Search

Ni-cellulose nanofiber (CNF) composite plated films were fabricated by electroless plating method. The deposition conditions and basic properties of the Ni-CNF composite film were investigated. A C1100 plate was used as the plated material, and a Ni-P electroless plating bath was prepared as the plating solution. 5 g/L of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) oxidized CNF or carboxymethyl cellulose was added to the plating solution. Sodium dodecyl sulfate (SDS) was added as a surfactant. It was confirmed that CNFs were complexed on the surface of the plated film, and the addition of SDS made CNFs disperse into the plated film. The surface of the plated film obtained by adding both TEMPO oxidized CNF and SDS had the highest Vickers hardness among all conditions investigated.

In this study, electrochemical measurements and observations investigated galvanic corrosion behavior between various metals with or without projection-shaped Ni–Cu alloy plating film and carbon-fiber-reinforced thermoplastic (CFRTP) of corroded areas. Stainless steel, aluminum alloy, and CFRTP plates were prepared. Ni and Ni–Cu alloy electroplating were performed on the stainless steel plate. Electroless zinc plating, Ni, and Ni–Cu alloy electroplating were performed on the aluminum alloy plate. The galvanic current between the metal and CFRTP plates was measured using an electrochemical measurement system. The test solution was 0.06 mol/L NaCl aqueous solution. For Stainless steel/CFRTP, the galvanic current flow was negligible with and without the Ni–Cu alloy plating film. For aluminum alloy/CFRTP without the Ni–Cu alloy plating film, the galvanic current ranged from-80 to-120 μA/cm2 at a test temperature of 60°C. For aluminum alloy with the Ni–Cu alloy plating film, the galvanic current ranged from-60 to-80 μA/cm2. The galvanic current for the aluminum alloy plate with Ni–Cu alloy plating was lower than that of the aluminum alloy plate without Ni–Cu alloy plating film. The result suggests that the formation of the Ni–Cu alloy plating on the aluminum alloy improves corrosion resistance.

The effects of plating conditions on nickel (Ni) electroplated films composited with 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-oxidized CNFs (CNFs) were investigated. Plating experiments were performed by varying the amount of CNFs added to the Watt's bath, the current density, and the stirring speed. The plated film obtained at 3 g/L, 2.5 A/cm2, and 300 rpm of them respectively, reached an average 483 HV of the surface hardness, which was the highest in this study. The surface hardness of the conventional Ni film without CNFs plated under the same conditions was an average of 239 HV, and the hardness improvement effect was more than twice as high. The hardness improvement effect due to dispersion enhancement tended to increase as more CNFs were more finely and densely composited into the Ni film, although different trends were observed when the current density was varied.

This study investigated the microstructure and melting point of the Zn–Al composite electroplating film. The cross-sectional microstructure and shear strength of the joints made from the plating films were also evaluated. Zn and Al were confirmed in the plating films from initial microstructure observation. The plating film prepared by a plating bath without cationic surfactant melted near the melting point of Zn and the eutectic point of Zn–Al. When jointed at a joining temperature of 443°C, joining pressure of 5 MPa, and holding time of 5 min, multiple intermetallic compounds, Zn–Al eutectic layers, and unreacted Al particles were observed in the joint layer. From quantitative analysis, the multiple intermetallic compounds were estimated to be Zn–Ni and Zn–Al–Ni intermetallic compounds. The shear strength of the joints increased with increasing joining pressure but was lower than that of Sn–5Sb solder. Fracture after the shear test was observed at the interface between unreacted Al particles and Zn–Al–Ni intermetallic compounds, and inside unreacted Al particles.

The effect of a small amount of Sb addition to Sn-3.0Ag-0.5Cu (mass%) solder on microstructures and impact properties of the solder ball joint was investigated. Cross-sectional microstructural observation revealed that scalloped Cu6Sn5 is formed at the solder/Cu interface, and Cu3Sn is formed at the interface between Cu6Sn5 and Cu with aging. It was confirmed that the growth of the reaction layer is suppressed by the addition of Sb. Moreover, the result of the impact ball shear test showed that the decrease in impact properties with aging can be suppressed in Sn-3.0Ag-0.5Cu-1.5Sb (mass%). It was also suggested that the suppression of linear crack propagation at the Cu3Sn/Cu6Sn5 interface is effective to prevent the reduction of absorbed energy.

This study investigated the electrochemical behavior of Ni–Cu alloy plating baths during plating and dealloying reactions. Furthermore, the potential and plating time effects on the shape of three-dimensional structural Ni–Cu alloy plating film and its adhesion to epoxy resin were investigated. Nodules were observed on the surface of the plating film generated at potentials from-0.5 V to-1.0 V. When the plating films formed at potentials of-1.0 V to-1.5 V were dealloyed, the formation of pores was observed. The shear test results showed that the average shear strength of the specimen joined with epoxy resin between two Cu plates with Ni–Cu alloy plating film formed at a potential of-1.0 V was the highest under all conditions.

The adhesive strength and degradation behavior of the Al/resin interface was investigated under high temperature and high humidity conditions. The adhesive strength of the joint without aging was approximately 14 MPa. The value is the same as the Cu/resin joint. With progress of aging at 85°C in 85%R. H., the strength decreased rapidly in the early aging stage and decreased gradually by further aging. The strength of the Al/resin joint was inferior to that of the Cu/resin joint after aging. The fracture mainly occurred in the interface of the joint. The result of Fourier transform infrared spectroscopy analysis for the fracture surface showed that water absorption in the Al/resin joint occurs by aging and causes the degradation of the strength.

Resistance spot welding was performed on steel and an Al alloy to investigate the microstructural and mechanical properties of the joint. An Al-Mg-Si aluminum alloy A6061 and an alloyed zinc-plated steel sheet GA980 were used as specimens. Resistance spot welding was performed at welding currents of 16 kA, 20 kA, and 22 kA, welding time of 0.24 s, and welding pressure of 5 kN. To investigate the strength of the welds, the tensile shear test and the cross tension test were conducted, and the fatigue test was also conducted. The nugget diameter increased with an increase in the welding current. The tensile shear strength and cross tension strength increased with the increase in the welding current. In the tensile shear fatigue test, interface fracture was observed in the low cycle fatigue region. In the cross tension fatigue test, it was confirmed that the higher the welding current, the better the fatigue properties in the low-cycle fatigue region.

