bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analytical Assessment of Kelvin‐Helmholtz Instability Growth at Ganymede's Upstream Magnetopause
Authors: Kaweeyanun N. , Masters A. , Jia X. 
Published: August 2021

AbstractGanymede is the only Solar System moon that generates a permanent magnetic field. Dynamics within the Ganymedean magnetosphere is thought to be driven by energy‐transfer interactions on its upstream magnetopause. Previously in Kaweeyanun et al. (2020), https://doi.org/10.1029/2019GL086228 we created a steady‐state analytical model of Ganymede's magnetopause and predicted global‐scale magnetic reconnection to occur frequently throughout the surface. This paper subsequently provides the first assessment of Kelvin‐Helmholtz (K‐H) instability growth on the magnetopause. Using the same analytical model, we find that linear K‐H waves are expected on both Ganymedean magnetopause flanks. Once formed, the waves propagate downstream at roughly half the speed of the external Jovian plasma flow. The Ganymedean K‐H instability growth is asymmetric between magnetopause flanks due to the finite Larmor radius effect arising from large gyroradii of Jovian plasma ions. A small but notable enhancement is expected on the sub‐Jovian flank according to the physical understanding of bulk plasma and local ion flows alongside comparisons to the well‐observed magnetopause of Mercury. Further evaluation shows that nonlinear K‐H vortices should be strongly suppressed by concurring global‐scale magnetic reconnection at Ganymede. Reconnection is therefore the dominant cross‐magnetopause energy‐transfer mechanism and driver of global‐scale plasma convection within Ganymede's magnetosphere.
A “Trap‐Release‐Amplify” Model of Chorus Waves
Authors: Tao Xin , Zonca Fulvio , Chen Liu 
Published: August 2021

AbstractWhistler mode chorus waves are quasi‐coherent electromagnetic emissions with frequency chirping. Various models have been proposed to understand the chirping mechanism, which is a long‐standing problem in space plasmas. Based on analysis of effective wave growth rate and electron phase space dynamics in a self‐consistent particle simulation, we propose a phenomenological model called the “Trap‐Release‐Amplify” (TaRA) model for chorus. In this model, phase space structures of correlated electrons are formed by nonlinear wave particle interactions, which mainly occur in the downstream of equator. When released from the wave packet in the upstream, these electrons lead to selective amplification of new emissions which satisfy the phase‐locking condition to maximize wave power transfer, resulting in frequency chirping. The phase‐locking condition at the release point gives a chirping rate that is, fully consistent with the one by Helliwell in case of a nonuniform background magnetic field. The nonlinear wave particle interaction part of the TaRA model results in a chirping rate that is, proportional to wave amplitude, a conclusion originally reached by Vomvoridis et al. Therefore, the TaRA model unifies two different results from seemingly unrelated studies. Furthermore, the TaRA model naturally explains fine structures of chorus waves, including subpackets and bandwidth, and their evolution through dynamics of phase‐trapped electrons. Finally, we suggest that this model could be applied to explain other related phenomena, including frequency chirping of chorus in a uniform background magnetic field and of electromagnetic ion cyclotron waves in the magnetosphere.
Cyclone‐Anticyclone Asymmetry of Eddy Detection on Gridded Altimetry Product in the Mediterranean Sea
Authors: Stegner A. , Le Vu B. , Dumas F. , Ghannami M. Ali , Nicolle A. , Durand C. , Faugere Y. 
Published: August 2021

AbstractWe perform an Observing System Simulation Experiment that simulates the satellite sampling and the mapping procedure on the sea surface of the high‐resolution model CROCO‐MED60v40, to investigate the reliability and the accuracy of the eddy detection. The main result of this study is a strong cyclone‐anticyclone asymmetry of the eddy detection on the altimetry products AVISO/CMEMS in the Mediterranean Sea. Large‐scale cyclones having a characteristic radius larger than the local deformation radius are much less reliable than large‐scale anticyclones. We estimate that less than 60% of these cyclones detected on gridded altimetry product are reliable, while more than 85% of mesoscale anticyclones are reliable. Besides, both the barycenter and the size of these mesoscale anticyclones are relatively accurate. This asymmetry comes from the difference of stability between cyclonic and anticyclonic eddies. Large mesoscale cyclones often split into smaller sub‐mesoscale structures having a rapid dynamical evolution. The numerical model CROCO‐MED60v40 shows that this complex dynamic is too fast and too small to be accurately captured by the gridded altimetry products. The spatio‐temporal interpolation smoothes out this sub‐mesoscale dynamics and tends to generate an excessive number of unrealistic mesoscale cyclones in comparison with the reference field. On the other hand, large mesoscale anticyclones, which are more robust and which evolve more slowly, can be accurately tracked by standard altimetry products. We also confirm that the AVISO/CMEMS products induce a bias on the eddy intensity. The azimuthal geostrophic velocities are always underestimated for large mesoscale anticyclones.
NDRG1 enhances the sensitivity of cetuximab by modulating EGFR trafficking in colorectal cancer
Authors: Yang Guang , Huang Ling , Jia Hongtao , Aikemu Batuer , Zhang Sen , Shao Yanfei , Hong Hiju , Yesseyeva Galiya , Wang Chenxing , Li Shuchun , Sun Jing , Zheng Minhua , Ma Junjun 
Published: August 2021

