bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Terrestrial Carbon Export From East Antarctica During the Early Eocene
Authors: Inglis Gordon N. , Toney Jaime L. , Zhu Jiang , Poulsen Christopher J. , Röhl Ursula , Jamieson Stewart S. R. , Pross Jörg , Cramwinckel Marlow J. , Krishnan Srinath , Pagani Mark , Bijl Peter K. , Bendle James 
Published: January 2022

AbstractTerrestrial organic carbon (TerrOC) acts as an important CO2 sink when transported via rivers to the ocean and sequestered in coastal marine sediments. This mechanism might help to modulate atmospheric CO2 levels over short‐ and long‐ timescales (103–106 years), but its importance during past warm climates remains unknown. Here we use terrestrial biomarkers preserved in coastal marine sediment samples from Wilkes Land, East Antarctica (∼67°S) to quantify TerrOC burial during the early Eocene (∼54.4–51.5 Ma). Terrestrial biomarker distributions indicate the delivery of plant‐, soil‐, and peat‐derived organic carbon (OC) into the marine realm. Mass accumulation rates of plant‐ (long‐chain n‐alkane) and soil‐derived (hopane) biomarkers dramatically increase between the earliest Eocene (∼54 Ma) and the early Eocene Climatic Optimum (EECO; ∼53 Ma). This coincides with increased OC mass accumulation rates and indicates enhanced TerrOC burial during the EECO. Leaf wax δ2H values indicate that the EECO was characterized by wetter conditions relative to the earliest Eocene, suggesting that hydroclimate exerts a first‐order control on TerrOC export. Our results indicate that TerrOC burial in coastal marine sediments could have acted as an important negative feedback mechanism during the early Eocene, but also during other warm climate intervals.
Influence of Surface Processes on Postrift Faulting During Divergent Margins Evolution
Authors: Silva R. M. , Sacek V. 
Published: January 2022

AbstractWe used thermomechanical numerical models to simulate the formation and evolution of divergent continental margins since continental rifting, taking into account surface processes of erosion of the continental escarpment. We found that the degree of crust–mantle coupling, the magnitude and extent of erosion of the coastal landscape, and the preexistence of weakness zones in the continental crust are important elements that control the reactivation of faults along divergent margins during the postrift phase. The numerical experiments indicated that the presence of a lower crust with a relatively low viscosity, facilitating the decoupling of the upper crust and the development of hyperextended margins, could also contribute to the development and/or reactivation of normal faults in the interior of the continent when the margin is continually subjected to differential denudation and consequent flexural response of the lithosphere. This effect is suppressed in scenarios where the lower crust presents a relatively high viscosity, consequently inducing the coupling of the upper crust with the lithospheric mantle. In this case, the long wavelength of the flexural response of a coupled lithosphere to erosional unloading has a minor impact on the reactivation of faults in the upper crust. As an application of our model, we propose that the combination of a decoupled continental lithosphere, escarpment retreat due to erosion, and the preexistence of shear zones parallel to the coast contributed to the development of postrift Cenozoic tectonism in southeastern Brazil.
Mechanical Stratigraphy Controls Normal Fault Growth and Dimensions, Outer Kwanza Basin, Offshore Angola
Authors: Redpath David , Jackson Christopher A.‐L. , Bell Rebecca E. 
Published: January 2022

