An Accurate Separation of Floating-Body and Self-Heating Effects for High-Frequency Characterization of SOI MOSFET's

Abstract -In this paper, we present an accurate highfrequency characterization of AC output conductance method to separate SOI specific floating-body effects (FBE) and self-heating effects (SHE) from DC I-V data. In DC measurement, the transistor TEG pattern dependence is essential in view of the SOI body potential, which is confirmed by 3-dimensional device simulation. In AC measurement, the power of smallsignal is the most critical issue for removing the FBE and SHE components

Bifidobacteria upregulate expression of toll-like receptor negative regulators counteracting enterotoxigenic Escherichia coli mediated inflammation in bovine intestinal epitheliocytes

We previously established a bovine intestinal epithelial cell line (BIE cells) and showed that BIE cells are useful in vitro model system for the study of interactions between pathogenic and beneficial microorganisms and bovine intestinal epithelial cells (IECs). In the present study we aimed to select potential immunomodulatory bifidobacteria that may be used to beneficially modulate the inflammatory response in bovine IECs. We also aimed to gain insight in the molecular mechanisms involved in the anti-inflammatory effect of bifidobacteria by evaluating the role of Toll-like receptor (TLR)-2 and TLR negative regulators in the regulation of proinflamatory cytokines production and MAPK, NF-κB and PI3K pathways activation in BIE cells. Five bifidobacteria strains were evaluated in this study and according to their capacity to modulate inflammatory response of BIE cells. Despite the unique effect of each strain, four common points were found when comparing the effect of the high and moderate anti-inflammatory strains: 1) Upregulation of TLR negative regulators and the intensity of that upregulation was related to the different immunomodulatory capacity of each bifidobacteria strain. 2) The balance between MAPK activation and MKP-1 upregulation affected the an- ti-inflammatory effect of bifidobacteria in BIE cells. 3) The inhibition of PI3K pathway was related to the an- ti-inflammatory effect of bifidobacteria. 4) The immunoregulatory effect of bifidobacteria in BIE cells is partially de- pendent on TLR2. This study shows that BIE cells can be used for the selection of immunoregulatory bifidobacteria and for studying the mechanisms involved in the protective activity of immunobiotics against TLR4-induced inflammatory damage. In addition, we have demonstrated that the anti-inflammatory effect of bifidobacteria was achieved by a com- plex interaction of multiple TLRs negative regulators as well as the inhibition/activation of multiple signaling pathways.Fil: Murata, Kozue. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina; Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Tomosada, Yohsuke. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Risa, Hara. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Chiba, Eriko. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Shimazu, Tomoyuki. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Breeding and Genetics; Japón;Fil: Aso, Hisashi. Tohoku University. Graduate School of Agricultural Science. Cell Biology Laboratory; Japón;Fil: Suda, Yoshihito. Miyagi University. Department of Food, Agriculture and Environmental Science; Japón;Fil: Iwabuchi, Noriyuki. Morinaga Milk Industry Co. Ltd. Food Science and Technology Institute; Japón;Fil: Xiao, Jin-zhong. Morinaga Milk Industry Co. Ltd. Food Science and Technology Institute; Japón;Fil: Saito, Tadao. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Kitazawa, Haruki. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón

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ABSTRACT. Objective. Recent advances in the management of patients with rheumatoid arthritis (RA) increased the rates of disease remission and patient life expectancy, while malignancy has become a more common cause of death. Here, we report the incidence of malignancy in a nationwide survey of Japanese patients with RA compared to the general population, focusing on the risk of lymphoma, which often arises in patients with RA. Methods. Data on the occurrence of malignancy were collected from patients registered in a nationwide Japanese cohort database, the National Database of Rheumatic Diseases by iR-net in Japan, from 2003 to 2012. To adjust for different population composition and to compare the incidence of malignancy with the general population, standardized incidence rates (SIR) were calculated. To identify risk factors for lymphoma, individual patient data were obtained for multivariate analysis for the year before lymphoma diagnosis. Results. In 10 years, the cohort composed of 66,953 patient-years yielded 559 malignancies, most frequently lung cancer, followed by gastric cancer, breast cancer, and lymphoma. The overall incidence of malignancies in patients with RA was slightly lower than in the general population (SIR 0.89, 95% CI 0.82-0.97). However, lymphoma risk was significantly higher (SIR 3.43, 95% CI 2.59-4.28), whereas risk of colon, rectal, or liver cancer was lower. Significant risk factors for lymphoma were the use of methotrexate or tacrolimus, and higher age. Conclusion. Patients with RA had no higher overall incidence of malignancies, but lymphoma was significantly more frequent than in the general population

