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The ex-situ incorporation of the secondary SiC reinforcement, along with the in-situ incorporation of the tertiary and quaternary Mg3N2 and Si3N4 phases, in the primary matrix of Mg2Si is employed in order to provide ultimate wear resistance based on the laser-irradiation-induced inclusion of N2 gas during laser powder bed fusion. This is substantialized based on both the thermal diffusion- and chemical reaction-based metallurgy of the Mg2Si–SiC/nitride hybrid composite. This study also proposes a functional platform for systematically modulating a functionally graded structure and modeling build-direction-dependent architectonics during additive manufacturing. This strategy enables the development of a compositional gradient from the center to the edge of each melt pool of the Mg2Si–SiC/nitride hybrid composite. Consequently, the coefficient of friction of the hybrid composite exhibits a 309.3% decrease to –1.67 compared to –0.54 for the conventional nonreinforced Mg2Si structure, while the tensile strength exhibits a 171.3% increase to 831.5 MPa compared to 485.3 MPa for the conventional structure. This outstanding mechanical behavior is due to the (1) the complementary and synergistic reinforcement effects of the SiC and nitride compounds, each of which possesses an intrinsically high hardness, and (2) the strong adhesion of these compounds to the Mg2Si matrix despite their small sizes and low concentrations.

Abstract The incidence of Alzheimer’s Disease in females is almost double that of males. To search for sex-specific gene associations, we build a machine learning approach focused on functionally impactful coding variants. This method can detect differences between sequenced cases and controls in small cohorts. In the Alzheimer’s Disease Sequencing Project with mixed sexes, this approach identified genes enriched for immune response pathways. After sex-separation, genes become specifically enriched for stress-response pathways in male and cell-cycle pathways in female. These genes improve disease risk prediction in silico and modulate Drosophila neurodegeneration in vivo. Thus, a general approach for machine learning on functionally impactful variants can uncover sex-specific candidates towards diagnostic biomarkers and therapeutic targets.

The design of turbines used to convert thermal energy into electrical energy in an organic Rankine cycle (ORC) is crucial. A high-speed turbine requires high-performance bearings, which increases turbine manufacturing costs. In this study, a high-efficiency two-stage axial turbine at a low rotational speed was developed, and the ORC performance was presented. We designed a 180-kW axial turbine of 12,000 rpm. To increase turbine efficiency, the number of turbine stages was set to two, and turbine blades were designed to reduce pressure losses. One-dimensional design parameters of blades that minimized the total pressure loss were selected using an in-house code based on a generalized reduced gradient (GRG) nonlinear algorithm. Three-dimensional turbine blade modeling and numerical analysis were performed using commercial software. The total-to-static isentropic efficiency and output of the two-stage axial turbine were predicted to be 85.1% and 176 kW, respectively. ORC performance was assessed using the predicted turbine performance results. Assuming the temperature of the condenser outlet working fluid to be 25 °C, the ORC thermal efficiency and exergy efficiency were found to be 7.40% and 34.49%, respectively. Our findings highlight the applicability of various rotational speeds and number of stages for an axial turbine in an ORC.

We report the use of four-layer graphene (4LG) as a highly reliable transparent conductive electrode (TCE) for polymer-dispersed liquid crystal (PDLC)-based smart window devices. The adhesion between 4LG and the substrate was successfully improved through a water-induced interface-cleaning (WIIC) process. We compared the performance of a device with a WIIC-processed 4LG electrode with that of devices with a conventional indium tin oxide (ITO) electrode and a 4LG electrode without a WIIC. With the application of the WIIC process, the PDLC smart window with a 4LG electrode exhibited reduced turn-on voltage and haze compared to 4LG without the WIIC process and characteristics comparable to those of the ITO electrode. The WIIC-processed 4LG electrode demonstrated enhanced electrical properties and better optical performance, leading to improved device efficiency and reliability. Furthermore, our study revealed that the WIIC process not only improved the adhesion between 4LG and the substrate but also enhanced the compatibility and interfacial interactions, resulting in the superior performance of the smart window device. These findings suggest that 4LG with WIIC holds great promise as a transparent conductive electrode for flexible smart windows, offering a cost-effective and efficient alternative to conventional ITO electrodes.

