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A variant in IL6ST with a selective IL-11 signaling defect in human and mouse

Bone research 2020年第2期8卷 157-168页

作者： Tobias Schwerd freia Krause stephen r.f.twigg Dominik Aschenbrenner Yin-Huai Chen Uwe Borgmeyer Miryam Müller Santiago Manrique Neele Schumacher Steven A.Wall Jonathan Jung Timo Damm Claus-Christian Glüer Jürgen Scheller Stefan rose-John E.Yvonne Jones Arian Laurence Andrew O.M.Wilkie Dirk Schmidt-Arras Holm H.Uhlig Translational Gastroenterology Unit John Radcliffe HospitalUniversity of OxfordOxfordUK Department of Pediatrics Dr von Hauner Children’s HospitalLMU MunichMunichGermany Christian-Albrechts-University Kiel Institute of BiochemistryKielGermany Clinical Genetics Group MRC Weatherall Institute of Molecular MedicineUniversity of OxfordJohn Radcliffe HospitalOxfordUK Center for Molecular Neurobiology Hamburg(ZMNH) University Medical Center Hamburg-EppendorfHamburgGermany Division of Structural Biology Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK Craniofacial Unit Department of Plastic and Reconstructive SurgeryOxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxfordUK Section Biomedical Imaging Department of Radiology and NeuroradiologyUniversity Medical Center Schleswig-HolsteinKielGermany Institute of Biochemistry and Molecular Biology Ⅱ Medical FacultyHeinrich-Heine-UniversityDüsseldorfGermany Department of Paediatrics University of OxfordOxfordUK NIHr Oxford Biomedical research Centre OxfordUK The Beatson Institute for Cancer research GlasgowUK School of Medicine University of GlasgowGlasgowUK

The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6 ST(p.r281 Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and support these findings using a mouse model with the corresponding genome-edited variant Il6 st p.r279 Q. We show that human GP130 p.r281 Q is associated with selective loss of IL-11 signaling without affecting IL-6, IL-27, OSM, LIf, CT1, CLC, and CNTf signaling. In mice Il6 st p.r279 Q lowers litter size and causes facial synostosis and teeth abnormalities. The effect on IL-11 signaling caused by the GP130 variant shows incomplete penetrance but phenocopies aspects of IL11 rA deficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.

关键词： IL11 cytokine facial

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The effects of local variations in conditions on carbon storage and release in the continental mantle

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National Science review 2024年第6期11卷 22-36页

作者： stephen f.foley Chunfei Chen Dorrit E.Jacob School of Natural Sciences Macquarie University research School of Earth Sciences Australian National University State Key Laboratory of Geological Processes and Mineral resources School of Earth Sciences China University of Geosciences

recent advances indicate that the amount of carbon released by gradual degassing from the mantle needs to be revised upwards, whereas the carbon supplied by plumes may have been overestimated in the *** in rock types and oxidation state may be very local and exert strong influences on carbon storage and release mechanisms. Deep subduction may be prevented by diapirism in thick sedimentary packages,whereas carbonates in thinner sequences may be subducted. Carbonates stored in the mantle transition zone will melt when they heat up, recognized by coupled stable isotope systems(e.g. Mg, Zn, Ca). There is no single ‘mantle oxygen fugacity’, particularly in the thermal boundary layer(TBL) and lowermost lithosphere, where very local mixtures of rock types coexist. Carbonate-rich melts from either subduction or melting of the uppermost asthenosphere trap carbon by redox freezing or as carbonate-rich dykes in this zone. Deeply derived, reduced melts may form further diamond reservoirs, recognized as polycrystalline diamonds associated with websteritic silicate minerals. Carbon is released by either edge-driven convection,which tears sections of the TBL and lower lithosphere down so that they melt by a mixture of heating and oxidation, or by lateral advection of solids beneath rifts. Both mechanisms operate at steps in lithosphere thickness and result in carbonate-rich melts, explaining the spatial association of craton edges and carbonate-rich magmatism. High-pressure experiments on individual rock types, and increasingly on reactions between rocks and melts, are fine-tuning our understanding of processes and turning up unexpected results that are not seen in studies of single rocks. future research should concentrate on elucidating local variations and integrating these with the interpretation of geophysical signals. Global concepts such as average sediment compositions and a uniform mantle oxidation state are not appropriate for small-scale processes; an increa

关键词： lithospheric mantle carbonate melts deep carbon cycle craton destruction continental rifts

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Circumscription of the East Asia clade (Apiaceae subfamily Apioideae) and the taxonomic placements of several problematic genera

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Plant Diversity 2024年第2期46卷 206-218页

