1,721,040 research outputs found
Numerical Study on Dynamic Response of Submerged Floating Tunnel Depending on Shore Connection
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Numerical Evaluation of Segmental Lining System with Compressible Layer in Deep Soft Rock
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Mutations at a split codon in the GTPase-encoding domain of OPA1 cause dominant optic atrophy through different molecular mechanisms
Full text linkExonic (i.e. coding) variants in genes associated with disease can exert pathogenic effects both at the protein and mRNA level, either by altering the amino acid sequence or by affecting pre-mRNA splicing. The latter is often neglected due to the lack of RNA analyses in genetic diagnostic testing. In this study we considered both pathomechanisms and performed a comprehensive analysis of nine exonic nucleotide changes in OPA1, which is the major gene underlying autosomal dominant optic atrophy (DOA) and is characterized by pronounced allelic heterogeneity. We focused on the GTPase-encoding domain of OPA1, which harbors most of the missense variants associated with DOA. Given that the consensus splice sites extend into the exons, we chose a split codon, namely codon 438, for our analyses. Variants at this codon are the second most common cause of disease in our large cohort of DOA patients harboring disease-causing variants in OPA1. In silico splice predictions, heterologous splice assays, analysis of patient's RNA when available, and protein modeling revealed different molecular outcomes for variants at codon 438. The wildtype aspartate residue at amino acid position 438 is directly involved in the dimerization of OPA1 monomers. We found that six amino acid substitutions at codon 438 (i.e. all substitutions of the first and second nucleotide of the codon) destabilized dimerization while only substitutions of the first nucleotide of the codon caused exon skipping. Our study highlights the value of combining RNA analysis and protein modeling approaches to accurately assign patients to future precision therapies
Numerical study on pre-fabricated composite segment with compressible layer combined at their extrados
No full textThe development of TBM technology enables continuous tunnel excavation with limited deformation of the ground, so it is also being utilized in challenging conditions. Nevertheless, geo-risk problems, such as squeezing during tunneling in overstressed rock, like deep soft rock, cause excessive stress in the segmental lining. The conventional structural solution based on the resistance principle causes the problem of overdesigning the segmental lining. Therefore, studies have been conducted on various yielding supports to reduce support pressure by allowing some internal displacement of the tunnel wall after excavation. Pre-fabricated composite segments with a compressible layer combined at their extrados can be considered in the shield tunnel, but this design is not well established. In this study, a numerical analysis based on the finite element method was performed to investigate the effect of the compressible layer on the segmental lining and the surrounding ground during the excavation of the shield tunnel in the deep soft rock. A parametric study was conducted with the characteristics of the compressible layer, the physical properties of the rock, and the presence or absence of backfill material as the main factors
Origami stacking of micro-fabricated coils for miniaturized eddy current sensors
No full textEddy current sensors are non-destructive and highly precise, relying on high-frequency magnetic fields that induce circulating currents in nearby conductive materials. Such operation principle allows for non-contact measurement of distance, thickness, cracks, and vibration, which can be widely applied in the field of advanced manufacturing and device maintenance. However, conventional sensors based on wire wound inductors often suffer from size constraints due to the trade-off between inductance and physical volume, therefore restricted in application where sensing needs to be compact or requires high lateral resolution. Lithography can fabricate micro inductors but the number of turns is limited in 2D configuration. To overcome these limitations, we present miniaturized eddy current sensors fabricated by micro-fabrication techniques with enhanced sensitivity via origami-stacking. Two-dimensional inductor coils with 25 mu m-width Cu lines were fabricated on a 25 mu m-thick polyimide film via high-resolution photolithography and metallization. The inductors were then stacked into multi-layered 3D architecture using an origami-inspired folding method. Finite element simulations confirmed that inductance increases with the number of layers according to a power-law trend due to the enhanced mutual magnetic coupling. Experimental measurements at 3 MHz validated the simulation, demonstrating 125-fold enhancement in inductance when micro-fabricated copper 2D coils is stacked to 12 levels. The overall thickness of 12 layered origami-sensor architecture was under 1 mm. Compared to a commercial 6 mm-diameter coil inductor, the origami inductor demonstrated 2.46-5.77 times higher inductance at similar thickness. The proposed sensor also exhibited high sensitivity to both metal thickness and proximity, enabling its application in endpoint detection during semiconductor planarization and other precision sensing tasks.
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