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In this paper, we discuss index theory for Toeplitz operators on a discrete quarter-plane of two-variable rational matrix function symbols. By using Gohberg–Kreĭn theory for matrix factorizations, we extend the symbols defined originally on a two-dimensional torus to some three-dimensional sphere and derive a formula to express their Fredholm indices through extended symbols. Variants for families of (self-adjoint) Fredholm quarter-plane Toeplitz operators and those preserving real structures are also included. For some bulk-edge gapped single-particle Hamiltonians of finite hopping range on a discrete lattice with a codimension-two right angle corner, topological invariants related to corner states are provided through extensions of bulk Hamiltonians.

The 2018 Hokkaido Eastern Iburi Earthquake struck the eastern Iburi region (epicenter: 42.691°N, 142.007°E, depth: 37.0 km) of Hokkaido, Japan, at 3:07.59 JST, September 6, 2018 (18:07.59, September 5, 2018 UTC). Many shallow landslides were triggered by this Mw 6.6 (Mj 6.7) earthquake. The basement complex in the affected area (sedimentary rocks) is covered with thick pyroclastic fall deposits derived from the Tarumae Volcano, etc., and the strong seismic shocks triggered shallow landsliding of them. Shallow landslides moving along valley type topography traveled greater distances than those moving along planar slope topography. Some shallow landslides occurred on relatively gentle slopes (< 30°). The earthquake also induced several large-scale deep-seated landslides, including one that has formed a landslide dam in the Hidaka-horonai River. Landslides were densely distributed over hilly regions (elevation: 200–400 m) within an area of approximately 400 km2 in Atsuma (landslides caused 36 deaths), Abira, and Mukawa, and the number of landslides and the total area of the landslides were the largest in Japan ever since the Meiji Era (1868–1912). The catchments where shallow landslides were concentrated were severely devastated.

As a method for three-dimensional quality assurance in boron neutron capture therapy (BNCT), micelle gel dosimeters are focused on. We are investigating dose-component discrimination method by using multiple gel dosimeters which have each different radiation quality specificity. In this study, the characteristics of each gel dosimeter for neutrons and gamma-rays were evaluated, and a dose-component discrimination method was suggested.

In allergic contact dermatitis (ACD) and contact hypersensitivity (CHS), the healed skin shows greater swelling than the naïve skin in the same individual upon re-exposure to the same hapten. This \"local skin memory\" (LSM) in healed skin was maintained for a prolonged period of time and mediated by skin CD8 -resident memory T (T ) cells in C57BL/6 mice. However, the number of CD4 T cells is elevated in ACD-healed human skin, and the contribution of CD4 T cells to the formation of LSM currently remains unclear. We herein demonstrated that immediately after CHS subsided, the healed skin in BALB/c mice showed an accumulation of hapten-specific CD4 and CD8 T cells, with a predominance of CD4 T cells. The presence of CD4 or CD8 T cells in the healed skin was sufficient for the induction of a flare-up reaction upon a re-challenge. The CD4 and CD8 T cells both produced interferon-γ and tumor necrosis factor early after the re-challenge. Moreover, while CD8 T cells gradually decreased over time and were eventually lost from the healed skin at 40-51 weeks after the resolution of CHS, the CD4 T cell numbers remained elevated during this period. The present results indicate that the long-term maintenance of LSM is mediated by CD4 T cells, and thus CD4 T cells are an important target for the treatment of recurrent human ACD.

Glypican‐3 (GPC3) is an onco‐fetal antigen that is overexpressed in human hepatocellular carcinoma (HCC), and is only expressed in the placenta and embryonic liver among normal tissues. Previously, we identified an HLA‐A2‐restricted GPC3144–152 (FVGEFFTDV) peptide that can induce GPC3‐reactive CTLs without inducing autoimmunity in HLA‐A2 transgenic mice. In this study, we carried out a phase I clinical trial of HLA‐A2‐restricted GPC3144–152 peptide vaccine in 14 patients with advanced HCC. Immunological responses were analyzed by ex vivoγ‐interferon enzyme‐linked immunospot assay. The frequency of GPC3144–152 peptide‐specific CTLs after vaccination (mean, 96; range, 5–441) was significantly larger than that before vaccination (mean, 6.5; range, 0–43) (P < 0.01). An increase in the GPC3144–152 peptide‐specific CTL frequency was observed in 12 (86%) of 14 patients after vaccination. Additionally, there was a significant correlation between the maximum value of GPC3144–152 peptide‐specific CTLs after vaccination and the dose of the peptide injected (P = 0.0166, r = 0.665). Moreover, we established several GPC3144–152 peptide‐specific CTL clones from PBMCs of patients vaccinated with GPC3144–152 peptide by single cell sorting using Dextramer and CD107a antibody. These CTL clones had high avidity (the recognition efficiency showing 50% cytotoxicity was 10−10 or 10−11 M) and could recognize HCC cell lines expressing GPC3 in an HLA‐class I‐restricted manner. These results suggest that GPC3144–152 peptide vaccine can induce high avidity CTLs capable of killing HCC cells expressing GPC3. This trial was registered with University Hospital Medical Information Network number 000001395. (Cancer Sci 2011; 102: 918–925)

