Immunohistochemical Localization of the Aquaporins AQP1, AQP3, AQP4, and AQP5 in the Mouse Respiratory System

Aquaporins are membrane water channel proteins that function mainly in water transfer across cellular membranes. In our present study, we investigated the immunohistochemical distribution of aquaporin 1 (AQP1), AQP3, AQP4, and AQP5 in the mouse respiratory system by immunofluorescence, immunoperoxidase, and immunoelectron microscopy. AQP3, AQP4, and AQP5 are expressed in epithelial cells, whereas AQP1 is expressed in subepithelial connective tissues and capillaries. In the airway surface epithelia from the nasal cavity to the intrapulmonary bronchioles, AQP5 was found to be mainly localized to the luminal side and both AQP3 and AQP4 to the abluminal side. In the alveolar epithelium, AQP5 is localized to the apical membranes of both type I and type II alveolar cells. Compared with the previous studies on the rat respiratory system, in which AQP5 is restricted to the alveolar type I cells and absent from the airway surface epithelia, we found that AQP5 in the mouse is much more widely distributed throughout the surface epithelia. These results suggest that AQP5 has a critical role in water-handling, such as the maintenance of airway surface liquid and clearance of alveolar fluid in the mouse respiratory system

Systematic study of the SO(10) symmetry breaking vacua in the matrix model for type IIB superstrings

We study the properties of the space-time that emerges dynamically from the matrix model for type IIB superstrings in ten dimensions. We calculate the free energy and the extent of space-time using the Gaussian expansion method up to the third order. Unlike previous works, we study the SO(d) symmetric vacua with all possible values of d within the range $2 \le d \le 7$, and observe clear indication of plateaus in the parameter space of the Gaussian action, which is crucial for the results to be reliable. The obtained results indeed exhibit systematic dependence on d, which turns out to be surprisingly similar to what was observed recently in an analogous work on the six-dimensional version of the model. In particular, we find the following properties: i) the extent in the shrunken directions is given by a constant, which does not depend on d; ii) the ten-dimensional volume of the Euclidean space-time is given by a constant, which does not depend on d except for d = 2; iii) The free energy takes the minimum value at d = 3. Intuitive understanding of these results is given by using the low-energy effective theory and some Monte Carlo results.Comment: 33 pages, 10 figures; minor corrections, reference added. arXiv admin note: substantial text overlap with arXiv:1007.088

Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation

Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated.We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients' backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p<0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAV-AS group, compared with the TAV-AS and CBAV-AR groups (both p<0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p<0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35).Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV

Testing the Gaussian expansion method in exactly solvable matrix models

The Gaussian expansion has been developed since early 80s as a powerful analytical method, which enables nonperturbative studies of various systems using `perturbative' calculations. Recently the method has been used to suggest that 4d space-time is generated dynamically in a matrix model formulation of superstring theory. Here we clarify the nature of the method by applying it to exactly solvable one-matrix models with various kinds of potential including the ones unbounded from below and of the double-well type. We also formulate a prescription to include a linear term in the Gaussian action in a way consistent with the loop expansion, and test it in some concrete examples. We discuss a case where we obtain two distinct plateaus in the parameter space of the Gaussian action, corresponding to different large-N solutions. This clarifies the situation encountered in the dynamical determination of the space-time dimensionality in the previous works.Comment: 30 pages, 15 figures, LaTeX; added references for section

Indications for cytoreductive surgery plus HIPEC in patients with colorectal cancer and peritoneal metastasis.

