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Dual-frequency ultrasonic cleaning with a diluted phosphoric acid solution was developed to remove oxide scales on surfaces of hot-stamped parts from uncoated steel sheets, and conventional shot blasting processes are omitted. The removal of the oxide scale by ultrasonic cleaning is accelerated by the phosphoric acid solution and the dual frequency. The removing time for the phosphoric acid solution was shorter than that for a hydrochloric acid solution, and rust appearing for leaving after cleaning was prevented by generating an iron phosphate layer. In dual-frequency ultrasonic cleaning with the diluted phosphoric acid solution, the oxide scale was dissolved, and then the oxide scales were exfoliated from the thin scale and high-pressure portions. The removing time decreased with decreasing pH and oxide scale thickness and with increasing solution temperature. The surface roughness and distortion of an ultrasonic-cleaned hot-stamped part were smaller than those for shot blasting, and the weldability and paintability were similar. The oxide scale of a hot-stamped part having a nonuniform distribution of oxide scale thickness was successfully removed by dual-frequency ultrasonic cleaning with the diluted phosphoric acid solution.

Protein kinase A promotes beige adipogenesis downstream from β-adrenergic receptor signaling by phosphorylating proteins, including histone H3 lysine 9 (H3K9) demethylase JMJD1A. To ensure homeostasis, this process needs to be reversible however, this step is not well understood. We show that myosin phosphatase target subunit 1- protein phosphatase 1β (MYPT1-PP1β) phosphatase activity is inhibited via PKA-dependent phosphorylation, which increases phosphorylated JMJD1A and beige adipogenesis. Mechanistically, MYPT1-PP1β depletion results in JMJD1A-mediated H3K9 demethylation and activation of the Ucp1 enhancer/promoter regions. Interestingly, MYPT1-PP1β also dephosphorylates myosin light chain which regulates actomyosin tension-mediated activation of YAP/TAZ which directly stimulates Ucp1 gene expression. Pre-adipocyte specific Mypt1 deficiency increases cold tolerance with higher Ucp1 levels in subcutaneous white adipose tissues compared to control mice, confirming this regulatory mechanism in vivo. Thus, we have uncovered regulatory cross-talk involved in beige adipogenesis that coordinates epigenetic regulation with direct activation of the mechano-sensitive YAP/TAZ transcriptional co-activators.

A punching test for simply estimating the tensile strength and total elongation of steel sheets and formed parts was proposed. The tensile strength and total elongation were estimated from the shear stress at the maximum punching load and percentage of the burnished depth at the sheared edge of the slug measured without cutting, respectively. For a variety of steel sheets with a range of the tensile strength from 360 to 1500 MPa, linear functions for the estimation were experimentally obtained. The correlation of the estimated tensile strength of the steel sheets with the measured one from the uniaxial tensile test was considerably high, and the correlation of the estimated total elongation was high. The distributions of tensile strength and total elongation for hot- and cold-stamped parts were estimated. The proposed punching test is available under not only a laboratory environment but also a factory environment.

The phase transformation and mechanical properties of non-quenchable steels partnered with the quenchable boron steel in hot stamping of tailor-welded blanks were evaluated to produce tailored components with partially balanced strength and ductility. The effect of the forming start temperature after natural air cooling on the phase transformation and mechanical properties for 270 MPa mild steel, non-quenchable steel, 440 MPa high strength steel, and 22MnB5 steel sheets was examined, and the 270 MPa and non-quenchable sheets had enough ductility after hot stamping. Tailored components having a hardness of about 500 HV1 in the high strength zone and a total elongation of about 30% in the high ductility zone were hot-stamped from a tailor-welded blank composed of 22MnB5 and 270 MPa sheets. It was found that the 270 MPa mild steel sheet is sufficient as a partner sheet of tailor-welded blanks. In addition, the safety of hot-stamped components was heightened by welding a 22MnB5 main blank with a 270 MPa steel patch. Even if the main blank is fractured by a collision, the hot-stamped component is not separated by the 270 MPa patch having high ductility.

