bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Time‐Dependent Two‐Dimensional Model Simulation of Lower Ionospheric Variations Under Intense SAID
Authors: Liang Jun , St‐Maurice J. P. , Donovan E. 
Published: December 2021

AbstractThe subauroral ion drift (SAID) denotes a latitudinally narrow channel of fast westward ion drift in the subauroral region, often observed during geomagnetically disturbed intervals. The recently recognized subauroral optical phenomena, the Strong Thermal Emission Velocity Enhancement (STEVE) and the Picket Fence, are both related to intense SAIDs. In this study, we present a 2D time‐dependent model simulation of the self‐consistent variations of the electron/ion temperature, density, and FAC, under strong SAID, with more focus in the lower ionosphere. The anomalous electron heating in the E‐region is evaluated using an empirical model. Our simulation reproduces many key features of SAID, such as the strong electron temperature enhancement in the upper F‐region, the intense ion frictional heating, and the plasma density depletion. Most importantly, the ion Pedersen drifts is found to play a crucial role in the density variations and FAC dynamics in the lower ionosphere. The transport effect of ion Pedersen drifts leads to strong density depletion in the lower ionosphere in a large portion of SAID. The FAC inside SAID is mainly downward with magnitude ≤ ∼1 μA/m2. At the poleward edge of SAID, the ion Pedersen drift leads to a pileup of the plasma density and an upward FAC. Our simulation results also corroborate the presence of strong gradients of plasma density, temperature, and flows, at the edge of SAID, which may be conducive to certain plasma instabilities. Our model provides a useful tool for the future exploration of the generation mechanisms of STEVE and Picket Fence.
Monitoring Brine Leakage From Deep Geologic Formations Storing Carbon Dioxide: Design Framework Validation Using Intermediate‐Scale Experiment
Authors: Askar Ahmad H. , Illangasekare Tissa H. , Ilie Ana Maria Carmen 
Published: December 2021

AbstractMonitoring brine leakage from CO2 geological storages (CGS) is necessary to protect shallow aquifers against contamination. A framework for designing CGS monitoring systems that optimally use both easily available shallow zone data and hard‐to‐obtain deep zone observations is developed and validated. This framework is based on calibrating a transport model using monitoring data to determine leakage source conditions and then predict the subsequent brine plume that potentially contaminates shallow aquifers. As cost considerations are expected to limit monitoring deep formations, the framework is developed to minimize the number of deep observation points (e.g., deep sensors). The best monitoring locations that yield the most worthful data for reducing predictive uncertainty is selected by integrating linear uncertainty analysis with Genetic Algorithm under this framework. Due to practical challenges, testing such a framework in the field is not feasible. Thus, the framework was tested in an intermediate‐scale soil tank, where monitoring data on brine leakage plume development from the storage zone to the shallow aquifer were collected. Predictions made by a transport model calibrated on these data were then compared with experimental measurements to evaluate data informativity and thus validate the framework's applicability. The results demonstrate the framework ability to select the optimum monitoring locations for leakage detection and model calibration. It was also found that not only deep observations, but also shallow zone data are worthful to determine source conditions. Moreover, the results showed the possibility of identifying the likely areas to be impacted in the shallow aquifer using early stage monitoring data.
Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism
Authors: Lindholm Päivi , Saarma Mart 
Published: December 2021

