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Sample records for delayed entry cox

  1. Secretory phospholipase A(2) induces delayed neuronal COX-2 expression compared with glutamate

    DEFF Research Database (Denmark)

    Nielsen, Marianne; Bazan, Nicolas G; Diemer, Nils H;

    2002-01-01

    and immunohistochemistry. An up-regulation of COX-2, c-fos, and c-jun, but not COX-1, was observed around the lesion as well as in the neocortex 4 hr after the injection. Hippocampal up-regulation of COX-2 was seen in dentate gyrus 8 hr after injection. When glutamate was injected, up-regulation of the early...

  2. Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1

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    Wong Helen WC

    2010-03-01

    Full Text Available Abstract Background After the WHO issued the global alert for 2009 pandemic influenza A (H1N1, many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission. Methods We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case. Results Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays. Conclusions Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.

  3. Estimating the Effects of Delayed Entry into Higher Education: A Discussion

    DEFF Research Database (Denmark)

    Humlum, Maria Knoth

    2007-01-01

    In Denmark many high school graduates choose to delay their entry into higher education. A number of studies have investigated the effects of the delay on the educational and labour market careers. The existing studies are likely to suffer from selection bias, and this problem is unlikely...... to be remedied by use of control variables. More advanced techniques that can eliminate the selection bias are needed in order to identify causal effects. For policy purposes it would thus be preferable to focus on the economic losses associated with the years lost in the skilled labour market which...

  4. Joint modelling of longitudinal and survival data: incorporating delayed entry and an assessment of model misspecification.

    Science.gov (United States)

    Crowther, Michael J; Andersson, Therese M-L; Lambert, Paul C; Abrams, Keith R; Humphreys, Keith

    2016-03-30

    A now common goal in medical research is to investigate the inter-relationships between a repeatedly measured biomarker, measured with error, and the time to an event of interest. This form of question can be tackled with a joint longitudinal-survival model, with the most common approach combining a longitudinal mixed effects model with a proportional hazards survival model, where the models are linked through shared random effects. In this article, we look at incorporating delayed entry (left truncation), which has received relatively little attention. The extension to delayed entry requires a second set of numerical integration, beyond that required in a standard joint model. We therefore implement two sets of fully adaptive Gauss-Hermite quadrature with nested Gauss-Kronrod quadrature (to allow time-dependent association structures), conducted simultaneously, to evaluate the likelihood. We evaluate fully adaptive quadrature compared with previously proposed non-adaptive quadrature through a simulation study, showing substantial improvements, both in terms of minimising bias and reducing computation time. We further investigate, through simulation, the consequences of misspecifying the longitudinal trajectory and its impact on estimates of association. Our scenarios showed the current value association structure to be very robust, compared with the rate of change that we found to be highly sensitive showing that assuming a simpler trend when the truth is more complex can lead to substantial bias. With emphasis on flexible parametric approaches, we generalise previous models by proposing the use of polynomials or splines to capture the longitudinal trend and restricted cubic splines to model the baseline log hazard function. The methods are illustrated on a dataset of breast cancer patients, modelling mammographic density jointly with survival, where we show how to incorporate density measurements prior to the at-risk period, to make use of all the available

  5. Delayed Workforce Entry and High Emigration Rates for Recent Canadian Radiation Oncology Graduates

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    Loewen, Shaun K., E-mail: shaun.loewen@cancercare.mb.ca [CancerCare Manitoba, Winnipeg, MB (Canada); Halperin, Ross; Lefresne, Shilo [BC Cancer Agency, Vancouver, BC (Canada); Trotter, Theresa [Tom Baker Cancer Centre, Calgary, AB (Canada); Stuckless, Teri [Dr H. Bliss Murphy Cancer Centre, St. John' s, NL (Canada); Brundage, Michael [Cancer Centre of Southeastern Ontario, Kingston, ON (Canada)

    2015-10-01

    Purpose: To determine the employment status and location of recent Canadian radiation oncology (RO) graduates and to identify current workforce entry trends. Methods and Materials: A fill-in-the-blank spreadsheet was distributed to all RO program directors in December 2013 and June 2014, requesting the employment status and location of their graduates over the last 3 years. Visa trainee graduates were excluded. Results: Response rate from program directors was 100% for both survey administrations. Of 101 graduates identified, 99 (98%) had known employment status and location. In the December survey, 5 2013 graduates (16%), 17 2012 graduates (59%), and 18 2011 graduates (75%) had permanent staff employment. Six months later, 5 2014 graduates (29%), 15 2013 graduates (48%), 24 2012 graduates (83%), and 21 2011 graduates (88%) had secured staff positions. Fellowships and temporary locums were common for those without staff employment. The proportion of graduates with staff positions abroad increased from 22% to 26% 6 months later. Conclusions: Workforce entry for most RO graduates was delayed but showed steady improvement with longer time after graduation. High emigration rates for jobs abroad signify domestic employment challenges for newly certified, Canadian-trained radiation oncologists. Coordination on a national level is required to address and regulate radiation oncologist supply and demand disequilibrium in Canada.

  6. Administration of L-arginine reduces the delay of the healing process caused by ibuprofen. Implication of COX and growth factors expression.

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    Sánchez-Fidalgo, S; Martín-Lacave, I; Illanes, M; Bruseghini, L; Esteras, A; Motilva, V

    2005-04-01

    The objective of the present study has been to advance knowledge of the gastric role played by the amino acid L-Arginine (L-Arg) in the evolution of a chronic gastric ulcer. In order to clarify it, L-Arg alone or together with Ibuprofen have been administrated in an experimental acetic acid chronic ulcer, analysing characteristic parameters of an active curative process, such as PGE2 production, COX expression, and also angiogenesis, proliferation/apoptosis and growth factors expression. Our results reveal that L-Arg is favourable in the healing process improving the curative course. Ibuprofen caused a delay in ulcer healing, more evident 14 days after ulcer induction; COX-2 expression was increased at the 7th day although no signal of protein could be detected after 14 days; PGE2 production was inhibited in intact and ulcerated areas at both times assayed. In contrast, treatment with L-Arg reduced the delay of the lesion, the increment in COX-2 expression induced by Ibuprofen, and was able to maintain PGE2 levels similar to the control group after 14 days. Additionally, the histological study showed that the healing effects of L-Arg might be associated with an increased angiogenesis and FGF-2 expression. These actions could be considered key factors in the healing response associated with L-Arg administration. However, the proliferation study assayed with the PCNA-immunostaining method did not reveal significant differences, as the same as the apoptosis analysis. In conclusion, the coupling of L-Arg to Ibuprofen is an attractive alternative to Ibuprofen administration alone because it not only attenuates but also improves the evolution of chronic lesions through mechanisms that implicate endogenous PG and FGF-2-associated pathways, which allow an increase of angiogenesis process.

  7. Delayed entry into HIV medical care in a nationally representative sample of HIV-infected adults receiving medical care in the USA.

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    Robertson, McKaylee; Wei, Stanley C; Beer, Linda; Adedinsewo, Demilade; Stockwell, Sandra; Dombrowski, Julia C; Johnson, Christopher; Skarbinski, Jacek

    2016-01-01

    Before widespread antiretroviral therapy (ART), an estimated 17% of people delayed HIV care. We report national estimates of the prevalence and factors associated with delayed care entry in the contemporary ART era. We used Medical Monitoring Project data collected from June 2009 through May 2011 for 1425 persons diagnosed with HIV from May 2004 to April 2009 who initiated care within 12 months. We defined delayed care as entry >three months from diagnosis. Adjusted prevalence ratios (aPRs) were calculated to identify risk factors associated with delayed care. In this nationally representative sample of HIV-infected adults receiving medical care, 7.0% (95% confidence interval [CI]: 5.3-8.8) delayed care after diagnosis. Black race was associated with a lower likelihood of delay than white race (aPR 0.38). Men who have sex with women versus women who have sex with men (aPR 1.86) and persons required to take an HIV test versus recommended by a provider (aPR 2.52) were more likely to delay. Among those who delayed 48% reported a personal factor as the primary reason. Among persons initially diagnosed with HIV (non-AIDS), those who delayed care were twice as likely (aPR 2.08) to develop AIDS as of May 2011. Compared to the pre-ART era, there was a nearly 60% reduction in delayed care entry. Although relatively few HIV patients delayed care entry, certain groups may have an increased risk. Focus on linkage to care among persons who are required to take an HIV test may further reduce delayed care entry.

  8. Interim analysis based on the weighted log-rank test for delayed treatment effects under staggered patient entry.

    Science.gov (United States)

    Yoshida, Mizuki; Matsuyama, Yutaka

    2016-01-01

    Fleming and Harrington's G(ρ,γ) class of weighted log-rank tests is appropriate for detecting delayed treatment effects such as those seen in cancer vaccines. A conditional power (CP) and an alpha spending function (ASF) approach are useful for interim analyses that are conducted with the aim of early termination due to futility and efficacy, respectively. However, calculation of the CP and the total Type I error probability are often not considered for delayed effects under the staggered patient entry. In this article, we first propose methods for calculating the CP analytically based on the weighted log-rank test. We compared the performances of the proposed methods with two other methods (i.e., usual log-rank test and optimal one) under the delayed alternatives. Our simulations demonstrated that the CP based on the weighted log-rank test was more powerful than that of the usual log-rank test and was comparable to the CP based on the optimal log-rank test. Second, we quantitatively evaluated the degree to which the Type I error probability was inflated when an ASF approach with forced independent increments assumption was applied to the weighted log-rank test. The proposed method will provide valuable tools in the decision-making stage of the interim analysis.

  9. Developmental Delay in Moderately Preterm-Born Children at School Entry

    NARCIS (Netherlands)

    Kerstjens, Jorien M.; de Winter, Andrea F.; Bocca-Tjeertes, Inger F.; ten Vergert, Elisabeth M. J.; Reijneveld, Sijmen A.; Bos, Arend F.; B0cca-Tjeertes, I.F.

    2011-01-01

    Objective To determine the prevalence and nature of developmental delay at preschool age in infants born moderately preterm compared with those born full-term and early preterm. Study design Parents of 927 moderate preterm infants (32-35(+) 6 weeks gestation), 512 early preterm infants ( Results Abn

  10. Developmental Delay in Moderately Preterm-Born Children at School Entry

    NARCIS (Netherlands)

    Kerstjens, Jorien M.; de Winter, Andrea F.; Bocca-Tjeertes, Inger F.; ten Vergert, Elisabeth M. J.; Reijneveld, Sijmen A.; Bos, Arend F.; B0cca-Tjeertes, I.F.

    Objective To determine the prevalence and nature of developmental delay at preschool age in infants born moderately preterm compared with those born full-term and early preterm. Study design Parents of 927 moderate preterm infants (32-35(+) 6 weeks gestation), 512 early preterm infants ( Results

  11. Exploring the associations between intimate partner violence victimization during pregnancy and delayed entry into prenatal care: Evidence from a population-based study in Bangladesh.

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    Islam, Md Jahirul; Broidy, Lisa; Baird, Kathleen; Mazerolle, Paul

    2017-04-01

    Intimate partner violence (IPV) during pregnancy can have serious health consequences for mothers and newborns. The aim of the study is to explore: 1) the influence of experiencing IPV during pregnancy on delayed entry into prenatal care; and 2) whether women's decision-making autonomy and the support for traditional gender roles act to mediate or moderate the relationship between IPV and delayed entry into prenatal care. cross-sectional survey. Multivariate logistic regression models were estimated that control for various socio-demographic and pregnancy related factors to assess whether women who experienced IPV during pregnancy were more likely to delay entry into prenatal care compared with women who had not experienced IPV. The influence of traditional gender roles acceptance and decision-making autonomy were examined both as independent variables and in interaction with IPV, to assess their role as potential mediators or moderators. Chandpur district, Bangladesh. the sample comprised of 426 Bangladeshi women, aged 15-49 years. Postpartum mothers who visited vaccinations centres to receive their children's vaccinations constitute the sampling frame. almost 70% of the women surveyed reported patterns consistent with delayed entry into prenatal care. Accounting for the influence of other covariates, women who experienced physical IPV during pregnancy were 2.61 times more likely (95% CI [1.33, 5.09]) to have delayed entry into prenatal care than their counterparts who did not report physical IPV. Neither sexual nor psychological IPV victimization during pregnancy was linked with late entry into prenatal care. Both gender role attitudes and levels of autonomy mediate the effect of IPV on prenatal care. the results suggest that the high rates of IPV in Bangladesh have effects that can compromise women's health seeking behaviour during pregnancy, putting them and their developing fetus at risk. Specifically, Bangladeshi women who experience physical IPV during

  12. Express attentional re-engagement but delayed entry into consciousness following invalid spatial cues in visual search.

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    Benoit Brisson

    Full Text Available BACKGROUND: In predictive spatial cueing studies, reaction times (RT are shorter for targets appearing at cued locations (valid trials than at other locations (invalid trials. An increase in the amplitude of early P1 and/or N1 event-related potential (ERP components is also present for items appearing at cued locations, reflecting early attentional sensory gain control mechanisms. However, it is still unknown at which stage in the processing stream these early amplitude effects are translated into latency effects. METHODOLOGY/PRINCIPAL FINDINGS: Here, we measured the latency of two ERP components, the N2pc and the sustained posterior contralateral negativity (SPCN, to evaluate whether visual selection (as indexed by the N2pc and visual-short term memory processes (as indexed by the SPCN are delayed in invalid trials compared to valid trials. The P1 was larger contralateral to the cued side, indicating that attention was deployed to the cued location prior to the target onset. Despite these early amplitude effects, the N2pc onset latency was unaffected by cue validity, indicating an express, quasi-instantaneous re-engagement of attention in invalid trials. In contrast, latency effects were observed for the SPCN, and these were correlated to the RT effect. CONCLUSIONS/SIGNIFICANCE: Results show that latency differences that could explain the RT cueing effects must occur after visual selection processes giving rise to the N2pc, but at or before transfer in visual short-term memory, as reflected by the SPCN, at least in discrimination tasks in which the target is presented concurrently with at least one distractor. Given that the SPCN was previously associated to conscious report, these results further show that entry into consciousness is delayed following invalid cues.

  13. Predictors of Delayed Entry into Medical Care of Children Diagnosed with HIV Infection: Data from an HIV Cohort Study in India

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    Gerardo Alvarez-Uria

    2013-01-01

    Full Text Available Data about the attrition before entry into care of children diagnosed with HIV in low- or middle-income countries are scarce. The aim of this study is to describe the attrition before engagement in HIV medical care in 523 children who were diagnosed with HIV from 2007 to 2012 in a cohort study in India. The cumulative incidence of children who entered into care was 87.2% at one year, but most children who did not enter into care within one year were lost to followup. The mortality before entry into care was low (1.3% at one year and concentrated during the first three months after HIV diagnosis. Factors associated with delayed entry into care were being diagnosed after mother’s HIV diagnosis, belonging to scheduled castes, age 90 minutes from the HIV centre. Children whose parents were alive and were living in a rented house were at a higher risk of delayed entry into care than those who were living in an owned house. The results of this study can be used to improve the linkage between HIV testing and HIV care of children diagnosed with HIV in India.

  14. Factors associated with delayed entry into HIV medical care after HIV diagnosis in a resource-limited setting: Data from a cohort study in India

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    Gerardo Alvarez-Uria

    2013-06-01

    Full Text Available Studies from sub-Saharan Africa have shown that a substantial proportion of patients diagnosed with HIV enter into HIV medical care late. However, data from low or middle-income countries outside Africa are scarce. In this study, we investigated risk factors associated with delayed entry into care stratified by gender in a large cohort study in India. 7701 patients were diagnosed with HIV and 5410 entered into care within three months of HIV diagnosis. Nearly 80% entered into care within a year, but most patients who did not enter into care within a year remained lost to follow up or died. Patient with risk factors related to having a low socio-economic status (poverty, being homeless, belonging to a disadvantaged community and illiteracy were more likely to enter into care late. In addition, male gender and being asymptomatic at the moment of HIV infection were factors associated with delayed entry into care. Substantial gender differences were found. Younger age was found to be associated with delayed entry in men, but not in women. Widows and unmarried men were more likely to enter into care within three months. Women belonging to disadvantaged communities or living far from a town were more likely to enter into care late. The results of this study highlight the need to improve the linkage between HIV diagnosis and HIV treatment in India. HIV programmes should monitor patients diagnosed with HIV until they engage in HIV medical care, especially those at increased risk of attrition.

  15. A delay prior to mitotic entry triggers caspase 8-dependent cell death in p53-deficient Hela and HCT-116 cells.

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    Silva, Victoria C; Plooster, Melissa; Leung, Jessica C; Cassimeris, Lynne

    2015-01-01

    Stathmin/Oncoprotein 18, a microtubule destabilizing protein, is required for survival of p53-deficient cells. Stathmin-depleted cells are slower to enter mitosis, but whether delayed mitotic entry triggers cell death or whether stathmin has a separate pro-survival function was unknown. To test these possibilities, we abrogated the cell cycle delay by inhibiting Wee1 in synchronized, stathmin-depleted cells and found that apoptosis was reduced to control levels. Synchronized cells treated with a 4 hour pulse of inhibitors to CDK1 or both Aurora A and PLK1 delayed mitotic entry and apoptosis was triggered only in p53-deficient cells. We did not detect mitotic defects downstream of the delayed mitotic entry, indicating that cell death is activated by a mechanism distinct from those activated by prolonged mitotic arrest. Cell death is triggered by initiator caspase 8, based on its cleavage to the active form and by rescue of viability after caspase 8 depletion or treatment with a caspase 8 inhibitor. In contrast, initiator caspase 9, activated by prolonged mitotic arrest, is not activated and is not required for apoptosis under our experimental conditions. P53 upregulates expression of cFLIPL, a protein that blocks caspase 8 activation. cFLIPL levels are lower in cells lacking p53 and these levels are reduced to a greater extent after stathmin depletion. Expression of FLAG-tagged cFLIPL in p53-deficient cells rescues them from apoptosis triggered by stathmin depletion or CDK1 inhibition during G2. These data indicate that a cell cycle delay in G2 activates caspase 8 to initiate apoptosis specifically in p53-deficient cells.

  16. Cell entry of bovine ephemeral fever virus requires activation of Src-JNK-AP1 and PI3K-Akt-NF-κB pathways as well as Cox-2-mediated PGE2 /EP receptor signalling to enhance clathrin-mediated virus endocytosis.

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    Cheng, Ching-Yuan; Huang, Wei-Ru; Chi, Pei-I; Chiu, Hung-Chuan; Liu, Hung-Jen

    2015-07-01

    Although we have previously demonstrated that cell entry of bovine ephemeral fever virus (BEFV) follows a clathrin-mediated and dynamin 2-dependent endocytosis pathway, the cellular mechanism mediating virus entry remains unknown. Here, we report that BEFV triggers simultaneously Src-JNK-AP1 and PI3K-Akt-NF-κB signalling pathways in the stage of virus binding to induce clathrin and dynamin 2 expressions, while vesicular stomatitis virus only activates Src-JNK signalling to enhance its entry. Activation of these pathways by ultraviolet-inactivated BEFV suggests a role for virus binding but not viral internalization and gene expression. By blocking these signalling pathways with specific inhibitors, BEFV-induced expressions of clathrin and dynamin 2 were significantly diminished. By labelling BEFV with 3,3'-dilinoleyloxacarbocyanine perchlorate to track viral entry, we found that virus entry was hindered by both Src and Akt inhibitors, suggesting that these signalling pathways are crucial for efficient virus entry. In addition, BEFV also triggers Cox-2-catalysed prostaglandin E2 (PGE2) synthesis and induces expressions of G-protein-coupled E-prostanoid (EP) receptors 2 and 4, leading to amplify signal cascades of Src-JNK-AP1 and PI3K-Akt-NF-κB, which elevates both clathrin and dynamin 2 expressions. Furthermore, pretreatment of cells with adenylate cyclase (cAMP) inhibitor SQ22536 reduced BEFV-induced Src phosphorylation as well as clathrin and dynamin 2 expressions. Our findings reveal for the first time that BEFV activates the Cox-2-mediated PGE2/EP receptor signalling pathways, further enhancing Src-JNK-AP1 in a cAMP-dependent manner and PI3K-Akt-NF-κB in a cAMP-independent manner. Accordingly, BEFV stimulates PGE2/EP receptor signalling amplifying Src-JNK-AP1 and PI3K-Akt-NF-κB pathways in an autocrine or paracrine fashion to enhance virus entry. © 2015 John Wiley & Sons Ltd.

  17. Delayed entry into first marriage and marital stability: Further evidence on the Becker-Landes-Michael hypothesis

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    Evelyn Lehrer

    2013-09-01

    Full Text Available BACKGROUND In their pioneering research, Becker, Landes, and Michael (1977 found that beyond age 30 there is a positive relationship between women's age at first marriage and marital instability. They interpreted this finding as a "poor-match effect" emerging when the biological clock begins to tick. OBJECTIVE Our objective was to ascertain with more recent data whether or not there is evidence of a poor match effect and if so, whether it is associated with higher marital instability. METHODS We used data on non-Hispanic white women from the 2006-2010 National Surveys of Family Growth (NSFG (N = 3,184. RESULTS We found evidence of the existence of a poor-match effect: women who delay marriage disproportionately make unconventional matches, which are generally associated with high marital instability. We also found, however, that their unions are very solid. Both of these results were consistent with earlier findings for the 1995 and 2002-2003 NSFG cycles. In attempting to explain this puzzle, we proposed and tested competing hypotheses. We found that the destabilizing effects associated with indicators of unconventional matches are also present in marriages contracted late, but are dwarfed by the stabilizing influences associated with higher levels of education and older ages. CONCLUSIONS This paper contributes to our understanding of the determinants of marital instability and the poor match effect by providing a new interpretation for the puzzle described above. COMMENTS Our findings have implications for analyses of changes over time in the extent of positive assortative mating in the marriage market, and for the extensive literature showing that heterogamy in traits that are complementary in the context of marriage is destabilizing -- heterogamous marriages contracted at a late age are likely to be stable.

  18. Hair Regenerative Mechanisms of Red Ginseng Oil and Its Major Components in the Testosterone-Induced Delay of Anagen Entry in C57BL/6 Mice

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    Van-Long Truong

    2017-09-01

    Full Text Available Hair loss (alopecia is a universal problem for numerous people in the world. The present study was conducted to investigate the effects of red ginseng oil (RGO and its major components on hair re-growth using testosterone (TES-induced delay of anagen entry in C57BL/6 mice and their mechanisms of action. Seven-week-old C57BL/6 mice were daily treated with TES for 1 h prior to topical application of 10% RGO, 1% linoleic acid (LA, 1% β-sitosterol (SITOS, or 1% bicyclo(10.1.0tridec-1-ene (BICYCLO once a day for 28 days. Hair regenerative capacity was significantly restored by treatment of RGO and its major compounds in the TES-treated mice. Histological analysis showed that RGO along with LA and SITOS but not BICYCLO promoted hair growth through early inducing anagen phase that was delayed by TES in mice. Treatment of mice with RGO, LA, or SITOS up-regulated Wnt/β-catenin and Shh/Gli pathways-mediated expression of genes such as β-catenin, Lef-1, Sonic hedgehog, Smoothened, Gli-1, Cyclin D1, and Cyclin E in the TES-treated mice. In addition, RGO and its major components reduced the protein level of TGF-β but enhanced the expression of anti-apoptotic protein Bcl-2. These results suggest that RGO is a potent novel therapeutic natural product for treatment of androgenic alopecia possibly through hair re-growth activity of its major components such as LA and SITOS.

  19. Patterns and Trends of Delayed Entry into Postsecondary Education: 1972, 1980, and 1982 High School Graduates. E.D. TABS. National Longitudinal Study 1972. High School and Beyond.

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    Eagle, Eva; Schmitt, Carl

    The data presented in this Department of Education (ED) Tabulation compare how the 1972, 1980, and 1982 high school graduate cohorts differ by type of program, type of institution, and time of entry into postsecondary education (PE). Three tables provide information for each cohort on enrollment in PE by type of postsecondary institution. Three…

  20. An Analysis of the Relationship between Student Success and Delayed Entry into the Mathematics Curriculum Following Completion of the Matriculation Process at Saddleback College.

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    Sworder, Steven

    In 1989, a study was conducted at Saddleback College (SC) to analyze the success rates of students who delayed enrollment into a mathematics class after completing the assessment process. The study population consisted of 1,027 students who participated in the mathematics assessment process between July and August 1988 and who enrolled in at least…

  1. Properties of spatial Cox process models

    DEFF Research Database (Denmark)

    Møller, Jesper

    Probabilistic properties of Cox processes of relevance for statistical modelling and inference are studied. Particularly, we study the most important classes of Cox processes, including log Gaussian Cox processes, shot noise Cox processes, and permanent Cox processes. We consider moment propertie...

  2. Membrane fusion during poxvirus entry.

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    Moss, Bernard

    2016-12-01

    Poxviruses comprise a large family of enveloped DNA viruses that infect vertebrates and invertebrates. Poxviruses, unlike most DNA viruses, replicate in the cytoplasm and encode enzymes and other proteins that enable entry, gene expression, genome replication, virion assembly and resistance to host defenses. Entry of vaccinia virus, the prototype member of the family, can occur at the plasma membrane or following endocytosis. Whereas many viruses encode one or two proteins for attachment and membrane fusion, vaccinia virus encodes four proteins for attachment and eleven more for membrane fusion and core entry. The entry-fusion proteins are conserved in all poxviruses and form a complex, known as the Entry Fusion Complex (EFC), which is embedded in the membrane of the mature virion. An additional membrane that encloses the mature virion and is discarded prior to entry is present on an extracellular form of the virus. The EFC is held together by multiple interactions that depend on nine of the eleven proteins. The entry process can be divided into attachment, hemifusion and core entry. All eleven EFC proteins are required for core entry and at least eight for hemifusion. To mediate fusion the virus particle is activated by low pH, which removes one or more fusion repressors that interact with EFC components. Additional EFC-interacting fusion repressors insert into cell membranes and prevent secondary infection. The absence of detailed structural information, except for two attachment proteins and one EFC protein, is delaying efforts to determine the fusion mechanism.

  3. Properties of spatial Cox process models

    DEFF Research Database (Denmark)

    Møller, Jesper

    2005-01-01

    Particularly, we study the most important classes of Cox processes, including log Gaussian Cox processes, shot noise Cox processes, and permanent Cox processes. We consider moment properties and point process operations such as thinning, displacements, and super positioning. We also discuss how t...

  4. COX-2 Inhibitors and Gastric Cancer

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    Zhen Wang

    2014-01-01

    Full Text Available The evidence that cyclooxygenase-2 (COX-2 is upregulated and plays an important role in carcinogenesis of gastric cancer has triggered the topic of COX-2 inhibitors as chemopreventive agents for gastric cancer. Studies find that COX-2 inhibitors are associated not only with chemoprophylactic effects, but also with chemotherapeutic potentials in gastric cancer. Both COX-dependent and COX-independent pathways have a role in the anticancer efficiency of COX-2 inhibitors. However, enthusiasm is thwarted by the potential toxicity, that is, gastrointestinal toxicity of nonselective COX-2 inhibitors and cardiovascular risk of selective COX-2 inhibitors. Therefore, more studies are needed to develop new targeted antitumor agents (such as prostaglandin E receptor antagonist and to define fundamental questions such as optimal treatment regimens, integration of cotherapy, and careful selection of candidates.

  5. Decomposition of variance for spatial Cox processes

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    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    2013-01-01

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models...

  6. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introducea general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with additive...

  7. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models...

  8. Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis

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    Richard Dela Cruz

    2016-06-01

    Full Text Available Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. We recovered independent colonies that propagated on glycerol/lactate medium for cox23∆ cells at 37°C. We mapped these mutations to the mitochondrial genome and specifically to COX1 yielding an I101F substitution. The I101F Cox1 allele is a gain-of-function mutation enabling yeast to respire in the absence of Cox23. CcO subunit steady-state levels were restored with the I101F Cox1 suppressor mutation and oxygen consumption and CcO activity were likewise restored. Cells harboring the mitochondrial genome encoding I101F Cox1 were used to delete genes for other CcO assembly factors to test the specificity of the Cox1 mutation as a suppressor of cox23∆ cells. The Cox1 mutant allele fails to support respiratory growth in yeast lacking Cox17, Cox19, Coa1, Coa2, Cox14 or Shy1, demonstrating its specific suppressor activity for cox23∆ cells.

  9. US Ports of Entry

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    Department of Homeland Security — HSIP Non-Crossing Ports-of-Entry A Port of Entry is any designated place at which a CBP officer is authorized to accept entries of merchandise to collect duties, and...

  10. COX-1 and COX-2 expression in feline oral squamous cell carcinoma.

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    Hayes, A; Scase, T; Miller, J; Murphy, S; Sparkes, A; Adams, V

    2006-01-01

    This study demonstrated immunohistochemically the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in feline oral squamous cell carcinoma (FOSCC), with primary polyclonal antibodies raised against human epitopes. COX-2 immunolabelling was intracytoplasmic and, in some neoplastic cells, perinuclear; it was demonstrated in a small proportion (tissues showed extensive nuclear and cytoplasmic COX-1 immunolabelling. Cytoplasmic COX-1 immunolabelling was less intense than nuclear labelling in neoplastic tissue. In the adjacent histologically normal oral mucosa, COX-2 immunolabelling was absent. The cytoplasmic and nuclear intensity and distribution of COX-1 immunolabelling was significantly higher in neoplastic tissue than in adjacent normal oral mucosa. The results indicate that COX-1 and COX-2 are overexpressed in FOSCC, but the clinical and pathophysiological significance of this finding remains to be determined.

  11. Cyclooxygenase (COX) Inhibitors and the Newborn Kidney

    OpenAIRE

    Wei Qi; Smith, Francine G.; Megan L. Lewis; Wade, Andrew W

    2012-01-01

    This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role...

  12. Digestive disease and COX - 1, COX - 2%COX-1和COX-2抑制剂与胃肠道疾病

    Institute of Scientific and Technical Information of China (English)

    李文晰; 梅冬艳; 段芳龄

    2001-01-01

    @@ COX(cvclo-oxygenase)有两种异构体:COX-1和COX-2,阿斯匹林和其它NSAIDs既有消炎镇痛作用也有较多的副作用,主要是由于其抑制COX的非选择性,因而较少副作用的选择性COX抑制剂(抑制COX异构体COX-2)在近几年越来越受到人们重视,这些药物有meloxicam、nimesulin、celecoxib、etodolac、尼美舒利(nimesulide)等.

  13. Design, Synthesis, and Evaluation of New Tripeptides as COX-2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Ermelinda Vernieri

    2013-01-01

    Full Text Available Cyclooxygenase (COX is a key enzyme in the biosynthetic pathway leading to the formation of prostaglandins, which are mediators of inflammation. It exists mainly in two isoforms COX-1 and COX-2. The conventional nonsteroidal anti-inflammatory drugs (NSAIDs have gastrointestinal side effects because they inhibit both isoforms. Recent data demonstrate that the overexpression of these enzymes, and in particular of cyclooxygenases-2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that the inhibition of cyclooxygenases-2 can delay or prevent certain forms of cancer. Agents that inhibit COX-2 while sparing COX-1 represent a new attractive therapeutic development and offer a new perspective for a further use of COX-2 inhibitors. The present study extends the evaluation of the COX activity to all 203 possible natural tripeptide sequences following a rational approach consisting in molecular modeling, synthesis, and biological tests. Based on data obtained from virtual screening, only those peptides with better profile of affinity have been selected and classified into two groups called S and E. Our results suggest that these novel compounds may have potential as structural templates for the design and subsequent development of the new selective COX-2 inhibitors drugs.

  14. COX-1 and COX-2 expression in canine cutaneous, oral and ocular melanocytic tumours.

    Science.gov (United States)

    Pires, I; Garcia, A; Prada, J; Queiroga, F L

    2010-01-01

    In order to evaluate the potential value of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of canine malignant melanoma, expression of cyclooxygenase (COX)-1 and COX-2 was determined in 20 cutaneous, nine oral and two ocular malignant melanomas, and in nine cutaneous melanocytomas. Almost all tumours expressed COX-1, but COX-2 expression was restricted to the malignant tumours being found in 11 of the 20 cutaneous malignant melanomas, all oral malignant melanomas and in one of two ocular malignant melanomas. COX-1 expression did not differ significantly between benign and malignant skin lesions, but COX-2 expression was significantly greater in cutaneous malignant melanoma compared with melanocytoma (P=0.047). COX-2 labelling was particularly intense in the more highly malignant oral tumours. The results of the study suggest that NSAIDs, particularly COX-2 inhibitors, may be useful in the treatment of canine malignant melanoma.

  15. Palm distributions for log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Coeurjolly, Jean-Francois; Møller, Jesper; Waagepetersen, Rasmus

    This paper reviews useful results related to Palm distributions of spatial point processes and provides a new result regarding the characterization of Palm distributions for the class of log Gaussian Cox processes. This result is used to study functional summary statistics for a log Gaussian Cox...

  16. Entry into the Postparental Phase of the Family Life Cycle

    Directory of Open Access Journals (Sweden)

    Barbara Wawrzyniak

    2015-02-01

    Full Text Available Der Originalbeitrag in deutscher Sprache ist verfügbar unter: Bd. 40 (2015: Ausgewählte deutsche BeiträgeThe article examines entry into the postparental phase of the family life cycle, which is the familial situation when all children have moved out of the parental household. We position this event chronologically within the life course and examine the probability of occurrence. Using panel data (3 survey waves covering a period of 40 years of a cohort of former North-Rhine Westphalian grammar school pupils, event history models (Cox regression are employed to analyse what factors accelerate or decelerate the transition. This revealed that the parent’s individual biography (in particular the age at the own move out, age at the birth of the first child and the number of children has a major impact on the time of occurrence, while the occupational history has no effect. In addition, sons delay the transition, while children’s academic studies and occupation accelerate it.

  17. Cyclooxygenase (COX Inhibitors and the Newborn Kidney

    Directory of Open Access Journals (Sweden)

    Wei Qi

    2012-10-01

    Full Text Available This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2 plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function.

  18. An Exponential Bound for Cox Regression☆

    Science.gov (United States)

    Kosorok, M. R.

    2012-01-01

    We present an asymptotic exponential bound for the deviation of the survival function estimator of the Cox model. We show that the bound holds even when the proportional hazards assumption does not hold. PMID:23565013

  19. An Exponential Bound for Cox Regression.

    Science.gov (United States)

    Goldberg, Y; Kosorok, M R

    2012-07-01

    We present an asymptotic exponential bound for the deviation of the survival function estimator of the Cox model. We show that the bound holds even when the proportional hazards assumption does not hold.

  20. Is COX-2 a perpetrator or a protector? Selective COX-2 inhibitors remain controversial

    Institute of Scientific and Technical Information of China (English)

    Cheng LUO; Ming-liang HE; Lars BOHLIN

    2005-01-01

    Aim: COX-2(cyclooxygenase-2) has sparked a surge in pharmaceutical interest since its discovery at the beginning of the 1990s. Several COX-2 selective inhibitors that avoid gastrointestinal side effects have been successfully launched into the market in recent years. The first selective COX-2 inhibitor, celecoxib, entered the market in December 1999. However, there are a few organs that physiologically and functionally express COX-2, particularly the glomeruli of the kidney and the cortex of the brain. Inhibition of COX-2 expression in these organs possibly causes heart attack and stroke in long-term COX-2 inhibitor users. Recently, a USA Food and Drug Agency (FDA) advisory panel re-evaluated COX-2 inhibitors and unanimously concluded that the entire class of COX-2 inhibitors increase the risk of cardiovascular problems. Thus the use of COX-2 inhibitors is still controversial, and there is a challenge for not only pharmacologists, but also the pharmaceutical industry, to develop improved painkilling and anti-inflammatory drugs. This may involve exploring a new generation of COX-2 inhibitors with different inhibitory mechanisms through computer-aided design, screening different sources of inhibitors with lower Selectivity, or seeking completely new targets.Synthetic COX-2 inhibitors have high selectivity and the advantage of irreversible inhibition, whereas naturally derived COX-2 inhibitors have lower selectivity and fewer side effects, with the medical effects in general not being as striking as those achieved using synthetic inhibitors. This review discusses the mechanism of COX-2 inhibitor therapy and a possible new way of exploration in the development of anti-inflammatory, analgetic, and antipyretic drugs.

  1. COX-2, VEGF and tumour angiogenesis.

    LENUS (Irish Health Repository)

    Toomey, D P

    2009-06-01

    Epidemiological evidence suggests a protective effective of regular NSAID use against developing cancer. Cyclooxygenase-2, a target of NSAIDs, is upregulated in many cancers and has been associated with increased VEGF production and angiogenesis. Angiogenesis is the formation of new vessels from existing vasculature and as an essential process for tumour development represents an important therapeutic target. Following an extensive review of the literature this article details the current knowledge on the role of COX-2 in tumorigenesis focusing on its relationship to angiogenesis and VEGF production by tumour cells. While COX-2 is clearly detrimental to prognosis and NSAIDs have a beneficial effect, the possibility of COX-2 independent effects being partly or wholly responsible for this benefit cannot be excluded.

  2. DLMS Voice Data Entry.

    Science.gov (United States)

    1980-06-01

    between operator and computer displayed on ADM-3A 20c A-I Possible Hardware Configuration for a Multistation Cartographic VDES ...this program a Voice Recognition System (VRS) which can be used to explore the use of voice data entry ( VDE ) in the DIMS or other cartographic data...Multi-Station Cartographic Voice Data Entry System An engineering development model voice data entry system ( VDES ) could be most efficiently

  3. Entry at Venus

    Science.gov (United States)

    Venkatapathy, Ethiraj; Smith, Brandon

    2016-01-01

    This is lecture to be given at the IPPW 2016, as part of the 2 day course on Short Course on Destination Venus: Science, Technology and Mission Architectures. The attached presentation material is intended to be introduction to entry aspects of Venus in-situ robotic missions. The presentation introduces the audience to the aerodynamic and aerothermodynamic aspects as well as the loads, both aero and thermal, generated during entry. The course touches upon the system design aspects such as TPS design and both high and low ballistic coefficient entry system concepts that allow the science payload to be protected from the extreme entry environment and yet meet the mission objectives.

  4. Pharmacologic inhibition of COX-1 and COX-2 in influenza A viral infection in mice.

    Directory of Open Access Journals (Sweden)

    Michelle A Carey

    Full Text Available BACKGROUND: We previously demonstrated that cyclooxygenase (COX-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560, a COX-2 inhibitor (celecoxib or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.

  5. Double entry bookkeeping vs single entry bookkeeping

    Directory of Open Access Journals (Sweden)

    Ileana Andreica

    2016-11-01

    Full Text Available Abstract: A financial management eficiently begin, primarily, with an accounting record kept in the best possible conditions, this being conditioned on the adoption of a uniform forms, rational, clear and simple accounting. Throughout history, there have been known two forms of accounting: the simple and double entry. Romanian society after 1990 underwent a substantial change in social structure, the sector on which put a great emphasis being private, that of small manufacturers, peddler, freelance, who work independently and authorized or as associative form (family enterprises, various associations (owners, tenants, etc., liberal professions, etc.. They are obliged to keep a simple bookkeeping, because they have no juridical personality. Companies with legal personality are required to keep double entry bookkeeping; therefore, knowledge and border demarcation between the two forms of organisation of accounting is an essential. The material used for this work is mainly represented by the financial and accounting documents, by the analysis of the economic, by legislative updated sources, and as the method was used the comparison method, using hypothetical data, in case of an authorized individual and a legal entity. Based on the chosen material, an authorized individual (who perform single entry accounting system and a juridical entity (who perform double entry accounting system were selected comparative case studies, using hypothetical data, were analysed advantages and disadvantages in term of fiscal, if using two accounting systems, then were highlighted some conclusion that result.

  6. The Mitochondrial Genome of Conus textile, coxI-coxII Intergenic Sequences and Conoidean Evolution

    OpenAIRE

    2007-01-01

    The cone snails belong to the superfamily Conoidea, comprising ∼10,000 venomous marine gastropods. We determined the complete mitochondrial DNA sequence of Conus textile. The gene order is identical in Conus textile, Lophiotoma cerithiformis (another Conoidean gastropod), and the neogastropod Ilyanassa obsoleta, (not in the superfamily Conoidea). However, the intergenic interval between the coxI/coxII genes, was much longer in C. textile (165 bp) than in any other previously analyzed gastropo...

  7. Randomized controlled trials of COX-2 inhibitors

    DEFF Research Database (Denmark)

    Stefansdottir, Gudrun; De Bruin, Marie L; Knol, Mirjam J

    2011-01-01

    BACKGROUND: Naproxen, ibuprofen and diclofenac are frequently used as comparators in randomized controlled trials (RCTs) on the safety and efficacy of cyclooxygenase (COX)-2 inhibitors. Different comparator doses may influence the results of RCTs. It has been hypothesized that RCTs of COX-2...... 1995 and 2009 in which celecoxib or rofecoxib were compared with naproxen, ibuprofen or diclofenac. All articles labelled as RCTs mentioning rofecoxib or celecoxib and one or more of the comparator drugs in the title and/or abstract were included. We extracted information on doses of both non...... dose trends in the case of rofecoxib. CONCLUSIONS: Although the dose trends over time differed for RCTs comparing rofecoxib and celecoxib with diclofenac, ibuprofen or naproxen, the results of our study do not support the hypothesis that dose trends influenced the decision to continue marketing...

  8. Delayed Puberty

    DEFF Research Database (Denmark)

    Kolby, Nanna; Busch, Alexander Siegfried; Juul, Anders

    2017-01-01

    Delayed puberty can be a source of great concern and anxiety, although it usually is caused by a self-limiting variant of the normal physiological timing named constitutional delay of growth and puberty (CDGP). Delayed puberty can, however, also be the first presentation of a permanent condition ...... mineral density) and psychological (e.g., low self-esteem) and underline the importance of careful clinical assessment of the patients.......Delayed puberty can be a source of great concern and anxiety, although it usually is caused by a self-limiting variant of the normal physiological timing named constitutional delay of growth and puberty (CDGP). Delayed puberty can, however, also be the first presentation of a permanent condition...

  9. Delayed fission

    Energy Technology Data Exchange (ETDEWEB)

    Hatsukawa, Yuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-07-01

    Delayed fission is a nuclear decay process that couples {beta} decay and fission. In the delayed fission process, a parent nucleus undergoes {beta} decay and thereby populates excited states in the daughter. If these states are of energies comparable to or greater than the fission barrier of the daughter, then fission may compete with other decay modes of the excited states in the daughter. In this paper, mechanism and some experiments of the delayed fission will be discussed. (author)

  10. Shuttle entry guidance

    Science.gov (United States)

    Harpold, J. C.; Graves, C. A., Jr.

    1978-01-01

    This paper describes the design of the entry guidance for the Space Shuttle Orbiter. This guidance provides the steering commands for trajectory control from initial penetration of the earth's atmosphere until the terminal area guidance is activated at an earth-relative speed of 2500 fps. At this point, the Orbiter is at a distance of about 50 nmi from the runway threshold, and at an altitude of about 80,000 ft. The entry guidance design is based on an analytic solution of the equations of motion defining the drag acceleration profile that meets the terminal criteria of the entry flight while maintaining the flight within systems and operational constraints. Guidance commands, which are based on a control law that ensures damping of oscillatory type trajectory motion, are computed to steer the Orbiter to this drag acceleration profile.

  11. Acute upregulation of COX-2 by renal artery stenosis

    DEFF Research Database (Denmark)

    Mann, Birgitte; Hartner, A; Jensen, B L

    2001-01-01

    This study aimed to characterize the influence of acute renal artery stenosis on cyclooxygenase-2 (COX-2) and renin expression in the juxtaglomerular apparatus. For this purpose, male Sprague-Dawley rats received a left renal artery clip, and COX-2 mRNA, COX-2 immunoreactivity, plasma renin...... causal relationship between the changes of COX-2 and of renin expression, clipped rats were treated with the COX-2 blocker celecoxib (40 mg. kg(-1). day(-1)). This treatment, however, did not change renin mRNA either in the clipped or in the contralateral intact kidney. Our findings indicate that renal...... artery stenosis causes ipsilaterally an acute upregulation and contralaterally a downregulation of juxtaglomerular COX-2 expression. The lacking effect of celecoxib on renin gene expression does not support the concept of a direct mediator function of COX-2-derived prostaglandins in the control of renin...

  12. Acute upregulation of COX-2 by renal artery stenosis

    DEFF Research Database (Denmark)

    Mann, Birgitte; Hartner, A; Jensen, B L

    2001-01-01

    This study aimed to characterize the influence of acute renal artery stenosis on cyclooxygenase-2 (COX-2) and renin expression in the juxtaglomerular apparatus. For this purpose, male Sprague-Dawley rats received a left renal artery clip, and COX-2 mRNA, COX-2 immunoreactivity, plasma renin...... activity, and renin mRNA levels were determined. COX-2 mRNA and COX-2 immunoreactivity in the macula densa region in the clipped kidneys increased as early as 6 h after clipping and reached a maximal expression 1-2 days after clipping. Although values for plasma renin activity were elevated markedly at all...... artery stenosis causes ipsilaterally an acute upregulation and contralaterally a downregulation of juxtaglomerular COX-2 expression. The lacking effect of celecoxib on renin gene expression does not support the concept of a direct mediator function of COX-2-derived prostaglandins in the control of renin...