AbstractComprehensive treatment (COMPT) consisting of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in selected patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The aim of the present study was to clarify clinicopathologic parameters that are indications to perform COMPT in CRC-patients with CRC-PM.Between 2006 and 2021, 447 patients were selected as eligible for COMPT among 906 CRC-patients with PM. Clinicopathologic parameters contributing to long-term survival and cure were analyzed.Results: A log-rank test showed a significant survival difference for peritoneal cancer index (PCI) (≤12 vs. ≥13), completeness of cytoreduction (CCR) score (CCR-0 vs. CCR-1), small bowel (SB)-PCI (≤2 vs. ≥3), liver/lung metastasis (LLM) (negative vs. positive), histologic type (differentiated type vs. signet ring cell (SRC) subtype), number of involved peritoneal sectors (≤6 vs. ≥7), HIPEC (done vs. not done) and postoperative complication (grade 0, 1, or 2 vs. grade 3, 4, or 5). Muti-variate analyses revealed that CCR score (CCR-0 vs. CCR-1), SB-PCI score (≤2 vs. ≥3), LLM (negative vs. positive), and HIPEC (performed vs. not done) were independent prognostic factors. The incidence of postoperative grade 3, 4 or 5 complication was 19.0% (85/447) and the mortality rate was 2.0% (9/447). One hundred and seventy patients fulfilled the following clinicopathologic factors,PCI ≤12, SB-PCI ≤2, number of involved peritoneal sectors ≤6, no LLM, differentiated histologic type and CCR-0. The MST of these patients was 5.5 years, and 5- and 10-year survival rates were 57.8% and 24.6%, respectively. Postoperative grade 3, 4, and 5 complications in these 170 patients occurred in 9 (5.3%), 15 (8.8%) and 1 (0.6%), respectively. Cured patients were defined as those alive without recurrence more than 5 years after CRS. All of the cured patients underwent CCR-0 resection. The PCI and SB-PCI of these 23 patients were ≤12 and ≤2, respectively

Integral role of receptor for advanced glycation end products (RAGE) in nondiabetic atherosclerosis

An advanced glycation end products (AGE)/a receptor for AGE (RAGE) axis plays a central role in the pathogenesis of diabetic vascular remodeling. This study was conducted to clarify the role of RAGE in nondiabetic atherosclerosis. We used the aortic and coronary atherosclerotic lesions of Watanabe heritable hyperlipidemic (WHHL) rabbits prone to myocardial infarction (WHHLMI) at 1 to 14 months. Immunohistochemistry demonstrated the significant expression of RAGE as early as at 1 month with the stronger expression at 3 and 7 months, which was remarkably diminished at 14 months. RAGE expression was concordant with AGE accumulation. The major original sources of RAGE expression were macrophages and smooth muscle cells in addition to endothelial cells, and RAGE expression was distributed in the areas of phospholipid products, a component of oxidized LDL and nitrotyrosine. The concentrations of serum AGE did not alter significantly with aging. These findings suggested the expression of RAGE was induced by hyperlipidemia and oxidative stress independent of diabetes in WHHLMI rabbits. Additionally, our in vitro study showed that silencing of RAGE tended to attenuate oxidized-LDL-triggered PAI-1 expression in human cultured macrophages, as well as oxidized-LDL-induced tissue factor expression in peritoneal macrophages, suggesting a possible role of RAGE in prothrombogenic molecular regulation. In conclusion, the present study provides in vivo evidence that RAGE plays an integral role in the initiation and progression of nondiabetic atherosclerosis, suggesting that RAGE may be a novel target for treating not only diabetic but also nondiabetic vascular complications

Report of the 4th World Climate Research Programme International Conference on Reanalyses

The 4th WCRP International Conference on Reanalyses provided an opportunity for the international community to review and discuss the observational and modelling research, as well as process studies and uncertainties associated with reanalysis of the Earth System and its components. Characterizing the uncertainty and quality of reanalyses is a task that reaches far beyond the international community of producers, and into the interdisciplinary research community, especially those using reanalysis products in their research and applications. Reanalyses have progressed greatly even in the last 5 years, and newer ideas, projects and data are coming forward. While reanalysis has typically been carried out for the individual domains of atmosphere, ocean and land, it is now moving towards coupling using Earth system models. Observations are being reprocessed and they are providing improved quality for use in reanalysis. New applications are being investigated, and the need for climate reanalyses is as strong as ever. At the heart of it all, new investigators are exploring the possibilities for reanalysis, and developing new ideas in research and applications. Given the many centres creating reanalyses products (e.g. ocean, land and cryosphere research centres as well as NWP and atmospheric centers), and the development of new ideas (e.g. families of reanalyses), the total number of reanalyses is increasing greatly, with new and innovative diagnostics and output data. The need for reanalysis data is growing steadily, and likewise, the need for open discussion and comment on the data. The 4th Conference was convened to provide a forum for constructive discussion on the objectives, strengths and weaknesses of reanalyses, indicating potential development paths for the future