Donor organ shortages for transplantation remain a serious global concern, and alternative treatment is in high demand. Fetal cells and tissues have considerable therapeutic potential as, for example, organoid technology that uses human induced pluripotent stem cells (hiPSCs) to generate unlimited human fetal-like cells and tissues. We previously reported the in vivo vascularization of early fetal liver–like hiPSC-derived liver buds (LBs) and subsquent improved survival of recipient mice with subacute liver failure. Here, we show hiPSC–liver organoids (LOs) that recapitulate midgestational fetal liver promote de novo liver generation when grafted onto the surface of host livers in chemical fibrosis models, thereby recovering liver function. We found that fetal liver, a hematopoietic tissue, highly expressed macrophage-recruiting factors and antifibrotic M2 macrophage polarization factors compared with the adult liver, resulting in fibrosis reduction because of CD163+M2-macrophage polarization. Next, we created midgestational fetal liver–like hiPSC-LOs by fusion of hiPSC-LBs to induce static cell-cell interactions and found that these contained complex structures such as hepatocytes, vasculature, and bile ducts after transplantation. This fusion allowed the generation of a large human tissue suitable for transplantation into immunodeficient rodent models of liver fibrosis. hiPSC-LOs showed superior liver function compared with hiPSC-LBs and improved survival and liver function upon transplantation. In addition, hiPSC-LO transplantation ameliorated chemically induced liver fibrosis, a symptom of liver cirrhosis that leads to organ dysfunction, through immunomodulatory effects, particularly on CD163+phagocytic M2-macrophage polarization. Together, our results suggest hiPSC-LO transplantation as a promising therapeutic option for liver fibrosis.

The chondrocyte-specific miR-140 miRNAs are necessary for normal endochondral bone growth in mice. miR-140 deficiency causes dwarfism and craniofacial deformity. However, the physiologically important targets of miR-140 miRNAs are still unclear. The miR-140 gene (Mir140) encodes three chondrocyte-specific microRNAs, miR-140-5p, derived from the 5′ strand of primary miR-140, and miR140-3p.1 and -3p.2, derived from the 3′ strand of primary miR-140. miR-140-3p miRNAs are 10 times more abundant than miR-140-5p likely due to the nonpreferential loading of miR-140-5p to Argonaute proteins. To differentiate the role of miR-140-5p and -3p miRNAs in endochondral bone development, two distinct mouse models, miR140-C > T, in which the first nucleotide of miR-140-5p was altered from cytosine to uridine, and miR140-CG, where the first two nucleotides of miR-140-3p were changed to cytosine and guanine, were created. These changes are expected to alter Argonaute protein loading preference of -5p and -3p to increase -5p loading and decrease -3p loading without changing the function of miR140-5p. These models presented a mild delay in epiphyseal development with delayed chondrocyte maturation. Using RNA-sequencing analysis of the two models, direct targets of miR140-5p, including Wnt11, were identified. Disruption of the predicted miR140-5p binding site in the 3′ untranslated region of Wnt11was shown to increase Wnt11 mRNA expression and caused a modest acceleration of epiphyseal development. These results show that the relative abundance of miRNA-5p and -3p can be altered by changing the first nucleotide of miRNAs in vivo, and this method can be useful to identify physiologically important miRNA targets.

In this study, the effect of surface treatment of Al with alkaline (pH 10.5 and pH 12.4) and acidic (pH 3.7) electrolyzed water was investigated on bonding strength of solid phase diffusion bonded Al. Aluminum hydroxide and hydroxyl groups were appeared on the surface of Al which was treated with alkaline electrolyzed water of pH 12.4 at 323 K for 2700 s. It was found that such treatment is similar to the one with NaOH aqueous solution at 323 K for 30 s. For bonding strength, shear strength of the bonded Al specimens treated with electrolyzed water of pH 12.4 at 293 K for 3 s and 30 s were higher than that of the untreated specimen.

This article reports on the degradation behavior of adhesion strength of the resin/copper interface under aging in high temperature and high humidity environment. The adhesion strength of a Cu joint with resin was investigated by a tensile test. The fracture surface was analyzed by Fourier transform infrared spectroscopy to investigate the degradation mechanism. As a result, it was found that the degradation of the adhesion strength is mainly caused by water absorption and subsequent volume expansion of the resin, and embrittlement of hydrogen bonding in the joint interface. Evaluation of deterioration life of the joint revealed that the relationships between the deterioration life and the temperature and humidity are confirmed above the glass transition temperature.

Metals with a three-dimensional microstructure film can be joined to plastics by the anchor effect. The three-dimensional microstructure films can be electrodeposited by a Ni-Cu alloy. In this study, the effects of the ratio of the concentration of Ni amidosulfate and Cu sulfate in the plating solution and plating current density on the shapes and microstructures of electrodeposited films were investigated. When the ratio of the concentration of the Ni amidosulfate and the Cu sulfate is 0.47-1.4:0.06 (M/L), a dendritic-type electrodeposited structure was generated at plating current density of 10 mA/cm2. When the ratio of the concentration of the Ni amidosulfate and the Cu sulfate is 0.47:0.6-1.2 (M/L), a feathery-type and needle-type electrodeposited structure was generated.

The effects of welding conditions such as the electrode type and welding current were investigated on the microstructure and joint strength of the resistance weld of A5052 and GA590. The reaction layer formed at the joint interface was inferred to consist of Fe-Al based intermetallic compounds (IMCs) which are FeAl, FeAl2, Fe2Al5 and FeAl3 by quantitative analysis. Although the thickness of the IMCs layer decreased from the center of the nugget towards the edge of it. When the DR type electrode was used, the cross tensile force became higher than those of the joints formed with the R type one. This is because the thickness of the reaction layer formed at the nugget end of A5052 was thin in the case of the DR type electrode. Also, it was found that cross tensile force increases when the thickness of the reaction layer is thin by multiple regression analysis.