  13. Differentials of Cox rings: Jaczewski's theorem revisited

    CERN Document Server

    Kedzierski, Oskar

    2011-01-01

    A generalized Euler sequence over a complete normal variety X is the unique "identity" extension of the trivial bundle H^1(X,\\Omega_X) \\otimes O_X by the sheaf of differentials \\Omega_X. We prove that, if X is a smooth Mori Dream Space and the bundle arising from the Euler sequence splits into a direct sum of line bundles, then X is a toric variety. The proof of this characterization of toric varieties depends on a somewhat more general result which, in the case of a Mori Dream Space, identifies the module of sections of the twisted sheaf coming from the Euler extension with the module of differentials of the Cox ring of the variety in question.

  14. HER2 and COX2 expression in human prostate cancer.

    Science.gov (United States)

    Edwards, J; Mukherjee, R; Munro, A F; Wells, A C; Almushatat, A; Bartlett, J M S

    2004-01-01

    COX2 and HER2 expression are associated with a poor prognosis in prostate cancer and HER2 has been linked to COX2 expression in colorectal cancer. The association between COX2 and HER2 expression was investigated in 117 patients with prostate cancer (89) or Benign prostatic hyperplasia (BPH) (28). Tissue was analysed for HER2 amplification by fluorescent in situ hybridisation, and HER2 and COX2 protein expression by immunohistochemistry (IHC). All tumours analysed expressed COX2 at a significantly higher level than BPH tissue (P=0.041). Only low levels of HER2 gene amplification (8%, 7/89) and HER2 protein expression (12%, 11/89) were observed. HER2 protein expression was rarely observed and did not correlate with HER2 amplification or COX2 expression. Although HER2 does not drive COX2 expression in prostate cancer, this study identified high levels of COX2 expressed in locally advanced prostate cancer, suggesting COX2 could be a potential therapeutic target. COX2 inhibitors are currently being used in clinical trials for the treatment of other tumour types.

  15. Binding Energy Calculation of Patchouli Alcohol Isomer Cyclooxygenase Complexes Suggested as COX-1/COX-2 Selective Inhibitor

    Directory of Open Access Journals (Sweden)

    Sentot Joko Raharjo

    2014-01-01

    Full Text Available To understand the structural features that dictate the selectivity of the two isoforms of the prostaglandin H2 synthase (PGHS/COX, the three-dimensional (3D structure of COX-1/COX-2 was assessed by means of binding energy calculation of virtual molecular dynamic with using ligand alpha-Patchouli alcohol isomers. Molecular interaction studies with COX-1 and COX-2 were done using the molecular docking tools by Hex 8.0. Interactions were further visualized by using Discovery Studio Client 3.5 software tool. The binding energy of molecular interaction was calculated by AMBER12 and Virtual Molecular Dynamic 1.9.1 software. The analysis of the alpha-Patchouli alcohol isomer compounds showed that all alpha-Patchouli alcohol isomers were suggested as inhibitor of COX-1 and COX-2. Collectively, the scoring binding energy calculation (with PBSA Model Solvent of alpha-Patchouli alcohol isomer compounds (CID442384, CID6432585, CID3080622, CID10955174, and CID56928117 was suggested as candidate for a selective COX-1 inhibitor and CID521903 as nonselective COX-1/COX-2.

  16. COX, LOX and platelet aggregation inhibitory properties of Lauraceae neolignans.

    Science.gov (United States)

    Coy, Ericsson David; Cuca, Luis Enrique; Sefkow, Michael

    2009-12-15

    The anti-inflammatory potential of 26 neolignans (14 of the bicyclooctane-type and 12 of the benzofuran-type), isolated from three Lauraceae species (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), was evaluated in vitro through inhibition of COX-1, COX-2, 5-LOX and agonist-induced aggregation of rabbit platelets. Benzofuran neolignans were found to be selective COX-2 inhibitors, whereas bicyclooctane neolignans inhibit selectively the PAF-action as well as COX-1 and 5-LOX. The neolignan 9-nor-7,8-dehydro-isolicarin B 15 and cinerin C 7 were found to be the most potent COX-2 inhibitor and PAF-antagonist, respectively. Nectamazin C 10 exhibited dual 5-LOX/COX-2 inhibition.

  17. Deployable Entry-system Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Deployable Entry-system ProjecT (ADEPT) will develop requirements for the ADEPT flight test.  Prior entry systems used high mass thermal protection...

  18. COX2 genetic variation, NSAIDs, and advanced prostate cancer risk

    OpenAIRE

    Cheng, I.; Liu, X.; Plummer, S J; Krumroy, L M; Casey, G; Witte, J S

    2007-01-01

    Collective evidence suggests that cyclooxygenase 2 (COX2) plays a role in prostate cancer risk. Cyclooxygenase 2 is the major enzyme that converts arachidonic acid to prostaglandins, which are potent mediators of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzymatic activity of COX2 and long-term use of NSAIDs appears to modestly lower the risk of prostate cancer. We investigated whether common genetic variation in COX2 influences the risk of advanced prostate canc...

  19. Consensus networks with time-delays over finite fields

    Science.gov (United States)

    Li, Xiuxian; Su, Housheng; Chen, Michael Z. Q.

    2016-05-01

    In this paper, we investigate the consensus problem in networks with time-delays over finite fields. The delays are categorised into three cases: single constant delay, multiple constant delays, and time-varying bounded delays. For all cases, some sufficient and necessary conditions for consensus are derived. Furthermore, assuming that the communication graph is strongly connected, some of the obtained necessary conditions reveal that the conditions for consensus with time-delays over finite fields depend not only on the diagonal entries but also on the off-diagonal entries, something that is intrinsically distinct from the case over real numbers (where having at least one nonzero diagonal entry is a sufficient and necessary condition to guarantee consensus). In addition, it is shown that delayed networks cannot achieve consensus when the interaction graph is a tree if the corresponding delay-free networks cannot reach consensus, which is consistent with the result over real numbers. As for average consensus, we show that it can never be achieved for delayed networks over finite fields, although it indeed can be reached under several conditions for delay-free networks over finite fields. Finally, networks with time-varying delays are discussed and one sufficient condition for consensus is presented by graph-theoretic method.

  20. Cox-2 inhibitors and the risk of cardiovascular thrombotic events.

    LENUS (Irish Health Repository)

    Khan, M

    2012-04-01

    In 1971, Vane showed that the analgesic action of traditional NSAIDs relies on inhibition of the cyclo-oxygenase (COX) enzyme, which in turn results in reduced synthesis of proalgesic prostaglandins. Two decades later COX was shown to exist as two distinct isoforms. The constitutive isoform COX-1, supports the beneficial homeostatic functions whereas the inducible isoform, COX-2 becomes up regulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis. Despite the benefits of NSAIDs for acute and chronic pain one of the most clinically significant and well characterized adverse effect is on GI mucosa. The search for NSAIDs with less gastrointestinal toxicity led to the introduction of the selective cyclo-oxygenase-2 (COX-2) inhibitors. The COX-2 selective (COX-1 sparing) inhibitors are associated with reduced GI mucosal damage as demonstrated in several trials. In light of the overwhelming and sometimes contradictory information for patients and physicians regarding the safety of COX-2 agents this article will summarize the available evidence regarding cardiovascular (CV) safety data and contemporary recommendations for prescribing of COX-2-selective NSAIDs.

  1. Re-entry and simulation

    Science.gov (United States)

    Jian, H.; Guangming, X.

    1983-11-01

    The physics of re-entry are discussed with emphasis on the re-entry trajectory of a ballistic missile. Factors discussed include re-entry speed, ablation, aerodynamic heating, and the plasma sheath shield. Experimental techniques used to simulate the aerodynamics and performance of missile systems include the computer, the wind tunnel, and free flight. Each of these is briefly discussed.

  2. Transport Properties of the Tunnel Junctions Al1-xCox/{Al1-xCox-oxide}/Al

    Institute of Scientific and Technical Information of China (English)

    X.F.Han; J. Murai; H.Kubota; Y.Ando; Q.Y.Wang; N.Tezuka; T.Miyazaki

    2000-01-01

    The oxides of Al1-xCox (x=0,0.25,0.5,0.75, and 1.0) alloys were chosen as barrier materials in this work. The tunnel junction consists of the bottom electrode Al1-xCox and the top electrode Al with an insulating layer { Al1-xCox-oxide} which was formed by natural oxidation in a baking-box at 333K. The oxidation time for forming an Al1-xCox-oxide layer on the surface of the bottom Al1-xCox layers were optimized.The resistance of Al1-xCox/{ Al1-xCox-oxide}/Al tunnel junctions varied between 101 and 106 Ω measured at 1 my and 4.2 K. The effective barrier height and width of insulating layers Al1-xCox-oxide ( x=0.25, 0.5, and 0.75 )varied between 0.6 and 2.7 eV and between 1.3 and 2.1 nm. It is shown that the thin oxide layer of Al1-xCox alloys can be chosen as barrier materials.

  3. The heme a synthase Cox15 associates with cytochrome c oxidase assembly intermediates during Cox1 maturation.

    Science.gov (United States)

    Bareth, Bettina; Dennerlein, Sven; Mick, David U; Nikolov, Miroslav; Urlaub, Henning; Rehling, Peter

    2013-10-01

    Cox1, the core subunit of the cytochrome c oxidase, receives two heme a cofactors during assembly of the 13-subunit enzyme complex. However, at which step of the assembly process and how heme is inserted into Cox1 have remained an enigma. Shy1, the yeast SURF1 homolog, has been implicated in heme transfer to Cox1, whereas the heme a synthase, Cox15, catalyzes the final step of heme a synthesis. Here we performed a comprehensive analysis of cytochrome c oxidase assembly intermediates containing Shy1. Our analyses suggest that Cox15 displays a role in cytochrome c oxidase assembly, which is independent of its functions as the heme a synthase. Cox15 forms protein complexes with Shy1 and also associates with Cox1-containing complexes independently of Shy1 function. These findings indicate that Shy1 does not serve as a mobile heme carrier between the heme a synthase and maturing Cox1 but rather cooperates with Cox15 for heme transfer and insertion in early assembly intermediates of cytochrome c oxidase.

  4. COX-2 is associated with periodontitis in Europeans

    NARCIS (Netherlands)

    Schaefer, A.S.; Richter, G.M.; Nothnagel, M.; Laine, M.L.; Noack, B.; Glas, J.; Schrezenmeir, J.; Groessner-Schreiber, B.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2010-01-01

    COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were

  5. On spatio-temporal Lévy based Cox processes

    DEFF Research Database (Denmark)

    Prokesova, Michaela; Hellmund, Gunnar; Jensen, Eva Bjørn Vedel

    2006-01-01

    The paper discusses a new class of models for spatio-temporal Cox point processes. In these models, the driving field is defined by means of an integral of a weight function with respect to a Lévy basis. The relations to other Cox process models studied previously are discussed and formulas for t...

  6. Extensions and Applications of the Cox-Aalen Survival Model

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2003-01-01

    Aalen additive risk model; competing risk; counting processes; Cox model; cumulative incidence function; goodness of fit; prediction of survival probability; time-varying effects......Aalen additive risk model; competing risk; counting processes; Cox model; cumulative incidence function; goodness of fit; prediction of survival probability; time-varying effects...

  7. COX-2 is associated with periodontitis in Europeans

    NARCIS (Netherlands)

    Schaefer, A.S.; Richter, G.M.; Nothnagel, M.; Laine, M.L.; Noack, B.; Glas, J.; Schrezenmeir, J.; Groessner-Schreiber, B.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2010-01-01

    COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were as

  8. Nuclear Chk1 prevents premature mitotic entry.

    Science.gov (United States)

    Matsuyama, Makoto; Goto, Hidemasa; Kasahara, Kousuke; Kawakami, Yoshitaka; Nakanishi, Makoto; Kiyono, Tohru; Goshima, Naoki; Inagaki, Masaki

    2011-07-01

    Chk1 inhibits the premature activation of the cyclin-B1-Cdk1. However, it remains controversial whether Chk1 inhibits Cdk1 in the centrosome or in the nucleus before the G2-M transition. In this study, we examined the specificity of the mouse monoclonal anti-Chk1 antibody DCS-310, with which the centrosome was stained. Conditional Chk1 knockout in mouse embryonic fibroblasts reduced nuclear but not centrosomal staining with DCS-310. In Chk1(+/myc) human colon adenocarcinoma (DLD-1) cells, Chk1 was detected in the nucleus but not in the centrosome using an anti-Myc antibody. Through the combination of protein array and RNAi technologies, we identified Ccdc-151 as a protein that crossreacted with DCS-310 on the centrosome. Mitotic entry was delayed by expression of the Chk1 mutant that localized in the nucleus, although forced immobilization of Chk1 to the centrosome had little impact on the timing of mitotic entry. These results suggest that nuclear but not centrosomal Chk1 contributes to correct timing of mitotic entry.

  9. Simultaneous abrogation of NOS-2 and COX-2 activities is lethal in partially hepatectomised mice.

    Science.gov (United States)

    Zeini, Miriam; Hortelano, Sonsoles; Través, Paqui G; Martín-Sanz, Paloma; Boscá, Lisardo

    2004-06-01

    We have investigated the role of the nitric oxide (NO) and prostaglandins (PGs), respectively, synthesized by nitric oxide synthase 2 (NOS-2) and cyclooxygenase-2 (COX-2), in the outcome of liver regeneration after partial hepatectomy (PH). Liver mass recovery and molecular parameters related to cell proliferation and apoptotic death have been determined. NOS-2 and COX-2 are normally both expressed in the remnant liver after PH, and inhibition of either one delays regeneration. We found, however, that simultaneous suppression of the activities of NOS-2 (by gene knockout) and COX-2 (by pharmacological inhibition) resulted in animal death between 24 and 72 h after PH. Analysis of liver mass recovery and molecular parameters related to cell proliferation and apoptotic death revealed increased liver-cell apoptosis and an insufficient proliferative response. Broad-specificity caspase inhibitors, such as z-Val-Ala-Asp.fmk (z-VAD), or administration of NO-donors, rescued animals from death, revealing a critical apoptotic bias at this stage of proliferation. These findings demonstrate that simultaneous signaling by NO and prostaglandins plays an important role in the mechanism of liver regeneration after PH by protecting the remnant tissue from apoptotic death.

  10. Radiolabeled COX-2 Inhibitors for Non-Invasive Visualization of COX-2 Expression and Activity — A Critical Update

    Directory of Open Access Journals (Sweden)

    Torsten Kniess

    2013-05-01

    Full Text Available Cyclooxygenase-2 (COX-2 is a key player in inflammation. Its overexpression is directly associated with various inflammatory diseases and, additionally, with several processes of carcinogenesis. The development of new selective COX-2 inhibitors (COXIBs for use in cancer treatment is in the focus of the medicinal chemistry research field. For this purpose, a set of methods is available to determine COX-2 expression and activity in vitro and ex vivo but it is still a problem to functionally characterize COX-2 in vivo. This review focusses on imaging agents targeting COX-2 which have been developed for positron emission tomography (PET and single photon emission computed tomography (SPECT since 2005. The literature reveals that different radiochemical methods are available to synthesize COXIBs radiolabeled with fluorine-18, carbon-11, and isotopes of radioiodine. Unfortunately, most of the compounds tested did not show sufficient stability in vivo due to de[18F]fluorination or de[11C]methylation or they failed to bind specifically in the target region. So, suitable stability in vivo, matching lipophilicity for the target compartment and both high affinity and selectivity for COX-2 were identified as prominent criteria for radiotracer development. Up to now, it is not clear what approach and which model is the most suited to evaluate COX-2 targeting imaging agents in vivo. However, for proof of principle it has been shown that some radiolabeled compounds can bind specifically in COX-2 overexpressing tissue which gives hope for future work in this field.

  11. Dynamics of Water Entry

    CERN Document Server

    Truscott, Tadd T; Techet, Alexandra H

    2008-01-01

    The hydrodynamics associated with water-entry of spheres can be highly variable with respect to the material and kinematic properties of the sphere. This series of five fluid dynamics videos illustrates several subtle but interesting variations that can be seen. The first series of videos contrasts the nature of impact ($Fr = U_o/\\sqrt{gd} = 5.15$) between a hydrophilic (wetting angle of $\\alpha$ = 60$^\\circ$) and hydrophobic sphere ($\\alpha$ = 120$^\\circ$), and illustrates how surface coating can affect whether or not an air cavity is formed; the views from the side and from above are synchronized in time. The second video series illustrates how spin and surface treatments can alter the splash and cavity formation following water entry. The spinning sphere ($S = \\omega r / U_o = 1.7$; $Fr = 5.15$) causes a wedge of fluid to be drawn into the cavity due to the no-slip condition and follows a curved trajectory. The non-spinning sphere ($Fr = 5.15$) has two distinct surface treatments on the left and right hemi...

  12. 19 CFR 142.17 - One entry summary for multiple entries.

    Science.gov (United States)

    2010-04-01

    ...; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Entry Summary Documentation § 142.17 One entry summary... for which entries or immediate transportation entries have been filed. However, this provision is not.... (ii) Immediate transportation entries. Immediate transportation entries may be consolidated if the...

  13. Shuttle entry guidance revisited

    Science.gov (United States)

    Mease, Kenneth D.; Kremer, Jean-Paul

    1992-08-01

    The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

  14. Shuttle entry guidance revisited

    Science.gov (United States)

    Mease, Kenneth D.; Kremer, Jean-Paul

    1992-01-01

    The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

  15. Water Entry of Projectiles

    Science.gov (United States)

    Truscott, Tadd T.; Epps, Brenden P.; Belden, Jesse

    2014-01-01

    The free-surface impact of solid objects has been investigated for well over a century. This canonical problem is influenced by many physical parameters, including projectile geometry, material properties, fluid properties, and impact parameters. Through advances in high-speed imaging and visualization techniques, discoveries about the underlying physics have improved our understanding of these phenomena. Improvements to analytical and numerical models have led to critical insights into cavity formation, the depth and time of pinch-off, forces, and trajectories for myriad different impact parameters. This topic spans a wide range of regimes, from low-speed entry phenomena dominated by surface tension to high-speed ballistics, for which cavitation is important. This review surveys experimental, theoretical, and numerical studies over this broad range, utilizing canonical images where possible to enhance intuition and insight into the rich phenomena.

  16. Green tea constituent epigallocatechin-3-gallate selectively inhibits COX-2 without affecting COX-1 expression in human prostate carcinoma cells.

    Science.gov (United States)

    Hussain, Tajamul; Gupta, Sanjay; Adhami, Vaqar M; Mukhtar, Hasan

    2005-02-10

    Overexpression of cyclooxygenase (COX)-2 has been implicated in many pathologic conditions, including cancer. One practical inference of this finding is that sustained inhibition of COX-2 could serve as a promising target for prevention or therapy of cancer. Conventional nonsteroidal antiinflammatory drugs (NSAIDs) and recently developed COX-2-specific inhibitors have shown considerable promise in prevention of some forms of human cancer; however, its application is limited due to severe toxic side effects on normal cells. Therefore, there is a need to define novel, nontoxic dietary constituents with proven chemopreventive effects through other pathways that also possess COX-2 but not COX-1 inhibitory activity. Recent studies on green tea and its major polyphenolic constituent (-)epigallocatechin-3-gallate (EGCG) have established its remarkable cancer preventive and some cancer therapeutic effects. Here, we show that EGCG inhibits COX-2 without affecting COX-1 expression at both the mRNA and protein levels, in androgen-sensitive LNCaP and androgen-insensitive PC-3 human prostate carcinoma cells. Based on our study, it is tempting to suggest that a combination of EGCG with chemotherapeutic drugs could be an improved strategy for prevention and treatment of prostate cancer.

  17. A Comparative Study of Cox Regression vs. Log-Logistic ...

    African Journals Online (AJOL)

    Journal of Medical and Biomedical Sciences ... using non-parametric Cox model and parametric Log-logistic model, factors influencing survival of ... colorectal cancer referred to Taleghani Medical and Training Center of Tehran between 2001 ...

  18. COX-2 and p53 in human sinonasal cancer

    DEFF Research Database (Denmark)

    Holmila, Reetta; Cyr, Diane; Luce, Danièle

    2008-01-01

    the exposures and p53 accumulation were found; however, the p53 accumulation pattern (p = 0.062 for wood dust exposure) resembled that of COX-2 expression. In summary, our findings show increased COX-2 expression in SNC adenocarcinoma with wood dust exposure, suggesting a role for inflammatory components......The causal role of wood-dust exposure in sinonasal cancer (SNC) has been established in epidemiological studies, but the mechanisms of SNC carcinogenesis are still largely unknown. Increased amounts of COX-2 are found in both premalignant and malignant tissues, and experimental evidence link COX-2......; 41 for p53). Occupational histories and smoking habits were available for majority of the cases. Most of the adenocarcinoma cases with exposure history data had been exposed to wood dust at work in the past (88%, 14/16). For smokers, 63% (12/19) presented with SSC, whereas 64% (7/11) of nonsmokers...

  19. Convergence of posteriors for discretized log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus Plenge

    2004-01-01

    In Markov chain Monte Carlo posterior computation for log Gaussian Cox processes (LGCPs) a discretization of the continuously indexed Gaussian field is required. It is demonstrated that approximate posterior expectations computed from discretized LGCPs converge to the exact posterior expectations...

  20. Comparison of Cox and Gray's survival models in severe sepsis

    DEFF Research Database (Denmark)

    Kasal, Jan; Andersen, Zorana Jovanovic; Clermont, Gilles

    2004-01-01

    Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate.......Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate....

  1. Simultaneous confidence bands for Cox regression from semiparametric random censorship.

    Science.gov (United States)

    Mondal, Shoubhik; Subramanian, Sundarraman

    2016-01-01

    Cox regression is combined with semiparametric random censorship models to construct simultaneous confidence bands (SCBs) for subject-specific survival curves. Simulation results are presented to compare the performance of the proposed SCBs with the SCBs that are based only on standard Cox. The new SCBs provide correct empirical coverage and are more informative. The proposed SCBs are illustrated with two real examples. An extension to handle missing censoring indicators is also outlined.

  2. COX2 genetic variation, NSAIDs, and advanced prostate cancer risk.

    Science.gov (United States)

    Cheng, I; Liu, X; Plummer, S J; Krumroy, L M; Casey, G; Witte, J S

    2007-08-20

    Collective evidence suggests that cyclooxygenase 2 (COX2) plays a role in prostate cancer risk. Cyclooxygenase 2 is the major enzyme that converts arachidonic acid to prostaglandins, which are potent mediators of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzymatic activity of COX2 and long-term use of NSAIDs appears to modestly lower the risk of prostate cancer. We investigated whether common genetic variation in COX2 influences the risk of advanced prostate cancer. Nine single-nucleotide polymorphisms (SNPs) in COX2 were genotyped among 1012 men in our case-control study of advanced prostate cancer. Gene-environment interactions between COX2 polymorphisms and NSAID use were also evaluated. Information on NSAID use was obtained by questionnaire. Three SNPs demonstrated nominally statistically significant associations with prostate cancer risk, with the most compelling polymorphism (rs2745557) associated with a lower risk of disease (odds ratio (OR) GC vs GG=0.64; 95% confidence interval (CI): 0.49-0.84; P=0.002). We estimated through permutation analysis that a similarly strong result would occur by chance 2.7% of the time. Nonsteroidal anti-inflammatory drug use was associated with a lower risk of disease in comparison to no use (OR=0.67; 95% CI: 0.52-0.87). No significant statistical interaction between NSAID use and rs2745557 was observed (P=0.12). Our findings suggest that variation in COX2 is associated with prostate cancer risk.

  3. Allan V. Cox: AGU President 1978”1980

    Science.gov (United States)

    Richman, Barbara T.

    When Allan V. Cox was presented AGU's John Adam Fleming Medal in 1969, John Verhoogen described Cox's work as “characterized by painstaking care, proper attention to and use of statistics, and great insight.” Those same thoughts were echoed on February 3, 1987, during the memorial service for Cox, who died in a bicycling accident on January 27. The Stanford Memorial Church was crowded with colleagues, students, and friends.The Fleming Medal was presented to Cox in recognition of his studies on the fluctuation of the geomagnetic field. These studies helped to confirm theories of continental drift and seafloor spreading. The medal is awarded annually by AGU for original research and technical leadership in geomagnetism, atmospheric electricity, aeronomy, and related sciences. In addition to the Fleming Medal, Cox received the Antarctic Service Medal in 1970, the Vetlesen Prize in 1971, and the Arthur L. Day Prize of the National Academy of Sciences in 1984. He was a Fellow of AGU and a member of the National Academy of Sciences.

  4. The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A.

    Science.gov (United States)

    Moghe, Saili; Jiang, Fei; Miura, Yoshie; Cerny, Ronald L; Tsai, Ming-Ying; Furukawa, Manabu

    2012-02-15

    The cullin-RING family of ubiquitin ligases regulates diverse cellular functions, such as cell cycle control, via ubiquitylation of specific substrates. CUL3 targets its substrates through BTB proteins. Here we show that depletion of CUL3 and the BTB protein KLHL18 causes a delay in mitotic entry. Centrosomal activation of Aurora-A, a kinase whose activity is required for entry into mitosis, is also delayed in depleted cells. Moreover, we identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes. We propose that the CUL3-KLHL18 ligase regulates mitotic entry through an Aurora-A-dependent pathway.

  5. The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A

    Directory of Open Access Journals (Sweden)

    Saili Moghe

    2012-02-01

    The cullin-RING family of ubiquitin ligases regulates diverse cellular functions, such as cell cycle control, via ubiquitylation of specific substrates. CUL3 targets its substrates through BTB proteins. Here we show that depletion of CUL3 and the BTB protein KLHL18 causes a delay in mitotic entry. Centrosomal activation of Aurora-A, a kinase whose activity is required for entry into mitosis, is also delayed in depleted cells. Moreover, we identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes. We propose that the CUL3-KLHL18 ligase regulates mitotic entry through an Aurora-A-dependent pathway.

  6. Human COX20 cooperates with SCO1 and SCO2 to mature COX2 and promote the assembly of cytochrome c oxidase.

    Science.gov (United States)

    Bourens, Myriam; Boulet, Aren; Leary, Scot C; Barrientos, Antoni

    2014-06-01

    Cytochrome c oxidase (CIV) deficiency is one of the most common respiratory chain defects in patients presenting with mitochondrial encephalocardiomyopathies. CIV biogenesis is complicated by the dual genetic origin of its structural subunits, and assembly of a functional holoenzyme complex requires a large number of nucleus-encoded assembly factors. In general, the functions of these assembly factors remain poorly understood, and mechanistic investigations of human CIV biogenesis have been limited by the availability of model cell lines. Here, we have used small interference RNA and transcription activator-like effector nucleases (TALENs) technology to create knockdown and knockout human cell lines, respectively, to study the function of the CIV assembly factor COX20 (FAM36A). These cell lines exhibit a severe, isolated CIV deficiency due to instability of COX2, a mitochondrion-encoded CIV subunit. Mitochondria lacking COX20 accumulate CIV subassemblies containing COX1 and COX4, similar to those detected in fibroblasts from patients carrying mutations in the COX2 copper chaperones SCO1 and SCO2. These results imply that in the absence of COX20, COX2 is inefficiently incorporated into early CIV subassemblies. Immunoprecipitation assays using a stable COX20 knockout cell line expressing functional COX20-FLAG allowed us to identify an interaction between COX20 and newly synthesized COX2. Additionally, we show that SCO1 and SCO2 act on COX20-bound COX2. We propose that COX20 acts as a chaperone in the early steps of COX2 maturation, stabilizing the newly synthesized protein and presenting COX2 to its metallochaperone module, which in turn facilitates the incorporation of mature COX2 into the CIV assembly line.

  7. Tactile Data Entry System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Building on our successful Phase I Tactile Data Entry program, Barron Associates proposes development of a Glove-Enabled Computer Operations (GECO) system to permit...

  8. Entry, Descent, Landing Animation (Animation)

    Science.gov (United States)

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for Entry, Descent, Landing animation This animation illustrates the path the Stardust return capsule will follow once it enters Earth's atmosphere.

  9. Entry, Descent, Landing Animation (Animation)

    Science.gov (United States)

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for Entry, Descent, Landing animation This animation illustrates the path the Stardust return capsule will follow once it enters Earth's atmosphere.

  10. Evaluation of the immunoexpression of COX-1, COX-2 and p53 in Crohn's disease Avaliação da imunoexpressão de COX-1, COX-2 e p53 na doença de Crohn

    Directory of Open Access Journals (Sweden)

    Mônica Romero

    2008-12-01

    Full Text Available BACKGROUND: Crohn's disease accompanied by nonspecific or idiopathic ulcerative proctocolitis corresponds to a condition called intestinal inflammatory disease. The immunoexpression of cyclooxygenase 2 (COX-2 in Crohn's disease becomes more marked with progression of the disease and the presence of wild-type p53 suppresses the transcription of COX-2. AIMS: To investigate the immunoexpression of cyclooxygenase 1 (COX-1, COX-2 and p53 in Crohn's ileocolitis and to correlated this expression with clinical and histopathological parameters. METHODS: Forty-five cases of Crohn's disease, 16 cases of actinic colitis (diseased-control group and 11 cases without a history of intestinal disease (normal control group were studied. Hematoxylin-eosin-stained sections were submitted to histopathological analysis and the immunohistochemical expression of COX-1, COX-2 and p53 was evaluated by the streptavidin-biotin-peroxidase method. RESULTS: Sixty percent of the Crohn's disease patients were women and 40% were men, with 75.5% whites and 25.5% non-whites. The disease involved the terminal ileum in 44.5% of cases, ileum in 33.3%, colon in 20% and duodenum-ileum in 2.2%. A significant association was observed between COX-2 immunoreactivity and age RACIONAL: A doença de Crohn, junto com a colite ulcerativa idiopática ou inespecífica constituem a doença inflamatória intestinal. A imunoexpressão de ciclooxigenase 2 (COX-2 na doença de Crohn acentua-se com a progressão da doença, enquanto que a presença do tipo selvagem de p53 suprime a transcrição de COX-2. OBJETIVOS: Investigar a imunoexpressão de ciclooxigenase 1 (COX-1, COX-2 e p53 na doença de Crohn e correlacionar os achados com parâmetros clínico-histopatológicos. MÉTODOS: Foram estudados 45 casos de doença de Crohn (grupo teste, 16 casos de colite actínica (grupo controle-doente e 11 casos sem história de doença intestinal (grupo controle normal. A avaliação histopatológica foi feita

  11. Orion Entry Handling Qualities Assessments

    Science.gov (United States)

    Bihari, B.; Tiggers, M.; Strahan, A.; Gonzalez, R.; Sullivan, K.; Stephens, J. P.; Hart, J.; Law, H., III; Bilimoria, K.; Bailey, R.

    2011-01-01

    The Orion Command Module (CM) is a capsule designed to bring crew back from the International Space Station (ISS), the moon and beyond. The atmospheric entry portion of the flight is deigned to be flown in autopilot mode for nominal situations. However, there exists the possibility for the crew to take over manual control in off-nominal situations. In these instances, the spacecraft must meet specific handling qualities criteria. To address these criteria two separate assessments of the Orion CM s entry Handling Qualities (HQ) were conducted at NASA s Johnson Space Center (JSC) using the Cooper-Harper scale (Cooper & Harper, 1969). These assessments were conducted in the summers of 2008 and 2010 using the Advanced NASA Technology Architecture for Exploration Studies (ANTARES) six degree of freedom, high fidelity Guidance, Navigation, and Control (GN&C) simulation. This paper will address the specifics of the handling qualities criteria, the vehicle configuration, the scenarios flown, the simulation background and setup, crew interfaces and displays, piloting techniques, ratings and crew comments, pre- and post-fight briefings, lessons learned and changes made to improve the overall system performance. The data collection tools, methods, data reduction and output reports will also be discussed. The objective of the 2008 entry HQ assessment was to evaluate the handling qualities of the CM during a lunar skip return. A lunar skip entry case was selected because it was considered the most demanding of all bank control scenarios. Even though skip entry is not planned to be flown manually, it was hypothesized that if a pilot could fly the harder skip entry case, then they could also fly a simpler loads managed or ballistic (constant bank rate command) entry scenario. In addition, with the evaluation set-up of multiple tasks within the entry case, handling qualities ratings collected in the evaluation could be used to assess other scenarios such as the constant bank angle

  12. Post-translational regulation of COX2 activity by FYN in prostate cancer cells.

    Science.gov (United States)

    Alexanian, Anna; Miller, Bradley; Chesnik, Marla; Mirza, Shama; Sorokin, Andrey

    2014-06-30

    While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity.

  13. Currency union entries and trade

    OpenAIRE

    Nitsch, Volker

    2005-01-01

    Recent research suggests that adopting a common currency increases bilateral trade. In this paper, I explore experiences of currency union entry in the post-war period and find no effect on trade. Previous results derived from a large panel data set (covering more than 200 countries from 1948 through 1997) appear to depend crucially on the assumption of symmetry between currency union exits and entries: While countries leaving a currency union experience significant declines in trade, currenc...

  14. Delayed childbearing.

    Science.gov (United States)

    Francis, H H

    1985-06-01

    In many Western nations, including England and Wales, Sweden, and the US, there is a current trend towards delayed childbearing because of women's pursuit of a career, later marriage, a longer interval between marriage and the 1st birth, and the increasing number of divorcees having children in a 2nd marriage. Wives of men in social classes I and II in England and Wales are, on average, having their 1st child at 27.9 years, 1.6 years later than in 1973, and in social classes IV and V, 1.0 years later than in 1973, at a mean age of 23.7 years. Consequently, the total period fertility rate for British women aged 30-34 years, 35-39 years, and 40 and over increased by 4%, 2%, and 4%, respectively, between 1982-83, in contrast to reductions of 2% and 3%, respectively, in the 15-19 year and 20-24 year age groups, with the 25-29-year-olds remaining static. The average maternal mortality for all parties in England and Wales during 1976-78 was 106/million for adolescents, 70.4/million for 20-24 year-olds, and 1162/million for those aged 40 years and older. The specific obstetric and allied conditions which increase with age are the hypertensive diseases of pregnancy, hemorrhage, pulmonary embolism, abortion, cardiac disease, caesarean section, ruptured uterus, and amniotic fluid embolism. The Swedish Medical Birth Registry of all live births and perinatal deaths since 1973 has shown that the risk of late fetal death is significantly greater in women aged 30-39 years than in those of the same parity and gravidity aged 20-24 years. The risk of giving birth to low birth weight babies preterm and at term and of premature labor are similarly increased. The early neonatal death rate also was increased for primigravidas and nulliparas in the 30-39 year age group but not in parous women. This is, in part, due to the rise in incidence of fetal abnormalities with advancing maternal age because of chromosomal and nonchromosomal anomalies. These also appear to be the cause of the

  15. Seizure following the Use of the COX-2 Inhibitor Etoricoxib

    Science.gov (United States)

    Arnao, Valentina; Riolo, Marianna; Fierro, Brigida

    2017-01-01

    We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this. Conclusion. Knowing the pharmacological history of a patient is important for understanding the clinical presentation and selecting appropriate treatment. This is, to the best of our knowledge, the first reported case of generalized seizures associated with the use of COX-2 inhibitors. PMID:28210513

  16. Delayed Hopf bifurcation in time-delayed slow-fast systems

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This paper presents an investigation on the phenomenon of delayed bifurcation in time-delayed slow-fast differential systems.Here the two delayed’s have different meanings.The delayed bifurcation means that the bifurcation does not happen immediately at the bifurcation point as the bifurcation parameter passes through some bifurcation point,but at some other point which is above the bifurcation point by an obvious distance.In a time-delayed system,the evolution of the system depends not only on the present state but also on past states.In this paper,the time-delayed slow-fast system is firstly simplified to a slow-fast system without time delay by means of the center manifold reduction,and then the so-called entry-exit function is defined to characterize the delayed bifurcation on the basis of Neishtadt’s theory.It shows that delayed Hopf bifurcation exists in time-delayed slow-fast systems,and the theoretical prediction on the exit-point is in good agreement with the numerical calculation,as illustrated in the two illustrative examples.

  17. COX-1 inhibitory effect of medicinal plants of Ghana

    DEFF Research Database (Denmark)

    Larsen, Birgitte HV; Soelberg, Jens; Jäger, Anna

    2015-01-01

    Plants used to treat inflammatory ailments, pain, fever and infections in Ghana, were tested for COX-1 inhibitory activity. Ethanolic extracts of 17 species were tested in a COX-1 assay. The extracts of Gardenia ternifolia, Thonningia sanguinea, Triumfetta rhomboidea, and the root of Zanthoxylum...... zanthoxyloides showed an inhibitory effect over 90% in the final concentration 0.1 μg/μL. The HPLC profiles indicated that the extracts of the four active species did not contain tannins. The observed in vitro activities support the use of some of the plant species in the traditional medicine system in Ghana....

  18. Multifocal fixed drug eruption with COX-2 inhibitor-celecoxib

    Directory of Open Access Journals (Sweden)

    Shikha Chugh

    2013-01-01

    Full Text Available Cyclooxygenase-2 (COX-2 inhibitors are rapidly becoming the first choice nonsteroidal anti-inflammatory drugs (NSAIDs for various rheumatological and other painful conditions. However, they might not be as safe or free of side effects as they are considered to be. These COX-2inhibitors may cause a variety of dermatological and systemic side effects of which we should be aware to avoid their indiscriminate use. We hereby report a case of multifocal fixed drug eruption (FDE with celecoxib which has not yet been reported in Indian settings.

  19. Multifocal Fixed Drug Eruption with COX-2 Inhibitor-Celecoxib

    Science.gov (United States)

    Chugh, Shikha; Sarkar, Rashmi; Garg, Vijay K; Singh, Avninder; Keisham, Chitralekha

    2013-01-01

    Cyclooxygenase-2 (COX-2) inhibitors are rapidly becoming the first choice nonsteroidal anti-inflammatory drugs (NSAIDs) for various rheumatological and other painful conditions. However, they might not be as safe or free of side effects as they are considered to be. These COX-2inhibitors may cause a variety of dermatological and systemic side effects of which we should be aware to avoid their indiscriminate use. We hereby report a case of multifocal fixed drug eruption (FDE) with celecoxib which has not yet been reported in Indian settings. PMID:23716804

  20. Race and socioeconomic status in substance use progression and treatment entry.

    Science.gov (United States)

    Lewis, Ben; Hoffman, Lauren; Garcia, Christian C; Nixon, Sara Jo

    2017-08-28

    This study examined trajectories of progression from early substance use to treatment entry as a function of race, among inpatient treatment seekers (N = 945). Following primary race-contingent analyses of use progression, secondary analyses were conducted to investigate the effects of socioeconomic status (SES) on the observed differences. African Americans reported significant delays in treatment entry relative to Caucasians. Racial differences in alcohol, marijuana, and cocaine use trajectories were observed. Accounting for SES rendered observations of accelerated use among African Americans nonsignificant. However, inclusion of SES failed to mitigate the marked racial disparity in treatment entry.

  1. 19 CFR 191.143 - Drawback entry.

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) DRAWBACK Foreign-Built Jet Aircraft Engines Processed in the United States § 191.143 Drawback entry. (a) Filing of entry. Drawback entries covering these foreign-built jet aircraft engines shall be filed on Customs Form 7551, modified to show that the entry covers jet aircraft engines processed...

  2. Post-translational regulation of COX2 activity by FYN in prostate cancer cells

    OpenAIRE

    Alexanian, Anna; Miller, Bradley; Chesnik, Marla; Mirza, Shama; Sorokin, Andrey

    2014-01-01

    While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates h...

  3. Prescriber adoption of newly approved selective COX-2 inhibitors

    NARCIS (Netherlands)

    Layton, Deborah; Souverein, Patrick C.; Heerdink, Eibert R.; Shakir, Saad A. W.; Egberts, A. G. C.

    2008-01-01

    Introduction There is no consistent definition of prescribers who adopt new drug treatments early. This study examines if COX-2 inhibitors (coxibs) were prescribed by subsets of practitioners and describes GP adoption patterns of coxibs and existing NSAIDs over time. Methods A population-based drug

  4. A time inhomogeneous Cox-Ingersoll-Ross diffusion with jumps

    CERN Document Server

    Hoepfner, Reinhard

    2009-01-01

    We consider a time inhomogeneous Cox-Ingersoll-Ross diffusion with positive jumps. We exploit a branching property to prove existence of a unique strong solution under a restrictive condition on the jump measure. We give Laplace transforms for the transition probabilities, with an interpretation in terms of limits of mixtures over Gamma laws.

  5. Role of COX-2 in microcirculatory disturbance in experimental pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Wen-Wei Yan; Zong-Guang Zhou; You-Dai Chen; Hong-Kai Gao

    2004-01-01

    AIM: To elucidate the role of COX-2 in the development of capillary leakage in rats with acute interstitial pancreatitis.METHODS: Rats with acute interstitial pancreatitis were induced by caerulein subcutaneous injection. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of COX-2 in pancreatic tissues, spectrophotometry was used to assay the parameters of acute pancreatitis such as the serum amylase and plasma myeloperoxidase, and determination of capillary permeability in the pancreas by quantifying the permeability index (PI) assisted response of pancreatic microvascular via intravital fluorescence microscope video image analysis system.RESULTS: A significant increase of COX-2 expression,elevation of serum amylase, and plasma myeloperoxidase were detected in rats with acute edematous pancreatitis compared with control rats. The changes of pancreatic microvascular after caerulein injection were as following: (a) the decrease of pancreatic capillary blood flow (4th h,0.56±0.09 nL/min, P<0.05; 8 th h, 0.34±0.10 nL/min, P<0.001);(b) reduction of functional capillary density (4 th h, 381±9 cm-1,P>0.05; 8th h, 277±13 cm-1 P<0.001); (c) irregular and intermittent capillary perfusion was observed at the 8th h and these vessels were also prone to permeation.CONCLUSION: COX-2 plays an important role in mediating capillary permeability in pancreatitis, thereby contributing to capillary leakage.

  6. Intravenous glutamine enhances COX-2 activity giving cardioprotection.

    LENUS (Irish Health Repository)

    McGuinness, Jonathan

    2009-03-01

    Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning.

  7. 19 CFR 142.16 - Entry summary documentation.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry summary documentation. 142.16 Section 142.16... TREASURY (CONTINUED) ENTRY PROCESS Entry Summary Documentation § 142.16 Entry summary documentation. (a) Entry summary not filed at time of entry. When the entry documentation is filed before the entry...

  8. Resistance of prostate cancer cell lines to COX-2 inhibitor treatment.

    Science.gov (United States)

    Wagner, Matthew; Loos, James; Weksler, Nicole; Gantner, Marin; Corless, Christopher L; Barry, John M; Beer, Tomasz M; Garzotto, Mark

    2005-07-08

    Targeting of cyclooxygenase-2 (COX-2) for cancer chemoprevention is well supported for several tumor types, most notably colon cancer. In contrast, the data for its role in prostate cancer carcinogenesis are correlative only. Thus, we compared the COX-2 expression, activity, and effects of inhibition in prostate cancer cells on COX-2-dependent colon cancer cells. COX-2 levels in benign and malignant human prostate tissue were determined by immunohistochemistry. Compared to colon cancer cells, prostate cancer cells expressed lower levels of COX-2, produced less PGE2, and were resistant to selective COX-2 inhibition. Examination of benign prostatic epithelium from prostatectomy samples demonstrated rare foci of COX-2. Whereas, human prostate cancer sections were uniformly negative for COX-2. In conclusion, these studies indicate the lack of a putative role for COX-2 in prostate cancer development. Direct evidence for the involvement of COX-2 in prostate cancer carcinogenesis is desperately needed.

  9. Autonomous gliding entry guidance with

    Directory of Open Access Journals (Sweden)

    Guo Jie

    2015-10-01

    Full Text Available This paper presents a novel three-dimensional autonomous entry guidance for relatively high lift-to-drag ratio vehicles satisfying geographic constraints and other path constraints. The guidance is composed of onboard trajectory planning and robust trajectory tracking. For trajectory planning, a longitudinal sub-planner is introduced to generate a feasible drag-versus-energy profile by using the interpolation between upper boundary and lower boundary of entry corridor to get the desired trajectory length. The associated magnitude of the bank angle can be specified by drag profile, while the sign of bank angle is determined by lateral sub-planner. Two-reverse mode is utilized to satisfy waypoint constraints and dynamic heading error corridor is utilized to satisfy no-fly zone constraints. The longitudinal and lateral sub-planners are iteratively employed until all of the path constraints are satisfied. For trajectory tracking, a novel tracking law based on the active disturbance rejection control is introduced. Finally, adaptability tests and Monte Carlo simulations of the entry guidance approach are performed. Results show that the proposed entry guidance approach can adapt to different entry missions and is able to make the vehicle reach the prescribed target point precisely in spite of geographic constraints.

  10. Reconstruction of the Genesis Entry

    Science.gov (United States)

    Desai, Prasun N.; Qualls, Garry D.; Schoenenberger, Mark

    2007-01-01

    An overview of the reconstruction analyses performed for the Genesis capsule entry is described. The results indicate that the actual entry prior to the drogue deployment failure was very close to the pre-entry predictions. The capsule landed 8.3 km south of the desired target at Utah Test and Training Range. Analysis on infrared video footage (obtained from the tracking stations) during the descent estimated the onset of the capsule tumble at Mach 0.9. Frequency analysis on the infrared video data indicates that the aerodynamics generated for the Genesis capsule reasonably predicted the drag and static stability. Observations of the heatshield support the pre-entry simulation estimates of a small hypersonic angles-of-attack, since there is very little, if any, charring of the shoulder region or the aftbody. Through this investigation, an overall assertion can be made that all the data gathered from the Genesis entry is consistent with flight performance that was close to the nominal preentry prediction. Consequently, the design principles and methodologies utilized for the flight dynamics, aerodynamics, and aerothermodynamics analyses have been corroborated.