AbstractMidbrain dopamine neurons deteriorate in Parkinson’s disease (PD) that is a progressive neurodegenerative movement disorder. No cure is available that would stop the dopaminergic decline or restore function of injured neurons in PD. Neurotrophic factors (NTFs), e.g., glial cell line-derived neurotrophic factor (GDNF) are small, secreted proteins that promote neuron survival during mammalian development and regulate adult neuronal plasticity, and they are studied as potential therapeutic agents for the treatment of neurodegenerative diseases. However, results from clinical trials of GDNF and related NTF neurturin (NRTN) in PD have been modest so far. In this review, we focus on cerebral dopamine neurotrophic factor (CDNF), an unconventional neurotrophic protein. CDNF delivered to the brain parenchyma protects and restores dopamine neurons in animal models of PD. In a recent Phase I-II clinical trial CDNF was found safe and well tolerated. CDNF deletion in mice led to age-dependent functional changes in the brain dopaminergic system and loss of enteric neurons resulting in slower gastrointestinal motility. These defects in Cdnf−/− mice intriguingly resemble deficiencies observed in early stage PD. Different from classical NTFs, CDNF can function both as an extracellular trophic factor and as an intracellular, endoplasmic reticulum (ER) luminal protein that protects neurons and other cell types against ER stress. Similarly to the homologous mesencephalic astrocyte-derived neurotrophic factor (MANF), CDNF is able to regulate ER stress-induced unfolded protein response (UPR) signaling and promote protein homeostasis in the ER. Since ER stress is thought to be one of the pathophysiological mechanisms contributing to the dopaminergic degeneration in PD, CDNF, and its small-molecule derivatives that are under development may provide useful tools for experimental medicine and future therapies for the treatment of PD and other neurodegenerative protein-misfolding diseases.
Infection of wild-type mice by SARS-CoV-2 B.1.351 variant indicates a possible novel cross-species transmission route
Authors: Pan Ting , Chen Ran , He Xin , Yuan Yaochang , Deng Xiaohui , Li Rong , Yan Haiping , Yan Shumei , Liu Jun , Zhang Yiwen , Zhang Xiantao , Yu Fei , Zhou Mo , Ke Changwen , Ma Xiancai , Zhang Hui 
Published: December 2021

AbstractCOVID-19 is identified as a zoonotic disease caused by SARS-CoV-2, which also can cross-transmit to many animals but not mice. Genetic modifications of SARS-CoV-2 or mice enable the mice susceptible to viral infection. Although neither is the natural situation, they are currently utilized to establish mouse infection models. Here we report a direct contact transmission of SARS-CoV-2 variant B.1.351 in wild-type mice. The SARS-CoV-2 (B.1.351) replicated efficiently and induced significant pathological changes in lungs and tracheas, accompanied by elevated proinflammatory cytokines in the lungs and sera. Mechanistically, the receptor-binding domain (RBD) of SARS-CoV-2 (B.1.351) spike protein turned to a high binding affinity to mouse angiotensin-converting enzyme 2 (mACE2), allowing the mice highly susceptible to SARS-CoV-2 (B.1.351) infection. Our work suggests that SARS-CoV-2 (B.1.351) expands the host range and therefore increases its transmission route without adapted mutation. As the wild house mice live with human populations quite closely, this possible transmission route could be potentially risky. In addition, because SARS-CoV-2 (B.1.351) is one of the major epidemic strains and the mACE2 in laboratory-used mice is naturally expressed and regulated, the SARS-CoV-2 (B.1.351)/mice could be a much convenient animal model system to study COVID-19 pathogenesis and evaluate antiviral inhibitors and vaccines.
Long noncoding RNA GSEC promotes neutrophil inflammatory activation by supporting PFKFB3-involved glycolytic metabolism in sepsis
Authors: Liu Dadong , Sun Wen , Zhang Danying , Yu Zongying , Qin Weiting , Liu Yishu , Zhang Kai , Yin Jiangtao 
Published: December 2021

AbstractMetabolic reprogramming is a hallmark of neutrophil activation in sepsis. LncRNAs play important roles in manipulating cell metabolism; however, their specific involvement in neutrophil activation in sepsis remains unclear. Here we found that 11 lncRNAs and 105 mRNAs were differentially expressed in three transcriptome datasets (GSE13904, GSE28750, and GSE64457) of gene expression in blood leukocytes and neutrophils of septic patients and healthy volunteers. After Gene Ontology biological process analysis and lncRNA–mRNA pathway network construction, we noticed that GSEC lncRNA and PFKFB3 were co-expressed and associated with enhanced glycolytic metabolism. Our clinical observations confirmed the expression patterns of GSEC lncRNA and PFKFB3 genes in neutrophils in septic patients. Performing in vitro experiments, we found that the expression of GSEC lncRNA and PFKFB3 was increased when neutrophils were treated with inflammatory stimuli. Knockdown and overexpression experiments showed that GSEC lncRNA was essential for mediating PFKFB3 mRNA expression and stability in neutrophil-like dHL-60 cells. In addition, we found that GSEC lncRNA-induced PFKFB3 expression was essential for mediating dHL-60 cell inflammatory cytokine expression. Performing mechanistic experiments, we found that glycolytic metabolism with PFKFB3 involvement supported inflammatory cytokine expression. In summary, our study uncovers a mechanism by which GSEC lncRNA promotes neutrophil inflammatory activation in sepsis by supporting glycolytic metabolism with PFKFB3.
Identification of mitochondrial RNA polymerase as a potential therapeutic target of osteosarcoma
Authors: Han Qi-cai , Zhang Xiang-yang , Yan Peng-hui , Chen Song-feng , Liu Fei-fei , Zhu Yun-Rong , Tian Qing 
Published: December 2021

