bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Absolute Hypocenter Accuracy With 3D Pg and Sg Body‐Wave Inversion Procedures and Application to Earthquakes in the Central Alps Region
Authors: Diehl Tobias , Kissling Edi , Herwegh Marco , Schmid Stefan M. 
Published: November 2021

AbstractAccuracy of hypocenter location, in particular focal depth, is a precondition for high‐resolution seismotectonic analysis of natural and induced seismicity. For instance, linking seismicity with mapped fault segments requires hypocenter accuracy at the sub‐kilometer scale. In this study, we demonstrate that inaccurate velocity models and improper phase selection can bias absolute hypocenter locations and location uncertainties, resulting in errors larger than the targeted accuracy. To avoid such bias in densely instrumented seismic networks, we propose a coupled hypocenter‐velocity inversion procedure restricted to direct, first‐arriving, mainly upper‐crustal Pg and Sg phases. On the basis of synthetic tests and selected ground‐truth events we demonstrate that a sub‐kilometer hypocenter accuracy can be achieved by regional‐scale, three‐dimensional Pg and Sg velocity models combined with dynamic phase selection and a non‐linear location algorithm. The tomographic inversion uses about 60,000 Pg and 30,000 Sg quality‐checked phases of local earthquakes in the Central Alps region. The derived models image the VP and VS structure of the Central Alps upper crust at unprecedented resolution, including small‐scale anomalies such as those caused by Subalpine Molasse units below the Alpine front. The relocation procedure is applied to more than 18,000 earthquakes and the relocated hypocenters reveal previously unrecognized seismogenic structures, for instance in the Swiss Molasse basin south of Bern. The ML 4.6 Urnerboden earthquake of 2017 is used as an example to demonstrate how the derived 3D velocity structure and relocated hypocenters can be jointly interpreted to constrain the lithology hosting upper‐crustal seismicity in the Central Alps.
Ephemeral Magma Reservoirs During the Incremental Growth of the Neoproterozoic Jiuling Composite Batholith in South China
Authors: Wang Di , Wang Xiao‐Lei , Bindeman Ilya N. , Du De‐Hong , Li Jun‐Yong , Jiang Chang‐Hong 
Published: November 2021

AbstractLarge‐volume magma bodies in the crust are crucial to magmatic differentiation and intracrustal mass redistribution. Their magmatic residence timescales during solidification in the upper crust reflect the intensity of magmatic activity and control the formation of economic deposits. Here we explore the use of zircon crystal size distributions (CSDs) and oxygen isotopic diffusion modeling to constrain the magmatic timescales of the four main intrusions of the Neoproterozoic Jiuling composite batholith in eastern Jiangnan Orogen, South China. We present laser‐ablation–inductively coupled plasma–mass spectrometry zircon U–Pb ages and co‐registered secondary ion mass spectrometry zircon O isotopes for the four main intrusions. The dating results show that the intrusions were emplaced at 826–810 Ma, with a few inherited zircon domains in the range of 3,800–3,835 Ma. The magmatic zircon grains/rims commonly have wide δ18O variations from 5.9‰ to 13.1‰, and magmatic centers have similar δ18O ranges (3.9‰–12.2‰) to those of inherited zircon domains (3.8‰–11.4‰). The application of zircon CSD measurements reveals short zircon crystallization timescales and thus possible magmatic residence times in the order of 103–104 yr, consistent with the maximum residence times (18–47 kyr, as an upper limit) constrained by zircon oxygen isotopic diffusion modeling. This study of such ephemeral reservoirs provides unique insights into the state of magmas and the processes that occur within magma reservoirs.
Caribbean Plate Boundaries Control on the Tectonic Duality in the Back‐Arc of the Lesser Antilles Subduction Zone During the Eocene
Authors: Cerpa N. G. , Hassani R. , Arcay D. , Lallemand S. , Garrocq C. , Philippon M. , Cornée J.‐J. , Münch P. , Garel F. , Marcaillou B. , Mercier de Lépinay B. , Lebrun J.‐F. 
Published: November 2021

