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Pituitary gigantism is a rare endocrinopathy characterized by tall stature due to growth hormone (GH) hypersecretion. This condition is generally linked to a genetic predisposition to tumors that produce GH or GH-releasing hormone (GHRH). Here, we report a Japanese woman who exhibited prominent body growth from infancy to reach an adult height of 197.4 cm (+7.4 standard deviation). Her blood GH levels were markedly elevated. She carried no pathogenic variants in known growth-controlling genes but had a hitherto unreported 752 kb heterozygous deletion at 20q11.23. The microdeletion was located 8.9 kb upstream of GHRH and encompassed exons 2–9 of a ubiquitously expressed gene TTI1 together with 12 other genes, pseudogenes and non-coding RNAs. Transcript analyses of the patient’s leukocytes showed that the microdeletion produced chimeric mRNAs consisting of exon 1 of TTI1 and all coding exons of GHRH. In silico analysis detected promoter-associated genomic features around TTI1 exon 1. Genome-edited mice carrying the same microdeletion recapitulated accelerated body growth from a few weeks after birth. The mutant mice developed pituitary hyperplasia and exhibited ectopic Ghrh expression in all tissues examined. Thus, the extreme phenotype of pituitary gigantism in the patient likely reflects GHRH overexpression driven by an acquired promoter. The results of this study indicate that germline submicroscopic deletions have the potential to cause conspicuous developmental abnormalities due to gene overexpression. Furthermore, this study provides evidence that constitutive expression of a hormone-encoding gene can result in congenital disease.

Biliary atresia (BA) is a rare disorder of unknown etiology. There is a debate as to whether maternal microchimerism plays a significant role in the development of BA or in graft tolerance after liver transplantation. Here, we performed quantitative-PCR-based assays for liver tissues of children with BA and other diseases. Maternal cells were detected in 4/13 and 1/3 of the BA and control groups, respectively. The estimated number of maternal cells ranged between 0 and 34.7 per 106 total cells. The frequency and severity of maternal microchimerism were similar between the BA and control groups, and between patients with and without acute rejection of maternal grafts. These results highlight the high frequency of maternal microchimerism in the liver. This study provides no evidence for roles of microchimerism in the etiology of BA or in graft tolerance. Thus, the biological consequences of maternal microchimerism need to be clarified in future studies.

—Corrosion attack in reinforced concrete and thus contribute to degradation of concrete influenced by aggressive environment, represent a great concern in relation to the durability of reinforced concrete structures. In this respect, an interesting need is required that is patch repair with additional protection known as ICCP method to prolong the serviceability of the concrete structures. However, details inspection is crucial to understand the effect of different repairing materials and chloride content towards application of ICCP. To clarify this issue, non-protected and protected test specimens were prepared, and analyzed up to 175 days of protection. The result reveals that, reference specimen was found as most corroded specimen unable to obtain 100 mV depolarization at 56 days installation compared to repaired ones. However, all specimens show only greater depolarization values beyond 129 days of installation. To clarity further effectiveness of ICCP system to the studied specimens, time-dependence within 24 hours disconnecting CP current has been carried out and depolarization values was recorded every 4 hours interval. In the final analysis, all specimens are satisfying the CP criteria by obtaining depolarization potential ranging 100 to 250 mV at 4 and 24 hours monitoring period. Index Terms— corrosion attacks, reinforced concrete, repaired concrete, repairing materials, impressed current

