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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

莫斯科-喀山高速铁路沿线大气冻融指数时空变化特征

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长沙理工大学学报(自然科学版) 2024年

作者：张志超游志浪许健彭洋 Gagarin leonid 西安建筑科技大学土木工程学院西安建筑科技大学陕西省岩土与地下空间工程重点实验室俄罗斯科学院西伯利亚分院梅尔尼科夫冻土研究所

【目的】“莫斯科-喀山高速铁路”（莫喀高铁）是我国参与高纬度地区的重要代表性工程，为助力此工程设计与建设，十分有必要掌握沿线气温特征。【方法】基于英国东英吉利大学（University of East Anglia， UEA）气候研究中心（Climati... 详细信息

【目的】“莫斯科-喀山高速铁路”（莫喀高铁）是我国参与高纬度地区的重要代表性工程，为助力此工程设计与建设，十分有必要掌握沿线气温特征。【方法】基于英国东英吉利大学（University of East Anglia， UEA）气候研究中心（Climatic Research Unit， CRU）1901-2021年CRU格点数据月平均气温数据集，研究了莫喀高铁沿线的气温冻融指数变化趋势及空间变化特征。【结果】莫喀高铁沿线地区1901-2021年年冻结指数平均值介于411.23℃·d～1773.70℃·d之间，总体呈现波动下降趋势；年融化指数平均值介于2223.69℃·d～3170.31℃·d之间，总体呈现波动上升趋势，这表明莫喀高铁沿线的年平均气温自1901年到2021年在逐渐升高。在空间分布上，莫喀高铁沿线地区1901-2021年的多年平均冻结指数呈现出明显的由西向东递增的趋势，多年平均冻结指数介于841.553℃·d～1360.13℃·d之间，而该地区多年平均融化指数整体相差不大，介于2654.4℃·d～2748.63℃·d之间，由中部向东西两侧递增，这表明：自下诺夫哥罗德到莫斯科地区气温逐渐降低，而自下诺夫哥罗德到喀山地区气温逐渐升高，得出莫喀高铁沿线气温自西向东逐渐升高，莫斯科地区升温相对不明显，而喀山是该沿线升温最明显的地区。【结论】采用CRU格点气温数据集来研究莫喀高铁沿线大气冻融指数时空变化特征是一种较为有效的手段，同时也为研究该高速铁路沿线的气候变化特征、冻土状态和其他工程建设提供科学借鉴。

关键词：莫喀高铁沿线月平均气温冻结指数融化指数时空变化特征冻土变化

Mechanisms Modeling the Double Rotation of the Elytra in Beetles （Coleoptera）

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Journal of Bionic Engineering 2011年第4期8卷 395-405页

作者： leonid Frantsevich Schmalhausen-Institute of Zoology B. Chmielnicki str. 15 Kiev-3 O 01601 Ukraine

We recorded transient movements, i.e. opening and closing, of beetle elytra. The beetles were tethered from below and filmed under a skew mirror; two markers were glued on each elytron at the apex and at the base. Body-fixed 3D traces of the apical and basal markers were reconstructed. The trace of the basal marker was, as a rule, non-parallel to the apical trace. The costal edge of the elytron uniformly supinated in the course of adduction of the apical marker. We found two essential attributes of double rotation：（1） the elytron to body articulation is approximately a spherical mechanism; （2） transient opening and closing possess single degree of freedom. The double rotation was modeled with two mechanisms：（1） a flexagon model of the Haas and Wootton＇s type simulated the elytral movement relative to the movement of one facet of the flexagon; （2） a screw and nut model provided traces as two sectors of a helical thread, one sector was phase shifted with respect to other one. Screw guideways in a spherical mechanism give rise to discrepancies. Exact solution for a spherical mechanism with two guideways was proposed. The modeling revealed the attribute （3）： the elytron is actuated by two linked but differently directed drives. Experimental investigations on the elytron to body articulation may be oriented at search of those mechanisms.

关键词： insect flight insect thorax flexagon screw and nut joint

基于一维和三维CFD方法的四级径流式鼓风机扩压器和回流器设计与优化

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风机技术 2024年第3期66卷 47-59页

作者： Vlad Goldenberg leonid Moroz Ti-shun Zhang Shigeyuki Tomimatsu Masatoshi Tomita SoftInWay Inc. USA DMWCorporation Japan

Soft In Way Inc. performed the aerodynamic design of a 4 stages high pressure radial blower with vaneless diffusers and deswirlers for DMW Corporation in 2021. The nominal pressure ratio of the machine is near *** a pressure ratio often characterizes what would typically be called a compressor, especially if the compression work is performed in one stage. For the subject machine of the present study, the compression work is split into 4 *** paper describes the design procedure for this blower, initially focusing in depth on the tradeoffs between work split,rotor diameter, and rotor vane back-sweep angle. The paper then presents a further design and optimization work of different variants of diffuser and deswirler based on aerodynamic performance for this 4 stages radial blower. The number of deswirler blades in the return channel was reduced from 19 to 10 in consideration of manufacturing requirements. To minimize losses in performance due to reduced blade number, several candidates of varied geometry shape deswirler blades were obtained from an automatic design and optimization workflow combining with 3D CFD calculation. All candidates of deswirler were implemented to the entire 4 stages radial blower to analyze machine performance by 3D CFD calculation and the best 10-blade deswirler geometry was determined. 3D CFD analysis shows that 10 blades of deswirler is unable to provide the same pressure rise and efficiency as the original design with 19 blades when all other parts of the design, such as rotor and diffuser are maintained the same. To further improve the blower performance, the similar automatic workflow was applied to study vaned diffuser influence to the blower performance based on the new blower configuration. The number and geometry of best diffuser blades was obtained from the automatic workflow and entire blower performance with vaned diffuser was analyzed and validated by 3D CFD calculation. After finalizing the aerodynamic flow path geome