The precise shape of a shift block support for the turbine blade of a hovercraft was additively manufactured using 17–4 precipitation-hardened stainless steel (STS 630) powder through laser powder bed fusion (LPBF). Subsequently, heat treatment under the H900 condition increased the yield strength and fracture strain of the shift block to 1313 MPa and 11.5%, respectively, and enhanced its corrosion resistance to seawater. This improvement in mechanical and physical properties is primarily because Cu precipitates were uniformly distributed at the interfacial boundaries along with the simultaneous suppression of the formation of Cr23C6 precipitates with weak corrosion resistance. Furthermore, this was attributed to the phase transformation from the as-built STS 630 comprising a mixture of austenite, ferrite, and martensite to a dual mixture of ferrite and martensite after the heat treatment. Thereafter, we topologically optimised the shift block and adopted a lattice structure to apply the design for additive manufacturing (DfAM).

Abstract Cholangiopathy is a diverse spectrum of chronic progressive bile duct disorders with limited treatment options and dismal outcomes. Scaffold‐ and stem cell‐based tissue engineering technologies hold great promise for reconstructive surgery and tissue repair. Here, we report a combined application of 3D scaffold fabrication and reprogramming of patient‐specific human hepatocytes to produce implantable artificial tissues that imitate the mechanical and biological properties of native bile ducts. The human chemically derived hepatic progenitor cells (hCdHs) were generated using two small molecules A83‐01 and CHIR99021 and seeded inside the tubular scaffold engineered as a synergistic combination of two layers. The inner electrospun fibrous layer was made of nanoscale–macroscale polycaprolactone fibers acting to promote the hCdHs attachment and differentiation, while the outer microporous foam layer served to increase mechanical stability. The two layers of fiber and foam were fused robustly together thus creating coordinated mechanical flexibility to exclude any possible breaking during surgery. The gene expression profiling and histochemical assessment confirmed that hCdHs acquired the biliary epithelial phenotype and filled the entire surface of the fibrous matrix after 2 weeks of growth in the cholangiocyte differentiation medium in vitro. The fabricated construct replaced the macroscopic part of the common bile duct (CBD) and re‐stored the bile flow in a rabbit model of acute CBD injury. Animals that received the acellular scaffolds did not survive after the replacement surgery. Thus, the artificial bile duct constructs populated with patient‐specific hepatic progenitor cells could provide a scalable and compatible platform for treating bile duct diseases.

Abstract This study quantifies the interaction between tacrolimus (TAC) and mycophenolate mofetil (MMF) in kidney transplant recipients. Concentrations of TAC, mycophenolic acid (MPA), and metabolites were analyzed and relevant genotypes were determined from 32 patients. A population model was developed to estimate the effect of interaction. Concentrations of TAC were simulated in clinical scenarios and dose-adjusted trough concentrations per dose (C/D) were compared. Effect of interaction was described as the inverse exponential relationship. Major determinants of trough levels of TAC were CYP3A5 genotype and interaction with MPA. The absolute difference in C/D of TAC according to co-administered MMF was higher in CYP3A5 non-expressers (0.55 ng/mL) than in CYP3A5 expressers (0.35 ng/mL). The effect of MMF in determining the TAC exposure is more pronounced in CYP3A5 non-expressers. Based on population pharmacokinetic model, we suggest the TAC dosing algorithm considering the effects of CYP3A5 and MMF drug interaction in stable kidney transplant recipients.

The organic Rankine cycle (ORC) is a thermodynamic cycle in which electrical power is generated using an organic refrigerant as a working fluid at low temperatures with low-grade enthalpy. We propose a turbine embedded in a generator (TEG), wherein the turbine rotor is embedded inside the generator rotor, thus simplifying turbine generator structure using only one bearing. The absence of tip clearance between the turbine rotor blade and casing wall in the TEG eliminates tip clearance loss, enhancing turbine efficiency. A single-stage axial-flow turbine was designed using mean-line analysis based on physical properties, and we conducted a parametric study of turbine performance, and predicted turbine efficiency and power using the tip clearance loss coefficient. When the tip clearance loss coefficient was applied, turbine isentropic efficiency and power were 0.89 and 20.42 kW, respectively, and ORC thermal efficiency was 4.81%. Conversely, the isentropic efficiency and power of the turbine without the tip clearance loss coefficient were 0.94 and 22.03 kW, respectively, and the thermal efficiency of the ORC was 5.08%. Therefore, applying the proposed TEG to the ORC system simplifies the turbine generator, while improving ORC thermal efficiency. A 3D turbine generator assembly with proposed TEG structure was also proposed.