  11. Membongkar Akuntansi Double Entry Systems

    Directory of Open Access Journals (Sweden)

    Whedy Prasetyo

    2013-08-01

    Full Text Available Double entry isa process of recording transactions that always involve at least two accounts ofwhich changes (increases or decreases have consequences to maintain a balance equation. This is a simple basic accounting, that the use of the funds must alwaysbe equal to the acquisition of funds. The equation is not able to include some business events that are responses to the development of business environment. A proposed view is based on the interaction of researcher (New Bond with accountant (Mrs M to dismantle the double entry accounting through Maurice Merleau Ponty's approach (1906-1961. The results prove that physical aspects of knowledge willcontinue to evolve according to environmental interactions.

  12. COX-2 gene promoter haplotypes and prostate cancer risk.

    Science.gov (United States)

    Panguluri, Ramesh C K; Long, Layron O; Chen, Weidong; Wang, Songping; Coulibaly, Aoua; Ukoli, Flora; Jackson, Aaron; Weinrich, Sally; Ahaghotu, Chiledum; Isaacs, William; Kittles, Rick A

    2004-06-01

    Cyclooxygenase-2 (COX-2) is a key rate-limiting enzyme that converts arachidonic acid into pro-inflammatory prostaglandins. COX-2 expression is strongly correlated with increased tumor microvasculature density and plays an important role in inhibiting apoptosis, stimulating angiogenesis and promoting tumor cell metastasis and invasion. However, little is known about the role that sequence variation of the COX-2 gene contributes to prostate cancer. Thus, we searched for polymorphisms in the promoter region of the COX-2 gene using denaturing high-performance liquid chromatography. Four single nucleotide polymorphisms (SNPs), -1285A/G, -1265G/A, -899G/C and -297C/G, were detected and confirmed by direct sequencing. Three of the SNPs in the promoter region of COX-2 gene create at least three putative transcription factor binding sites and eliminate CCAAT/enhancer binding protein alpha (C/EBP alpha) and NF-kappa B binding sites. A case-control study of the four SNPs in African American (n = 288), Bini Nigerian (n = 264) and European American (n = 184) prostate cancer cases and age-matched controls revealed that SNP -297G was associated with a decreased risk for prostate cancer [odds ratio (OR) = 0.49; CI = 0.2-0.9; P = 0.01]. The effect on risk was observed in both African Americans (OR = 0.51; CI = 0.2-0.9; P = 0.01) and European Americans (OR = 0.33; CI = 0.1-0.9; P = 0.02). In addition, SNPs -1265A and -899C were associated with increased prostate cancer risk in African Americans (OR = 2.72; CI = 1.3-5.8; P = 0.007 and OR = 3.67; CI = 1.4-9.9; P = 0.007, respectively). Haplotype analyses revealed modest effects on susceptibility to prostate cancer across populations. Haplotype GGCC conferred increased risk in the African American and Nigerian populations. Conversely, haplotype AGGG exhibited a negative association with prostate cancer risk in African Americans (OR = 0.4; CI = 0.1-0.9; P = 0.02) and European Americans (OR = 0.2; CI = 0.1-0.9; P = 0.03). These data

  13. In Silico Analysis of the Potential of the Active Compounds Fucoidan and Alginate Derived from Sargassum Sp. as Inhibitors of COX-1 and COX-2

    Science.gov (United States)

    Dewi, Lestari

    2016-01-01

    Introduction: The enzyme cyclooxygenase (COX) is an enzyme that catalyzes the formation of one of the mediators of inflammation, the prostaglandins. Inhibition of COX allegedly can improve inflammation-induced pathological conditions. Aim: The purpose of the present study was to evaluate the potential of Sargassum sp. components, Fucoidan and alginate, as COX inhibitors. Material and methods: The study was conducted by means of a computational (in silico) method. It was performed in two main stages, the docking between COX-1 and COX-2 with Fucoidan, alginate and aspirin (for comparison) and the analysis of the amount of interactions formed and the residues directly involved in the process of interaction. Results: Our results showed that both Fucoidan and alginate had an excellent potential as inhibitors of COX-1 and COX-2. Fucoidan had a better potential as an inhibitor of COX than alginate. COX inhibition was expected to provide a more favorable effect on inflammation-related pathological conditions. Conclusion: The active compounds Fucoidan and alginate derived from Sargassum sp. were suspected to possess a good potential as inhibitors of COX-1 and COX-2. PMID:27594740

  14. Re-entry flight clearance

    NARCIS (Netherlands)

    Juliana, S.

    2006-01-01

    The objective of the research was to identify and evaluate promising mathematical techniques for re-entry flight clearance. To fulfil this objective, two mathematical methods were investigated and developed: μ analysis for linear models and interval analysis for both linear and non-linear model

  15. Components of Visual Prior Entry

    Science.gov (United States)

    Schneider, Keith A.; Bavelier, Daphne

    2003-01-01

    The prior entry hypothesis contends that attention accelerates sensory processing, shortening the time to perception. Typical observations supporting the hypothesis may be explained equally well by response biases, changes in decision criteria, or sensory facilitation. In a series of experiments conducted to discriminate among the potential…

  16. Entry Facilitation by Environmental Groups

    NARCIS (Netherlands)

    van der Made, Allard; Schoonbeek, Lambert

    We consider a model of vertical product differentiation where consumers care about the environmental damage their consumption causes. An environmental group is capable of increasing consumers' environmental concern via a costly campaign. We show that the prospect of such a campaign can induce entry

  17. Entry Facilitation by Environmental Groups

    NARCIS (Netherlands)

    van der Made, Allard; Schoonbeek, Lambert

    2009-01-01

    We consider a model of vertical product differentiation where consumers care about the environmental damage their consumption causes. An environmental group is capable of increasing consumers' environmental concern via a costly campaign. We show that the prospect of such a campaign can induce entry

  18. Multivariate Product-Shot-noise Cox Point Process Models

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Mateu, Jorge

    We introduce a new multivariate product-shot-noise Cox process which is useful for model- ing multi-species spatial point patterns with clustering intra-specific interactions and neutral, negative or positive inter-specific interactions. The auto and cross pair correlation functions of the proces...... can be obtained in closed analytical forms and approximate simulation of the process is straightforward. We use the proposed process to model interactions within and among five tree species in the Barro Colorado Island plot.......We introduce a new multivariate product-shot-noise Cox process which is useful for model- ing multi-species spatial point patterns with clustering intra-specific interactions and neutral, negative or positive inter-specific interactions. The auto and cross pair correlation functions of the process...

  19. Jackknifed random weighting for Cox proportional hazards model

    Institute of Scientific and Technical Information of China (English)

    LI Xiao; WU YaoHua; TU DongSheng

    2012-01-01

    The Cox proportional hazards model is the most used statistical model in the analysis of survival time data.Recently,a random weighting method was proposed to approximate the distribution of the maximum partial likelihood estimate for the regression coefficient in the Cox model.This method was shown not as sensitive to heavy censoring as the bootstrap method in simulation studies but it may not be second-order accurate as was shown for the bootstrap approximation.In this paper,we propose an alternative random weighting method based on one-step linear jackknife pseudo values and prove the second accuracy of the proposed method.Monte Carlo simulations are also performed to evaluate the proposed method for fixed sample sizes.

  20. Prostanoids in tumor angiogenesis: therapeutic intervention beyond COX-2.

    Science.gov (United States)

    Salvado, M Dolores; Alfranca, Arántzazu; Haeggström, Jesper Z; Redondo, Juan Miguel

    2012-04-01

    Prostanoids regulate angiogenesis in carcinoma and chronic inflammatory disease progression. Although prostanoid biosynthetic enzymes and signaling have been extensively analyzed in inflammation, little is known about how prostanoids mediate tumor-induced angiogenesis. Targeted cyclooxygenase (COX)-2 inhibition in tumor, stromal and endothelial cells is an attractive antiangiogenic strategy; however, the associated cardiovascular side effects have led to the development of a new generation of nonsteroidal anti-inflammatory drugs (NSAIDs) acting downstream of COX. These agents target terminal prostanoid synthases and prostanoid receptors, which may also include several peroxisome proliferator-activated receptors (PPARs). Here, we discuss the role of prostanoids as modulators of tumor angiogenesis and how prostanoid metabolism reflects complex cell-cell crosstalk that determines tumor growth. Finally, we discuss the potential of new NSAIDs for the treatment of angiogenesis-dependent tumor development.

  1. Targeting Estrogen-Induced COX-2 Activity in Lymphangioleiomyomatosis (LAM)

    Science.gov (United States)

    2014-12-01

    rapamycin treatment. However both Torin 1 treatment and Rictor knockdown, led to reduced COX-2 expression and phospho-Akt-S473. Prostaglandin... rapamycin complex 1 (mTORC1), a master regulator of cell growth, protein translation, and metabolism. In LAM patients the mTORC1 inhibitor Rapamycin ...published PLOS One 2014. “ Rapamycin -insensitive up-regulation of adipocyte phospholipase A2 in tuberous sclerosis complex and

  2. Some functional limit theorems for compound Cox processes

    Science.gov (United States)

    Korolev, Victor Yu.; Chertok, A. V.; Korchagin, A. Yu.; Kossova, E. V.; Zeifman, Alexander I.

    2016-06-01

    An improved version of the functional limit theorem is proved establishing weak convergence of random walks generated by compound doubly stochastic Poisson processes (compound Cox processes) to Lévy processes in the Skorokhod space under more realistic moment conditions. As corollaries, theorems are proved on convergence of random walks with jumps having finite variances to Lévy processes with variance-mean mixed normal distributions, in particular, to stable Lévy processes.

  3. Positively skewed data: revisiting the box-cox power transformation.

    OpenAIRE

    2015-01-01

    Although the normal probability distribution is the cornerstone of applying statistical methodology; data do not always meet the necessary normal distribution assumptions. In these cases, researchers often transform non-normal data to a distribution that is approximately normal. Power transformations constitute a family of transformations, which include logarithmic and fractional exponent transforms. The Box-Cox method offers a simple method for choosing the most appropriate power transformat...

  4. COX-2 Inhibitors for Cancer Treatment in Dogs

    Directory of Open Access Journals (Sweden)

    Andrigo Barboza De Nardi*, Talita Mariana Morata Raposo1, Rafael Ricardo Huppes1, Carlos Roberto Daleck2 and Renée Laufer Amorim3

    2011-10-01

    Full Text Available Cancer is one of the main causes of death in canines and felines, and this fact is probably related to the increase in the longevity of these species. The longer the animals live, the higher the exposure to carcinogenic agents will be. With the high incidence of cancer in companion animals, new studies are currently being performed with the aim of finding therapeutic options which make the complete inhibition of the development of neoplasms in animals possible in the future. The correlation of cyclooxygenase-2 (COX-2 whith the development of cancer opens the way for the use of new therapeutic approaches. This relationship has been suggested based on various studies which established an association between the chronic use of nonsteroidal anti-inflammatory drugs (NSAID and a decrease in the incidence of colon carcinoma. As cancer progresses, COX-2 participates in the arachidonic acid metabolism by synthesizing prostaglandins which can mediate various mechanisms related to cancer development such as: increase in angiogenesis, inhibition of apoptosis, suppression of the immune response, acquisition of greater invasion capacity and metastasis. Accordingly, overexpression of this enzyme in tumors has been associated with the most aggressive, poor-prognosis cancer types, especially carcinomas. Therefore, treatments which use COX-2 inhibitors such as coxibs, whether administered as single agents or in combination with conventional antineoplastic chemotherapy, are an alternative for extending the survival of our cancer patients.

  5. [New studies of COX-inhibitors, yet issues remain].

    Science.gov (United States)

    Wollheim, Frank A

    2003-09-18

    Advantages and risks related to the use of selective COX-2 inhibitors when treating arthritis are currently being scrutinized by authorities and public. The discussion tends towards exaggerated claims for or against their usefulness. The issue of cardiovascular safety is still not finally settled. In an experimental study using patients with severe coronary disease, administration of celecoxib resulted in improved endothelial function together with reduced CRP levels. Gastrointestinal tolerance was studied in patients who had recently recovered from peptic ulcer bleeding. In this group of high risk patients, celecoxib was as safe as combined therapy using omeprazol and diclofenac when given for 6 months. However, both COX inhibitors caused hypertension and adverse renal effects. The second generation of selective inhibitors is being launched. Etoricoxib--related to rofecoxib--was shown to be as potent as indomethacin in the treatment of acute gout, but it caused fewer adverse reactions. In general, however, any advantage of second generation as compared to first generation COX-2 inhibitors remains to be proven. The Swedish Council on Technology Assessment in Health Care, in its "SBU Alert", has published an appraisal of celecoxib and rofecoxib, in which the need for further long-term safety studies is emphasized.

  6. Survival analysis of cervical cancer using stratified Cox regression

    Science.gov (United States)

    Purnami, S. W.; Inayati, K. D.; Sari, N. W. Wulan; Chosuvivatwong, V.; Sriplung, H.

    2016-04-01

    Cervical cancer is one of the mostly widely cancer cause of the women death in the world including Indonesia. Most cervical cancer patients come to the hospital already in an advanced stadium. As a result, the treatment of cervical cancer becomes more difficult and even can increase the death's risk. One of parameter that can be used to assess successfully of treatment is the probability of survival. This study raises the issue of cervical cancer survival patients at Dr. Soetomo Hospital using stratified Cox regression based on six factors such as age, stadium, treatment initiation, companion disease, complication, and anemia. Stratified Cox model is used because there is one independent variable that does not satisfy the proportional hazards assumption that is stadium. The results of the stratified Cox model show that the complication variable is significant factor which influent survival probability of cervical cancer patient. The obtained hazard ratio is 7.35. It means that cervical cancer patient who has complication is at risk of dying 7.35 times greater than patient who did not has complication. While the adjusted survival curves showed that stadium IV had the lowest probability of survival.

  7. Efeito dos anti-inflamatórios não-esteroidais convencionais e seletivos para COX-2 sobre o reparo ósseo Effect of conventional and COX-2 selective non-steroidal antiinflammatory drugs on bone healing

    Directory of Open Access Journals (Sweden)

    Teresa Lúcia Lamano-Carvalho

    2007-01-01

    Full Text Available Na presente revisão de literatura foram relacionados trabalhos experimentais e clínicos dos últimos 15 anos referentes aos efeitos dos antiinflamatórios não-esteroidais (AINEs convencionais e seletivos para COX-2 sobre a formação óssea reparacional. A maioria dos trabalhos mostra que os AINEs convencionais podem atrasar o reparo de fratura de ossos longos e a fusão espinhal, em animais, e interferir negativamente com a taxa de fusão espinhal, em humanos. Apesar da importância comprovada da prostaglandina E2, sintetizada por osteoblastos sob estímulo da enzima ciclooxigenase-2 (COX-2, no controle da formação óssea, os resultados experimentais acerca dos prováveis efeitos inibitórios dos AINEs seletivos sobre o reparo ósseo além de raros são ainda controversos e não há comprovação de que eles interferem com a neoformação óssea reparacional em humanos.In the present literature review, experimental and clinical studies of the last 15 years concerning the effects of conventional and COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs on bone healing were reported. Most of the data pertaining to conventional NSAIDs have shown to cause delayed fracture healing and impairment of spinal fusion in animal studies, as well as a negative interference on spinal fusion rate in human beings. In spite of the established importance of prostaglandin E2, synthesized by osteoblasts under COX-2 stimulation, in controlling bone formation, the results regarding the potential inhibitory effects of selective NSAIDs on experimental bone healing are still controversial and there is no clinical data to confirm that they interfere negatively with repairing bone formation.

  8. 19 CFR 142.3a - Entry numbers.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry numbers. 142.3a Section 142.3a Customs... (CONTINUED) ENTRY PROCESS Entry Documentation § 142.3a Entry numbers. (a) Placement on CBP forms. The importer or broker shall place an 11 character entry number on the entry and corresponding entry...

  9. Effect of isolated fractions of Harpagophytum procumbens D.C. (devil's claw) on COX-1, COX-2 activity and nitric oxide production on whole-blood assay.

    Science.gov (United States)

    Anauate, Maria Cecilia; Torres, Luce Maria; de Mello, Suzana Beatriz Veríssimo

    2010-09-01

    The present study evaluates the effect of isolated fractions of Harpagophytum procumbens (devil's claw) on cyclooxygenase (COX-1 and COX-2) activities and NO production using a whole blood assay. The activity of COX-1 was quantified as platelet thromboxane B(2) production in blood clotting and COX-2 as prostaglandin E(2) production in LPS-stimulated whole blood. Total NO(2) (-)/NO(3) (-) concentration was determined by Griess reaction in LPS stimulated blood. Assays were performed by incubation of isolated fractions obtained by flash chromatography monitored with HPLC, TLC and identified by (1)HNMR, containing different amounts of harpagoside with blood from healthy donors. Indomethacin and etoricoxib were the positive controls of COX-1 and COX-2 Inhibition. Data shows that fraction containing the highest concentration of harpagoside inhibited indistinctively COX-1 and COX-2 (37.2 and 29.5% respectively) activity and greatly inhibited NO production (66%). In contrast the fraction including iridoid pool increased COX-2 and did not alter NO and COX-1 activities. The fraction containing cinnamic acid was able to reduce only NO production (67%). Our results demonstrated that the harpagoside fraction is the main responsible for the effect of devils claw on these enzyme activities. However, other components from devil's claw crude extract could antagonize or increase the synthesis of inflammatory mediators.

  10. Expression of gelatinases (MMP-2, MMP-9) and cyclooxygenases (COX-1, COX-2) in some benign salivary gland tumors.

    Science.gov (United States)

    Lipari, L; Mauro, A; Gallina, S; Tortorici, S; Buscemi, M; Tete, S; Gerbino, A

    2012-01-01

    Salivary gland tumors, most of which are rare benign tumors, represent a histologically heterogenous group with the greatest diversity of morphological and cellular features. The aim of this study is to analyse the expression and possible interactions between gelatinases (MMP-2, MMP-9) and cyclooxygenases (COX-1, COX-2) in some benign salivary gland tumors. We investigated the expression of gelatinases and cyclooxigenases in control salivary gland, Pleomorphic adenoma and Warthin's tumor through immunohistochemistry and Reverse Transcription - Polymerase Chain Reaction (PCR). We identified the expression of both classes of enzyme in normal samples and in the two types of pathological samples without any quantitative differences. From the present data no significant differences emerge in the expression of these enzymes among the different pathologies examined. Nevertheless, due to the small number of samples included in this study, general statements regarding correlation between the degree of severity of the tumoral pathology and the quantitative expression of these potential tumoral markers can not be made.

  11. Immunohistochemical and morphometric evaluation of COX 1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Edwin Roger Parra

    2013-12-01

    Full Text Available OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc and idiopathic pulmonary fibrosis (IPF patients, correlating that expression with patient survival.METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP in SSc patients and usual interstitial pneumonia (UIP in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival.RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP, and low COX-1 expression in alveolar septa.CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that.

  12. The Arabidopsis COX11 Homolog is Essential for Cytochrome c Oxidase Activity.

    Science.gov (United States)

    Radin, Ivan; Mansilla, Natanael; Rödel, Gerhard; Steinebrunner, Iris

    2015-01-01

    Members of the ubiquitous COX11 (cytochrome c oxidase 11) protein family are involved in copper delivery to the COX complex. In this work, we characterize the Arabidopsis thaliana COX11 homolog (encoded by locus At1g02410). Western blot analyses and confocal microscopy identified Arabidopsis COX11 as an integral mitochondrial protein. Despite sharing high sequence and structural similarities, the Arabidopsis COX11 is not able to functionally replace the Saccharomyces cerevisiae COX11 homolog. Nevertheless, further analysis confirmed the hypothesis that Arabidopsis COX11 is essential for COX activity. Disturbance of COX11 expression through knockdown (KD) or overexpression (OE) affected COX activity. In KD lines, the activity was reduced by ~50%, resulting in root growth inhibition, smaller rosettes and leaf curling. In OE lines, the reduction was less pronounced (~80% of the wild type), still resulting in root growth inhibition. Additionally, pollen germination was impaired in COX11 KD and OE plants. This effect on pollen germination can only partially be attributed to COX deficiency and may indicate a possible auxiliary role of COX11 in ROS metabolism. In agreement with its role in energy production, the COX11 promoter is highly active in cells and tissues with high-energy demand for example shoot and root meristems, or vascular tissues of source and sink organs. In COX11 KD lines, the expression of the plasma-membrane copper transporter COPT2 and of several copper chaperones was altered, indicative of a retrograde signaling pathway pertinent to copper homeostasis. Based on our data, we postulate that COX11 is a mitochondrial chaperone, which plays an important role for plant growth and pollen germination as an essential COX complex assembly factor.

  13. Bi-weekly waterfowl survey data entry

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Data sheet for the entry of bi-weekly waterfowl survey data from the state of Kansas. This Excel file contains the data entry sheet and a chart displaying waterfowl...

  14. The Right Delay

    NARCIS (Netherlands)

    Datadien, A.H.R.; Haselager, W.F.G.; Sprinkhuizen-Kuyper, I.G.

    2011-01-01

    Axonal conduction delays should not be ignored in simulations of spiking neural networks. Here it is shown that by using axonal conduction delays, neurons can display sensitivity to a specific spatio-temporal spike pattern. By using delays that complement the firing times in a pattern, spikes can ar

  15. Computation of the pseudoskin factor for a restricted-entry well

    Energy Technology Data Exchange (ETDEWEB)

    Ding, W. (Joshi Technologies International Inc., Tulsa, OK (United States)); Reynolds, A.C. Jr. (Univ. of Tulsa, OK (United States))

    1994-03-01

    Wells frequently are completed over a fraction of the oil zone to delay water and gas coning. This type of completion is called a restricted-entry or partially penetrating well. When analyzing well-test data from a restricted-entry well, semilog analysis of pseudoradial flow data yields an estimate of the total skin factor, which is a linear combination of the mechanical skin factor and the pseudoskin factor caused by restricted entry. This work presented two new equations for computing the pseudoskin factor from a restricted-entry well completed in a multilayer reservoir. These equations represent generalization of formulas presented by Papatzacos and Vrbik for single-layer homogeneous reservoirs. For ranges of reservoir and well parameters ordinarily encountered, the new equations provide results approximately equal to those obtained from the Yeh-Reynolds calculation procedure, but are easier to use than this equation.

  16. Flavivirus Entry Receptors: An Update

    Directory of Open Access Journals (Sweden)

    Manuel Perera-Lecoin

    2013-12-01

    Full Text Available Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM and TYRO3, AXL and MER (TAM. Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.

  17. 19 CFR 122.42 - Aircraft entry.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Aircraft entry. 122.42 Section 122.42 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements...

  18. Sunk costs, entry deterrence, and financial constraints

    NARCIS (Netherlands)

    Arping, S.; Diaw, K.M.

    2008-01-01

    This paper studies how sunk costs affect a financially constrained incumbent's ability to deter entry into its market. Sunk costs make it less attractive to the incumbent to accommodate entry by liquidating assets in place and exiting the market. This may render entry by a prospective rival

  19. Sport entries and qualification manual: Nanjing 2014

    OpenAIRE

    2014-01-01

    Sport entries constitute an important part of the delegation registration process of the Nanjing 2014 Summer Youth Olympic Games. This manual aims to introduce to NOCs the process, relevant policies and requirements regarding sport entries so as to ensure that NOCs can successfully complete the entries for their athletes to the Nanjing 2014 Youth Olympic Games.

  20. In vitro and In Silico Studies on Curcumin and Its Analogues as Dual Inhibitors for cyclooxygenase-1 (COX-1 and cyclooxygenase-2 (COX-2

    Directory of Open Access Journals (Sweden)

    Nunung Yuniarti

    2012-03-01

    Full Text Available Curcumin has been widely reported as an anti-inflammatory agent isolated from the plant Curcuma longa L. (turmeric. This anti-inflammatory activity was associated with the ability of this compound to inhibit the activity of both cyclooxygenase-1 (COX-1 and cyclooxygenase-2 (COX-2 in arachidonic acid metabolism. Dual COX-1 and COX-2 inhibitors are preferred to be employed in the therapy of chronic inflammatory diseases compared to selective inhibitors, since it was reported that the use of selective inhibitors led to severe adverse side effect. In the present study, in vitro and in silico assays on curcumin and its analogues as dual inhibitors for both COX-1 and COX-2 were performed. The results provide theoretical contribution in understanding the ligand-protein interactions at the molecular level to develop new curcumin analogues which possess better anti-inflammatory activity as well as to avoid unsolicited side effects.

  1. LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression pattern reveals non-vascular sites of COX-2 expression.

    Directory of Open Access Journals (Sweden)

    Nicholas S Kirkby

    Full Text Available There are two schools of thought regarding the cyclooxygenase (COX isoform active in the vasculature. Using urinary prostacyclin markers some groups have proposed that vascular COX-2 drives prostacyclin release. In contrast, we and others have found that COX-1, not COX-2, is responsible for vascular prostacyclin production. Our experiments have relied on immunoassays to detect the prostacyclin breakdown product, 6-keto-PGF1α and antibodies to detect COX-2 protein. Whilst these are standard approaches, used by many laboratories, antibody-based techniques are inherently indirect and have been criticized as limiting the conclusions that can be drawn. To address this question, we measured production of prostanoids, including 6-keto-PGF1α, by isolated vessels and in the circulation in vivo using liquid chromatography tandem mass spectrometry and found values essentially identical to those obtained by immunoassay. In addition, we determined expression from the Cox2 gene using a knockin reporter mouse in which luciferase activity reflects Cox2 gene expression. Using this we confirm the aorta to be essentially devoid of Cox2 driven expression. In contrast, thymus, renal medulla, and regions of the brain and gut expressed substantial levels of luciferase activity, which correlated well with COX-2-dependent prostanoid production. These data are consistent with the conclusion that COX-1 drives vascular prostacyclin release and puts the sparse expression of Cox2 in the vasculature in the context of the rest of the body. In doing so, we have identified the thymus, gut, brain and other tissues as target organs for consideration in developing a new understanding of how COX-2 protects the cardiovascular system.

  2. In Silico Analysis of the Potential of the Active Compounds Fucoidan and Alginate Derived from Sargassum Sp. as Inhibitors of COX-1 and COX-2

    OpenAIRE

    Dewi, Lestari

    2016-01-01

    Introduction: The enzyme cyclooxygenase (COX) is an enzyme that catalyzes the formation of one of the mediators of inflammation, the prostaglandins. Inhibition of COX allegedly can improve inflammation-induced pathological conditions. Aim: The purpose of the present study was to evaluate the potential of Sargassum sp. components, Fucoidan and alginate, as COX inhibitors. Material and methods: The study was conducted by means of a computational (in silico) method. It was performed in two main ...

  3. 19 CFR 143.36 - Form of immediate delivery, entry and entry summary.

    Science.gov (United States)

    2010-04-01

    ... Form of immediate delivery, entry and entry summary. (a) Electronic form of data. If Customs determines... 19 Customs Duties 2 2010-04-01 2010-04-01 false Form of immediate delivery, entry and entry summary. 143.36 Section 143.36 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF...

  4. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    Directory of Open Access Journals (Sweden)

    Lagerstedt Kristina

    2011-06-01

    Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

  5. Synthesis and biological evaluation of 3-amino-2-pyrones as selective cyclooxygenase-1 (COX-1) inhibitors

    Institute of Scientific and Technical Information of China (English)

    Xue-Ping Chu; Qing-Fa Zhou; Shen Zhao; Fei-Fei Ge; Mian Fu; Jia-Peng Chen; Tao Lu

    2013-01-01

    A group of 3-amino-2-pyrones were synthesized and their biological activities were evaluated for inhibiting cyclooxygenase (COX) activity.This study has led to the identification of COX-1-selective inhibitors.Among the tested compounds,the compound 5j exhibited the most potent COX-1 inhibitory activity (IC50 =19.32 μg/mL) and COX-1 selectivity index (SI =41.98).

  6. An Analytical Delay Model

    Institute of Scientific and Technical Information of China (English)

    MIN Yinghua; LI Zhongcheng

    1999-01-01

    Delay consideration has been a majorissue in design and test of high performance digital circuits. Theassumption of input signal change occurring only when all internal nodesare stable restricts the increase of clock frequency. It is no longertrue for wave pipelining circuits. However, previous logical delaymodels are based on the assumption. In addition, the stable time of arobust delay test generally depends on the longest sensitizable pathdelay. Thus, a new delay model is desirable. This paper explores thenecessity first. Then, Boolean process to analytically describe thelogical and timing behavior of a digital circuit is reviewed. Theconcept of sensitization is redefined precisely in this paper. Based onthe new concept of sensitization, an analytical delay model isintroduced. As a result, many untestable delay faults under thelogical delay model can be tested if the output waveforms can be sampledat more time points. The longest sensitizable path length is computedfor circuit design and delay test.

  7. Extended cox regression model: The choice of timefunction

    Science.gov (United States)

    Isik, Hatice; Tutkun, Nihal Ata; Karasoy, Durdu

    2017-07-01

    Cox regression model (CRM), which takes into account the effect of censored observations, is one the most applicative and usedmodels in survival analysis to evaluate the effects of covariates. Proportional hazard (PH), requires a constant hazard ratio over time, is the assumptionofCRM. Using extended CRM provides the test of including a time dependent covariate to assess the PH assumption or an alternative model in case of nonproportional hazards. In this study, the different types of real data sets are used to choose the time function and the differences between time functions are analyzed and discussed.

  8. Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

    NARCIS (Netherlands)

    Bijnsdorp, Irene; Berg, van den Jaap; Kuipers, Gitta; Wedekind, Laurine; Slotman, Ben; Rijn, van Johannes; Lafleur, M.; Sminia, Peter

    2007-01-01

    The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 in

  9. COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice

    DEFF Research Database (Denmark)

    Norregaard, Rikke; Madsen, Kirsten Morill; Hansen, Pernille Bl

    2011-01-01

    It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2(-/-), C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP...

  10. Atmospheric Entry Experiments at IRS

    Science.gov (United States)

    Auweter-Kurtz, M.; Endlich, P.; Herdrich, G.; Kurtz, H.; Laux, T.; Löhle, S.; Nazina, N.; Pidan, S.

    2002-01-01

    Entering the atmosphere of celestial bodies, spacecrafts encounter gases at velocities of several km/s, thereby being subjected to great heat loads. The thermal protection systems and the environment (plasma) have to be investigated by means of computational and ground facility based simulations. For more than a decade, plasma wind tunnels at IRS have been used for the investigation of TPS materials. Nevertheless, ground tests and computer simulations cannot re- place space flights completely. Particularly, entry mission phases encounter challenging problems, such as hypersonic aerothermodynamics. Concerning the TPS, radiation-cooled materials used for reuseable spacecrafts and ablator tech- nologies are of importance. Besides the mentioned technologies, there is the goal to manage guidance navigation, con- trol, landing technology and inflatable technologies such as ballutes that aim to keep vehicles in the atmosphere without landing. The requirement to save mass and energy for planned interplanetary missions such as Mars Society Balloon Mission, Mars Sample Return Mission, Mars Express or Venus Sample Return mission led to the need for manoeuvres like aerocapture, aero-breaking and hyperbolic entries. All three are characterized by very high kinetic vehicle energies to be dissipated by the manoeuvre. In this field flight data are rare. The importance of these manoeuvres and the need to increase the knowledge of required TPS designs and behavior during such mission phases point out the need of flight experiments. As result of the experience within the plasma diagnostic tool development and the plasma wind tunnel data base, flight experiments like the PYrometric RE-entry EXperiment PYREX were developed, fully qualified and successfully flown. Flight experiments such as the entry spectrometer RESPECT and PYREX on HOPE-X are in the conceptual phase. To increase knowledge in the scope of atmospheric manoeuvres and entries, data bases have to be created combining both

  11. COX-2 in Cancer: Gordian knot or Achilles heel?

    Directory of Open Access Journals (Sweden)

    Ioannis eStasinopoulos

    2013-03-01

    Full Text Available The networks of blood and lymphatic vessels and of the extracellular matrix and their cellular and structural components, that are collectively termed the tumor microenvironment, are frequently co-opted and shaped by cancer cells to survive, invade and form distant metastasis. With an enviable capacity to adapt to continually changing environments, cancer represents the epitome of functional chaos, a stark contrast to the hierarchical and organized differentiation processes that dictate the development and life of biological organisms. The consequences of changing landscapes such as hypoxia and acidic extracellular pH in and around tumors create a cascade of, or themselves are results of, changes in multiple pathways and networks that become apparent only several years later as recurrence and metastasis. These molecular and phenotypic changes approach the complexities of a ‘Gordian Knot’. We review evidence from our studies and from literature suggesting that COX-2 biology presents a nodal point in cancer biology and an ‘Achilles heel’ of COX-2-dependent tumors.

  12. Thrombosis is reduced by inhibition of COX-1, but unaffected by inhibition of COX-2, in an acute model of platelet activation in the mouse.

    Directory of Open Access Journals (Sweden)

    Paul C Armstrong

    Full Text Available BACKGROUND: Clinical use of selective inhibitors of cyclooxygenase (COX-2 appears associated with increased risk of thrombotic events. This is often hypothesised to reflect reduction in anti-thrombotic prostanoids, notably PGI(2, formed by COX-2 present within endothelial cells. However, whether COX-2 is actually expressed to any significant extent within endothelial cells is controversial. Here we have tested the effects of acute inhibition of COX on platelet reactivity using a functional in vivo approach in mice. METHODOLOGY/PRINCIPAL FINDINGS: A non-lethal model of platelet-driven thromboembolism in the mouse was used to assess the effects of aspirin (7 days orally as control diclofenac (1 mg.kg(-1, i.v. and parecoxib (0.5 mg.kg(-1, i.v. on thrombus formation induced by collagen or the thromboxane (TX A(2-mimetic, U46619. The COX inhibitory profiles of the drugs were confirmed in mouse tissues ex vivo. Collagen and U46619 caused in vivo thrombus formation with the former, but not latter, sensitive to oral dosing with aspirin. Diclofenac inhibited COX-1 and COX-2 ex vivo and reduced thrombus formation in response to collagen, but not U46619. Parecoxib inhibited only COX-2 and had no effect upon thrombus formation caused by either agonist. CONCLUSIONS/SIGNIFICANCE: Inhibition of COX-1 by diclofenac or aspirin reduced thrombus formation induced by collagen, which is partly dependent upon platelet-derived TXA(2, but not that induced by U46619, which is independent of platelet TXA(2. These results are consistent with the model demonstrating the effects of COX-1 inhibition in platelets, but provide no support for the hypothesis that acute inhibition of COX-2 in the circulation increases thrombosis.

  13. Statistical Inference in Cox-Ingersoll-Ross Model%Cox-Ingersoll-Ross模型的统计推断

    Institute of Scientific and Technical Information of China (English)

    陈萍; 杨孝平

    2005-01-01

    本文研究了Cox-Ingersoll-Ross模型的统计推断问题.给出了CIR过程的平稳均值m与平稳方差v的矩估计,并利用m和v给出了CIR过程中尺度参数α与波动率β之间的关系,讨论了参数α的条件矩估计和渐近极大似然估计.并通过数值模拟对条件矩估计,渐近极大似然估计这两种方法作了比较.

  14. Matrix Completion from Noisy Entries

    CERN Document Server

    Keshavan, Raghunandan H; Oh, Sewoong

    2009-01-01

    Given a matrix M of low-rank, we consider the problem of reconstructing it from noisy observations of a small, random subset of its entries. The problem arises in a variety of applications, from collaborative filtering (the `Netflix problem') to structure-from-motion and positioning. We study a low complexity algorithm introduced by Keshavan et al.(2009), based on a combination of spectral techniques and manifold optimization, that we call here OptSpace. We prove performance guarantees that are order-optimal in a number of circumstances.

  15. Nonsteroidal Anti-Inflammatory Treatment Prevents Delayed Effects of Early Life Stress in Rats

    Science.gov (United States)

    Brenhouse, Heather C.; Andersen, Susan L.

    2017-01-01

    Background Early developmental insults can cause dysfunction within parvalbumin (PVB)-containing interneurons in the prefrontal cortex. The neuropsychiatric disorders associated with such dysfunction might involve neuroinflammatory processes. Cyclooxygenase-2 (COX-2) is a key mediator of inflammation and is therefore a potential target for preventive treatment. Here, we investigated whether the developmental trajectories of PVB expression and COX-2 induction in the prelimbic region of the prefrontal cortex are altered after maternal separation stress in male rats. Methods Male rat pups were separated from their mother and littermates for 4 hours/day between postnatal Days 2 and 20. Western blotting and immunohistochemistry were used to analyze PVB and COX-2 expression in the prefrontal cortex and hippocampus. A separate cohort of animals was treated with a COX-2 inhibitor during preadolescence and analyzed for PVB, COX-2, and working memory performance. Results We demonstrate that maternal separation causes a reduction of PVB and an increase in COX-2 expression in the prefrontal cortex in adolescence, with concurrent working memory deficits. Parvalbumin was not affected earlier in development. Prophylactic COX-2 inhibition preadolescence prevents PVB loss and improves working memory deficits induced by maternal separation. Conclusions These data are the first to show a preventive pharmacological intervention for the delayed effects of early life stress on prefrontal cortex interneurons and working memory. Our results suggest a possible mechanism for the relationship between early life stress and interneuron dysfunction in adolescence. PMID:21679927

  16. Niacin and biosynthesis of PGD₂ by platelet COX-1 in mice and humans

    DEFF Research Database (Denmark)

    Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela

    2012-01-01

    The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1-dependent formation of PGD₂ and PGE₂ followed by COX-2-dependent production of PGE₂. Consistent with this, niacin......-induced flushing in humans is attenuated when niacin is combined with an antagonist of the PGD₂ receptor DP1. NSAID-mediated suppression of COX-2-derived PGI₂ has negative cardiovascular consequences, yet little is known about the cardiovascular biology of PGD₂. Here, we show that PGD₂ biosynthesis is augmented....... Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1-derived PGD₂ biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased...

  17. Cox26 is a novel stoichiometric subunit of the yeast cytochrome c oxidase.

    Science.gov (United States)

    Levchenko, Maria; Wuttke, Jan-Moritz; Römpler, Katharina; Schmidt, Bernhard; Neifer, Klaus; Juris, Lisa; Wissel, Mirjam; Rehling, Peter; Deckers, Markus

    2016-07-01

    The cytochrome c oxidase (COX) is the terminal enzyme of the respiratory chain. The complex accepts electrons from cytochrome c and passes them onto molecular oxygen. This process contributes to energy capture in the form of a membrane potential across the inner membrane. The enzyme complex assembles in a stepwise process from the three mitochondria-encoded core subunits Cox1, Cox2 and Cox3, which associate with nuclear-encoded subunits and cofactors. In the yeast Saccharomyces cerevisiae, the cytochrome c oxidase associates with the bc1-complex into supercomplexes, allowing efficient energy transduction. Here we report on Cox26 as a protein found in respiratory chain supercomplexes containing cytochrome c oxidase. Our analyses reveal Cox26 as a novel stoichiometric structural subunit of the cytochrome c oxidase. A loss of Cox26 affects cytochrome c oxidase activity and respirasome organization.

  18. Cyclooxygenases (COX-1 and COX-2) for tissue engineering of articular cartilage--from a developmental model to first results of tissue and scaffold expression.

    Science.gov (United States)

    Brochhausen, Christoph; Zehbe, Rolf; Gross, Ulrich; Libera, Jeanette; Schubert, Helmut; Nüsing, Rolf M; Klaus, Günter; Kirkpatrick, C James

    2008-01-01

    Tissue engineering of articular cartilage remains an ongoing challenge. Since tissue regeneration recapitulates ontogenetic processes the growth plate can be regarded as an innovative model to target suitable signalling molecules and growth factors for the tissue engineering of cartilage. In the present study we analysed the expression of cyclooxygenases (COX) in a short-term chondrocyte culture in gelatin-based scaffolds and in articular cartilage of rats and compared it with that in the growth plate. Our results demonstrate the strong cellular expression of COX-1 but only a focal weak expression of COX-2 in the seeded scaffolds. Articular cartilage of rats expresses homogeneously COX-1 and COX-2 with the exception of the apical cell layer. Our findings indicate a functional role of COX in the metabolism of articular chondrocytes. The expression of COX in articular cartilage and in the seeded scaffolds opens interesting perspectives to improve the proliferation and differentiation of chondrocytes in scaffold materials by addition of specific receptor ligands of the COX system.

  19. Hepatic ischemia and reperfusion injury in the absence of myeloid cell-derived COX-2 in mice.

    Directory of Open Access Journals (Sweden)

    Sergio Duarte

    Full Text Available Cyclooxygenase-2 (COX-2 is a mediator of hepatic ischemia and reperfusion injury (IRI. While both global COX-2 deletion and pharmacologic COX-2 inhibition ameliorate liver IRI, the clinical use of COX-2 inhibitors has been linked to increased risks of heart attack and stroke. Therefore, a better understanding of the role of COX-2 in different cell types may lead to improved therapeutic strategies for hepatic IRI. Macrophages of myeloid origin are currently considered to be important sources of the COX-2 in damaged livers. Here, we used a Cox-2flox conditional knockout mouse (COX-2-M/-M to examine the function of COX-2 expression in myeloid cells during liver IRI. COX-2-M/-M mice and their WT control littermates were subjected to partial liver ischemia followed by reperfusion. COX-2-M/-M macrophages did not express COX-2 upon lipopolysaccharide stimulation and COX-2-M/-M livers showed reduced levels of COX-2 protein post-IRI. Nevertheless, selective deletion of myeloid cell-derived COX-2 failed to ameliorate liver IRI; serum transaminases and histology were comparable in both COX-2-M/-M and WT mice. COX-2-M/-M livers, like WT livers, developed extensive necrosis, vascular congestion, leukocyte infiltration and matrix metalloproteinase-9 (MMP-9 expression post-reperfusion. In addition, myeloid COX-2 deletion led to a transient increase in IL-6 levels after hepatic reperfusion, when compared to controls. Administration of celecoxib, a selective COX-2 inhibitor, resulted in significantly improved liver function and histology in both COX-2-M/-M and WT mice post-reperfusion, providing evidence that COX-2-mediated liver IRI is caused by COX-2 derived from a source(s other than myeloid cells. In conclusion, these results support the view that myeloid COX-2, including myeloid-macrophage COX-2, is not responsible for the hepatic IRI phenotype.

  20. Delayed emergence after anesthesia.

    Science.gov (United States)

    Tzabazis, Alexander; Miller, Christopher; Dobrow, Marc F; Zheng, Karl; Brock-Utne, John G

    2015-06-01

    In most instances, delayed emergence from anesthesia is attributed to residual anesthetic or analgesic medications. However, delayed emergence can be secondary to unusual causes and present diagnostic dilemmas. Data from clinical studies is scarce and most available published material is comprised of case reports. In this review, we summarize and discuss less common and difficult to diagnose reasons for delayed emergence and present cases from our own experience or reference published case reports/case series. The goal is to draw attention to less common reasons for delayed emergence, identify patient populations that are potentially at risk and to help anesthesiologists identifying a possible cause why their patient is slow to wake up.

  1. Delayed-onset akathisia due to amisulpride

    Directory of Open Access Journals (Sweden)

    Murad Atmaca

    2011-01-01

    Full Text Available Despite the fact that second-generation antipsychotics have a lower potential to cause extrapyramidal side-effects, including akathisia, their incidence is not negligible. Recent work suggests that tardive akathisia may have pharmacological differences from acute akathisia. In the present study, we have evaluated the nature of delayed-onset akathisia in patients on amisülpride monotherapy. Overall, we screened 56 patients on amisulpride treatment for 2 months at a stabilized amisulpride dose. However, 18 patients with diagnostic and statistical manual of mental disorders-IV (DSM-IV presented with acute or delayed-onset akathisia, and all of them also met the entry criteria. The patients were evaluated at baseline and at the time when akathisia presented clinically, with respect to the Positive and Negative Syndrome Scale and Barnes Akathisia Scale (BAS. Using the primary categorical criterion of akathisia (≥2 points of the BAS global scale, 12 (21.4% of the 56 patients experienced delayed-onset akathisia, and six (10.7% showed acute akathisia. The mean time for onset of acute or delayed-onset akathisia was 5.8 ± 2.1 and 39.4 ± 11.3 days, respectively. The mean BAS scores at baseline and after the period of 2 months were 1.3 ± 0.6 and 3.9 ± 2.4, respectively (P < 0.001. Our results revealed that amisulpride could considerably lead to delayed-onset akathisia. However, studies comprising larger samples receiving different antipsychotics, and more comprehensive assessment, will help to ascertain the role of amisulpride in delayed-onset akathisia.

  2. COX-2 inhibitors: a CLASS act or Just VIGORously promoted.

    Science.gov (United States)

    Malhotra, Samir; Shafiq, N; Pandhi, P

    2004-03-23

    Abstract Selective cyclo-oxygenase (COX)-2 inhibitors were developed with the hope of producing lesser gastrointestinal (GI) side effects as compared with the conventional nonsteroidal anti-inflammatory drugs (NSAIDs). Soon after their introduction into the market, the sales of celecoxib and rofecoxib went up considerably. Most of this was attributed to the results of the Celecoxib Long-term Arthritis Safety Study (CLASS) and Vioxx Gastrointestinal Outcome Research (VIGOR) trials. However, several discrepancies were noted in the presentation of the actual trial results submitted to the US Food and Drug Administration (FDA) and those used for the purpose of publication in scientific journals. These issues were discussed subsequently by the way of scientific communications. Moreover, with increasing use of these agents, evidence of their adverse effects is coming to light. The present review aims at discussing the above issues, with emphasis on the results of the CLASS and VIGOR trials.

