Orientation Optimization Based on Topological Derivatives in Cooperation with Multi-Material Topology Optimization Based on Extended Level Set Method

This paper provides an orientation angle optimization method for the design of fiber-reinforced composite materials using topology optimization. The orientation angle optimization is based on a topological derivative, which measures the sensitivity of an objective function with respect to a topological change of anisotropic materials. The sensitivity is incorporated into a new gradient-based optimization algorithm. This method allows us to avoid local optima and seek a global optimal solution. We provide some numerical examples and verify the effectiveness of the proposed method.Comment: 24 pages, 16 figure

Wide-bandgap GaN-based watt-class photonic-crystal lasers

青色GaN系フォトニック結晶レーザーの高出力・高ビーム品質動作に成功 --次世代の高品位レーザー加工、高輝度照明、水中LiDAR等の実現に向けて--. 京都大学プレスリリース. 2022-11-04.Short-wavelength (blue-violet-to-green) lasers with high power and high beam quality are required for various applications including the machining of difficult-to-process materials and high-brightness illuminations and displays. Promising light sources for such applications are wide-bandgap GaN-based photonic-crystal surface-emitting lasers (PCSELs), which are based on two-dimensional resonance in the photonic crystal. Developments of these devices have lagged behind those of longer-wavelength GaAs-based PCSELs, because device designs for achieving robust two-dimensional resonance and a nanofabrication process that avoids introducing disorders have remained elusive for wide-bandgap GaN-based materials. Here, we address these issues and successfully realize GaN-based PCSELs with high, watt-class (>1 W) output power and a circular, single-lobed beam with a very narrow (~0.2°) divergence angle at blue wavelengths. In addition, we demonstrate continuous-wave operation with a high output power (~320 mW) and a high beam quality (M²~1). Our results will enable the use of GaN-based PCSELs in the above-mentioned applications

The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein–induced bone formation

Osteoporosis is a major health problem; however, the mechanisms regulating adult bone mass are poorly understood. Cas-interacting zinc finger protein (CIZ) is a nucleocytoplasmic shuttling protein that localizes at cell adhesion plaques that form where osteoblasts attach to substrate. To investigate the potential role of CIZ in regulating adult bone mass, we examined the bones in CIZ-deficient mice. Bone volume was increased and the rates of bone formation were increased in CIZ-deficient mice, whereas bone resorption was not altered. CIZ deficiency enhanced the levels of mRNA expression of genes encoding proteins related to osteoblastic phenotypes, such as alkaline phosphatase (ALP) as well as osterix mRNA expression in whole long bones. Bone marrow cells obtained from the femora of CIZ-deficient mice revealed higher ALP activity in culture and formed more mineralized nodules than wild-type cells. CIZ deficiency enhanced bone morphogenetic protein (BMP)–induced osteoblastic differentiation in bone marrow cells in cultures, indicating that BMP is the target of CIZ action. CIZ deficiency increased newly formed bone mass after femoral bone marrow ablation in vivo. Finally, BMP-2–induced bone formation on adult mouse calvariae in vivo was enhanced by CIZ deficiency. These results establish that CIZ suppresses the levels of adult bone mass through inhibition of BMP-induced activation of osteoblasts

Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips

新型コロナウイルス感染症（COVID-19）研究のための肝臓チップの開発 --肝障害の病態解明と治療薬の評価--. 京都大学プレスリリース. 2023-03-08.Using organ-on-a-chip technology to elucidate the liver pathophysiology of COVID-19 patients. 京都大学プレスリリース. 2023-03-08.SARS-CoV-2 induces severe organ damage not only in the lung but also in the liver, heart, kidney, and intestine. It is known that COVID-19 severity correlates with liver dysfunction, but few studies have investigated the liver pathophysiology in COVID-19 patients. Here, we elucidated liver pathophysiology in COVID-19 patients using organs-on-a-chip technology and clinical analyses. First, we developed liver-on-a-chip (LoC) which recapitulating hepatic functions around the intrahepatic bile duct and blood vessel. We found that hepatic dysfunctions, but not hepatobiliary diseases, were strongly induced by SARS-CoV-2 infection. Next, we evaluated the therapeutic effects of COVID-19 drugs to inhibit viral replication and recover hepatic dysfunctions, and found that the combination of anti-viral and immunosuppressive drugs (Remdesivir and Baricitinib) is effective to treat hepatic dysfunctions caused by SARS-CoV-2 infection. Finally, we analyzed the sera obtained from COVID-19 patients, and revealed that COVID-19 patients, who were positive for serum viral RNA, are likely to become severe and develop hepatic dysfunctions, as compared with COVID-19 patients who were negative for serum viral RNA. We succeeded in modeling the liver pathophysiology of COVID-19 patients using LoC technology and clinical samples

Risk factors for incisional hernia according to different wound sites after open hepatectomy using combinations of vertical and horizontal incisions: A multicenter cohort study.

Background:Although several risk factors for incisional hernia after hepatectomy have been reported, their relationship to different wound sites has not been investigated. Therefore, this study aimed to examine the risk factors for incisional hernia according to various wound sites after hepatectomy.Methods:Patients from the Osaka Liver Surgery Study Group who underwent open hepatectomy using combinations of vertical and horizontal incisions (J-shaped incision, reversed L-shaped incision, reversed T-shaped incision, Mercedes incision) between January 2012 and December 2015 were included. Incisional hernia was defined as a hernia occurring within 3 y after surgery. Abdominal incisional hernia was classified into midline incisional hernia and transverse incisional hernia. The risk factors for each posthepatectomy incisional hernia type were identified.Results:A total of 1057 patients met the inclusion criteria. The overall posthepatectomy incisional hernia incidence rate was 5.9% (62 patients). In the multivariate analysis, the presence of diabetes mellitus and albumin levels <3.5 g/dL were identified as independent risk factors. Moreover, incidence rates of midline and transverse incisional hernias were 2.4% (25 patients), and 2.3% (24 patients), respectively. In multivariate analysis, the independent risk factor for transverse incisional hernia was the occurrence of superficial or deep incisional surgical site infection, and interrupted suturing for midline incisional hernia.Conclusions:Risk factors for incisional hernia after hepatectomy depend on the wound site. To prevent incisional hernia, running suture use might be better for midline wound closure. The prevention of postoperative wound infection is important for transverse wounds, under the presumption of preoperative nutrition and normoglycemia

A series of ENU-induced single-base substitutions in a long-range cis-element altering Sonic hedgehog expression in the developing mouse limb bud

AbstractMammal–fish-conserved-sequence 1 (MFCS1) is a highly conserved sequence that acts as a limb-specific cis-acting regulator of Sonic hedgehog (Shh) expression, residing 1 Mb away from the Shh coding sequence in mouse. Using gene-driven screening of an ENU-mutagenized mouse archive, we obtained mice with three new point mutations in MFCS1: M101116, M101117, and M101192. Phenotype analysis revealed that M101116 mice exhibit preaxial polydactyly and ectopic Shh expression at the anterior margin of the limb buds like a previously identified mutant, M100081. In contrast, M101117 and M101192 show no marked abnormalities in limb morphology. Furthermore, transgenic analysis revealed that the M101116 and M100081 sequences drive ectopic reporter gene expression at the anterior margin of the limb bud, in addition to the normal posterior expression. Such ectopic expression was not observed in the embryos carrying a reporter transgene driven by M101117. These results suggest that M101116 and M100081 affect the negative regulatory activity of MFCS1, which suppresses anterior Shh expression in developing limb buds. Thus, this study shows that gene-driven screening for ENU-induced mutations is an effective approach for exploring the function of conserved, noncoding sequences and potential cis-regulatory elements