Isolated hypogonadotropic hypogonadism (IHH), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) constitute a disease spectrum whose etiology remains largely unknown. This study aimed to clarify whether mutations in SMCHD1, an epigenetic regulator gene, might underlie this disease spectrum. SMCHD1 is a causative gene for Bosma arhinia microphthalmia syndrome characterized by arhinia, microphthalmia and IHH. We performed mutation screening of SMCHD1 in patients with etiology-unknown IHH (n = 31) or CPHD (n = 43, 19 of whom also satisfied the SOD diagnostic criteria). Rare variants were subjected to in silico analyses and classified according to the American College of Medical Genetics and Genomics guidelines. Consequently, a rare likely pathogenic variant, p.Asp398Asn, was identified in one patient. The patient with p.Asp398Asn exhibited CPHD, optic nerve hypoplasia, and a thin retinal nerve fiber layer, and therefore satisfied the criteria of SOD. This patient showed a relatively low DNA methylation level of the 52 SMCHD1-target CpG sites at the D4Z4 locus. Exome sequencing for the patient excluded additional variants in other IHH/CPHD-causative genes. In vitro assays suggested functional impairment of the p.Asp398Asn variant. These results provide the first indication that SMCHD1 mutations represent a rare genetic cause of the HH-related disease spectrum.

We report a case of 15-yr-old phenotypically normal male with short stature associated with the chromosomal abnormalities of 46,X,psu idic(Y)(q11.2)/45,X. At 3 yr of age, he underwent urethroplasty for scrotal hypospadias. At 15 yr of age, he was referred to our hospital due to short stature (–3.71 SD). The results of blood examination were mostly normal. A radiological examination revealed his bone age was 15.7 yr (based on the TW2-RUS method). Chromosome analysis of peripheral lymphocytes revealed 46,X,psu idic(Y)(q11.2)[16]/45,X[14], and array comparative genomic hybridization (aCGH) showed a large deletion of Yq which was located distal to the Y chromosome growth-control gene (GCY) region. It is likely that these structural abnormalities in the Y chromosome were responsible for the short stature. This case might provide new insights regarding GCY and emphasizes the importance of chromosome analysis in not only females but also males with short stature, especially when associated with genital anomalies.

During gametogenesis, the human genome can acquire various de novo rearrangements. Most constitutional genomic rearrangements are created through 1 of the 4 well-known mechanisms, i.e., nonallelic homologous recombination, erroneous repair after double-strand DNA breaks, replication errors, and retrotransposition. However, recent studies have identified 2 types of extremely complex rearrangements that cannot be simply explained by these mechanisms. The first type consists of chaotic structural changes in 1 or a few chromosomes that result from “chromoanagenesis (an umbrella term that covers chromothripsis, chromoanasynthesis, and chromoplexy).” The other type is large independent rearrangements in multiple chromosomes indicative of “transient multifocal genomic crisis.” Germline chromoanagenesis (chromothripsis) likely occurs predominantly during spermatogenesis or postzygotic embryogenesis, while multifocal genomic crisis appears to be limited to a specific time window during oogenesis and early embryogenesis or during spermatogenesis. This review article introduces the current understanding of the molecular basis of de novo rearrangements in the germline.

Adult men are, on average, ∼13 cm taller than adult women. Although previous studies have suggested a significant contribution of sex chromosomal genes to sexual dimorphism in height, all attempts to identify a male-specific growth gene have failed. In the present study, we analyzed transcripts from cartilage tissues, and found that the expression of SHOX, a growth-promoting gene in the pseudoautosomal region on the X and Y chromosomes, was lower in females than in males. DNA methylation analyses showed that SHOX has some characteristics of genes subjected to X chromosome inactivation (XCI). These findings indicate that sex difference in human height is mainly ascribed to incomplete spreading of XCI on a pseudoautosomal gene. More importantly, RT-PCR of fibroblast clones revealed XCI-independent random clonal monoallelic expression of SHOX. We presume that during eutherian evolution, SHOX translocated from an autosome to the proto-sex chromosome without losing the epigenetic memory of random clonal monoallelic expression and subsequently underwent partial XCI. This study provides a novel model of epigenetic gene regulation leading to phenotypic diversity in humans.