AbstractMechanical stratigraphy controls the growth patterns and dimensions of relatively small normal faults, yet how it influences the development of much larger structures remains unclear. Here, we use 3D seismic reflection data from the Outer Kwanza Basin, offshore Angola to constrain the geometry and kinematics of several normal faults formed in a deep‐water clastic succession. The faults are up to 6.3‐km long and 1.9‐km tall and have up to 44 m of throw. Aspect ratios and lower‐tip throw gradients are greater for faults that terminate downward at a c. 100 m thick, mass‐transport complex (MTC; up to 5.2 and 0.12) than for those that offset it (up to 2.7 and 0.01). Faults that offset the MTC invariably have >30 m of throw. Based on their geometric properties and throw patterns, we interpret that the faults nucleated above the MTC and propagated down toward it. Upon encountering this unit, which we infer behaved in a more ductile manner than encasing strata, tip propagation was halted until tip stresses were sufficiently high (corresponding to minimum throw of c. 30 m) to breach it. Faults with smaller throw were unable to breach the MTC. We argue that using only geometric criteria to determine fault growth patterns can mask the significant control mechanical stratigraphy has on fault kinematics. Mechanical stratigraphy is therefore a key control on the growth of large, seismic‐scale normal faults, in a similar way to that observed for far smaller structures.
Length-based separation of Bacillus subtilis bacterial populations by viscoelastic microfluidics
Authors: Liu Ping , Liu Hangrui , Semenec Lucie , Yuan Dan , Yan Sheng , Cain Amy K. , Li Ming 
Published: January 2022

AbstractIn this study, we demonstrated the label-free continuous separation and enrichment ofBacillus subtilispopulations based on length using viscoelastic microfluidics.B. subtilis, a gram-positive, rod-shaped bacterium, has been widely used as a model organism and an industrial workhorse.B. subtiliscan be arranged in different morphological forms, such as single rods, chains, and clumps, which reflect differences in cell types, phases of growth, genetic variation, and changing environmental factors. The ability to prepareB. subtilispopulations with a uniform length is important for basic biological studies and efficient industrial applications. Here, we systematically investigated how flow rate ratio, poly(ethylene oxide) (PEO) concentration, and channel length affected the length-based separation ofB. subtiliscells. The lateral positions ofB. subtiliscells with varying morphologies in a straight rectangular microchannel were found to be dependent on cell length under the co-flow of viscoelastic and Newtonian fluids. Finally, we evaluated the ability of the viscoelastic microfluidic device to separate the two groups ofB. subtiliscells by length (i.e., 1–5 μm and >5 μm) in terms of extraction purity (EP), extraction yield (EY), and enrichment factor (EF) and confirmed that the device could separate heterogeneous populations of bacteria using elasto-inertial effects.
Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany
Authors: Endres Dominique , Lüngen Eva , Hasan Alkomiet , Kluge Michael , Fröhlich Sabrina , Lewerenz Jan , Bschor Tom , Haußleiter Ida Sibylle , Juckel Georg , Then Bergh Florian , Ettrich Barbara , Kertzscher Lisa , Oviedo-Salcedo Tatiana , Handreka Robert , Lauer Martin , Winter Klaas , Zumdick Norbert , Drews Anna , Obrocki Jost , Yalachkov Yavor , Bubl Anna , von Podewils Felix , Schneider Udo , Szabo Kristina , Mattern Margarete , Philipsen Alexandra , Domschke Katharina , Wandinger Klaus-Peter , Neyazi Alexandra , Stich Oliver , Prüss Harald , Leypoldt Frank , Tebartz van Elst Ludger 
Published: January 2022

AbstractAutoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study’s aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as “probable psychiatric AE (pAE),” if well-characterized neuronal IgG autoantibodies were detected or “possible pAE” (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed.
Functional brain rewiring and altered cortical stability in ulcerative colitis
Authors: Wang Hao , Labus Jennifer S. , Griffin Fiona , Gupta Arpana , Bhatt Ravi R. , Sauk Jenny S. , Turkiewicz Joanna , Bernstein Charles N. , Kornelsen Jennifer , Mayer Emeran A. 
Published: January 2022