The polymer gel dosimeter has been proposed for use as a 3D dosimeter for complex dose distribution measurement of high dose-rate (HDR) brachytherapy. However, various shapes of catheter/applicator for sealed radioactive source transport used in clinical cases must be placed in the gel sample. The absorbed dose readout for the magnetic resonance (MR)-based polymer gel dosimeters requires calibration data for the dose-transverse relaxation rate (R2) response. In this study, we evaluated in detail the dose uncertainty and dose resolution of three calibration methods, the multi-sample and distance methods using the Ir-192 source and the linear accelerator (linac) method using 6MV X-rays. The use of Ir-192 sources increases dose uncertainty with steep dose gradients. We clarified that the uniformly irradiated gel sample improved the signal-to-noise ratio (SNR) due to the large slice thickness of MR images and could acquire an accurate calibration curve using the linac method. The curved tandem and ovoid applicator used for intracavitary irradiation of HDR brachytherapy for cervical cancer were reproduced with a glass tube to verify the dose distribution. The results of comparison with the treatment planning system (TPS) calculation by gamma analysis on the 3%/2 mm criterion were in good agreement with a gamma pass rate of 90%. In addition, the prescription dose could be evaluated accurately. We conclude that it is easy to place catheter/applicator in the polymer gel dosimeters, making them a useful tool for verifying the 3D dose distribution of HDR brachytherapy with accurate calibration methods.

Laboratory investigations on admission found an estimated glomerular filtration rate (eGFR) of 21·4 mL/min/1·73m2 (normal >90) and a serum B-type natriuretic peptide (BNP) concentration of 263 pg/mL (normal <18·4), indicating possible damage to the kidneys and heart; additional tests and examinations—including an echocardiogram, and brain and adrenal CTs—were normal, thereby ruling out any cerebral or cardiovascular emergencies that may have caused the raised blood pressure. After 90 days of treatment, the flow-mediated dilation was 7·5%, indicating significant improvement (figure 2; appendix). [...]the urinary albumin-to-creatinine ratio—measured to complement assessment of vascular endothelial damage—showed a significant decrease to 44·7 mg/g (normal <30); on admission the ratio had been 411·6 mg/g. Malignant hypertension is a term used for patients with elevated blood pressure and multiple complications; hypertensive crisis describes patients with systolic blood pressure >180 mm Hg and diastolic >120 mm Hg.

Histone deacetylase (HDAC) 6 is a subtype of the HDAC family; it deacetylates α -tubulin and increases cell motility. Here, we investigate the impact of an alteration of HDAC6 expression in estrogen receptor α (ER)-positive breast cancer MCF-7 cells, as we identified that HDAC6 is a novel estrogen-regulated gene. MCF-7 treated with estradiol showed increased expression of HDAC6 mRNA and protein and a four-fold increase in cell motility in a migration assay. Cell motility was increased to the same degree by stably transfecting the HDAC6 expression vector into MCF-7 cells. In both cases, the cells changed in appearance from their original round shape to an axon-extended shape, like a neuronal cell. This HDAC6 accumulation caused the deacetylation of α -tubulin. Either the selective estrogen receptor modulator tamoxifen (TAM) or the pure antiestrogen ICI 182,780 prevented estradiol-induced HDAC6 accumulation and deacetylation of α -tubulin, leading to reduced cell motility. Tubacin, an inhibitory molecule that binds to the tubulin deacetylation domain of HDAC6, also prevented estradiol-stimulated cell migration. Finally, we evaluated HDAC6 protein expression in 139 consecutively archived human breast cancer tissues by immunohistochemical staining. The prognostic analyses for these patients revealed no significant differences based on HDAC6 expression. However, subset analysis of ER-positive patients who received adjuvant treatment with TAM ( n =67) showed a statistically significant difference in relapse-free survival and overall survival in favor of the HDAC6-positive group ( P <0.02 and P <0.05, respectively). HDAC6 expression was an independent prognostic indicator by multivariate analysis (odds ratio=2.82, P =0.047). These results indicate the biological significance of HDAC6 regulation via estrogen signaling.

Angiopoietin (Ang) and its receptor, TIE signaling, contribute to the development and maturation of embryonic vasculature as well as vascular remodeling and permeability in adult tissues. Targeting both this signaling pathway and the major pathway with vascular endothelial growth factor (VEGF) is expected to permit clinical applications, especially in antiangiogenic therapies against tumors. Several drugs targeting the Ang-TIE signaling pathway in cancer patients are under clinical development. Similar to how cancer increases with age, unsuitable angiogenesis or endothelial dysfunction is often seen in other ageing-associated diseases (AADs) such as atherosclerosis, Alzheimer’s disease, type 2 diabetes, chronic kidney disease and cardiovascular diseases. Thus, the Ang-TIE pathway is a possible molecular target for AAD therapy. In this review, we focus on the potential role of the Ang-TIE signaling pathway in AADs, especially non-cancer-related AADs. We also suggest translational insights and future clinical applications of this pathway in those AADs.

In recent years, a novel radiochromic gel dosimeter was developed that utilizes the color development of a polyvinyl alcohol-iodide (PVA-I) complex. In this study, we explore the effects of different iodide salts (LiI, NaI, KI, CsI, NH 4 I, CaI 2 , and ZnI 2 ) and PVAs with different degrees of polymerization (500, 1000, and 1500) and saponification (80, 88, and 98 mol%) were investigated on a PVA-GTA-I gel dosimeter using PVA that was chemically crosslinked with glutaraldehyde (GTA) as a matrix. The results showed that these substitutions had negligible effect on dose-responses, such as sensitivity and dose-rate independence.