Background The co-occurrence of multiple de novo copy number variations (CNVs) is a rare phenomenon in the human genome. Recently, an “organismal CNV mutator phenotype” has been reported to result in transient genomic instability introducing multiple de novo CNVs in primary oocytes and early-stage zygotes. These findings opened a new area of human genome research. Methods We performed genome-wide copy number analysis for ~ 2100 individuals with various congenital defects. Furthermore, extensive molecular analyses, including synthetic long-read whole-genome sequencing and haplotype-phasing, were carried out for an individual with multiple de novo CNVs. Results A boy was found to have de novo rearrangements on five chromosomes. The rearrangements comprised simple duplication and inversion as well as chaotic changes, all of which affected paternally derived chromosomes. Postzygotic genomic instability was ruled out. The duplicated regions on 6q and 13q contained both diallelic and triallelic loci, indicating that the genomic rearrangements were initially created during premeiotic mitosis and subsequently modified by physiological cross-over during meiosis I. Breakpoints of the rearrangements were indicative of non-homologous end joining, replication-based errors, and/or chromothripsis. The mutagenic event was independent of specific local DNA motifs or de novo point mutations, but may be driven by spermatogenesis-specific factors. Conclusions These results indicate that during spermatogenesis, a transient multifocal genomic crisis can introduce several chromothriptic and non-chromothriptic changes into the genome. These findings broaden the concept of the “organismal CNV mutator phenotype”. This study provides insights into mechanisms for altering the global chromosomal architecture of human embryos. Electronic supplementary material The online version of this article (10.1186/s12920-019-0526-3) contains supplementary material, which is available to authorized users.

SHOX resides in the short arm pseudoautosomal region (PAR1) of the sex chromosomes and escapes X inactivation. SHOX haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). A substantial percentage of cases with SHOX haploinsufficiency arise from pseudoautosomal copy number variations (CNVs) involving putative enhancer regions of SHOX. Our previous study using peripheral blood samples showed that some CpG dinucleotides adjacent to SHOX exon 1 were hypomethylated in a healthy woman and methylated in a woman with gross X chromosomal rearrangements. However, it remains unknown whether submicroscopic pseudoautosomal CNVs cause aberrant DNA methylation of SHOX-flanking CpG islands. In this study, we examined the DNA methylation status of SHOX-flanking CpG islands in 50 healthy individuals and 10 ISS/LWD patients with pseudoautosomal CNVs. In silico analysis detected 3 CpG islands within the 20-kb region from the translation start site of SHOX. Pyrosequencing and bisulfite sequencing of genomic DNA samples revealed that these CpG islands were barely methylated in peripheral blood cells and cultured chondrocytes of healthy individuals, as well as in peripheral blood cells of ISS/LWD patients with pseudoautosomal CNVs. These results, in conjunction with our previous findings, indicate that the DNA methylation status of SHOX-flanking CpG islands can be affected by gross X-chromosomal abnormalities, but not by submicroscopic CNVs in PAR1. Such CNVs likely disturb SHOX expression through DNA methylation-independent mechanisms, which need to be determined in future studies.

To comply with defect specification, Extreme Ultra-Violet (EUV) lithography necessitates performance improvement for both bulk and point-of-use (POU) filters. In this study, the data represent novel polyethylene and nylon filters for a variety of bulk and POU applications, specifically designed to: i) dramatically reduce differential pressure while achieving excellent retention, and ii) provide outstanding cleanliness for EUV grade application. Each filter was assessed by differential pressure (dP), liquid particle counter (LPC), GC-MS, and ICP-MS measurements. Finally, defect data were obtained from blanket and pattern wafers, prepared at the imec EUV cluster comprised of TEL Cleantrack LITHIUS Pro-Z and ASML NXE:3400B with a 16nm L/S test vehicle and characterized by a KLA-2935 and an eDR-7380 tools.