AbstractDespite recent advances, there is still a major need to better understand the interactions between brain function and chronic gut inflammation and its clinical implications. Alterations in executive function have previously been identified in several chronic inflammatory conditions, including inflammatory bowel diseases. Inflammation-associated brain alterations can be captured by connectome analysis. Here, we used the resting-state fMRI data from 222 participants comprising three groups (ulcerative colitis (UC), irritable bowel syndrome (IBS), and healthy controls (HC),N = 74 each) to investigate the alterations in functional brain wiring and cortical stability in UC compared to the two control groups and identify possible correlations of these alterations with clinical parameters. Globally, UC participants showed increased functional connectivity and decreased modularity compared to IBS and HC groups. Regionally, UC showed decreased eigenvector centrality in the executive control network (UC < IBS < HC) and increased eigenvector centrality in the visual network (UC > IBS > HC). UC also showed increased connectivity in dorsal attention, somatomotor network, and visual networks, and these enhanced subnetwork connectivities were able to distinguish UC participants from HCs and IBS with high accuracy. Dynamic functional connectome analysis revealed that UC showed enhanced cortical stability in the medial prefrontal cortex (mPFC), which correlated with severe depression and anxiety-related measures. None of the observed brain changes were correlated with disease duration. Together, these findings are consistent with compromised functioning of networks involved in executive function and sensory integration in UC.
The antigenicity of SARS-CoV-2 Delta variants aggregated 10 high-frequency mutations in RBD has not changed sufficiently to replace the current vaccine strain
Authors: Wu Jiajing , Nie Jianhui , Zhang Li , Song Hao , An Yimeng , Liang Ziteng , Yang Jing , Ding Ruxia , Liu Shuo , Li Qianqian , Li Tao , Cui Zhimin , Zhang Mengyi , He Peng , Wang Youchun , Qu Xiaowang , Hu Zhongyu , Wang Qihui , Huang Weijin 
Published: January 2022

AbstractEmerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment. To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine, the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was compared. The neutralization activities of Alpha, Beta and Gamma variants’ spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant, which were constructed using pseudotyped viruses. Meanwhile, the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta variants. Eight HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–2019. Our results indicate that the antigenicity changes of possible Delta variants were mostly within four folds, whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–100-fold. Structural analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization results. This study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.
The hospital exemption pathway for the approval of advanced therapy medicinal products: an underused opportunity? The case of the CAR-T ARI-0001
Authors: Trias Esteve , Juan Manel , Urbano-Ispizua Alvaro , Calvo Gonzalo 
Published: January 2022

AbstractIn February 2021, the ‘Advanced Therapy Medicinal Product’ (ATMP) ARI-0001 (CART19-BE-01), developed at Hospital Clínic de Barcelona (Spain), received authorization from the Spanish Agency of Medicines and Medical Devices (AEMPS) under the ‘hospital exemption’ (HE) approval pathway for the treatment of patients aged >25 years with relapsed/refractory (RR) acute lymphoblastic leukemia (ALL). The HE pathway foreseen by the European Regulation establishing the legal framework for ATMPs intended to be placed on the market in the EU, allows access to ATMPs prepared on a non-routine basis, according to quality standards, like a custom-made product for an individual patient. Its use is limited to the same Member State where it was developed, in a hospital under the responsibility of a medical practitioner. HE-ATMPs must comply with national traceability and pharmacovigilance requirements and specific quality standards. HE offers an opportunity to develop ATMPs in close contact with clinical practice, with the quality and rapid access needed by patients and at a lower cost compared to regular market authorization. However, many barriers need to be overcome. Here we discuss relevant aspects of the development and authorization of ARI-0001 in the context of the heterogeneous frame of the European Regulation implementation across the Member States.
DDX39B contributes to the proliferation of colorectal cancer through direct binding to CDK6/CCND1
Authors: Zhang Haonan , He Chengcheng , Guo Xuxue , Fang Yuxin , Lai Qiuhua , Wang Xinke , Pan Xingzhu , Li Haolin , Qin Kaiwen , Li Aimin , Liu Side , Li Qingyuan 
Published: January 2022