AbstractN-myc downstream-regulated gene 1 (NDRG1) is a key regulator that interacts with many classic tumor signaling pathways, including some molecules downstream of the epidermal growth factor receptor (EGFR). However, whether NDRG1 is involved in the mechanism of resistance to cetuximab (CTX), the first monoclonal antibody targeting the EGFR has not been reported. Here, we found that NDRG1 enhanced the sensitivity of CTX in colorectal cancer (CRC) cell lines. Afterwards, we determined the underlying mechanism of this phenomenon. We demonstrated that NDRG1 inhibited the expression of EGFR; blocked EGFR phosphorylation and reduced the EGFR distribution in the cell membrane, cytoplasm and nucleus. And then, NDRG1 suppressed the EGFR downstream signaling: RAS/RAF/ERK and PI3k/AKT/mTOR pathways. Moreover, we discovered that NDRG1 attenuated the endocytosis and degradation of EGFR induced by caveolin-1 (Cav1). Additionally, our findings were further observed in an animal model and human tissues. Our results represent a potentially significant discovery that explains the mechanisms of NDRG1 in CTX resistance. NDRG1 could be a promising biomarker to predict optimum responses to CTX, and a key target to enhance CTX activity in the treatment of metastatic CRC (mCRC).
Toll-like receptor 4 is a master regulator for colorectal cancer growth under high-fat diet by programming cancer metabolism
Authors: Hu Xianjing , Fatima Sarwat , Chen Minting , Xu Keyang , Huang Chunhua , Gong Rui-Hong , Su Tao , Wong Hoi Leong Xavier , Bian Zhaoxiang , Kwan Hiu Yee 
Published: August 2021

AbstractAlthough high-fat diet (HFD) has been implicated in the development of colorectal cancer (CRC), the critical signaling molecule that mediates the cancer growth is not well-defined. Identifying the master regulator that controls CRC growth under HFD can facilitate the development of effective therapeutics for the cancer treatment. In this study, the global lipidomics and RNA sequencing data show that, in the tumor tissues of CRC-bearing mouse models, HFD not only increases tumor weight, but also the palmitic acid level and TLR4 expression, which are reduced when HFD is replaced by control diet. These concomitant changes suggest the roles of palmitic acid and TLR4 in CRC growth. Subsequent studies show that palmitic acid regulates TLR4 expression in PU.1-dependent manner. Knockdown of PU.1 or mutations of PU.1-binding site on TLR4 promoter abolish the palmitic acid-increased TLR4 expression. The role of palmitic acid/PU.1/TLR4 axis in CRC growth is further examined in cell model and animal models that are fed either HFD or palmitic acid-rich diet. More importantly, iTRAQ proteomics data show that knockdown of TLR4 changes the metabolic enzyme profiles in the tumor tissues, which completely abolish the HFD-enhanced ATP production and cancer growth. Our data clearly demonstrate that TLR4 is a master regulator for CRC growth under HFD by programming cancer metabolism.
Potent prophylactic and therapeutic efficacy of recombinant human ACE2-Fc against SARS-CoV-2 infection in vivo
Authors: Zhang Zhaoyong , Zeng Eric , Zhang Lu , Wang Weiming , Jin Yingkang , Sun Jiye , Huang Shuxiang , Yin Wenguang , Dai Jun , Zhuang Zhen , Chen Zhao , Sun Jing , Zhu Airu , Li Fang , Cao Weitao , Li Xiaobo , Shi Yongxia , Gan Mian , Zhang Shengnan , Wei Peilan , Huang Jicheng , Zhong Nanshan , Zhong Guocai , Zhao Jingxian , Wang Yanqun , Shao Weihui , Zhao Jincun 
Published: August 2021