Background X-chromosome inactivation (XCI) is a mechanism in which one of two X chromosomes in females is randomly inactivated in order to compensate for imbalance of gene dosage between sexes. However, about 15% of genes on the inactivated X chromosome (Xi) escape from XCI. The methylation level of the promoter region of the escape gene is lower than that of the inactivated genes. Dxz4 and/or Firre have critical roles for forming the three-dimensional (3D) structure of Xi. In mice, disrupting the 3D structure of Xi by deleting both Dxz4 and Firre genes led to changing of the escape genes list. To estimate the impact for escape genes by X-chromosome rearrangements, including DXZ4 and FIRRE, we examined the methylation status of escape gene promoters in patients with various X-chromosome rearrangements. Results To detect the breakpoints, we first performed array-based comparative genomic hybridization and whole-genome sequencing in four patients with X-chromosome rearrangements. Subsequently, we conducted array-based methylation analysis and reduced representation bisulfite sequencing in the four patients with X-chromosome rearrangements and controls. Of genes reported as escape genes by gene expression analysis using human hybrid cells in a previous study, 32 genes showed hypomethylation of the promoter region in both male controls and female controls. Three patients with X-chromosome rearrangements had no escape genes with abnormal methylation of the promoter region. One of four patients with the most complicated rearrangements exhibited abnormal methylation in three escape genes. Furthermore, in the patient with the deletion of the FIRRE gene and the duplication of DXZ4, most escape genes remained hypomethylated. Conclusion X-chromosome rearrangements are unlikely to affect the methylation status of the promoter regions of escape genes, except for a specific case with highly complex rearrangements, including the deletion of the FIRRE gene and the duplication of DXZ4.

The current therapeutic approach for Parkinson's disease (PD) is mainly dopamine replacement with levodopa and other anti-parkinsonian drugs. As PD progresses, the number of these drugs used steadily increases. Using prescription-based database for 10 or more years up to October 2019, we investigated actual prescribing patterns for anti-parkinsonian drugs in Japan. The main analyses included data from patients continuously prescribed levodopa for 1 or more years (n=16,270), and of these, those continuously prescribed adjuvants to levodopa for 1 or more years (n=3,675). The results showed that the number of anti-parkinsonian drugs, their daily dose frequencies, and the number of tablets increased over time. These trends were observed not only for levodopa but also for adjuvants to levodopa; the number of adjuvants, their daily dose frequencies and number of tablets also increased. As the daily number of tablets increased, the proportion of dopamine agonists increased. Moreover, as the daily dosage of levodopa increased, the daily number of tablets increased for both overall anti-parkinsonian drugs and adjuvants to levodopa. This study revealed the process of polypharmacy in PD treatment objectively. Our results are valuable for maintaining and improving therapeutic adherence in PD. (Received 25 August, 2020; Accepted 23 October, 2020; Published 1 March, 2021).

As the semiconductor industry continues to advance and on-wafer defect reduction by liquid filtration has become “universal” as a process enabler for advanced technology nodes, the need for innovative filtration solutions that reduces target contaminants has become critical. Filtration technologies for metal cleanliness in photochemicals, including lithography materials and solvents, continue to grow and contribute to die yield improvement at wafer level. Both point-of-use (POU) and bulk filtration play important roles in achieving high-purity chemicals and processes by eliminating metal contaminants in critical fluids. However, the increasing complexity of photochemicals, such as multicomponent resist formulations (organic or inorganic), necessitates advanced filtration membrane technology that is compatible with their various components, including the metal oxide nanoparticles. In this regard, the ideal filtration technology should rely on functionalization with tailored chemistries to selectively remove target metals, without interactions with the key components in photoresist formulations. Also, due to the variation in forms and species of metals in different fluids, the next generation filtration technology should be able to act as a versatile platform with customization capability to optimize removal efficiency in each fluid. The objective of this study is to demonstrate the metal removal performance of different functionalization chemistries on PTFE and HDPE membrane and investigate the impact of various surface modification designs on removal selectivity and efficiency.