关键词： Radial Blower Blower Design Blower 1D Analysis Deswirler Diffuser Automatic Optimization 3DCFD Surge Determination

The Dependence of Stellar Activity Cycles on Effective Temperature

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Research in Astronomy and Astrophysics 2022年第12期22卷 198-210页

作者： leonid Kitchatinov Institute of Solar-Terrestrial Physics SB RAS Lermontov Str.126AIrkutsk 664033Russia

This paper proposes the idea that the observed dependence of stellar activity cycles on rotation rate can be a manifestation of a stronger dependence on the effective temperature. Observational evidence is recalled and theoretical arguments are given for the presence of cyclic activity in the case of sufficiently slow rotation only. Slow rotation means proximity to the observed upper bound on the rotation period of solar-type stars. This maximum rotation period depends on temperature and shortens for hotter stars. The maximum rotation period is interpreted as the minimum rotation rate for operation of a large-scale dynamo. A combined model for differential rotation and the dynamo is applied to stars of different mass rotating with a rate slightly above the threshold rate for the *** show shorter dynamo cycles for hotter stars. As the hotter stars rotate faster, the computed cycles are also shorter for faster rotation. The observed smaller upper bound for rotation period of hotter stars can be explained by the larger threshold amplitude of the α-effect for onset of their dynamos: a larger α demands faster rotation. The amplitude of the(cycling) magnetic energy in the computations is proportional to the difference between the rotation period and its upper bound for the dynamo. Stars with moderately different rotation rates can differ significantly in super-criticality of their dynamos and therefore in their magnetic activity, as observed.

关键词： dynamo stars:activity stars:magnetic field stars:solar-type stars:rotation

Association between Exposure to Metals during Pregnancy,Childhood Gut Microbiome,and Risk of Intestinal Inflammation in Late Childhood

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Environment & Health 2024年第10期2卷 739-749页

作者： Vishal Midya Manasi Agrawal Jamil M.Lane Chris Gennings leonid Tarassishin Libni A.Torres-Olascoaga Joseph Eggers Jill K.Gregory Mellissa Picker Inga Peter Jeremiah J.Faith Manish Arora Martha M.Tellez-Rojo Robert O.Wright Jean-Frederic Colombel Shoshannah Eggers Department of Environmental Medicine and Climate Science Icahn School of Medicine at Mount SinaiNew York 10029-6574New YorkUnited States Division of Gastroenterology Icahn School of Medicine at Mount SinaiNew York 10029-6574New YorkUnited States Center for Molecular Prediction of Inflammatory Bowel Disease(PREDICT) Department of Clinical MedicineAalborg UniversityCopenhagen 9220Denmark Department of Genetics and Genomic Sciences Icahn School of MedicineNew York 10029-6574New YorkUnited States Center for Research on Nutrition and Health National Institute of Public HealthCuernavaca 62508Mexico Department of Immunology and Immunotherapy Icahn School of Medicine at Mount SinaiNew York 10029-6574New YorkUnited States Department of Epidemiology University of Iowa College of Public HealthIowa City 52242 IowaUnited States Instructional Technology Group Icahn School of Medicine at Mount SinaiNew York 10029-6574New YorkUnited States

Alterations to the gut microbiome and exposure to metals during pregnancy have been suggested to impact inflammatory bowel ***,how prenatal exposure to metals eventually results in long-term effects on the gut microbiome,leading to subclinical intestinal inflammation,particularly during late childhood,has not been *** is also unknown whether such an interactive effect drives a specific subgroup of children toward elevated susceptibility to intestinal *** used an amalgamation of machine-learning techniques with a regression-based framework to explore if children with distinct sets of gut microbes and certain patterns of exposure to metals during pregnancy(metal−microbial clique signature)had a higher likelihood of intestinal inflammation,measured based on fecal calprotectin(FC)in late *** obtained samples from a well-characterized longitudinal birth cohort from Mexico City(n=108),*** the second and third trimesters of pregnancy,11 metals were measured in whole *** microbial abundances and FC were measured in stool samples from children 9−11 years of *** FC was defined as having FC above 100μg/g of *** identified subgroups of children in whom microbial and metal−microbial clique signatures were associated with elevated FC(false discovery rate(FDR)<0.05).In particular,we found two metal−microbial clique signatures significantly associated with elevated FC:(1)low cesium(Cs)and copper(Cu)in the third trimester and low relative abundance of Eubacterium ventriosum(OR[95%CI]:10.27[3.57,29.52],FDR<0.001)and(2)low Cu in the third trimester and high relative abundances of Roseburia inulinivorans and Ruminococcus torques(OR[95%CI]:7.21[1.81,28.77],FDR<0.05).This exploratory study demonstrates that children with specific gut microbes and specific exposure patterns to metals during pregnancy may have higher fecal calprotectin levels in late childhood,denoting an elevated risk of intestinal inflammation.