AbstractThe Eocene tectonic evolution of the easternmost Caribbean Plate (CP) boundary, that is the Lesser Antilles subduction zone (LASZ), is debated. Recents works shed light on a peculiar period of tectonic duality in the arc/back‐arc regions. A compressional‐to‐transpressional regime occurred in the north, while rifting and seafloor spreading occurred in Grenada basin to the south. The mechanism for this strong spatial variation and its evolution through time has yet to be established. Here, using 3‐D subduction mechanical models, we evaluate whether the change in the trench‐curvature radius at the northeast corner of the CP could have modulated the duality. We assume asymmetrical CP boundaries at the north (from east to west: oblique subduction to strike‐slip) and at the south (subduction‐transform edge propagator‐like behavior). Regardless of the imposed trench curvature, the southern half of our modeled CP undergoes a NW‐to‐W‐oriented extension due to the tendency of the southernmost part of the South‐America oceanic slab to rollback. In contrast, the tectonic regime in the northeast corner of the CP depends on the trench‐curvature radius. A low radius promotes transtension‐to‐transpression, with a NE‐oriented compressive component of the principal stress. A high radius largely reduces the compressive component and promotes an extensional regime similar to that in the south. We thus propose that an initially low‐curvature radius of the NE‐LASZ triggered the tectonic N‐S duality in the Eocene and led to an ephemeral period of transpression/compression at the north. However, an additional mechanism might have been required to locally enhance compression.
Genetic inhibition of RIPK3 ameliorates functional outcome in controlled cortical impact independent of necroptosis
Authors: Wu Limin , Chung Joon Yong , Cao Tian , Jin Gina , Edmiston William J. , Hickman Suzanne , Levy Emily S. , Whalen Jordyn A. , Abrams Eliza Sophie LaRovere , Degterev Alexei , Lo Eng H. , Tozzi Lorenzo , Kaplan David L. , El Khoury Joseph , Whalen Michael J. 
Published: November 2021

AbstractTraumatic brain injury (TBI) is a leading cause of death and disability with no specific effective therapy, in part because disease driving mechanisms remain to be elucidated. Receptor interacting protein kinases (RIPKs) are serine/threonine kinases that assemble multi-molecular complexes that induce apoptosis, necroptosis, inflammasome and nuclear factor kappa B activation. Prior studies using pharmacological inhibitors implicated necroptosis in the pathogenesis of TBI and stroke, but these studies cannot be used to conclusively demonstrate a role for necroptosis because of the possibility of off target effects. Using a model of cerebral contusion and RIPK3 and mixed lineage kinase like knockout (MLKL−/−) mice, we found evidence for activation of RIPK3 and MLKL and assembly of a RIPK1-RIPK3-MLKL necrosome complex in pericontusional brain tissue. Phosphorylated forms of RIPK3 and MLKL were detected in endothelium, CD11b + immune cells, and neurons, and RIPK3 was upregulated and activated in three-dimensional human endothelial cell cultures subjected to CCI. RIPK3−/− and MLKL−/− mice had reduced blood-brain barrier damage at 24 h (p < 0.05), but no differences in neuronal death (6 h, p = ns in CA1, CA3 and DG), brain edema (24 h, p = ns), or lesion size (4 weeks, p = ns) after CCI. RIPK3−/−, but not MLKL−/− mice, were protected against postinjury motor and cognitive deficits at 1–4 weeks (RIPK3−/− vs WT: p < 0.05 for group in wire grip, Morris water maze hidden platform trials, p < 0.05 for novel object recognition test, p < 0.01 for rotarod test). RIPK3−/− mice had reduced infiltrating leukocytes (p < 0.05 vs WT in CD11b + cells, microglia and macrophages), HMGB1 release and interleukin-1 beta activation at 24–48 h (p < 0.01) after CCI. Our data indicate that RIPK3 contributes to functional outcome after cerebral contusion by mechanisms involving inflammation but independent of necroptosis.
A GeV-TeV particle component and the barrier of cosmic-ray sea in the Central Molecular Zone
Authors: Huang Xiaoyuan , Yuan Qiang , Fan Yi-Zhong 
Published: November 2021

AbstractCosmic rays are important probe of a number of fundamental physical problems such as the acceleration of high and very high energy particles in extreme astrophysical environments. The Galactic center is widely anticipated to be an important cosmic-ray source and the observations of some Imaging Atmospheric Cherenkov Telescopes did successfully reveal a component of TeV-PeV cosmic rays in the vicinity of the Galactic center. Here we report the identification of GeV-TeV cosmic rays in the central molecular zone with the γ-ray observations of the Fermi Large Area Telescope, whose spectrum and spatial gradient are consistent with that measured by the Imaging Atmospheric Cherenkov Telescopes but the corresponding cosmic-ray energy density is substantially lower than the so-called cosmic-ray sea component, suggesting the presence of a high energy particle accelerator at the Galactic center and the existence of a barrier that can effectively suppress the penetration of the particles from the cosmic-ray sea to the central molecular zone.
Extended antibody-framework-to-antigen distance observed exclusively with broad HIV-1-neutralizing antibodies recognizing glycan-dense surfaces
Authors: Lee Myungjin , Changela Anita , Gorman Jason , Rawi Reda , Bylund Tatsiana , Chao Cara W. , Lin Bob C. , Louder Mark K. , Olia Adam S. , Zhang Baoshan , Doria-Rose Nicole A. , Zolla-Pazner Susan , Shapiro Lawrence , Chuang Gwo-Yu , Kwong Peter D. 
Published: November 2021