AbstractThe current COVID-19 pandemic, caused by SARS-CoV-2, poses a serious public health threat. Effective therapeutic and prophylactic treatments are urgently needed. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, which binds to the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Here, we developed recombinant human ACE2-Fc fusion protein (hACE2-Fc) and a hACE2-Fc mutant with reduced catalytic activity. hACE2-Fc and the hACE2-Fc mutant both efficiently blocked entry of SARS-CoV-2, SARS-CoV, and HCoV-NL63 into hACE2-expressing cells and inhibited SARS-CoV-2 S protein-mediated cell–cell fusion. hACE2-Fc also neutralized various SARS-CoV-2 strains with enhanced infectivity including D614G and V367F mutations, as well as the emerging SARS-CoV-2 variants, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.1 (Kappa), and B.1.617.2 (Delta), demonstrating its potent and broad-spectrum antiviral effects. In addition, hACE2-Fc proteins protected HBE from SARS-CoV-2 infection. Unlike RBD-targeting neutralizing antibodies, hACE2-Fc treatment did not induce the development of escape mutants. Furthermore, both prophylactic and therapeutic hACE2-Fc treatments effectively protected mice from SARS-CoV-2 infection, as determined by reduced viral replication, weight loss, histological changes, and inflammation in the lungs. The protection provided by hACE2 showed obvious dose-dependent efficacy in vivo. Pharmacokinetic data indicated that hACE2-Fc has a relative long half-life in vivo compared to soluble ACE2, which makes it an excellent candidate for prophylaxis and therapy for COVID-19 as well as for SARS-CoV and HCoV-NL63 infections.
IFNγ signaling integrity in colorectal cancer immunity and immunotherapy
Authors: Du Wan , Frankel Timothy L. , Green Michael , Zou Weiping 
Published: August 2021

AbstractThe majority of colorectal cancer patients are not responsive to immune checkpoint blockade (ICB). The interferon gamma (IFNγ) signaling pathway drives spontaneous and ICB-induced antitumor immunity. In this review, we summarize recent advances in the epigenetic, genetic, and functional integrity of the IFNγ signaling pathway in the colorectal cancer microenvironment and its immunological relevance in the therapeutic efficacy of and resistance to ICB. Moreover, we discuss how to target IFNγ signaling to inform novel clinical trials to treat patients with colorectal cancer.
A novel frameshift pathogenic variant in ST3GAL5 causing salt and pepper developmental regression syndrome (SPDRS): A case report
Authors: Manoochehri Jamal , Dastgheib Seyed Alireza , Khamirani Hossein Jafari , Mollaie Maryam , Sharifi Zahra , Zoghi Sina , Tabei Seyed Mohammad Bagher , Mohammadi Sanaz , Dehghanian Fatemeh , Farbod Zahra , Dianatpour Mehdi 
Published: August 2021

AbstractGM3 synthase deficiency is associated with salt and pepper developmental regression syndrome (SPDRS), a rare genetic disorder. Herein, we report the first Iranian patient with SPDRS. We detected a novel pathogenic variant of ST3GAL5 (NM_003896.4: c.1030_1031del, p.Ile344Cysfs*11). The proband had intellectual disability (ID), failure to thrive, cerebral atrophy, microcephaly, and atonic seizures. The main future challenge proceeding from the results of this study is the prenatal detection of the newly discovered variant; the next step would involve further studies to elucidate the phenotypic spectrum of SPDRS and detect new variants that could cause symptoms ranging from mild to severe.
Engineering Na+-layer spacings to stabilize Mn-based layered cathodes for sodium-ion batteries
Authors: Zuo Wenhua , Liu Xiangsi , Qiu Jimin , Zhang Dexin , Xiao Zhumei , Xie Jisheng , Ren Fucheng , Wang Jinming , Li Yixiao , Ortiz Gregorio F. , Wen Wen , Wu Shunqing , Wang Ming-Sheng , Fu Riqiang , Yang Yong 
Published: August 2021

