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A dNA-Binding Bromodomain-Containing Protein Interacts with and Reduces Rx1-Mediated Immune Response to Potato Virus X

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Plant Communications 2020年第4期1卷 101-114页

作者： Octavina C.A.Sukarta philip d.townsend Alexander Llewelyn Christopher H.dixon Erik J.Slootweg Lars-Olof Pålsson Frank L.W.Takken Aska Goverse Martin J.Cann Laboratory of Nematology Department of Plant SciencesWageningen University6708 PB WageningenThe Netherlands department of Biosciences Durham UniversitySouth RoadDurham DH13LEUK Biophysical Sciences Institute Durham UniversitySouth RoadDurham DH13LEUK department of Chemistry Durham UniversitySouth RoadDurham DH13LEUK Molecular Plant Pathology Swammerdam Institute for Life SciencesUniversity of AmsterdamScience Park 9041098 XH AmsterdamThe Netherlands

Plant NLR proteins enable the immune systemto recognize and respond to pathogen *** early consequence of immune activation is transcriptional *** have been shownto act in the nucleus and interact with transcription *** Rx1 NLR protein of potato binds and distorts doublestranded ***,the components of the chromatin-localized Rx1 complex are largely ***,we report a physical and functional interaction between Rx1 and NbdBCP,a bromodomaincontaining chromatin-interacting *** accumulates in the nucleoplasmand nucleolus,interacts with chromatin,and redistributes Rx1 tothe nucleolus in a subpopulation of imaged ***1 overexpression reduces the interaction between NbdBCP and *** is a negative regulator of Rx1-mediated immune responses to potato virus X(PVX),and this activity requires an intact ***,Rx1 has been shown to regulate the dNA-binding activity of a Golden2-like transcription factor,***1 and NbdBCP act synergistically to reduce NbGlk1 dNA binding,suggesting a mode of action for NbdBCP’s inhibitory effect on *** study provides new mechanistic insight into the mechanism by which a chromatin-localized NLR complex co-ordinates immune signaling after pathogen perception.

关键词： cellular immune response dNA-binding protein host-pathogen interaction plant biochemistry plant defense plant virus

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Modelling the brittle rock failure by the quaternion-based bonded-particle model in dEM

Rock Mechanics Bulletin

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Rock Mechanics Bulletin 2024年第2期3卷 87-95页

作者： Tao Zhao philip E.F.Collins department of Civil and Environmental Engineering Brunel University LondonLondonUB83PHUnited Kingdom

This paper presents an investigation of brittle rock failure by the quaternion-based bonded-particle model in discrete element method(dEM).Unlike traditional approaches that utilize Euler angles or rotation matrices,this model employs unit quaternions to represent the spatial rotations of *** method simplifies the rep-resentation of 3d rotations,providing a more intuitive framework for modelling complex interactions in granular *** numerical model was validated by the uniaxial compression tests on rock,with good agreement with well-documented experimental data in terms of the rock uniaxial compression strength(UCS)and failure *** loading,the rock sample demonstrated a linear-elastic response at an axial strain of smaller than 0.45%.However,as internal bond breakage accumulated,this linear relationship weakened,and the stress-strain curve began to deviate from its initial linear *** bond breakage and the overall deformation of the rock were primarily controlled by the shear bonding *** UCS was achieved at an axial strain of 0.625%,at which point the internal shear bonding force chains were predominantly aligned *** brittle failure occurred when the internal damage of solids nucleated to form an interconnected failure plane,accompanied by a sharp rise in the internal damage *** area of failure plane increased with the loading strain rate,gradually transforming the failure pattern from the local damage to a complete fragmentation.

关键词： Brittle failure Quaternion dEM bonded model Uniaxial compression test Rate dependent Internal damage

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MicroRNAs as potential diagnostic biomarkers for bipolar disorder

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Neural Regeneration Research 2025年第6期20卷 1681-1695页

作者： Bridget Martinez philip V.Peplow department of Pharmacology University of Nevada-RenoRenoNVUSA department of Medicine University of Nevada-RenoRenoNVUSA department of Anatomy University of OtagoDunedinNew Zealand

Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed i

关键词： biomarker bipolar disorder blood leukocytes blood plasma blood plasma extracellular vesicles/exosomes blood serum brain tissue brain tissue extracellular vesicles/exosomes lymphoblastoid cell lines microRNA neural progenitor cells whole blood

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A novel homozygous missense variant in ARSK causes MPS X,a new subtype of mucopolysaccharidosis

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Genes & diseases 2024年第3期11卷 87-90页