Electrodeposited Ni-11 mass%P alloy plating film was fabricated on the surface of stainless steel SUS304 to conduct brazing of SUS304 plates for a heat exchanger. Brazing of SUS304 plates with electrodeposited Ni-11P layers was carried out using a hydrogen reducing furnace. The microstructure and joint strength of the brazed joint were also investigated. From the result of the microstructural observation of the cross section of the joint, it was found that the brazing filler metal is homogeneously distributed without defects such as voids between the SUS304 plates. The results of electrochemical measurements showed that the P-concentrated phase in the Ni-11P alloy is preferentially dissolved in NaCl aqueous solution.

Background and Aims: Artificial Intelligence (AI) based embryo evaluation may objective and reduce inter-observer disagreement. Most commercially available AI models use blastocyst morphokinetics from time-lapse monitoring (TLM). Lifewhisperer (LW, FUJIFILM) is an AI-scoring model that uses a single-focus blastocyst image at a single-time point. LW may be more acceptable to many facilities than the TLM model as it does not require a time-lapse incubator. This study analyzed the predictive ability of LW for pregnant embryos and compared it to an AI model based on morphokinetics (iDAscore, Vitrolife) to assess their usefulness.Methods: This retrospective single-center study analyzed 666 vitrified-warmed blastocyst transfer cycles from January 2019 to December 2022. Inclusion criteria were blastocysts that developed within 5 days from insemination (maximum 120 h) using EmbryoScope+ (Vitrolife), intracytoplasmic sperm injection (ICSI) cycle, and a single-blastocyst transfer cycle. LW score (1.0–9.9) was calculated from single-focus blastocyst images taken before vitrification, while iDAScore (1.0–9.9) was calculated from time-lapse image sequences taken at 11 focal every 10 min after ICSI. We calculated the odds ratio for pregnancy and ROC analysis to compare these models.Results: The mean score was higher in pregnant blastocysts than in non-pregnant blastocysts in both models (LW: 7.47 vs. 6.72, p<0.01; iDAScore: 8.50 vs. 8.04, p<0.01, Willcoxon-test). The odds ratio (95% confidence interval) for pregnancy was 1.19 (1.10–1.28) for LW and 1.48 (1.27–1.74) for iDAScore, with the odds for clinical pregnancy increasing with higher scores (p<0.01). ROC curve analysis showed that the AUC values were 0.60 for LW and 0.62 for iDAScore. There was no significant difference in the predictive ability for pregnant blastocysts (p=0.51).Conclusions: LW allowed objective score calculation from a single focus at single time point blastocyst images without TLM. Moreover, in day 5 blastocyst, LW and iDAscore had comparable predictive pregnancy ability.

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Heterozygous loss-of-function point mutations of miRNA genes are associated with several human congenital disorders1–5, but neomorphic (gain-of-new-function) mutations in miRNAs due to nucleotide substitutions have not been reported. Here we describe a neomorphic seed region mutation in the chondrocyte-specific, super-enhancer-associated MIR140gene encoding microRNA-140 (miR-140) in a novel autosomal dominant human skeletal dysplasia. Mice with the corresponding single nucleotide substitution show skeletal abnormalities similar to those of the patients but distinct from those of miR-140-null mice6. This mutant miRNA gene yields abundant mutant miR-140-5p expression without miRNA-processing defects. In chondrocytes, the mutation causes widespread derepression of wild-type miR-140-5p targets and repression of mutant miR-140-5p targets, indicating that the mutation produces both loss-of-function and gain-of-function effects. Furthermore, the mutant miR-140-5p seed competes with the conserved RNA-binding protein Ybx1 for overlapping binding sites. This finding may explain the potent target repression and robust in vivo effect by this mutant miRNA even in the absence of evolutionary selection of miRNA–target RNA interactions, which contributes to the strong regulatory effects of conserved miRNAs7,8. Our study presents the first case of a pathogenic gain-of-function miRNA mutation and provides molecular insight into neomorphic actions of emerging and/or mutant miRNAs.

Microstructures and mechanical properties of lap fillet welded joints of several high and ultra-high tensile strength steel by arc welding were investigated. Steel plates having tensile strength of 400 (SPH400W), 590 (SPC590Y, SPC590R), 980 (SPC980Y) and 1500 MPa (SAC1500HP) class with 2 mm thickness were prepared. Four types of joints were formed by MAG welding; SPH400W/SPH400W, SPC590Y/SPC590Y, SPC980Y/SPC980Y and SAC1500HP/SPC590R. In joints with SPC590Y, SPC980Y and SAC1500HP steel which matrixes are martensitic microstructures, the HAZ softens due to transformation of martensite into ferrite with precipitating cementite. By using high and ultra-high tensile strength steel, the weld metal is strengthened due to dilution of the matrix into the weld metal and thus tensile shear strength of the welded joint increases. In the fatigue test, similar S-N diagrams were obtained in the all welded joints investigated. It seems that the effect of stress concentration due to the shape of the welded joint on fatigue properties is larger than that of the strength of the matrix.

Tensile and low cycle fatigue properties of Sn-3.5Ag-0.5Cu-0.07Ni-0.01Ge (mass%) lead-free solder were investigated using miniature size specimens and obtained data were compared to those of Sn-3.0Ag-0.5Cu (mass%). The microstructure of Sn-3.5Ag-0.5Cu-0.07Ni-0.01Ge consists of dendritic β-Sn phases and ternary eutectic phases surrounding them which are composed of β-Sn, (Cu,Ni)6Sn5 and Ag3Sn. Tensile strength and 0.1% proof stress of Sn-3.5Ag-0.5Cu-0.07Ni-0.01Ge are superior to those of Sn-3.0Ag-0.5Cu at 25°C and 150°C. However, elongation of it is inferior to that of Sn-3.0Ag-0.5Cu at both temperatures. Fatigue lives of both alloys obey the Manson-Coffin equation and are analogous at 25°C. Although fatigue lives of both alloys decrease at 150°C, the fatigue life of Sn-3.5Ag-0.5Cu-0.07Ni-0.01Ge is inferior to that of Sn-3.0Ag-0.5Cu. At 150°C, the crack mainly progresses at grain boundaries of recrystallized grains. Sn-3.5Ag-0.5Cu-0.07Ni-0.01Ge has several grain boundaies which can be the origin of the crack so that fatigue lives degrade at 150°C.