AbstractDDX39B (also called UAP56 or BAT1) which is a kind of DEAD-box family helicase plays pivotal roles in mRNA binding, splicing, and export. It has been found upregulated in many kinds of tumors as an oncogene. Nevertheless, the underlying molecular mechanisms of DDX39B in the proliferation of human colorectal cancer (CRC) remain fairly elusive. In our study, function experiments including the CCK8 and colony formation assay revealed that DDX39B facilitates CRC proliferation in vitro. DDX39B knockdown cells were administered for the orthotopic CRC tumor xenograft mouse model, after which tumor growth was monitored and immunohistochemistry (IHC) was performed to prove that DDX39B can also facilitates CRC proliferation in vivo. Flow cytometry demonstrated that DDX39B promotes the proliferation of CRC cells by driving the cell cycle from G0/G1 phase to the S phase. Mechanistically, RNA-binding protein immunoprecipitation-sequencing (RIP-seq) confirmed that DDX39B binds directly to the first exon of the CDK6/CCND1 pre-mRNA and upregulates their expression. Splicing experiments in vitro using a RT-PCR and gel electrophoresis assay confirmed that DDX39B promotes CDK6/CCND1 pre-mRNA splicing. Rescue experiments indicated that CDK6/CCND1 is a downstream effector of DDX39B-mediated CRC cell proliferation. Collectively, our results demonstrated that DDX39B and CDK6/CCND1 direct interactions serve as a CRC proliferation promoter, which can accelerate the G1/S phase transition to enhance CRC proliferation, and can offer novel and emerging treatment strategies targeting this cell proliferation-promoting gene.
A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs
Authors: Liu Zezhong , Zhou Jie , Xu Wei , Deng Wei , Wang Yanqun , Wang Meiyu , Wang Qian , Hsieh Ming , Dong Jingming , Wang Xinling , Huang Weijin , Xing Lixiao , He Miaoling , Tao Chunlin , Xie Youhua , Zhang Yilong , Wang Youchun , Zhao Jincun , Yuan Zhenghong , Qin Chuan , Jiang Shibo , Lu Lu 
Published: January 2022

AbstractThe emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights the need for pan-sarbecovirus vaccines. Here, we discovered a new STING agonist, CF501, and found that CF501-adjuvanted RBD-Fc vaccine (CF501/RBD-Fc) elicited significantly stronger neutralizing antibody (nAb) and T cell responses than Alum- and cGAMP-adjuvanted RBD-Fc in mice. Vaccination of rabbits and rhesus macaques (nonhuman primates, NHPs) with CF501/RBD-Fc elicited exceptionally potent nAb responses against SARS-CoV-2 and its nine variants and 41 S-mutants, SARS-CoV and bat SARSr-CoVs. CF501/RBD-Fc-immunized hACE2-transgenic mice were almost completely protected against SARS-CoV-2 challenge, even 6 months after the initial immunization. NHPs immunized with a single dose of CF501/RBD-Fc produced high titers of nAbs. The immunized macaques also exhibited durable humoral and cellular immune responses and showed remarkably reduced viral load in the upper and lower airways upon SARS-CoV-2 challenge even at 108 days post the final immunization. Thus, CF501/RBD-Fc can be further developed as a novel pan-sarbecovirus vaccine to combat current and future outbreaks of sarbecovirus diseases.
Ultrastable microwave and soliton-pulse generation from fibre-photonic-stabilized microcombs
Authors: Kwon Dohyeon , Jeong Dongin , Jeon Igju , Lee Hansuek , Kim Jungwon 
Published: January 2022

AbstractThe ability to generate lower-noise microwaves has greatly advanced high-speed, high-precision scientific and engineering fields. Microcombs have high potential for generating such low-noise microwaves from chip-scale devices. To realize an ultralow-noise performance over a wider Fourier frequency range and longer time scale, which is required for many high-precision applications, free-running microcombs must be locked to more stable reference sources. However, ultrastable reference sources, particularly optical cavity-based methods, are generally bulky, alignment-sensitive and expensive, and therefore forfeit the benefits of using chip-scale microcombs. Here, we realize compact and low-phase-noise microwave and soliton pulse generation by combining a silica-microcomb (with few-mm diameter) with a fibre-photonic-based timing reference (with few-cm diameter). An ultrastable 22-GHz microwave is generated with −110 dBc/Hz (−88 dBc/Hz) phase noise at 1-kHz (100-Hz) Fourier frequency and 10−13-level frequency instability within 1-s. This work shows the potential of fully packaged, palm-sized or smaller systems for generating both ultrastable soliton pulse trains and microwaves, thereby facilitating a wide range of field applications involving ultrahigh-stability microcombs.
Absent thermal equilibration on fractional quantum Hall edges over macroscopic scale
Authors: Melcer Ron Aharon , Dutta Bivas , Spånslätt Christian , Park Jinhong , Mirlin Alexander D. , Umansky Vladimir 
Published: January 2022