作者： Miao Sun Cornelia K.Kaminsky philip deppe Mai-Brittllse Frederic M.Vaz Barbara Plecko Torben Lubke Linda M.Randolph division of Genomic Medicine Department of Pathology and Laboratory MedicineChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA department of Radiology Children's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA department of Chemistry BiochemistryBielefeld UniversityBielefeld 33615Germany Amsterdam UMC Location University of Amsterdam Department of Clinical Chemistry and PediatricsLaboratory Genetic Metabolic DiseasesEmma Children's HospitalMeibergdreef 9Amsterdam 1100 DEthe Netherlands Amsterdam Gastroenterology Endocrinology Metabolism Inborn Errors of MetabolismAmsterdam 1105 BKthe Netherlands Core Facility Metabolomics Amsterdam UMC Location University of AmsterdamAmsterdam 1100DDthe Netherlands department of Pediatrics Division of General PediatricsMedical Universityof GrazGraz8036Austria division of Medical Genetics Department of PediatricsChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA

Mucopolysaccharidoses(MPS)are a group of rare inborn errors of metabolism caused by defective lysosomal enzymes which prevent cells from degrading and recycling certain carbohydrates and fats,resulting in the storage of glycosaminoglycans in cells throughout the *** leads to multisystem abnormalities involving bone,connective tissues,brain,blood,spinal cord,skin,and other tissues.

关键词： metabolism doses polys

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An illustrated guide to:Parsimonious multi-scale full-waveform inversion

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Earthquake Science 2024年第6期37卷 574-583页

作者： Andreas Fichtner Solvi Thrastarson dirk-philip van Herwaarden Sebastian Noe department of Earth Sciences ETH ZürichZürich 8049Switzerland

Having been a seemingly unreachable ideal for decades,3-d full-waveform inversion applied to massive seismic datasets has become reality in recent *** achieving unprecedented resolution,it has provided new insight into the structure of the Earth,from the upper few metres of soil to the entire *** by these successes,the technology is now being translated to medical ultrasound and non-destructive *** remarkable progress,the computational cost of fullwaveform inversion continues to be a major *** limits the amount of data that can be exploited,and it largely inhibits quantitative and comprehensive uncertainty *** notes complement a presentation on recent developments in full-waveform inversion that are intended to reduce computational cost and assimilate more data,thereby improving tomographic *** suite of strategies includes flexible and user-friendly spectral-element simulations,the design of wavefieldadapted meshes that harness prior information on wavefield geometry,dynamic mini-batch optimisation that naturally takes advantage of data redundancies,and collaborative multi-scale updating to jointly constrain crustal and mantle structure.

关键词： Earth model seismology full-waveform inversion

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Boosting Adaptive Weighted Broad Learning System for Multi-Label Learning

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IEEE/CAA Journal of Automatica Sinica 2024年第11期11卷 2204-2219页

作者： Yuanxin Lin Zhiwen Yu Kaixiang Yang Ziwei Fan C.L.philip Chen the School of Computer Science and Engineering in South China University of Technology IEEE the Pengcheng Laboratory

Multi-label classification is a challenging problem that has attracted significant attention from researchers, particularly in the domain of image and text attribute annotation. However, multi-label datasets are prone to serious intra-class and inter-class imbalance problems, which can significantly degrade the classification performance. To address the above issues, we propose the multi-label weighted broad learning system(MLW-BLS) from the perspective of label imbalance weighting and label correlation mining. Further, we propose the multi-label adaptive weighted broad learning system(MLAW-BLS) to adaptively adjust the specific weights and values of labels of MLW-BLS and construct an efficient imbalanced classifier set. Extensive experiments are conducted on various datasets to evaluate the effectiveness of the proposed model, and the results demonstrate its superiority over other advanced approaches.

关键词： Broad learning system label correlation mining label imbalance weighting multi-label imbalance

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK department of Neurology Oslo University HospitalOsloNorway Research and development Norwegian Air Ambulance FoundationOsloNorway department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5d,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(Sd),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWd)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWd 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREAdY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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Unveiling a novel metal-to-metal transition in LuH_(2):Critically challenging superconductivity claims in lutetium hydrides

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Matter and Radiation at Extremes 2024年第3期9卷 65-73页

作者： dong Wang Ningning Wang Caoshun Zhang Chunsheng Xia Weicheng Guo Xia Yin Kejun Bu Takeshi Nakagawa Jianbo Zhang Federico Gorelli philip dalladay-Simpson Thomas Meier Xujie Lü Liling Sun Jinguang Cheng Qiaoshi Zeng Yang ding Ho-kwang Mao Center for High-Pressure Science and Technology Advanced Research Beijing 100094China Beijing National Laboratory for Condensed Matter Physics and Institute of Physics Chinese Academy of SciencesBeijing 100190China Shanghai Key Laboratory of Material Frontiers Research in Extreme Environments(MFree) Shanghai Advanced Research in Physical Sciences(SHARPS)Shanghai 201203China