AbstractPOLRMT (RNA polymerase mitochondrial) is essential for transcription of mitochondrial genome encoding components of oxidative phosphorylation process. The current study tested POLRMT expression and its potential function in osteosarcoma (OS). The Cancer Genome Atlas (TCGA) cohorts and Gene Expression Profiling Interactive Analysis (GEPIA) database both show that POLRMT transcripts are elevated in OS tissues. In addition, POLRMT mRNA and protein levels were upregulated in local OS tissues as well as in established and primary human OS cells. In different OS cells, shRNA-induced stable knockdown of POLRMT decreased cell viability, proliferation, migration, and invasion, whiling inducing apoptosis activation. CRISPR/Cas9-induced POLRMT knockout induced potent anti-OS cell activity as well. Conversely, in primary OS cells ectopic POLRMT overexpression accelerated cell proliferation and migration. In vivo, intratumoral injection of adeno-associated virus-packed POLRMT shRNA potently inhibited U2OS xenograft growth in nude mice. Importantly, levels of mitochondrial DNA, mitochondrial transcripts and expression of respiratory chain complex subunits were significantly decreased in U2OS xenografts with POLRMT shRNA virus injection. Together, POLRMT is overexpressed in human OS, promoting cell growth in vitro and in vivo. POLRMT could be a novel therapeutic target for OS.
A randomized study to evaluate safety and immunogenicity of the BNT162b2 COVID-19 vaccine in healthy Japanese adults
Authors: Haranaka Miwa , Baber James , Ogama Yoichiro , Yamaji Masako , Aizawa Masakazu , Kogawara Osamu , Scully Ingrid , Lagkadinou Eleni , Türeci Ӧzlem , Şahin Uğur , Dormitzer Philip R. , Gruber William C. , Lockhart Stephen 
Published: December 2021

AbstractWe report interim safety and immunogenicity findings from an ongoing phase 1/2 study of BNT162b2 in healthy Japanese adults. Participants were randomized 3:1 to receive 2 intramuscular injections of 30 μg BNT162b2 or placebo 21 days apart. Overall, 160 individuals were randomized: 119 received BNT162b2, and 41 received placebo. Participants were stratified by age: 20–64 years (n = 130) and 65–85 years (n = 30). More than 97% of BNT162b2 recipients received 2 doses. Local reactions and systemic events were generally transient and mild to moderate. Severe adverse events were uncommon; there were no serious adverse events. One month after dose 2, SARS-CoV-2 50% serum neutralizing geometric mean titers were 571 and 366, and geometric mean fold rises were 55.8 and 36.6, in the younger and older age groups, respectively. In summary, BNT162b2 has an acceptable safety profile and produces a robust immune response, regardless of age, in Japanese adults. (ClinicalTrials.gov, NCT04588480).
Increased labor losses and decreased adaptation potential in a warmer world
Authors: Parsons Luke A. , Shindell Drew , Tigchelaar Michelle , Zhang Yuqiang , Spector June T. 
Published: December 2021

AbstractWorking in hot and potentially humid conditions creates health and well-being risks that will increase as the planet warms. It has been proposed that workers could adapt to increasing temperatures by moving labor from midday to cooler hours. Here, we use reanalysis data to show that in the current climate approximately 30% of global heavy labor losses in the workday could be recovered by moving labor from the hottest hours of the day. However, we show that this particular workshift adaptation potential is lost at a rate of about 2% per degree of global warming as early morning heat exposure rises to unsafe levels for continuous work, with worker productivity losses accelerating under higher warming levels. These findings emphasize the importance of finding alternative adaptation mechanisms to keep workers safe, as well as the importance of limiting global warming.
Metabolic drug survey highlights cancer cell dependencies and vulnerabilities
Authors: Pemovska Tea , Bigenzahn Johannes W. , Srndic Ismet , Lercher Alexander , Bergthaler Andreas , César-Razquin Adrián , Kartnig Felix , Kornauth Christoph , Valent Peter , Staber Philipp B. , Superti-Furga Giulio 
Published: December 2021