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

JASMINE: Near-infrared astrometry and time-series photometry science

The Japan Astrometry Satellite Mission for INfrared Exploration (JASMINE) is a planned M-class science space mission by the Institute of Space and Astronautical Science, the Japan Aerospace Exploration Agency. JASMINE has two main science goals. One is Galactic archaeology with a Galactic Center survey, which aims to reveal the Milky Way’s central core structure and formation history from Gaia-level (∼25 ${\mu}$as) astrometry in the near-infrared (NIR) Hw band (1.0–1.6 ${\mu}$m). The other is an exoplanet survey, which aims to discover transiting Earth-like exoplanets in the habitable zone from NIR time-series photometry of M dwarfs when the Galactic Center is not accessible. We introduce the mission, review many science objectives, and present the instrument concept. JASMINE will be the first dedicated NIR astrometry space mission and provide precise astrometric information on the stars in the Galactic Center, taking advantage of the significantly lower extinction in the NIR. The precise astrometry is obtained by taking many short-exposure images. Hence, the JASMINE Galactic Center survey data will be valuable for studies of exoplanet transits, asteroseismology, variable stars, and microlensing studies, including discovery of (intermediate-mass) black holes. We highlight a swath of such potential science, and also describe synergies with other missions

Isolation and characterization of cDNA clones for epidermis-specific and muscle-specific genes in Ciona savignyi embryos

Ascidian eggs and embryos have provided an appropriate experimental system to explore the cellular and molecular mechanisms involved in the embryonic cell specification and pattern formation of the embryo. In Japan, most of the studies of ascidian embryology have been carried out with the large eggs of Halocynthia roretzi. However, for future studies, Ciona species may provide a better experimental system, in particular with respect to the incorporation of genetic approaches. In order to establish Ciona as an experimental system, molecular markers with which to examine cellular differentiation are required. In the present study, we isolated and characterized cDNA clones for two epidermis-specific genes (CsEpi-1 and CsEpi-2) and for two muscle-specific genes (CsMA-1 and CsMu-1). CsEpi-1 encodes a polypeptide with three trefoil domains, while CsMA-1 encodes a muscle-type actin from C. savignyi Although CsEpi-2 and CsMu-1 transcripts seem to have a poly(A) tail at the 3' end, we could not find a distinct open reading frame in the sequences. Probes for CsEpi-1, CsMA-1 and CsMu-1 cross-reacted with C. intestinalis embryos. These cDNAs are useful as molecular markers for the specification of epidermis and muscle of Ciona embryos

Ten-year trends in the treatment and intervention timing for patients with metastatic spinal tumors: a retrospective observational study

Abstract Background Cancer treatment has recently evolved due to the advances in comprehensive therapies, including chemotherapy and radiotherapy. The aspect of cancer-related bone metastasis has undergone a paradigm shift with the transformation of orthopedic interventions for spinal metastasis. We performed this retrospective observational study to investigate the changes in patient status and metastatic spine-tumor treatment over the past decade. Methods We included 186 patients (122 men and 64 women; mean age: 67.6 years) who were referred to our hospital between 2009 and 2018 and were diagnosed and treated for metastatic spinal tumors. We classified the patients into early (81 patients from 2009 to 2013) and late (105 patients from 2014 to 2018) groups. The following components were investigated and compared between the groups: primary tumor, time taken from subjective-symptom onset to hospital visit, primary tumor evaluation during the visit, walking capacity due to lower paralysis during the visit, local treatment details, and post-treatment functional prognosis. Results Predominant primary tumors with similar trends in both groups included lung cancer, multiple myeloma, and prostate cancer. The percentage of non-ambulatory patients during the consultation was significantly lower in the late group (28% vs. 16%, P = 0.04). Among non-ambulatory patients at the time of hospital visit, the mean time from the primary doctor consultation to our hospital visit was 2.8 and 2.1 days in the early and late groups, respectively. In both groups, surgical procedures were performed promptly on the non-ambulatory patients; however, postoperative lower function did not improve in approximately half of the patients. Conclusions Our findings demonstrated that in recent years, patients tended to be referred promptly from their previous doctors under a favorable collaboration system. However, the effectiveness of lower paralysis treatment remains limited, and it is important to raise awareness regarding the importance of early consultation among the general public for earlier detection

brachyury null mutant-induced defects in juvenile ascidian endodermal organs

We report the isolation of a recessive ENU-induced short-tailed mutant in the ascidian Ciona intestinalis that is the product of a premature stop in the brachyury gene. Notochord differentiation and morphogenesis are severely disrupted in the mutant line. At the larval stage, variable degrees of ectopic endoderm staining were observed in the homozygous mutants, indicating that loss of brachyury results in stochastic fate transformation. In post-metamorphosis mutants, a uniform defect in tail resorption was observed, together with variable defects in digestive tract development. Some cells misdirected from the notochord lineage were found to be incorporated into definitive endodermal structures, such as stomach and intestine