Hydrogen-induced delayed cracking of punched 1.5 GPa ultra-high strength steel sheets was prevented by ironing with a slug ejected from punching, because the risk of delayed cracking for sheared 1.5 GPa sheets is very high due to high tensile residual stress and large plastic deformation. To prevent the occurrence of delayed cracking, the sheet was punched, and then, the punched hole was ironed by passing the punched slug. Although the residual stress around the punched edge of the 1.5 GPa sheet was tensile, the stress was turned to compressive stress by slug ironing. In addition, the fracture surface of the sheared edge was changed to a smooth ironed surface. A cathode hydrogen charging test of the punched edge for delayed cracking was performed. Although delayed cracks were caused at the punched hole by hydrogen charging, no cracks occurred at the ironed hole for charging. It was found that slug ironing of the punched hole is effective in preventing delayed cracking.

A warm stamping process of 1 and 1.2 GPa ultra-high strength steel sheets at comparatively low temperatures using rapid resistance heating was investigated to produce high strength parts. The effects of the heating temperature and rate on mechanical and surface properties of warm-stamped parts were examined. For a rapid heat rate of 100 °C/s around a heating temperature of 300 °C, the hardness of the formed parts increased from that of the as-received sheets, and the hardness for the 1.2 GPa sheet approached that of conventional hot-stamped parts from 22MnB5 steel sheets. The increase in hardness appeared only for rapid heating, and not for slow heating using a furnace. The increase in hardness is due to the transformation of retained austenite into martensite at comparatively low temperatures using rapid resistance heating and cooling. For the comparative low heating temperature, the non-coated sheet hardly oxidised, and the galvannealed sheet having high corrosion resistance did not exhibit the exfoliation of the coating layer, whereas the springback did not improve.

Discovering new genetic mutations is vital for expanding genetic resources for exploring the functions and breeding applications of genes. In this study, we created new mutant populations of rice and evaluated its effectiveness by using a chemical mutagen diepoxybutane (DEB) with the expectation of manageably causing small-scale deletions that induce knock-out mutations. Compared with the more common mutagen, ethyl methanesulfonate (EMS), DEB exhibited approximately 160 times the adverse impact on the early growth of rice. At 0.3 mM, which was 1/160 the concentration of EMS in the control population, the heading date in the DEB-mutated population showed dispersion, albeit with a small standard deviation. Therefore, similar to EMS, DEB has been shown to induce DNA mutations. According to the screening of waxy mutants using the Targeting Induced Local Lesions in Genomes (TILLING) method, DEB-mutated populations had nearly similar mutation frequencies to those of EMS-mutated populations. Therefore, we successfully isolated five mutant lines from the DEB-mutated population. Some of these mutants exhibited a low-amylose phenotype, which is applicable to breeding leading to enhanced taste evaluation. To utilize these mutated alleles, we developed co-dominant DNA markers. In this study, EMS induced transition mutations, as previously reported. In contrast, DEB specifically induced transversion mutations rather than small-scale deletions contrary to our initial expectations. These results demonstrate that DEB has a novel point of action for mutation and is useful for expanding genetic resources for crops.

Because of the elastic deformation of rolling mills in rolling, the edge drop in thickness of rolled ultra-high strength steel sheet was remarkable, thus the thickness distribution was not uniform. The distribution of angle before and after unloading in V-bending of the ultra-high strength steel sheets having such a thickness distribution was measured. The bend angle was nonuniformly distributed by the insufficient bend angle at the bottom dead centre and springback during unloading. The effects of the bent angle and thickness distribution on the springback in thin and thick edges were discussed. The distribution of bend angle was reduced by bottoming with a three-piece die using a rubber pad. It was found that bottoming with a divided die using a rubber pad in bending is effective in improving the dimensional accuracy of ultra-high strength steel sheets having a thickness distribution by finite element simulation and experiment.

