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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

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

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)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],FDRster and high relative abundances of Roseburia inulinivorans and Ruminococcus torques(OR[95%CI]:7.21[1.81,28.77],FDRs 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

Artificial intelligence applications in finance:a survey

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Journal of Management Analytics 2023年第4期10卷 676-692页

作者： Xuemei Li Alexander sigov leonid Ratkin leonid A.Ivanov Ling Li Department of Information Technology and Decision sciences Strome College of BusinessOld Dominion UniversityNorfolkVAUSA Department of Electronic Machinery University of Electronic Science and Technology of ChinaChengduPeople’s Republic of China Russian Technological University MoscowRussian Federation Russian Academy of sciences MoscowRussian Federation Russian Academy of Engineering MoscowRussian Federation

Finance is in our daily *** invest,borrow,lend,budget,and save *** also provides guidelines for corporation and government spending and revenue *** statistical solutions such as regression,PCA,and CFA have been widely used in financial forecasting and *** the increasing interest in artificial intelligence in recent years,this paper reviews the Artificial Intelligence(AI)techniques in the finance domain systematically and attempts to identify the current AI technologies used,major applications,challenges,and trends in *** explores AI-related articles in Finance in IEEE Xplore and EI compendex *** suggest AI has been engaged in Finance in financial forecasting,financial protection,and financial analysis and decision-making *** forecasting is one of the main sub-fields of Finance affected by AI *** major AI technology used is supervised *** learning has gained popular in recent *** could be used to address some emerging topics.

关键词： machine learning artificial intelligence finance

subcritical dynamo and hysteresis in a Babcock-Leighton type kinematic dynamo model

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Research in Astronomy and Astrophysics 2021年第10期21卷 250-256页

作者： Vindya Vashishth Bidya Binay Karak leonid Kitchatinov Department of Physics Indian Institute of Technology(BHU)Varanasi 221005India Institute of solar-Terrestrial Physics sB RAs Lermontov Str.126A664033IrkutskRussia Pulkovo Astronomical Observatory Pulkovskoe Sh.65St.Petersberg196140Russia

In the sun and sun-like stars,it is believed that cycles of the large-scale magnetic field are produced due to the existence of differential rotation and helicity in the plasma flows in their convection zones(CZs).Hence,it is expected that for each star,there is a critical dynamo number for the operation of a large-scale *** a star slows down,it is expected that the large-scale dynamo ceases to operate above a critical rotation *** our study,we explore the possibility of the operation of the dynamo in the subcritical region using the Babcock–Leighton type kinematic dynamo *** some parameter regimes,we find that the dynamo shows hysteresis behavior,i.e.,two dynamo solutions are possible depending on the initial parameters—decaying solution if starting with weak field and strong oscillatory solution(subcritical dynamo)when starting with a strong ***,under large fluctuations in the dynamo parameter,the subcritical dynamo mode is unstable in some parameter ***,our study supports the possible existence of subcritical dynamo in some stars which was previously demonstrated in a mean-field dynamo model with distributedαand MHD turbulent dynamo simulations.

关键词： magnetic field sun:activity sun:magnetic fields stars:rotation stars:dynamo stars

Dynamo saturation in rapidly rotating solar-type stars

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Research in Astronomy and Astrophysics 2015年第11期15卷 1801-1812页

作者： leonid L.Kitchatinov serge V.Olemskoy Institute for solar-Terrestrial Physics Pulkovo Astronomical Observatory

The magnetic activity of solar-type stars generally increases with stellar rotation rate. The increase, however, saturates for fast rotation. The Babcock-Leighton mechanism of stellar dynamos saturates as well when the mean tilt angle of active regions approaches ninety degrees. saturation of magnetic activity may be a consequence of this property of the Babcock-Leighton mechanism. stellar dynamo models with a tilt angle proportional to the rotation rate are constructed to probe this *** versions of the model- treating the tilt angles globally and using Joy＇s law for its latitude dependence- are considered. Both models show a saturation of dynamogenerated magnetic flux at high rotation rates. The model with latitude-dependent tilt angles also shows a change in dynamo regime in the saturation region. The new regime combines a cyclic dynamo at low latitudes with an（almost） steady polar dynamo.

