models chosen. We carefully compared the electron flux predictions for 20 energy levels and all five models can present valid short‐time flux forecasts. The DNN model has the poorest result. The LR model is good for short‐term forecasting but not so good for long‐term forecasting. The LightGBM ensemble model is highly stable, and it has always outperformed other independent models in terms of forecast accuracy. Then the comparison by adding AE and SYM‐H indexes is given and the influence of geomagnetic activity conditions can be negligible for this short‐time prediction. Furthermore, we applied these five models on Saturn and finally got very similar prediction results. Our results will be significantly useful in instrument designs and system control of future scientific satellites in deep space explorations.
It Takes a Village to Run a Model—The Social Practices of Hydrological Modeling
Authors: Melsen L. A. 
Published: February 2022

AbstractComputer models are frequently used tools in hydrological research. Many decisions related to the model set‐up and configuration have to be made before a model can be run, influencing the model results. This study is an empirical investigation of the motivations for certain modeling decisions. Fourteen modelers from three different institutes were interviewed about their modeling decisions. In total, 83 different motivations were identified. Most motivations were related to the team of the modeler and the modelers themselves, “Experience from colleagues” was the most frequently mentioned motivation. Both institutionalization and internalization were observed: a modeler can introduce a concept that subsequently becomes the teams' standard, or a modeler can internalize the default team approach. These processes depend on the experience of the modeler. For model selection, two types of motivations were identified: experience (from colleagues or the modelers themselves), and model vision (the model has assets that align with the modeling vision). Model studies are mainly driven by context, such as time constraints, colleagues, and facilities at the institute, rather than epistemic (such as aligning with the modeling vision). The role of local context in the construction of and the value assigned to models shows that models are social constructs, making model results time, and place dependent. To account for this context in the estimation of the robustness of model results, we need a diversity of opinions, perspectives, and approaches. This requires transparent modeling procedures and an explicit modeling vision for each model study.
The BCL-2 family member BOK promotes KRAS-driven lung cancer progression in a p53-dependent manner
Authors: Meinhardt Anna-Lena , Munkhbaatar Enkhtsetseg , Höckendorf Ulrike , Dietzen Michelle , Dechant Marta , Anton Martina , Jacob Anne , Steiger Katja , Weichert Wilko , Brcic Luka , McGranahan Nicholas , Branca Caterina , Kaufmann Thomas , Dengler Michael A. , Jost Philipp J. 
Published: February 2022

AbstractA variety of cancer entities are driven by KRAS mutations, which remain difficult to target clinically. Survival pathways, such as resistance to cell death, may represent a promising treatment approach in KRAS mutated cancers. Based on the frequently observed genomic deletions of BCL-2-related ovarian killer (BOK) in cancer patients, we explored the function of BOK in a mutant KrasG12D-driven murine model of lung cancer. Using KrasG12D/+Bok−/− mice, we observed an overall tumor-promoting function of BOK in vivo. Specifically, loss of BOK reduced proliferation both in cell lines in vitro as well as in KrasG12D-driven tumor lesions in vivo. During tumor development in vivo, loss of BOK resulted in a lower tumor burden, with fewer, smaller, and less advanced tumors. Using KrasG12D/+Tp53Δ/ΔBok−/− mice, we identified that this phenotype was entirely dependent on the presence of functional p53. Furthermore, analysis of a human dataset of untreated early-stage lung tumors did not identify any common deletion of the BOK locus, independently of the TP53 status or the histopathological classification. Taken together our data indicate that BOK supports tumor progression in Kras-driven lung cancer.
Brain microRNAs are associated with variation in cognitive trajectory in advanced age
Authors: Wingo Aliza P. , Wang Mengli , Liu Jiaqi , Breen Michael S. , Yang Hyun-Sik , Tang Beisha , Schneider Julie A. , Seyfried Nicholas T. , Lah James J. , Levey Allan I. , Bennett David A. , Jin Peng , De Jager Philip L. , Wingo Thomas S. 
Published: February 2022

