Numerical study on remaining strength prediction of corroded Steel bridge plates

Corrosion causes strength deterioration of aged steel infrastructures and hence careful evaluation of their remaining load-carrying capacities are of high importance in maintenance engineering. To develop a more reliable strength estimation technique, only experimental approach is not enough as actual corroded surfaces are different from each other. However in modern practices, numerical simulation is being used to replace the time-consuming and expensive experimental work and to comprehend on the lack of knowledge of mechanical behavior, stress distribution, ultimate behavior and so on. Therefore, using of numerical analysis method will give important knowledge not only for strength estimation but also for subsequent repair and retrofitting plan. The results of non-linear FEM analysis of many actual corroded plates with different corrosion conditions and comparison of them with the respective tensile coupon tests results are presented in this paper. Further, the feasibility of establishing of an analytical methodology to predict the residual strength capacities of a corroded steel member with fewer number of measuring points are also discussed

Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression

Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm(2) to 475/mm(2) in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3 alpha and PPAR coactivator-1 alpha (PGC-1 alpha) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis. Copyright (C) 2012 S. Karger AG, Base

Pharyngeal Lavage Lymphocytosis in Patients with Obstructive Sleep Apnea: A Preliminary Observation

Background: Upper airway inflammation has been previously demonstrated in obstructive sleep apnea (OSA). However, investigation has been hampered by the necessity of invasive tissue biopsies. Objective: To evaluate the pharyngeal lavage (PHAL) as a new tool to analyze mucosal inflammation in the pharynx of patients with sleep-related disordered breathing. Patients and Methods: 36 patients with a diagnosis of OSA, 14 patients with heavy snorer syndrome (HS) or body position dependent OSA (bd-OSA), and 14 healthy volunteers underwent PHAL. Inflammatory cell counts were compared. Results: Neutrophils were the predominant cells in PHAL in all groups (94.3%60.7%, 98.5%60.6%, 94.3%60.7%, and 96.2%61.4%). OSA patients had significantly increased numbers of lymphocytes (3.2%60.4%) compared to bd-OSA/HS and controls group (0.5%60.1 % and 0.6%60.2%, respectively; P,0.05). Patients with moderate to severe OSA had significantly higher numbers of lymphocytes compared to patients with mild OSA (P,0.05). Conclusions: Data from this study suggest that PHAL is a feasible tool to investigate upper airway inflammation in OSA. In addition, PHAL demonstrates lymphocytic inflammation of the pharynx in OSA patients. Future studies are warranted to evaluate whether PHAL can be used to monitor disease and whether lymphocytic inflammation is affected by OSA treatment

Tumor-Derived Microvesicles Induce Proangiogenic Phenotype in Endothelial Cells via Endocytosis

Background: Increasing evidence indicates that tumor endothelial cells (TEC) differ from normal endothelial cells (NEC). Our previous reports also showed that TEC were different from NEC. For example, TEC have chromosomal abnormality and proangiogenic properties such as high motility and proliferative activity. However, the mechanism by which TEC acquire a specific character remains unclear. To investigate this mechanism, we focused on tumor-derived microvesicles (TMV). Recent studies have shown that TMV contain numerous types of bioactive molecules and affect normal stromal cells in the tumor microenvironment. However, most of the functional mechanisms of TMV remain unclear. Methodology/Principal Findings: Here we showed that TMV isolated from tumor cells were taken up by NEC through endocytosis. In addition, we found that TMV promoted random motility and tube formation through the activation of the phosphoinositide 3-kinase/Akt pathway in NEC. Moreover, the effects induced by TMV were inhibited by the endocytosis inhibitor dynasore. Our results indicate that TMV could confer proangiogenic properties to NEC partly via endocytosis. Conclusion: We for the first time showed that endocytosis of TMV contributes to tumor angiogenesis. These findings offer new insights into cancer therapies and the crosstalk between tumor and endothelial cells mediated by TMV in the tumor microenvironment

The establishment of two paclitaxel-resistant prostate cancer cell lines and the mechanisms of paclitaxel resistance with two cell lines

BACKGROUND Although paclitaxel is used for hormone-resistant prostate cancer, relapse definitely occurs later. Details of the molecular mechanism responsible for paclitaxel- resistance remain unclear. METHODS We established paclitaxel-resistant cells, DU145-TxR and PC-3-TxR from parent DU145 and PC-3. To characterize these cells, we examined cross-resistance to other anticancer drugs. Expression of several potential genes that had been related to drug-resistance was compared with parent cells by RT-PCR and Western blotting. Methylation analysis of multiple drug resistance (MDR1) promoter was carried out using bisulfite-modified DNA from cell lines. Knockdown experiments using small interfering RNA (siRNA) were also performed to confirm responsibility of drug-resistance. Finally, cDNA microarray was performed to quantify gene expression in PC-3 and PC-3-TxR cells. RESULTS The IC 50 for paclitaxel in DU145-TxR and PC-3-TxR was 34.0- and 43.4-fold higher than that in both parent cells, respectively. Both cells showed cross-resistance to some drugs, but not to VP-16 and cisplatin. Methylation analysis revealed that methylated CpG sites of MDR1 promoter in DU145 and PC-3 cells were demethylated in DU145-TxR cells, but not in PC-3-TxR cells. Knockdown of P-glycoprotein (P-gp), which was up-regulated in resistant cells, by MDR-1 siRNA restored paclitaxel sensitivity in DU145-TxR but not in PC-3-TxR, indicating that up-regulation of P-gp was not always main cause of paclitaxel-resistance. Microarray analysis identified 201 (1.34%) up-regulated genes and 218 (1.45%) out of screened genes in PC-3-TxR. CONCLUSIONS Our data will provide molecular mechanisms of paclitaxel-resistance and be useful for screening target genes to diagnose paclitaxel sensitivity. Prostate 67: 955–967, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56002/1/20581_ftp.pd

Novel Mouse Xenograft Models Reveal a Critical Role of CD4+ T Cells in the Proliferation of EBV-Infected T and NK Cells

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients' PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rγnull strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Expression of the EBV nuclear antigen 1 (EBNA1), the latent membrane protein 1 (LMP1), and LMP2, but not EBNA2, in the engrafted cells is consistent with the latency II program of EBV gene expression known in CAEBV. High levels of human cytokines, including IL-8, IFN-γ, and RANTES, were detected in the peripheral blood of the model mice, mirroring hypercytokinemia characteristic to both CAEBV and EBV-HLH. Transplantation of individual immunophenotypic subsets isolated from patients' PBMC as well as that of various combinations of these subsets revealed a critical role of CD4+ T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4+ T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases