New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Effect of inclination angle on hooked end steel fiber pullout behavior in ultra-high performance concrete

The bond relationship between the concrete matrix and steel fiber is a significant factor that affects the performance of ultra-high performance fiber reinforced concrete (UHPFRC). In the present research, pullout performances of hooked end fibers embedded in ultra-high performance concrete matrix under various inclination angles are systematically investigated, with special attention on fiber dimension and embedded length. Pullout load-slip curves are obtained and experimental observations including complete fiber pull-out, fiber rupture and matrix failure are analyzed in detail. The effects of the pullout angle are then studied quantitatively by parameter calculations and mechanism analysis. A new analytical model for evaluating the snubbing and spalling effects of the hooked end steel fiber is proposed and validated. It is shown that the influences of the inclination angle on the peak pullout load vary with different fiber types, embedded lengths and fiber diameters, which are also associated with the occurrences of the fiber rupture and the matrix failure. In addition, optical microscope and scanning electron microscopy observations at mesoscale are performed to further analyze the effects of orientation angle

Resistance of multi-layered UHPFRC against in-service projectile: experimental investigation and modelling prediction

The present paper studies the ballistic performance of Ultra-High Performance Fiber Reinforced Concrete (UHPFRC) applying multi-layered concept against the 7.62 mm projectile at 840 m/s. Coarse basalt aggregates are incorporated in the UHPFRC under the premise of reducing the cement powder consumption and taking advantages of their superior ballistic resistance. We found that the designed triple-layered UHPFRC 16a1s(40)-8a1s(10)-16a1s(40) achieves a superior impact resistance compared to the single-layered reference, with a 32% reduction of the penetration depth. The improved resistance of the triple-layered UHPFRC is associated with the multiple effects of the coarse aggregate, the layer interface, the fibers direction in the thin middle layer, and the edge confinement of the rear layer. Moreover, a new analytical model is proposed to predict the penetration depth in the multi-layered UHFRC, which can take the varying mechanical properties of the layered targets into consideration. The results from this study shed light on understanding the ballistic performance of layered UHPFRC, and promote its application in protective constructions

Numerical investigation on ballistic performance of coarse-aggregated layered UHPFRC

The impact resistance of coarse-aggregated layered Ultra-High Performance Fiber Reinforced Concrete (UHPFRC) is investigated numerically with LS-DYNA. The Holmquist Johnson Concrete (HJC) model is employed to describe the dynamic behavior of the UHPFRC, and the effect of the coarse aggregates is reflected in the pressure-compaction relation. Mechanical tests are conducted to obtain the material-related inputs for the numerical model, and ballistic experiments are applied to calibrate the model parameter as well as to validate the simulation results. After valuation, the ballistic histories of the projectile and the penetration processes in the UHPFRC targets are analyzed. Furthermore, the study discusses the effects of the target thickness on the depth of penetration, showing the possibility to replace a thicker single-layered target by a thinner triple-layered one to achieve the same level of protection. Finally, perforation limits of the single- and tripled-layered UHPFRC at different impact velocities are estimated, based on which the ACE formulae are modified to accurately predict the perforation limit of the coarse-aggregated layered UHPFRC. The numerical simulations in this study reveal that the triple-layered target requires fewer dosages of cement and steel fibers in comparison to its single-layered counterpart with the same level of ballistic protection

Reversely modulated optical single sideband scheme and its application in a 60-GHz full duplex ROF system

The reversely modulated optical single sideband scheme (IM-OSSB) based on a parallel Mach-Zehnder modulator (P-MZM) is proposed. In this P-MZM, one sub-MZM is employed for data modulation and the other is used for optical millimeter wave (mm-wave) generation. Due to the individual modulation, this scheme is data-format-transparent and can be used to generate a high performance optical mm-wave signal at the optimized direct current (dc) bias. There is electrical mixer free at the transmitter and thus the bandwidth limitation, nonlinearity and conversion loss from the electrical mixer are released in this scheme. Moreover, the modulation power efficiency of IM-OSSB can be improved by adjusting the dc bias in the modulator. Based on IM-OSSB, we demonstrate a 60-GHz full duplex radio-over-fiber system. The experimental results show that the power penalty of 2.9-Gb/s on-off keying data carried by 58-GHz mm-wave after transmission over 50-km SMF-28 is negligibl