  3. Gaussian estimation for discretely observed Cox-Ingersoll-Ross model

    Science.gov (United States)

    Wei, Chao; Shu, Huisheng; Liu, Yurong

    2016-07-01

    This paper is concerned with the parameter estimation problem for Cox-Ingersoll-Ross model based on discrete observation. First, a new discretized process is built based on the Euler-Maruyama scheme. Then, the parameter estimators are obtained by employing the maximum likelihood method and the explicit expressions of the error of estimation are given. Subsequently, the consistency property of all parameter estimators are proved by applying the law of large numbers for martingales, Holder's inequality, B-D-G inequality and Cauchy-Schwarz inequality. Finally, a numerical simulation example for estimators and the absolute error between estimators and true values is presented to demonstrate the effectiveness of the estimation approach used in this paper.

  4. Random weighting method for Cox's proportional hazards model

    Institute of Scientific and Technical Information of China (English)

    CUI WenQuan; LI Kai; YANG YaNing; WU YueHua

    2008-01-01

    Variance of parameter estimate in Cox's proportional hazards model is based on asymptotic variance.When sample size is small,variance can be estimated by bootstrap method.However,if censoring rate in a survival data set is high,bootstrap method may fail to work properly.This is because bootstrap samples may be even more heavily censored due to repeated sampling of the censored observations.This paper proposes a random weighting method for variance estimation and confidence interval estimation for proportional hazards model.This method,unlike the bootstrap method,does not lead to more severe censoring than the original sample does.Its large sample properties are studied and the consistency and asymptotic normality are proved under mild conditions.Simulation studies show that the random weighting method is not as sensitive to heavy censoring as bootstrap method is and can produce good variance estimates or confidence intervals.

  5. Inverse probability weighted Cox regression for doubly truncated data.

    Science.gov (United States)

    Mandel, Micha; de Uña-Álvarez, Jacobo; Simon, David K; Betensky, Rebecca A

    2017-09-08

    Doubly truncated data arise when event times are observed only if they fall within subject-specific, possibly random, intervals. While non-parametric methods for survivor function estimation using doubly truncated data have been intensively studied, only a few methods for fitting regression models have been suggested, and only for a limited number of covariates. In this article, we present a method to fit the Cox regression model to doubly truncated data with multiple discrete and continuous covariates, and describe how to implement it using existing software. The approach is used to study the association between candidate single nucleotide polymorphisms and age of onset of Parkinson's disease. © 2017, The International Biometric Society.

  6. Regularization for Cox's Proportional Hazards Model With NP-Dimensionality

    CERN Document Server

    Bradic, Jelena; Jiang, Jiancheng

    2010-01-01

    High throughput genetic sequencing arrays with thousands of measurements per sample and a great amount of related censored clinical data have increased demanding need for better measurement specific model selection. In this paper we establish strong oracle properties of non-concave penalized methods for {\\it non-polynomial} (NP) dimensional data with censoring in the framework of Cox's proportional hazards model. A class of folded-concave penalties are employed and both LASSO and SCAD are discussed specifically. We unveil the question under which dimensionality and correlation restrictions can an oracle estimator be constructed and grasped. It is demonstrated that non-concave penalties lead to significant reduction of the "irrepresentable condition" needed for LASSO model selection consistency. The large deviation result for martingales, bearing interests of its own, is developed for characterizing the strong oracle property. Moreover, the non-concave regularized estimator, is shown to achieve asymptotically ...

  7. Adaptive Text Entry for Mobile Devices

    DEFF Research Database (Denmark)

    Proschowsky, Morten Smidt

    for mobile devices and a framework for adaptive context-aware language models. Based on analysis of current text entry methods, the requirements to the new text entry methods are established. Transparent User guided Prediction (TUP) is a text entry method for devices with one dimensional touch input. It can......The reduced size of many mobile devices makes it difficult to enter text with them. The text entry methods are often slow or complicated to use. This affects the performance and user experience of all applications and services on the device. This work introduces new easy-to-use text entry methods...... to improve the models of human motor behaviour. TUP-Key is a variant of TUP, designed for 12 key phone keyboards. It is introduced in the thesis but has not been implemented or evaluated. Both text entry methods support adaptive context-aware language models. YourText is a framework for adaptive context...

  8. Preventing re-entry to foster care.

    Science.gov (United States)

    Carnochan, Sarah; Rizik-Baer, Daniel; Austin, Michael J

    2013-01-01

    Re-entry to foster care generally refers to circumstances in which children who have been discharged from foster care to be reunified with their family of origin, adopted, or provided kinship guardianship are returned to foster care. In the context of the federal performance measurement system, re-entry refers specifically to a return to foster care following an unsuccessful reunification. The federal Children and Family Services Review measures re-entry to foster care with a single indicator, called the permanency of reunification indicator, one of four indicators comprising the reunification composite measure. This review focuses on research related to the re-entry indicator, including the characteristics of children, caregivers and families, as well as case and child welfare services that are associated with a higher or lower risk of re-entry to foster care. Promising post-reunification services designed to prevent re-entry to foster care are described.

  9. Box-Cox Mixed Logit Model for Travel Behavior Analysis

    Science.gov (United States)

    Orro, Alfonso; Novales, Margarita; Benitez, Francisco G.

    2010-09-01

    To represent the behavior of travelers when they are deciding how they are going to get to their destination, discrete choice models, based on the random utility theory, have become one of the most widely used tools. The field in which these models were developed was halfway between econometrics and transport engineering, although the latter now constitutes one of their principal areas of application. In the transport field, they have mainly been applied to mode choice, but also to the selection of destination, route, and other important decisions such as the vehicle ownership. In usual practice, the most frequently employed discrete choice models implement a fixed coefficient utility function that is linear in the parameters. The principal aim of this paper is to present the viability of specifying utility functions with random coefficients that are nonlinear in the parameters, in applications of discrete choice models to transport. Nonlinear specifications in the parameters were present in discrete choice theory at its outset, although they have seldom been used in practice until recently. The specification of random coefficients, however, began with the probit and the hedonic models in the 1970s, and, after a period of apparent little practical interest, has burgeoned into a field of intense activity in recent years with the new generation of mixed logit models. In this communication, we present a Box-Cox mixed logit model, original of the authors. It includes the estimation of the Box-Cox exponents in addition to the parameters of the random coefficients distribution. Probability of choose an alternative is an integral that will be calculated by simulation. The estimation of the model is carried out by maximizing the simulated log-likelihood of a sample of observed individual choices between alternatives. The differences between the predictions yielded by models that are inconsistent with real behavior have been studied with simulation experiments.

  10. American Dream Delayed

    DEFF Research Database (Denmark)

    Khorunzhina, Natalia; Miller, Robert A.

    This paper investigates the delay in homeownership and a subsequent reduction in homeownership rate observed over the past decades. We focus on the delay in giving birth to children and increased labor market participation as contributing factors to homeownership dynamics for prime-age female hou...

  11. Prognostic relevance of cyclooxygenase-2 (COX-2) expression in Chinese patients with prostate cancer.

    Science.gov (United States)

    Bin, Wu; He, Wang; Feng, Zhang; Xiangdong, Lu; Yong, Chen; Lele, Kou; Hongbin, Zhang; Honglin, Guo

    2011-02-01

    Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, has been reported to be correlated with tumorigenesis, tumor progression and metastasis. The present study was designed to investigate the clinicopathological and prognostic significance of COX-2 in Chinese patients with prostate cancer. Firstly, RT-PCR and Western blot assays were performed to detect the expression of COX-2 mRNA and protein in prostate cancer cell lines and 20 tissue samples (tumor or corresponding non-tumor). Next, immunohistochemistry was performed to detect the expression of COX-2 protein in 88 prostate cancer tissue samples. Finally, the correlation between COX-2 expression and clinicopathological factors and patient survival was evaluated. We found that the expression levels of COX-2 mRNA and protein showed significant difference among four prostate cancer cell lines. Moreover, the levels of COX-2 mRNA and protein were significantly higher in prostate cancer tissues than in corresponding non-tumor tissues. COX-2 staining was positive in the cytoplasm of prostate cancer cells. High-COX-2 expression was correlated with the Gleason score (P=0.009), tumor stage (P=0.012), and lymph-node status (P=0.036). Furthermore, patients with high-COX-2 expression showed lower disease-free (P=0.014) and overall survival (P=0.047) rates than those with low-COX-2 expression. Univariate and multivariate analyses suggested that the status of COX-2 protein expression was an independent prognostic indicator for patients' survival. Taken together, higher COX-2 protein expression might provide an independent prognostic marker for Chinese patients with prostate cancer who have undergone surgery.

  12. COX-2 mRNA expression in esophageal squamous cell carcinoma (ESCC) and effect by NSAID.

    Science.gov (United States)

    Liu, X; Li, P; Zhang, S-T; You, H; Jia, J-D; Yu, Z-L

    2008-01-01

    To investigate cyclooxygenase-2 (COX-2) mRNA expression in human esophageal squamous cell carcinoma and the effect of a non-steroidal anti-inflammatory drug (NSAID) on it, in order to explore the mechanism of COX-2 in esophageal squamous cell carcinoma (ESCC) carcinogenesis and the ability of NSAID to prevent or treat ESCC. Frozen specimens of human ESCC and adjacent normal esophageal squamous epithelium pairs (n = 22) were examined for COX-2 mRNA expression by reverse-transcription polymerase chain reaction (RT-PCR). After incubation with aspirin (a non-selective COX inhibitor) or Nimesulide (a selective COX-2 inhibitor), the proliferation status of two human esophageal squamous cancer cell lines, EC-9706 and EC-109, was quantified by 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide assay. The expression of COX-2 mRNA in these cells was detected by RT-PCR. COX-2 mRNA was expressed in 12 of 22 (54.5%) ESCC tissue samples, but it was undetectable in all the specimens of adjacent normal esophageal squamous epithelium COX-2 mRNA expression. Both aspirin (5-20 mmol/L) and Nimesulide (0.1-0.8 mmol/L) inhibited EC-9706 cell line proliferation and suppressed its COX-2 mRNA expression dose-dependently. However, only aspirin (5-20 mmol/L) could inhibit proliferation in the EC-109 cell line and suppress COX-2 mRNA expression. Nimesulide (0.1-0.8 mmol/L) could neither inhibit EC-109 cell growth nor suppress COX-2 mRNA expression. COX-2 mRNA expression is a frequent phenomenon in human ESCC tissue samples and plays an important role in the carcinogenesis of ESCC. NSAID may be useful in the chemoprevention and therapy of human ESCC and its effects are likely to be mediated by modulating COX-2 activity.

  13. Stakeholder identification of advanced technology opportunities at international ports of entry

    Energy Technology Data Exchange (ETDEWEB)

    Parker, S.K. [Sandia National Labs., Albuquerque, NM (United States). Energy Policy and Planning Dept.; Icerman, L. [Icerman and Associates, Santa Fe, NM (United States)

    1997-01-01

    As part of the Advanced Technologies for International and Intermodal Ports of Entry (ATIPE) Project, a diverse group of stakeholders was engaged to help identify problems experienced at inland international border crossings, particularly those at the US-Mexican border. The fundamental issue at international ports of entry is reducing transit time through the required documentation and inspection processes. Examples of other issues or problems, typically manifested as time delays at border crossings, repeatedly mentioned by stakeholders include: (1) lack of document standardization; (2) failure to standardize inspection processes; (3) inadequate information and communications systems; (4) manual fee and tariff collection; (5) inconsistency of processes and procedures; and (6) suboptimal cooperation among governmental agencies. Most of these issues can be addressed to some extent by the development of advanced technologies with the objective of allowing ports of entry to become more efficient while being more effective. Three categories of technologies were unambiguously of high priority to port of entry stakeholders: (1) automated documentation; (2) systems integration; and (3) vehicle and cargo tracking. Together, these technologies represent many of the technical components necessary for pre-clearance of freight approaching international ports of entry. Integration of vehicle and cargo tracking systems with port of entry information and communications systems, as well as existing industry legacy systems, should further enable border crossings to be accomplished consistently with optimal processing times.

  14. Lineage-specific fragmentation and nuclear relocation of the mitochondrial cox2 gene in chlorophycean green algae (Chlorophyta).

    Science.gov (United States)

    Rodríguez-Salinas, Elizabeth; Riveros-Rosas, Héctor; Li, Zhongkui; Fucíková, Karolina; Brand, Jerry J; Lewis, Louise A; González-Halphen, Diego

    2012-07-01

    In most eukaryotes the subunit 2 of cytochrome c oxidase (COX2) is encoded in intact mitochondrial genes. Some green algae, however, exhibit split cox2 genes (cox2a and cox2b) encoding two polypeptides (COX2A and COX2B) that form a heterodimeric COX2 subunit. Here, we analyzed the distribution of intact and split cox2 gene sequences in 39 phylogenetically diverse green algae in phylum Chlorophyta obtained from databases (28 sequences from 22 taxa) and from new cox2 data generated in this work (23 sequences from 18 taxa). Our results support previous observations based on a smaller number of taxa, indicating that algae in classes Prasinophyceae, Ulvophyceae, and Trebouxiophyceae contain orthodox, intact mitochondrial cox2 genes. In contrast, all of the algae in Chlorophyceae that we examined exhibited split cox2 genes, and could be separated into two groups: one that has a mitochondrion-localized cox2a gene and a nucleus-localized cox2b gene ("Scenedesmus-like"), and another that has both cox2a and cox2b genes in the nucleus ("Chlamydomonas-like"). The location of the split cox2a and cox2b genes was inferred using five different criteria: differences in amino acid sequences, codon usage (mitochondrial vs. nuclear), codon preference (third position frequencies), presence of nucleotide sequences encoding mitochondrial targeting sequences and presence of spliceosomal introns. Distinct green algae could be grouped according to the form of cox2 gene they contain: intact or fragmented, mitochondrion- or nucleus-localized, and intron-containing or intron-less. We present a model describing the events that led to mitochondrial cox2 gene fragmentation and the independent and sequential migration of cox2a and cox2b genes to the nucleus in chlorophycean green algae. We also suggest that the distribution of the different forms of the cox2 gene provides important insights into the phylogenetic relationships among major groups of Chlorophyceae.

  15. Cox-Ingersoll-Ross模型的统计推断%Statistical Inference of Cox-Ingersoll-Ross Model

    Institute of Scientific and Technical Information of China (English)

    舒丽玲; 周占功

    2006-01-01

    该文在离散样本观察下,研究了Cox-Ingersoll-Ross模型的统计推问题,给出了CIR过程的平稳均值m与平稳方差ν的矩估计,并用-m和-ν给出了CIR过程中尺度参数α与β波动率之间的关系,基于CIR过程的平方变差,得到参数β的平方变差估计和参数α的估计.通过数值模拟的方法对平方变差估计与条件矩估计([9])方法作了比较,并选择1997-2006年的R007数据对这两种方法进行了实证分析.

  16. Border Crossing/Entry Data - Border Crossing/Entry Data Time Series tool

    Data.gov (United States)

    Department of Transportation — The dataset is known as “Border Crossing/Entry Data.” The Bureau of Transportation Statistics (BTS) Border Crossing/Entry Data provides summary statistics to the...

  17. Entry Into a Care Trajectory

    Directory of Open Access Journals (Sweden)

    Normand Carpentier

    2013-06-01

    Full Text Available A broad range of services are developing in response to the needs of an aging population. Although most interventions are carried out in the patient’s living environment—at the heart of society—few studies on service utilization refer to social theory. This paper suggests that studies on older people with chronic health conditions would benefit from a stronger theoretical foundation. Drawing on 15 in-depth interviews, it highlights the relevance of individualization processes and the network society, 2 central theoretical concerns in sociology. The research provides a unique perspective on the entry into the care trajectory and expands our comprehension of the emergence of a social organization that can respond to the needs of elderly patients. Data of this nature may be useful in service planning and the development of a care-centered approach.

  18. Expression of beta-catenin, COX-2 and iNOS in colorectal cancer: relevance of COX-2 adn iNOS inhibitors for treatment in Malaysia.

    Science.gov (United States)

    Hong, Seok Kwan; Gul, Yunus A; Ithnin, Hairuszah; Talib, Arni; Seow, Heng Fong

    2004-01-01

    Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS. A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral. COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores. the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

  19. COX-2: A Pivotal Enzyme in Mucosal Protection and Resolution of Inflammation

    Directory of Open Access Journals (Sweden)

    John L. Wallace

    2006-01-01

    Full Text Available The discovery of a second form of cyclooxygenase, COX-2, led to a burst of research aimed at the development of nonsteroidal anti-inflammatory drugs that would not damage the gastrointestinal tract. In the years since, this promise has only been partially fulfilled. Selective COX-2 inhibitors cause less gastric damage than conventional, nonselective COX inhibitors, but their use is still associated with significant gastrointestinal injury, and with toxicity in the renal and cardiovascular systems. COX-2 is now recognized as a source of mediators that produce many beneficial and detrimental effects in the digestive system. In this review, the roles of COX-2 in mucosal defense and injury are discussed. Furthermore, contributions of COX-2–derived products to the long-term consequences of intestinal inflammation, including cancer, are reviewed.

  20. GLOBAL EXPONENTIAL STABILITY IN HOPFIELD AND BIDIRECTIONAL ASSOCIATIVE MEMORY NEURAL NETWORKS WITH TIME DELAYS

    Institute of Scientific and Technical Information of China (English)

    RONG LIBIN; LU WENLIAN; CHEN TIANPING

    2004-01-01

    Without assuming the boundedness, strict monotonicity and differentiability of the activation functions, the authors utilize the Lyapunov functional method to analyze the global convergence of some delayed models. For the Hopfield neural network with time delays, a new sufficient condition ensuring the existence, uniqueness and global exponential stability of the equilibrium point is derived. This criterion concerning the signs of entries in the connection matrix imposes constraints on the feedback matrix independently of the delay parameters. From a new viewpoint, the bidirectional associative memory neural network with time delays is investigated and a new global exponential stability result is given.

  1. Regulation of COX-2 expression by miR-146a in lung cancer cells.

    Science.gov (United States)

    Cornett, Ashley L; Lutz, Carol S

    2014-09-01

    Prostaglandins are a class of molecules that mediate cellular inflammatory responses and control cell growth. The oxidative conversion of arachidonic acid to prostaglandin H2 is carried out by two isozymes of cyclooxygenase, COX-1 and COX-2. COX-1 is constitutively expressed, while COX-2 can be transiently induced by external stimuli, such as pro-inflammatory cytokines. Interestingly, COX-2 is overexpressed in numerous cancers, including lung cancer. MicroRNAs (miRNAs) are small RNA molecules that function to regulate gene expression. Previous studies have implicated an important role for miRNAs in human cancer. We demonstrate here that miR-146a expression levels are significantly lower in lung cancer cells as compared with normal lung cells. Conversely, lung cancer cells have higher levels of COX-2 protein and mRNA expression. Introduction of miR-146a can specifically ablate COX-2 protein and the biological activity of COX-2 as measured by prostaglandin production. The regulation of COX-2 by miR-146a is mediated through a single miRNA-binding site present in the 3' UTR. Therefore, we propose that decreased miR-146a expression contributes to the up-regulation and overexpression of COX-2 in lung cancer cells. Since potential miRNA-mediated regulation is a functional consequence of alternative polyadenylation site choice, understanding the molecular mechanisms that regulate COX-2 mRNA alternative polyadenylation and miRNA targeting will give us key insights into how COX-2 expression is involved in the development of a metastatic condition.

  2. Population death sequences and Cox processes driven by interacting Feller diffusions

    CERN Document Server

    Wei Gang; Feng Jian Feng

    2002-01-01

    We carry out a complete study on the relationship between Cox processes driven by interacting Feller diffusions and death sequences of immigration-emigration linked population networks. It is first proved that the Cox process driven by a Feller diffusion is equivalent to the death sequence of a birth and death process. The conclusion is then generalized to the case of Cox processes driven by interacting Feller diffusions and death sequences of interacting populations.

  3. Foreign Entry and Heterogeneous Growth of Firms

    DEFF Research Database (Denmark)

    Deng, Paul Duo; Jefferson, Gary H.

    We adopt the framework of Schumpeterian creative destruction formalized by Aghion et al. (2009) to analyze the impact of foreign entry on the productivity growth of domestic firms. In the face of foreign entry, domestic firms exhibit heterogeneous patterns of growth depending on their technological...

  4. Predicting the Diversity of Foreign Entry Modes

    DEFF Research Database (Denmark)

    Hashai, Niron; Geisler Asmussen, Christian; Benito, Gabriel;

    2007-01-01

    diversity across value chain activities and host markets. Analyzing a sample of Israeli based firms we show that larger firms exhibit a higher degree of entry mode diversity both across value chain activities and across host markets. Higher levels of knowledge intensity are also associated with more...... diversity in firms' entry modes across both dimensions....

  5. Foreign Entry and Heterogeneous Growth of Firms

    DEFF Research Database (Denmark)

    Deng, Paul Duo; Jefferson, Gary H.

    We adopt the framework of Schumpeterian creative destruction formalized by Aghion et al. (2009) to analyze the impact of foreign entry on the productivity growth of domestic firms. In the face of foreign entry, domestic firms exhibit heterogeneous patterns of growth depending on their technologic...

  6. Use of cox-2 inhibitors in patients with retinal venous occlusive disease.

    Science.gov (United States)

    Recchia, Franco M; Chen, Eric; Li, Chun; Maguluri, Srilakshmi

    2008-01-01

    To determine the prevalence of prior or current usage of COX-2 inhibitors among patients with retinal venous occlusion (RVO). Records of all patients with RVO and control patients matched by age and gender without the diagnosis of RVO seen in a retina referral practice between May 1999 and October 2004 were reviewed. Prevalence of COX-2 inhibitor usage was compared. Multivariable analysis was used to assess the independent correlation of COX-2 inhibitor usage with RVO. A total of 111 consecutive patients with RVO and 316 controls without RVO were identified. There was no significant difference in race or presence of hypertension between cases and controls. Ten of the RVO patients (9%) had a history of using COX-2 inhibitors. Of these 10 patients, one had a central RVO, one had a hemi-central RVO, and eight had a branch RVO. Thirty-nine of the 321 controls (12%) had a history of COX-2 inhibitor use. The prevalence of COX-2 inhibitor usage among RVO patients was not significantly different from that of controls (9% versus 12%; P = 0.37). In a multivariable analysis adjusting for effects of age, gender, hypertension, diabetes, and cardiovascular disease, the association of COX-2 inhibitor usage and RVO was still not significant (P = 0.48). A few patients with RVO had prior or concurrent use of COX-2 inhibitors. The prevalence of COX-2 inhibitor usage does not appear to be significantly higher in patients with RVO.

  7. Structural insight into DNA binding and oligomerization of the multifunctional Cox protein of bacteriophage P2.

    Science.gov (United States)

    Berntsson, Ronnie P-A; Odegrip, Richard; Sehlén, Wilhelmina; Skaar, Karin; Svensson, Linda M; Massad, Tariq; Högbom, Martin; Haggård-Ljungquist, Elisabeth; Stenmark, Pål

    2014-02-01

    The Cox protein from bacteriophage P2 is a small multifunctional DNA-binding protein. It is involved in site-specific recombination leading to P2 prophage excision and functions as a transcriptional repressor of the P2 Pc promoter. Furthermore, it transcriptionally activates the unrelated, defective prophage P4 that depends on phage P2 late gene products for lytic growth. In this article, we have investigated the structural determinants to understand how P2 Cox performs these different functions. We have solved the structure of P2 Cox to 2.4 Å resolution. Interestingly, P2 Cox crystallized in a continuous oligomeric spiral with its DNA-binding helix and wing positioned outwards. The extended C-terminal part of P2 Cox is largely responsible for the oligomerization in the structure. The spacing between the repeating DNA-binding elements along the helical P2 Cox filament is consistent with DNA binding along the filament. Functional analyses of alanine mutants in P2 Cox argue for the importance of key residues for protein function. We here present the first structure from the Cox protein family and, together with previous biochemical observations, propose that P2 Cox achieves its various functions by specific binding of DNA while wrapping the DNA around its helical oligomer.

  8. Evaluating COX-2-765 G →C Genetic Polymorphism in Migraineurs

    Directory of Open Access Journals (Sweden)

    E Mozaffari

    2015-08-01

    Results: The study results revealed that the frequency of the COX-2-765CC and COX-2-765CG genotypes in migraine cases were significantly higher than those of controls. Conclusion: The study findings demonstrated that COX-2-765G→C polymorphism can increase the risk of migraine susceptibility. However, further studies are necessitated to be conducted on larger samples in different nations in other parts of the world in order to assess the role of COX-2 gene variants in the migraine development.

  9. COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells.

    Science.gov (United States)

    Ramer, Robert; Heinemann, Katharina; Merkord, Jutta; Rohde, Helga; Salamon, Achim; Linnebacher, Michael; Hinz, Burkhard

    2013-01-01

    The antitumorigenic mechanism of cannabidiol is still controversial. This study investigates the role of COX-2 and PPAR-γ in cannabidiol's proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis. Apoptotic cell death by cannabidiol was suppressed by NS-398 (COX-2 inhibitor), GW9662 (PPAR-γ antagonist), and siRNA targeting COX-2 and PPAR-γ. Cannabidiol-induced apoptosis was paralleled by upregulation of COX-2 and PPAR-γ mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 hours and continuous increases of PPAR-γ mRNA when compared with vehicle. In response to cannabidiol, tumor cell lines exhibited increased levels of COX-2-dependent prostaglandins (PG) among which PGD(2) and 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) caused a translocation of PPAR-γ to the nucleus and induced a PPAR-γ-dependent apoptotic cell death. Moreover, in A549-xenografted nude mice, cannabidiol caused upregulation of COX-2 and PPAR-γ in tumor tissue and tumor regression that was reversible by GW9662. Together, our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-γ and a subsequent nuclear translocation of PPAR-γ by COX-2-dependent PGs.

  10. Cox7a2 mediates steroidogenesis in TM3 mouse Leydig cells

    Institute of Scientific and Technical Information of China (English)

    Liang Chen; Zhong-Cheng Xin; Xin Li; Long Tian; Yi-Ming Yuan; Gang Liu; Xue-Jun Jiang; Ying-Lu Guo

    2006-01-01

    Aim: To investigate the regulatory function of Cox7a2 on steroidogenesis and the mechanism involved in TM3 mouse Leydig cells. Methods: The cDNA of Cox7a2 was cloned from TM3 mouse Leydig cells. It was subcloned to pDsRedExpress-N1 and transfected back into TM3 mouse Leydig cells for Cox7a2 overexpression by transient gene transfection.Steroidogenesis affected by overexpressed Cox7a2 was studied by ELISA. To elicit the mechanism of this effect,expression of steroidogenic acute regulatory (StAR) protein and reactive oxygen species (ROS) were examined by Western blot and fluorometer, respectively. Results: The cDNA of Cox7a2 (249 bp) was cloned from Leydig cells and confirmed by DNA sequencing. After constructed pDsRed-Express-Nl-Cox7a2 was transfected back into TM3 mouse Leydig cells, Cox7a2 inhibited not only luteinizing hormone (LH)-induced secretion of testosterone but also the expression of StAR protein. At the same time, Cox7a2 increased the activity of ROS in TM3 mouse Leydig cells. Conclusion:Cox7a2 inhibited LH-induced StAR protein expression, and consequent testosterone production, at least in part, by increasing ROS activity in TM3 mouse Leydig cells.

  11. Thermal Soak Analysis of Earth Entry Vehicles

    Science.gov (United States)

    Agrawal, Parul; Sepka, Steven A.; Aliaga, Jose F.; Venkatapathy, Ethiraj; Samareh, Jamshid A.

    2012-01-01

    The Multi-Mission Earth Entry Vehicle project is developing an integrated tool called Multi Mission System Analysis for Planetary Entry Descent and Landing that will provide key technology solutions including mass sizing, aerodynamics, aerothermodynamics, and thermal and structural analysis for any given sample return mission. Thermal soak analysis and temperature predictions of various components including the payload container of the entry vehicle are part of the solution that this tool will offer to mission designers. The present paper focuses on the thermal soak analysis of an entry vehicle design based on the Mars Sample Return entry vehicle geometry and discusses a technical approach to develop parametric models for thermal soak analysis that will be integrated into the tool.

  12. commensurate point delays

    Directory of Open Access Journals (Sweden)

    M. de la Sen

    2005-01-01

    nominal controller is maintained. In the current approach, the finite spectrum assignment is only considered as a particular case of the designer's choice of a (delay-dependent arbitrary spectrum assignment objective.

  13. Expression and significance of COX-2 and VEGF in osteosarcoma%骨肉瘤组织中COX-2、VEGF的表达及意义

    Institute of Scientific and Technical Information of China (English)

    马隽; 陈晓明; 钟艳平; 黎丹戎; 肖增明

    2011-01-01

    目的 观察骨肉瘤组织中环氧化酶2(COX-2)、血管内皮生长因子(VEGF)的表达情况,并探讨其意义.方法 对骨肉瘤患者45例行截肢术或瘤段切除假体置换术.术中分别切取骨肉瘤组织及对应癌旁(肿瘤组织边缘外5.0 cm处)组织标本.采用免疫组化SP法检测骨肉瘤组织及其癌旁组织中的COX-2、VEGF;以CD34为标记,计算微血管密度(MVD).结果 COX-2和VEGF阳性表达率及MVD在骨肉瘤组织中分别为80.0%、75.6%和(43.6±11.4)条/HP,均高于癌旁组织的22.2%、17.8%和(13.5±7.3)条/HP,且三者与骨肉瘤的外科分期有关(P均<0.05).COX-2与VEGF的表达呈正相关,COX-2和VEGF的表达均与MVD呈正相关(r分别为0.75、0.58和0.75,P均<0.05).COX-2和VEGF同时阳性表达时,MVD显著增高(P<0.05).结论 COX-2和VEGF在骨肉瘤组织中呈高表达,且与骨肉瘤外科分期呈正相关.二者共同参与了骨肉瘤的发生、发展,其机制可能是促进骨肉瘤组织中血管生成.%Objective To investigate the expression of cyclooxygenase 2 (COX-2) and vascular endothelial growth factor (VEGF) in osteosarcoma and explore the significance.Methods 45 patients with osteosarcoma were treated with amputation or prosthesis replacement.Osteosarcoma and corresponding adjacent ( > 5.0 cm at the outer edge of the tumor tissue) tissue samples were obtained during operation.The expression of COX-2, VEGF and MVD marked by CD34 of osteosarcoma and their adjacent tissues were detected by immuno histochemistry.Results The positive rates of COX-2, VEGF and MVD in osteosarcoma tissues were 80.0%, 75.6% and (43.6 ± 11.4) stripe/HP, respectively, which were higher than those in adjacent tissues(P all <0.05).In patients with osteosarcoma, the expression of COX-2, VEGF and MVD were associated with Enneking stage( P all <0.05).There was a positive relationship between the expression of COX-2 and VEGF,the expression of COX-2 and VEGF were positively correlated with MVD

  14. Adiamento do ingresso no mercado de trabalho sob o enfoque demográfico: uma análise das regiões metropolitanas brasileiras Aplazamiento del ingreso al mercado laboral bajo el enfoque demográfico: un análisis de las regiones metropolitanas brasileñas Demographic perspectives on delayed labor market entry in metropolitan areas in Brazil

    Directory of Open Access Journals (Sweden)

    Maria Carolina Tomás

    2008-06-01

    Full Text Available O trabalho analisa o adiamento do ingresso no mercado de trabalho entre jovens, através de duas técnicas demográficas: o método singulate mean age; e tabelas de sobrevivência. A base de dados utilizada foi a Pesquisa Mensal de Emprego (PME, considerando-se as seis regiões metropolitanas estudadas (São Paulo, Belo Horizonte, Salvador, Rio de Janeiro, Porto Alegre e Recife conjuntamente. Os períodos analisados foram 1983 e 2001. Ao final, contatou-se um adiamento maior entre os homens, o que os aproxima do padrão de transição feminino, embora eles continuem entrando mais cedo no mercado de trabalho. Ademais, está ocorrendo uma alteração no padrão etário de inserção, já que houve diminuição no contingente de jovens entrando no mercado de trabalho até os 17 anos.El trabajo analiza el aplazamiento del ingreso al mercado laboral entre jóvenes, a través de dos técnicas demográficas: El método singulate mean age; y tablas de sobrevivencia. La base de datos utilizada fue la Encuesta Mensual de Empleo (PME, considerándose las seis regiones metropolitanas estudiadas (San Pablo, Belo Horizonte, Salvador, Río de Janeiro, Porto Alegre y Recife conjuntamente. Los períodos analizados fueron 1983 y 2001. Al final, se constató un aplazamiento mayor entre los hombres, lo que los aproxima al padrón de transición femenino, aunque éstos continúen entrando más temprano al mercado laboral. Además, está ocurriendo una modificación en el padrón etario de inserción, ya que hubo una disminución en el contingente de jóvenes entrando al mercado laboral hasta los 17 años.The article analyzes late entry into the labor market among Brazilian youth, using two demographic techniques: the singulate mean age, and survival tables. The data basis used is the Monthly Employment Survey (PME carried out and published by the Brazilian Census Office (IBGE. The analysis considers six metropolitan areas (São Paulo, Belo Horizonte, Salvador, Rio

  15. Time Delay Cosmography

    OpenAIRE

    Treu, Tommaso; Marshall, Philip J.

    2016-01-01

    Gravitational time delays, observed in strong lens systems where the variable background source is multiply-imaged by a massive galaxy in the foreground, provide direct measurements of cosmological distance that are very complementary to other cosmographic probes. The success of the technique depends on the availability and size of a suitable sample of lensed quasars or supernovae, precise measurements of the time delays, accurate modeling of the gravitational potential of the main deflector,...

  16. 19 CFR 142.3 - Entry documentation required.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry documentation required. 142.3 Section 142.3... TREASURY (CONTINUED) ENTRY PROCESS Entry Documentation § 142.3 Entry documentation required. (a) Contents. Except as provided in paragraph (b) of this section, the entry documentation required to secure...

  17. 沉默COX-2抑制A549细胞的恶性增殖%COX-2 silencing inhibits cell proliferation in A549 cell

    Institute of Scientific and Technical Information of China (English)

    Weiying Li; Wentao Yue; Lina Zhang; Xiaoting Zhao; Li Ma; Xuehui Yang; Chunyan Zhang; Yue Wang; Meng Gu

    2011-01-01

    Objective: The aim of this study was to explore the effects on malignant proliferation of A549 cell by silencing cyclooxygenase (COX)-2. Methods: In the present study, we constructed three siRNA vectors producing small interference RNA. The siRNA vectors and the vacant vectors were transfected into A549 cell with lipofectamine respectively and the transfected cell strains were constructed. The change of COX-2 expression levels was examined by Western blot and RT-PCR. The effects on the proliferation of lung cancer cells were studied by cell growth curve, clonogenic assay and xenograft assays. Results: The siRNA expression vectors produced marked effects in A549 cell but the inhibited effects were different. The effect of psi-10 was best and the mRNA and protein levels of COX-2 reduced 61.2% and 56.2% respectively in A549-si10 cell in contrast to the control.The growth of A549 cell slowed and the colony formation rate reduced after silencing COX-2. In xenograft assays, the growth speeds of tumor became slow and the numbers of tumor reduced after silencing COX-2. Conclusion: The si10 target of COX-2 has the best silencing effect in A549 cell and the best inhibition effect on malignant proliferation of A549 cell in vivo and in vitro.

  18. LABORATORY VOICE DATA ENTRY SYSTEM.

    Energy Technology Data Exchange (ETDEWEB)

    PRAISSMAN,J.L.SUTHERLAND,J.C.

    2003-04-01

    We have assembled a system using a personal computer workstation equipped with standard office software, an audio system, speech recognition software and an inexpensive radio-based wireless microphone that permits laboratory workers to enter or modify data while performing other work. Speech recognition permits users to enter data while their hands are holding equipment or they are otherwise unable to operate a keyboard. The wireless microphone allows unencumbered movement around the laboratory without a ''tether'' that might interfere with equipment or experimental procedures. To evaluate the potential of voice data entry in a laboratory environment, we developed a prototype relational database that records the disposal of radionuclides and/or hazardous chemicals Current regulations in our laboratory require that each such item being discarded must be inventoried and documents must be prepared that summarize the contents of each container used for disposal. Using voice commands, the user enters items into the database as each is discarded. Subsequently, the program prepares the required documentation.

  19. Prognostic Significance and Clinicopathological Associations of COX-2 SNP in Patients with Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Peter P. Grimminger

    2009-01-01

    Full Text Available Background. To further improve the screening, diagnosis, and therapy of patients with nonsmall cell lung cancer (NSCLC additional diagnostic tools are urgently needed. Gene expression of Cyclooxygenase-2 (COX-2 has been linked to prognosis in patients with NSCLC. The role of the COX-2 926G>C Single Nucleotide Polymorphism (SNP in patients with NSCLC remains unclear. The aim of this study was to investigate the potential of the COX-2 926G>C SNP as a molecular marker in this disease. Methods. COX-2 926G>C SNP was analyzed in surgically resected tumor tissue of 85 patients with NSCLC using a PCR-based RFLP technique. Results. The COX-2 926G>C SNP genotypes were detected with the following frequencies: GG n=62 (73%, GC n=20 (23%, CC n=3 (4%. There were no associations between COX-2 SNP genotype and histology, grading or gender detectable. COX-2 SNP was significantly associated with tumor stage (P=.032 and lymph node status (P=.016, Chi-square test. With a median followup of 85.9 months, the median survival was 59.7 months. There were no associations seen between the COX-2 SNP genotype and patients prognosis. Conclusions. The COX-2 926G>C SNP is detectable at a high frequency in patients with NSCLC. The COX-2 926G>C SNP genotype is not a prognostic molecular marker in this disease. However, patients with the GC or CC genotype seem more susceptible to lymph node metastases and higher tumor stage than patients with the GG genotype. The results suggest COX-2 926G>C SNP as a molecular marker for lymph node involvement in this disease.

  20. Novel Approaches to Inhibit HIV Entry

    Directory of Open Access Journals (Sweden)

    Chukwuka A. Didigu

    2012-02-01

    Full Text Available Human Immunodeficiency Virus (HIV entry into target cells is a multi-step process involving binding of the viral glycoprotein, Env, to its receptor CD4 and a coreceptor—either CCR5 or CXCR4. Understanding the means by which HIV enters cells has led to the identification of genetic polymorphisms, such as the 32 base-pair deletion in the ccr5 gene (ccr5∆32 that confers resistance to infection in homozygous individuals, and has also resulted in the development of entry inhibitors—small molecule antagonists that block infection at the entry step. The recent demonstration of long-term control of HIV infection in a leukemic patient following a hematopoietic stem cell transplant using cells from a ccr5∆32 homozygous donor highlights the important role of the HIV entry in maintaining an established infection and has led to a number of attempts to treat HIV infection by genetically modifying the ccr5 gene. In this review, we describe the HIV entry process and provide an overview of the different classes of approved HIV entry inhibitors while highlighting novel genetic strategies aimed at blocking HIV infection at the level of entry.

  1. Genomic, Lipidomic and Metabolomic Analysis of Cyclooxygenase-null Cells: Eicosanoid Storm, Cross Talk, and Compensation by COX-1.

    Science.gov (United States)

    Islam, Abul B M M K; Dave, Mandar; Amin, Sonia; Jensen, Roderick V; Amin, Ashok R

    2016-04-01

    The constitutively-expressed cyclooxygenase 1 (COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA) to prostaglandins (PGs). However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT) mice and COX-2(-/-) or COX-1(-/-) mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2(-/-)>COX-1(-/-)>WT+IL-1β. COX-1(-/-) or COX-2(-/-) cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive "anti-inflammatory, proinflammatory, and redox-activated" signature in the protein-protein interactome map was observed in COX-2(-/-) cells. The augmented COX-1 mRNA (in COX-2(-/-) cells) was associated with the upregulation of mRNAs for glutathione S-transferase (GST), superoxide dismutase (SOD), NAD(P)H dehydrogenase quinone 1 (NQO1), aryl hydrocarbon receptor (AhR), peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4), PGF1α, thromboxane B2 (TXB2), and PGF2α. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2(-/-) cells generated an "eicosanoid storm". The genomic characteristics of COX-2(-/-) is similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1(-/-) and COX-2(-/-) cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

  2. Genomic, Lipidomic and Metabolomic Analysis of Cyclooxygenase-null Cells: Eicosanoid Storm, Cross Talk, and Compensation by COX-1

    Directory of Open Access Journals (Sweden)

    Abul B.M.M.K. Islam

    2016-04-01

    Full Text Available The constitutively-expressed cyclooxygenase 1 (COX-1 and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA to prostaglandins (PGs. However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT mice and COX-2-/- or COX-1-/- mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2-/- > COX-1-/- > WT + IL-1β. COX-1-/- or COX-2-/- cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive “anti-inflammatory, proinflammatory, and redox-activated” signature in the protein–protein interactome map was observed in COX-2-/- cells. The augmented COX-1 mRNA (in COX-2-/- cells was associated with the upregulation of mRNAs for glutathione S-transferase (GST, superoxide dismutase (SOD, NAD(PH dehydrogenase quinone 1 (NQO1, aryl hydrocarbon receptor (AhR, peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4, PGF1α, thromboxane B2 (TXB2, and PGF2α. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2-/- cells generated an “eicosanoid storm”. The genomic characteristics of COX-2-/- is similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1-/- and COX-2-/- cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

  3. Imaging of cyclooxygenase-2 (COX-2) expression : Potential use in diagnosis and drug evaluation

    NARCIS (Netherlands)

    de Vries, E. F. J.

    2006-01-01

    Cyclooxygenase is an enzyme that catalyzes the first two steps in the biosynthesis of prostanoids. The constitutively expressed isoform COX-1 is regarded as a housekeeping enzyme that is responsible for the normal production of prostanoids. The inducible isoform COX-2, on the other hand, is transien

  4. Correlation of VEGF and COX-2 Expression with VM in Malignant Melanomas

    Institute of Scientific and Technical Information of China (English)

    BaocunSun; ShiwuZhang; XiulanZhao; YanxueLiu; ChunshengNi; DanfangZhang; HongQi; ZhiyongLiu; XishanHao

    2004-01-01

    OBJECTIVE To investigate the relationship between vascular epithelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in melanomas and the expressive difference of VEGF and COX-2 between melanomas with and without vasculogenic mimicry(VM).METHODS Sixty cases of malignant melanomas emoeaaea In paraffin were studied. The tumors were divided into a high-grade malignant group and a low-grade malignant group based on their tumor type, atypia and survival time of the patient. Then tissue microarrays were produced from these paraffin-embedded tumor tissues which were stained for VEGF, COX-2 and PAS. The difference in expression between VEGF and COX-2 in the malignant melanomas was compared using a grid-count. In addition, the tumors were also divided into mimicry and non-mimicry groups based on their PAS staining. Then the differences between the PAS positive and negative areas of the 2 groups were compared.RESULTS In malignant melanomas with VM, VEGF and COX-2 expression was less in tumors in which VM was absent, but VEGF, COX-2 expression in high-grade malignant melanomas was higher than that in low-grade grade malignant melanomas. Expression of VEGF was correlated with COX-2 expression.CONCLUSION VM exists in some high-grade malignant melanomas. The differences and relations between VEGF and COX-2 showed that some high-grade malignant melanomas possess a unique molecular-mechanism of tumor metastasis and blood supply.

  5. COX-2 and TGF-β expression in proliferative disorders of canine prostate

    OpenAIRE

    Marcela M.P. Rodrigues; Di Santis, Giovana W.; De Moura, Veridiana M.B.D.; Amorim, Renée Laufer [UNESP

    2010-01-01

    COX-2 and TGF-β expression was determined in order to correlate non-neoplastic lesions, preneoplastic lesions and carcinoma in the prostate of dogs. The results show that neoplastic and preneoplastic lesions express more COX-2 and TGF-β when compared to carcinomas, which suggests these proteins may cooperate in the process of prostate tumorigenesis.

  6. Protective effect of NSAIDs on cancer and influence of COX-2 C-765G genotype

    NARCIS (Netherlands)

    C. Siemes (Claire); L.E. Visser (Loes); J.W.W. Coebergh (Jan Willem); A. Hofman (Albert); A.G. Uitterlinden (André); B.H.Ch. Stricker (Bruno)

    2008-01-01

    textabstractPurpose: Inhibition of COX-2 enzymes is a frequently suggested mechanism for the beneficial effects of NSAIDs on carcinogenesis. The aim of this study was to explore the role of cumulative NSAID use on four common non-skin related cancers and modification by COX-2 G-765C genotype. Patien

  7. Predicting and Modelling of Survival Data when Cox's Regression Model does not hold

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2002-01-01

    Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects......Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects...

