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the bumpy road of purinergic inhibitors to clinical application in immune-mediated diseases

Neural Regeneration Research 2024年第6期19卷 1206-1211页

作者： matihias t.Wyss Christine Heuer marina Herwerth Institute of Pharmacology and toxicology University of Zurich Neuroscience Center Zurich (ZNZ) University of Zurich and ETH Zurich 3. Neurology Department University Hospital of Zurich

Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis. this is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2) with numerous subtypes. In the last few decades, there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions. mainly, signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies. thus, interference with P2 receptors may be a promising strategy for the modulation of immune responses. Although only a few clinical studies have been conducted in isolated entities with limited success, preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases. Despite the association of P2 receptors with several disorders from this field, the use of P2 receptor antagonists in clinical therapy is still very scarce. In this narrative review, we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes. We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events. Using suramin, a non-specific purinergic inhibitor, as an example, we further show that off-target effects could be responsible for observed effects in immunological settings, which may have interesting implications. Overall, we believe that it is worthwhile to further investigate this hitherto underexplored area.

关键词： autoimmune diseases neurological disorders purinergic system P2 receptor inhibitors suramin

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Solvation Effects on the Dielectric Constant of 1 m LiPF6 in Ethylene Carbonate:Ethyl methyl Carbonate 3:7

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Energy & Environmental materials 2024年第1期7卷 257-260页

作者： Julian Self Nathan t.Hahn Kristin A.Persson Department of Chemical Engineering Polytechnique Montreal Department of materials Science and Engineering University of California Energy technologies Area Lawrence Berkeley National Laboratory material Physical and Chemical Sciences Center Sandia National Laboratories

We report the dielectric constant of 1 m LiPF6in EC:EmC 3:7 w/w（ethylene carbonate/ethyl methyl carbonate） in addition to neat EC:EmC 3:7 w/*** three Debye relaxations,the static permittivity value,or dielectric con... 详细信息

关键词： batteries dielectric relaxation spectroscopy electrolytes

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Effects of layer interactions on instantaneous stability of finite Stokes flows

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Applied mathematics and mechanics(English Edition) 2024年第1期45卷 69-84页

作者： Chen ZHAO Zhenli CHEN C.t.mUtASA Dong LI School of Aeronautics Northwestern Polytechnical UniversityXi'an 710072China

the stability analysis of a finite Stokes layer is of practical importance in flow control. In the present work, the instantaneous stability of a finite Stokes layer with layer interactions is studied via a linear stability analysis of the frozen phases of the base flow. the oscillations of two plates can have different velocity amplitudes, initial phases, and frequencies. the effects of the Stokes-layer interactions on the stability when two plates oscillate synchronously are analyzed. the growth rates of two most unstable modes when δ most equal, and δ = δ*/h*, where δ*and h*are the Stokes-layer thickness and the half height of the channel, respectively. However, their vorticities are different. the vorticity of the most unstable mode is symmetric, while the other is asymmetric. the Stokes-layer interactions have a destabilizing effect on the most unstable mode when δ tabilizing effect when δ > 0.68. However, the interactions always have a stabilizing effect on the other unstable mode. It is explained that one of the two unstable modes has much higher dissipation than the other one when the Stokes-layer interactions are strong. We also find that the stability of the Stokes layer is closely related to the inflectional points of the base-flow velocity profile. the effects of inconsistent velocity-amplitude, initial phase, and frequency of the oscillations on the stability are analyzed. the energy of the most unstable eigenvector is mainly distributed near the plate of higher velocity amplitude or higher oscillation frequency. the effects of the initial phase difference are complicated because the base-flow velocity is extremely sensitive to the initial phase.

关键词： finite Stokes layer instantaneous stability Stokes-layer interaction asynchronous oscillation

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Engineering of efficient visible light photocatalysts:ti_(1-x+y)Cu_(x)La_(y)O_(2)(x=0.03;y=0,0.005,0.01) compositions

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Journal of Rare Earths 2024年第3期42卷 497-505,I0003页

作者： S.m.Yakout A.m.Youssef Inorganic Chemistry Department National Research Centre(NRC)El Buhouth StDokkiCairo12622Egypt