Enhancer activation is essential for cell-type specific gene expression during cellular differentiation, however, how enhancers transition from a hypoacetylated “primed” state to a hyperacetylated-active state is incompletely understood. Here, we show SET domain-containing 5 (SETD5) forms a complex with NCoR-HDAC3 co-repressor that prevents histone acetylation of enhancers for two master adipogenic regulatory genes Cebpa and Pparg early during adipogenesis. The loss of SETD5 from the complex is followed by enhancer hyperacetylation. SETD5 protein levels were transiently increased and rapidly degraded prior to enhancer activation providing a mechanism for the loss of SETD5 during the transition. We show that induction of the CDC20 co-activator of the ubiquitin ligase leads to APC/C mediated degradation of SETD5 during the transition and this operates as a molecular switch that facilitates adipogenesis., How enhancers transition from a hypoacetylated primed state to a hyperacetylated-active state in response to differentiation stimuli is incompletely understood. Here the authors show that SETD5 forms a complex with NCoR-HDAC3 co-repressor to prevent histone acetylation of master adipogenic gene enhancers, while SETD5 degradation triggers enhancer hyperacetylation and transition to active state.

The applicability of plastic tools additively manufactured by fused deposition modelling for sheet metal forming processes was evaluated. Aluminium and steel sheets were V-bent and deeply drawn with the plastic tools. The dimensional accuracy of bent sheets with the plastic tools was lower than that with steel tools due to low stiffness, and deteriorated with increasing flow stress of a sheet. The stiffness was increased by reinforcing the plastic tools with steel bars, and thus, the dimensional accuracy of the bent sheets was improved. Not only springback of the sheet but also elastic deformation of the plastic tools was successfully corrected by modifying the shapes of the tools. In addition, the deep drawability of a cylindrical cup with a plastic die was examined.

To improve the formability in stamping, a blank was locally work-hardened by indentation with a punch. Local strength expressed as a product of flow stress and thickness is increased up to a certain punch stroke by indentation, because the influence on the local strength contributed by the flow stress increase is larger than that by the thickness reduction. The effects of the indentation ratio, the number of punches and blank materials on the deformation behaviour in stamping were evaluated. The formability was increased by indenting thinning portions of the blank. The approach is effective for a sheet metal having a high work-hardening exponent such as stainless steel.

Two large clinical studies showed that fenofibrate, a commonly used peroxisome proliferator-activated receptor α (PPARα) agonist, has protective effects against diabetic retinopathy. However, the underlying mechanism has not been clarified. We performed genome-wide analyses of gene expression and PPARα binding sites in vascular endothelial cells treated with the selective PPARα modulator pemafibrate and identified 221 target genes of PPARα including THBD, which encodes thrombomodulin (TM). ChIP-qPCR and luciferase reporter analyses showed that PPARα directly regulated THBD expression via binding to the promoter. In the rat diabetic retina, treatment with pemafibrate inhibited the expression of inflammatory molecules such as VCAM-1 and MCP1, and these effects were attenuated by intravitreal injection of small interfering RNA targeted to THBD. Furthermore, pemafibrate treatment inhibited diabetes-induced vascular leukostasis and leakage through the upregulation of THBD. Our results indicate that PPARα activation inhibits inflammatory and vasopermeable responses in the diabetic retina through the upregulation of TM.

The hybrid method using a discrete element method (DEM) and an incompressible smoothed particle hydrodynamics (ISPH) method was developed to clarify the slag formation process during submerged arc welding. As a result, the weld pool formation and the slag formation processes were simulated simultaneously using the hybrid method. Moreover, the edge of the slag obtained by the simulation was thinner and the center of it was thicker, which were same tendency of actual slag. The maximum thickness of the slag near the weld line was equivalent to about 2.5 mm. Although the slag thickness obtained from the computation was a little thinner than the experiment, it supported the validity of this hybrid model. Thereafter, the ensemble average processing was carried out to discuss about the velocity field of a weld pool. The averaged result showed that velocity field of a weld pool was synchronized periodically with the transportation of a molten metal droplet.