The effect of the cooling rate in bonding on IMCs formation and their morphology in the solder joint with Sn-3.0Ag-0.7Cu-5.0In (mass%) lead-free solder was investigated. As the substrate, the Cu plate and the Cu plate with electroplated Ni were prepared. Bonding was conducted in the vacuum atmosphere, and bonding temperature and time were 300°C and 10 minutes, respectively. The cooling rates in the bonding were changed from 0.02°C/s to 0.2°C/s. In both Cu/Cu and Cu/Ni joints, scallop-shaped IMCs form at the joint interfaces regardless of the cooling rate. In the Cu/Cu joint, Cu6(Sn,In)5 and Cu3(Sn,In) layers form at the joint interface. In the Cu/Ni joint, (Cu,Ni)6(Sn,In)5 and (Cu,Ni)3(Sn,In) layers form at the joint interface with Cu and the (Cu,Ni)6(Sn,In)5 layer forms at the joint interface with Ni. Die shear force of the Cu/Ni joints are a little larger than those of the Cu/Cu joints. Fracture occurs in the boundary between the scallop-shaped layer or the granular IMC layer and the layered IMC in both joints. The cooling rate from the peak temperature to solidification is an important factor to decide the shape of formed IMC. When the cooling rate is high and supercooling becomes large, formation of pillar-shaped IMCs occurs easily.

To investigate the mechanism of crack initiation in the glass substrate, residual stress in the substrate was analyzed by the finite element method (FEM). A Si wafer that has the same mechanical properties of glass was prepared as the substrate. The thin Cu film layer was fabricated on the Si wafer by plating. The warpage of the wafer in the heat treatment process was investigated by laser displacement measurement. Residual stress was calculated by the obtained warpage value using the Stoney formula. It was found that the warpage becomes zero and the stress-free state occurs around at 150°C. On the basis of the FEM analysis result from 150°C to the room temperature in the cooling process, it was found that analyzed warpage values are almost analogous to measured ones. Also, it was confirmed that equivalent stress in the wafer in the vicinity of the Cu/Si interface increases and the stress-concentrated area expands there with increasing the thickness of the Cu film. The results indicates that crack initiation easily occurs in the glass substrate when the thickness of the Cu film increases. Moreover, from the results of the FEM analysis for the warpage of the wafer in the heating process, it was found that the analyzed warpage is good accordance with the measured one from room temperature to around 150°C.

A cold forging process of Mo-alloyed sintered steel was simulated by finite element method (FEM) analysis considering density change in the process. Moreover, the effect of sintering time on the behavior of the densification and the plastic deformation of it in the cold-forging process was also investigated. Using the true stress-true strain diagram obtained by the compression test with a sintered specimen, the modified true stress-true strain diagram was derived for large plastic deformation analysis with the porous material model. The result of FEM analysis for the cold compression process of the sintered specimen revealed that the analysis can simulate the shape of the excessive metal part and density change of it. Also, it was found that local deformation becomes large and thus the excessive metal part extends with increasing sintering time although the difference in the true stress-true strain diagrams is negligible.

Brain damage caused by hypoxic ischemic insult during the perinatal period causes hypoxic ischemic encephalopathies (HIEs). Therapeutic hypothermia is indicated for HIE, but because the therapeutic burden is large for its limited therapeutic effectiveness, another strategy is needed. Progesterone (P4) plays a neuroprotective role through the actions of its metabolite, allopregnanolone (Allo), on P4 receptor, γ-aminobutyric acid type A receptors or both. We examined the therapeutic potential of P4 using a newborn rat model of HIE. Fetal rats were exposed to transient ischemic hypoxia by 30-minute bilateral uterine artery clamping on gestational day 18. After spontaneous birth, newborn pups were subcutaneously injected with P4 (0.10 or 0.01 mg), medroxyprogesterone acetate (MPA; 0.12 mg), or Allo (0.10 mg) through postnatal days (PDs) 1 to 9. Brain damage in the rats was assessed using the rotarod test at PD50. The HIE insult reduced the rats' ability in the rotarod task, which was completely reversed by P4 and Allo, but not by MPA. Histological examination revealed that the HIE insult decreased neuronal (the cortex and the hippocampal CA1 region) and oligodendroglial cell density (the corpus callosum) through PD0 to PD50. The axon fiber density and myelin sheath thickness in the corpus callosum were also reduced at PD50. The time-course study revealed that P4 restored oligodendroglial cells by PD5, which was followed by neuroprotective action of P4 that lasted long over the injection period. These results suggest that P4 protects the neonatal brain from HIE insult via restoration of oligodendroglial cells.

RNA interference (RNAi) is a major, powerful platform for gene perturbations, but is restricted by off-target mechanisms. Communication between RNAs, small RNAs, and RNA-binding proteins (RBPs) is a pervasive feature of cellular RNA networks. We present a crosstalk scenario, designated as ‘crosstalk with endogenous RBPs’ (ceRBP), in which small interfering RNAs or microRNAs with seed sequences that overlap RBP motifs have extended biological effects by perturbing endogenous RBP activity. Systematic analysis of small interfering RNA (siRNA) off-target data and genome-wide RNAi cancer lethality screens using 501 human cancer cell lines, a cancer dependency map, identified that seed-to-RBP crosstalk is widespread, contributes to off-target activity, and affects RNAi performance. Specifically, deconvolution of the interactions between gene knockdown and seed-mediated silencing effects in the cancer dependency map showed widespread contributions of seed-to-RBP crosstalk to growth-phenotype modulation. These findings suggest a novel aspect of microRNA biology and offer a basis for improvement of RNAi agents and RNAi-based functional genomics. This study presents evidence that siRNAs or miRNAs with seed sequences that overlap RBP motifs have extended biological effects by perturbing RBP activity. Seed-to-RBP crosstalk contributes to off-target activity and growth phenotype modulation.