AbstractInterrogation of cellular metabolism with high-throughput screening approaches can unravel contextual biology and identify cancer-specific metabolic vulnerabilities. To systematically study the consequences of distinct metabolic perturbations, we assemble a comprehensive metabolic drug library (CeMM Library of Metabolic Drugs; CLIMET) covering 243 compounds. We, next, characterize it phenotypically in a diverse panel of myeloid leukemia cell lines and primary patient cells. Analysis of the drug response profiles reveals that 77 drugs affect cell viability, with the top effective compounds targeting nucleic acid synthesis, oxidative stress, and the PI3K/mTOR pathway. Clustering of individual drug response profiles stratifies the cell lines into five functional groups, which link to specific molecular and metabolic features. Mechanistic characterization of selective responses to the PI3K inhibitor pictilisib, the fatty acid synthase inhibitor GSK2194069, and the SLC16A1 inhibitor AZD3965, bring forth biomarkers of drug response. Phenotypic screening using CLIMET represents a valuable tool to probe cellular metabolism and identify metabolic dependencies at large.
The effect of COVID-19 vaccination in Italy and perspectives for living with the virus
Authors: Marziano Valentina , Guzzetta Giorgio , Mammone Alessia , Riccardo Flavia , Poletti Piero , Trentini Filippo , Manica Mattia , Siddu Andrea , Bella Antonino , Stefanelli Paola , Pezzotti Patrizio , Ajelli Marco , Brusaferro Silvio , Rezza Giovanni , Merler Stefano 
Published: December 2021

AbstractCOVID-19 vaccination is allowing a progressive release of restrictions worldwide. Using a mathematical model, we assess the impact of vaccination in Italy since December 27, 2020 and evaluate prospects for societal reopening after emergence of the Delta variant. We estimate that by June 30, 2021, COVID-19 vaccination allowed the resumption of about half of pre-pandemic social contacts. In absence of vaccination, the same number of cases is obtained by resuming only about one third of pre-pandemic contacts, with about 12,100 (95% CI: 6,600-21,000) extra deaths (+27%; 95% CI: 15–47%). Vaccination offset the effect of the Delta variant in summer 2021. The future epidemic trend is surrounded by substantial uncertainty. Should a pediatric vaccine (for ages 5 and older) be licensed and a coverage >90% be achieved in all age classes, a return to pre-pandemic society could be envisioned. Increasing vaccination coverage will allow further reopening even in absence of a pediatric vaccine.
A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus
Authors: Bhatia Bharti , Meade-White Kimberly , Haddock Elaine , Feldmann Friederike , Marzi Andrea , Feldmann Heinz 
Published: December 2021

AbstractKyasanur Forest disease virus (KFDV) is a tick-borne flavivirus endemic in India known to cause severe hemorrhagic and encephalitic disease in humans. In recent years, KFDV has spread beyond its original endemic zone raising public health concerns. Currently, there is no treatment available for KFDV but a vaccine with limited efficacy is used in India. Here, we generated two new KFDV vaccine candidates based on the vesicular stomatitis virus (VSV) platform. We chose the VSV-Ebola virus (VSV-EBOV) vector either with the full-length or a truncated EBOV glycoprotein as the vehicle to express the precursor membrane (prM) and envelope (E) proteins of KFDV (VSV-KFDV). For efficacy testing, we established a mouse disease model by comparing KFDV infections in three immunocompetent mouse strains (BALB/c, C57Bl/6, and CD1). Both vaccine vectors provided promising protection against lethal KFDV challenge in the BALB/c model following prime-only prime-boost and immunizations. Only prime-boost immunization with VSV-KFDV expressing full-length EBOV GP resulted in uniform protection. Hyperimmune serum derived from prime-boost immunized mice protected naïve BALB/c mice from lethal KFDV challenge indicating the importance of antibodies for protection. The new VSV-KFDV vectors are promising vaccine candidates to combat an emerging, neglected public health problem in a densely populated part of the world.
Cytokine autoantibodies are stable throughout the haematopoietic stem cell transplantation course and are associated with distinct biomarker and blood cell profiles
Authors: von Stemann Jakob Hjorth , Gjærde Lars Klingen , Haastrup Eva Kannik , Minculescu Lia , Brooks Patrick Terrence , Sengeløv Henrik , Hansen Morten Bagge , Ostrowski Sisse Rye 
Published: December 2021

