Engineered gene drives are being explored as a potential strategy for the control of vector-borne diseases due to their ability to rapidly spread genetic modifications through a population. While an effective CRISPR homing gene drive for population suppression has recently been demonstrated in mosquitoes, formation of resistance alleles that prevent Cas9 cleavage remains the major obstacle for drive strategies aiming at population modification, rather than elimination. Here, we present a homing drive in Drosophila melanogaster that reduces resistance allele formation below detectable levels by targeting a haplolethal gene with two gRNAs while also providing a rescue allele. This is because any resistance alleles that form by end-joining repair will typically disrupt the haplolethal target gene, rendering the individuals carrying them nonviable. We demonstrate that our drive is highly efficient, with 91% of the progeny of drive heterozygotes inheriting the drive allele and with no resistance alleles observed in the remainder. In a large cage experiment, the drive allele successfully spread to all individuals. These results show that a haplolethal homing drive can be a highly effective tool for population modification.
The determination of the RhD phenotype is important in transfusion medicine. However, due to the complexity of D antigen expression, the routine serological method cannot differentiate all RhD variants. In addition, the induction of the anti-D antibody is still the major cause of severe hemolytic disease of the newborn (HDN). Therefore, it is important to understand RHD gene profiles. To analyze the RHD gene profiles of Taiwanese RhD-negative donors, the multiplex PCR method was applied to amplify RHD specific exons 3, 4, 5, 7, and 9. Based on the PCR results, the 156 RhD-negative donors were divided into 12 groups according to the different expression patterns of the RHD gene. These 12 groups were further divided into three categories: type I=Rh D(el) (21.8%); type II = partial D, containing some exons (9.0%); and type III = true RhD-negative (69.2%). The results indicated that 21.8% of RhD-negative donors in Taiwan were RhD(el), and 9% carried a part of the RHD gene. Six defined RhD variants were found in this study: four R(O) (Har), one D(Va), and two D(IVb). However, no true RhD-negative or RhD(el) donor with the CcdEe phenotype was found in this analysis.
Coexistence of sinonasal myeloid sarcoma and acute fulminant invasive fungal sinusitis poses an urgent diagnostic and management challenge to clinicians. Timely recognition of this rare comorbid condition is warranted as application of appropriate treatment can save lives.
This article presents a novel study on curvature sensing and crack monitoring in lightweight foamed concrete structural beam using the packaged fibre-based in-line Mach–Zehnder interferometer curvature sensor. The Mach–Zehnder interferometer sensors which consist of two abrupt biconic tapers were fabricated and packaged into polypropylene slabs to protect the sensors under harsh condition of the real sensing environment, as the sensors were embedded into lightweight foamed concrete structural beams for field tests. Pretest characterizations of Mach–Zehnder interferometer sensors based on the packaging thicknesses at different operating wavelengths (1310, 1490 and 1550 nm) were done before the field tests. Three packages with different thicknesses were prepared to justify the effect of the packaging thicknesses on the curvature sensitivity of sensors. Results showed that the Mach–Zehnder interferometer sensor with a thicker bottom slab has the highest sensitivity of up to 3.53 µW m−1 which is capable of detecting a minimum curvature of 0.25 km−1 and a maximum curvature radius of up to 4 km. In the field tests, three Mach–Zehnder interferometer sensors were embedded into the lightweight foamed concrete structural beams with different polypropylene percentages (0.4%, 0.25% and 0%, respectively) to characterize the sensor performance according to the concrete environments with different tensile capacities. Mach–Zehnder interferometer sensor managed to hold up to a maximum loading force of 26 kN in the concrete environment before stopping functioning. Optical powers in response to the loading forces imposed to the beams were mapped to the strains measured by the lead wire alloy foil strain gauges (brand: TML, model: FLK-6-11) with a good correlation value of up to 0.968. Furthermore, the double-sided sensing property of Mach–Zehnder interferometer sensors preponderates over the conventional strain gauges in detecting the internal cracking within the concretes before any earlier sighting of the macrocracks.
A new test setup and data concerning the ultimate strength behavior of resistance spot welds in a mild strength steel subjected to combined tension and shear loads are presented. A test plan based on a design of experiments (DOE) with three design factors (coupon width, coupon length, and nugget diameter) was conducted to investigate the influence of the factors on the ultimate strength of the resistance spot welds under different loading angles. In this program, test loads were monotonically applied to the resistance spot weld at a specific angle until the load carrying capacity of the resistance spot weld was exceeded. It was found that the nugget diameter contributes the most (more than 70%) to the total variation of the recorded ultimate strength and that the coupon length has little effect. A deterministic ultimate strength model was proposed to take into account the interaction of in-plane shear and 90° out-of-plane tensile loading in the resistance spot weld. A reliability model was also demonstrated to evaluate the ultimate strength of a single resistance spot weld.
An improved methodology to quantitatively assess fatigue lives of automotive structures and to identify critical and non-damaging areas for design enhancement and weight reduction is presented. The methodology of automated fatigue assessment, called CAE-FATIGUE (Computer Aided Engineering in Fatigue), combines a load-time history file with the result file from an elastic finite element analysis to estimate fatigue lives (damage contours). The CAE-FATIGUE methodology is of particular value when it is used as a proactive tool in the early design stage to reduce design iterations and prototype costs.
CAE-FATIGUE is applicable to elastic finite element analysis results because the Glinka energy density method (plasticity correction approach) is used to approximate true stresses and strains from the elastic stresses. CAE-FATIGUE cannot be applied to cases where loading frequency is of importance, since the elastic stress components from all loading channels are superimposed to the resultant stresses at the same specific time. CAE-FATIGUE calculates fatigue lives based on the maximum normal stress and strain range on a critical plane on which maximum principal stresses for the entire loading history are maximized. Also, CAE-FATIGUE can generate life/damage contour plots to identify critical and nondamaging areas for design enforcement and weight reduction.
This report focuses on practical aspects of designing automotive suspension components to avoid fatigue failure. The design process for a proposed front suspension knuckle is presented for illustration purposes. Critical planes highlighted with damage contours can also be used to develop “smart” and efficient prototype tests. Emphasis is placed on how to optimize the component to meet the durability criteria through mechanical life test procedure and test field endurance schedules.
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