作者： Jing Zhou Xinyue Wang Shilin Zhou Junmei Niu Jiarui Yue Zhenwen Liu stephen r.Downie School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products Kunming Medical University1168 Western Chunrong RoadYuhua StreetChenggong New CityKunming 650500China Yunnan Academy of forestry and Grassland Kunming 650201China Gaoligong Mountain Forest EcosystemObservation and Research Station of Yunnan ProvinceKunming 650201China Yunnan Key Laboratory of Biodiversity of Gaoligong Mountain Kunming 650201China Department of Plant Biology University of Illinois at Urbana-ChampaignUrbanaIL 61801USA College of Modern Biomedical Industry Kunming Medical UniversityKunming 650500China

The East Asia(or Physospermopsis) clade was recognized in previous molecular phylogenetic investigations into the higher-level relationships of Apiaceae subfamily Apioideae. The composition of this clade, the phylogenetic relationships among its constituent taxa, and the placement of species previously determined to be problematic have yet to be resolved. Herein, nr DNA ITS sequences were obtained for150 accessions of Apioideae, representing species whose distributions are in East Asia or genera having one or more species included within the East Asia clade. These data, along with published ITS sequences from other Apioideae(for 3678 accessions altogether), were subjected to maximum likelihood and Bayesian inference analyses. The results show that the East Asia clade contains representatives of 11currently recognized genera: Hansenia, Hymenolaena, Keraymonia, Sinolimprichtia, Acronema, Hymenidium, Physospermopsis, Pimpinella, Sinocarum, Tongoloa, and Trachydium. However, the latter seven genera have members falling outside of the East Asia clade, including the generic types of all except Tongoloa. Within the clade, the species comprising these seven genera are widely intermingled, greatly increasing confusion among relationships than previously realized. The problematic species Physospermopsis cuneata is confirmed as falling within the East Asia clade, whereas P. rubrinervis allies with the generic type in tribe Pleurospermeae. Physospermopsis kingdon-wardii is confirmed as a member of the genus Physospermopsis, whereas the generic attributions of P. cuneata and Tongoloa stewardii remain unclear. Two species of Sinocarum(S. filicinum and S. wolffianum) are transferred into the genus Meeboldia. This is the most comprehensive molecular phylogenetic investigation of the East Asia clade to date, and while the results increase systematic understanding of the clade, they also highlight the need for further studies of one of the most taxonomically intractable groups in Api

关键词： Physospermopsis Pimpinella Sinocarum Tongoloa Trachydium

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DEM investigation of strength and critical state behaviours of granular materials under true triaxial loadings

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Particuology 2024年第2期85卷 198-212页

作者： Minyi Zhu Guobin Gong Jun Xia stephen Wilkinson Department of Civil Engineering Xi'an Jiaotong-Liverpool UniversityChina Department of Civil Engineering and Industrial Design University of LiverpoolLiverpoolUK faculty of Engineering and Information Sciences University of Wollongong in DubaiUnited Arab Emirates

This paper investigates the strength and critical state(CS)behaviours of granular materials via DEM simulations of true triaxial drained tests under three different loading modes including constant b(in-termediate stress ratio)tests with constantσ'1(major principal stress),constant p(mean pressure)and constantσ'3(minor principal stress)*** this end,a series of samples are generated with the same particle size distribution,and with the confining stresses ranging from 100 kPa to 900 *** CS is achieved for all *** the macroscopic behaviours and the microscopic behaviours are examined and compared considering different loading modes,confining stresses and intermediate stress ratios(b).The critical state lines(CSLs)are found to be unique and independent of the loading modes,but dependent on the b *** CSLs with b=0 and b=1 form the two boundaries of CSLs respectively beyond which CSLs under all other b tests cannot go *** different strength criteria are examined and compared in terms of both peak and CS *** Mohr-Coulomb strength criterion is found to be only suitable for axisymmetric loading *** Lade-Duncan criterion is only suitable for describing peak strengths,which is dependent on the loading modes and confining *** Satake criterion and Matsuoka-Nakai criterion are the more appropriate strength criteria for describing CS failures,indicating that the CS values of both the Satake parameter and the Matsuoka-Nakai parameter describe an inherent property that characterizes the CS failure for a given type of *** CS mechanical coordination number is fitted by a curved line for a given b value,which is unique regardless of the loading *** peak and CS values of both major and minor principal fabric tensors decrease with increasing b values,while they increase with increasing b values for the intermediate principal fabric tensor.