Tensile properties of Sn-5Sb (mass%) and Sn-3.5Ag-0.5Cu-0.07Ni-0.01Ge (mass%) were investigated using miniature size specimens and obtained results were compared. Tensile strength of both alloys increase with increasing the strain rate and decrease with increasing the temperature. Although similar dependency to the temperature is observed in 0.1% proof stress, the effect of the strain rate on it is obscure. The tensile strength and the 0.1% proof stress of Sn-3.5Ag-0.5Cu-0.07Ni-0.01Ge are higher than those of Sn-5Sb. The elongation of Sn-5Sb is relatively stable at the range from 0.4 to 0.6. The elongation of Sn-3.5Ag-0.5Cu-0.07Ni-0.01Ge which is approximately 0.3, is inferior to that of Sn-5Sb. On the basis of investigation of stress exponent, n, it was clarified that dispersion strengthening by Ag3Sn particulates in Sn-3.5Ag-0.5Cu-0.07Ni-0.01Ge is effective to prevent the degradation of creep resistance compared with Sn-5Sb that is strengthened by solid-solution of Sb in β-Sn phases and dispersion of SbSn compounds.

Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive “reverse” screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass producing homogeneous and miniaturized liver buds on a clinically relevant large scale (>108). Vascularized and functional liver tissues generated entirely from iPSCs significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacturing platform for multicellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations.

The blood calcium concentration during fetal life is tightly regulated within a narrow range by highly interactive homeostatic mechanisms that include transport of calcium across the placenta and fluxes in and out of bone; the mechanisms of this regulation are poorly understood. Our findings that endochondral bone-specific PTH/PTHrP receptor (PPR) knockout (KO) mice showed significant reduction of fetal blood calcium concentration compared with that of control littermates at embryonic day 18.5 led us to focus on bone as a possibly major determinant of fetal calcium homeostasis. We found that the fetal calcium concentration of Runx2KO mice was significantly higher than that of control littermates, suggesting that calcium flux into bone had a considerable influence on the circulating calcium concentration. Moreover, Runx2:PTHdouble mutant fetuses showed calcium levels similar to those of Runx2KO mice, suggesting that part of the fetal hypocalcemia in PTHKO mice was caused by the increment of the mineralized bone mass allowed by the formation of osteoblasts. Finally, Rank:PTHdouble mutant mice had a blood calcium concentration even lower than that of the either RankKO or PTHKO mice alone at embryonic day 18.5. These observations in our genetic models suggest that PTH/PTHrP receptor signaling in bones has a significant role of the regulation of fetal blood calcium concentration and that both placental transport and osteoclast activation contribute to PTH's hypercalcemic action. They also show that PTH-independent deposition of calcium in bone is the major controller of fetal blood calcium level.

In recent years, there has been a growing demand for safe soft robots that work in a work environment similar to that of humans. The use of 3D modeling technology in the manufacturing of soft robot chassis, soft electronic parts, and wiring processes is expected to lead to more efficient and smaller soft robot manufacturing. The objective of this study is to fabricate a gel capacitor using ionic liquid as an electrolyte, which has characteristics such as non-volatility, flame retardance, and conductivity. We fabricate ionic liquid gels that possess flexibility and conductivity after curing using a photoformable 3D gel printer, and discuss their performance as capacitors.

We have performed multi-frequency electron spin resonance (ESR) measurements on EuFe2As2, which is one of the parent compounds of Fe-based superconductors. At TSDW=190 K, this compound shows a spin-density-wave (SDW) transition. At temperatures above TSDW, the relaxation of Eu2+spins takes place via the coupling of conduction electrons, resulting in a Korringa-type increase in the linewidth. At temperatures below TSDW, however, this compound shows an anisotropic temperature-independent linewidth except at temperatures near the long-range ordering temperature (19 K) of Eu2+spins, giving evidence for a gap opening at TSDW. This change of physical properties indicates a change in the exchange interaction between localized Eu2+spins and conduction electrons in the FeAs layers. We evaluate the exchange constant, which was not reported in previous X-band ESR studies, and compare it with the value for another Eu metallic compound.

Anterior dislocation after total knee arthroplasty (TKA) is rare; 9 cases have been reported in the English literature. Five patients sustained subluxation, with recurvatum as the clinical manifestation, and 4 patients sustained complete dislocation, usually accompanying other serious complications.This article describes a case of complete dislocation that developed atraumatically 16 years after TKA and was characterized by dislocation in extension and spontaneous reduction in flexion. Revision TKA was planned, with several alternative procedures under consideration, ranging in degree of invasiveness from simple polyethylene exchange to conversion to a hinge-typed prosthesis. Intraoperatively, extensive areas of blackened synovium and posterior-dominant polyethylene wear existed medially and laterally. Considering the patient’s age of 82 years, low activity level in activities of daily living, edematous skin, and number of stable components, we performed simple polyethylene exchange to a cruciate-retaining component that left the partial metal defect in the tibial plate untouched. Successful outcome was achieved for >2 years. The dislocation mechanism was polyethylene thinning, leading to relative valgus and anteroposterior instability that aggravated the anterior cruciate ligament dysfunction, which is speculated as the inherent key causative factor in every TKA.Complete dislocation, usually accompanying other complications, requires prompt treatment because the possibility of serious consequences exists. Due to the absence of a gold standard, the treatment of choice needs to be made on a case-by-case basis.

Macro-scale temperature fluctuations, which have long radial correlation length (of the order of the plasma radius), have been discovered on Large Helical Device (LHD). In this paper, non-linear coupling between the long-range fluctuations and microscopic fluctuations is investigated using cross bi-coherence analysis. The significant cross bi-coherence between long-range fluctuations and micro-fluctuations is observed in the range of frequency $f < 100$ kHz, where $f$ is the frequency of microscopic fluctuations. It is found that the squared bi-coherence and bi-phase for this three-wave coupling is weakly dependent on the frequency of microscopic fluctuations. These observations demonstrate that the microscopic fluctuations are coherently interacting with long-range fluctuations.

Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered clinical application despite little definition of their function in residence. Here, we report genetic pulse-chase experiments that define osteoblastic cells as short-lived and nonreplicative, requiring replenishment from bone-marrow-derived, Mx1+stromal cells with “MSC” features. These cells respond to tissue stress and migrate to sites of injury, supplying new osteoblasts during fracture healing. Single cell transplantation yielded progeny that both preserve progenitor function and differentiate into osteoblasts, producing new bone. They are capable of local and systemic translocation and serial transplantation. While these cells meet current definitions of MSCs in vitro, they are osteolineage restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived MSCs may be a heterogeneous population with the Mx1+population, representing a highly dynamic and stress responsive stem/progenitor cell population of fate-restricted potential that feeds the high cell replacement demands of the adult skeleton.

The aim of this study is to investigate the relationship between the inelastic strain range and the thermal fatigue lives of chip size package solder joints with Sn-Pb and Sn-Ag-Cu solder balls. The inelastic strain range was examined by finite element analysis. In both solder joints, the exponential terms in the inelastic strain range term in the Coffin-Manson equation were evaluated as 1.8 - 2.3. These values are very close to the conventional one used in Sn-Pb and the Pb containing solders. The inelastic strain range is almost proportional to the temperature range in the Sn-Pb solder joint. On the contrary, the inelastic strain range is proportional to approximately the square root of the temperature range in the Sn-Ag-Cu solder joint. The deference depends on the change of the stress-strain hysteresis curve in the thermal cycle.

Semiconductor packages that use metallization and lead-free solders are increasingly being used in electronic products. In this study, interface reactions and joint-strength reliability were investigated for Sn-3W%Ag-0.5W%Cu solder ball joints joined to Cr/Cu and Cr/Ni-40W% metallization layers that were heat treated at 260°C. The strength of the joint with the Cr/Cu metallization layer decreased as the duration of the heat treatment increased. Sn and Cr interface reactive layers were generated after the loss of Cu in the Cr/Cu metallization layer, but the connection was maintained. By contrast, the connection of the joint to the Cr/Ni-40W metallization layer was relatively stable under the heat treatment conditions investigated.

The purpose of this study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for primary and metastatic liver tumors using the Novalis image-guided radiotherapy system. After preliminarily treating liver tumors using the Novalis system from July 2006, we started a protocol-based study in February 2008. Eighteen patients (6 with primary hepatocellular carcinoma and 12 with metastatic liver tumor) were treated with 55 or 50 Gy, depending upon their planned dose distribution and liver function, delivered in 10 fractions over 2 weeks. Four non-coplanar and three coplanar static beams were used. Patient age ranged from 54 to 84 years (median: 72 years). The Child-Pugh classification was Grade A in 17 patients and Grade B in 1. Tumor diameter ranged from 12 to 35 mm (median: 23 mm). Toxicities were evaluated according to the Common Terminology Criteria of Adverse Events version 4.0, and radiation-induced liver disease (RILD) was defined by Lawrence's criterion. The median follow-up period was 14.5 months. For all patients, the 1-year overall survival and local control rates were 94% and 86%, respectively. A Grade 1 liver enzyme change was observed in 5 patients, but no RILD or chronic liver dysfunction was observed. SBRT using the Novalis image-guided system is safe and effective for treating primary and metastatic liver tumors. Further investigation of SBRT for liver tumors is warranted. In view of the acceptable toxicity observed with this protocol, we have moved to a new protocol to shorten the overall treatment time and escalate the dose.

The purpose of this study was to evaluate the effect of megavoltage photon beam attenuation (PBA) by couch tops and to propose a method for correction of PBA. Four series of phantom measurements were carried out. First, PBA by the exact couch top (ECT, Varian) and Imaging Couch Top (ICT, BrainLAB) was evaluated using a water-equivalent phantom. Second, PBA by Type-S system (Med-Tec), ECT and ICT was compared with a spherical phantom. Third, percentage depth dose (PDD) after passing through ICT was measured to compare with control data of PDD. Forth, the gantry angle dependency of PBA by ICT was evaluated. Then, an equation for PBA correction was elaborated and correction factors for PBA at isocenter were obtained. Finally, this method was applied to a patient with hepatoma. PBA of perpendicular beams by ICT was 4.7% on average. With the increase in field size, the measured values became higher. PBA by ICT was greater than that by Type-S system and ECT. PBA increased significantly as the angle of incidence increased, ranging from 4.3% at 180 degrees to 11.2% at 120 degrees . Calculated doses obtained by the equation and correction factors agreed quite well with the measured doses between 120 degrees and 180 degrees of angles of incidence. Also in the patient, PBA by ICT was corrected quite well by the equation and correction factors. In conclusion, PBA and its gantry angle dependency by ICT were observed. This simple method using the equation and correction factors appeared useful to correct the isocenter dose when the PBA effect cannot be corrected by a treatment planning system.

To investigate the antitumor effects of the selective HIF-1 inhibitors echinomycin and PX-478 on uterine fibroids.

PM10samples were collected at an urban site of Nagoya City during September, 2003, to August, 2004, and annual variations of the concentrations of the elements in PM10samples were examined by inductively coupled plasma atomic emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS). The annual concentration variations of ca. 30 elements in ambient air were in the range from sub-ng m-3to several μg m-3. From an evaluation by the enrichment factors of the elements, elements such as Al, Ca, Fe, Mg, Ti, Mn, Ba, Sr, Ce, La, Nd, Co, Cs, and Pr, in PM10samples were found to have originated mostly from natural sources, while the elements such as S, Zn, Pb, Cu, Ni, Sb, Sn, Cd, Bi, W, Tl, and In originated from anthropogenic emission sources. Furthermore, in seasonal variations of the elemental concentrations of PM10samples in ambient air, the elements originated mostly from natural sources provided significantly high concentrations in spring during the “Kosa” period (the dust season from March to May). On the other hand, the elements mainly from anthropogenic emission sources provided relatively higher concentrations in autumn and winter, which may be explained by the fact that the urban atmospheric structure is stabilized by the temperature-inversion layer formed over the city in those seasons. In addition, all of the elements provided significantly low concentrations in the summer, due to the dilution effect of the oceanic winds as well as due to the convection of air mass up to the high levels.