AbstractTwo-dimensional topological insulators, and in particular quantum Hall states, are characterized by an insulating bulk and a conducting edge. Fractional states may host both downstream (dictated by the magnetic field) and upstream propagating edge modes, which leads to complex transport behavior. Here, we combine two measurement techniques, local noise thermometry and thermal conductance, to study thermal properties of states with counter-propagating edge modes. We find that, while charge equilibration between counter-propagating edge modes is very fast, the equilibration of heat is extremely inefficient, leading to an almost ballistic heat transport over macroscopic distances. Moreover, we observe an emergent quantization of the heat conductance associated with a strong interaction fixed point of the edge modes. Such understanding of the thermal equilibration on edges with counter-propagating modes is a natural route towards extracting the topological order of the exotic 5/2 state.
Detailed modelling of contact line motion in oscillatory wetting
Authors: Amberg Gustav 
Published: January 2022

AbstractThe experimental results of Xia and Steen for the contact line dynamics of a drop placed on a vertically oscillating surface are analyzed by numerical phase field simulations. The concept of contact line mobility or friction is discussed, and an angle-dependent model is formulated. The results of numerical simulations based on this model are compared to the detailed experimental results of Xia and Steen with good general agreement. The total energy input in terms of work done by the oscillating support, and the dissipation at the contact line, are calculated from the simulated results. It is found that the contact line dissipation is almost entirely responsible for the dissipation that sets the amplitude of the response. It is argued that angle-dependent line friction may be a fruitful interpretation of the relations between contact line speed and dynamic contact angle that are often used in practical computational fluid dynamics.
Metabolic modeling of host–microbe interactions for therapeutics in colorectal cancer
Authors: Bhalla Prerna , Rengaswamy Raghunathan , Karunagaran Devarajan , Suraishkumar G. K. , Sahoo Swagatika 
Published: January 2022

AbstractThe onset of colorectal cancer (CRC) is often attributed to gut bacterial dysbiosis, and thus gut microbiota are highly relevant in devising treatment strategies. Certain gut microbes, like Enterococcus spp., exhibit remarkable anti-neoplastic and probiotic properties, which can aid in silver nanoparticle (AgNPs) induced reactive oxygen species (ROS)-based CRC treatment. However, the effects of AgNPs on gut microbial metabolism have not been reported thus far. In this study, a detailed systems-level understanding of ROS metabolism in Enterococcus durans (E. durans), a representative gut microbe, was gained using constraint-based modeling, wherein, the critical association between ROS and folate metabolism was established. Experimental studies involving low AgNP concentration treatment of E. durans cultures confirmed these modeling predictions (an increased extracellular folate concentration by 52%, at the 9th h of microbial growth, was observed). Besides, the computational studies established various metabolic pathways involving amino acids, energy metabolites, nucleotides, and SCFAs as the key players in elevating folate levels on ROS exposure. The anti-cancer potential of E. durans was also studied through MTT analysis of HCT 116 cells treated with microbial culture (AgNP treated) supernatant. A decrease in cell viability by 19% implicated the role of microbial metabolites (primarily folate) in causing cell death. The genome-scale modeling approach was then extended to extensively model CRC metabolism, as well as CRC–E. durans interactions in the context of CRC treatment, using tissue-specific metabolic models of CRC and healthy colon. These findings on further validation can facilitate the development of robust and effective cancer therapy.