445 research outputs found

    Differentiation Of Displacement Factor For Stiff And Soft Clay In Additional Modulus Of Subgrade Reaction Of Nailed-Slab Pavement System

    Get PDF
    Displacement factor was proposed to use in calculation of additional modulus of subgrade reaction. The moduli is used in designing the Nailed-slab Pavement System. A curve of displacement factor was proposed by Puri (2017) for soft clay and the inverse one was recomended by Hardiyatmo (2011b) for stiff clay. This paper is aimed to develop displacement factor for stiff clay based on Hardiyatmo data and compared to Puri’s curve. Results show that there is no significant differentaition of displacement factor between both clay consistencies. It can be concluded that the curve of dispalcement factor for soft clay from Puri’s curve can be used for stiff clay

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

    Get PDF
    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Cysteamine Suppresses Invasion, Metastasis and Prolongs Survival by Inhibiting Matrix Metalloproteinases in a Mouse Model of Human Pancreatic Cancer

    Get PDF
    Background: Cysteamine, an anti-oxidant aminothiol, is the treatment of choice for nephropathic cystinosis, a rare lysosomal storage disease. Cysteamine is a chemo-sensitization and radioprotection agent and its antitumor effects have been investigated in various tumor cell lines and chemical induced carcinogenesis. Here, we investigated whether cysteamine has anti-tumor and anti-metastatic effects in transplantable human pancreatic cancer, an aggressive metastatic disease. Methodology/Principal Findings: Cysteamine’s anti-invasion effects were studied by matrigel invasion and cell migration assays in 10 pancreatic cancer cell lines. To study mechanism of action, we examined cell viability and matrix metalloproteinases (MMPs) activity in the cysteamine-treated cells. We also examined cysteamine’s anti-metastasis effect in two orthotopic murine models of human pancreatic cancer by measuring peritoneal metastasis and survival of animals. Cysteamine inhibited both migration and invasion of all ten pancreatic cancer cell lines at concentrations (,25 mM) that caused no toxicity to cells. It significantly decreased MMPs activity (IC50 38–460 mM) and zymographic gelatinase activity in a dose dependent manner in vitro and in vivo; while mRNA and protein levels of MMP-9, MMP-12 and MMP-14 were slightly increased using the highest cysteamine concentration. In vivo, cysteamine significantly decreased metastasis in two established pancreatic tumor models, although it did not affect the size of primary tumors. Additionally, cysteamin

    Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas of the breast and its clinicopathologic relationships

    Get PDF
    INTRODUCTION: The anaphase-promoting complex (APC) is a multiprotein complex with E3 ubiquitin ligase activity, which is required for the ubiquitination of securin and cyclin-B. Moreover, the mitotic spindle checkpoint is activated if APC activation is prevented. In addition, several APC-targeting molecules such as securin, polo-like kinase, aurora kinase, and SnoN have been reported to be oncogenes. Therefore, dysregulation of APC may be associated with tumorigenesis. However, the clinical significance and the involvement of APC in tumorigenesis have not been investigated. METHODS: The expression of APC7 was immunohistochemically investigated in 108 invasive ductal carcinomas of the breast and its relationship with clinicopathologic parameters was examined. The expression of APC7 was defined as positive when the summed scores of staining intensities (0 to 3+) and stained proportions (0 to 3+) exceeded 3+. RESULTS: Positive APC7 expression was less frequent than its negative expression when histologic (P = 0.009) or nuclear grade (P = 0.009), or mitotic number (P = 0.0016) was elevated. The frequency of APC7 negative expression was higher in high Ki-67 or aneuploid groups than in low Ki-67 or diploid groups. CONCLUSION: These data show that loss of APC7 expression is more common in breast carcinoma cases with poor prognostic parameters or malignant characteristics. They therefore suggest that dysregulation of APC activity, possibly through downregulation of APC7, may be associated with tumorigenesis in breast cancer

    Motives for corporate cash holdings:the CEO optimism effect

    Get PDF
    We examine the chief executive officer (CEO) optimism effect on managerial motives for cash holdings and find that optimistic and non-optimistic managers have significantly dissimilar purposes for holding more cash. This is consistent with both theory and evidence that optimistic managers are reluctant to use external funds. Optimistic managers hoard cash for growth opportunities, use relatively more cash for capital expenditure and acquisitions, and save more cash in adverse conditions. By contrast, they hold fewer inventories and receivables and their precautionary demand for cash holdings is less than that of non-optimistic managers. In addition, we consider debt conservatism in our model and find no evidence that optimistic managers’ cash hoarding is related to their preference to use debt conservatively. We also document that optimistic managers hold more cash in bad times than non-optimistic managers do. Our work highlights the crucial role that CEO characteristics play in shaping corporate cash holding policy

    Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients.</p> <p>Methods</p> <p>Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples.</p> <p>Results</p> <p>HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p < 0.001).</p> <p>Conclusions</p> <p>IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.</p

    Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway

    Get PDF
    The gene and protein expression profiles in myeloproliferative neoplasms (MPNs) may reveal gene and protein markers of a potential clinical relevance in diagnosis, treatment and prediction of response to therapy. Using cDNA microarray analysis of 25,100 unique genes, we studied the gene expression profile of CD34(+) cells and granulocytes obtained from peripheral blood of subjects with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). The microarray analyses of the CD34(+) cells and granulocytes were performed from 20 de novo MPN subjects: JAK2 positive ET, PV, PMF subjects, and JAK2 negative ET/PMF subjects. The granulocytes for proteomic studies were pooled in 4 groups: PV with JAK2 mutant allele burden above 80%, ET with JAK2 mutation, PMF with JAK2 mutation and ET/PMF with no JAK2 mutation. The number of differentially regulated genes was about two fold larger in CD34(+) cells compared to granulocytes. Thirty-six genes (including RUNX1, TNFRSF19) were persistently highly expressed, while 42 genes (including FOXD4, PDE4A) were underexpressed both in CD34(+) cells and granulocytes. Using proteomic studies, significant up-regulation was observed for MAPK and PI3K/AKT signaling regulators that control myeloid cell apoptosis and proliferation: RAC2, MNDA, S100A8/9, CORO1A, and GNAI2. When the status of the mTOR signaling pathway related genes was analyzed, PI3K/AKT regulators were preferentially up-regulated in CD34(+) cells of MPNs, with down-regulated major components of the protein complex EIF4F. Molecular profiling of CD34(+) cells and granulocytes of MPN determined gene expression patterns beyond their recognized function in disease pathogenesis that included dominant up-regulation of PI3K/AKT signaling

    Review of genetic factors in intestinal malrotation

    Get PDF
    Intestinal malrotation is well covered in the surgical literature from the point of view of operative management, but few reviews to date have attempted to provide a comprehensive examination of the topic from the point of view of aetiology, in particular genetic aetiology. Following a brief overview of molecular embryology of midgut rotation, we present in this article instances of and case reports and case series of intestinal malrotation in which a genetic aetiology is likely. Autosomal dominant, autosomal recessive, X-linked and chromosomal forms of the disorder are represented. Most occur in syndromic form, that is to say, in association with other malformations. In many instances, recognition of a specific syndrome is possible, one of several examples discussed being the recently described association of intestinal malrotation with alveolar capillary dysplasia, due to mutations in the forkhead box transcription factor FOXF1. New advances in sequencing technology mean that the identification of the genes mutated in these disorders is more accessible than ever, and paediatric surgeons are encouraged to refer to their colleagues in clinical genetics where a genetic aetiology seems likely

    The Effect of Diel Temperature and Light Cycles on the Growth of Nannochloropsis oculata in a Photobioreactor Matrix

    Get PDF
    A matrix of photobioreactors integrated with metabolic sensors was used to examine the combined impact of light and temperature variations on the growth and physiology of the biofuel candidate microalgal species Nannochloropsis oculata. The experiments were performed with algal cultures maintained at a constant 20u C versus a 15°C to 25°C diel temperature cycle, where light intensity also followed a diel cycle with a maximum irradiance of 1920 μmol photons m-2 s-1. No differences in algal growth (Chlorophyll a) were found between the two environmental regimes; however, the metabolic processes responded differently throughout the day to the change in environmental conditions. The variable temperature treatment resulted in greater damage to photosystem II due to the combined effect of strong light and high temperature. Cellular functions responded differently to conditions before midday as opposed to the afternoon, leading to strong hysteresis in dissolved oxygen concentration, quantum yield of photosystem II and net photosynthesis. Overnight metabolism performed differently, probably as a result of the temperature impact on respiration. Our photobioreactor matrix has produced novel insights into the physiological response of Nannochloropsis oculata to simulated environmental conditions. This information can be used to predict the effectiveness of deploying Nannochloropsis oculata in similar field conditions for commercial biofuel production. © 2014 Tamburic et al
    corecore