AbstractLayered transition metal oxides are the most important cathode materials for Li/Na/K ion batteries. Suppressing undesirable phase transformations during charge-discharge processes is a critical and fundamental challenge towards the rational design of high-performance layered oxide cathodes. Here we report a shale-like NaxMnO2 (S-NMO) electrode that is derived from a simple but effective water-mediated strategy. This strategy expands the Na+ layer spacings of P2-type Na0.67MnO2 and transforms the particles into accordion-like morphology. Therefore, the S-NMO electrode exhibits improved Na+ mobility and near-zero-strain property during charge-discharge processes, which leads to outstanding rate capability (100 mAh g−1 at the operation time of 6 min) and cycling stability (>3000 cycles). In addition, the water-mediated strategy is feasible to other layered sodium oxides and the obtained S-NMO electrode has an excellent tolerance to humidity. This work demonstrates that engineering the spacings of alkali-metal layer is an effective strategy to stabilize the structure of layered transition metal oxides.
Heritability and interindividual variability of regional structure-function coupling
Authors: Gu Zijin , Jamison Keith Wakefield , Sabuncu Mert Rory , Kuceyeski Amy 
Published: August 2021

AbstractWhite matter structural connections are likely to support flow of functional activation or functional connectivity. While the relationship between structural and functional connectivity profiles, here called SC-FC coupling, has been studied on a whole-brain, global level, few studies have investigated this relationship at a regional scale. Here we quantify regional SC-FC coupling in healthy young adults using diffusion-weighted MRI and resting-state functional MRI data from the Human Connectome Project and study how SC-FC coupling may be heritable and varies between individuals. We show that regional SC-FC coupling strength varies widely across brain regions, but was strongest in highly structurally connected visual and subcortical areas. We also show interindividual regional differences based on age, sex and composite cognitive scores, and that SC-FC coupling was highly heritable within certain networks. These results suggest regional structure-function coupling is an idiosyncratic feature of brain organisation that may be influenced by genetic factors.
Interferon lambda 4 impairs hepatitis C viral antigen presentation and attenuates T cell responses
Authors: Chen Qian , Coto-Llerena Mairene , Suslov Aleksei , Teixeira Raphael Dias , Fofana Isabel , Nuciforo Sandro , Hofmann Maike , Thimme Robert , Hensel Nina , Lohmann Volker , Ng Charlotte K. Y. , Rosenberger George , Wieland Stefan , Heim Markus H. 
Published: August 2021

AbstractGenetic variants of the interferon lambda (IFNL) gene locus are strongly associated with spontaneous and IFN treatment-induced clearance of hepatitis C virus (HCV) infections. Individuals with the ancestral IFNL4-dG allele are not able to clear HCV in the acute phase and have more than a 90% probability to develop chronic hepatitis C (CHC). Paradoxically, the IFNL4-dG allele encodes a fully functional IFNλ4 protein with antiviral activity against HCV. Here we describe an effect of IFNλ4 on HCV antigen presentation. Only minor amounts of IFNλ4 are secreted, because the protein is largely retained in the endoplasmic reticulum (ER) where it induces ER stress. Stressed cells are significantly weaker activators of HCV specific CD8+ T cells than unstressed cells. This is not due to reduced MHC I surface presentation or extracellular IFNλ4 effects, since T cell responses are restored by exogenous loading of MHC with HCV antigens. Rather, IFNλ4 induced ER stress impairs HCV antigen processing and/or loading onto the MHC I complex. Our results provide a potential explanation for the IFNλ4–HCV paradox.
CO2 enhances the formation, nutrient scavenging and drug resistance properties of C. albicans biofilms
Authors: Pentland Daniel R. , Davis Jack , Mühlschlegel Fritz A. , Gourlay Campbell W. 
Published: August 2021

AbstractC. albicans is the predominant human fungal pathogen and frequently colonises medical devices, such as voice prostheses, as a biofilm. It is a dimorphic yeast that can switch between yeast and hyphal forms in response to environmental cues, a property that is essential during biofilm establishment and maturation. One such cue is the elevation of CO2 levels, as observed in exhaled breath for example. However, despite the clear medical relevance, the effect of CO2 on C. albicans biofilm growth has not been investigated to date. Here we show that physiologically relevant CO2 elevation enhances each stage of the C. albicans biofilm-forming process: from attachment through maturation to dispersion. The effects of CO2 are mediated via the Ras/cAMP/PKA signalling pathway and the central biofilm regulators Efg1, Brg1, Bcr1 and Ndt80. Biofilms grown under elevated CO2 conditions also exhibit increased azole resistance, increased Sef1-dependent iron scavenging and enhanced glucose uptake to support their rapid growth. These findings suggest that C. albicans has evolved to utilise the CO2 signal to promote biofilm formation within the host. We investigate the possibility of targeting CO2-activated processes and propose 2-deoxyglucose as a drug that may be repurposed to prevent C. albicans biofilm formation on medical airway management implants. We thus characterise the mechanisms by which CO2 promotes C. albicans biofilm formation and suggest new approaches for future preventative strategies.
Alternating magnetic fields and antibiotics eradicate biofilm on metal in a synergistic fashion
Authors: Wang Qi , Vachon Jonathan , Prasad Bibin , Pybus Christine A. , Lapin Norman , Chopra Rajiv , Greenberg David E. 
Published: August 2021