关键词： Discrete element method Intermediate stress ratio Dilation Critical state failure criterion

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Inflow and outflow permeability tests in a very soft clay under low stresses

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Journal of rock Mechanics and Geotechnical Engineering 2024年第8期16卷 3270-3283页

作者： J.W.S.Vargas f.A.B.Danziger f.r.Lopes T.Lunne federal University of rio de Janeiro Rio de JaneiroBrazil Norwegian Geotechnical Institute OsloNorway

In situ inflow and outflow permeability tests with the BAT probe at SarapuíII soft clay test site are presented.A description of the BAT permeability test is provided,discussing its advantages and shortcomings,especially in the case of very soft clays under low *** pressures were monitored during probe installation and were found to be slightly lower than piezocone u2 pore pressures,consistent with the position of the *** role of filter tip saturation was investigated after the usual saturation procedure provided an unsatisfactory pore pressure response during probe *** show that the vacuum saturation procedure provides adequate response during installation and increases the reliability of the coefficient of permeability determination in early *** inflow and outflow tests yielded similar results,indicating that careful execution of the test can lead to good test repeatability regardless of the loading *** sequences of alternated inflow and outflow tests have yielded similar results,indicating that soil reconsolidation and filter clogging were negligible in the tests *** are presented concerning the relationship between index parameters and the in situ coefficient of permeability for SarapuíII clay,which plot outside the range of existing databases.

关键词： Permeability test Soft clay BAT probe Inflow and outflow tests

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Nonlinear corrections for the nuclear gluon distribution in eA processes

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Chinese Physics C 2024年第3期48卷 52-64页

作者： G.r.Boroun B.rezaei f.Abdi Department of Physics Razi UniversityKermanshah 67149Iran.

An analytical study with respect to the nonlinear corrections for the nuclear gluon distribution function in the next-to-leading order approximation at small x is *** consider the nonlinear corrections to the nuclear gluon distribution functions at low values of x and Q^(2) using the parametrization f_(2)(x,Q^(2))and the nuclear modification factors obtained from the Khanpour-Soleymaninia-Atashbar-Spiesberger-Guzey *** CT18 gluon distribution is used for the baseline proton gluon density at Q^(2)_(0)=*** discuss the behavior of the gluon densities in the next-to-leading order and the next-to-next-to-leading order approximations at the initial scale Q^(2)_(0),as well as the modifications due to the nonlinear *** find that the QCD nonlinear corrections are more significant for the next-to-leading order accuracy than the next-to-next-to-leading order for light and heavy *** results of the nonlinear GLr-MQ evolution equation are similar to those obtained with the rausch-Guzey-Klasen gluon upward and downward evolutions within the *** magnitude of the gluon distribution with the nonlinear corrections increases with a decrease in x and an increase in atomic number A.

关键词： gluon distribution nonlinear corrections light and heavy nuclei low x physics

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Non-canonical BrAf variants and rearrangements in hairy cell leukemia

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Oncology research 2024年第9期32卷 1423-1427页

作者： stephen E.LANGABEEr Cancer Molecular Diagnostics St.James’s HospitalDublinD08 W9RTIreland

Hairy cell leukemia(HCL)is an uncommon mature B-cell malignancy characterized by a typical morphology,immunophenotype,and clinical *** vast majority of HCL patients harbor the canonical BrAf V600E mutation which has become a rationalized target of the subsequently deregulated rAS-rAf-MEK-MAPK signaling pathway in HCL patients who have relapsed or who are refractory to front-line ***,several HCL patients with a classical phenotype display non-canonical BrAf mutations or *** include sequence variants within alternative exons and an oncogenic fusion with the IGH *** must be taken in the molecular diagnostic work-up of patients with typical HCL but without the BrAf V600E to include investigation of these uncommon ***,functional characterization,and reporting of further such patients is likely to provide insights into the pathogenesis of HCL and enable rational selection of targeted inhibitors in such patients if required.

关键词： Hairy cell leukemia BrAf Molecular diagnostics Targeted therapy

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DCfNet:Discriminant Correlation filters Network for Visual Tracking

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Journal of Computer Science & Technology 2024年第3期39卷 691-714页

作者：胡卫明王强高晋李兵 stephen Maybank State Key Laboratory of Multimodal Artificial Intelligence Systems Institute of AutomationChinese Academy of Sciences Beijing 100190China Department of Computer Science and Information Systems Birkbeck CollegeLondon WC1E 7HXU.K.