关键词： saturation stellar latitude rotation rotating stars polar regime meridional consequence

Alkali control of high-grade metamorphism and granitization

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Geoscience Frontiers 2014年第5期5卷 711-727页

作者： Oleg G.safonov leonid Y.Aranovich Institute of Experimental Mineralogy RAs ChernogolovkaMoscow RegionRussia Department of Petrology Moscow State UniversityMoscowRussia Department of Geology.University of Johannesburg Johannesburg.south Africa Institute of Geology of Ore Deposits PetrographyMineralogy and Geochemistry

We review petrologic observations of reaction textures from high-grade rocks that suggest the passage of fluids with variable alkali activities. Development of these reaction textures is accompanied by regular compositional variations in plagioclase, pyroxenes, biotite, amphibole and garnet. The textures are interpreted in terms of exchange and net-transfer reactions controlled by the K and Na activities in the fluids. On the regional scale, these reactions operate in granitized, charnockitized, syenitized etc. shear zones within high-grade complexes. Thermodynamic calculations in simple chemical systems show that changes in mineral assemblages, including the transition from the hydrous to the anhydrous ones, may occur at constant pressure and temperature due only to variations in the H2O and the alkali activities. A simple procedure for estimating the activity of the two major alkali oxides, K2O and Na2O, is imple- mented in the TWQ software. Examples of calculations are presented for well-documented dehydration zones from south Africa, southern India, and sri Lanka. The calculations have revealed two end-member regimes of alkalis during specific metamorphic processes： rock buffered, which is characteristic for the precursor rocks containing two feldspars, and fluid-buffered for the precursor rocks without K-feldspar. The observed reaction textures and the results of thermodynamic modeling are compared with the results of available experimental studies on the interaction of the alkali chloride and carbonate-bearing fluids with metamorphic rocks at mid-crustal conditions. The experiments show the complex effect of alkali activities in the fluid phase on the mineral assemblages. Both thermodynamic calculations and experiments closely reproduce paragenetic relations theoretically predicted by D.s. Korzhinskii in the 1940s.

关键词： High-grade metamorphismAlkali activityFluidsReaction texturesFluid-mineral reactionsThermodynamic modeling

Little effect of climate change on body size of herbivorous beetles

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Insect science 2018年第2期25卷 309-316页

作者： Yuval Baar Ariel Leib leonid Friedman shai Meiri Inon scharf Department of Zoology Faculty of Life Sciences ＆ Steinhardt Museum of Natural History and National Research Center Tel Aviv University Tel Aviv Israe

Ongoing climate change affects various aspects of an animal＇s life, with impor- tant effects on distribution range and phenology. The relationship between global warming and body size changes in mammals and birds has been widely studied, with most find- ings indicating a decline in body size over time. Nevertheless, little data exist on similar size change patterns of invertebrates in general and insects in particular, and it is unclear whether insects should decrease in size or not with climate warming. We measured over 4000 beetle specimens, belonging to 29 beetle species in 8 families, collected in Israel during the last 100 years. The sampled species are all herbivorous. We examined whether beetle body size had changed over the years, while also investigating the relationships between body size and annual temperature, precipitation, net primary productivity （NPP） at the collection site and collection month. None of the environmental variables, including the collection year, was correlated with the size of most of the studied beetle species, while there were strong interactions of all variables with species. Our results, though mostly neg- ative, suggest that the effect of climate change on insect body size is species-specific and by no means a general macro-ecological rule. They also suggest that the intrapopulation variance in body size of insects collected as adults in the field is large enough to conceal intersite environmental effects on body size, such as the effect of temperature and NPE

关键词： Coleoptera museum collections rain temperature-size rule thermal ecol-ogy

High-pressure, High-temperature synthesis and Properties of the Monoclinic Phase of Y2O3

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Chemical Research in Chinese Universities 2016年第4期32卷 545-548页

作者： ZHANG Qian WU Xiang OVsYANNIKOV V. sergey DONG Juncai QIN shan DUBROVINsKY s. leonid CHEN Dongliang Gemological Institute China University of Geosciences Wuhan 430074 P. R. China state Key Laboratory of Geological Processes and Mineral Resources China University of Geosciences Wuhan 430074 P R. China Key Laboratory of Orogenic Belts and Crustal Evolution Ministry of Education & School of Earth and Space Sciences Peking University Beo'ing 100871 P. R. China Bayerisches Geoinstitut Universitat Bayreuth Bayreuth D-95447 Germany Beijing synchrotron Radiation Facility Institute of High Energy Physics Chinese Academy of Sciences Beijing 100049 P. R. China

The monoclinic phase of Y2O3（B-REs） has been synthesized using a Kawai-type multi-anvil apparatus under 20 GPa at 1800℃. samples of the cubic Y2O3（C-REs） and monoclinic Y2O3 phases were characterized by synchrotron radiation X-ray diffraction, X-ray absorption near edge structure and Raman spectroscopy. Crystal structures of the cubic and monoclinic phases have been examined using Rietveld refinement of the X-ray diffraction data. The cubic-to-monoclinic transition of Y2O3 was reconstructive and irreversible. The X-ray diffraction results were further confirmed by simulation of the X-ray absorption spectra.

关键词： Y2O3 High pressure Multi-anvil synthesis