  8. Comparing treatment effects after adjustment with multivariable Cox proportional hazards regression and propensity score methods

    NARCIS (Netherlands)

    Martens, Edwin P|info:eu-repo/dai/nl/088859010; de Boer, Anthonius|info:eu-repo/dai/nl/075097346; Pestman, Wiebe R; Belitser, Svetlana V; Stricker, Bruno H Ch; Klungel, Olaf H|info:eu-repo/dai/nl/181447649

    PURPOSE: To compare adjusted effects of drug treatment for hypertension on the risk of stroke from propensity score (PS) methods with a multivariable Cox proportional hazards (Cox PH) regression in an observational study with censored data. METHODS: From two prospective population-based cohort

  9. Loss of COX5B inhibits proliferation and promotes senescence via mitochondrial dysfunction in breast cancer.

    Science.gov (United States)

    Gao, Shui-Ping; Sun, He-Fen; Jiang, Hong-Lin; Li, Liang-Dong; Hu, Xin; Xu, Xiao-En; Jin, Wei

    2015-12-22

    COX5B, a peripheral subunit of the cytochrome c oxidase complex, has previously been reported to maintain the stability of this complex. However, its functions and mechanisms involved in breast cancer progression remain unclear. Here, by performing SILAC assays in breast cancer cell models and detecting COX5B expression in tissues, we found that COX5B expression was elevated in breast cancer. Down-regulation of COX5B in breast cancer cell lines can suppress cell proliferation and induced cell senescence which was accompanied by elevating production of IL-8 and other cytokines. Interestingly, conditioned medium from COX5B knockdown cells could promote breast cancer cell migration. Mechanistic studies reveal that COX5B silence induces an increase in production of ROS, depolarization of MMP and a decrease in ATP. What's more, silence of COX5B leads to metabolic disorders, such as increased glucose uptake and decreased lactate secretion. Collectively, our study shows that loss of COX5B induces mitochondrial dysfunction and subsequently leads to cell growth suppression and cell senescence. Cytokines such as IL-8 secreted by senescent cells may in turn alter the microenvironment which could enhance cell migration. These findings may provide a novel paradigm for the treatment which combined anti-cancer drugs with particular cytokine inhibitors such as IL-8 blockers.

  10. Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease.

    Science.gov (United States)

    Indrieri, Alessia; van Rahden, Vanessa Alexandra; Tiranti, Valeria; Morleo, Manuela; Iaconis, Daniela; Tammaro, Roberta; D'Amato, Ilaria; Conte, Ivan; Maystadt, Isabelle; Demuth, Stephanie; Zvulunov, Alex; Kutsche, Kerstin; Zeviani, Massimo; Franco, Brunella

    2012-11-02

    Microphthalmia with linear skin lesions (MLS) is an X-linked dominant male-lethal disorder associated with mutations in holocytochrome c-type synthase (HCCS), which encodes a crucial player of the mitochondrial respiratory chain (MRC). Unlike other mitochondrial diseases, MLS is characterized by a well-recognizable neurodevelopmental phenotype. Interestingly, not all clinically diagnosed MLS cases have mutations in HCCS, thus suggesting genetic heterogeneity for this disorder. Among the possible candidates, we analyzed the X-linked COX7B and found deleterious de novo mutations in two simplex cases and a nonsense mutation, which segregates with the disease, in a familial case. COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase (COX), the MRC complex IV. We demonstrated that COX7B is indispensable for COX assembly, COX activity, and mitochondrial respiration. Downregulation of the COX7B ortholog (cox7B) in medaka (Oryzias latipes) resulted in microcephaly and microphthalmia that recapitulated the MLS phenotype and demonstrated an essential function of complex IV activity in vertebrate CNS development. Our results indicate an evolutionary conserved role of the MRC complexes III and IV for the proper development of the CNS in vertebrates and uncover a group of mitochondrial diseases hallmarked by a developmental phenotype.

  11. Effect of uric acid on inflammatory COX-2 and ROS pathways in vascular smooth muscle cells.

    Science.gov (United States)

    Oğuz, Nurgül; Kırça, Mustafa; Çetin, Arzu; Yeşilkaya, Akın

    2017-10-01

    Hyperuricemia is thought to play a role in cardiovascular diseases (CVD), including hypertension, coronary artery disease and atherosclerosis. However, exactly how uric acid contributes to these pathologies is unknown. An underlying mechanism of inflammatory diseases, such as atherosclerosis, includes enhanced production of cyclooxygenase-2 (COX-2) and superoxide anion. Here, we aimed to examine the effect of uric acid on inflammatory COX-2 and superoxide anion production and to determine the role of losartan. Primarily cultured vascular smooth muscle cells (VSMCs) were time and dose-dependently induced by uric acid and COX-2 and superoxide anion levels were measured. COX-2 levels were determined by ELISA, and superoxide anion was measured by the superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome c method. Uric acid elevated COX-2 levels in a time-dependent manner. Angiotensin-II receptor blocker, losartan, diminished uric-acid-induced COX-2 elevation. Uric acid also increased superoxide anion level in VSMCs. Uric acid plays an important role in CVD pathogenesis by inducing inflammatory COX-2 and ROS pathways. This is the first study demonstrating losartan's ability to reduce uric-acid-induced COX-2 elevation.

  12. Cox-2 expression in ovarian malignancies: a review of the clinical aspects.

    Science.gov (United States)

    Menczer, Joseph

    2009-10-01

    COX-2 is an inducible enzyme expressed only in response to stimuli such as mitogens, cytokines, growth factors or hormones, and is pro-inflammatory. It plays an important role in tumorigenesis. The purpose of the present report is to review the clinical aspects of COX-2 expression in ovarian malignancies. A PubMed (http://www.pubmed.gov/) search of investigations published from July 2001 until August 2008 and containing the term COX-2 in combination with ovarian malignancies was conducted. The clinical aspects of the relevant investigations were reviewed. COX-2 is expressed in ovarian tumors of low malignant potential (LMP), in epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma (PPC) and apparently plays a role in their carcinogenesis. Its expression seems to be correlated with VEGF that serves as a predictor of poor prognosis in some non-gynecologic malignancies. COX-2 expression is higher in EOC than in LMPs. The results with regard to the association between COX-2 expression and prognostic factors, response to treatment and outcome in ovarian malignancies are inconsistent. Clinical studies dealing with the effect of COX-2 inhibitors on outcome are scarce. The use of COX-2 expression in gynecological malignancies in clinical practice remains to be elucidated.

  13. Nucleobindin co-localizes and associates with cyclooxygenase (COX-2 in human neutrophils.

    Directory of Open Access Journals (Sweden)

    Patrick Leclerc

    Full Text Available The inducible cyclooxygenase isoform (COX-2 is associated with inflammation, tumorigenesis, as well as with physiological events. Despite efforts deployed in order to understand the biology of this multi-faceted enzyme, much remains to be understood. Nucleobindin (Nuc, a ubiquitous Ca(2+-binding protein, possesses a putative COX-binding domain. In this study, we investigated its expression and subcellular localization in human neutrophils, its affinity for COX-2 as well as its possible impact on PGE(2 biosynthesis. Complementary subcellular localization approaches including nitrogen cavitation coupled to Percoll fractionation, immunofluorescence, confocal and electron microscopy collectively placed Nuc, COX-2, and all of the main enzymes involved in prostanoid synthesis, in the Golgi apparatus and endoplasmic reticulum of human neutrophils. Immunoprecipitation experiments indicated a high affinity between Nuc and COX-2. Addition of human recombinant (hr Nuc to purified hrCOX-2 dose-dependently caused an increase in PGE(2 biosynthesis in response to arachidonic acid. Co-incubation of Nuc with COX-2-expressing neutrophil lysates also increased their capacity to produce PGE(2. Moreover, neutrophil transfection with hrNuc specifically enhanced PGE(2 biosynthesis. Together, these results identify a COX-2-associated protein which may have an impact in prostanoid biosynthesis.

  14. New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis.

    Science.gov (United States)

    Hugo, Honor J; Saunders, C; Ramsay, R G; Thompson, E W

    2015-12-01

    The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

  15. Glutathione selectively modulates the binding of platinum drugs to human copper chaperone Cox17.

    Science.gov (United States)

    Zhao, Linhong; Wang, Zhen; Wu, Han; Xi, Zhaoyong; Liu, Yangzhong

    2015-12-01

    The copper chaperone Cox17 (cytochrome c oxidase copper chaperone) has been shown to facilitate the delivery of cisplatin to mitochondria, which contributes to the overall cytotoxicity of the drug [Zhao et al. (2014) Chem. Commun. 50: , 2667-2669]. Kinetic data indicate that Cox17 has reactivity similar to glutathione (GSH), the most abundant thiol-rich molecule in the cytoplasm. In the present study, we found that GSH significantly modulates the reaction of platinum complexes with Cox17. GSH enhances the reactivity of three anti-cancer drugs (cisplatin, carboplatin and oxaliplatin) to Cox17, but suppresses the reaction of transplatin. Surprisingly, the pre-formed cisplatin-GSH adducts are highly reactive to Cox17; over 90% platinum transfers from GSH to Cox17. On the other hand, transplatin-GSH adducts are inert to Cox17. These different effects are consistent with the drug activity of these platinum complexes. In addition, GSH attenuates the protein aggregation of Cox17 induced by platination. These results indicate that the platinum-protein interactions could be substantially influenced by the cellular environment.

  16. Endomicroscopic Imaging of COX-2 Activity in Murine Sporadic and Colitis-Associated Colorectal Cancer.

    Science.gov (United States)

    Foersch, Sebastian; Neufert, Clemens; Neurath, Markus F; Waldner, Maximilian J

    2013-01-01

    Although several studies propose a chemopreventive effect of aspirin for colorectal cancer (CRC) development, the general use of aspirin cannot be recommended due to its adverse side effects. As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identification of patients who would possibly benefit from aspirin treatment. In this pilot trial, we used a COX-2-specific fluorescent probe for detection of colitis-associated and sporadic CRC in mice using confocal microscopy. Following the injection of the COX-2 probe into tumor-bearing APCmin mice or mice exposed to the AOM + DSS model of colitis-associated cancer, the tumor-specific upregulation of COX-2 could be validated with in vivo fluorescence imaging. Subsequent confocal imaging of tumor tissue showed an increased number of COX-2 expressing cells when compared to the normal mucosa of healthy controls. COX-2-expression was detectable with subcellular resolution in tumor cells and infiltrating stroma cells. These findings pose a proof of concept and suggest the use of CLE for the detection of COX-2 expression during colorectal cancer surveillance endoscopy. This could improve early detection and stratification of chemoprevention in patients with CRC.

  17. Endomicroscopic Imaging of COX-2 Activity in Murine Sporadic and Colitis-Associated Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Sebastian Foersch

    2013-01-01

    Full Text Available Although several studies propose a chemopreventive effect of aspirin for colorectal cancer (CRC development, the general use of aspirin cannot be recommended due to its adverse side effects. As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identification of patients who would possibly benefit from aspirin treatment. In this pilot trial, we used a COX-2-specific fluorescent probe for detection of colitis-associated and sporadic CRC in mice using confocal microscopy. Following the injection of the COX-2 probe into tumor-bearing APCmin mice or mice exposed to the AOM + DSS model of colitis-associated cancer, the tumor-specific upregulation of COX-2 could be validated with in vivo fluorescence imaging. Subsequent confocal imaging of tumor tissue showed an increased number of COX-2 expressing cells when compared to the normal mucosa of healthy controls. COX-2-expression was detectable with subcellular resolution in tumor cells and infiltrating stroma cells. These findings pose a proof of concept and suggest the use of CLE for the detection of COX-2 expression during colorectal cancer surveillance endoscopy. This could improve early detection and stratification of chemoprevention in patients with CRC.

  18. Advances in spacecraft atmospheric entry guidance

    Science.gov (United States)

    Benito Manrique, Joel

    In order to advance entry guidance technology two different research areas have been explored with the objective of increasing the reachable landing area and the landing accuracy for future Mars missions. Currently only the northern hemisphere of Mars is available for landing due to its low elevation. Only low elevation landing sites have the necessary atmospheric density to allow landing using current Entry, Descent and Landing (EDL) technology. In order to reach most of the Ancient Highlands, the majority of the southern hemisphere, advanced EDL technology is needed in multiple fields, including entry guidance. The first research area is the definition and applications of reachable and controllable sets for entry. The definition of the reachable and controllable sets provides a framework for the study of the capabilities of an entry vehicle in a given planet. Reachable and controllable sets can be used to comprehensively characterize the envelope of trajectories that a vehicle can fly, the sites it can reach and the entry states that can be accommodated. The sets can also be used for the evaluation of trajectory planning algorithms and to assist in the selection of the entry or landing sites. In essence, the reachable and controllable sets offer a powerful vehicle and trajectory analysis and design framework that allows for better mission design choices. In order to illustrate the use of the sets, they are computed for a representative Mars mission using two different vehicle configurations. The sets characterize the impact of the vehicle configuration on the entry capability. Furthermore, the sets are used to find the best skip-entry trajectory for a return from the Moon mission, highlighting the utility of the sets in atmospheric maneuvers other than entry. The second research area is the development of the components of an entry guidance algorithm that allow high elevation landing and provide as well high landing accuracy. The approach taken follows the

  19. Entry Regulation under Asymmetric Information about Demand

    Directory of Open Access Journals (Sweden)

    Paula Sarmento

    2010-01-01

    Full Text Available We investigate how an incumbent firm can use the regulatory policy about entry and the informational advantage to protect his market position. This question is studied through the construction of a signalling game where we assume that the regulator has less information about demand than the firms. We conclude that there is a pooling equilibrium and partially separating equilibria in which entry is deterred and, if demand is high, there will be insufficient entry. The final effect on welfare depends on the tradeoff between short-run benefits (lower price and long-run losses (weaker competition.

  20. Market entry strategies into the BRIC countries

    DEFF Research Database (Denmark)

    Boyd, Britta; Dyhr Ulrich, Anna Marie

    2014-01-01

    Based on a sample of 177 exporting SMEs, this study investigates what market entry strategy is used by Danish family and non-family businesses. From a resource-based view, three critical internal factors (risk, flexibility and control) affecting the entry mode choice into the BRIC markets...... when entering the BRIC markets. In contrast, family firms choose high commitment entry modes which involve high risk and low flexibility when entering the BRIC markets. Further implications discuss the suitability of export strategies to BRIC markets for managers of Danish family and non-family firms....

  1. Texting while driving: is speech-based text entry less risky than handheld text entry?

    Science.gov (United States)

    He, J; Chaparro, A; Nguyen, B; Burge, R J; Crandall, J; Chaparro, B; Ni, R; Cao, S

    2014-11-01

    Research indicates that using a cell phone to talk or text while maneuvering a vehicle impairs driving performance. However, few published studies directly compare the distracting effects of texting using a hands-free (i.e., speech-based interface) versus handheld cell phone, which is an important issue for legislation, automotive interface design and driving safety training. This study compared the effect of speech-based versus handheld text entries on simulated driving performance by asking participants to perform a car following task while controlling the duration of a secondary text-entry task. Results showed that both speech-based and handheld text entries impaired driving performance relative to the drive-only condition by causing more variation in speed and lane position. Handheld text entry also increased the brake response time and increased variation in headway distance. Text entry using a speech-based cell phone was less detrimental to driving performance than handheld text entry. Nevertheless, the speech-based text entry task still significantly impaired driving compared to the drive-only condition. These results suggest that speech-based text entry disrupts driving, but reduces the level of performance interference compared to text entry with a handheld device. In addition, the difference in the distraction effect caused by speech-based and handheld text entry is not simply due to the difference in task duration.

  2. Cox-2 levels in canine mammary tumors, including inflammatory mammary carcinoma: clinicopathological features and prognostic significance.

    Science.gov (United States)

    Queiroga, Felisbina Luisa; Perez-Alenza, Maria Dolores; Silvan, Gema; Peña, Laura; Lopes, Carlos; Illera, Juan Carlos

    2005-01-01

    Cyclo-oxygenase (Cox-2) plays an important role in mammary carcinogenesis, nevertheless, its role in canine mammary tumors, and particularly in inflammatory mammary carcinoma (IMC), is unknown. Tumor Cox-2 levels were analyzed by enzyme immunoassay, in post-surgical tumor homogenates of 129 mammary tumors (62 dysplasias and benign tumors, 57 malignant non-IMC and 10 IMC) from 57 female dogs. The highest Cox-2 values were detected in the IMC group. In non-IMC malignant tumors, high values of Cox-2 were related to skin ulceration (p IMC cases could indicate a special role of Cox-2 in the inflammatory phenotype and open the possibility of additional new therapeutic approaches in this special type of mammary cancer in humans and dogs.

  3. Stathmin and microtubules regulate mitotic entry in HeLa cells by controlling activation of both Aurora kinase A and Plk1.

    Science.gov (United States)

    Silva, Victoria C; Cassimeris, Lynne

    2013-12-01

    Depletion of stathmin, a microtubule (MT) destabilizer, delays mitotic entry by ∼4 h in HeLa cells. Stathmin depletion reduced the activity of CDC25 and its upstream activators, Aurora A and Plk1. Chemical inhibition of both Aurora A and Plk1 was sufficient to delay mitotic entry by 4 h, while inhibiting either kinase alone did not cause a delay. Aurora A and Plk1 are likely regulated downstream of stathmin, because the combination of stathmin knockdown and inhibition of Aurora A and Plk1 was not additive and again delayed mitotic entry by 4 h. Aurora A localization to the centrosome required MTs, while stathmin depletion spread its localization beyond that of γ-tubulin, indicating an MT-dependent regulation of Aurora A activation. Plk1 was inhibited by excess stathmin, detected in in vitro assays and cells overexpressing stathmin-cyan fluorescent protein. Recruitment of Plk1 to the centrosome was delayed in stathmin-depleted cells, independent of MTs. It has been shown that depolymerizing MTs with nocodazole abrogates the stathmin-depletion induced cell cycle delay; in this study, depolymerization with nocodazole restored Plk1 activity to near normal levels, demonstrating that MTs also contribute to Plk1 activation. These data demonstrate that stathmin regulates mitotic entry, partially via MTs, to control localization and activation of both Aurora A and Plk1.

  4. Time Delay Cosmography

    CERN Document Server

    Treu, Tommaso

    2016-01-01

    Gravitational time delays, observed in strong lens systems where the variable background source is multiply-imaged by a massive galaxy in the foreground, provide direct measurements of cosmological distance that are very complementary to other cosmographic probes. The success of the technique depends on the availability and size of a suitable sample of lensed quasars or supernovae, precise measurements of the time delays, accurate modeling of the gravitational potential of the main deflector, and our ability to characterize the distribution of mass along the line of sight to the source. We review the progress made during the last 15 years, during which the first competitive cosmological inferences with time delays were made, and look ahead to the potential of significantly larger lens samples in the near future.

  5. Prediction of delayed subsidence

    Science.gov (United States)

    Burns, K.

    A predictive model of delayed subsidence is discussed. A numerical implementation is tested on one of the best-described study areas, Allegheny County in Pennsylvania. In planning insurance of restitution measures, a predictive model is of value in estimating the magnitude of the problem and the size of long-term budgetary commitments. Contrary to active subsidence, which occurs concurrently with mining operations, or is completed within a few days following coal extraction, delayed subsidence may take many years to appear at the surface after coal mines are abandoned. There are two principal morphological types of delayed subsidence: troughs, which are shallow depressions, and sinks, which are steep-sided crown pits. Both types are damaging to surface structures, and a variety of methods were introduced to deal with the problem, ranging from subsidence insurance to site restitution.

  6. Time delay cosmography

    Science.gov (United States)

    Treu, Tommaso; Marshall, Philip J.

    2016-07-01

    Gravitational time delays, observed in strong lens systems where the variable background source is multiply imaged by a massive galaxy in the foreground, provide direct measurements of cosmological distance that are very complementary to other cosmographic probes. The success of the technique depends on the availability and size of a suitable sample of lensed quasars or supernovae, precise measurements of the time delays, accurate modeling of the gravitational potential of the main deflector, and our ability to characterize the distribution of mass along the line of sight to the source. We review the progress made during the last 15 years, during which the first competitive cosmological inferences with time delays were made, and look ahead to the potential of significantly larger lens samples in the near future.

  7. Survival Prognostic Factors of Male Breast Cancer in Southern Iran: a LASSO-Cox Regression Approach.

    Science.gov (United States)

    Shahraki, Hadi Raeisi; Salehi, Alireza; Zare, Najaf

    2015-01-01

    We used to LASSO-Cox method for determining prognostic factors of male breast cancer survival and showed the superiority of this method compared to Cox proportional hazard model in low sample size setting. In order to identify and estimate exactly the relative hazard of the most important factors effective for the survival duration of male breast cancer, the LASSO-Cox method has been used. Our data includes the information of male breast cancer patients in Fars province, south of Iran, from 1989 to 2008. Cox proportional hazard and LASSO-Cox models were fitted for 20 classified variables. To reduce the impact of missing data, the multiple imputation method was used 20 times through the Markov chain Mont Carlo method and the results were combined with Rubin's rules. In 50 patients, the age at diagnosis was 59.6 (SD=12.8) years with a minimum of 34 and maximum of 84 years and the mean of survival time was 62 months. Three, 5 and 10 year survival were 92%, 77% and 26%, respectively. Using the LASSO-Cox method led to eliminating 8 low effect variables and also decreased the standard error by 2.5 to 7 times. The relative efficiency of LASSO-Cox method compared with the Cox proportional hazard method was calculated as 22.39. The19 years follow of male breast cancer patients show that the age, having a history of alcohol use, nipple discharge, laterality, histological grade and duration of symptoms were the most important variables that have played an effective role in the patient's survival. In such situations, estimating the coefficients by LASSO-Cox method will be more efficient than the Cox's proportional hazard method.

  8. A Three-Decade Survival Analysis of Intraventricular Conduction Delay in Adults Without Ischemic Heart Disease.

    Science.gov (United States)

    Tiosano, Shmuel; Hod, Hanoch; Oberman, Bernice; Chetrit, Angela; Dankner, Rachel

    2016-11-01

    The prognosis of an incidental finding of intraventricular conduction delay in individuals without ischemic heart disease is debatable. Intraventricular conduction delay presents electrocardiographically as bundle branch block or nonspecific intraventricular conduction delay. We aimed to assess the long-term survival of an incidental intraventricular conduction delay finding in a cohort of individuals without ischemic heart disease, followed up for 3 decades. A randomized stratified cohort of the adult Israeli population underwent medical examinations and electrocardiography between 1976 and 1982. Patients with ischemic heart disease were excluded, and the cohort was followed for all-cause mortality for a median of 30.4 years. Major intraventricular conduction delay was defined as having complete bundle branch block or nonspecific intraventricular conduction delay, and minor intraventricular conduction delay was defined as having incomplete bundle branch block. Cox proportional hazard model was performed, comparing individuals by electrocardiogram finding, adjusting for demographic, clinical, and electrocardiographic variables. Of 2465 subjects, 2385 (96.8%) were without intraventricular conduction delay, 38 (1.5%) had minor intraventricular conduction delay, and 42 (1.7%) had major intraventricular conduction delay. All-cause mortality rates were higher among minor and major intraventricular conduction delay groups (57.9% and 66.7%, P = .43 and P = .04, respectively) compared with no intraventricular conduction delay (52.1%). By controlling for sex, age, and body mass index, intraventricular conduction delay was not associated with all-cause mortality: hazard ratios, 0.82 (95% confidence interval, 0.52-1.25) and 1.06 (95% confidence interval, 0.72-1.54) for minor and major intraventricular conduction delay, respectively. Intraventricular conduction delay was not found to be an independent risk factor for all-cause mortality in individuals without ischemic heart

  9. Demand Uncertainty: Exporting Delays and Exporting Failures

    DEFF Research Database (Denmark)

    Nguyen, Daniel Xuyen

    2012-01-01

    This paper presents a model of trade that explains why firms wait to export and why many exporters fail. Firms face uncertain demands that are only realized after the firm enters the destination. The model retools the timing of the resolution of uncertainty found in models with heterogeneity...... to forecast unknown demands in untested destinations. The option to forecast demands causes firms to delay exporting in order to gather more information about foreign demand. Third, since uncertainty is resolved after entry, many firms enter a destination and then exit after learning that they cannot profit....... This prediction reconciles the high rate of exit seen in the first years of exporting. Finally, when faced with multiple destinations to which they can export, many firms will choose to sequentially export in order to slowly learn more about its chances for success in untested markets....

  10. Delayed Random Relays

    CERN Document Server

    Ohira, Toru

    2016-01-01

    We present here a system with collection of random walks relaying a signal in one dimension with a presence of a delay. We are interested in the time for a signal to travel from one end (start) to the other end (finish) of the lined group of random walkers. It is found that there is an optimal number of walkers for the signal to travel fastest if the delay is present. We discuss implications of this model and associated behaviors to physical and biological systems.

  11. Approximation of distributed delays

    CERN Document Server

    Lu, Hao; Eberard, Damien; Simon, Jean-Pierre

    2010-01-01

    We address in this paper the approximation problem of distributed delays. Such elements are convolution operators with kernel having bounded support, and appear in the control of time-delay systems. From the rich literature on this topic, we propose a general methodology to achieve such an approximation. For this, we enclose the approximation problem in the graph topology, and work with the norm defined over the convolution Banach algebra. The class of rational approximates is described, and a constructive approximation is proposed. Analysis in time and frequency domains is provided. This methodology is illustrated on the stabilization control problem, for which simulations results show the effectiveness of the proposed methodology.

  12. Integrated Entry Guidance for Reusable Launch Vehicle

    Institute of Scientific and Technical Information of China (English)

    NING Guo-dong; ZHANG Shu-guang; FANG Zhen-ping

    2007-01-01

    A method for the implementation of integrated three-degree-of-freedom constrained entry guidance for reusable launch vehicle is presented. Given any feasible entry conditions, terminal area energy management interface conditions, and the reference trajectory generated onboard then, the method can generate a longitudinal guidance profile rapidly, featuring linear quadratic regular method and a proportional-integral-derivative tracking law with time-varying gains, which satisfies all the entry corridor constraints and meets the requirements with high precision. Afterwards, by utilizing special features of crossrange parameter, establishing bank-reversal corridor,and determining bank-reversals according to dynamically adjusted method, the algorithm enables the lateral entry guidance system to fly a wide range of missions and provides reliable and good performance in the presence of significant aerodynamic modeling uncertainty.Fast trajectory guidance profiles and simulations with a reusable launch vehicle model for various missions and aerodynamic uncertainties are presented to demonstrate the capacity and reliability of this method.

  13. Border Crossing/Entry Data - Boarder Crossing

    Data.gov (United States)

    Department of Transportation — Border Crossing/Entry Data provides summary statistics for incoming crossings at the U.S.-Canadian and the U.S.-Mexican border at the port level. Data are available...

  14. Entry Mode and Performance of Nordic Firms

    DEFF Research Database (Denmark)

    Wulff, Jesper

    2015-01-01

    This study investigates whether the relationship between mode of international market entry and non-location bound international experience is weaker for firms that are large or have a high foreign to total sales ratio, labeled multinational experience. Empirical evidence based on 250 foreign...... market entries made by Norwegian, Danish and Swedish firms suggests that the association between equity mode choice and non-location bound international experience diminishes in the presence of higher levels of multinational experience. Furthermore, firms whose entry mode choice is predicted by the model...... including the proposed moderating effect, on average, yield higher post-entry performance. This study sheds light on inconsistent results found in previous research investigating the impact of international experience and has practical implications for managerial decision-making....

  15. The Effects of Entry in Bilateral Oligopoly

    Directory of Open Access Journals (Sweden)

    Alex Dickson

    2013-06-01

    Full Text Available The purpose of this paper is to study the effects of entry into the market for a single commodity in which both sellers and buyers are permitted to interact strategically. With the inclusion of an additional seller, the market is quasi-competitive: the price falls and volume of trade increases, as expected. However, contrary to the conventional wisdom, existing sellers’ payoffs may increase. The conditions under which entry by new sellers raises the equilibrium payoffs of existing sellers are derived. These depend in an intuitive way on the elasticity of a strategic analog of demand and the market share of existing sellers, and encompass entirely standard economic environments. Similar results are derived relating to the entry of additional buyers and the effects of entry on both sides of the market are investigated.

  16. Entry and exit decisions under uncertainty

    DEFF Research Database (Denmark)

    Kongsted, Hans Christian

    1996-01-01

    This paper establishes the general deterministic limit that corresponds to Dixit's model of entry and exit decisions under uncertainty. The interlinked nature of decisions is shown to be essential also in the deterministic limit. A numerical example illustrates the result......This paper establishes the general deterministic limit that corresponds to Dixit's model of entry and exit decisions under uncertainty. The interlinked nature of decisions is shown to be essential also in the deterministic limit. A numerical example illustrates the result...

  17. Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

    Science.gov (United States)

    Fernandes, Carla; Palmeira, Andreia; Ramos, Inês I.; Carneiro, Carlos; Afonso, Carlos; Tiritan, Maria Elizabeth; Cidade, Honorina; Pinto, Paula C.A.G.; Saraiva, M. Lúcia M.F.S.; Reis, Salette; Pinto, Madalena M.M.

    2017-01-01

    Searching of new enantiomerically pure chiral derivatives of xanthones (CDXs) with potential pharmacological properties, particularly those with anti-inflammatory activity, has remained an area of interest of our group. Herein, we describe in silico studies and in vitro inhibitory assays of cyclooxygenases (COX-1 and COX-2) for different enantiomeric pairs of CDXs. The evaluation of the inhibitory activities was performed by using the COX Inhibitor Screening Assay Kit. Docking simulations between the small molecules (CDXs; known ligands and decoys) and the enzyme targets were undertaken with AutoDock Vina embedded in PyRx—Virtual Screening Tool software. All the CDXs evaluated exhibited COX-1 and COX-2 inhibition potential as predicted. Considering that the (S)-(−)-enantiomer of the nonsteroidal anti-inflammatory drug ketoprofen preferentially binds to albumin, resulting in lower free plasma concentration than (R)-(+)-enantiomer, protein binding affinity for CDXs was also evaluated by spectrofluorimetry as well as in in silico. For some CDXs enantioselectivity was observed. PMID:28561772

  18. Flavocoxid Inhibits Phospholipase A2, Peroxidase Moieties of the Cyclooxygenases (COX, and 5-Lipoxygenase, Modifies COX-2 Gene Expression, and Acts as an Antioxidant

    Directory of Open Access Journals (Sweden)

    Bruce P. Burnett

    2011-01-01

    Full Text Available The multiple mechanisms of action for flavocoxid relating to arachidonic acid (AA formation and metabolism were studied in vitro. Flavocoxid titrated into rat peritoneal macrophage cultures inhibited cellular phospholipase A2 (PLA2 (IC50 = 60 μg/mL. In in vitro enzyme assays, flavocoxid showed little anti-cyclooxygenase (CO activity on COX-1/-2 enzymes, but inhibited the COX-1 (IC50 = 12.3 and COX-2 (IC50 = 11.3 μg/mL peroxidase (PO moieties as well as 5-lipoxygenase (5-LOX (IC50 = 110 μg/mL. No detectable 5-LOX inhibition was found for multiple traditional and COX-2 selective NSAIDs. Flavocoxid also exhibited strong and varied antioxidant capacities in vitro and decreased nitrite levels (IC50 = 38 μg/mL in rat peritoneal macrophages. Finally, in contrast to celecoxib and ibuprofen, which upregulated the cox-2 gene, flavocoxid strongly decreased expression. This work suggests that clinically favourable effects of flavocoxid for management of osteoarthritis (OA are achieved by simultaneous modification of multiple molecular pathways relating to AA metabolism, oxidative induction of inflammation, and neutralization of reactive oxygen species (ROS.

  19. Minimizing the cancer-promotional activity of cox-2 as a central strategy in cancer prevention.

    Science.gov (United States)

    McCarty, Mark F

    2012-01-01

    A recent meta-analysis examining long-term mortality in subjects who participated in controlled studies evaluating the impact of daily aspirin on vascular risk, has concluded that aspirin confers substantial protection from cancer mortality. Remarkably, low-dose aspirin was as effective as higher-dose regimens; hence this protection may be achievable with minimal risk. There is reason to believe that this protection stems primarily from inhibition of cox-2 in pre-neoplastic lesions. Since safe aspirin regimens can only achieve a partial and transitory inhibition of cox-2, it may be feasible to complement the cancer-protective benefit of aspirin with other measures which decrease cox-2 expression or which limit the bioactivity of cox-2-derived PGE2. Oxidative stress boosts cox-2 expression by up-regulating activation of NF-kappaB and MAP kinases; NADPH oxidase activation may thus promote carcinogenesis by increasing cox-2 expression while also amplifying oxidant-mediated mutagenesis. A prospective cohort study has observed that relatively elevated serum bilirubin levels are associated with a marked reduction in subsequent cancer mortality; this may reflect bilirubin's physiological role as a potent inhibitor of NADPH oxidase. It may be feasible to mimic this protective effect by supplementing with spirulina, a rich source of a phycobilin which shares bilirubin's ability to inhibit NADPH oxidase. Ancillary antioxidant measures - phase 2 inducing phytochemicals, melatonin, N-acetylcysteine, and astaxanthin - may also aid cox-2 down-regulation. The cancer protection often associated with high-normal vitamin D status may be attributable, in part, to the ability of the activated vitamin D receptor to decrease cox-2 expression while promoting PGE2 catabolism and suppressing the expression of PGE2 receptors. Diets with a relatively low ratio of omega-6 to long-chain omega-3 fats may achieve cancer protection by antagonizing the production and bioactivity of PGE2. Growth

  20. Delay Bounds for Multiclass FIFO

    OpenAIRE

    Jiang, Yuming; Misra, Vishal

    2016-01-01

    FIFO is perhaps the simplest scheduling discipline. For single-class FIFO, its delay guarantee performance has been extensively studied: The well-known results include a stochastic delay bound for $GI/GI/1$ by Kingman and a deterministic delay bound for $D/D/1$ by Cruz. However, for multiclass FIFO, few such results are available. To fill the gap, we prove delay bounds for multiclass FIFO in this work, considering both deterministic and stochastic cases. Specifically, delay bounds are present...

  1. Hypersonic and planetary entry flight mechanics

    Science.gov (United States)

    Vinh, N. X.; Busemann, A.; Culp, R. D.

    1980-01-01

    The book treats hypersonic flight trajectories and atmospheric entry flight mechanics in light of their importance for space shuttle entry. Following a review of the structures of planetary atmospheres and aerodynamic forces, equations are derived for flight over a spherical planet, and the performance of long-range hypervelocity vehicles in extra-atmospheric flight is analyzed. Consideration is then given to vehicle trajectories in the powered and atmospheric reentry phases of flight, and several first-order solutions are derived for various planetary entry situations. The second-order theory of Loh for entry trajectories is presented along with the classical theories of Yaroshevskii and Chapman for entry into planetary atmospheres, and the thermal problems encountered in hypersonic flight are analyzed. A unified theory for entry into planetary atmospheres is then introduced which allows the performance of a general type of lifting vehicle to be studied, and applied to the analysis of orbit contraction due to atmospheric drag, flight with lift modulation and lateral maneuvers.

  2. Mitotic delay following inhibition by 5'-fluorodeoxyuridine of S-phase in Physarum is not due to delay in termination of S-phase.

    Science.gov (United States)

    Kauffman, S A; Shymko, R M

    1982-02-01

    It has been known for several years that inhibition by 5'-fluorodeoxyuridine (FdUrd) of DNA synthesis in plasmodia of Physarum polycephalum delays subsequent nuclear mitosis. To test whether this delay is due to delay in the termination of S-phase, we blocked DNA synthesis with FdUrd + uridine for 3 h at different stages of S-phase, and in plasmodia with different cycle times. The results show that in short-cycling plasmodia the delay in mitosis can be as long as 9 h, despite little delay in termination of S-phase, and is longest when plasmodia are blocked in early S-phase. In plasmodia with long cycle times, no mitotic delay following 3 h inhibition by FdUrd of S-phase is observed. Our results suggest that mitotic delay after pulses of FdUrd is not due to delay in termination of S-phase, which therefore does not appear to 'gate' entry into a G2 period of fixed length. The fact that delay is longest after FdUrd blocks in early S-phase suggests that normal progress through S-phase, not its termination, is critical for the timing of the subsequent mitosis. This may reflect an obligate coupling between replication and transcription of specific genes needed for progress toward mitosis. The lack of mitotic delay in long-cycling plasmodia shows that S-phase-coupled processes need not act as 'timers' if other processes become rate-limiting.

  3. Delayed breast implant reconstruction

    DEFF Research Database (Denmark)

    Hvilsom, Gitte B.; Hölmich, Lisbet R.; Steding-Jessen, Marianne;

    2012-01-01

    We evaluated the association between radiation therapy and severe capsular contracture or reoperation after 717 delayed breast implant reconstruction procedures (288 1- and 429 2-stage procedures) identified in the prospective database of the Danish Registry for Plastic Surgery of the Breast during...... reconstruction approaches other than implants should be seriously considered among women who have received radiation therapy....

  4. Delayed traumatic diaphragmatic hernia

    Science.gov (United States)

    Lu, Jing; Wang, Bo; Che, Xiangming; Li, Xuqi; Qiu, Guanglin; He, Shicai; Fan, Lin

    2016-01-01

    Abstract Background: Traumatic diaphragmatic hernias (TDHs) are sometimes difficult to identify at an early stage and can consequently result in diagnostic delays with life-threatening outcomes. It is the aim of this case study to highlight the difficulties encountered with the earlier detection of traumatic diaphragmatic hernias. Methods: Clinical data of patients who received treatment for delayed traumatic diaphragmatic hernias in registers of the First Affiliated Hospital of Xi’an Jiaotong University from 1998 to 2014 were analyzed retrospectively. Results: Six patients were included in this study. Left hemidiaphragm was affected in all of them. Most of the patients had a history of traffic accident and 1 a stab-penetrating injury. The interval from injury to developing symptoms ranged from 2 to 11 years (median 5 years). The hernial contents included the stomach, omentum, small intestine, and colon. Diaphragmatic injury was missed in all of them during the initial managements. All patients received operations once the diagnosis of delayed TDH was confirmed, and no postoperative mortality was detected. Conclusions: Delayed TDHs are not common, but can lead to serious consequences once occurred. Early detection of diaphragmatic injuries is crucial. Surgeons should maintain a high suspicion for injuries of the diaphragm in cases with abdominal or lower chest traumas, especially in the initial surgical explorations. We emphasize the need for radiographical follow-up to detect diaphragmatic injuries at an earlier stage. PMID:27512848

  5. 'No delays achiever'.

    Science.gov (United States)

    2007-05-01

    The latest version of the NHS Institute for Innovation and Improvement's 'no delays achiever', a web based tool created to help NHS organisations achieve the 18-week target for GP referrals to first treatment, is available at www.nodelaysachiever.nhs.uk.

  6. Permissible Delay in Payments

    Directory of Open Access Journals (Sweden)

    Yung-Fu Huang

    2007-01-01

    Full Text Available The main purpose of this paper wants to investigate the optimal retailer's lot-sizing policy with two warehouses under partially permissible delay in payments within the economic order quantity (EOQ framework. In this paper, we want to extend that fully permissible delay in payments to the supplier would offer the retailer partially permissible delay in payments. That is, the retailer must make a partial payment to the supplier when the order is received. Then the retailer must pay off the remaining balance at the end of the permissible delay period. In addition, we want to add the assumption that the retailer's storage space is limited. That is, the retailer will rent the warehouse to store these exceeding items when the order quantity is larger than retailer's storage space. Under these conditions, we model the retailer's inventory system as a cost minimization problem to determine the retailer's optimal cycle time and optimal order quantity. Three theorems are developed to efficiently determine the optimal replenishment policy for the retailer. Finally, numerical examples are given to illustrate these theorems and obtained a lot of managerial insights.

  7. Planetary/DOD entry technology flight experiments. Volume 2: Planetary entry flight experiments

    Science.gov (United States)

    Christensen, H. E.; Krieger, R. J.; Mcneilly, W. R.; Vetter, H. C.

    1976-01-01

    The technical feasibility of launching a high speed, earth entry vehicle from the space shuttle to advance technology for the exploration of the outer planets' atmospheres was established. Disciplines of thermodynamics, orbital mechanics, aerodynamics propulsion, structures, design, electronics and system integration focused on the goal of producing outer planet environments on a probe shaped vehicle during an earth entry. Major aspects of analysis and vehicle design studied include: planetary environments, earth entry environment capability, mission maneuvers, capabilities of shuttle upper stages, a comparison of earth entry planetary environments, experiment design and vehicle design.

  8. Demethoxycurcumin Preserves Renovascular Function by Downregulating COX-2 Expression in Hypertension

    Science.gov (United States)

    2016-01-01

    Hypertension-associated endothelial dysfunction is largely due to the exaggerated vasoconstrictor generation by cyclooxygenase-2 (COX-2). COX-2 is induced under inflammatory condition. Demethoxycurcumin (DMC) is a major component of Curcuma longa L, which possesses anti-inflammatory action. This study aimed to examine whether DMC protects endothelial function in hypertension by modulating COX-2. Changes in isometric tension showed that in vivo and ex vivo treatment with DMC rescued the attenuated endothelium-dependent relaxations (EDRs) and elevated endothelium-dependent contractions (EDCs) in the renal arteries of SHR, which were also corrected by acute usage of the COX-2 inhibitor celecoxib. The restoration of renovascular activity by DMC was accompanied by the normalization of COX-2 expression. The enhanced COX-2 expression observed in the renal arteries of hypertensive patients was suppressed by incubation of excised arteries with DMC for 12 hrs. In the renal arteries of Wistar-Kyoto rats (WKY), DMC prevented the endothelial dysfunction caused by angiotensin II. The reduction in the generation of nitric oxide (NO) and expression of eNOS phosphorylation (Ser1177) in human umbilical vein endothelial cells caused by angiotensin II (Ang II) were restored by DMC or celecoxib. Our findings suggest that DMC may decrease COX-2 expression and improve endothelial function in hypertension. PMID:28105253

  9. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  10. Delayed fluorescence in photosynthesis.

    Science.gov (United States)

    Goltsev, Vasilij; Zaharieva, Ivelina; Chernev, Petko; Strasser, Reto J

    2009-01-01

    Photosynthesis is a very efficient photochemical process. Nevertheless, plants emit some of the absorbed energy as light quanta. This luminescence is emitted, predominantly, by excited chlorophyll a molecules in the light-harvesting antenna, associated with Photosystem II (PS II) reaction centers. The emission that occurs before the utilization of the excitation energy in the primary photochemical reaction is called prompt fluorescence. Light emission can also be observed from repopulated excited chlorophylls as a result of recombination of the charge pairs. In this case, some time-dependent redox reactions occur before the excitation of the chlorophyll. This delays the light emission and provides the name for this phenomenon-delayed fluorescence (DF), or delayed light emission (DLE). The DF intensity is a decreasing polyphasic function of the time after illumination, which reflects the kinetics of electron transport reactions both on the (electron) donor and the (electron) acceptor sides of PS II. Two main experimental approaches are used for DF measurements: (a) recording of the DF decay in the dark after a single turnover flash or after continuous light excitation and (b) recording of the DF intensity during light adaptation of the photosynthesizing samples (induction curves), following a period of darkness. In this paper we review historical data on DF research and recent advances in the understanding of the relation between the delayed fluorescence and specific reactions in PS II. An experimental method for simultaneous recording of the induction transients of prompt and delayed chlorophyll fluorescence and decay curves of DF in the millisecond time domain is discussed.

  11. Soman increases neuronal COX-2 levels: possible link between seizures and protracted neuronal damage.

    Science.gov (United States)

    Angoa-Pérez, Mariana; Kreipke, Christian W; Thomas, David M; Van Shura, Kerry E; Lyman, Megan; McDonough, John H; Kuhn, Donald M

    2010-12-01

    Nerve agent-induced seizures cause neuronal damage in brain limbic and cortical circuits leading to persistent behavioral and cognitive deficits. Without aggressive anticholinergic and benzodiazepine therapy, seizures can be prolonged and neuronal damage progresses for extended periods of time. The objective of this study was to determine the effects of the nerve agent soman on expression of cyclooxygenase-2 (COX-2), the initial enzyme in the biosynthetic pathway of the proinflammatory prostaglandins and a factor that has been implicated in seizure initiation and propagation. Rats were exposed to a toxic dose of soman and scored behaviorally for seizure intensity. Expression of COX-2 was determined throughout brain from 4h to 7 days after exposure by immunohistochemistry and immunoblotting. Microglial activation and astrogliosis were assessed microscopically over the same time-course. Soman increased COX-2 expression in brain regions known to be damaged by nerve agents (e.g., hippocampus, amygdala, piriform cortex and thalamus). COX-2 expression was induced in neurons, and not in microglia or astrocytes, and remained elevated through 7 days. The magnitude of COX-2 induction was correlated with seizure intensity. COX-1 expression was not changed by soman. Increased expression of neuronal COX-2 by soman is a late-developing response relative to other signs of acute physiological distress caused by nerve agents. COX-2-mediated production of prostaglandins is a consequence of the seizure-induced neuronal damage, even after survival of the initial cholinergic crisis is assured. COX-2 inhibitors should be considered as adjunct therapy in nerve agent poisoning to minimize nerve agent-induced seizure activity.

  12. A cyclooxygenase (COX) inhibitory biflavonoid from the seeds of Semecarpus anacardium.

    Science.gov (United States)

    Selvam, C; Jachak, Sanjay M

    2004-12-01

    Semecarpus anacardium Linn., Anacardiaceae, is being most commonly used in India for the treatment of rheumatoid arthritis and other inflammatory disorders. Bioactivity guided fractionation of ethyl acetate extract led to the isolation of major active principle, tetrahydroamentoflavone (THA), a biflavonoid. The in vitro cyclooxygenase (COX-1) catalyzed prostaglandin biosynthesis assay of THA gave an IC(50) value of 29.5 microM (COX-1) and 40.5% inhibition at 100 microg/mL (COX-2). The in vivo carrageenan induced paw edema assay resulted in dose dependent anti-inflammatory effect of THA and the activity was comparable to that of ibuprofen, one of the well known NSAIDs.