Extreme Ultra-Violet (EUV) lithography is pushing material suppliers to provide the cleanest possible products for tight quality standards. The emphasis on minimizing residual particles, metals, and organics coming from materials and equipment continues to increase. Filter design and its key sub-components such as membrane continue to play a significant role to enhance performance in EUV lithography by reducing defectivity. This necessitates an improvement in retention and cleanliness for both bulk and point-of-use (POU) filters. While POU filtration targets high retention, typically achieved by membrane’s reduced pore size, the main requirement of bulk filtration is maximizing the amount of material recirculated through the filter per unit of time and is achieved with improved tortuosity and well-defined pore structure. In this study, we present a novel HDPE filter specifically designed to provide a high flow (lower differential pressure) without sacrificing retention characteristics. The new membrane was assembled in a POU filter format and compared head-to-head with a state-of-the-art HDPE membrane filter for POU application. The flow performance was assessed by differential pressure (dP) measurement, which showed an enhanced performance benefit of dP reduction by 50% compared to the reference filter, while all other test parameters are improved or at least comparable. The filter cleanliness was quantified by liquid particle counter (LPC), GC-MS, and ICP/MS measurements. Finally, comparative defect data was obtained from the blanket and pattern wafers, prepared on imec EUV cluster comprised of TEL Clean Track LITHIUS Pro-Z and ASML NXE:3400B with a 16nm L/S test vehicle.

Although NDNF was recently reported as a novel causative gene for congenital hypogonadotropic hypogonadism (CHH), this conclusion has yet to be validated. In this study, we sequenced NDNF in 61 Japanese CHH patients. No variants, except for nine synonymous substitutions that appear to have no effect on splice-site recognition, were identified in NDNF coding exons or flanking intronic sequences. These results indicate the rarity of NDNF variants in CHH patients and highlight the genetic heterogeneity of CHH.

The acquisition of medical images from multiple medial institutions has become important for high-quality clinical studies. In recent years, electronic data submission has enabled the transmission of image data to independent institutions more quickly and easily than before. However, the selection, anonymization, and transmission of medical images still require human resources in the form of clinical research collaborators. In this study, we developed an image collection system that works with the electronic data capture (EDC) system. In this image collection system, medical images are selected based on EDC input information, patient ID is anonymized to a subject ID issued by the EDC, and the selected anonymized images are transferred to the research institute without human intervention. In the research institute, clinical information registered by the EDC and clinical images collected by the image collection system are managed by the same subject ID and can be used for clinical studies. In October 2019, our image collection system was introduced to 13 medical institutions and has now begun collecting medical images from the in-hospital picture archiving and communication system (PACS) of those institutions.

The availability of EUV lithography is the mainstream for resolving critical dimension of the advanced technology nodes, currently in the range of 18nm and below [1]. The first insertion of EUVL into manufacturing utilizes chemically amplified resist (CAR) [2]. The filtration of CAR, both at bulk and point-of-use (POU), has already demonstrated in ArF and ArF immersion lithography to play a significant role for microbridges reduction essentially by removing hard particle and gels [3-6]. With respect to ArFi, EUV is bringing new challenges not only for the achievement of the required line roughness, sensitivity and resolution, but also for the need of a substantial reduction of defects such as line collapse, microbridges and broken lines. In this study, it demonstrated the ability of utilizing novel POU filtration to modulate microbridges and achieving superior start-up behavior, both crucial for enabling EUVL at high volume manufacturing. Different POU filters were tested at the imec EUV cluster comprised of TEL CleanTrack LITHIUS Pro-Z and ASML NXE:3400B. The start-up performance, assessed by measuring defects down to 19nm size as a function of the flushing solvent volume, has shown the fast achievement of attaining a stable baseline. Lithography experiments targeting reduction of on-wafer defectivity, carried out with commercially available photoresists, have consistently shown a substantial reduction of after resist development (ADI) and after resist etch (AEI) microbridges on a 16nm L/S test vehicles. The effect of membrane physical intrinsic designs and novel cleaning of POU devices are discussed.

Carbon fiber reinforced polymer (CFRP), plates bonding repair method is one of the simple repair methods for cracked steel structures. In this study, the influence of width of CFRP plates on bending fatigue life of out-of-plane gusset joint strengthened with CFRP plates was investigated from the experimental and numerical point of view. In the bending fatigue test of cracked out-of-plane gusset joint strengthened with CFRP plates, the effect of width of CFRP plates on crack growth life was clarified experimentally. Namely, it was revealed that the crack growth life becomes larger with increasing the width of CFRP plates. In the numerical approach, the stress intensity factor (SIF) at the surface point of a semi-elliptical surface crack was estimated based on the linear fracture mechanics. Furthermore, the extended fatigue life of cracked out-of-plane gusset joint strengthened with CFRP plates was evaluated by using the estimated SIF at the surface point and the empirical formula of the aspect ratio of semi-elliptical crack. As the results of numerical analysis, the estimated fatigue life of the specimen strengthened with CFRP plates showed the good agreement with the test results.