In dye-photocatalysis, widening the wavelengths absorption range of catalysts as well as aborting the recombination of the photoexcited charge carriers(electrons-holes pairs) are of paramount *** the current study, we report the photocatalytic characteristics of four compositions composed of tiO_(2),ti_(0.97)Cu_(0.03)O_(2), ti_(0.965)Cu_(0.03)La_(0.005)O_(2)and ti_(0.96)Cu_(0.03)La_(0.01)O_(2)powders for two harmful dyes(Congo red and methylene blue). the X-ray diffraction technique verified the configuration of mixed anatase and rutile phases in pure tiO_(2)and ti_(0.97)Cu_(0.03)O_(2)powders while ti_(0.965)Cu_(0.03)La_(0.005)O_(2)and ti_(0.96)Cu_(0.03)La_(0.01)O_(2)powders possess anatase phase only. the changes of the band gap structure and dimensions of the unit cell volume of tiO_(2)confirm the substitution of ti^(4+)sites by Cu^(2+)and La^(3+)ions. Remarkable widening of wavelengths absorption with formation of long absorption tails were found in tiO_(2)(3.13 e V) through insertion of La^(3+)plus Cu^(2+)ions. ti_(0.965)Cu_(0.03)La_(0.005)O_(2)and ti_(0.96)Cu_(0.03)La_(0.01)O_(2)samples exhibit a visible light band gap of 2.3 and 2.7 e V, respectively. Based on SEm images, incorporation of Cu^(2+)and La^(3+)ions influences the surface morphology of tiO_(2). the resulting ti_(0.97)Cu_(0.03)O_(2), ti_(0.965)Cu_(0.03)La_(0.005)O_(2)and ti_(0.96)Cu_(0.03)La_(0.01)O_(2)powders present enhanced photocatalytic activity towards Congo red dye degradation compared to pure one under natural solar spectrum. the best ti_(0.96)Cu_(0.03)La_(0.01)O_(2)catalyst exhibits superior photocatalytic activity of 96% for 10 ppm CR dye in 20 min as well as above average photocatalytic efficiency of 63% for 30 ppm CR dye in 120 min. As well, it showed acceptable photodegradation activity of 52% for 30 ppm mB solution in 140 min of sunlight irradiation. the heightened photodegradation efficiency of ti_(0.96)Cu_(0.03)La_(0.01)O_(2)catalyst can be clarified in terms of higher ch

关键词： Semiconductor tiO_(2) Rare earths Congo red methylene blue Solar spectrum Photodegradation

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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

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the Radcliffe Wave Parameters from Data on Open Star Clusters

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Research in Astronomy and Astrophysics 2024年第3期24卷 106-109页

作者： V.V.Bobylev A.t.Bajkova Pulkovo Astronomical Observatory St-Petersburg 196140Russia

A spectral analysis of the vertical positions and velocities of 374 open star clusters(OSCs)was carried *** took these OSCs from the Hunt and Reffert catalog;they have an average age of about 10 million years,and are located on the galactic plane XY in a narrow zone inclined by 25°to the galactic axis *** following estimates of the parameters of the Radcliffe wave were obtained:(a)the maximum value in periodic perturbations of vertical coordinates Z_(max)=92±10pc with the wavelength of these perturbations λ_(z)=4.82±0.09 kpc;(b)the maximum value of the velocity of vertical disturbances Wmax=4.36±0.12km s^(-1) with disturbance wavelengthλ_(W)=1.78±0.02 *** that the results of the vertical velocity analysis are first-class in accuracy and completely new.

关键词： (Galaxy) local interstellar matter-Galaxy structure-(Galaxy) solar neighborhood

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Voids size distribution in gelled waxy crude oil under dynamic and static cooling

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Petroleum Research 2024年第1期9卷 109-114页

作者： Girma t.Chala Shaharin A.Sulaiman Department of mechanical Engineering(Well Engineering) International College of Engineering and ManagementP.O.Box 2511C.P.O Seeb 111MuscatOman Department of mechanical Engineering Universiti Teknologi PETRONASBandar Seri Iskandar37500TronohPerakMalaysia

Waxy crude oil is known for its high wax contents that can potentially result in gelling following sufficient cooling of the transportation line in the subsea bed at offshore *** gelling over the entire lines requires an accurately predicted restart pressure to restart the clogged and idle ***,the common way of predicting the restart pressure has been reported to result in over-designed and predicted piping *** research findings evidenced the formation of voids which would reduce the restart pressure *** study conducted in this paper is aimed at investigating the voids size distribution in gelled crude oil across and along transportation *** of experiments simulating crude oil transportation during both static and dynamic cooling were *** gelled crude oil below the pour point temperature was then scanned using a magnetic Resonance Imaging(mRI)system to detect the voids *** resulting voids at each scanning cross-section were quantified,and their distributions were *** was observed that dynamic cooling had minimal impacts on the voids size difference along the pipeline with the difference in voids areas within 10 mm^(2) to be twice and uniform for the entire flow rates ***,voids size in statically cooled waxy crude oil was found to be highly distributed with a maximum of 6 voids size distribution in 10 mm2 *** low-end temperature had the highest size difference while the difference was decreasing with higher end *** study shows that the voids amount in dynamically cooled waxy crude oil could also be estimated with lower numbers of cross-sectional voids ***,the higher cross-sectional voids detection is recommended while estimating voids in statically cooled waxy crude oil.

关键词： Gelled crude oil Voids size distribution Dynamic cooling Static cooling

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Some results for operators on a model space

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Frontiers of mathematics in China 2018年第2期13卷 287-300页

作者： mehmet GURDAL Ulas YAmANCI mubariz garayev Suleyman Demirel University Department of Mathematics 32260 Isparta Turkey Suleyman Demirel University Department of Statistics 32260 Isparta Turkey Department of mathematics College of Science King Saud University P. O. Box 2455Riyadh 11451 Saudi Arabia

We investigate some problems for truncated toeplitz operators. Namely, the solvability of the Riccati operator equation on the set of all truncated toeplitz operators on the model space Kθ = H^2θθH^2 is studied. We study in terms of Berezin symbols invertibility of model operators. We also prove some results for the Berezin number of the truncated toeplitz operators. moreover, we study some property for H2-functions in terms of noncyclicity of co-analytic toeplitz operators and hypercyclicity of model operators.

关键词： Reproducing kernel Hilbert space (RKHS) reproducing kernel,Berezin symbol Berezin number truncated toeplitz operator modeloperator toeplitz operator

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Nonlinear dynamic modeling of planar moving timoshenko beam considering non-rigid non-elastic axial effects

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Applied mathematics and mechanics(English Edition) 2024年第3期45卷 479-496页

作者： m.ABBASI GAVARI m.R.HOmAEINEZHAD Faculty of mechanical Engineering K.N.Toosi University of TechnologyTehran 19991-43344Iran

Due to the importance of vibration effects on the functional accuracy of mechanical systems,this research aims to develop a precise model of a nonlinearly vibrating single-link mobile flexible *** manipulator consists of an elastic arm,a rotary motor,and a rigid carrier,and undergoes general in-plane rigid body motion along with elastic transverse *** accurately model the elastic behavior,timoshenko’s beam theory is used to describe the flexible arm,which accounts for rotary inertia and shear deformation *** applying Newton’s second law,the nonlinear governing equations of motion for the manipulator are derived as a coupled system of ordinary differential equations(ODEs)and partial differential equations(PDEs).then,the assumed mode method(Amm)is used to solve this nonlinear system of governing equations with appropriate shape *** assumed modes can be obtained after solving the characteristic equation of a timoshenko beam with clamped boundary conditions at one end and an attached mass/inertia at the *** addition,the effect of the transverse vibration of the inextensible arm on its axial behavior is *** the axial rigidity,the effect makes the rigid body dynamics invalid for the axial behavior of the ***,numerical simulations are conducted to evaluate the performance of the developed model,and the results are compared with those obtained by the finite element *** comparison confirms the validity of the proposed dynamic model for the *** to the mentioned features,this model can be reliable for investigating the system’s vibrational behavior and implementing vibration control algorithms.

关键词： planar moving timoshenko beam non-rigid non-elastic axial effect as-sumed mode method(Amm) nonlinear motion analysis

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Free vibration and buckling analysis of polymeric composite beams reinforced by functionally graded bamboo fbers

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Applied mathematics and mechanics(English Edition) 2024年第3期45卷 543-562页

作者： H.m.FEIZABAD m.H.YAS Department of mechanical Engineering Razi UniversityKermanshah ***Iran

Natural fibers have been extensively researched as reinforcement materials in polymers on account of their environmental and economic advantages in comparison with synthetic fibers in the recent *** fibers are renowned for their good mechanical properties,abundance,and short cycle *** beams are one of the fundamental structural components and are susceptible to mechanical loads in engineering applications,this paper performs a study on the free vibration and buckling responses of bamboo fiber reinforced composite(BFRC)beams on the elastic *** different functionally graded(FG)layouts and a uniform one are the considered distributions for unidirectional long bamboo fibers across the *** elastic properties of the composite are determined with the law of *** Hamilton’s principle,the governing equations of motion are *** generalized differential quadrature method(GDQm)is then applied to the equations to obtain the *** achieved outcomes exhibit that the natural frequency and buckling load values vary as the fiber volume fractions and distributions,elastic foundation stiffness values,and boundary conditions(BCs)and slenderness ratio of the beam ***,a comparative study is conducted between the derived analysis outcomes for BFRC and homogenous polymer beams to examine the effectiveness of bamboo fibers as reinforcement materials,demonstrating the significant enhancements in both vibration and buckling responses,with the exception of natural frequencies for cantilever beams on the Pasternak foundation with the FG-◇fiber ***,the obtained analysis results of BFRC beams are also compared with those for carbon nanotube reinforced composite(CNtRC)beams found in the literature,indicating that the buckling loads and natural frequencies of BFRC beams are lower than those of CNtRC beams.

关键词： bamboo fiber free vibration buckling analysis functionally graded(FG)beam elastic foundation generalized differential quadrature method(GDQm)

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