Laser-Based Ultrasonics on Gr/Epoxy Composite a Systems Analysis

Critical issues are examined in the application of laser generation and detection of ultrasound to the inspection of large area air-frame composites. Among these issues are surface roughness, signal-to-noise ratio, insensitivity to the path length between the part and detector, and wide-band versus narrow-band generation. Supporting experiments are reported on broad-band and narrow-band generation in Gr/Epoxy panels and angular reflectance measurements on painted and unpainted Gr/Epoxy. On the basis of these measurements, a laser-in/laser-out systems analysis is carried out for a 10 mm diameter delamination about 1 cm deep. The analysis assumes that a Spherical Fabry-Perot interferometer is used for detection and a 10 nsec laser pulse with a peak power of 13 MW/cm2 for generation. The estimates indicate a S/N ≈ 20 dB for a detection probe laser power of about 400 mW.</p

Correlation of Thin-Film Bond Compliance and Bond Fracture Resistance

The integrity of the interfacial bond between a coating and its substrate is of primary importance for any application. A technique for the quantitative nondestructive measurement of the bond fracture energy is essential for evaluating bond integrity. Scanning acoustic microscopy (SAM) provides a method for making localized measurements of film dis-bonds and film bond compliance based on the changes in the surface acoustic wave velocity in the layered medium. The results of these measurements for chrome/gold and gold films on glass substrates are summarized. The compliance of the bond and its fracture energy can be correlated in some film systems. An experiment to determine if this correlation exists for chrome/gold and gold films on sapphire substrates is described. Results of such an experiment would provide an empirical correlation between surface acoustic wave velocity measurements and the fracture energy of the film. The results of an experiment to measure the fracture energy of the interfacial bond between a gold film and the sapphire substrate are described.</p

Adjunctive Dexamethasone Affects the Expression of Genes Related to Inflammation, Neurogenesis and Apoptosis in Infant Rat Pneumococcal Meningitis

Streptococcus pneumoniae is the most common pathogen causing non-epidemic bacterial meningitis worldwide. The immune response and inflammatory processes contribute to the pathophysiology. Hence, the anti-inflammatory dexamethasone is advocated as adjuvant treatment although its clinical efficacy remains a question at issue. In experimental models of pneumococcal meningitis, dexamethasone increased neuronal damage in the dentate gyrus. Here, we investigated expressional changes in the hippocampus and cortex at 72 h after infection when dexamethasone was given to infant rats with pneumococcal meningitis. Nursing Wistar rats were intracisternally infected with Streptococcus pneumoniae to induce experimental meningitis or were sham-infected with pyrogen-free saline. Besides antibiotics, animals were either treated with dexamethasone or saline. Expressional changes were assessed by the use of GeneChip® Rat Exon 1.0 ST Arrays and quantitative real-time PCR. Protein levels of brain-derived neurotrophic factor, cytokines and chemokines were evaluated in immunoassays using Luminex xMAP® technology. In infected animals, 213 and 264 genes were significantly regulated by dexamethasone in the hippocampus and cortex respectively. Separately for the cortex and the hippocampus, Gene Ontology analysis identified clusters of biological processes which were assigned to the predefined categories “inflammation”, “growth”, “apoptosis” and others. Dexamethasone affected the expression of genes and protein levels of chemokines reflecting diminished activation of microglia. Dexamethasone-induced changes of genes related to apoptosis suggest the downregulation of the Akt-survival pathway and the induction of caspase-independent apoptosis. Signalling of pro-neurogenic pathways such as transforming growth factor pathway was reduced by dexamethasone resulting in a lack of pro-survival triggers. The anti-inflammatory properties of dexamethasone were observed on gene and protein level in experimental pneumococcal meningitis. Further dexamethasone-induced expressional changes reflect an increase of pro-apoptotic signals and a decrease of pro-neurogenic processes. The findings may help to identify potential mechanisms leading to apoptosis by dexamethasone in experimental pneumococcal meningitis

Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines

This article discusses the definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis. Acute cholangitis and cholecystitis mostly originate from stones in the bile ducts and gallbladder. Acute cholecystitis also has other causes, such as ischemia; chemicals that enter biliary secretions; motility disorders associated with drugs; infections with microorganisms, protozoa, and parasites; collagen disease; and allergic reactions. Acute acalculous cholecystitis is associated with a recent operation, trauma, burns, multisystem organ failure, and parenteral nutrition. Factors associated with the onset of cholelithiasis include obesity, age, and drugs such as oral contraceptives. The reported mortality of less than 10% for acute cholecystitis gives an impression that it is not a fatal disease, except for the elderly and/or patients with acalculous disease. However, there are reports of high mortality for cholangitis, although the mortality differs greatly depending on the year of the report and the severity of the disease. Even reports published in and after the 1980s indicate high mortality, ranging from 10% to 30% in the patients, with multiorgan failure as a major cause of death. Because many of the reports on acute cholecystitis and cholangitis use different standards, comparisons are difficult. Variations in treatment and risk factors influencing the mortality rates indicate the necessity for standardized diagnostic, treatment, and severity assessment criteria

Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe

CXCR2 Inhibition Combined with Sorafenib Improved Antitumor and Antiangiogenic Response in Preclinical Models of Ovarian Cancer