关键词： exposome metals machine learning microbiome environmental epidemiology intestinal inflammation

Pulsed THz radiation under ultrafast optical discharge of vacuum photodiode

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Frontiers of Optoelectronics 2024年第2期 100-113页

作者： Aleksandr A.Ushakov Kseniia A.Mamaeva leonid V.Seleznev Georgy E.Rizaev Vladimir Bukin Timophey V.Dolmatov Pavel A.Chizhov Vladimir Bagdasarov Sergey V.Garnov Prokhorov General Physics Institute of the Russian Academy of Sciences Physical Institute Russian Academy of Sciences Moscow Institute of Physics and Technology Russian Institute for Scientific and Technical Information

In this paper, we first present an experimental demonstration of terahertz radiation pulse generation with energy up to 5 pJ under the electron emission during ultrafast optical discharge of a vacuum photodiode. We use a femtosecond optical excitation of metallic copper photocathode for the generation of ultrashort electron bunch and up to 45 kV/cm external electric field for the photo-emitted electron acceleration. Measurements of terahertz pulses energy as a function of emitted charge density, incidence angle of optical radiation and applied electric field have been provided. Spectral and polarization characteristics of generated terahertz pulses have also been studied. The proposed semi-analytical model and simulations in COMSOL Multiphysics prove the experimental data and allow for the optimization of experimental conditions aimed at flexible control of radiation parameters.

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小国的大气象亚美尼亚的地道风物

环球人文地理 2024年第1期 36-45页

作者：读书康梁庭俊宣砚 leonid Andronov katiekk2 v unsplash 摄图网

亚美尼亚人将水果杏奉为国宝，爱吃重油重盐的烤肉、大饼。在市中心的购物大街与教堂中，能一窥他们的生活与精神世界。说到葡萄酒，除了法国，亚美尼亚的葡萄酒也是历史悠久。除此以外，随处可见的修道院也是亚美尼亚的标志之一。左页...

亚美尼亚人将水果杏奉为国宝，爱吃重油重盐的烤肉、大饼。在市中心的购物大街与教堂中，能一窥他们的生活与精神世界。说到葡萄酒，除了法国，亚美尼亚的葡萄酒也是历史悠久。除此以外，随处可见的修道院也是亚美尼亚的标志之一。左页大图为当地的葡萄园。右页图为亚美尼亚的修道院。在杰尔穆克的日子，说得上是此行节奏最慢的时候。

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来源：博看期刊

Computational study of laser fragmentation in liquid:Phase explosion,inverse Leidenfrost effect at the nanoscale,and evaporation in a nanobubble

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Science China(Physics,Mechanics & Astronomy) 2022年第7期65卷 99-114页

作者： Hao Huang leonid V.Zhigilei School of Mechanical Science and Engineering Huazhong University of Science and TechnologyWuhan 430074China Department of Materials Science and Engineering University of VirginiaCharlottesville 22904-4745USA

Laser fragmentation in liquid is an effective and environment-friendly processing technique capable of yielding colloidal nanoparticles and atomic clusters with a narrow size distribution. The advancement of this technique can be facilitated by an improved understanding of processes that control the sizes, shapes, and structures of the produced nanoparticles. In this work, the dependence of the fragmentation mechanisms on the energy density deposited by the laser pulse is investigated in atomistic simulations performed for 20 nm Au nanoparticles irradiated in water by 10 ps laser pulses. The simulations reveal that the decrease in the absorbed laser energy leads to sequential transitions from the regime of “strong” phase explosion, when all products of an explosive phase decomposition of the irradiated nanoparticle are promptly injected into the water surrounding a nanobubble formed around the nanoparticle, to two distinct regimes of nanoparticle fragmentation leading to the formation of a large central nanoparticle surrounded by smaller satellite fragments. First, in the regime of “mild” phase explosion, the central nanoparticle is produced by the reflection of some of the hot metal droplets generated by the explosive decomposition of the nanoparticle from the boundary of the nanobubble. This reflection is attributed to the inverse Leidenfrost effect acting at the nanoscale. The reflected droplets converge in the center of the nanobubble and coalesce into a single droplet that solidifies shortly after the collapse of the nanobubble. Further decrease in the absorbed laser energy brings the irradiation conditions below the threshold for the phase explosion and results in the formation of a core-satellite structure of the fragmentation products through an interplay of the intense evaporation from the surface of the irradiated nanoparticle, evolution of the nanobubble, and condensation of the metal vapor into clusters and small satellite nanoparticles. The computationa

关键词： laser fragmentation in liquid molecular dynamics simulations phase explosion inverse Leidenfrost effect nanobubble nanoparticles