AbstractAntibody-Framework-to-Antigen Distance (AFAD) – the distance between the body of an antibody and a protein antigen – is an important parameter governing antibody recognition. Here, we quantify AFAD for ~2,000 non-redundant antibody-protein-antigen complexes in the Protein Data Bank. AFADs showed a gaussian distribution with mean of 16.3 Å and standard deviation (σ) of 2.4 Å. Notably, antibody-antigen complexes with extended AFADs (>3σ) were exclusively human immunodeficiency virus-type 1 (HIV-1)-neutralizing antibodies. High correlation (R2 = 0.8110) was observed between AFADs and glycan coverage, as assessed by molecular dynamics simulations of the HIV-1-envelope trimer. Especially long AFADs were observed for antibodies targeting the glycosylated trimer apex, and we tested the impact of introducing an apex-glycan hole (N160K); the cryo-EM structure of the glycan hole-targeting HIV-1-neutralizing antibody 2909 in complex with an N160K-envelope trimer revealed a substantially shorter AFAD. Overall, extended AFADs exclusively recognized densely glycosylated surfaces, with the introduction of a glycan hole enabling closer recognition.
Mouse strain-specific polymorphic provirus functions as cis-regulatory element leading to epigenomic and transcriptomic variations
Authors: Zhou Xuemeng , Sam Tsz Wing , Lee Ah Young , Leung Danny 
Published: November 2021

AbstractPolymorphic integrations of endogenous retroviruses (ERVs) have been previously detected in mouse and human genomes. While most are inert, a subset can influence the activity of the host genes. However, the molecular mechanism underlying how such elements affect the epigenome and transcriptome and their roles in driving intra-specific variation remain unclear. Here, by utilizing wildtype murine embryonic stem cells (mESCs) derived from distinct genetic backgrounds, we discover a polymorphic MMERGLN (GLN) element capable of regulating H3K27ac enrichment and transcription of neighboring loci. We demonstrate that this polymorphic element can enhance the neighboringKlhdc4gene expression incis, which alters the activity of downstream stress response genes. These results suggest that the polymorphic ERV-derivedcis-regulatory element contributes to differential phenotypes from stimuli between mouse strains. Moreover, we identify thousands of potential polymorphic ERVs in mESCs, a subset of which show an association between proviral activity and nearby chromatin states and transcription. Overall, our findings elucidate the mechanism of how polymorphic ERVs can shape the epigenome and transcriptional networks that give rise to phenotypic divergence between individuals.
The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma
Authors: Pan Min , Wright William C. , Chapple Richard H. , Zubair Asif , Sandhu Manbir , Batchelder Jake E. , Huddle Brandt C. , Low Jonathan , Blankenship Kaley B. , Wang Yingzhe , Gordon Brittney , Archer Payton , Brady Samuel W. , Natarajan Sivaraman , Posgai Matthew J. , Schuetz John , Miller Darcie , Kalathur Ravi , Chen Siquan , Connelly Jon Patrick , Babu M. Madan , Dyer Michael A. , Pruett-Miller Shondra M. , Freeman Burgess B. , Chen Taosheng , Godley Lucy A. , Blanchard Scott C. , Stewart Elizabeth , Easton John , Geeleher Paul 
Published: November 2021