Background Electronic medical records (EMRs) are widely used, but in many cases, they are used within a network physically separated from the Internet. Multicenter clinical studies use Internet-connected electronic data capture (EDC) systems to collect data, where data entered into the EMR are manually transcribed into the EDC system. In addition, medical images for clinical research are also collected manually. Variations in EMRs and differing data structures among vendors hamper the use of data for clinical research. Methods We solved this problem by developing a network infrastructure for clinical research between Osaka University Hospital and affiliated hospitals in the Osaka area and introducing a clinical data collection system (CDCS). In each hospital's EMR network, we implemented a CRF reporter that accumulated data for clinical research using a template and then sent the data to a management server in the Osaka University Hospital Data Center. To organize the patient profile data and clinical laboratory data stored in each EMR for use in clinical research, the data are retrieved from the template by an interface module developed by each vendor, according to our common data output interface specification. The data entered into the CRF reporter template for clinical research are also recorded in the EMR progress notes and sent to the data management server. This network infrastructure can also be used as a medical image collection system that automatically collects images for research from PACS at each hospital. These systems are managed under common subject numbers issued by the CDCS. Results A network infrastructure was established among 19 hospitals, and a CRF reporter was incorporated into the EMR. A medical image transfer system was introduced in 13 hospitals. Since 2013, 28 clinical studies have been conducted using this system, and data for 9,987 cases have been collected as of December 31, 2020. Conclusion Incorporating a CRF reporter with medical image transfer system into the EMR has proven useful for collecting research data.

Although mutations in ACAN, FGFR3, NPR2, and SHOX typically lead to skeletal dysplasia, and mutations in GHRHR, GH1, GHR, STAT5B, IGF1, IGFALS, and IGF1R usually underlie hormonal defects of the growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis, such mutations have also been identified in patients with idiopathic short stature (ISS). Of these, SHOX abnormalities are known to account for a certain percentage of ISS cases, whereas the frequency of mutations in the other 10 genes in ISS cohorts remains unknown. Here, we performed next-generation sequencing-based mutation screening of the 10 genes in 86 unrelated Japanese ISS patients without SHOX abnormalities. We searched for rare protein-altering variants. The functional significance of the identified variants was assessed by in silico analyses. Consequently, we identified 18 heterozygous rare variants in 19 patients, including four probable damaging variants in ACAN, six pathogenicity-unknown variants in FGFR3, GHRHR, GHR, and IGFALS, and eight possible benign variants. Pathogenic variants in NPR2, GH1, and IGF1 were absent from our cohort. Unlike previously reported patients with ACAN mutations, our four patients with ACAN variants manifested non-specific short stature with age-appropriate or mildly delayed bone ages, and had parents of normal stature. These results indicate that ACAN mutations can underlie ISS without characteristic skeletal features, and that such mutations are possibly associated with de novo occurrence or low penetrance. In addition, our data imply that mutations in FGFR3, NPR2, and GH-IGF1 axis genes play only limited roles in the etiology of ISS.

SHOX resides in the short arm pseudoautosomal region (PAR1) of the sex chromosomes and escapes X inactivation. SHOX haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). A substantial percentage of cases with SHOX haploinsufficiency arise from pseudoautosomal copy number variations (CNVs) involving putative enhancer regions of SHOX. Our previous study using peripheral blood samples showed that some CpG dinucleotides adjacent to SHOX exon 1 were hypomethylated in a healthy woman and methylated in a woman with gross X chromosomal rearrangements. However, it remains unknown whether submicroscopic pseudoautosomal CNVs cause aberrant DNA methylation of SHOX-flanking CpG islands. In this study, we examined the DNA methylation status of SHOX-flanking CpG islands in 50 healthy individuals and 10 ISS/LWD patients with pseudoautosomal CNVs. In silico analysis detected 3 CpG islands within the 20-kb region from the translation start site of SHOX. Pyrosequencing and bisulfite sequencing of genomic DNA samples revealed that these CpG islands were barely methylated in peripheral blood cells and cultured chondrocytes of healthy individuals, as well as in peripheral blood cells of ISS/LWD patients with pseudoautosomal CNVs. These results, in conjunction with our previous findings, indicate that the DNA methylation status of SHOX-flanking CpG islands can be affected by gross X-chromosomal abnormalities, but not by submicroscopic CNVs in PAR1. Such CNVs likely disturb SHOX expression through DNA methylation-independent mechanisms, which need to be determined in future studies.

Microfluidic devices using droplets make it possible to perform high-throughput screening of single-cell samples through encapsulating cells into droplets. In conventional encapsulation methods, devices have T-junction and flow-focusing geometry for droplet generation. Using those techniques, it is difficult to achieve uniform distribution of cells, or to place single cells in droplets. Moreover, in screening samples, it is necessary to have a mechanism to hold the droplets at one place for a long time. However, it is somewhat difficult to add such a function to conventional devices. Thus, we propose a new single-cell encapsulation method using triangular microwells. In this approach, each single cell is isolated, encapsulated, and held in one place by triangular microwells. This approach has the benefit that the droplet size can be regulated by the size of the microwells. In addition, optimization of encapsulation is easier than in conventional methods because the flow rate of the oil phase does not affect the encapsulation.

To improve the efficiency of clinical research, we developed a system to integrate electronic medical records (EMRs) and the electronic data capture system (EDC). EDC is divided into case report form (CRF) reporter and CDMS with CRF receiver with data communication using the operational data model (ODM). The CRF reporter is incorporated into the EMR to share data witth the EMR. In the data transcription type, doctors enter data using a progress note template, which are transmitted to the reporter template. It then generates the ODM. In the direct record type, reporter templates open from the progress note and generate narrative text to make record in the progress note. The configuration files for a study are delivered from the contents server to minimize the setup. This system has been used for 15 clinical studies including 3 clinical trials. This system can save labor and financial costs in clinical research.

In steel members strengthened with carbon-fiber reinforced polymer (CFRP) plate, thermal stresses are introduced in the steel members, the CFRP plates and the adhesive layers when temperature changes because the linear thermal expansion coefficients of steel and CFRP are mismatched. Therefore, the thermal stress caused by temperature change has to be considered when designing the repair or strengthening of a steel member with CFRP plates. With this in mind, the authors proposed a technique to reduce thermal stress in steel members strengthened by CFRP plate on both side, which involves bonding aluminum alloy plates with CFRP plates. In this proposed method, the thermal stresses in steel member can be reduced so that there are negligible levels of stress when the cross sectional areas of CFRP and aluminum plates are designed to correspond the coefficient of thermal expansion of steel, even though the thermal stresses are introduced in the CFRP and aluminum plates. So far, a thermal bending moment was not considered in the proposed method, because the steel members strengthened by CFRP-aluminum laminated plate on top and bottom sides were assumed. However, if the proposed method is applied on one side of steel member, the thermal stress in the steel member might not be reduced completely by generated thermal bending moment. Therefore, to confirm the effectiveness of the proposed method for one-sided bonding, heat tests were conducted on a steel plate with a laminated plate bonded on one side. Additionally, to verify test results and calculate the shear and peel stresses in the adhesive layers, a numerical model that used Eigenvalue analysis was proposed and applied. The tests revealed that using the proposed method to create a two-layered laminated plate consisting of CFRP and aluminum plates could not reduce the thermal stress completely in a thin steel plate. However, it was found that the thermal stress in steel plate can be completely reduced, even in thin steel plate, when the proposed method is used to create a three-layered laminated plate consisting of one CFRP plate between two aluminum plates, which when composited has a thermal bending moment equal to zero.