AbstractHundreds of thousands of human implant procedures require surgical revision each year due to infection. Infections are difficult to treat with conventional antibiotics due to the formation of biofilm on the implant surface. We have developed a noninvasive method to eliminate biofilm on metal implants using heat generated by intermittent alternating magnetic fields (iAMF). Here, we demonstrate that heat and antibiotics are synergistic in biofilm elimination. ForPseudomonas aeruginosabiofilm, bacterial burden was reduced >3 log with iAMF and ciprofloxacin after 24 h compared with either treatment alone (p < 0.0001). This effect was not limited by pathogen or antibiotic as similar biofilm reductions were seen with iAMF and either linezolid or ceftriaxone inStaphylococcus aureus. iAMF and antibiotic efficacy was seen across various iAMF settings, including different iAMF target temperatures, dose durations, and dosing intervals. Initial mechanistic studies revealed membrane disruption as one factor important for AMF enhanced antibacterial activity in the biofilm setting. This study demonstrates the potential of utilizing a noninvasive approach to reduce biofilm off of metallic implants.
Impaired cerebro-cerebellar white matter connectivity and its associations with cognitive function in patients with schizophrenia
Authors: Kim Sung Eun , Jung Sungcheol , Sung Gyhye , Bang Minji , Lee Sang-Hyuk 
Published: August 2021

AbstractSchizophrenia is a complex brain disorder of unknown etiology. Based on the notion of “cognitive dysmetria,” we aimed to investigate aberrations in structural white matter (WM) connectivity that links the cerebellum to cognitive dysfunction in patients with schizophrenia. A total of 112 participants (65 patients with schizophrenia and 47 healthy controls [HCs]) were enrolled and underwent diffusion tensor imaging. Between-group voxel-wise comparisons of cerebellar WM regions (superior/middle [MCP]/inferior cerebellar peduncle and pontine crossing fibers) were performed using Tract-Based Spatial Statistics. Cognitive function was assessed using the Trail Making Test Part A/B (TMT-A/B), Wisconsin Card Sorting Test (WCST), and Rey-Kim Memory Test in 46 participants with schizophrenia. WM connectivity, measured as fractional anisotropy (FA), was significantly lower in the MCP in participants with schizophrenia than in HCs. The mean FAs extracted from the significant MCP cluster were inversely correlated with poorer cognitive performance, particularly longer time to complete the TMB-B (r = 0.559, p < 0.001) and more total errors in the WCST (r = 0.442, p = 0.003). Our findings suggest that aberrant cerebro-cerebellar communication due to disrupted WM connectivity may contribute to cognitive impairments, a core characteristic of schizophrenia. Our results may expand our understanding of the neurobiology of schizophrenia based on the cerebro-cerebellar interconnectivity of the brain.
National control laboratory independent lot testing of COVID-19 vaccines: the UK experience
Authors: Rose Nicola J. , Stickings Paul , Schepelmann Silke , Bailey Marc J. A. , Burns Chris 
Published: August 2021

AbstractThe past 18 months have seen an unprecedented approach to vaccine development in the global effort against the COVID-19 pandemic. The process from discovery research, through clinical trials and regulatory approval often takes more than 10 years. However, the critical need to expedite vaccine availability in the pandemic has meant that new approaches to development, manufacturing, and regulation have been required: this has necessitated many stages of product development, clinical trials, and manufacturing to be undertaken in parallel at a global level. Through the development of these innovative products, the world has the best chance of finding individual, or combinations of, vaccines that will provide adequate protection for the world’s population. Despite the huge scientific and regulatory achievements and significant investment to accelerate vaccine availability, it is essential that safety measures are not compromised. Here we focus on the post regulatory approval testing by independent laboratories that provides an additional assurance of the safety and quality of a product, with an emphasis on the UK experience through the National Institute for Biological Standards and Control (NIBSC), an expert centre of the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).