Reversely modulated optical single sideband scheme and its application in a 60-GHz full duplex ROF system

The reversely modulated optical single sideband scheme (IM-OSSB) based on a parallel Mach-Zehnder modulator (P-MZM) is proposed. In this P-MZM, one sub-MZM is employed for data modulation and the other is used for optical millimeter wave (mm-wave) generation. Due to the individual modulation, this scheme is data-format-transparent and can be used to generate a high performance optical mm-wave signal at the optimized direct current (dc) bias. There is electrical mixer free at the transmitter and thus the bandwidth limitation, nonlinearity and conversion loss from the electrical mixer are released in this scheme. Moreover, the modulation power efficiency of IM-OSSB can be improved by adjusting the dc bias in the modulator. Based on IM-OSSB, we demonstrate a 60-GHz full duplex radio-over-fiber system. The experimental results show that the power penalty of 2.9-Gb/s on-off keying data carried by 58-GHz mm-wave after transmission over 50-km SMF-28 is negligibl

Enhancing the low-velocity impact resistance of Ultra-High Performance Concrete by an optimized layered-structure concept

Low-velocity impacts are common in the civil engineering field. Ultra-High Performance Fiber Reinforced Concrete (UHPFRC) is a promising material to resist these impacts. When a UHPFRC beam is under low-velocity impacts, the damage in its distant region caused by the reflected tensile waves is far more serious than that in the impacted region caused by compression. This damage distribution and the more significant effects of steel fibers on the tensile properties of UHPFRC inspire the concept of applying a layered structure with different fiber amounts at different regions of the beam. This study investigates the dynamic resistance of layered UHPFRC under repeated low-velocity drop-weight impacts. The results show that the double-layered UHPFRC achieves a superior resistant capacity compared to its single-layered counterpart, e.g. an approximate 28% enhancement of the absorbed impact energy is obtained by the double-layered beam U0.6h-1.6h than that of the corresponding single-layered UHPFRC with an identical fiber amount. Further, a new model to estimate the absorbed energy of the layered UHPFRC under multiple drop-weight impacts is developed and validated using the experimental results. By separating the contributions of the matrix and the fiber, the model confirms the important effects of the steel fibers on the beam absorbed impact energy, as well as the improved fiber utilization efficiency of the double-layered beam. This study contributes to improving the dynamic performance of UHPFRC under low-velocity impacts, and promotes the potential utilization of layered UHPFRC composite in civil engineering

Synergistic effect of steel fibres and coarse aggregates on impact properties of ultra-high performance fibre reinforced concrete

This study investigates the synergistic effect of steel fibres and coarse aggregates on impact behaviour of ultra-high performance fibre reinforced concrete (UHPFRC). UHPFRC matrices with a low cement content and maximum aggregate sizes of 8 mm and 25 mm are designed by using a particle packing model. Three types of steel fibres (13 mm short straight, 30 mm medium hook-ended and 60 mm long 5D) are studied in terms of the utilization efficiencies. The results show that UHPFRC with coarser aggregates tends to have a lower cement consumption but slightly weaker mechanical strength, and the largest aggregate size is suggested to be no more than 25 mm considering the reduction on flexural toughness and impact resistance. The medium and long fibres contribute to an excellent deflection/strain hardening behaviour instead of short ones. A preferential synergistic effect on impact and flexural properties is observed between the medium fibres and the finer aggregates, while the longer fibres are more compatible to the coarser aggregates. The length of steel fibre is recommended between 2 and 5 times the maximum aggregate size. The flexural strength controls the impact resistance under low-energy impact loadings, and flexural toughness determines it under relatively high-energy (beyond energy threshold) impact loadings. Keywords Synergistic effectUltra-high performance fibre reinforced concreteImpact resistanceFlexural propertySteel fibreCoarse aggregat