Good boundary lubrication is necessary during cold stamping of high-strength steel sheets to prevent die wear and seizure of the parts owing to the high contact pressure. This study is aimed to improve the seizure resistance in a 1-step combined process of deep drawing and ironing of ultra-high-strength steel cylindrical cups using a commercial lubricant containing SiO2 nanoparticles with an uncoated die. In this study, the extreme pressure performance of the lubricant containing 0.0, 0.5, 1.0, 1.5, 2.0 and 2.5 wt% of SiO2 was first evaluated using a deep drawing process under increased blank holding forces. The optimum concentration of SiO2 was determined, i.e. 2 wt%, based on successful drawing of cups having smooth surfaces under the highest holding force. Then, the ironing limits of the cups for the lubricants containing 0 and 2 wt% of SiO2 respectively were investigated with the 1-step combined process under increased ironing ratios. The experimental results showed that seizure was observed for the lubricant containing no nanoparticles at an ironing ratio of −16.7 %. However, no seizures were observed for ironing ratios up to 4.2 % using the lubricant containing 2 wt% of SiO2. The resistance to seizure of the cup was significantly increased, leading to the formation of cylindrical cups having smooth surfaces and uniform side wall thickness.

SETD5, a gene linked to intellectual disability (ID) and autism spectrum disorder (ASD), is a member of the SET-domain family and encodes a putative histone methyltransferase (HMT). To date, the mechanism by which SETD5 haploinsufficiency causes ASD/ID remains an unanswered question. Setd5 is the highly conserved mouse homolog, and although the Setd5 null mouse is embryonic lethal, the heterozygote is viable. Morphological tracing and multielectrode array was used on cultured cortical neurons. MRI was conducted of adult mouse brains and immunohistochemistry of juvenile mouse brains. RNA-Seq was used to investigate gene expression in the developing cortex. Behavioral assays were conducted on adult mice. Setd5+/− cortical neurons displayed significantly reduced synaptic density and neuritic outgrowth in vitro, with corresponding decreases in network activity and synchrony by electrophysiology. A specific subpopulation of fetal Setd5+/− cortical neurons showed altered gene expression of neurodevelopment-related genes. Setd5+/− animals manifested several autism-like behaviors, including hyperactivity, cognitive deficit, and altered social interactions. Anatomical differences were observed in Setd5+/− adult brains, accompanied by a deficit of deep-layer cortical neurons in the developing brain. Our data converge on a picture of abnormal neurodevelopment driven by Setd5 haploinsufficiency, consistent with a highly penetrant risk factor.

The joinability of hot-dip coated steel sheets using a mechanical clinching was investigated by an experiment. The distributions of the layer thickness of Zn alloy coating of the joined sheets were examined. Although the sheets were joined, the layer of coating on the side wall of the punch was scratched and the layer thickness on the bottom of the die was reduced. In order to increase the layer thickness of coating of the joined sheets, shapes of the punch and die were optimised by controlling of the deforming behaviours of the sheets using means of the finite element simulation. The layer thickness of coating of the joined sheets was improved by the modification of the punch and die shapes.

The joinability of the self-pierce riveting process of three high strength steel and aluminium alloy sheets was investigated. The effects of the sheet strength and sheet combination on the deforming behaviour were examined under the fixture of the lower aluminium alloy sheet. Although the joining of three aluminium alloy and mild steel sheets is comparatively easy due to small difference of strength, the joining becomes difficult with the increase in strength of the high strength steel sheet. To improve the joinability with the high strength steel sheets, a shape of the die was optimised by controlling the deforming behaviours of the sheets and rivet by means of the finite element simulation. The joining range of three high strength steel and aluminium alloy sheets was extended by means of the optimised die.