AbstractIn advancing age, some individuals maintain a stable cognitive performance over time, while others experience a rapid decline. Such variation in cognitive trajectory is only partially explained by common neurodegenerative pathologies. Hence, we aimed to identify new molecular processes underlying variation in cognitive trajectory using brain microRNA profile followed by an integrative analysis with brain transcriptome and proteome. Individual cognitive trajectories were derived from longitudinally assessed cognitive-test scores of older-adult brain donors from four longitudinal cohorts. Postmortem brain microRNA profiles, transcriptomes, and proteomes were derived from the dorsolateral prefrontal cortex. The global microRNA association study of cognitive trajectory was performed in a discovery (n = 454) and replication cohort (n = 134), followed by a meta-analysis that identified 6 microRNAs. Among these, miR-132-3p and miR-29a-3p were most significantly associated with cognitive trajectory. They explain 18.2% and 2.0% of the variance of cognitive trajectory, respectively, and act independently of the eight measured neurodegenerative pathologies. Furthermore, integrative transcriptomic and proteomic analyses revealed that miR-132-3p was significantly associated with 24 of the 47 modules of co-expressed genes of the transcriptome, miR-29a-3p with 3 modules, and identified 84 and 214 downstream targets of miR-132-3p and miR-29a-3p, respectively, in cognitive trajectory. This is the first global microRNA study of cognitive trajectory to our knowledge. We identified miR-29a-3p and miR-132-3p as novel and robust contributors to cognitive trajectory independently of the eight known cerebral pathologies. Our findings lay a foundation for future studies investigating mechanisms and developing interventions to enhance cognitive stability in advanced age.
The osteoprotective role of USP26 in coordinating bone formation and resorption
Authors: Li Changwei , Qiu Minglong , Chang Leilei , Qi Jin , Zhang Lianfang , Ryffel Bernhard , Deng Lianfu 
Published: February 2022

AbstractBone homeostasis is maintained through a balance of bone formation by osteoblasts and bone resorption by osteoclasts. Ubiquitin-specific proteases (USPs) are involved in regulating bone metabolism by preserving bone formation or antagonizing bone resorption. However, the specific USPs that maintain bone homeostasis by orchestrating bone formation and bone resorption simultaneously are poorly understood. Here, we identified USP26 as a previously unknown regulator of bone homeostasis that coordinates bone formation and resorption. Mechanistically, USP26 stabilizes β-catenin to promote the osteogenic activity of mesenchymal cells (MSCs) and impairs the osteoclastic differentiation of bone myelomonocytes (BMMs) by stabilizing inhibitors of NF-κBα (IκBα). Gain-of-function experiments revealed thatUsp26supplementation significantly increased bone regeneration in bone defects in aged mice and decreased bone loss resulting from ovariectomy. Taken together, these data show the osteoprotective effect of USP26 via the coordination of bone formation and resorption, suggesting that USP26 represents a potential therapeutic target for osteoporosis.
First use of gene therapy to treat growth hormone resistant dwarfism in a mouse model
Authors: Sia Kian Chuan , Gan Shu Uin , Mohd Rodhi Siti Humairah , Fu Zhen Ying , Kopchick John J. , Waters Michael J. , Lee Kok Onn 
Published: February 2022

AbstractThe only treatment tested for growth hormone receptor (GHR) defective Laron Syndrome (LS) is injections of recombinant insulin-like-growth factor 1 (rhIGF1). The response is suboptimal and associated with progressive obesity. In this study, we treated 4–5-week-old Laron dwarf mice (GHR−/−) with an adeno-associated virus expressing murine GHR (AAV-GHR) injection at a dose of 4 × 1010 vector genome per mouse. Serum growth hormone (GH) levels decreased, and GH-responsive IGF1, IGF binding protein 3 (IGFBP3) and acid labile subunit (ALS) increased. There was a significant but limited increase in body weight and length, similar to the response to rhIGF1 treatment in LS patients. All the major organs increased in weight except the brain. Our study is the first to use gene therapy to treat GH-receptor deficiency. We propose that gene therapy with AAV-GHR may eventually be useful for the treatment of human LS.
Chiral and degenerate perfect absorption on exceptional surfaces
Authors: Soleymani S. , Zhong Q. , Mokim M. , Rotter S. , El-Ganainy R. , Özdemir Ş. K. 
Published: February 2022