AbstractSurvival in high-risk pediatric neuroblastoma has remained around 50% for the last 20 years, with immunotherapies and targeted therapies having had minimal impact. Here, we identify the small molecule CX-5461 as selectively cytotoxic to high-risk neuroblastoma and synergistic with low picomolar concentrations of topoisomerase I inhibitors in improving survival in vivo in orthotopic patient-derived xenograft neuroblastoma mouse models. CX-5461 recently progressed through phase I clinical trial as a first-in-human inhibitor of RNA-POL I. However, we also use a comprehensive panel of in vitro and in vivo assays to demonstrate that CX-5461 has been mischaracterized and that its primary target at pharmacologically relevant concentrations, is in fact topoisomerase II beta (TOP2B), not RNA-POL I. This is important because existing clinically approved chemotherapeutics have well-documented off-target interactions with TOP2B, which have previously been shown to cause both therapy-induced leukemia and cardiotoxicity—often-fatal adverse events, which can emerge several years after treatment. Thus, while we show that combination therapies involving CX-5461 have promising anti-tumor activity in vivo in neuroblastoma, our identification of TOP2B as the primary target of CX-5461 indicates unexpected safety concerns that should be examined in ongoing phase II clinical trials in adult patients before pursuing clinical studies in children.
Gateway-driven weakening of ocean gyres leads to Southern Ocean cooling
Authors: Sauermilch Isabel , Whittaker Joanne M. , Klocker Andreas , Munday David R. , Hochmuth Katharina , Bijl Peter K. , LaCasce Joseph H. 
Published: November 2021

AbstractDeclining atmospheric CO2 concentrations are considered the primary driver for the Cenozoic Greenhouse-Icehouse transition, ~34 million years ago. A role for tectonically opening Southern Ocean gateways, initiating the onset of a thermally isolating Antarctic Circumpolar Current, has been disputed as ocean models have not reproduced expected heat transport to the Antarctic coast. Here we use high-resolution ocean simulations with detailed paleobathymetry to demonstrate that tectonics did play a fundamental role in reorganising Southern Ocean circulation patterns and heat transport, consistent with available proxy data. When at least one gateway (Tasmanian or Drake) is shallow (300 m), gyres transport warm waters towards Antarctica. When the second gateway subsides below 300 m, these gyres weaken and cause a dramatic cooling (average of 2–4 °C, up to 5 °C) of Antarctic surface waters whilst the ACC remains weak. Our results demonstrate that tectonic changes are crucial for Southern Ocean climate change and should be carefully considered in constraining long-term climate sensitivity to CO2.
A site of vulnerability at V3 crown defined by HIV-1 bNAb M4008_N1
Authors: Chan Kun-Wei , Luo Christina C. , Lu Hong , Wu Xueling , Kong Xiang-Peng 
Published: November 2021

AbstractIdentification of vulnerable sites defined by broadly neutralizing antibodies (bNAbs) on HIV-1 envelope (Env) is crucial for vaccine design, and we present here a vulnerable site defined by bNAb M4008_N1, which neutralizes about 40% of a tier-2 virus panel. A 3.2 Å resolution cryo-EM structure of M4008_N1 in complex with BG505 DS-SOSIP reveals a large, shallow protein epitope surface centered at the V3 crown of gp120 and surrounded by key glycans. M4008_N1 interacts with gp120 primarily through its hammerhead CDR H3 to form a β-sheet interaction with the V3 crown hairpin. This makes M4008_N1 compatible with the closed conformation of the prefusion Env trimer, and thus distinct from other known V3 crown mAbs. This mode of bNAb approaching the immunogenic V3 crown in the native Env trimer suggests a strategy for immunogen design targeting this site of vulnerability.
Laughlin anyon complexes with Bose properties
Authors: Kulik L. V. , Zhuravlev A. S. , Musina L. I. , Belozerov E. I. , Van’kov A. B. , Volkov O. V. , Zagitova A. A. , Kukushkin I. V. , Umansky V. Y. 
Published: November 2021

AbstractTwo-dimensional electron systems in a quantizing magnetic field are regarded as of exceptional interest, considering the possible role of anyons—quasiparticles with non-boson and non-fermion statistics—in applied physics. To this day, essentially none but the fractional states of the quantum Hall effect (FQHE) have been experimentally realized as a system with anyonic statistics. In determining the thermodynamic properties of anyon matter, it is crucial to gain insight into the physics of its neutral excitations. We form a macroscopic quasi-equilibrium ensemble of neutral excitations - spin one anyon complexes in the Laughlin state ν = 1/3, experimentally, where ν is the electron filling factor. The ensemble is found to have such a long lifetime that it can be considered the new state of anyon matter. The properties of this state are investigated by optical techniques to reveal its Bose properties.
Integrated polarization-sensitive amplification system for digital information transmission
Authors: Ran Wenhao , Ren Zhihui , Wang Pan , Yan Yongxu , Zhao Kai , Li Linlin , Li Zhexin , Wang Lili , Yang Juehan , Wei Zhongming , Lou Zheng , Shen Guozhen 
Published: November 2021