The multielement determination of PM10(airborne particulate matter smaller than 10 μm) samples, which was collected by a high volume air sampler at the urban site of Nagoya City, was carried out by inductively coupled plasma atomic emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS). The present analytical method was validated by analyzing urban particulate matter standard reference material of NIST SRM 1648. The analytical data for ca. 30 elements in PM10samples collected during a period from 8 September to 9 October, 2003, were obtained in the concentration range from sub-μg g-1to several-10 mg g-1, but the data for 18 elements among ca. 30 elements were available for the characterization of PM10samples in ambient air, because of problems caused by the filter blanks. Then, the trends concerning the distributions of diverse elements in PM10samples were analyzed based on the enrichment factors and size distribution factors. The lithophile and siderophile elements were distributed more than 50% in coarse particle fraction (<2.1 μm), which was derived mainly from natural sources, such as soils and crustal minerals. On the other hand, chalcophile elements were distributed more than 50% in fine particle fraction (>2.1 μm), which was derived mostly from anthropogenic emission sources. The large enrichment of chalcophile elements in PM10samples as well as their mining influence factors (MIFs) suggested their wide use in industrial productions.

Signaling by the parathyroid hormone/parathyroid hormone‐related protein receptor (Ppr) is necessary for mammary gland development beyond the early induction stage in mice. We used a series of murine models of reduced Ppr expression to determine how diminished receptor signaling influences mammary development. Reduction of Ppr expression to very low levels prevented mammary gland development. A less‐severe reduction in Ppr expression permitted progression of mammary gland development beyond the induction stage, but the nipples of these mice were dramatically smaller than those of controls, with altered epidermis and connective tissue. Mothers with reduced expression of Ppr could not successfully nurse pups; however, the lactating glands did produce milk but could not efficiently deliver it. This finding was associated with reduced levels of matrix metalloproteinase‐2 and an absence of pregnancy‐associated remodeling of connective tissue matrix in the nipple. Reduced smooth muscle appears to underlie the majority of nipple deficiencies in mice with lower levels of the Ppr expression. Developmental Dynamics 233:794–803, 2005. © 2005 Wiley‐Liss, Inc.

Gsα is a ubiquitously expressed G protein α‐subunit that couples receptors to adenylyl cyclase. Mice with chondrocyte‐specific ablation of the Gsα gene had severe epiphyseal and growth plate abnormalities and ectopic cartilage formation within the metaphyseal region of the tibia. These results show that Gsα negatively regulates chondrocyte differentiation and is the critical signaling mediator of the PTH/PTH‐rP receptor in growth plate chondrocytes.

Gsα is a ubiquitously expressed G protein α‐subunit that couples receptors to adenylyl cyclase. Mice with chondrocyte‐specific ablation of the Gsα gene had severe epiphyseal and growth plate abnormalities and ectopic cartilage formation within the metaphyseal region of the tibia. These results show that Gsα negatively regulates chondrocyte differentiation and is the critical signaling mediator of the PTH/PTH‐rP receptor in growth plate chondrocytes.Introduction:Gsα is a ubiquitously expressed G protein α‐subunit that mediates signaling through G protein‐coupled receptors to activate the cAMP/protein kinase A signaling pathway. Although studies suggest an important role for Gsα in regulating growth plate development, direct in vivo results examining this role are lacking.Materials and Methods:The Gsα gene was ablated in murine cartilage by mating mice with loxP sites surrounding the Gsα promoter and first exon with collagen 2a1 promoter‐Cre recombinase transgenic mice. Skeletal tissues were studied by gross and microscopic pathology, and gene expression was determined by in situ hybridization.Results and Conclusions:Mice with complete chondrocyte‐specific Gsα deficiency (homozygotes) died within minutes after birth and had severe epiphyseal and growth plate defects with shortening of the proliferative zone and accelerated hypertrophic differentiation of growth plate chondrocytes, a phenotype similar to that of PTH/PTH‐related peptide (PTHrP) receptor knockout mice. Indian hedgehog and PTH/PTHrP receptor expression in prehypertrophic chondrocytes was unaffected in mutant mice. PTHrP expression in periarticular cartilage was increased in the mutant mice, probably because of the closer proximity of Ihh‐secreting chondrocytes to the periarticular zone. In addition, these mice developed ectopic cartilage at the anterior side of the metaphyseal region in the tibia. Mice with partial Gsα deficiency (heterozygotes) exhibited no phenotype. These results show that Gsα negatively regulates chondrocyte differentiation and is the critical signaling mediator of the PTH/PTHrP receptor in epiphyseal and growth plate chondrocytes.

In contrast to selenoprotein Ps (SeIPs) from other animal species, bovine selenoprotein P-like-protein (SeIPLP) was found to contain a tandem repeat of (CAYYCC)11. During an investigation into whether SeIPLP was a bovine substitute for SeIP or uniquely bovine, its mRNA was found to consist of multiple variants with different length tandem repeat, namely p(0) with (CAYYCC)11, p(−4) lacking (CAYYCC)4, p(−8) lacking (CAYYCC)8, and p(−9) lacking (CAYYCC)9. Although they were encoded on a single gene locus, neither classicalGT-AGnor minor classAT-ACdonator-acceptor sequences for alternative splicing were identified. A subsequent S1 protection assay using oligonucleotides, whose sequence may occur as variants, performed against bovine poly(A)+RNA identified a total of nine variants. Judging from the sequence of these variants and the branch point mapping, the consensus sequence for recognition of the donator was CACCCCCACand of the acceptor and the branch point A nucleotide,ACCCCCAT orACCCCCATCCCCAT. Furthermore, when the p(0) insert mRNA was expressed in COS-7 cells derived from an African green monkey kidney, cDNAs corresponding to p(−8) and p(−9) could be isolated. Therefore, the bovine SeIPLP mRNAs consisted of multiple variants probably due to a novel splicing mechanism which was not bovine-specific but common to other mammals.

How podocytes respond to injury is poorly understood, although podocyte injury in the glomerulus has been proposed as the crucial mechanism in the pathogenesis of proteinuria and focal segmental glomerulosclerosis. An increase in sodium/myo-inositol co-transporter (SMIT) transcripts, an osmoprotective gene, has been demonstrated in a variety of brain injury models. In the present study, we investigated SMIT expression in podocytes in experimental nephrosis.