  13. The Distribution of the Interval between Events of a Cox Process with Shot Noise Intensity

    Directory of Open Access Journals (Sweden)

    Angelos Dassios

    2008-01-01

    Full Text Available Applying piecewise deterministic Markov processes theory, the probability generating function of a Cox process, incorporating with shot noise process as the claim intensity, is obtained. We also derive the Laplace transform of the distribution of the shot noise process at claim jump times, using stationary assumption of the shot noise process at any times. Based on this Laplace transform and from the probability generating function of a Cox process with shot noise intensity, we obtain the distribution of the interval of a Cox process with shot noise intensity for insurance claims and its moments, that is, mean and variance.

  14. 19 CFR 142.44 - Entry number range.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry number range. 142.44 Section 142.44 Customs... (CONTINUED) ENTRY PROCESS Line Release § 142.44 Entry number range. After an application for Line Release has received final approval, filers must provide the port director, in writing, with a range of entry...

  15. 77 FR 5681 - Establishment of Global Entry Program

    Science.gov (United States)

    2012-02-06

    ... assist in developing a marketing strategy. The firm has created a new Global Entry logo and tag line... SENTRI II. Analysis of Comments A. Program Performance and Entry Process B. Marketing of Global Entry C.... Marketing of Global Entry Comment: CBP received two comments suggesting that CBP should expand marketing...

  16. Recollections on the early days of the Marcé Society for Perinatal Mental Health from Professor John Cox.

    Science.gov (United States)

    Cox, John L; Wisner, Katherine L

    2016-02-01

    Dr. Katherine Wisner interviewed Dr. John Cox, a founding member of the Marcé Society. Dr. Cox discussed the beginnings of the Marcé Society, his views about the current Society, and his vision for the future.

  17. Expression of COX-2 and p53 in juvenile polyposis coli and its correlation with adenomatous changes

    Directory of Open Access Journals (Sweden)

    Shatavisha Das Gupta

    2016-01-01

    Conclusion: We observed significantly higher COX-2 expression in JPC. Establishment of the role of COX-2 in JPC will help us formulate chemopreventive therapies as an adjunct to its surgical management.

  18. Delay-independent stabilization for teleoperation with time varying delay

    OpenAIRE

    Fujita, Hiroyuki; Namerikawa, Toru

    2009-01-01

    This paper deals with the stability for nonlinear teleoperation with time varying communication delays. The proposed method is passivity-based controllers with time varying gains which depend on the rate of change of time varying delay. In our proposed method, stability condition is independent of the magnitude of the communication delay and the damping of the system. The delay-independent stability is shown via Lyapunov stability methods. Several experimental results show the effectiveness o...

  19. Lessons learned from planetary entry probe missions

    Science.gov (United States)

    Niemann, Hasso; Atreya, Sushil K.; Kasprzak, Wayne

    Probing the atmospheres and surfaces of the planets and their moons with fast moving entry probes has been a very useful and essential technique to obtain in situ or quasi in situ scientific data (ground truth) which could not otherwise be obtained from fly by or orbiter only missions and where balloon, aircraft or lander missions are too complex and too costly. Planetary entry probe missions have been conducted successfully on Venus, Mars, Jupiter and Titan after having been first demonstrated in the Earth's atmosphere. Future planetary missions should also include more entry probe missions back to Venus and to the outer planets. The success of and science returns from past missions, the need for more and unique data, and a continuously advancing technology generate confidence that future missions will be even more successful with respect to science return and technical performance. There are, however, unique challenges associated with entry probe missions and with building instruments for an entry probe, as compared to orbiters, landers, or rovers. Conditions during atmospheric entry are extreme. There are operating time constraints due to the usually short duration of the probe descent, and the instruments experience rapid environmental changes in temperature and pressure. In addition, there are resource limitations, i.e. mass, power, size and bandwidth. Because of the protective heat shield and the high acceleration the probe experiences during entry, the ratio of payload to total probe mass is usually much smaller than in other missions. Finally, the demands on the instrument design are determined in large part by conditions (pressure, temperature, composition) unique to the particular body under study, and as a result, there is no one-size-fits-all instrument for an atmospheric probe. Many of these requirements are more easily met by miniaturizing the probe instrumentation and consequently reducing the required size of the probe. Improved heat shield

  20. 76 FR 82315 - Agency Information Collection Activities: Entry/Immediate Delivery Application and Simplified Entry

    Science.gov (United States)

    2011-12-30

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Entry/Immediate... Budget (OMB) for review and approval in accordance with the Paperwork Reduction Act: Entry/Immediate... process is conducted in accordance with 5 CFR 1320.10. DATES: Written comments should be received on or...

  1. Autonomous gliding entry guidance with geographic constraints

    Institute of Scientific and Technical Information of China (English)

    Guo Jie; Wu Xuzhong; Tang Shengjing

    2015-01-01

    This paper presents a novel three-dimensional autonomous entry guidance for relatively high lift-to-drag ratio vehicles satisfying geographic constraints and other path constraints. The guidance is composed of onboard trajectory planning and robust trajectory tracking. For trajectory planning, a longitudinal sub-planner is introduced to generate a feasible drag-versus-energy profile by using the interpolation between upper boundary and lower boundary of entry corridor to get the desired trajectory length. The associated magnitude of the bank angle can be specified by drag profile, while the sign of bank angle is determined by lateral sub-planner. Two-reverse mode is utilized to satisfy waypoint constraints and dynamic heading error corridor is utilized to satisfy no-fly zone constraints. The longitudinal and lateral sub-planners are iteratively employed until all of the path constraints are satisfied. For trajectory tracking, a novel tracking law based on the active disturbance rejection control is introduced. Finally, adaptability tests and Monte Carlo simulations of the entry guidance approach are performed. Results show that the proposed entry guidance approach can adapt to different entry missions and is able to make the vehicle reach the prescribed target point precisely in spite of geographic constraints.

  2. Financial Performance of Entry Mode Decisions

    DEFF Research Database (Denmark)

    Boyd, Britta; Dyhr Ulrich, Anna Marie; Hollensen, Svend

    2012-01-01

    Based on a survey of 170 Danish SMEs the paper examines influences on entry mode choices and the financial outcome of these decisions. The main research objectives are divided into two steps: Step 1: To determine the factors influencing the choice of foreign entry modes by Danish companies. Step ...... and implications are provided for companies willing to invest more into foreign markets in order to achieve a higher degree of control and better financial results.......Based on a survey of 170 Danish SMEs the paper examines influences on entry mode choices and the financial outcome of these decisions. The main research objectives are divided into two steps: Step 1: To determine the factors influencing the choice of foreign entry modes by Danish companies. Step 2......: To determine the relationship between the choice of entry mode and export performance, measured in terms of financial outcome. Drawing from transaction cost theory the authors develop and test a model where different factors affect the level of control chosen by the parent company. This study contributes...

  3. Enforced Expression of miR-101 Inhibits Prostate Cancer Cell Growth by Modulating the COX-2 Pathway In Vivo

    OpenAIRE

    Hao, Yubin; Gu, Xinbin; Zhao, Yuan; Greene, Stephen; Sha, Wei; Smoot, Duane T.; Califano, Joseph; Wu, T.-C.; Pang, Xiaowu

    2011-01-01

    It is commonly agreed that there is an association of chronic inflammation with tumorigenesis. COX-2, a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth; thus, overexpression of COX-2 is often found in tumor tissues. Therefore, a better understanding of the regulatory mechanism(s) of COX-2 could lead to novel targeted cancer therapies. In this study, we investigated the mechanism of microRNA-101 (miR-101)-regulated COX-2 expression and the therape...

  4. Cyclooxygenases in human and mouse skin and cultured human keratinocytes: association of COX-2 expression with human keratinocyte differentiation

    Science.gov (United States)

    Leong, J.; Hughes-Fulford, M.; Rakhlin, N.; Habib, A.; Maclouf, J.; Goldyne, M. E.

    1996-01-01

    Epidermal expression of the two isoforms of the prostaglandin H-generating cyclooxygenase (COX-1 and COX-2) was evaluated both by immunohistochemistry performed on human and mouse skin biopsy sections and by Western blotting of protein extracts from cultured human neonatal foreskin keratinocytes. In normal human skin, COX-1 immunostaining is observed throughout the epidermis whereas COX-2 immunostaining increases in the more differentiated, suprabasilar keratinocytes. Basal cell carcinomas express little if any COX-1 or COX-2 immunostaining whereas both isozymes are strongly expressed in squamous cell carcinomas deriving from a more differentiated layer of the epidermis. In human keratinocyte cultures, raising the extracellular calcium concentration, a recognized stimulus for keratinocyte differentiation, leads to an increased expression of both COX-2 protein and mRNA; expression of COX-1 protein, however, shows no significant alteration in response to calcium. Because of a recent report that failed to show COX-2 in normal mouse epidermis, we also looked for COX-1 and COX-2 immunostaining in sections of normal and acetone-treated mouse skin. In agreement with a previous report, some COX-1, but no COX-2, immunostaining is seen in normal murine epidermis. However, following acetone treatment, there is a marked increase in COX-1 expression as well as the appearance of significant COX-2 immunostaining in the basal layer. These data suggest that in human epidermis as well as in human keratinocyte cultures, the expression of COX-2 occurs as a part of normal keratinocyte differentiation whereas in murine epidermis, its constitutive expression is absent, but inducible as previously published.

  5. [Striated and delayed nephrography].

    Science.gov (United States)

    Marlois, O; Padovani, J; Faure, F; Devred, P; Grangier, M L; Panuel, M

    1985-10-01

    About a case of striated and delayed nephrogram seen on a diabetic child, authors come back to the different etiologies. Among them, the tubular precipitation of Tamm-Horsfall protein seems to be given like on the right possibilities. Whatever is its etiology, the mechanism of striated appearance is always the same, being founded on the radiated disposal of the collecting ducts and on a tubular stasis beeing with iodine concentration.

  6. Theoretical Delay Time Distributions

    CERN Document Server

    Nelemans, Gijs; Bours, Madelon

    2012-01-01

    We briefly discuss the method of population synthesis to calculate theoretical delay time distributions of type Ia supernova progenitors. We also compare the results of the different research groups and conclude that although one of the main differences in the results for single degenerate progenitors is the retention efficiency with which accreted hydrogen is added to the white dwarf core, this cannot explain all the differences.

  7. Theoretical Delay Time Distributions

    Science.gov (United States)

    Nelemans, Gijs; Toonen, Silvia; Bours, Madelon

    2013-01-01

    We briefly discuss the method of population synthesis to calculate theoretical delay time distributions of Type Ia supernova progenitors. We also compare the results of different research groups and conclude that, although one of the main differences in the results for single degenerate progenitors is the retention efficiency with which accreted hydrogen is added to the white dwarf core, this alone cannot explain all the differences.

  8. Geometric Time Delay Interferometry

    OpenAIRE

    Vallisneri, Michele

    2005-01-01

    The space-based gravitational-wave observatory LISA, a NASA-ESA mission to be launched after 2012, will achieve its optimal sensitivity using Time Delay Interferometry (TDI), a LISA-specific technique needed to cancel the otherwise overwhelming laser noise in the inter-spacecraft phase measurements. The TDI observables of the Michelson and Sagnac types have been interpreted physically as the virtual measurements of a synthesized interferometer. In this paper, I present Geometric TDI, a new an...

  9. Time-Delay Interferometry

    OpenAIRE

    Dhurandhar Sanjeev V.; Tinto Massimo

    2005-01-01

    Equal-arm interferometric detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set overall performance. If, however, the two arms have different lengths (...

  10. Delay in atomic photoionization

    CERN Document Server

    Kheifets, A S

    2010-01-01

    We analyze the time delay between emission of photoelectrons from the outer valence $ns$ and $np$ sub-shells in noble gas atoms following absorption of an attosecond XUV pulse. By solving the time dependent Schr\\"odinger equation and carefully examining the time evolution of the photoelectron wave packet, we establish the apparent "time zero" when the photoelectron leaves the atom. Various processes such as elastic scattering of the photoelectron on the parent ion and many-electron correlation affect the quantum phase of the dipole transition matrix element, the energy dependence of which defines the emission timing. This qualitatively explains the time delay between photoemission from the $2s$ and $2p$ sub-shells of Ne as determined experimentally by attosecond streaking [{\\em Science} {\\bf 328}, 1658 (2010)]. However, with our extensive numerical modeling, we were only able to account for less than a half of the measured time delay of $21\\pm5$~as. We argue that the XUV pulse alone cannot produce such a larg...

  11. Time-Delay Interferometry

    Directory of Open Access Journals (Sweden)

    Massimo Tinto

    2014-08-01

    Full Text Available Equal-arm detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set the overall performance. If, however, the two arms have different lengths (as will necessarily be the case with space-borne interferometers, the laser noise experiences different delays in the two arms and will hence not directly cancel at the detector. In order to solve this problem, a technique involving heterodyne interferometry with unequal arm lengths and independent phase-difference readouts has been proposed. It relies on properly time-shifting and linearly combining independent Doppler measurements, and for this reason it has been called time-delay interferometry (TDI. This article provides an overview of the theory, mathematical foundations, and experimental aspects associated with the implementation of TDI. Although emphasis on the application of TDI to the Laser Interferometer Space Antenna (LISA mission appears throughout this article, TDI can be incorporated into the design of any future space-based mission aiming to search for gravitational waves via interferometric measurements. We have purposely left out all theoretical aspects that data analysts will need to account for when analyzing the TDI data combinations.

  12. Forecasts of non-Gaussian parameter spaces using Box-Cox transformations

    CERN Document Server

    Joachimi, B

    2011-01-01

    Forecasts of statistical constraints on model parameters using the Fisher matrix abound in many fields of astrophysics. The Fisher matrix formalism involves the assumption of Gaussianity in parameter space and hence fails to predict complex features of posterior probability distributions. Combining the standard Fisher matrix with Box-Cox transformations, we propose a novel method that accurately predicts arbitrary posterior shapes. The Box-Cox transformations are applied to parameter space to render it approximately multivariate Gaussian, performing the Fisher matrix calculation on the transformed parameters. We demonstrate that, after the Box-Cox parameters have been determined from an initial likelihood evaluation, the method correctly predicts changes in the posterior when varying various parameters of the experimental setup and the data analysis, with marginally higher computational cost than a standard Fisher matrix calculation. We apply the Box-Cox-Fisher formalism to forecast cosmological parameter con...

  13. COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1.

    Science.gov (United States)

    Ban-Ishihara, Reiko; Tomohiro-Takamiya, Shiho; Tani, Motohiro; Baudier, Jacques; Ishihara, Naotada; Kuge, Osamu

    2015-10-07

    Mitochondria are dynamic organelles that alter their morphology in response to cellular signaling and differentiation through balanced fusion and fission. In this study, we found that the mitochondrial inner membrane ATPase ATAD3A interacted with ccdc56/MITRAC12/COA3, a subunit of the cytochrome oxidase (COX)-assembly complex. Overproduction of ccdc56 in HeLa cells resulted in fragmented mitochondrial morphology, while mitochondria were highly elongated in ccdc56-repressed cells by the defective recruitment of the fission factor Drp1. We also found that mild and chronic inhibition of COX led to mitochondrial elongation, as seen in ccdc56-repressed cells. These results indicate that ccdc56 positively regulates mitochondrial fission via regulation of COX activity and the mitochondrial recruitment of Drp1, and thus, suggest a novel relationship between COX assembly and mitochondrial morphology.

  14. a study of the slope of cox proportional hazard and weibull models

    African Journals Online (AJOL)

    Adejumo & Ahmadu

    the values of the unknown parameters. These include the ... semi parametric cox proportional hazard model when the parametric ... simulated and the real life data approach. ... greatest risk progression of TB infection to active disease. People.

  15. Neoplasms escape selective COX-2 inhibition in an animal model of breast cancer.

    LENUS (Irish Health Repository)

    Barry, M

    2009-06-01

    Cyclo-oxygenase-2 (COX-2) is up-regulated in malignant tumours rendering it an attractive target for cancer therapeutics. However, whether long-term antagonism maintains its initial efficacy on established tumours is unclear.

  16. Study of gastrointestinal toxicity of selective COX-2 inhibitors in comparison with conventional NSAIDs

    Directory of Open Access Journals (Sweden)

    Hima Bindu K.

    2016-12-01

    Conclusions: In our short-term study, selective COX-2 inhibitors did not show any advantage over non-selective NSAIDs regarding their gastrointestinal toxicity. [Int J Res Med Sci 2016; 4(12.000: 5180-5184

  17. Shuttle program. MCC Level C formulation requirements: Entry guidance and entry autopilot

    Science.gov (United States)

    Harpold, J. C.; Hill, O.

    1980-01-01

    A set of preliminary entry guidance and autopilot software formulations is presented for use in the Mission Control Center (MCC) entry processor. These software formulations meet all level B requirements. Revision 2 incorporates the modifications required to functionally simulate optimal TAEM targeting capability (OTT). Implementation of this logic in the MCC must be coordinated with flight software OTT implementation and MCC TAEM guidance OTT. The entry guidance logic is based on the Orbiter avionics entry guidance software. This MCC requirements document contains a definition of coordinate systems, a list of parameter definitions for the software formulations, a description of the entry guidance detailed formulation requirements, a description of the detailed autopilot formulation requirements, a description of the targeting routine, and a set of formulation flow charts.

  18. Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor.

    Science.gov (United States)

    Hasegawa, Kiyoshi; Ishikawa, Kunimi; Kawai, Satoshi; Torii, Yutaka; Kawamura, Kyoko; Kato, Rina; Tsukada, Kazuhiko; Udagawa, Yasuhiro

    2013-12-01

    Cyclooxygenase (COX)-2 inhibitors have been reported to potentially modulate the resistance of cancer cells to chemotherapeutic drugs by affecting multidrug resistance 1 (MDR1) expression. In the present study, we investigated the association between COX-2 and MDR1 expression in endometrial cancers and evaluated the effects of the COX-2 inhibitor, etodolac, in combination with paclitaxel on paclitaxel-resistant endometrial cancer cells. The relationship between COX-2 and MDR1 mRNA expression was examined by quantitative PCR in 36 endometrial cancer specimens. The paclitaxel-resistant cell line OMC-2P was established from OMC-2 cells. Paclitaxel (1 µg/ml) with or without etodolac (10 µg/ml) was added to OMC-2 and OMC-2P cells, and COX-2 and MDR1 mRNA expression levels were examined. The concentration of prostaglandin E2 (PGE2) in the supernatant of each cell line was examined by enzyme-linked immunosorbent assay. The function of MDR1 was determined by intracellular accumulation of rhodamine 123 using flow cytometry, and the concentration of intracellular paclitaxel was determined by high-performance liquid chromatography. We found a positive relationship between COX-2 and MDR1 mRNA expression in endometrial cancer. Both COX-2 mRNA expression and PGE2 production were elevated in resistant OMC-2P cells when compared to non-resistant OMC-2 cells. Additionally, MDR1 mRNA expression was markedly upregulated in OMC-2P cells. In OMC-2 cells, COX-2 and MDR1 mRNA levels were significantly upregulated by paclitaxel treatment and downregulated by co-administration with etodolac. In OMC-2P cells, COX-2 mRNA expression was also significantly upregulated by paclitaxel treatment and tended to be downregulated by co-administration with etodolac. Moreover, co-administration of paclitaxel and etodolac suppressed the induction of MDR1 mRNA. Rhodamine 123 efflux was increased in OMC-2P cells when compared to the efflux in the OMC-2 cells and was increased in response to paclitaxel

  19. An observational study of the discrediting of COX-2 NSAIDs in Australia: Vioxx or class effect?

    Directory of Open Access Journals (Sweden)

    Parkinson Lynne

    2011-11-01

    Full Text Available Abstract Background When a medicine such as rofecoxib (Vioxx is withdrawn, or a whole class of medicines discredited such as the selective COX-2 inhibitors (COX-2s, follow-up of impacts at consumer level can be difficult and costly. The Australian Longitudinal Study on Women's Health provides a rare opportunity to examine individual consumer medicine use following a major discrediting event, the withdrawal of rofecoxib and issuing of safety warnings on the COX-2 class of medicines. The overall objective of this paper was to examine the impact of this discrediting event on dispensing of the COX-2 class of medicines, by describing medicine switching behaviours of older Australian women using rofecoxib in September 2004; the uptake of other COX-2s; and the characteristics of women who continued using a COX-2. Methods Participants were concessional beneficiary status women from the Older cohort (born 1921-26 of the Australian Longitudinal Study on Women's Health who consented to linkage to Pharmaceutical Benefits Scheme data, with at least one rofecoxib prescription dispensed in the 12 months before rofecoxib withdrawal. A prescription was defined as one dispensing occasion. Women were grouped by rofecoxib pattern of use: continuous (nine or more prescriptions dispensed in the 12 months prior to rofecoxib withdrawal or non-continuous (eight or less prescriptions dispensed in the 12 months prior to rofecoxib withdrawal users. Incidence rate per 100,000 person days and incidence risk ratio described uptake of alternate medicines, following rofecoxib withdrawal. Kaplan-Meier curves described differences in uptake patterns by medicine and pattern of rofecoxib use. Patterns of use of COX-2s in the next 100 days after first COX-2 uptake were described. Results Medicine switches and pattern of medicines uptake differed significantly depending upon whether a woman was a continuous or non-continuous rofecoxib user prior to rofecoxib discrediting. Continuous

  20. Variations from Zn1-xCoxO Magnetic Semiconductor to Co-ZnCoO Granular Composite

    Institute of Scientific and Technical Information of China (English)

    CHEN Yan-Xue; YAN Shi-Shen; LIU Guo-Lei; MEI Liang-Mo; REN Miao-Juan

    2007-01-01

    @@ We investigate the variations from as-deposited Zn1-xCoxO magnetic semiconductors to the post-annealed CoZnCoO granular composite. The as-deposited Zn1-xCoxO magnetic semiconductor deposited under thermal nonequilibrium conditions is composed of Zn1-xCoxO nanograins of high Co concentration.

  1. Ester Prodrugs of Ketoprofen: Synthesis, In Vitro Stability, In Vivo Biological Evaluation and In Silico Comparative Docking Studies Against COX-1 and COX-2.

    Science.gov (United States)

    Ahmed, Musa; Azam, Faizul; Gbaj, Abdul; Zetrini, Abdulmottaleb E; Abodlal, Amna Salem; Rghigh, Abir; Elmahdi, Eman; Hamza, Amel; Salama, Mabruk; Bensaber, Salah M

    2016-01-01

    Prompted by the ineptness of the currently used non-steroidal antiinflammatory drugs (NSAIDs) to control gastric mucosal and renal adverse reactions, several ester prodrugs of ketoprofen were synthesized and characterized by IR, 1H NMR and mass spectral data. Physicochemical properties such as aqueous solubility, octanol-water partition coefficient log P, chemical stability and enzymatic hydrolysis of the synthesized molecules have been studied to assess their potential as prodrugs. The obtained results confirmed that all ester prodrugs are chemically stable, possess increased lipophilicity compared to their parent compounds and converted to the active drugs in vivo. All of the tested ester prodrugs exhibited marked anti-inflammatory activity ranging from 91.8% to 113.3% in comparison with the parent drug, ketoprofen. A mutual prodrug obtained from two antiinflammatory molecules, ketoprofen and salicylic acid has been noted to potentiate the activity making it most active molecule of the series. The ulcerogenic index of the ester prodrugs was significantly lower than the parent drug, ketoprofen. Comparative docking studies against X-ray crystal structures of COX-1 and COX-2 further provided understanding of their interaction with the cyclooxygenases that will facilitate design of better inhibitors (or prodrugs) with sufficient specificity for COX-2 against COX-1. The study offers an innovative strategy for finding a molecule with safer therapeutic profile for longterm treatment of inflammatory diseases.

  2. Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension.

    Science.gov (United States)

    Avendaño, M S; Martínez-Revelles, S; Aguado, A; Simões, M R; González-Amor, M; Palacios, R; Guillem-Llobat, P; Vassallo, D V; Vila, L; García-Puig, J; Beltrán, L M; Alonso, M J; Cachofeiro, M V; Salaices, M; Briones, A M

    2016-05-01

    Prostanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension. Spontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mg · kg(-1) · day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mg · kg(-1) · day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mg · kg(-1) · day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used. Celecoxib and SC19220 treatment did not modify the altered lumen diameter and wall : lumen ratio in mesenteric resistance arteries from SHR-infused and/or AngII-infused animals. However, both treatments and COX-2 deficiency decreased the augmented vascular stiffness in vessels from hypertensive animals. This was accompanied by diminished vascular collagen deposition, normalization of altered elastin structure and decreased connective tissue growth factor and plasminogen activator inhibitor-1 gene expression. COX-2 deficiency and SC19220 treatment diminished the increased vasoconstrictor responses and endothelial dysfunction induced by AngII infusion. Hypertensive animals showed increased mPGES-1 expression and PGE2 production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF-α expression. Macrophage conditioned media (MCM) increased COX-2 and collagen type I expression in vascular smooth muscle cells; the latter was reduced by celecoxib treatment. COX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE2 receptors might have benefits in hypertension-associated vascular damage. © 2016 The British Pharmacological Society.

  3. Delayed Speech or Language Development

    Science.gov (United States)

    ... to 2-Year-Old Delayed Speech or Language Development KidsHealth > For Parents > Delayed Speech or Language Development ... child is right on schedule. Normal Speech & Language Development It's important to discuss early speech and language ...

  4. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

    Devkanya Dutta

    2000-12-01

    Activation of receptors coupled to the phospholipase C/IP3 signalling pathway results in a rapid release of calcium from its intracellular stores, eventually leading to depletion of these stores. Calcium store depletion triggers an influx of extracellular calcium across the plasma membrane, a mechanism known as the store-operated calcium entry or capacitative calcium entry. Capacitative calcium current plays a key role in replenishing calcium stores and activating various physiological processes. Despite considerable efforts, very little is known about the molecular nature of the capacitative channel and the signalling pathway that activates it. This review summarizes our current knowledge about store operated calcium entry and suggests possible hypotheses for its mode of activation.

  5. Modes and orders of market entry

    DEFF Research Database (Denmark)

    Ulhøi, John Parm

    2012-01-01

    This paper focuses on the initial questions of how and when to enter a market from the perspective of a firm. By entry mode is meant a firm’s strategy (innovation or imitation) for entering the market in response to environmental changes. Entry order refers to the related issue of market timing...... strategies are more ambiguous. Based on a corporate technology and innovation strategy perspective, the paper reconceptualises and extends existing modes and orders of market entry, and in particular clarifies the ambiguity associated with imitative strategies. Four distinct imitator strategies...... are identified. The paper closes with a brief discussion of limitations, avenues for future research, and implications for managers and affected policymakers....

  6. Evaluating the Tailored Adaptive Personality Assessment System on Delayed Entry Program Attrition

    Science.gov (United States)

    2014-03-01

    DEP Participants in Sample g. Education Individuals’ education levels are identified by seven categories. All of these education levels are...individual is a high school graduate. “Some College” indicates an individual attended and completed at least one semester of college but less than...what is required for a degree. “College Graduate” includes individuals with associates, bachelors, masters, doctorate , and other professional degrees

  7. Analysis of Recruit Attrition from the Navy’s Delayed Entry Program and Recruit Training Command

    Science.gov (United States)

    2007-12-01

    know their friends’ parents well.”31 Further: “ Teenagers who take on adult responsibilities—becoming a parent, getting married, and holding down a job...important than a man’s age, primarily because age is related to both pregnancy and disability rates for first- term women.80 Women historically have had...the “z-score”. Using this knowledge , the probit regression coefficients can be directly interpreted. The results of the theoretical model are

  8. Chiapas' Delayed Entry into the International Labour Market: A Story of Peasant Isolation, Exploitation, and Coercion.

    Science.gov (United States)

    Davis, Jason; Eakin, Hallie

    2013-06-01

    This manuscript presents a synthetic view of Chiapas' migration history over the last century through a thorough examination of relevant English and Spanish-language literature sources. Unlike most Mexican states, Chiapas did not heavily rely upon migration, especially international migration, as an economic strategy until very recently. The reasons that underlie Chiapas' late adoption of economic migration include socio-political and economic structural factors that shaped rural and agrarian policy and demographic trends. This paper evaluates these structural factors with regards to several migration theories to assist our understanding of how and why Chiapans were prevented or discouraged from leaving their native communities. The paper concludes by detailing the perfect cascade of climatic, demographic, economic and political factors that ultimately forced Chiapans to resort to international migration as a major economic diversification strategy.

  9. DYPES: Vertical differentiation, schedule delay and entry deterrence: Low cost vs. full service airlines

    OpenAIRE

    Jorge Valido; M. Pilar Socorro; Francesca Medda

    2013-01-01

    We consider a market with a full-service (FS) carrier (the incumbent) and a low-cost (LC) carrier (the potential entrant). If the LC carrier enters the market, airlines compete in ticket prices and frequency with vertically differentiated products. The higher the frequency, the lower passenger’s generalized price. Thus, more frequency allows airlines to increase ticket prices without losing demand. In this context, we show that the incumbent may increase the frequency offered in order to dete...

  10. The Role of the Delayed Entry Program in Recruiting the All-Volunteer Force

    Science.gov (United States)

    2013-10-01

    checking applicant Facebook pages for obvious signs of disqualification (e.g., weight, tattoos , and discussion of problems with education, drugs, or...disqualifying conditions, such as weight, tattoos , or references to problems with education, drug use, or police involvement. Applicant-aged youth frequently...to motivate DEP members and attract new applicants. DEP referrals The Navy, Army, and Marine Corps offer promotion opportunities to DEP members

  11. COX-independent mechanisms of cancer chemoprevention by anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Evrim eGurpinar

    2013-07-01

    Full Text Available Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs, including cyclooxygenase (COX-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention.

  12. Hypermethylation of the COX-2 gene is a potential prognostic marker for cervical cancer.

    Science.gov (United States)

    Jo, Hoenil; Kang, Sokbom; Kim, Jae W; Kang, Gyeong H; Park, Noh H; Song, Yong S; Park, Sang Y; Kang, Soon B; Lee, Hyo P

    2007-06-01

    The aim of the present study was to evaluate the DNA hypermethylation profiles of 14 genes known to be associated with tumor behavior and their clinical significance in cervical cancer. The clinical features of 82 patients with stage IB cervical cancer were analyzed in terms of DNA hypermethylation of 14 genes (hMLH1, p16, COX-2, CDH1, APC, DAPK, MGMT, p14, RASSF1A, RUNX3, TIMP3, FHIT, THBS1, and HLTF). Of 14 genes investigated, only hypermethylation of COX-2 showed significant association with poor disease-free survival (P = 0.001). To further investigate an alteration in COX-2 expression by DNA hypermethylation, immunohistochemistry for COX-2 protein was performed in the cervical cancer tissues. We found no significant association between hypermethylation and expression patterns of the COX-2 gene. The present results suggest that DNA hypermethylation of the COX-2 gene may be a potential prognostic marker in early stage cervical cancer, the underlying mechanism of which is independent of gene silencing.

  13. Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation.

    Science.gov (United States)

    Hermanson, Daniel J; Hartley, Nolan D; Gamble-George, Joyonna; Brown, Naoko; Shonesy, Brian C; Kingsley, Phillip J; Colbran, Roger J; Reese, Jeffrey; Marnett, Lawrence J; Patel, Sachin

    2013-09-01

    Augmentation of endogenous cannabinoid (eCB) signaling represents an emerging approach to the treatment of affective disorders. Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid to form prostaglandins, but also inactivates eCBs in vitro. However, the viability of COX-2 as a therapeutic target for in vivo eCB augmentation has not been explored. Using medicinal chemistry and in vivo analytical and behavioral pharmacological approaches, we found that COX-2 is important for the regulation of eCB levels in vivo. We used a pharmacological strategy involving substrate-selective inhibition of COX-2 to augment eCB signaling without affecting related non-eCB lipids or prostaglandin synthesis. Behaviorally, substrate-selective inhibition of COX-2 reduced anxiety-like behaviors in mice via increased eCB signaling. Our data suggest a key role for COX-2 in the regulation of eCB signaling and indicate that substrate-selective pharmacology represents a viable approach for eCB augmentation with broad therapeutic potential.

  14. Antiinflammatory and antinociceptive activities of gossypin and procumbentin--cyclooxygenase-2 (COX-2) inhibition studies.

    Science.gov (United States)

    Mada, Sripal Reddy; Metukuri, Mallikarjuna Reddy; Burugula, Laxminarayana; Reddanna, Pallu; Krishna, Devarakonda Rama

    2009-06-01

    In the present study the antiinflammatory and antinociceptive activities of a few selected flavonoids were investigated. Procumbentin, gossypin, chrysin and methylhespiridin were studied for antiinflammatory and antinociceptive activities using in vitro enzymatic assays and in animal models utilizing acetic acid-induced writhing in mice and hind paw edema in rats. In vitro studies were performed using TMPD (NNN'N'-tetramethyl-p-phenylene diamine) and oxygraphic methods for COX-1 (cyclooxygenase-1), COX-2, 5-LOX (5-lipoxygenase) and 15-LOX. Gossypin and procumbentin showed COX-2 inhibitory activity and exhibited IC(50) (COX-2/COX-1) ratios of 0.14 and 0.11, respectively. None of the flavonoids tested in this study showed LOX inhibitory activity. Four groups were studied for each test compound following intraperitoneal (i.p.) administration of doses of 10, 30 and 100 mg/kg. Antiinflammatory activity was measured by the carrageenin-induced rat hind paw edema model and antinociceptive activity by acetic acid-induced writhing. Procumbentin and gossypin showed antinociceptive activity at the 100 mg/kg dose. Gossypin showed antiinflammatory activity at doses of 10, 30, 100 mg/kg. Procumbentin and gossypin exhibited COX-2 inhibitory activity when tested by in vitro methods. Procumbentin and gossypin showed antinociceptive, and gossypin showed antiinflammatory, activities.

  15. Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition.

    Science.gov (United States)

    Qiu, Han-Yue; Wang, Peng-Fei; Li, Zhen; Ma, Jun-Ting; Wang, Xiao-Ming; Yang, Yong-Hua; Zhu, Hai-Liang

    2016-02-01

    COX-2 has long been exploited in the treatment of inflammation and relief of pain; however, research increasingly suggests COX-2 inhibitors might possess potential benefits to thwart tumour processes. In the present study, we designed a series of novel COX-2 inhibitors based on analysis of known inhibitors combined with an in silico scaffold modification strategy. A docking simulation combined with a primary screen in vitro were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. Derivative 4d was identified as a potent COX-2 enzyme inhibitor and exerted an anticancer effect through COX-2 inhibition. Further investigation confirmed that 4d could induce A549 cell apoptosis and arrest the cell cycle at the G2/M phase. Moreover, treatment with 4d reduced A549 cell adhesive ability and COX-2 expression. The morphological variation of treated cells was also visualized by confocal microscopy. Overall, the biological profile of 4d suggests that this compound may be developed as a potential anticancer agent.

  16. Expression of COX-2 and bcl-2 in oral lichen planus lesions and lichenoid reactions

    Science.gov (United States)

    Arreaza, Alven J; Rivera, Helen; Correnti, María

    2014-01-01

    Oral lichen planus and lichenoid reactions are autoimmune type inflammatory conditions of the oral mucosa with similar clinical and histological characteristics. Recent data suggest that oral lichenoid reactions (OLR) present a greater percentage of malignant transformation than oral lichen planus (OLP). Objective To compare the expression of bcl-2 and COX-2 in OLP and OLR. Methods The study population consisted of 65 cases; 34 cases diagnosed as OLR and 31 as OLP. A retrospective study was done, and bcl-2 and COX-2 expression was semiquantitatively analysed. Results Fifty-three per cent (18/34) of the ORL samples tested positive for COX-2, whereas in the OLP group, 81% of the samples (25/31) immunostained positive for COX-2. The Fisher’s exact test for the expression of COX-2 revealed that there are significant differences between the two groups, P = 0.035. With respect to the expression of the bcl-2 protein, 76% (26/34) of the samples were positive in OLR, while 97% (30/31) were positive in the group with OLP. The Fisher’s exact test for the expression of bcl-2 revealed that there are significant statistical differences between the two groups, P = 0.028. Conclusions The expression of bcl-2 and COX-2 was more commonly expressed in OLP when compared with OLR. PMID:24834112

  17. Survival analysis of gastric cancer patients using Cox model: a five year study

    Directory of Open Access Journals (Sweden)

    Biglarian A

    2009-08-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Gastric cancer is the second most common cancer and known as the second cause of death due to cancers worldwide. Adenocarcinoma is the most fatal cancer in Iran and a patient with this kind of cancer, has a lower lifetime than others. In this research, the survival of patients with gastric carcinoma who were registered at Taleghani Hospital, were studied."n"nMethods: 291 patients with Gastric carcinoma who had received care, chemotherapy or chemoradiotherapy, at Taleghani Hospital in Tehran from 2002 to 2007 were studied as a historical cohort. Their survival rates and its relationship with 12 risk factors were assessed."n"nResults: Of the 291 patients with Gastric carcinoma, 70.1 percent were men and others (29.9% were women. The mean age of men was 62.26 years and of women was 59.32 years at the time of diagnosis. Most of patients (93.91% were advanced stage and metastasis. The Cox proportional hazards model showed that age at diagnosis, tumor stage and histology type with survival time had significant relationships (p=0.039, p=0.042 and p=0.032 respectively."n"n Conclusion: The five-year survival rate and median lifetime of gastric cancer patients who underwent chemotherapy or chemoradiotherapy are very

  18. Down regulation of cyclooxygenase-2 is involved in delayed neuroprotec-tion by ischemic preconditioning in rats

    Institute of Scientific and Technical Information of China (English)

    Liang XIAO; Fei-li ZHAO; Xing-zu ZHU

    2005-01-01

    Aim: To examine whether the prostaglandins (PGs) pathway is involved in triggering delayed neuroprotection by ischemic preconditioning (IPC) and evaluate the effects of IPC on cyclooxygenase-2 (COX-2) expression following focal cerebral ischemia and reperfusion in rats. Methods: IPC was induced by 10 min of saline infusion into the left internal carotid artery with the right common carotid artery clamped at the same time. Middle cerebral artery occlusion (MCAO) and reperfusion model was produced using intraluminal filament method. Results: IPC 48 h prior to MCAO significantly reduced infarct area as compared with MCAO alone. A nonselective inhibitor of COX indomethacin (3 mg/kg ip) applied 1 h prior to or 1 h after IPC failed to affect its protective effects. IPC had no direct effect on the cortex COX-2 mRNA and protein expression 72 h later, but decreased the expres sion of COX-2 mRNA and protein following ischemia and reperfusion insult. Conclusion: PGs pathways was not involved in triggering delayed neuroprotection by IPC, and IPC induced down-regulation of COX-2 following focal cerebral ischemia and reperfusion in rats in vivo.

  19. Activation of COX-2/PGE2 Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production.

    Science.gov (United States)

    Alfajaro, Mia Madel; Choi, Jong-Soon; Kim, Deok-Song; Seo, Ja-Young; Kim, Ji-Yun; Park, Jun-Gyu; Soliman, Mahmoud; Baek, Yeong-Bin; Cho, Eun-Hyo; Kwon, Joseph; Kwon, Hyung-Jun; Park, Su-Jin; Lee, Woo Song; Kang, Mun-Il; Hosmillo, Myra; Goodfellow, Ian; Cho, Kyoung-Oh

    2017-02-01

    Enteric caliciviruses in the genera Norovirus and Sapovirus are important pathogens that cause severe acute gastroenteritis in both humans and animals. Cyclooxygenases (COXs) and their final product, prostaglandin E2 (PGE2), are known to play important roles in the modulation of both the host response to infection and the replicative cycles of several viruses. However, the precise mechanism(s) by which the COX/PGE2 pathway regulates sapovirus replication remains largely unknown. In this study, infection with porcine sapovirus (PSaV) strain Cowden, the only cultivable virus within the genus Sapovirus, markedly increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced PGE2 production, as well as PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We observed that pharmacological inhibition of COX-2 dramatically increased NO production, causing a reduction in PSaV replication that could be restored by inhibition of nitric oxide synthase via the inhibitor N-nitro-l-methyl-arginine ester. This study identified a pivotal role for the COX/PGE2 pathway in the regulation of NO production during the sapovirus life cycle, providing new insights into the life cycle of this poorly characterized family of viruses. Our findings also reveal potential new targets for treatment of sapovirus infection. Sapoviruses are among the major etiological agents of acute gastroenteritis in both humans and animals, but little is known about sapovirus host factor requirements. Here, using only cultivable porcine sapovirus (PSaV) strain Cowden, we demonstrate that PSaV induced the vitalization of the cyclooxygenase (COX) and prostaglandin E2 (PGE2) pathway. Targeting

  20. Automated Re-Entry System using FNPEG

    Science.gov (United States)

    Johnson, Wyatt R.; Lu, Ping; Stachowiak, Susan J.

    2017-01-01

    This paper discusses the implementation and simulated performance of the FNPEG (Fully Numerical Predictor-corrector Entry Guidance) algorithm into GNC FSW (Guidance, Navigation, and Control Flight Software) for use in an autonomous re-entry vehicle. A few modifications to FNPEG are discussed that result in computational savings -- a change to the state propagator, and a modification to cross-range lateral logic. Finally, some Monte Carlo results are presented using a representative vehicle in both a high-fidelity 6-DOF (degree-of-freedom) sim as well as in a 3-DOF sim for independent validation.

  1. Form, its meaning, and dictionary entries

    Directory of Open Access Journals (Sweden)

    Violetta Koseska-Toszewa

    2015-11-01

    It is worth stressing that distinguishing between the form and its meaning in comparing the material 6 languages belonging to three different groups of Slavic languages (as is the case in the MONDILEX Project will allow us to avoid numeorus substantiva mistakes and erroneous conclusions. Hence dictionary entries should be verified and made uniform in that respect before they are “digitalized”... Distinction between the form and its meaning in a dictionary entry is fully possible, as shown by works of Z. Saloni (2002 and A.Przepiórkowski (2008.

  2. Project Prometheus and Future Entry Probe Missions

    Science.gov (United States)

    Spilker, Thomas R.

    2005-01-01

    A viewgraph presentation on project Prometheus and future entry probe missions is shown. The topics include: 1) What Is Project Prometheus?; 2) What Capabilities Can Project Prometheus Offer? What Mission Types Are Being Considered?; 3) Jupiter Icy Moons Orbiter (JIMO); 4) How Are Mission Opportunities Changing?; 5) Missions Of Interest a Year Ago; 6) Missions Now Being Considered For Further Study; 7) Galileo-Style (Conventional) Probe Delivery; 8) Galileo-Style Probe Support; 9) Conventional Delivery and Support of Multiple Probes; 10) How Entry Probe Delivery From an NEP Vehicle Is Different; and 11) Concluding Remarks.

  3. "Generic Entry and the Pricing of Pharmaceuticals"

    OpenAIRE

    Frank, Richard G.; David S. Salkever

    1995-01-01

    During the 1980s the share of prescriptions sold by retail pharmacies that was accounted for by generic products roughly doubled. The price response to generic entry of brand-name products has been a source of controversy. In this paper we estimate models of price responses to generic entry in the market for brand-name and generic drugs. We study a sample of 32 drugs that lost patent protection during the early to mid-1980s. Our results provide strong evidence that brand-name prices increase ...

  4. The expression of COX-2 in VEGF-treated endothelial cells is mediated through protein tyrosine kinase

    Directory of Open Access Journals (Sweden)

    Pravit Akarasereenont

    2002-01-01

    Full Text Available Cyclooxygenase (COX, existing as the COX-1 and COX-2 isoforms, converts arachidonic acid to prostaglandin H2, which is then further metabolized to various prostaglandins. Vascular endothelial growth factor (VEGF has been shown to play important roles in inflammation and is upregulated by the prostaglandin E series through COX-2 in several cell types. Here, we have investigated the effects of VEGF on the COX isoform expressed in human umbilical vein endothelial cells (HUVEC. The signalling mechanism of the COX isoform expressed in endothelial cells activated with VEGF will be also investigated using the tyrosine kinase inhibitor, genistein, and protein kinase C inhibitor, staurosporine. The activity of COX2 was assessed by measuring the production of 6-keto-prostaglandin F1α in the presence of exogenous arachidonic acids (10 μM, 10 min by enzyme immunoassay. The expression of COX isoform protein was detected by immunoblot using specific antibodies. Untreated HUVEC contained no COX-2 protein. In HUVEC treated with VEGF (0.01-50 ng/ml, COX-2 protein, but not COX-1, and COX activity were increased in a dose-dependent manner. Interestingly, the increased COX-2 protein and activity in response to VEGF (10 ng/ml was inhibited by the tyrosine kinase inhibitor, genistein (0.05-5 μg/ml, but not by the protein kinase C inhibitor, staurosporine (0.1-10 ng/ml. Thus, the induction of COX-2 by VEGF in endothelial cells was mediated through protein tyrosine kinase, and the uses of specific COX-2 inhibitors in these conditions, in which VEGF was involved, might have a role.