AbstractCytokine-specific autoantibodies (c-aAbs) represent an emerging field in endogenous immunodeficiencies, and the immunomodulatory potential of c-aAbs is now well documented. Here, we investigated the hypothesis that c-aAbs affects inflammatory, immunoregulatory and injury-related processes and hence the clinical outcome of haematopoietic stem cell transplantation (HSCT). C-aAbs against IL-1α, IL-6, IL-10, IFNα, IFNγ and GM-CSF were measured in 131 HSCT recipients before and after (days + 7, + 14, + 28) HSCT and tested for associations with 33 different plasma biomarkers, leukocyte subsets, platelets and clinical outcomes, including engraftment, GvHD and infections. We found that c-aAb levels were stable over the course of HSCT, including at high titres, with few individuals seeming to acquire high-titre levels of c-aAbs. Both patients with stable and those with acquired high-titre c-aAb levels displayed significant differences in biomarker concentrations and blood cell counts pre-HSCT and at day 28, and the trajectories of these variables varied over the course of HSCT. No clinical outcomes were associated with high-titre c-aAbs. In this first study of c-aAbs in HSCT patients, we demonstrated that high-titre levels of c-aAb may both persist and emerge in patients over the course of HSCT and may be associated with altered immune biomarkers and cell profiles.
Water stress intensified the relation of seed color with lignan content and seed yield components in flax (Linum usitatissimum L.)
Authors: Zare Sara , Mirlohi Aghafakhr , Saeidi Ghodratollah , Sabzalian Mohammad R. , Ataii Ehsan 
Published: December 2021

AbstractThis study aimed to investigate the effect of yellow and brown seed coat color of flax on lignan content, seed yield, and yield components under two contrasting environments of non-stress and water stress conditions. The water stress environment intensified the discrimination between the two seed color groups as the yellow seeded families had lower values for seed yield components under the water stress. Heritability and the genetic advance for seed yield were significantly higher in brown-seeded families than those of yellow-seeded ones at water stress conditions. Secoisolariciresinol diglucoside (SDG) as the chief lignan in flaxseed was more abundant in yellow-seeded families under the non-stress environment but under water stress conditions, it increased in brown seeded families and exceeded from yellow ones. Considering that the brown and yellow seed color families were full sibs and shared a similar genetic background but differed in seed color, it is concluded that a considerable interaction exists between the flax seed color and moisture stress concerning its effect on seed yield and yield components and also the seed SDG content. Brown-seeded genotypes are probably preferred for cultivation under water stress conditions for better exploitation of flax agronomic and nutritional potentials.
Analysis of light-wave nonstaticity in the coherent state
Authors: Choi Jeong Ryeol 
Published: December 2021

AbstractThe characteristics of nonstatic quantum light waves in the coherent state in a static environment is investigated. It is shown that the shape of the wave varies periodically as a manifestation of its peculiar properties of nonstaticity like the case of the Fock-state analysis for a nonstatic wave. A belly occurs in the graphic of wave evolution whenever the wave is maximally displaced in the quadrature space, whereas a node takes place every time the wave passes the equilibrium point during its oscillation. In this way, a belly and a node appear in turn successively. Whereas this change of wave profile is accompanied by the periodic variation of electric and magnetic energies, the total energy is conserved. The fluctuations of quadratures also vary in a regular manner according to the wave transformation in time. While the resultant time-varying uncertainty product is always larger than (or, at least, equal to) its quantum-mechanically allowed minimal value ($$\hbar /2$$

ħ
/
2

), it is smallest whenever the wave constitutes a belly or a node. The mechanism underlying the abnormal features of nonstatic light waves demonstrated here can be interpreted by the rotation of the squeezed-shape contour of the Wigner distribution function in phase space.