AbstractPolarized light can provide significant information about objects, and can be used as information carrier in communication systems through artificial modulation. However, traditional polarized light detection systems integrate polarizers and various functional circuits in addition to detectors, and are supplemented by complex encoding and decoding algorithms. Although the in-plane anisotropy of low-dimensional materials can be utilized to manufacture polarization-sensitive photodetectors without polarizers, the low anisotropic photocurrent ratio makes it impossible to realize digital output of polarized information. In this study, we propose an integrated polarization-sensitive amplification system by introducing a nanowire polarized photodetector and organic semiconductor transistors, which can boost the polarization sensitivity from 1.24 to 375. Especially, integrated systems are universal in that the systems can increase the anisotropic photocurrent ratio of any low-dimensional material corresponding to the polarized light. Consequently, a simple digital polarized light communication system can be realized based on this integrated system, which achieves certain information disguising and confidentiality effects.
Usefulness of MRI targeted prostate biopsy for detecting clinically significant prostate cancer in men with low prostate-specific antigen levels
Authors: Bang Seokhwan , Yu Jiwoong , Chung Jae Hoon , Song Wan , Kang Minyong , Sung Hyun Hwan , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong Il , Lee Hyun Moo , Jeon Seong Soo 
Published: November 2021

AbstractWe aimed to evaluate the detection rates of prostate cancer (PCa) and clinically significant PCa (csPCa) using magnetic resonance imaging-targeted biopsy (MRI-TBx) in men with low prostate-specific antigen (PSA) levels (2.5–4.0 ng/mL). Clinicopathologic data of 5502 men with PSA levels of 2.5–10.0 ng/mL who underwent transrectal ultrasound-guided biopsy (TRUS-Bx) or MRI-TBx were reviewed. Participants were divided into four groups: LP-T [low PSA (2.5–4.0 ng/mL) and TRUS-Bx, n = 2018], LP-M (low PSA and MRI-TBx, n = 186), HP-T [high PSA (4.0–10.0 ng/mL) and TRUS-Bx, n = 2953], and HP-M (high PSA and MRI-TBx, n = 345). The detection rates of PCa and csPCa between groups were compared, and association of biopsy modality with detection of PCa and csPCa in men with low PSA levels were analyzed. The detection rates of PCa (20.0% vs. 38.2%; P < 0.001) and csPCa (11.5% vs. 32.3%; P < 0.001) were higher in the LP-M group than in the LP-T group. Conversely, there were no significant differences in the detection rates of PCa (38.2% vs. 43.2%; P = 0.263) and csPCa (32.3% vs. 39.4%; P = 0.103) between the LP-M and HP-M groups. Multivariate analyses revealed that using MRI-TBx could predict the detection of csPCa (odds ratio 2.872; 95% confidence interval 1.996‒4.132; P < 0.001) in men with low PSA levels. In summary, performing MRI-TBx in men with low PSA levels significantly improved the detection rates of PCa and csPCa as much as that in men with high PSA levels.
An enhanced version of Harris Hawks Optimization by dimension learning-based hunting for Breast Cancer Detection
Authors: Kaur Navneet , Kaur Lakhwinder , Cheema Sikander Singh 
Published: November 2021

AbstractSwarm intelligence techniques have a vast range of real world applications.Some applications are in the domain of medical data mining where, main attention is on structure models for the classification and expectation of numerous diseases. These biomedical applications have grabbed the interest of numerous researchers because these are most serious and prevalent causes of death among the human whole world out of which breast cancer is the most serious issue. Mammography is the initial screening assessment of breast cancer. In this study, an enhanced version of Harris Hawks Optimization (HHO) approach has been developed for biomedical databases, known as DLHO. This approach has been introduced by integrating the merits of dimension learning-based hunting (DLH) search strategy with HHO. The main objective of this study is to alleviate the lack of crowd diversity, premature convergence of the HHO and the imbalance amid the exploration and exploitation. DLH search strategy utilizes a dissimilar method to paradigm a neighborhood for each search member in which the neighboring information can be shared amid search agents. This strategy helps in maintaining the diversity and the balance amid global and local search. To evaluate the DLHO lot of experiments have been taken such as (i) the performance of optimizers have analysed by using 29-CEC -2017 test suites, (ii) to demonstrate the effectiveness of the DLHO it has been tested on different biomedical databases out of which we have used two different databases for Breast i.e. MIAS and second database has been taken from the University of California at Irvine (UCI) Machine Learning Repository.Also to test the robustness of the proposed method its been tested on two other databases of such as Balloon and Heart taken from the UCI Machine Learning Repository. All the results are in the favour of the proposed technique.