Purpose: To investigate improvement in nocturia and nocturnal polyuria in nocturnal polyuria patients after silodosin administration by using a 3-day frequency volume chart. Methods: This was a prospective multicenter study. We enrolled nocturnal polyuria patients (nocturnal polyuria index [NPi]>0.33), aged ≥60 years, diagnosed with the 3-day frequency volume charts of patients with benign prostatic hyperplasia taking α-blockers. Of the 54 patients, 30 (55.6%) completed the study according to the study protocol (per-protocol group), and 24 dropped out (dropout group). Results: Of the 24 patients in the dropout group, 5 withdrew consent due to side effects or lack of efficacy, 7 were lost to follow-up at 4 weeks, 8 were lost to follow-up at 12 weeks, and 4 dropped out due to failure to complete 3-day frequency volume charts at 12 weeks. In the per-protocol group, there was significant improvement in the International Prostate Symptom Score (IPSS), especially question numbers 1, 3, 4, 5, 6, 7, and the quality of life question (P=0.001, P=0.007, P0.33. Considering the high dropout rate of our study due to no implementation of 3-day frequency volume charts, prospective and large-scale studies are needed to confirm our results.

Cancer cells explore a broad mutational landscape, bringing the possibility that tumor-specific somatic mutations could fall in the same codons as germline SNVs and leverage their presence to produce substitutions with a larger impact on protein function. While multiple, temporally consecutive mutations to the same codon have in the past been detected in the germline, this phenomenon has not yet been explored in the context of germline-somatic variant co-occurrences during cancer development. We examined germline context at somatic mutation sites for 1395 patients across four cancer cohorts (breast, skin, colon, and head and neck) and found 392 codon-level co-occurrences between germline and somatic variants, including over a dozen in well-known cancer genes. We found that for the majority of these co-occurrence events, traditional somatic calling led to an inaccurate representation of the protein site and a significantly lower predicted impact on protein fitness. We conclude that these events often lead to imprecise annotation of somatic variants but do not appear to be a frequent source of driver events during cancer development.

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD. [ABSTRACT FROM AUTHOR]

The gas atomization is a production technique of a metallic powder. In this study, the β-solidifying Ti--44Al--6Nb--1.2Cr alloy powder fabricated by gas-atomization was investigated regarding the evolving shape, phase constitution, and chemical distribution as a result of the high solidification rate. The powder showed a spherical shape regardless of its size, indicating no relation of solidification rate to powder shape. However, the small powder (D50 = 36.0 µm) showed less segregation and was composed of β and α2 dual phases. Whereas, the large powder (D50 = 78.7 µm) is relatively high segregation and composed of almost a single α2 phase because of the difference in the cooling rates. The findings obtained here demonstrated the understanding of phase transformation during the rapid solidification and continuous microstructural evolution process in the β-solidifying alloy. [ABSTRACT FROM AUTHOR]

Recently, the concepts of virtual reality (VR), augmented reality (AR), and mixed reality (MR) are combined with 5G, blockchain, immersive content, and digital twin technology to converge reality and virtual space. The metaverse keyword as a comprehensive concept that creates a digital world has emerged, and interest in it continues worldwide to the extent that Apple recently announced a headset named Vision Pro[1]. In this paper, the trend of the currently used global foreign metaverse platform, the development and application of realistic content on the platform, and the limitations, and the self-developed local tour metaverse platform centered on Busan Yongdusan park, using only the Unity game engine[2] to overcome the limitations Introducing immersive content, artificial intelligence technology applied to it, methods for using it in the educational field, and practical examples. [ABSTRACT FROM AUTHOR]