Following the recent report by dasenbrock-Gammon et al.[Nature 615,244–250(2023)]of near-ambient superconductivity in nitrogendoped lutetium trihydride(LuH_(3-δ)N_(ε)),significant debate has emerged surrounding the composition and interpretation of the observed sharp resistance ***,we meticulously revisit these claims through comprehensive characterization and *** definitively identify the reported material as lutetium dihydride(LuH_(2)),resolving the ambiguity surrounding its *** similar conditions(270–295 K and 1–2 GPa),we replicate the reported sharp decrease in electrical resistance with a 30%success rate,aligning with the observations by dasenbrock-Gammon et ***,our extensive investigations reveal this phenomenon to be a novel pressure-induced metal-to-metal transition intrinsic to LuH_(2),distinct from ***,nitrogen doping exerts minimal impact on this *** work not only elucidates the fundamental properties of LuH_(2)andLuH_(3),but also critically challenges the notion of superconductivity in these lutetium hydride *** findings pave the way for future research on lutetium hydride systems,while emphasizing the crucial importance of rigorous verification in claims of ambient-temperature superconductivity.

关键词： resistance hydride superconductivity

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The association of diet quality and physical activity with cardiovascular disease and mortality in 85,545 older Australians:A longitudinal study

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Journal of Sport and Health Science 2024年第6期13卷 841-850页

作者： ding ding Joe Van Buskirk Stephanie Partridge philip Clare Edward Giovannucci Adrian Bauman Nicole Freene Robyn Gallagher Binh Nguyen Sydney School of Public Health Faculty of Medicine and Healththe University of SydneyCamperdownNSW 2006Australia Charles Perkins Centre the University of SydneyCamperdownNSW 2006Australia Sydney Local Health district CamperdownNSW 2050Australia School of Health Sciences Faculty of Medicine and Healththe University of SydneyCamperdownNSW 2006Australia National drug and Alcohol Research Centre UNSW SydneySydneyNSW 2052Australia departments of Nutrition and Epidemiology Harvard T.H.Chan School of Public HealthBostonMA 02115USA Faculty of Health University of CanberraCanberraACT 2617Australia Susan Wakil School of Nursing and Midwifery the University of SydneyCamperdownNSW 2050Australia

Background:A quality diet and an active lifestyle are both important cornerstones of cardiovascular disease(CVd)***,despite their interlinked effects on metabolic health,the 2 behaviors are rarely considered jointly,particularly within the context of CVd *** examined the independent,interactive,and joint associations of diet and physical activity with CVd hospitalization,CVd mortality,and all-cause ***:CVd-free Australian participants aged 4574 years(n=85,545)reported physical activity,diet,sociodemographic,and lifestyle characteristics at baseline(20062009)and follow-up(20122015),and data were linked to hospitalization and death registries(03/31/2019 for CVd hospitalization and all-cause mortality and 12/08/2017 for CVd mortality).diet quality was categorized as low,medium,and high based on meeting dietary *** activity was operationalized as(a)total moderate-to-vigorous physical activity(MVPA)as per guidelines,and(b)the composition of MVPA as the ratio of vigorous-intensity physical activity(VPA)to total *** used a left-truncated cause-specific Cox proportional hazards model using time-varying ***:during a median of 10.7 years of follow-up,6576 participants were admitted to the hospital for CVd and 6581 died from all causes(876 from CVd during 9.3 years).A high-quality diet was associated with a 17%lower risk of all-cause mortality than a low-quality diet,and the highest MVPA category(compared with the lowest)was associated with a 44%and 48%lower risk of CVd and all-cause mortality,*** interactions between diet and physical activity were *** all outcomes,the lowest risk combinations involved a high-quality diet and the highest MVPA *** for total MVPA,some VPA was associated with further risk reduction of CVd hospitalization and all-cause ***:For CVd prevention and longevity,one should adhere to both a healthy d

关键词： diet Physical activity Cardiovascular disease Mortality Cohort studies

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Pandemic Policymaking

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Journal of Social Computing 2021年第1期2卷 14-26页

作者： philip d.Waggoner niversity of Chicago ChicagoIL 60637USAand also with Columbia UniversityNew YorkNY 10027USA.

This study leverages a high dimensional manifold learning design to explore the latent structure of the pandemic policymaking space only based on bill-level characteristics of pandemic-focused bills from 1973 to *** indicate the COVId-19 era of policymaking maps extremely closely onto prior periods of related *** suggests that there is striking uniformity in Congressional policymaking related to these types of large-scale crises over time,despite currently operating in a unique era of hyperpolarization,division,and ineffective governance.

关键词： manifold learning computational social science congress policymaking COVId-19

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