AbstractEngineering light-matter interactions using non-Hermiticity, particularly through spectral degeneracies known as exceptional points (EPs), is an emerging field with potential applications in areas such as cavity quantum electrodynamics, spectral filtering, sensing, and thermal imaging. However, tuning and stabilizing a system to a discrete EP in parameter space is a challenging task. Here, we circumvent this challenge by operating a waveguide-coupled resonator on a surface of EPs, known as an exceptional surface (ES). We achieve this by terminating only one end of the waveguide with a tuneable symmetric reflector to induce a nonreciprocal coupling between the frequency-degenerate clockwise and counterclockwise resonator modes. By operating the system at critical coupling on the ES, we demonstrate chiral and degenerate perfect absorption with squared-Lorentzian lineshape. We expect our approach to be useful for studying quantum processes at EPs and to serve as a bridge between non-Hermitian physics and other fields that rely on radiation engineering.
Perfect flat band with chirality and charge ordering out of strong spin-orbit interaction
Authors: Nakai Hiroki , Hotta Chisa 
Published: February 2022

AbstractSpin-orbit interaction has established itself as a key player in the emergent phenomena in modern condensed matter, including topological insulator, spin liquid and spin-dependent transports. However, its function is rather limited to adding topological nature to band kinetics, leaving behind the growing interest in the direct interplay with electron correlation. Here, we prove by our spinor line graph theory that a very strong spin-orbit interaction realized in 5d pyrochlore electronic systems generates multiply degenerate perfect flat bands. Unlike any of the previous flat bands, the electrons in this band localize in real space by destructively interfering with each other in a spin selective manner governed by the SU(2) gauge field. These electrons avoid the Coulomb interaction by self-organizing their localized wave functions, which may lead to a flat-band state with a stiff spin chirality. It also causes perfectly trimerized charge ordering, which may explain the recently discovered exotic low-temperature insulating phase of CsW2O6.
Electron transfer-triggered imaging of EGFR signaling activity
Authors: Tan Jie , Li Hao , Ji Cailing , Zhang Lei , Zhao Chenxuan , Tang Liming , Zhang Caixin , Sun Zhijun , Tan Weihong , Yuan Quan 
Published: February 2022

AbstractIn vivo electron transfer processes are closely related to the activation of signaling pathways, and, thus, affect various life processes. Indeed, the signaling pathway activation of key molecules may be associated with certain diseases. For example, epidermal growth factor receptor (EGFR) activation is related to the occurrence and development of tumors. Hence, monitoring the activation of EGFR-related signaling pathways can help reveal the progression of tumor development. However, it is challenging for current detection methods to monitor the activation of specific signaling pathways in complex biochemical reactions. Here we designed a highly sensitive and specific nanoprobe that enables in vivo imaging of electronic transfer over a broad range of spatial and temporal scales. By using the ferrocene-DNA polymer “wire”, the electrons transferred in a biochemical reaction can flow to persistent luminescent nanoparticles and change their electron distribution, thereby altering the optical signal of the particles. This electron transfer-triggered imaging probe enables mapping the activation of EGFR-related signaling pathways in a temporally and spatially precise manner. By offering precise visualization of signaling activity, this approach may offer a general platform not only for understanding molecular mechanisms in various biological processes but also for promoting disease therapies and drug evaluation.
Impacts of rapid mass vaccination against SARS-CoV2 in an early variant of concern hotspot
Authors: Paetzold Jörg , Kimpel Janine , Bates Katie , Hummer Michael , Krammer Florian , von Laer Dorothee , Winner Hannes 
Published: February 2022

AbstractWe study the real-life effect of an unprecedented rapid mass vaccination campaign. Following a large outbreak of the Beta variant in the district of Schwaz/Austria, 100,000 doses of BNT162b2 (Pfizer/BioNTech) were procured to mass vaccinate the entire adult population of the district between the 11th and 16th of March 2021. This made the district the first widely inoculated region in Europe. We examine the effect of this campaign on the number of infections, cases of variants of concern, hospital and ICU admissions. We compare Schwaz with (i) a control group of highly similar districts, and (ii) with populations residing in municipalities along the border of Schwaz which were just excluded from the campaign. We find large and significant decreases for all outcomes after the campaign. Our results suggest that rapid mass vaccination is an effective tool to curb the spread of SARS-CoV-2.
Adaptation to genome decay in the structure of the smallest eukaryotic ribosome
Authors: Nicholson David , Salamina Marco , Panek Johan , Helena-Bueno Karla , Brown Charlotte R. , Hirt Robert P. , Ranson Neil A. , Melnikov Sergey V. 
Published: February 2022