  5. Delay Choice vs. Delay Maintenance: Different Measures of Delayed Gratification in Capuchin Monkeys (Cebus apella)

    Science.gov (United States)

    Addessi, Elsa; Paglieri, Fabio; Beran, Michael J.; Evans, Theodore A.; Macchitella, Luigi; De Petrillo, Francesca; Focaroli, Valentina

    2013-01-01

    Delaying gratification involves two components: (i) delay choice (selecting a delayed reward over an immediate one), and (ii) delay maintenance (sustaining the decision to delay gratification even if the immediate reward is available during the delay). In primates, two tasks most commonly have explored these components, the Intertemporal choice task and the Accumulation task. It is unclear whether these tasks provide equivalent measures of delay of gratification. Here, we compared the performance of the same capuchin monkeys, belonging to two study populations, between these tasks. We found only limited evidence of a significant correlation in performance. Consequently, in contrast to what is often assumed, our data provide only partial support to the hypothesis that these tasks provide equivalent measures of delay of gratification. PMID:23544770

  6. Position-optimization on retained entry and backfilling wall in gob-side entry retaining techniques

    Institute of Scientific and Technical Information of China (English)

    Xiaowei Feng; Nong Zhang

    2015-01-01

    This study investigates the stability problem of gob-side entry retaining (GER) and backfilling wall which located under the key block B. Based on the combined research of elastic–plastic mechanics, structure mechanics and modern theory of mining-induced pressure, the caving characteristic and roof structure over the GER were analyzed, and the vertical force and the torque on retained entry roof were also derived as the position for the retained entry varies. On the basis of the specific geology in Huainan mining area, the results indicate that a relatively more stable position for retained entry neighbors the hinge point of block A and B, and it also located at a scope ranging from this point to the one-third length of block B in horizontal direction. As to appropriate position for backfilling wall, this study recommends partial-road-in backfilling method for GER. Field trial conducted at panel face 12418 of Xieqiao Mine demonstrates that the recommended width for original entry is 3.6 m and the preferred width proportion between original retained entry and original entry is 75%or so whereas the avoidable one is 88%or so. These findings provide qualitative references to the mines which share similar geology as what Huainan mining area characterized.

  7. NS-398, Ibuprofen and COX-2 RNAi produce significantly different gene expression profiles in prostate cancer cells

    OpenAIRE

    John-Aryankalayil, Molykutty; Palayoor, Sanjeewani T.; Cerna, David; Falduto, Michael T.; Magnuson, Scott R.; Coleman, C. Norman

    2009-01-01

    Cyclooxygenase-2 (COX-2) plays a significant role in tumor development and progression. Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit potent anticancer effects in vitro and in vivo by COX-2 dependent and independent mechanisms. In this study, we used microarray analysis to identify the change of expression profile regulated by a COX-2 specific NSAID NS-398 (0.01 and 0.1mM), a non-specific NSAID ibuprofen (0.1 and 1.5mM) and RNA interference-mediated COX-2 inhibition (COX-2 RNAi) in PC...

  8. Delaying information search

    Directory of Open Access Journals (Sweden)

    Yaniv Shani

    2012-11-01

    Full Text Available In three studies, we examined factors that may temporarily attenuate information search. People are generally curious and dislike uncertainty, which typically encourages them to look for relevant information. Despite these strong forces that promote information search, people sometimes deliberately delay obtaining valuable information. We find they may do so when they are concerned that the information might interfere with future pleasurable activities. Interestingly, the decision to search or to postpone searching for information is influenced not only by the value and importance of the information itself but also by well-being maintenance goals related to possible detrimental effects that negative knowledge may have on unrelated future plans.

  9. Supply Network Planning for New Product Market Entry in the Pharmaceutical Industry

    DEFF Research Database (Denmark)

    Hansen, Klaus Reinholdt Nyhuus; Grunow, Martin

    2011-01-01

    uncertainty and the risk of a forced label change and includes solution robustness. While considering limited shelf life of the drug, the supply of packaging material and outsourcing, the objective of our model is to reduce supply chain cost including lost peak sales from delayed market entry.......It is well known, that the pharmaceutical industry is struggling with increasing cost and length of R&D projects. Earnings of a drug drop drastically after patent expiration. Thus, the industry spends much effort on reducing Time-to-Market. In the literature, no attention is given to supply chain...... planning before and during the market entry of the drug after the drug has been approved. Production of the active pharmaceutical ingredient [API] is characterized by long change-over times due to cleaning requirements. Production planning is long term, multiple batches of each drug are produced...

  10. COX-2-dependent PGE2 acts as a growth factor in mycosis fungoides (MF)

    DEFF Research Database (Denmark)

    Kopp, Katharina Luise Maria; Kauczok, C. S.; Lauenborg, Britt Thyssing

    2010-01-01

    production of PGE(2) in malignant T cells in vitro. These cells express prostaglandin receptors EP3 and EP4 and the receptor antagonist as well as small interfering RNA (siRNA) directed against COX-2, and specific COX-2 inhibitors strongly reduce their spontaneous proliferation. In conclusion, our data...... in prostaglandin synthesis. Aberrant COX-2 expression and prostaglandin E(2) (PGE(2)) production have been implicated in tumorigenesis. In this study we show that COX-2 is ectopically expressed in malignant T-cell lines from patients with cutaneous T-cell lymphoma (CTCL) as well as in situ in lymphocytic cells...... in 21 out of 22 patients suffering from mycosis fungoides (MF) in plaque or tumor stage. COX-2 is not expressed in lymphocytes of 11 patients with patch-stage MF, whereas sporadic COX-2 staining of stromal cells is observed in the majority of patients. COX-2 expression correlates with a constitutive...

  11. The synthesis of isotopic fluorine and iodine-labeled COX-II inhibitor and in vitro validation

    Energy Technology Data Exchange (ETDEWEB)

    An, Gwang Gil; Lee, Tae Sub; Lee, Kyo Chul; Moon, Byung Seok; Choi, Chang Woon; Chun, Kwon Soo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2005-07-01

    In these day, NASIDs (non-steroidal antiinflammatory drugs) such as aspirin, diclofenac and ibuprofen are the most common medications used to reduce pain and inflammation. However, they act by inhibiting both COX-I and COX-II which can cause serious gastrointestinal side effects such as ulcers, stomach perforations and bleeds. COX-I produces prostaglandins believed to be responsible for the protection of the stomach lining. However, COX-II produces prostaglandins believed to be responsible for pain and inflammation. Recently, the most widely studied selective COX-II inhibitor such as celecoxib and rofecoxib' one work by inhibiting the effect of COX-II on pain and inflammation without inhibiting COX-I which protects gastrointestinal lining.

  12. Experimental realization of Wheeler's delayed-choice gedanken experiment.

    Science.gov (United States)

    Jacques, Vincent; Wu, E; Grosshans, Frédéric; Treussart, François; Grangier, Philippe; Aspect, Alain; Roch, Jean-François

    2007-02-16

    Wave-particle duality is strikingly illustrated by Wheeler's delayed-choice gedanken experiment, where the configuration of a two-path interferometer is chosen after a single-photon pulse has entered it: Either the interferometer is closed (that is, the two paths are recombined) and the interference is observed, or the interferometer remains open and the path followed by the photon is measured. We report an almost ideal realization of that gedanken experiment with single photons allowing unambiguous which-way measurements. The choice between open and closed configurations, made by a quantum random number generator, is relativistically separated from the entry of the photon into the interferometer.

  13. 19 CFR 4.8 - Preliminary entry.

    Science.gov (United States)

    2010-04-01

    ... electronic equivalent of a complete Customs Form 1302 (Cargo Declaration), in the manner provided in § 4.7(b... 19 Customs Duties 1 2010-04-01 2010-04-01 false Preliminary entry. 4.8 Section 4.8 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE...

  14. 19 CFR 145.25 - Entry correct.

    Science.gov (United States)

    2010-04-01

    ... director believes the duty originally assessed was correct, he shall send the addressee a notice in writing... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry correct. 145.25 Section 145.25 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE...

  15. Continuous Aerodynamic Modelling of Entry Shapes

    NARCIS (Netherlands)

    Dirkx, D.; Mooij, E.

    2011-01-01

    During the conceptual design phase of a re-entry vehicle, the vehicle shape can be varied and its impact on performance evaluated. To this end, the continuous modeling of the aerodynamic characteristics as a function of the shape is useful in exploring the full design space. Local inclination method

  16. Radon entry into a simple test structure

    DEFF Research Database (Denmark)

    Andersen, C.E.; Søgaard-Hansen, J.; Majborn, B.

    1992-01-01

    A simple test structure for studies of radon entry into houses has been constructed at a field site at Riso National Laboratory. It consists of a 40 1, stainless-steel cylinder placed in a 0.52 m deep quadratic excavation with a side length of 2.4 m. The excavation is lined with an airtight...

  17. Flavivirus cell entry and membrane fusion

    NARCIS (Netherlands)

    Smit, Jolanda M.; Moesker, Bastiaan; Rodenhuis-Zybert, Izabela; Wilschut, Jan

    2011-01-01

    Flaviviruses, such as dengue virus and West Nile virus, are enveloped viruses that infect cells through receptor-mediated endocytosis and fusion from within acidic endosomes. The cell entry process of flaviviruses is mediated by the viral E glycoprotein. This short review will address recent advance

  18. Processes with multiple entries and exits

    NARCIS (Netherlands)

    Bergstra, J.A.; Stefanescu, G.

    1995-01-01

    This paper is an attempt to integrate the algebra of communicating processes (ACP) and the algebra of flownomials (AF). Basically, this means to combine axiomatized parallel and looping operators. To this end we introduce a model of process graphs with multiple entries and exits. In this model the u

  19. HIV-1 Entry Inhbitors: An Overview

    Science.gov (United States)

    Kuritzkes, Daniel R.

    2009-01-01

    Purpose of review This review provides an overview of HIV-1 entry inhibitors, with a focus on chemokine receptor antagonists. Recent findings Entry of HIV-1 into target cells is an ordered multi-step process involving attachment, co-receptor binding and fusion. Inhibitors of each step have been identified and shown to have antiviral activity in clinical trials. Phase 1-2 trials of monoclonal antibodies and small-molecule attachment inhibitors have demonstrated activity in HIV-1-infected subjects, but none has progressed to later phase clinical trials. The post-attachment inhibitor ibalizumab has shown activity in phase 1 and 2 trials; further studies are anticipated. The CCR5 antagonists maraviroc (now been approved for clinical use) and vicriviroc (in phase 3 trials) have shown significant benefit in controlled trials in treatment-experienced subjects; additional CCR5 antagonists are in various stages of clinical development. Targeting CXCR4 has proven to be more challenging. Although proof of concept has been demonstrated in phase 1-2 trials of two compounds, neither proved suitable for chronic administration. Little progress has been reported in developing longer acting or orally bioavailable fusion inhibitors. Summary ACCR5 antagonist and a fusion inhibitor are approved for use as HIV-1 entry inhibitors. Development of drugs targeting other steps in HIV-1 entry is ongoing. PMID:19339945

  20. Duopoly Dynamics with a Barrier to Entry

    NARCIS (Netherlands)

    Abbring, J.H.; Campbell, Jeffrey R.

    2007-01-01

    This paper considers the effects of raising the cost of entry for a potential competitor on infinite-horizon Markov-perfect duopoly dynamics with ongoing demand uncertainty. All entrants serving the model industry incur sunk costs, and exit avoids future fixed costs. We focus on the unique equilibri

  1. Entry modes of European firms in Vietnam

    Directory of Open Access Journals (Sweden)

    Daniel Simonet

    2012-09-01

    Full Text Available Purpose: The purpose of the paper is to explore the entry modes of EU firms setting up operations in Vietnam. Design/methodology/approach: we use a case study approach on Haymarket, Cadbury, Creative Education, Fairchild, Aventis and Artemisinin and Farming International using interviews from managerial professionals in Vietnam. Findings: Despite the fact that Vietnam has been opening up for more than 20 years, licensing is the preferred entry mode because of the risks involved in venturing with local firms; that preference signals a low level commitment and a high perception of risk and state interference. In line with Vietnam transition to state - rather than private market - capitalism, a foreign company opting for a joint-venture will do so with a state-owned rather than privately-owned company. The choice of a subsidiary can be explained by the lack of trust in partners and institutions, not by improvement in the socio-political environment. Limitations: In determining the entry mode strategy, the paper focuses on the Uppsala school’s “psychic distance” (e.g. cultural distance, lack of trust rather than on firm-specific advantages (Rugman, 1980; 2006. Key-words: international entry mode; emerging markets; subsidiary; joint-venture; India; Vietnam

  2. Internet portals as portfolios of entry options

    NARCIS (Netherlands)

    Perotti, E.C.; Rossetto, S.

    2000-01-01

    We investigate the valuation of platform investment, such as a software operating system or an Internet portal WebPage. Platform investment is the creation of an innovative distribution and production infrastructure, which increases access to customers; as a result it reduces entry costs in related

  3. Internet portals as portfolios of entry options

    NARCIS (Netherlands)

    Perotti, E.C.; Rossetto, S.

    2000-01-01

    We investigate the valuation of platform investment, such as a software operating system or an Internet portal WebPage. Platform investment is the creation of an innovative distribution and production infrastructure, which increases access to customers; as a result it reduces entry costs in related

  4. Flavivirus cell entry and membrane fusion

    NARCIS (Netherlands)

    Smit, Jolanda M.; Moesker, Bastiaan; Rodenhuis-Zybert, Izabela; Wilschut, Jan

    2011-01-01

    Flaviviruses, such as dengue virus and West Nile virus, are enveloped viruses that infect cells through receptor-mediated endocytosis and fusion from within acidic endosomes. The cell entry process of flaviviruses is mediated by the viral E glycoprotein. This short review will address recent advance

  5. Foreign Entry and Heterogeneous Growth of Firms

    DEFF Research Database (Denmark)

    Deng, Paul Duo; Jefferson, Gary H.

    distance from foreign firms. Domestic firms with smaller technological distance from their foreign counterparts tend to experience faster productivity growth, while firms with larger technological distance tend to lag further behind. We test this hypothesis using a unique firm-level data of Chinese...... manufacturing. Our empirical results confirm that foreign entry indeed generates strong heterogeneous growth patterns among domestic firms....

  6. Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish.

    Science.gov (United States)

    Teraoka, Hiroki; Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi; Peterson, Richard E; Stegeman, John J; Kitazawa, Takio; Hiraga, Takeo; Kubota, Akira

    2014-09-01

    The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish.

  7. CONVERGENT SYNTHESIS AND EVALUATION OF 18F-LABELED AZULENIC COX2 PROBES FOR CANCER IMAGING

    Directory of Open Access Journals (Sweden)

    Donald D. Nolting

    2013-01-01

    Full Text Available The overall objectives of this research are to (i develop azulene-based PET probes and (ii image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8+2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further

  8. Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2 inhibitors

    Directory of Open Access Journals (Sweden)

    Alshafie Galal A

    2006-01-01

    Full Text Available Abstract Background Epidemiologic and laboratory investigations suggest that nonsteroidal anti-inflammatory drugs (NSAIDs have chemopreventive effects against breast cancer due to their activity against cyclooxygenase-2 (COX-2, the rate-limiting enzyme of the prostaglandin cascade. Methods We conducted a case control study of breast cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A total of 323 incident breast cancer patients were ascertained from the James Cancer Hospital, Columbus, Ohio, during 2003–2004 and compared with 649 cancer free controls matched to the cases at a 2:1 ratio on age, race, and county of residence. Data on the past and current use of prescription and over the counter medications and breast cancer risk factors were ascertained using a standardized risk factor questionnaire. Effects of COX-2 inhibiting agents were quantified by calculating odds ratios (OR and 95% confidence intervals. Results Results showed significant risk reductions for selective COX-2 inhibitors as a group (OR = 0.29, 95% CI = 0.14–0.59, regular aspirin (OR = 0.49, 95% CI = 0.26–0.94, and ibuprofen or naproxen (0.36, 95% CI = 0.18–0.72. Acetaminophen, a compound with negligible COX-2 activity and low dose aspirin (81 mg produced no significant change in the risk of breast cancer. Conclusion Selective COX-2 inhibitors (celecoxib and rofecoxib were only recently approved for use in 1999, and rofecoxib (Vioxx was withdrawn from the marketplace in 2004. Nevertheless, even in the short window of exposure to these compounds, the selective COX-2 inhibitors produced a significant (71% reduction in the risk of breast cancer, underscoring their strong potential for breast cancer chemoprevention.

  9. Losartan reverses COX-2-dependent vascular dysfunction in offspring of hyperglycaemic rats.

    Science.gov (United States)

    de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; Duarte, Gloria Pinto; Xavier, Fabiano Elias

    2017-09-01

    This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT1R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day(-1)) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements. COX-2 expression was analyzed by Western blot; TxA2, PGE2 and PGF2α release was measured using commercial kits. O-DR showed increased blood pressure, impaired acetylcholine-induced vasodilation and increased noradrenaline-induced vasoconstriction than O-CR. All these parameters were normalized by losartan in O-DR. Pre-incubation of MRA with indomethacin (COX-1/2 inhibitor), NS-398 (COX-2 inhibitor) or tempol (superoxide dismutase mimetic) increased relaxation to acetylcholine and reduced contraction to noradrenaline only in O-DR. COX-2 expression, TxA2, PGE2 and PGF2α release were increased in O-DR. In losartan-treated O-DR, NS-398, indomethacin or tempol failed to produce any effect on acetylcholine or noradrenaline responses. Losartan treatment reduced COX-2 expression, TxA2, PGE2 and PGF2α release in O-DR. The present results reveal that chronic losartan administration in O-DR normalizes endothelial function in MRA by correcting the existing COX-2 overexpression and the imbalance between endothelium-derived relaxing and contracting factors. These findings not only support the beneficial effects of AT1 receptor antagonist in O-DR, but also suggest the implication of angiotensin II as a putative mediator of hyperglycemia-programmed vascular dysfunction in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Different role of COX-2 and angiogenesis in canine inflammatory and non-inflammatory mammary cancer.

    Science.gov (United States)

    Clemente, Mónica; Sánchez-Archidona, Ana Rodríguez; Sardón, David; Díez, Lucía; Martín-Ruiz, Asunción; Caceres, Sara; Sassi, Francesco; Dolores Pérez-Alenza, M; Illera, Juan C; Dunner, Susana; Peña, Laura

    2013-08-01

    Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most aggressive and fatal types of mammary cancer, and both have a very poor prognosis and low survival rate. Human IBC is characterised by exacerbated angiogenesis, lymphangiogenesis, and lymphangiotropism. Lymphangiotropism is also characteristic of IMC, but microvascular density (MVD) and lymphangiogenesis have not been previously studied in canine IMC. In this study immunohistochemical expression of several angiogenesis-related factors (cyclooxygenase [COX]-2, vascular endothelial growth factors A and D [VEGF-A, VEGF-D], and vascular endothelial growth factor receptor 3 [VEGFR-3]), MVD, lymphatic proliferation index (LPI), and Ki-67 tumour proliferation index (PI) were studied in 21 canine IMC samples, 20 canine high-grade malignant non-IMC mammary tumours (MMTs), and four normal mammary gland samples (NMGs). All mammary neoplasms were histologically categorised as grade III. COX-2 values were also analysed by RT-PCR in seven IMCs, six MMTs and four NMGs. The expressions of COX-2, VEGF-A, and VEGF-D were significantly higher in IMC, MVD and LPI tumours, but not PI. In MMTs, COX-2 immunoexpression was significantly associated with VEGF-A, while in IMCs COX-2 was associated with VEGF-D (lymphangiogenic factor), its receptor VEGFR-3, and LPI. These results suggested that lymphangiogenic pathway stimulation isa specific role of COX-2 in IMC angiogenesis, which justifies the use of COX-2-based targeted palliative therapies in dogs. The exacerbated angiogenesis and lymphangiogenesis and the increased expression of angiogenesis-related factors further support canine IMC as a natural model for the study of human IBC.

  11. Pseudotumoral delayed cerebral radionecrosis

    Energy Technology Data Exchange (ETDEWEB)

    Ciaudo-Lacroix, C.; Lapresle, J. (Centre Hospitalier de Bicetre, 94 - Le Kremlin-Bicetre (France))

    1985-01-01

    A 60 year-old woman with a scalp epithelioma underwent radiotherapy, the dose being 57 Gray. A first epileptic seizure occurred twenty months later. Neurological examination revealed signs of left hemisphere involvement. ..gamma..EG, angiography, CT scans, demonstrated a pseudotumoral avascular process. On account of the localisation, the patient being right-handed, no surgical procedure was performed. In spite of corticotherapy and anticonvulsive treatment, seizures recurred and neurological signs slowly progressed. The patient died, 22 months after the first seizure, of an associated disseminated carcinoma with cachexia. Neuropathological examination showed a massive lesion presenting all the features of delayed radionecrosis in the left hemisphere: situated mainly in the white matter; numerous vascular abnormalities; wide-spread demyelination; disappearance of oligoglial cells. The Authors recall the clinical and anatomical aspects of this condition for which the only successful treatment is surgical removal when location and size of the lesion permit. Finally, the mechanisms which have been proposed to explain this delayed cerebral radionecrosis are discussed.

  12. Epidemiology of delayed ejaculation.

    Science.gov (United States)

    Di Sante, Stefania; Mollaioli, Daniele; Gravina, Giovanni Luca; Ciocca, Giacomo; Limoncin, Erika; Carosa, Eleonora; Lenzi, Andrea; Jannini, Emmanuele A

    2016-08-01

    A large body of literature on diminished ejaculatory disorders has been generated without the use of a clear diagnostic definition. Many studies have not distinguished between the orgasm and ejaculation disorders leading to doubtful results. Delayed ejaculation (DE) is one of the diminished ejaculatory disorders, which range from varying delays in ejaculatory latency to a complete inability to ejaculate. The present review is aimed at providing a comprehensive overview of the current knowledge on the definition and epidemiology of diminished ejaculatory disorders. We focus on the acquired diseases, such as benign prostatic hyperplasia (BPH) and specific drug regimens that may cause an iatrogenic form of ejaculatory disorder. In addition, the impact of aging is discussed since the prevalence of DE appears to be moderately but positively related to age. Finally, we also focus on the importance of the hormonal milieu on male ejaculation. To date, evidence on the endocrine control of ejaculation is derived from small clinical trials, but the evidence suggests that hormones modulate the ejaculatory process by altering its overall latency.

  13. Stability and delay sensitivity of neutral fractional-delay systems

    Science.gov (United States)

    Xu, Qi; Shi, Min; Wang, Zaihua

    2016-08-01

    This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

  14. COX-2, MMP-7 expression in oral lichen planus and oral squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Tie-Jun Li; Jun Cui

    2013-01-01

    Objective:To observe cyclooxygenase (COX)-2 expression in normal oral mucosa (NOM), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) and explore its significance in the incidence of oral cancer. Methods: The immunohistochemical method and RT-PCR method were applied to detect the expression of COX-2 and MMP-7 in 10 cases with NOM, 33 cases of with OLP and 38 cases with OSCC. Results: The expression of COX-2 mRNA in OSCC tissues (68.4%, 26/38) was significantly higher than in the OLP (24.2%, 8/33) and NOM (0.0%, 0/10) (P<0.01). The expression of MMP-7 mRNA in OSCC tissues (65.8%, 25/38) was significantly higher than in the OLP (30.3%, 10/33) and NOM (0.0%, 0/10) (P<0.01). The expression of MMP-7 in OLP was significantly higher than in the NOM (P<0.05). There was no significant expression of COX-2 protein in NOM, and the positive rate was 42.4% (14/33) and 89.5% (34/38) in OLP and OSCC group, respectively. The COX-2 expression in cancer tissues was significantly higher than in NOM and OLP (P<0.05). The MMP-7 protein expression in cancer tissues (84.2%, 32/38) was significantly higher than in NOM (10.0%, 1/10) and in OLP (42.4%, 14/33), and the positive rate in OLP was significantly higher than in NOM (P<0.01). The COX-2 expression was associated with clinical stage (P<0.05), the MMP-7 expression was associated with clinical stage and lymph node metastasis (P<0.05). The expressions of COX-2 and MMP-7 mRNA were positively correlated with OSCC. Conclusions:The abnormal expressions of COX-2 and MMP-7 are closely related to the biological behavior of OSCC, the MMP-7 may be induced by COX-2, and further lead to the invasion and metastasis of OSCC.

  15. COX-2 Elevates Oncogenic miR-526b in Breast Cancer by EP4 Activation.

    Science.gov (United States)

    Majumder, Mousumi; Landman, Erin; Liu, Ling; Hess, David; Lala, Peeyush K

    2015-06-01

    MicroRNAs (miRs) are small regulatory molecules emerging as potential biomarkers in cancer. Previously, it was shown that COX-2 expression promotes breast cancer progression via multiple mechanisms, including induction of stem-like cells (SLC), owing to activation of the prostaglandin E2 receptor EP4 (PTGER4). COX-2 overexpression also upregulated microRNA-526b (miR-526b), in association with aggressive phenotype. Here, the functional roles of miR-526b in breast cancer and the mechanistic role of EP4 signaling in miR-526b upregulation were examined. A positive correlation was noted between miR-526b and COX-2 mRNA expression in COX-2 disparate breast cancer cell lines. Stable overexpression of miR-526b in poorly metastatic MCF7 and SKBR3 cell lines resulted in increased cellular migration, invasion, EMT phenotype and enhanced tumorsphere formation in vitro, and lung colony formation in vivo in immunodeficient mice. Conversely, knockdown of miR-526b in aggressive MCF7-COX-2 and SKBR3-COX-2 cells reduced oncogenic functions and reversed the EMT phenotype, in vitro. Furthermore, it was determined that miR-526b expression is dependent on EP4 receptor activity and downstream PI3K-AKT and cyclic AMP (cAMP) signaling pathways. PI3K-AKT inhibitors blocked EP4 agonist-mediated miR-526b upregulation and tumorsphere formation in MCF7 and SKBR3 cells. NF-κB inhibitor abrogates EP agonist-stimulated miRNA expression in MCF7 and T47D cells, indicating that the NF-κB pathway is also involved in miR-526b regulation. In addition, inhibition of COX-2, EP4, PI3K, and PKA in COX-2-overexpressing cells downregulated miR-526b and its functions in vitro. Finally, miR-526b expression was significantly higher in cancerous than in noncancerous breast tissues and associated with reduced patient survival. In conclusion, miR-526b promotes breast cancer progression, SLC-phenotype through EP4-mediated signaling, and correlates with breast cancer patient survival. This study presents novel

  16. Analysis of the cytochrome c oxidase subunit II (COX2) gene in giant panda, Ailuropoda melanoleuca.

    Science.gov (United States)

    Ling, S S; Zhu, Y; Lan, D; Li, D S; Pang, H Z; Wang, Y; Li, D Y; Wei, R P; Zhang, H M; Wang, C D; Hu, Y D

    2017-01-23

    The giant panda, Ailuropoda melanoleuca (Ursidae), has a unique bamboo-based diet; however, this low-energy intake has been sufficient to maintain the metabolic processes of this species since the fourth ice age. As mitochondria are the main sites for energy metabolism in animals, the protein-coding genes involved in mitochondrial respiratory chains, particularly cytochrome c oxidase subunit II (COX2), which is the rate-limiting enzyme in electron transfer, could play an important role in giant panda metabolism. Therefore, the present study aimed to isolate, sequence, and analyze the COX2 DNA from individuals kept at the Giant Panda Protection and Research Center, China, and compare these sequences with those of the other Ursidae family members. Multiple sequence alignment showed that the COX2 gene had three point mutations that defined three haplotypes, with 60% of the sequences corresponding to haplotype I. The neutrality tests revealed that the COX2 gene was conserved throughout evolution, and the maximum likelihood phylogenetic analysis, using homologous sequences from other Ursidae species, showed clustering of the COX2 sequences of giant pandas, suggesting that this gene evolved differently in them.

  17. Bond and CDS Pricing via the Stochastic Recovery Black-Cox Model

    Directory of Open Access Journals (Sweden)

    Albert Cohen

    2017-04-01

    Full Text Available Building on recent work incorporating recovery risk into structural models by Cohen & Costanzino (2015, we consider the Black-Cox model with an added recovery risk driver. The recovery risk driver arises naturally in the context of imperfect information implicit in the structural framework. This leads to a two-factor structural model we call the Stochastic Recovery Black-Cox model, whereby the asset risk driver At defines the default trigger and the recovery risk driver Rt defines the amount recovered in the event of default. We then price zero-coupon bonds and credit default swaps under the Stochastic Recovery Black-Cox model. Finally, we compare our results with the classic Black-Cox model, give explicit expressions for the recovery risk premium in the Stochastic Recovery Black-Cox model, and detail how the introduction of separate but correlated risk drivers leads to a decoupling of the default and recovery risk premiums in the credit spread. We conclude this work by computing the effect of adding coupons that are paid continuously until default, and price perpetual (consol bonds in our two-factor firm value model, extending calculations in the seminal paper by Leland (1994.

  18. Oms1 associates with cytochrome c oxidase assembly intermediates to stabilize newly synthesized Cox1.

    Science.gov (United States)

    Bareth, Bettina; Nikolov, Miroslav; Lorenzi, Isotta; Hildenbeutel, Markus; Mick, David U; Helbig, Christin; Urlaub, Henning; Ott, Martin; Rehling, Peter; Dennerlein, Sven

    2016-05-15

    The mitochondrial cytochrome c oxidase assembles in the inner membrane from subunits of dual genetic origin. The assembly process of the enzyme is initiated by membrane insertion of the mitochondria-encoded Cox1 subunit. During complex maturation, transient assembly intermediates, consisting of structural subunits and specialized chaperone-like assembly factors, are formed. In addition, cofactors such as heme and copper have to be inserted into the nascent complex. To regulate the assembly process, the availability of Cox1 is under control of a regulatory feedback cycle in which translation of COX1 mRNA is stalled when assembly intermediates of Cox1 accumulate through inactivation of the translational activator Mss51. Here we isolate a cytochrome c oxidase assembly intermediate in preparatory scale from coa1Δ mutant cells, using Mss51 as bait. We demonstrate that at this stage of assembly, the complex has not yet incorporated the heme a cofactors. Using quantitative mass spectrometry, we define the protein composition of the assembly intermediate and unexpectedly identify the putative methyltransferase Oms1 as a constituent. Our analyses show that Oms1 participates in cytochrome c oxidase assembly by stabilizing newly synthesized Cox1.

  19. The Characterization And Role of Zinc Binding in Yeast Cox4

    Energy Technology Data Exchange (ETDEWEB)

    Coyne, H.J., III; Ciofi-Baffoni, S.; Banci, L.; Bertini, I.; Zhang, L.; George, G.N.; Winge, D.R.; /Utah U. /Florence U. /Saskatchewan U.

    2007-07-09

    Yeast Cox4 is a zinc binding subunit of cytochrome c oxidase. Cox4 is the only cofactor-containing subunit that is not directly part of the catalytic core of the enzyme located in the mitochondrial inner membrane. The Zn(II) site is shown to be distinct from the bovine ortholog, as it results from the x-ray structure of the entire cytochrome c oxidase in having a single histidyl residue and three conserved cysteines residues in the coordination sphere. Substitutions at the Cys ligand positions result in non-functional Cox4 proteins that fail to lead to cytochrome oxidase assembly. Limited function exists in His-119 mutants when overexpressed. Zn(II) binding in Cox4 is, therefore, important for the stability of the complex. The solution structure of yeast Cox4 elucidated by multidimensional NMR reveals a C-terminal globular domain consisting of two {beta} sheets analogous to the bovine ortholog except the loop containing the coordinating His in the yeast protein and the fourth Cys in the bovine protein are in different positions in the two structures. The conformation of this loop is dictated by the different sequence position of the fourth coordinating zinc ligand. The Zn(II) ion is buried within the domain, consistent with its role in structural stability. Potential functions of this matrix-facing subunit are discussed.

  20. The flavouring phytochemical 2-pentanone reduces prostaglandin production and COX-2 expression in colon cancer cells.

    Science.gov (United States)

    Pettersson, Jenny; Karlsson, Pernilla Christina; Göransson, Ulf; Rafter, Joseph James; Bohlin, Lars

    2008-03-01

    Many phytochemicals found in the diet may prevent colon carcinogenesis by affecting biochemical processes in the colonic mucosa. Inflammation and subsequent elevation of the enzyme cyclooxygenase-2 (COX-2) are two such factors involved in the development of colon cancer, and inhibition of these processes could be important targets for chemoprevention. We have previously shown COX-2 inhibitory activity locally in the colon; e.g. in human fecal water from a group of vegetarians. In this study we focus on 2-pentanone, a frequently occurring compound in common foods such as banana and carrot. The aim was to study the inhibitory effects on prostaglandin production and COX-2 protein expression in tumour necrosis factor-alpha stimulated colon cancer cells (HT29) by radioimmunoassay and Western blotting. 2-Pentanone inhibited both prostaglandin production and COX-2 protein expression in human colon cancer cells. A concentration of 400 mumol/l 2-pentanone inhibited the prostaglandin production by 56.9+/-12.9% which is in the same range as the reference compound NS398 (59.8+/-7.6%). The two highest concentrations of 2-pentanone were further analyzed by Western blot, and 400 micromol/l and 200 micromol/l 2-pentanone resulted in a 53.3+/-9.6% and +/-27.1% reduction of the COX-2 protein levels respectively. Further studies on flavouring compounds, for example 2-pentanone, as colon cancer chemopreventives would be very valuable, and such results may contribute to future dietary recommendations.

  1. Leptin induces CREB-dependent aromatase activation through COX-2 expression in breast cancer cells.

    Science.gov (United States)

    Kim, Hyung Gyun; Jin, Sun Woo; Kim, Yong An; Khanal, Tilak; Lee, Gi Ho; Kim, Se Jong; Rhee, Sang Dal; Chung, Young Chul; Hwang, Young Jung; Jeong, Tae Cheon; Jeong, Hye Gwang

    2017-08-01

    Leptin plays a key role in the control of adipocyte formation, as well as in the associated regulation of energy intake and expenditure. The goal of this study was to determine if leptin-induced aromatase enhances estrogen production and induces tumor cell growth stimulation. To this end, breast cancer cells were incubated with leptin in the absence or presence of inhibitor pretreatment, and changes in aromatase and cyclooxygenase-2 (COX-2) expression were evaluated at the mRNA and protein levels. Transient transfection assays were performed to examine the aromatase and COX-2 gene promoter activities and immunoblot analysis was used to examine protein expression. Leptin induced aromatase expression, estradiol production, and promoter activity in breast cancer cells. Protein levels of phospho-STAT3, PKA, Akt, ERK, and JNK were increased by leptin. Leptin also significantly increased cAMP levels, cAMP response element (CRE) activation, and CREB phosphorylation. In addition, leptin induced COX-2 expression, promoter activity, and increased the production of prostaglandin E2. Finally, a COX-2 inhibitor and aromatase inhibitor suppressed leptin-induced cell proliferation in MCF-7 breast cancer cells. Together, our data show that leptin increased aromatase expression in breast cancer cells, which was correlated with COX-2 upregulation, mediated through CRE activation and cooperation among multiple signaling pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Associations between COX-2 polymorphisms, blood cholesterol and risk of acute coronary syndrome

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Segel, Stine; Dethlefsen, Claus

    2010-01-01

    significant interactions between genotypes and alcohol intake, smoking and NSAID use in relation to risk of ACS. Among males, there was interaction between COX-2 T8473C and alcohol in relation to total cholesterol, non-HDL cholesterol and LDL levels (p for interaction: 0.003, 0.007 and 0.01, respectively......Background: The use of specific COX-2 inhibitors in cancer prevention has been associated with higher risk of acute coronary syndrome (ACS) and myocardial infarction. The aim of this study was to investigate if the polymorphisms COX2 T8473C (rs5275), and COX2 A-1195G (rs689466), which modify...... the enzyme levels of COX-2, were associated with risk of ACS and if alcohol intake, smoking, and use of NSAID would modify the associations. We also wanted to investigate associations with blood lipid levels. Methods: A case–cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested...

  3. Study the role of COX-2 and its Selective Inhibitor NS-398 in the Laser Wound Healing%COX-2及其选择性抑制剂NS-398对激光术后创面修复的实验研究

    Institute of Scientific and Technical Information of China (English)

    周莹; 曾维惠; 覃静净; 徐磊; 耿松梅; 乔莉; 张磐谏

    2011-01-01

    目的:探讨COX-2及其选择性抑制剂NS-398对激光术后大鼠创面修复的影响.方法:点阵CO2激光照射形成大鼠创伤模型,分为正常、术后第1、3、5、7、10、14天共7个时相点,基质对照组、NS-398药物组术后分别外用75%酒精、NS-398,肉眼观察创面结痂及愈合时间,HE染色计数中性粒细胞、成纤维样细胞,免疫组化方法检测COX-2、PGE2及TGF-β1的表达情况.结果:NS-398药物组结痂时间明显短于对照组,各组间愈合时间无统计学差异;术后第1、3天,NS-398药物组中性粒细胞的数量及PGE2、TGF-β1表达量均明显低于对照组;术后第5天,NS-398药物组成纤维样细胞的数量明显高于对照组;激光术后(尤炎症期)大鼠创面明显表达COX-2.结论:COX-2对大鼠创面修复的炎症期及细胞增殖期具有重要作用;NS-398能降低激光术后创面炎症反应及瘢痕形成率,同时不会延缓创面愈合.%Objective To investigate the role of COX-2 and its selective inhibitor NS-398 during rat wound healing caused by factional laser. Methods Wound samples were removed from day 0 (normal)、 1、3、5、7、10、14 after injury, 75% ethanol、NS-398 were administrated respectively between matrix-control and NS-398-drug group.comparing the crust-formation and healing time, numbers of neutrophils and fibroblasts with HE staining, and the expression of COX-2 ,PGE2,TGF-P1 with IHC. Results The crust-formation time of NS-398-drug group was shorter than the control groups, but the healing time had no satistical difference. The numbers of neutrophils,expression of PGE2 and TGF-01 of NS-398-drug group were less than contro groups on day 1、3;and the fibroblasts were more than control groups on day 5.Wound expressed COX-2 obviously (special during inflammatory phase) after injury. Conclusion COX-2 plays a pivotal role during the inflammotary and cell proliferate phase of wound healing; selective COX-2 inhibitors NS-398 could reduce

  4. Synchronizing time delay systems using variable delay in coupling

    Energy Technology Data Exchange (ETDEWEB)

    Ambika, G., E-mail: g.ambika@iiserpune.ac.in [Indian Institute of Science Education and Research, Pune 411 021 (India); Amritkar, R.E., E-mail: amritkar@prl.res.in [Physical Research Laboratory, Ahmedabad 380 009 (India)

    2011-11-15

    Highlights: > Delay and anticipation in coupling function varies with system dynamics. > Delay or anticipation of the synchronized state is independent of system delay. > Stability analysis developed is quite general. > We demonstrate enhanced security in communication. > Generalized synchronization possible over a wide range of parameter mismatch. - Abstract: We present a mechanism for synchronizing time delay systems using one way coupling with a variable delay in coupling that is reset at finite intervals. We present the analysis of the error dynamics that helps to isolate regions of stability of the synchronized state in the parameter space of interest for single and multiple delays. We supplement this by numerical simulations in a standard time delay system like Mackey Glass system. This method has the advantage that it can be adjusted to be delay or anticipatory in synchronization with a time which is independent of the system delay. We demonstrate the use of this method in communication using the bi channel scheme. We show that since the synchronizing channel carries information from transmitter only at intervals of reset time, it is not susceptible to an easy reconstruction.

  5. Small delay approximation of stochastic delay differential equations

    Science.gov (United States)

    Guillouzic, Steve; L'heureux, Ivan; Longtin, André

    1999-04-01

    Delay differential equations evolve in an infinite-dimensional phase space. In this paper, we consider the effect of external fluctuations (noise) on delay differential equations involving one variable, thus leading to univariate stochastic delay differential equations (SDDE's). For small delays, a univariate nondelayed stochastic differential equation approximating such a SDDE is presented. Another approximation, complementary to the first, is also obtained using an average of the SDDE's drift term over the delayed dynamical variable, which defines a conditional average drift. This second approximation is characterized by the fact that the diffusion term is identical to that of the original SDDE. For small delays, our approach yields a steady-state probability density and a conditional average drift which are in close agreement with numerical simulations of the original SDDE. We illustrate this scheme with the delayed linear Langevin equation and a stochastic version of the delayed logistic equation. The technique can be used with any type of noise, and is easily generalized to multiple delays.

  6. A model of HIV-1 infection with two time delays: mathematical analysis and comparison with patient data

    OpenAIRE

    Pawelek, Kasia A.; Liu, Shengqiang; Pahlevani, Faranak; Rong, Libin

    2011-01-01

    Mathematical models have made considerable contributions to our understanding of HIV dynamics. Introducing time delays to HIV models usually brings challenges to both mathematical analysis of the models and comparison of model predictions with patient data. In this paper, we incorporate two delays, one the time needed for infected cells to produce virions after viral entry and the other the time needed for the adaptive immune response to emerge to control viral replication, into an HIV-1 mode...

  7. A comparison between the use of Cox regression and the use of partial least squares-Cox regression to predict the survival of kidney-transplant patients

    Science.gov (United States)

    Solimun

    2017-05-01

    The aim of this research is to model survival data from kidney-transplant patients using the partial least squares (PLS)-Cox regression, which can both meet and not meet the no-multicollinearity assumption. The secondary data were obtained from research entitled "Factors affecting the survival of kidney-transplant patients". The research subjects comprised 250 patients. The predictor variables consisted of: age (X1), sex (X2); two categories, prior hemodialysis duration (X3), diabetes (X4); two categories, prior transplantation number (X5), number of blood transfusions (X6), discrepancy score (X7), use of antilymphocyte globulin(ALG) (X8); two categories, while the response variable was patient survival time (in months). Partial least squares regression is a model that connects the predictor variables X and the response variable y and it initially aims to determine the relationship between them. Results of the above analyses suggest that the survival of kidney transplant recipients ranged from 0 to 55 months, with 62% of the patients surviving until they received treatment that lasted for 55 months. The PLS-Cox regression analysis results revealed that patients' age and the use of ALG significantly affected the survival time of patients. The factor of patients' age (X1) in the PLS-Cox regression model merely affected the failure probability by 1.201. This indicates that the probability of dying for elderly patients with a kidney transplant is 1.152 times higher than that for younger patients.

  8. Analytic Guidance for the First Entry in a Skip Atmospheric Entry

    Science.gov (United States)

    Garcia-Llama, Eduardo

    2007-01-01

    This paper presents an analytic method to generate a reference drag trajectory for the first entry portion of a skip atmospheric entry. The drag reference, expressed as a polynomial function of the velocity, will meet the conditions necessary to fit the requirements of the complete entry phase. The generic method proposed to generate the drag reference profile is further simplified by thinking of the drag and the velocity as density and cumulative distribution functions respectively. With this notion it will be shown that the reference drag profile can be obtained by solving a linear algebraic system of equations. The resulting drag profile is flown using the feedback linearization method of differential geometric control as guidance law with the error dynamics of a second order homogeneous equation in the form of a damped oscillator. This approach was first proposed as a revisited version of the Space Shuttle Orbiter entry guidance. However, this paper will show that it can be used to fly the first entry in a skip entry trajectory. In doing so, the gains in the error dynamics will be changed at a certain point along the trajectory to improve the tracking performance.

  9. Entry Location and Entry Timing (ELET Decision Model for International Construction Firms

    Directory of Open Access Journals (Sweden)

    Che Maznah Mat Isa

    2014-09-01

    Full Text Available This paper proposes a model for entry location (EL and entry timing (ET decisions to guide construction firms in accessing targeted international markets.  Neglecting to properly choose the right combination of the entry location and entry timing (ELET decisions can lead to poor performance of the firms’ international ventures.  The sampling frame was from the Malaysian construction firms that have undertaken and completed projects abroad.  Survey questionnaires sent to 115 firms registered with Construction Industry Development Board (CIDB Malaysia, operating in more than 50 countries, achieved a 39.1 per cent response rate. Based on a comprehensive statistical analysis of survey data it was found that the mutually inclusive significant factors that influenced the firms’ ELET decisions were: the firm’s ability to assess market signals and opportunities, international experience, financial capacity, competencies and capabilities (project management, specialist expertise and technology, resources (level of knowledge based on research and development, experience in similar works, financial support from the home country banks, technical complexities of projects and availability of funds for projects.  Hence, the present research builds on and extends the literature on the ELET decisions in a more integrated way. Keywords: Entry location, entry timing, resource-based view, international markets, Malaysian construction firms.

  10. Delay tolerant networks

    CERN Document Server

    Gao, Longxiang; Luan, Tom H

    2015-01-01

    This brief presents emerging and promising communication methods for network reliability via delay tolerant networks (DTNs). Different from traditional networks, DTNs possess unique features, such as long latency and unstable network topology. As a result, DTNs can be widely applied to critical applications, such as space communications, disaster rescue, and battlefield communications. The brief provides a complete investigation of DTNs and their current applications, from an overview to the latest development in the area. The core issue of data forward in DTNs is tackled, including the importance of social characteristics, which is an essential feature if the mobile devices are used for human communication. Security and privacy issues in DTNs are discussed, and future work is also discussed.

  11. Reducing Marine Container Terminal Gate Congestion with Vessel-Dependent Time Windows For Truck Entries

    DEFF Research Database (Denmark)

    Chen, Gang; Yang, Zhongzhen; Jiang, Liping

    In recent years, marine container terminal gate congestion has become a serious issue, because it not only limits the efficiency of the logistics system but also generates serious air pollution. The direct reason has been recognized to be the unmanaged container truck arrivals. One of the possible...... solutions is that the terminal operator provides vessel-dependent time windows for the truck entries, which has already been used in many Chinese seaports. Previously, the authors proposed the idea of time window optimization and analyzed its economic feasibility in the context of the export direction gate...... problems are also discussed, such as vessel delays and yard capacity....

  12. Adaptive Deployable Entry and Placement Technology (ADEPT) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The ADEPT Project is developing a mechanically deployable low-ballistic coefficient aeroshell entry system to perform entry descent landing (EDL) functions for...

  13. Design and Simulation Tools for Planetary Atmospheric Entry Vehicles Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Atmospheric entry is one of the most critical phases of flight during planetary exploration missions. During the design of an entry vehicle, experimental and...

  14. Increased COX2 in the trigeminal nucleus caudalis is involved in orofacial pain induced by experimental tooth movement.

