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Gene therapy with caspase-3 small interfering RNA-nanoparticles is neuroprotective after optic nerve damage 被引量:1
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作者 Mohamed Tawfik Xiwei Zhang +5 位作者 Lisa Grigartzik Peter Heiduschka Werner Hintz Petra Henrich-Noack berend van wachem Bernhard A.Sabel 《Neural Regeneration Research》 SCIE CAS CSCD 2021年第12期2534-2541,共8页
Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral g... Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17). 展开更多
关键词 apoptosis brain CASPASE-3 drug delivery gene therapy in vivo confocal neuroimaging NANOPARTICLES NEURODEGENERATION neuroprotection retina siRNA
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Comparing two IBM implementations for the simulation of uniform packed beds 被引量:2
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作者 Christian Gorges Maximilian Brommer +5 位作者 Christin Velten Siegmar Wirtz Enric Illana Mahiques Viktor Scherer Katharina Zahringer berend van wachem 《Particuology》 SCIE EI CAS CSCD 2024年第3期1-12,共12页
Nowadays,the design of fixed packed bed reactors still relies on empirical correlations,which,especially for small tube to particle diameter ratios,are mostly too inaccurate because of the presence of wall effects.The... Nowadays,the design of fixed packed bed reactors still relies on empirical correlations,which,especially for small tube to particle diameter ratios,are mostly too inaccurate because of the presence of wall effects.Therefore,the simulation of fixed packed bed reactors plays an important role to predict and control the flow and process parameters in such,nowadays and in the future.Because of its straightforward applicability to non-uniform packings with particles of arbitrary shapes,the immersed boundary method(IBM)has advantages over other numerical methods and is used more and more frequently.This paper compares two approaches of IBMs for the simulation of fixed bed reactors with spherical shaped particles.The classic,smooth approach is compared to the straightforward to implement blocked-off method for velocity fields above the fixed bed for particle Reynolds numbers of 300 and 500.Results from experimental inline PIV-measurements of the reactor to be simulated serve as a basis for comparison.Very good agreement with the experiment is found for both simulation methodologies with higher resolutions,considering the more stable flow at a particle Reynolds number of 300.Differences in the different IBM approaches occurred for the more unsteady flow at a particle Reynolds number of 500.Compared to the blocked-off method,the smooth IBM reflects the formation of additional jets and recirculation zones better right above the bed,though increasing the fluid mesh resolution improves the accuracy of the blocked-off method.Overall,a more diffusive behaviour is found for the blocked-off simulations due to the stairstep representation,which is avoided by using interpolation stencils as in the smooth IBM.With higher mesh refinement in the blocked-off IBM this effect can be reduced,but this also increases the computational effort. 展开更多
关键词 Immersed boundary method Packed bed reactor Uniform particle packing
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Experimental and numerical investigation to elucidate the fluid flow through packed beds with structured particle packings
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作者 Shirin Patil Christian Gorges +3 位作者 Joel Lòpez Bonilla Moritz Stelter Frank Beyrau berend van wachem 《Particuology》 SCIE EI CAS CSCD 2024年第6期218-237,共20页
The present paper presents an experimental and numerical investigation of the dispersion of the gaseous jet flow and co-flow for the simple unit cell(SUC)and body-centred cubic(BCC)configuration of particles in packed... The present paper presents an experimental and numerical investigation of the dispersion of the gaseous jet flow and co-flow for the simple unit cell(SUC)and body-centred cubic(BCC)configuration of particles in packed beds.The experimental setup is built in such a way that suitable and simplified boundary conditions are imposed for the corresponding numerical framework,so the simulations can be done under very similar conditions as the experiments.Accordingly,a porous plate is used for the co-flow to achieve the uniform velocity and the fully developed flow is ensured for the jet flow.The SUC and BCC particle beds consist of 3D-printed spheres,and the non-isotropy near the walls is mostly eliminated by placing half-spheres at the channel walls.The flow velocities are analysed directly at the exit of the particle bed for both beds over 36 pores for the SUC configuration and 60 pores for the BCC configuration,for particle Reynolds numbers of 200,300,and 400.Stereo particle image velocimetry is experimentally arranged in such a way that the velocities over the entire region at the exit of the packed bed are obtained instantaneously.The numerical method consists of a state-of-the-art immersed boundary method with adaptive mesh refinement.The paper presents the pore jet structure and velocity field exiting from each pore for the SUC and BCC packed particle beds.The numerical and experimental studies show a good agreement for the SUC configuration for all flow velocities.For the BCC configuration,some differences can be observed in the pore jet flow structure between the simulations and the experiments,but the general flow velocity distribution shows a good overall agreement.The axial velocity is generally higher for the pores located near the centre of the packed bed than for the pores near the wall.In addition,the axial velocities are observed to increase near the peripheral pores of the packed bed.This behaviour is predominant for the BCC configuration as compared to the SUC configuration.The velocities near the peripheral pores can become even higher than those at the central pores for the BCC configuration.It is shown that both the experiments as well as the simulations can be used to study the complex fluid structures inside a packed bed reactor. 展开更多
关键词 Uniform particle packing Packed bed reactor Stereo particle image velocimetry Immersed boundary method
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The effect of side walls on particles mixing in rotating drums 被引量:3
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作者 Aman Jain Fabien Evrard berend van wachem 《Particuology》 SCIE EI CAS CSCD 2023年第1期112-121,共10页
In this paper, we study the effects of the presence and shape of side walls and of the overall length of rotating cylindrical drums on the mixing of particles with differing sizes by application of the discrete elemen... In this paper, we study the effects of the presence and shape of side walls and of the overall length of rotating cylindrical drums on the mixing of particles with differing sizes by application of the discrete element method (DEM). By varying the semi-axis of the spheroidally shaped side walls and the length of the overall drum, we observe the formation of circulation patterns near the side walls. Although there is a vast amount of literature studying mixing regimes in rotating drums, little is known about the effect of the side walls of the drum on particle mixing. The results of our study demonstrate that introducing curved side walls induces a strong circulation pattern near these side walls, but has, paradoxically, a negative impact on mixing and actually promotes segregation. The cause for this segregation is the difference in velocity of differently sized particles near the curved side walls. Large particles accumulate at the curved side walls, whereas small particles move away from the curved side walls. When the length of the drum is increased, the overall effect of the side walls is decreased, although it does remain observable, even in very large drums. 展开更多
关键词 Discrete element method Rotating drums Particle mixing Side walls of rotating drums
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