Angiotensin II (Ang II) type 1 receptor (AT1R) has been confirmed to confer renoprotection in the progressive, immune-mediated nephritis in animal models as well as in humans. However, the relative contributions of direct AT1R blockade, indirect counteractivation of Ang II type 2 receptor (AT2R), or both, to renoprotection through AT1R antagonism remains to be clarified. Immunohistochemical studies in the nephritic kidney revealed that tubular epithelial cells and infiltrating immune cells were positive for AT1R and AT2R. In the present study, we investigated the action of Ang II on both receptors on immune cells. A subpopulation of lipopolysaccharide-activated splenic lymphocytes (mixed lymphocyte populations) was positive for AT1R and AT2R. Ang II alone could not induce gene expression of a pro-inflammatory chemokine JE or a pro-fibrotic cytokine transforming growth factor-β1 in those cells. However, Ang II could significantly suppress the expression of both genes in those cells under AT1R blockade, and this action was mediated through AT2R. Conversely, the pro-inflammatory/pro-fibrotic gene expression could be enhanced by AT2R blockade, and this was mediated through AT1R. AT1R and AT2R expressed in activated immune cells can modulate pro-inflammatory and pro-fibrotic reactions reciprocally. In advanced immune-mediated nephritic kidneys, AT1R antagonism likely confers renoprotection via activation of AT2R.

We established a cis-diamminedichloroplatinum (II) (CDDP) resistant cell line and determined the mechanisms of CDDP resistance.

Brief treatment of metaphase II (MII) stage porcine oocytes with 0.4 μg/mL demecolcine in the presence of 0.05 M sucrose produces a membrane protrusion that contains a condensed chromosome mass. The present study examined the optimal conditions for demecolcine and nocodazole treatment in chemically assisted removal of chromosomes. When matured oocytes were treated with 0.1-0.4 μg/mL demecolcine for 60 min or with 0.4 μg/mL demecolcine for 30 min or 3 μg/mL nocodazole for 30 or 60 min, more than 70% of oocytes had a membrane protrusion containing condensed chromosomes were located. There was no difference in the in vitro developmental potential of enucleated oocytes assisted by 0.1 and 0.4 μg/mL demecolcine or 3 μg/mL nocodazole that received porcine somatic cells. After transfer to 10 recipients, however, two of six recipients that received demecolcine-treated enucleated eggs produced four healthy cloned piglets, but none of the four recipients of nocodazole-treated enucleated eggs produced piglets. Further studies are required to increase the successful development to term because the proportion of live piglets was low (4/2, 672, 0.15%).

Hepatocyte growth factor (HGF) has been demonstrated to attenuate acute tubular necrosis and interstitial fibrosis in a variety of rodent models of kidney disease. We investigated how HGF could affect chronic toxic nephropathy/interstitial fibrosis caused by aristolochic acid (AA).

Background:Cell-to-cell interaction is thought to be an important feature of a variety of biological processes. As far as the proinflammatory process is concerned, the interaction between mesangial cells and monocytes/macrophages induces the expression of monocyte chemoattractant protein-1 (MCP-1), and this may play a role in glomerulonephritis. In this study, we investigated whether the cell-to-cell interaction between immune cells and renal fibroblasts induces MCP-1 gene expression, which may be involved in interstitial inflammation in the kidney. Methods:Human renal fibroblast cell lines, tNKF (from a normal kidney) and tFKIF (from a kidney with fibrosis), and peripheral blood mononuclear cells (PBMC) were used to assess the effect of cell-to-cell contact on the expression of MCP-1 mRNA in the fibroblasts. The expression of the MCP-1 gene in the fibroblasts was also examined after stimulation with tumor necrosis factor-α (TNF-α) and the culture supernatant from PBMC. RT-PCR was used to detect MCP-1 mRNA expression. Neutralizing antibodies to intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial adhesion molecule-1 (VCAM-1) were used to block the cell-to-cell contact between the fibroblasts and PBMC. Results:TNF-α and the culture supernatant from PBMC increased MCP-1 gene expression in tNKF cells. Contact culture with PBMC also significantly increased MCP-1 gene expression in tNKF cells. Although the basal level of MCP-1 mRNA was higher in tFKIF than tNKF cells, tFKIF cells did not respond significantly to any stimulation in this study. Following pretreatment with anti-ICAM-1 antibody, MCP-1 gene expression in tNKF cells was significantly suppressed in contact culture with PBMC. Anti-VCAM-1 antibody treatment had no effects. Conclusion:It is suggested that the interaction between renal fibroblasts and PBMC was mediated through direct contact and by secreted humoral factors. ICAM-1 on renal fibroblasts may be involved in the direct cell-to-cell interaction inducing MCP-1 gene expression, which seems to be involved in renal interstitial inflammation.

In developing murine growth plates, chondrocytes near the articular surface (periarticular chondrocytes) proliferate, differentiate into flat column-forming proliferating cells (columnar chondrocytes), stop dividing and finally differentiate into hypertrophic cells. Indian hedgehog (Ihh), which is predominantly expressed in prehypertrophic cells, stimulates expression of parathyroid hormone (PTH)-related peptide (PTHrP) which negatively regulates terminal chondrocyte differentiation through the PTH/PTHrP receptor (PPR). However, the roles of PTHrP and Ihh in regulating earlier steps in chondrocyte differentiation are unclear. We present novel mouse models with PPR abnormalities that help clarify these roles. In mice with chondrocyte-specific PPR ablation and mice with reduced PPR expression, chondrocyte differentiation was accelerated not only at the terminal step but also at an earlier step: periarticular to columnar differentiation. In these models, upregulation of Ihh action in the periarticular region was also observed. In the third model in which the PPR was disrupted in about 30% of columnar chondrocytes, Ihh action in the periarticular chondrocytes was upregulated because of ectopically differentiated hypertrophic chondrocytes that had lost PPR. Acceleration of periarticular to columnar differentiation was also noted in this mouse, while most of periarticular chondrocytes retained PPR signaling. These data suggest that Ihh positively controls differentiation of periarticular chondrocytes independently of PTHrP. Thus, chondrocyte differentiation is controlled at multiple steps by PTHrP and Ihh through the mutual regulation of their activities.