The authors thank Drs. Kar-Ming Fung and Muralidharan Jayaraman, and Ms. Sheeja Aravindan for their help with the IHC experiments. The authors also thank the OUHSC Histology and Molecular Imaging Cores for their service and technical assistance.Antiangiogenic therapy is important for the treatment of gynecological cancer. However, the therapeutic benefit derived from these treatments is transient, predominantly due to the selective activation of compensatory proangiogenic pathways that lead to rapid development of resistance. We aimed to identify and target potential alternative signaling to anti-vascular endothelial growth factor (VEGF) therapy, with a view toward developing a combination of antiangiogenic agents to provide extended therapeutic benefits. We developed a preclinical in vivo phenotypic resistance model of ovarian cancer resistant to antiangiogenic therapy. We measured dynamic changes in secreted chemokines and angiogenic signaling in tumors and plasma in response to anti-VEGF treatment, as tumors advanced from the initial responsive phase to progressive disease. In tumors that progressed following sorafenib treatment, gene and protein expression levels of proangiogenic CXC chemokines and their receptors were significantly elevated, compared with responsive tumors. The chemokine (C-X-C motif) ligand 8 (CXCL8), also known as interleukin-8 (IL-8) increase was time-dependent and coincided with the dynamics of tumor progression. We used SB225002, a pharmacological inhibitor of chemokine (C-X-C motif) receptor 2 (CXCR2), to disrupt the CXC chemokine-mediated functions of ovarian cancer cells in in vitro assays of cell growth inhibition, spheroid formation, and cell migration. The combination of CXCR2 inhibitor with sorafenib led to a synergistic inhibition of cell growth in vitro, and further stabilized tumor progression following sorafenib in vivo. Our results suggest that CXCR2-mediated chemokines may represent an important compensatory pathway that promotes resistance to antiangiogenic therapy in ovarian cancer. Thus, simultaneous blockage of this proangiogenic cytokine pathway using CXCR2 inhibitors and the VEGF receptor (VEGFR) pathway could improve the outcomes of antiangiogenic therapy.Yeshttp://www.plosone.org/static/editorial#pee

Species-specific regulation of angiogenesis by glucocorticoids reveals contrasting effects on inflammatory and angiogenic pathways

<div><p>Glucocorticoids are potent inhibitors of angiogenesis in the rodent <i>in vivo</i> and <i>in vitro</i> but the mechanism by which this occurs has not been determined. Administration of glucocorticoids is used to treat a number of conditions in horses but the angiogenic response of equine vessels to glucocorticoids and, therefore, the potential role of glucocorticoids in pathogenesis and treatment of equine disease, is unknown. This study addressed the hypothesis that glucocorticoids would be angiostatic both in equine and murine blood vessels.The mouse aortic ring model of angiogenesis was adapted to assess the effects of cortisol in equine vessels. Vessel rings were cultured under basal conditions or exposed to: foetal bovine serum (FBS; 3%); cortisol (600 nM), cortisol (600nM) plus FBS (3%), cortisol (600nM) plus either the glucocorticoid receptor antagonist RU486 or the mineralocorticoid receptor antagonist spironolactone. In murine aortae cortisol inhibited and FBS stimulated new vessel growth. In contrast, in equine blood vessels FBS alone had no effect but cortisol alone, or in combination with FBS, dramatically increased new vessel growth compared with controls. This effect was blocked by glucocorticoid receptor antagonism but not by mineralocorticoid antagonism. The transcriptomes of murine and equine angiogenesis demonstrated cortisol-induced down-regulation of inflammatory pathways in both species but up-regulation of pro-angiogenic pathways selectively in the horse. Genes up-regulated in the horse and down-regulated in mice were associated with the extracellular matrix. These data call into question our understanding of glucocorticoids as angiostatic in every species and may be of clinical relevance in the horse.</p></div

The significance of dynamic dysfunction of critically short telomeres in directing the evolution of chromosomal structural instability in human cells undergoing immortalization

Nonrandom patterns of chromosomal aberrations are universally observed in all types of cancers as well as immortalized cell lines, for which the mechanism of initiation and progression is unknown. To examine whether dynamic telomere dysfunction contributes to the initiation and evolution of the preferential chromosomal aberrations during cellular immortalization, we developed a new technique which allowed, for the first time, telomere quantitative FISH and 24-colour spectral karyotyping in the same human cells. Two human ovarian surface epithelial cell lines (HOSE6-3, HOSE11-12), two esophageal cell lines (NE1-E6E7, NE6-E6E7), and one nasopharyngeal cell line (NP460-E6E7) immortalized by expression of HPV16 E6E7 oncogenes, were studied. We detected striking consistent differences in telomere signal intensities between homologous chromosomes and among non-homologous chromosomes in all five cell lines. The cell lines established from specimens from different donors had different distributions of the shortest telomeres. During cellular aging in vitro, chromosomes with the shortest telomeres were the first to show increased frequencies of chromosomal structural aberrations including dicentrics, translocations, insertions, deletions and duplications, independent of cell lines and cell types. With further cell proliferation towards crisis, progressive increases in frequencies of chromosomal structural aberrations occurred preferentially on specific chromosomes that had increasing frequencies of signal-free telomeres. None of analyzed pre-crisis or crisis metaphases had completely identical aberrations. In post-crisis (immortalized) cells, the majority of clonal stable aberrations again involved the chromosomes with signal-free telomeres before and during crisis. The existence of clonal aberrations in post-crisis cells demonstrates that chromosomes in post-crisis cells are far more stable than those during crisis. Parallel to this, the frequencies of chromosomal ends with undetectable telomeres dropped dramatically in post-crisis cells. Taken together, this study showed that the dysfunction of critically short telomeres played a fundamental role in directing the evolution of chromosomal structural instability leading to formation of nonrandom chromosomal aberrations in human cells undergoing immortalization, and this phenomenon appeared to be independent of cell lines and cell-types