CNN(convolutional neural network)based real time trackers usually do not carry out online network update in order to maintain rapid tracking *** inevitably influences the adaptability to changes in object *** filter based trackers can update the model parameters online in real *** this paper,we present an end-to-end lightweight network architecture,namely Discriminant Correlation filter Network(DCfNet).A differentiable DCf(discriminant correlation filter)layer is incorporated into a Siamese network architecture in order to learn the convolutional features and the correlation filter *** correlation filter can be efficiently updated *** previous work,we introduced a joint scale-position space to the DCfNet,forming a scale DCfNet which carries out the predictions of object scale and position *** combine the scale DCfNet with the convolutional-deconvolutional network,learning both the high-level embedding space representations and the low-level fine-grained representations for *** adaptability of the fine-grained correlation analysis and the generalization capability of the semantic embedding are complementary for visual *** back-propagation is derived in the fourier frequency domain throughout the entire work,preserving the efficiency of the *** evaluations on the OTB(Object Tracking Benchmark)and VOT(Visual Object Tracking Challenge)datasets demonstrate that the proposed trackers have fast speeds,while maintaining tracking accuracy.

关键词： correlation filter convolutional neural network(CNN) visual tracking

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role of intravascular ultrasound and optical coherence tomography in intracoronary imaging for coronary artery disease:a systematic review

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Journal of Geriatric Cardiology 2024年第1期21卷 104-129页

作者： Maruf Sarwar stephen Adedokun Mahesh Anantha Narayanan Department of Cardiovascular Sciences White River HealthBatesvilleARUSA Division of Cardiology University of Tennessee at MemphisTNUSA University of Arkansas Medical Sciences Little RockARUSA

Coronary angiography has long been the standard for coronary imaging,but it has limitations in assessing vessel wall anatomy and guiding percutaneous coronary intervention(PCI).Intracoronary imaging techniques like intravascular ultrasound(IVUS)and optical coherence tomography(OCT)can overcome these *** uses ultrasound and OCT uses near-infrared light to visualize coronary pathology in unique ways due to differences in temporal and spatial *** techniques have evolved to offer clinical utility in plaque characterization and vessel assessment during ***-analyses and adjusted observational studies suggest that both IVUS and OCT-guided PCI correlate with reduced cardiovascular risks compared to angiographic guidance *** IVUS demonstrates consistent clinical outcome benefits,OCT evidence is less *** has progressed from early motion detection to high-resolution systems,with smaller compatible *** utilizes near infrared light to achieve unparalleled resolutions,but requires temporary blood clearance for optimal *** visualization and guidance make IVUS and OCT well-suited for higher risk PCI in patients with diabetes and chronic kidney disease by allowing detailed visualization of complex lesions and ensuring optimal stent deployment and positioning in PCI for patients with type 2 diabetes and chronic kidney disease,improving *** and recent advancements in zero-and low-contrast OCT techniques can reduce nephrotoxic contrast exposure,thus helping to minimize PCI complications in these high-risk patient *** and OCT provide valuable insights into coronary pathophysiology and guide interventions precisely compared to angiography *** have comparable clinical outcomes,emphasizing the need for tailored imaging choices based on clinical *** refinement and integration of intravascular imaging will likely play a pivotal role in optimizing coronary interventions and outcomes.

关键词： coronary anatomy limitations

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2024 Wheelchair Compendium of Physical Activities:An update of activity codes and energy expenditure values

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Journal of Sport and Health Science 2024年第1期13卷 18-23页

作者： Scott A.Conger stephen D.Herrmann Erik A.Willis Tom E.Nightingale Joseph r.Sherman Barbara E.Ainsworth Department of Kinesiology Boise State UniversityBoiseID 83725USA Kansas Center for Metabolism and Obesity research The University of Kansas Medical CenterKansas CityKS 66160USA Center for Health Promotion and Disease Prevention University of North Carolina at Chapel HillChapel HillNC 27599USA School of Sport Exercise and Rehabilitation SciencesUniversity of BirminghamBirmingham AL B152TTUK Centre for Trauma Sciences research University of BirminghamEdgbastonBirmingham AL B152TTUK College of Health Solutions Arizona State UniversityPhoenixAZ 85003USA School of Exercise and Health Shanghai University of SportShanghai 200438China

Purpose:This paper presents an update of the 2011 Wheelchair Compendium of Physical Activities designed for wheelchair users and is referred to as the 2024 Wheelchair *** Wheelchair Compendium aims to curate existing knowledge of the energy expenditure for wheelchair physical activities(PAs).Methods:A systematic review of the published energy expenditure of PA for wheelchair users was completed between 2011 and May *** added these data to the 2011 Wheelchair Compendium data that was compiled previously in a systematic review through ***:A total of 47 studies were included,and 124 different wheelchair PA reported energy expenditure values ranging from 0.8 metabolic equivalents for wheelchair users(filing papers,light effort)to 11.8 metabolic equivalents for wheelchair users(Nordic sit skiing).Conclusion:In introducing the updated 2024 Wheelchair Compendium,we hope to bridge the resource gap and challenge the prevailing narratives that inadvertently exclude wheelchair users from physical fitness and health PAs.

关键词： Disability Exercise MET Mobility

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