AbstractThe evolution of microbial parasites involves the counterplay between natural selection forcing parasites to improve and genetic drifts forcing parasites to lose genes and accumulate deleterious mutations. Here, to understand how this counterplay occurs at the scale of individual macromolecules, we describe cryo-EM structure of ribosomes from Encephalitozoon cuniculi, a eukaryote with one of the smallest genomes in nature. The extreme rRNA reduction in E. cuniculi ribosomes is accompanied with unparalleled structural changes, such as the evolution of previously unknown molten rRNA linkers and bulgeless rRNA. Furthermore, E. cuniculi ribosomes withstand the loss of rRNA and protein segments by evolving an ability to use small molecules as structural mimics of degenerated rRNA and protein segments. Overall, we show that the molecular structures long viewed as reduced, degenerated, and suffering from debilitating mutations possess an array of compensatory mechanisms that allow them to remain active despite the extreme molecular reduction.
Role of ACSL4 in the chemical-induced cell death in human proximal tubule epithelial HK-2 cells
Authors: Kuwata Hiroshi , Tomitsuka Yuki , Yoda Emiko , Hara Shuntaro 
Published: February 2022

Abstract
Acyl-CoA synthetase long-chain family member 4 (ACSL4) activates polyunsaturated fatty acids (PUFAs) to produce PUFA-derived acyl-CoAs, which are utilised for the synthesis of various biological components, including phospholipids (PLs). Although the roles of ACSL4 in non-apoptotic programmed cell death ferroptosis are well-characterised, its role in the other types of cell death is not fully understood. In the present study, we investigated the effects of ACSL4 knockdown on the levels of acyl-CoA, PL, and ferroptosis in the human normal kidney proximal tubule epithelial (HK-2) cells. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) analyses revealed that the knockdown of ACSL4 markedly reduced the levels of PUFA-derived acyl-CoA, but not those of other acyl-CoAs. In contrast with acyl-CoA levels, the docosahexaenoic acid (DHA)-containing PL levels were preferentially decreased in the ACSL4-knockdown cells compared with the control cells. Cell death induced by the ferroptosis inducers RSL3 and FIN56 was significantly suppressed by treatment with ferrostatin-1 or ACSL4 knockdown, and, unexpectedly, upon treating with a necroptosis inhibitor. In contrast, ACSL4 knockdown failed to suppress the other oxidative stress-induced cell deaths initiated by cadmium chloride and sodium arsenite. In conclusion, ACSL4 is involved in the biosynthesis of DHA-containing PLs in HK-2 cells and is specifically involved in the cell death induced by ferroptosis inducers.
The Adaptation of Developmental Sentence Scoring and Index of Productive Syntax to Turkish
Authors: Saban-Dülger Nur Seda , Turan Figen , Özcebe Esra 
Published: February 2022

Purpose:
Language sampling analysis (LSA) plays an important role in evaluating language skills; hence, the study aimed to develop new assessment measures for the LSA in Turkish as alternatives to mean length of utterance (MLU) and the Language Assessment, Remediation and Screening Procedure. With this aim, Developmental Sentence Scoring (DSS) and the Index of Productive Syntax (IPSyn) were adapted to Turkish.

Method:
Eighty monolingual Turkish children were included in the study, and the age range was from 2;0 to 5;11 (years;months). The children were grouped with 6-month intervals, and each group had an equal number of participants in terms of gender. Their general and language development were tested with standardized tests, and language sampling was recorded during play with farm toys for 15–20 min. Reviewing literature and observing participants' production schemas were created for DSS for Turkish (DSS-TR) and the IPSyn for Turkish (IPSyn-TR) separately, and final versions were determined in consultation with experts.

Results:

DSS-TR and IPSyn-TR were significantly correlated with standardized tests, and MLU values were statistically significant (
p
< .05). Total scores increased with age; however, grammatical categories did not go up. No difference was observed between genders (
p
> .05). In DSS-TR, the “sentence point” did not affect the participants' total scores because of language characteristics (
p
> .05). Finally, DSS-TR and IPSyn-TR were seen to be correlated with each other (
p
< .05).

Conclusions:
DSS-TR and IPSyn-TR are valid, being correlated with other assessment tools, and reliable, showing a high correlation with other raters, to reflect morphosyntactic skills. Therefore, they both are alternative assessment measures that will be used in LSA and give an opportunity to clinicians to plan their intervention goals. Also, they enable clinicians to observe progress not only specific to grammatical category but also in the total scores of the children either during or at the end of the therapy.