    Science.gov (United States)

    Gao, Yuan; Duan, Yin-Zhong

    2010-03-01

    Pain is among the major problems during orthodontic treatment. Recent studies have shown that central Cyclooxygenase2 (COX2) pathway was involved in several pain models. The present study investigated whether inducible COX2 within the trigeminal nucleus caudalis (Vc) contributed to experimental tooth movement pain in freely moving rats. Elastic rubber bands were inserted between the first and second maxillary molars bilaterally to establish tooth movement model. The directed mouth wiping behavior was used to evaluate the pain during tooth movement. COX2 distribution in Vc was studied by immunohistochemistry and the changes of COX2 expression were detected by Western blot at different time point after rubber band insertion. Our results showed that tooth movement significantly increased COX2 expression in Vc and the time spent on mouth wiping, reaching a maximum at 1 day and then decreasing gradually. Furthermore, the rhythm change of COX2 expression in Vc and the mouth wiping behavior were much correlative with each other. All of the COX2-immunoreactive structures in Vc exhibited NeuN-immunopositive staining and most of these COX2-immunoreactive neurons were Fos-immunopositive. Importantly, the mouth wiping behavior could be attenuated by intracisternal injection of NS-398 (a selective COX2 inhibitor) but not by periodontal administration of NS-398. All these results suggested that increased COX2 in Vc was involved in tooth movement pain and thus may be a central target for orthodontic pain treatment.

  15. In vitro import and assembly of the nucleus-encoded mitochondrial subunit III of cytochrome c oxidase (Cox3).

    Science.gov (United States)

    Vázquez-Acevedo, Miriam; Rubalcava-Gracia, Diana; González-Halphen, Diego

    2014-11-01

    The cox3 gene, encoding subunit III of cytochrome c oxidase (Cox3) is in mitochondrial genomes except in chlorophycean algae, where it is localized in the nucleus. Therefore, algae like Chlamydomonas reinhardtii, Polytomella sp. and Volvox carteri, synthesize the Cox3 polypeptide in the cytosol, import it into mitochondria, and integrate it into the cytochrome c oxidase complex. In this work, we followed the in vitro internalization of the Cox3 precursor by isolated, import-competent mitochondria of Polytomella sp. In this colorless alga, the precursor Cox3 protein is synthesized with a long, cleavable, N-terminal mitochondrial targeting sequence (MTS) of 98 residues. In an import time course, a transient Cox3 intermediate was identified, suggesting that the long MTS is processed more than once. The first processing step is sensitive to the metalo-protease inhibitor 1,10-ortophenantroline, suggesting that it is probably carried out by the matrix-located Mitochondrial Processing Protease. Cox3 is readily imported through an energy-dependent import pathway and integrated into the inner mitochondrial membrane, becoming resistant to carbonate extraction. Furthermore, the imported Cox3 protein was assembled into cytochrome c oxidase, as judged by the presence of a labeled band co-migrating with complex IV in Blue Native Electrophoresis. A model for the biogenesis of Cox3 in chlorophycean algae is proposed. This is the first time that the in vitro mitochondrial import of a cytosol-synthesized Cox3 subunit is described.

  16. Characterization of the Cytochrome C Oxidase Assembly Factor Cox19 of 'Saccharomyces Cerevisiae'

    Energy Technology Data Exchange (ETDEWEB)

    Rigby, K.; Zhang, L.; Cobine, P.A.; George, G.N.; Winge, D.R.; /Utah U. /Saskatchewan U.

    2007-07-12

    Cox19 is an important accessory protein in the assembly of cytochrome c oxidase in yeast. The protein is functional when tethered to the mitochondrial inner membrane, suggesting its functional role within the intermembrane space. Cox19 resembles Cox17 in having a twin CX{sub 9}C sequence motif that adopts a helical hairpin in Cox17. The function of Cox17 appears to be a Cu(I) donor protein in the assembly of the copper centers in cytochrome c oxidase. Cox19 also resembles Cox17 in its ability to coordinate Cu(I). Recombinant Cox19 binds 1 mol eq of Cu(I) per monomer and exists as a dimeric protein. Cox19 isolated from the mitochondrial intermembrane space contains variable quantities of copper, suggesting that Cu(I) binding may be a transient property. Cysteinyl residues important for Cu(I) binding are also shown to be important for the in vivo function of Cox19. Thus, a correlation exists in the ability to bind Cu(I) and in vivo function.

  17. The potential role of COX-2 in cancer stem cell-mediated canine mammary tumor initiation: an immunohistochemical study.

    Science.gov (United States)

    Huang, Jian; Zhang, Di; Xie, Fuqiang; Lin, Degui

    2015-01-01

    Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding transcription factor (Oct)-3/4, and epidermal growth factor receptor (EGFR) expression were examined in malignant mammary tumor (MMT) samples and analyzed in terms of clinicopathological characteristics. COX-2 and Oct-3/4 expression was higher in MMTs compared to other histological samples with heterogeneous patterns. In MMTs, COX-2 expression correlated with tumor malignancy features. Significant associations between COX-2, CD44, and EGFR were observed in low-differentiated MMTs. Comparative analysis showed that the levels of COX-2, CD44, and Oct-3/4 expression varied significantly among TSs of three histological grades. Enhanced COX-2 staining was consistently observed in TSs. Similar levels of staining intensity were found for CD44 and Oct-3/4, but EGFR expression was weak. Our findings indicate the potential role of COX-2 in CSC-mediated tumor initiation, and suggest that COX-2 inhibition may help treat canine mammary tumors by targeting CSCs.

  18. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    Energy Technology Data Exchange (ETDEWEB)

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Cook-Moreau, Jeanne [Université de Limoges, FR 3503 GEIST, UMR CNRS 7276 “Contrôle de la réponse immune B et lymphoproliférations”, Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Beneytout, Jean-Louis [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France)

    2013-04-15

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression.

  19. Effect of nimesulide-a preferential COX-2 inhibitor on arterial blood pressure, compared to ketoprofen.

    Science.gov (United States)

    Saran, Tomasz; Sodolski, Wojciech; Sodolska, Katarzyna; Danilkiewicz, Wit Cezary; Schabowski, Janusz

    2004-01-01

    Clinical and experimental studies have shown that renal and cardiovascular effects of most selective COX-2 inhibitors (rofecoxib, celecoxib) are similar to other traditional NSAIDs (dual COX inhibitors). In these study the effect of nimesulide--preferential COX-2 inhibitor, administration on 24-hour blood pressure profile was investigated in 40 adult individuals on antihypertensive therapy with pain states caused by osteoartritis. Nimesulide was administered orally, twice a day at the conventional dose of 0.1 g for five days. In the next (or previous) 5 days the same patients were administered with ketoprofen at the dose of 0.05 g three times a day. On the last day of the NSAID administration period, 24-hour blood pressure monitoring was performed. Our results indicate no difference between nimesulide and ketoprofen effects on mean blood pressure values during antihypertensive therapy.

  20. The respiratory chain supercomplex organization is independent of COX7a2l isoforms.

    Science.gov (United States)

    Mourier, Arnaud; Matic, Stanka; Ruzzenente, Benedetta; Larsson, Nils-Göran; Milenkovic, Dusanka

    2014-12-01

    The organization of individual respiratory chain complexes into supercomplexes or respirasomes has attracted great interest because of the implications for cellular energy conversion. Recently, it was reported that commonly used mouse strains harbor a short COX7a2l (SCAFI) gene isoform that supposedly precludes the formation of complex IV-containing supercomplexes. This claim potentially has serious implications for numerous mouse studies addressing important topics in metabolism, including adaptation to space flights. Using several complementary experimental approaches, we show that mice with the short COX7a2l isoform have normal biogenesis and steady-state levels of complex IV-containing supercomplexes and consequently have normal respiratory chain function. Furthermore, we use a mouse knockout of Lrpprc and show that loss of complex IV compromises respirasome formation. We conclude that the presence of the short COX7a2l isoform in the commonly used C57BL/6 mouse strains does not prevent their use in metabolism research.

  1. Electrochemical performance of compounds Ho6Fe23-xCox (x=0,1,3)

    Institute of Scientific and Technical Information of China (English)

    HE Wei; ZHAO Yunhong; HUANG Jinli; ZHANG Yongzhi; ZENG Lingmin

    2011-01-01

    Alloys with composition of Ho6Fe23-xCox(x=0, 1, 3) were prepared and e xamined by X-ray diffraction technique and automatic battery testing instrument. The compounds Ho6Fe23-xCox(x=0, 1, 3) crystallized in cubic Th6Mn23-type structure with space group Fm(-3)m (No. 225). The electrochemical properties of these alloys such as discharge capacity, cycling performance and high rate dischargeability were investigated by battery testing instruments in alkaline electrolyte. Substitution of small amounts of Co for Fe in Ho6Fe23-xCox improved the activation, discharge capacity and the high rate dischargeability. The alloy with x=3 (Ho6Fe20Co3) had better discharge capacity, HRD and plateau pressure at discharge current density of 150 mA/g.

  2. Dietary glycerol for quail: association between productive performance and COX III mRNA expression.

    Science.gov (United States)

    Silva, S C C; Gasparino, E; Batista, E; Tanamati, F; Vesco, A P D; Lala, B; de Oliveira, D P

    2016-05-25

    This study was carry out to evaluate mRNA expression of mitochondrial cytochrome c oxidase III in the Pectoralis superficialis muscle of 28-day-old quails fed diets containing 0, 8, and 12% glycerol. Total RNA was extracted (N = 10) and cDNA was amplified using specifics primers for qRT-PCR. Feed efficiency and feed intake were evaluated. COX III mRNA expression in breast muscle was higher in the group fed with 12% glycerol (0.863 AU); no differences were observed in the expression of this gene between the muscle of animals fed diets without glycerol (0.357 AU) and 8% glycerol (0.415 AU). Quails that showed greater COX III mRNA expression also showed the lowest feed efficiency. These results show that there is a difference in COX III mRNA expression in breast muscle of 28-day-old quail fed diets different concentrations of glycerol.

  3. On the Gravitomagnetic Time Delay

    OpenAIRE

    Ciufolini, I.; Kopeikin, S.; Mashhoon, B.; Ricci, F

    2002-01-01

    We study the gravitational time delay in ray propagation due to rotating masses in the linear approximation of general relativity. Simple expressions are given for the gravitomagnetic time delay that occurs when rays of radiation cross a slowly rotating shell and propagate in the field of a distant rotating source. Moreover, we calculate the local gravitational time delay in the Goedel universe. The observational consequences of these results in the case of weak gravitational lensing are disc...

  4. Demographic determinants of delayed divorce.

    Science.gov (United States)

    Chan, L Y; Heaton, T B

    1989-01-01

    This study identifies factors that predict delayed divorce in the US. The findings show that factors which influence marital stability in general also correlate with delayed divorce in the same direction. Wife's age at marriage, age of the youngest child, wife's religion, region of residence, and metropolitan residence have substantial effects of delayed divorce, but the effects of race, parental divorce, premarital pregnancy, and socioeconomic status are small.

  5. Location Estimation using Delayed Measurements

    DEFF Research Database (Denmark)

    Bak, Martin; Larsen, Thomas Dall; Nørgård, Peter Magnus

    1998-01-01

    When combining data from various sensors it is vital to acknowledge possible measurement delays. Furthermore, the sensor fusion algorithm, often a Kalman filter, should be modified in order to handle the delay. The paper examines different possibilities for handling delays and applies a new techn...... technique to a sensor fusion system for estimating the location of an autonomous guided vehicle. The system fuses encoder and vision measurements in an extended Kalman filter. Results from experiments in a real environment are reported...

  6. Targeting CXCR4 in HIV Cell-Entry Inhibition

    DEFF Research Database (Denmark)

    Steen, Anne; Schwartz, T W; Rosenkilde, M M

    2010-01-01

    CXCR4 and CCR5 constitute the two major coreceptors for HIV-1 entry into host cells. In the course of an HIV-infection, a coreceptor switch takes place in approximately half of the patients - from R5 HIV-1 (CCR5 utilizing) strains to X4 HIV-1 (CXCR4 utilizing) strains. Treatment of HIV......-infected individuals with CXCR4 antagonists delays the onset of AIDS by preventing the CCR5 to CXCR4 coreceptor switch. In addition to the endogenous CXCR4 and CCR5 ligands, other chemokines, for example the human herpesvirus 8 encoded CC-chemokine, vCCL2, and modifications hereof, have proven efficient HIV-1 cell...... no oral bioavailability. The hunt for orally active small-molecule CXCR4 antagonists led to the development of monocyclam-based compounds, and recently to the non-cyclam antagonist AMD070, which is orally active and currently in Phase II clinical trial as anti-HIV treatment. Current review provides...

  7. Timosaponin AIII inhibits melanoma cell migration by suppressing COX-2 and in vivo tumor metastasis.

    Science.gov (United States)

    Kim, Ki Mo; Im, A-Rang; Kim, Seung Hyung; Hyun, Jin Won; Chae, Sungwook

    2016-02-01

    Melanoma is the leading cause of death from skin disease, due in large part to its propensity to metastasize. We examined the effects of timosaponin AIII, a compound isolated from Anemarrhena asphodeloides Bunge, on melanoma cancer cell migration and the molecular mechanisms underlying these effects using B16-F10 and WM-115 melanoma cells lines. Overexpression of COX-2, its metabolite prostaglandin E2 (PGE2), and PGE2 receptors (EP2 and EP4) promoted cell migration in vitro. Exposure to timosaponin AIII resulted in concentration-dependent inhibition of cell migration, which was associated with reduced levels of COX-2, PGE2, and PGE2 receptors. Transient transfection of COX-2 siRNA also inhibited cell migration. Exposure to 12-O-tetradecanoylphorbal-13-acetate enhanced cell migration, whereas timosaponin AIII inhibited 12-O-tetradecanoylphorbal-13-acetate-induced cell migration and reduced basal levels of EP2 and EP4. Moreover, timosaponin AIII inhibited activation of nuclear factor-kappa B (NF-κB), an upstream regulator of COX-2 in B16-F10 cells. Consistent with our in vitro findings, in vivo studies showed that timosaponin AIII treatment significantly reduced the total number of metastatic nodules in the mouse lung and improved histological alterations in B16-F10-injected C57BL/6 mice. In addition, C57BL/6 mice treated with timosaponin AIII showed reduced expression of COX-2 and NF-κB in the lung. Together, these results indicate that timosaponin AIII has the capacity to inhibit melanoma cell migration, an essential step in the process of metastasis, by inhibiting expression of COX-2, NF-κB, PGE2, and PGE2 receptors.

  8. RELATIONSHIP AMONG COX-2 PROTEIN EXPRESSION, PGs LEVELS AND BIOLOGIC BEHAVIOR IN OVARIAN CARCINOMA TISSUES

    Institute of Scientific and Technical Information of China (English)

    王敏; 王欣彦; 唐丽霞; 高岩

    2004-01-01

    Objective: To study the relationship among cyclooxygenase-2 (COX-2) protein expression, prostaglandins levels and biologic behavior in ovarian carcinoma tissues. Methods: The expression of COX-2 protein, levels of prostaglandin (PG)E2, 6-keto-PGF1( and thromboxane (TX)B2 in 54 biopsy specimens from patients with ovarian serous tumors which included three groups: 33 samples of ovarian serous carcinoma; 10 samples of borderline ovarian serous tumors and 11 samples of benign ovarian serous tumors and 10 samples of normal ovarian tissues were detected by Western blot analysis and radioimmunoassay to investigate their clinical significance. Results: The expression of COX-2 protein (82%, 27/33) and its relative content (20.08±3.53) in ovarian serous carcinoma tissues were statistically higher than those in benign ovarian serous tumor tissues and normal ovary tissues i.e., 0 and (15.04(0.12), 0 and (15.33(0.60) (P0.05). The levels of PGE2, 6-keto-PGF1( and TXB2 showed no significant differences in ovarian carcinoma tissues with different clinical stages (I to II and III to IV), different histological grades, with or without ascites and lymph metastasis. COX-2 expression was correlated with the levels of PGE2, 6-KETO-PGF1( and TXB2 (P<0.01). Conclusion: Our data suggest that COX-2 overexpression leads to increased PGE2, 6-KETA-PGF1( and TXB2 biosynthesis, which may be mechanisms underlying the contribution of COX-2 to the development of ovarian serous carcinoma. BGF2, 6-keto-PGF1( and TXB2 may be helpful parameters of diagnosis and differentiate diagnosis in ovarian serous carcinoma.

  9. The first characterization of free radicals formed from cellular COX-catalyzed peroxidation.

    Science.gov (United States)

    Gu, Yan; Xu, Yi; Law, Benedict; Qian, Steven Y

    2013-04-01

    Through free radical-mediated peroxidation, cyclooxygenase (COX) can metabolize dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) to form well-known bioactive metabolites, namely, the 1-series of prostaglandins (PGs1) and the 2-series of prostaglandins (PGs2), respectively. Unlike PGs2, which are generally viewed as proinflammatory and procarcinogenic PGs, PGs1 may possess anti-inflammatory and anti-cancer activity. Previous studies using ovine COX along with spin trapping and the LC/ESR/MS technique have shown that certain exclusive free radicals are generated from different free radical reactions in DGLA and AA peroxidation. However, it has been unclear whether the differences were associated with the contrasting bioactivity of DGLA vs AA. The aim of this study was to refine the LC/MS and spin trapping technique to make it possible for the association between free radicals and cancer cell growth to be directly tested. Using a colon cancer cell line, HCA-7 colony 29, and LC/MS along with a solid-phase extraction, we were able to characterize the reduced forms of radical adducts (hydroxylamines) as the free radicals generated from cellular COX-catalyzed peroxidation. For the first time, free radicals formed in the COX-catalyzed peroxidation of AA vs DGLA and their association with cancer cell growth were assessed (cell proliferation via MTS and cell cycle distribution via propidium iodide staining) in the same experimental setting. The exclusive free radicals formed from the COX-catalyzed peroxidation of AA and DGLA were shown to be correlated with the cell growth response. Our results indicate that free radicals generated from the distinct radical reactions in COX-catalyzed peroxidation may represent the novel metabolites of AA and DGLA that correspond to their contrasting bioactivity.

  10. Concurrent Delay in Construction Disputes

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    period of delay can potentially be attributed to several events falling within both parties' spheres of responsibility, commonly termed concurrent delay, is rarely regulated in construction contracts in spite of its common occurrence. This book analyses both the theoretical foundations and the practical......Delay is one of the issues most frequently encountered in today’s construction industry; it causes significant economic damage to all parties involved. Construction contracts, standard and bespoke, almost invariably consider delay from a perspective of single liability. If the event causing...

  11. Time Delay of CGM Sensors

    Science.gov (United States)

    Schmelzeisen-Redeker, Günther; Schoemaker, Michael; Kirchsteiger, Harald; Freckmann, Guido; Heinemann, Lutz; del Re, Luigi

    2015-01-01

    Background: Continuous glucose monitoring (CGM) is a powerful tool to support the optimization of glucose control of patients with diabetes. However, CGM systems measure glucose in interstitial fluid but not in blood. Rapid changes in one compartment are not accompanied by similar changes in the other, but follow with some delay. Such time delays hamper detection of, for example, hypoglycemic events. Our aim is to discuss the causes and extent of time delays and approaches to compensate for these. Methods: CGM data were obtained in a clinical study with 37 patients with a prototype glucose sensor. The study was divided into 5 phases over 2 years. In all, 8 patients participated in 2 phases separated by 8 months. A total number of 108 CGM data sets including raw signals were used for data analysis and were processed by statistical methods to obtain estimates of the time delay. Results: Overall mean (SD) time delay of the raw signals with respect to blood glucose was 9.5 (3.7) min, median was 9 min (interquartile range 4 min). Analysis of time delays observed in the same patients separated by 8 months suggests a patient dependent delay. No significant correlation was observed between delay and anamnestic or anthropometric data. The use of a prediction algorithm reduced the delay by 4 minutes on average. Conclusions: Prediction algorithms should be used to provide real-time CGM readings more consistent with simultaneous measurements by SMBG. Patient specificity may play an important role in improving prediction quality. PMID:26243773

  12. Concurrent Delay in Construction Disputes

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    Delay is one of the issues most frequently encountered in today’s construction industry; it causes significant economic damage to all parties involved. Construction contracts, standard and bespoke, almost invariably consider delay from a perspective of single liability. If the event causing...... period of delay can potentially be attributed to several events falling within both parties' spheres of responsibility, commonly termed concurrent delay, is rarely regulated in construction contracts in spite of its common occurrence. This book analyses both the theoretical foundations and the practical...

  13. Dependency of radon entry on pressure difference

    Science.gov (United States)

    Kokotti, H.; Kalliokoski, P.; Jantunen, M.

    Radon levels, ventilation rate and pressure differences were monitored continuously in four apartment houses with different ventilation systems. Two of them were ventilated by mechanical exhaust, one by mechanical supply and exhaust, and one by natural ventilation. The two-storey houses were constructed from concrete elements on a slab and located on a gravel esker. It was surprising to find that increasing the ventilation rate increased levels of radon in the apartments. Increased ventilation caused increased outdoor-indoor pressure difference, which in turn increased the entry rate of radon and counteracted the diluting effect of ventilation. The increase was significant when the outdoor-indoor pressure difference exceeded 5 Pa. Especially in the houses with mechanical exhaust ventilation the pressure difference was the most important factor of radon entry rate, and contributed up to several hundred Bq m -3 h -1.

  14. Prototipicality in entries of school dictionaries

    Directory of Open Access Journals (Sweden)

    Everton Castro de Almeida

    2015-01-01

    Full Text Available Theoretical Lexicography is the discipline which, in a general way, studies and criticizes the dictionaries. It is open to the theoretical contribution from other fields of research, such as Text Linguistics, Pragmatics, and Multimodality, once they may show another lexical dimension. Thus, we base our analysis on the theoretical support from Prototypes Theory, from cognitive sciences. In that sense, this paper aims to identify and describe the prototypicality in entries from the five type 3 dictionaries from the PNLD 2012 (National Plan for the Didactic Books. In order to do so, we use theories from Pontes (2008; 2009 and Geeraerts (2007. We analyze five entries, one from each dictionary type 3.

  15. 14 CFR 375.24 - Entry and clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Entry and clearance. 375.24 Section 375.24 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL... Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  16. 19 CFR 143.35 - Procedure for electronic entry summary.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Procedure for electronic entry summary. 143.35 Section 143.35 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) SPECIAL ENTRY PROCEDURES Electronic Entry Filing § 143.35...

  17. 77 FR 17492 - Expansion of Global Entry to Additional Airports

    Science.gov (United States)

    2012-03-26

    ... selection process, and the initial airport locations. See 77 FR 5681 and 8 CFR 235.12. Travelers who wish to... SECURITY U.S. Customs and Border Protection Expansion of Global Entry to Additional Airports AGENCY: U.S... as Global Entry, at twenty major U.S. airports. Global Entry allows pre-approved,...

  18. 40 CFR 90.1207 - Entry and access.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Entry and access. 90.1207 Section 90... § 90.1207 Entry and access. (a) To allow the Administrator to determine whether a manufacturer is... maintenance. (c) The provisions of § 90.705(c), (d), (e), (f) and (g) also apply to entry and access...

  19. Maximum Atmospheric Entry Angle for Specified Retrofire Impulse

    Directory of Open Access Journals (Sweden)

    T. N. Srivastava

    1969-07-01

    Full Text Available Maximum atmospheric entry angles for vehicles initially moving in elliptic orbits are investigated and it is shown that tangential retrofire impulse at the apogee results in the maximum entry angle. Equivalence of maximizing the entry angle and minimizing the retrofire impulse is also established.

  20. 19 CFR 143.16 - Substitution of warehouse entry.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Substitution of warehouse entry. 143.16 Section 143.16 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... warehouse entry. The importer may substitute an entry for warehouse at any time within 1 year from the...

  1. 50 CFR 91.16 - Submission procedures for entry.

    Science.gov (United States)

    2010-10-01

    ... (CONTINUED) MISCELLANEOUS PROVISIONS MIGRATORY BIRD HUNTING AND CONSERVATION STAMP CONTEST Procedures for.... Each entry must be accompanied by a non-refundable entrance fee and a completed and signed Reproduction... the Reproduction Rights Agreement must be attached to the back of the entry. (b) Each entry should...

  2. 31 CFR 337.6 - Conversions to book-entry.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Conversions to book-entry. 337.6... HOUSING ADMINISTRATION DEBENTURES Certificated Debentures § 337.6 Conversions to book-entry. Upon implementation of the book-entry debenture system, to be announced in advance by separate public notice, all...

  3. Sport entries & qualification manual: Innsbruck 2012 Youth Olympic Games

    OpenAIRE

    2015-01-01

    Sport entries constitute an important part of the delegation registration process of the Innsbruck 2012 Winter Youth Olympic Games. This manual aims to introduce to NOCs the process, relevant policies and requirements regarding sport entries so as to ensure that NOCs can successfully complete the entries for their athletes to the Innsbruck 2012 Winter Youth Olympic Games.

  4. The polyacetylene falcarindiol with COX-1 activity isolated from Aegopodium podagraria L.

    Science.gov (United States)

    Prior, Rikke M; Lundgaard, Nanna H; Light, Marnie E; Stafford, Gary I; van Staden, Johannes; Jäger, Anna K

    2007-08-15

    Extracts of Aegopodium podagraria L. were screened in vitro for cyclooxygenase-1 (COX-1) inhibitory activity. The isolation of the active compound falcarindiol was achieved by bioassay-guided fractionation. The identification of the active compound was confirmed by (1)H NMR and (13)C NMR. The IC(50)-value of falcarindiol was 0.3 microM in the COX-1 assay. A quantitative determination of the seasonal variation in the content of falcarindiol in different plant parts was carried out by HPLC analysis. The flowers from Aegopodium podagraria collected in June 2006 had the highest concentration of falcarindiol (88 mg/g plant material).

  5. A comparison of the newer COX-2 drugs and older nonnarcotic oral analgesics.

    Science.gov (United States)

    Sunshine, A

    2000-09-01

    The newer COX-2 drugs are safer analgesics than the older NSAIDs. At the usual dose used in osteoarthritis, they have less analgesic effect than the older NSAIDs. The non-narcotic analgesics such as acetaminophen, salicylate, NSAIDs, and the newer COX-2 drugs seem to have distinctly different mechanisms of action. In limited clinical trials, some of these drugs in combination give additive analgesia. Consideration should be given to using these drugs in combination, after suitable clinical trials, to enhance the efficacy of this category of analgesics.

  6. Cox report and the US-China arms control technical exchange program

    Energy Technology Data Exchange (ETDEWEB)

    Di Capua, M S

    1999-09-01

    The ACE program furthered the national security interests of the US by promoting technical approaches to the implementation and verification of arms control treaties that the international community embraces. The Cox Committee report suggests that uncontrolled interactions were taking place between US and Chinese nuclear weapons scientists in the course of the ACE program. On the contrary, elaborate controls were in place at the very beginning and remained in place to control the interactions and protect US national security information. The ACE program payoff to national security was just beginning and its suspension, resulting from the Cox reports allegations, is a setback to US-China progress on arms control.

  7. Non-Asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso.

    Science.gov (United States)

    Kong, Shengchun; Nan, Bin

    2014-01-01

    We consider finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz.We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulties caused by lacking iid Lipschitz losses.

  8. Non-asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso

    CERN Document Server

    Kong, Shengchun

    2012-01-01

    We consider the finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz. We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulty caused by the lack of iid and Lipschitz property.

  9. Continuum in HIV care from entry to ART initiation in rural KwaZulu-Natal, South Africa.

    Science.gov (United States)

    Plazy, Mélanie; Dray-Spira, Rosemary; Orne-Gliemann, Joanna; Dabis, François; Newell, Marie-Louise

    2014-06-01

    To quantify time from entry in HIV care until Antiretroviral therapy (ART) initiation and identify factors associated with ART initiation in rural KwaZulu-Natal, South Africa. Adults ≥16 years entering the decentralised Hlabisa ART programme between 2007 and 2011 were followed until June 2013. Median survival times to ART initiation from date of programme entry and from date of ART eligibility were estimated with Kaplan-Meier methods. Associated factors were evaluated in Cox regressions, censoring for deaths. Of 37 749 adults (71.6% female), 17 638 (46.7%) initiated ART. Nearly half (46.9%) met the CD4 criteria for treatment eligibility at programme entry. Among the 20 039 individuals not yet ART-eligible at entry, only 62.5% were retained in care with at least one further CD4 measurement, of whom 6688 subsequently became ART-eligible. Overall, 65.5% of the 24 398 ART-eligible individuals initiated ART over the study period. ART initiation was more likely in women (P < 0.001), in individuals ≥ 25 years old (P < 0.001) and in patients with low CD4 count (P < 0.001). Patients who became eligible during follow up were significantly more likely to initiate ART than those eligible at programme entry (72.6% vs. 62.9%, Adjusted Hazard Ratio = 1.46; 95% Confidence Interval [1.41-1.51]), adjusting for sex, age, year and CD4 count at eligibility. In this rural programme, continuation of care remains challenging, especially in men and younger adults. ART initiation is more likely in those engaged prior eligibility than in those entering HIV care only late in their HIV disease. © 2014 John Wiley & Sons Ltd.

  10. Hypersonic Flight Mechanics. [for atmospheric entry trajectories

    Science.gov (United States)

    Busemann, A.; Vinh, N. X.; Culp, R. D.

    1976-01-01

    The effects of aerodynamic forces on trajectories at orbital speeds are discussed in terms of atmospheric models. The assumptions for the model are spherical symmetry, nonrotating, and an exponential atmosphere. The equations of flight, and the performance in extra-atmospheric flight are discussed along with the return to the atmosphere, and the entry. Solutions of the exact equations using directly matched asymptotic expansions are presented.

  11. Unified treatment of lifting atmospheric entry

    Science.gov (United States)

    Nachtsheim, P. R.; Lehman, L. L.

    1980-01-01

    This paper presents a unified treatment of the effect of lift on peak acceleration during atmospheric entry. Earlier studies were restricted to different regimes because of approximations invoked to solve the same transcendental equation. This paper shows the connection between the earlier studies by employing a general expression for the peak acceleration and obtains solutions to the transcendental equation without invoking the earlier approximations. Results are presented and compared with earlier studies where appropriate.

  12. Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells

    Directory of Open Access Journals (Sweden)

    Yu Danny CW

    2008-07-01

    Full Text Available Abstract Background Cyclooxygenase (COX-2 has been implicated in tumour progression, angiogenesis and metastasis in non-small cell lung cancer (NSCLC. We speculated that inhibition of COX-2 activity might reduce expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF and interleukin-8 (IL-8 in lung cancer cells. Methods The levels of IL-8, VEGF and prostaglandin E2 (PGE2 were measured by ELISA. Expression of COX-1 and COX-2 was determined by Western blotting. Inhibition or knockdown of COX-2 was achieved by treating NSCLC cells with specific COX-2 inhibitor NS-398 or COX-2 siRNA, respectively. Results We found that NSCLC cell lines produced more IL-8 than VEGF (p 2 was significantly higher in NSCLC cell lines than SCLC cell lines (p 2 production. VEGF was significantly reduced following the treatment of NS-398 in A549 (by 31% and MOR/P (by 47% cells lines which expressing strong COX-2, but not in H460 cell line which expressing very low COX-2. However, IL-8 was not reduced in these cell lines. To confirm these results, we knocked down COX-2 expression with COX-2 siRNA in these cell lines. VEGF was significantly decreased in A549 (by 24% and in MOR/P (by 53%, but not in H460 whereas IL-8 was not affected in any cell line. Conclusion We conclude that NSCLC cells produce much higher levels of IL-8 than SCLC cells whereas both NSCLC and SCLC cells produce similar levels of VEGF. COX-2 is only expressed in NSCLC cells, but not in SCLC cells. VEGF is produced in both NSCLC and SCLC cells regardless of COX-2 expression. However, VEGF production is, at least partly, COX-2 dependent in NSCLC cells expressing COX-2. In contrast, IL-8 production is COX-2 independent in both NSCLC and SCLC cells. We speculate that combined targeting of COX-2 and IL-8 may be useful in the treatment of patients with NSCLC and targeting VEGF may be useful in the treatment of patients with SCLC.

  13. Cell entry by human pathogenic arenaviruses.

    Science.gov (United States)

    Rojek, Jillian M; Kunz, Stefan

    2008-04-01

    The arenaviruses Lassa virus (LASV) in Africa and Machupo (MACV), Guanarito (GTOV) and Junin viruses (JUNV) in South America cause severe haemorrhagic fevers in humans with fatality rates of 15-35%. The present review focuses on the first steps of infection with human pathogenic arenaviruses, the interaction with their cellular receptor molecules and subsequent entry into the host cell. While similarities exist in genomic organization, structure and clinical disease caused by pathogenic Old World and New World arenaviruses these pathogens use different primary receptors. The Old World arenaviruses employ alpha-dystroglycan, a cellular receptor for proteins of the extracellular matrix, and the human pathogenic New World arenaviruses use the cellular cargo receptor transferrin receptor 1. While the New World arenavirus JUNV enters cells via clathrin-dependent endocytosis, evidence occurred for clathrin-independent entry of the prototypic Old World arenavirus lymphocytic choriomeningitis virus. Upon internalization, arenaviruses are delivered to the endosome, where pH-dependent membrane fusion is mediated by the envelope glycoprotein (GP). While arenavirus GPs share characteristics with class I fusion GPs of other enveloped viruses, unusual mechanistic features of GP-mediated membrane fusion have recently been discovered for arenaviruses with important implications for viral entry.

  14. Kinetics of virus entry by endocytosis

    Science.gov (United States)

    Zhdanov, Vladimir P.

    2015-04-01

    Entry of virions into the host cells is either endocytotic or fusogenic. In both cases, it occurs via reversible formation of numerous relatively weak bonds resulting in wrapping of a virion by the host membrane with subsequent membrane rupture or scission. The corresponding kinetic models are customarily focused on the formation of bonds and do not pay attention to the energetics of the whole process, which is crucially dependent, especially in the case of endocytosis, on deformation of actin filaments forming the cytoskeleton of the host cell. The kinetic model of endocytosis, proposed by the author, takes this factor into account and shows that the whole process can be divided into a rapid initial transient stage and a long steady-state stage. The entry occurs during the latter stage and can be described as a first-order reaction. Depending on the details of the dependence of the grand canonical potential on the number of bonds, the entry can be limited either by the interplay of bond formation and membrane rupture (or scission) or by reaching a maximum of this potential.

  15. Filovirus tropism: Cellular molecules for viral entry

    Directory of Open Access Journals (Sweden)

    Ayato eTakada

    2012-02-01

    Full Text Available In human and nonhuman primates, filoviruses (Ebola and Marburg viruses cause severe hemorrhagic fever.Recently, other animals such as pigs and some species of fruit bats have also been shown to be susceptible to these viruses. While having a preference for some cell types such as hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages, filoviruses are known to be pantropic in infection of primates. The envelope glycoprotein (GP is responsible for both receptor binding and fusion of the virus envelope with the host cell membrane. It has been demonstrated that filovirus GP interacts with multiple molecules for entry into host cells, whereas none of the cellular molecules so far identified as a receptor/coreceptor fully explains filovirus tissue tropism and host range. Available data suggest that the mucin-like region (MLR on GP plays an important role in attachment to the preferred target cells, whose infection is likely involved in filovirus pathogenesis, whereas the MLR is not essential for the fundamental function of the GP in viral entry into cells in vitro. Further studies elucidating the mechanisms of cellular entry of filoviruses may shed light on the development of strategies for prophylaxis and treatment of Ebola and Marburg hemorrhagic fevers.

  16. Efek ekstrak daun singkong (Manihot utilissima terhadap ekspresi COX-2 pada monosit yang dipapar LPS E.coli (The effect of Manihot utilissima extracts on COX-2 expression of monocytes induced by LPS E. coli

    Directory of Open Access Journals (Sweden)

    Zahara Meilawaty

    2013-12-01

    Full Text Available Background: Periodontal disease is a common and widespread disease in the community. Gram negative bacteria have a role inperiodontitis. These bacteria secrete a variety of products such as endotoxin lipopolysaccharide (LPS, which causes the occurrenceof inflammation or infection. The body defense responses are neutrophils and mononuclear cells (monocytes and macrophages. Inresponse to defense mechanism, the body will be expressed enzyme cyclooxygenase (COX which functions convert arachidonic acidto prostaglandins. Cassava leaf cells known to play a role in reducing inflammation, but the mechanism for inhibiting COX-2, is notknown. Purpose: The study was aimed to determine the effect of cassava leaf extract (Manihot utilissima on expression of enzyme COX-2 in monocytes which were exposed by LPS E. coli. Methods: This study was in vitro experimental studies with the design of posttestonly control group design. The sample was the cassava leaves extract (Manihot utilissima at concentration of 12.5 % and 25 %. Theexpression of COX-2 was determined by immunocytochemistry method. Isolated monocytes were incubated in cassava leaf extract, andthen exposed to LPS, after washing imunostaning procedure was performed using a monoclonal antibody (MAb anti-human COX-2.The research data was the number of monocytes that express COX-2. Results: Expression of COX-2 in the group cassava leaf extractwas higher than the group that induced by LPS E. coli only. Conclusion: Cassava leaf extract did not inhibit the expression of COX-2in monocytes which were exposed by LPS E. coli.Latar belakang: Penyakit periodontal merupakan penyakit umum dan tersebar luas di masyarakat. Bakteri yang banyak berperanpada periodontitis adalah Gram negatif. Bakteri ini mengeluarkan berbagai produk antara lain endotoksin lipopolisakarida (LPS yangmenyebabkan inflamasi atau infeksi. Respon pertahanan tubuh pertama adalah netrofil dan sel mononuklear (monosit dan makrofag.Pada respon

  17. Glycogen synthase kinase 3 β activity is required for hBora/Aurora A-mediated mitotic entry.

    Science.gov (United States)

    Lee, Yu-Cheng; Liao, Po-Chi; Liou, Yih-Cherng; Hsiao, Michael; Huang, Chi-Ying; Lu, Pei-Jung

    2013-03-15

    The synthesis and degradation of hBora is important for the regulation of mitotic entry and exist. In G 2 phase, hBora can complex with Aurora A to activate Plk1 and control mitotic entry. However, whether the post-translational modification of hBora is relevant to the mitotic entry still unclear. Here, we used the LC-MS/MS phosphopeptide mapping assay to identify 13 in vivo hBora phosphorylation sites and characterized that GSK3β can interact with hBora and phosphorylate hBora at Ser274 and Ser278. Pharmacological inhibitors of GSK3β reduced the retarded migrating band of hBora in cells and diminished the phosphorylation of hBora by in vitro kinase assay. Moreover, as well as in GSK3β activity-inhibited cells, specific knockdown of GSK3β by shRNA and S274A/S278 hBora mutant-expressing cells also exhibited the reduced Plk1 activation and a delay in mitotic entry. It suggests that GSK3β activity is required for hBora-mediated mitotic entry through Ser274 and Ser278 phosphorylation.

  18. Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive.

    Science.gov (United States)

    Baertling, Fabian; Al-Murshedi, Fathiya; Sánchez-Caballero, Laura; Al-Senaidi, Khalfan; Joshi, Niranjan P; Venselaar, Hanka; van den Brand, Mariël Am; Nijtmans, Leo Gj; Rodenburg, Richard Jt

    2017-03-01

    COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia, failure to thrive, and isolated complex IV deficiency are presented. We show that the variant lies within the evolutionarily conserved COX5A/COX4 interface domain, suggesting that it alters the interaction between these two subunits during complex IV biogenesis. In patient skin fibroblasts, the enzymatic activity and protein levels of complex IV and several of its subunits are reduced. Lentiviral complementation rescues complex IV deficiency. The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts.

  19. COX-2 expression positively correlates with PD-L1 expression in human melanoma cells.

    Science.gov (United States)

    Botti, Gerardo; Fratangelo, Federica; Cerrone, Margherita; Liguori, Giuseppina; Cantile, Monica; Anniciello, Anna Maria; Scala, Stefania; D'Alterio, Crescenzo; Trimarco, Chiara; Ianaro, Angela; Cirino, Giuseppe; Caracò, Corrado; Colombino, Maria; Palmieri, Giuseppe; Pepe, Stefano; Ascierto, Paolo Antonio; Sabbatino, Francesco; Scognamiglio, Giosuè

    2017-02-23

    The resistance to PD-1/PD-L1 inhibitors for the treatment of melanoma have prompted investigators to implement novel clinical trials which combine immunotherapy with different treatment modalities. Moreover is also important to investigate the mechanisms which regulate the dynamic expression of PD-L1 on tumor cells and PD-1 on T cells in order to identify predictive biomarkers of response. COX-2 is currently investigated as a major player of tumor progression in several type of malignancies including melanoma. In the present study we investigated the potential relationship between COX-2 and PD-L1 expression in melanoma. Tumor samples obtained from primary melanoma lesions and not matched lymph node metastases were analyzed for both PD-L1 and COX-2 expression by IHC analysis. Status of BRAF and NRAS mutations was analyzed by sequencing and PCR. Co-localization of PD-L1 and COX-2 expression was analyzed by double fluorescence staining. Lastly the BRAF(V600E) A375 and NRAS(Q61R) SK-MEL-2 melanoma cell lines were used to evaluate the effect of COX-2 inhibition by celecoxib on expression of PD-L1 in vitro. BRAF(V600E/V600K) and NRAS(Q61R/Q61L) were detected in 57.8 and 8.9% of the metastatic lesions, and in 65.9 and 6.8% of the primary tumors, respectively. PD-L1 and COX-2 expression were heterogeneously expressed in both primary melanoma lesions and not matched lymph node metastases. A significantly lower number of PD-L1 negative lesions was found in primary tumors as compared to not matched metastatic lesions (P = 0.002). COX-2 expression significantly correlated with PD-L1 expression in both primary (P = 0.001) and not matched metastatic (P = 0.048) lesions. Furthermore, in melanoma tumors, cancer cells expressing a higher levels of COX-2 also co-expressed a higher level of PD-L1. Lastly, inhibition of COX-2 activity by celecoxib down-regulated the expression of PD-L1 in both BRAF(V600E) A375 and NRAS(Q61R) SK-MEL-2 melanoma cell lines. COX-2 expression

  20. 19 CFR 149.6 - Entry and entry summary documentation and Importer Security Filing submitted via a single...

    Science.gov (United States)

    2010-04-01

    ... Security Filing submitted via a single electronic transmission. 149.6 Section 149.6 Customs Duties U.S... submitted via a single electronic transmission. If the Importer Security Filing is filed pursuant to § 149.2 of this part via the same electronic transmission as entry or entry/entry summary...

  1. COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Goodman Julie E

    2010-11-01

    Full Text Available Abstract Background Inducible cyclooxgenase-2 (COX-2 is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation. Methods Tumor COX-2, HER2 and estrogen receptor α (ER expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival. Results COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR = 2.72; 95% confidence interval (CI, 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52. However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9. Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196. Conclusions Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype.

  2. Effects of Ge Gen Decoction on PGE2 Content and COX Activity in the Degenarated Cervical Intervertebral Discs of Rats

    Institute of Scientific and Technical Information of China (English)

    Zhou Jun; Fang Suping; Huo Hairu; Qi Yun; Guo Shuying; Jiang Tingliang; Shi Qi; Wang Youjing

    2005-01-01

    After the rat model of cervical spondylosis was developed for 6 months, the PGE2 content and COX activity in the cervical intervertebral discs were determined respectively by radioimmunoassay and catalytic activity assay.The results indicated that the PGF2 content and COX activity in the model rat increased significantly, and that Ge Gen Decoction could down-regulate the PGE2 content and inhibit COX activity. This is possibly one of the mechanisms of Ge Gen Decoction for treating cervical spondylosis.

  3. The potential role of COX-2 in cancer stem cell-mediated canine mammary tumor initiation: an immunohistochemical study

    OpenAIRE

    Huang, Jian; Zhang, Di; Xie, Fuqiang; LIN, Degui

    2015-01-01

    Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding tran...

  4. Immediate Extinction Causes a Less Durable Loss of Performance than Delayed Extinction following Either Fear or Appetitive Conditioning

    Science.gov (United States)

    Woods, Amanda M.; Bouton, Mark E.

    2008-01-01

    Five experiments with rat subjects compared the effects of immediate and delayed extinction on the durability of extinction learning. Three experiments examined extinction of fear conditioning (using the conditioned emotional response method), and two experiments examined extinction of appetitive conditioning (using the food-cup entry method). In…

  5. Parent Concern and Enrollment in Intervention Services for Young Children with Developmental Delays: 2007 National Survey of Children's Health

    Science.gov (United States)

    Marshall, Jennifer; Kirby, Russell S.; Gorski, Peter A.

    2016-01-01

    This study sought to address underenrollment and late entry to early intervention by identifying factors associated with parental concern and services for developmental delays. The authors analyzed responses from 27,566 parents of children from birth to age 5 from the 2007 National Survey of Children's Health to quantify and to identify factors…

  6. Entry and Exit Dynamics of Nascent Business Owners

    DEFF Research Database (Denmark)

    Rocha, Vera; Carneiro, Anabela; Varum, Celeste

    2015-01-01

    in the labor market and entry modes shape the post-entry dynamics of nascent business owners. By differentiating between different entry and exit routes, this paper provides new evidence on different human capital patterns among nascent business owners and on key determinants of entrepreneurial survival. Our...... results suggest that different exit modes can be predicted by business owners’ entry route. Furthermore, different exit modes exhibit different duration dependence patterns according to the entry mode. Additionally, the paper shows that businesses started after a displacement episode are not necessarily...

  7. Exporting Complex Digital Products: Motives and Entry Modes

    DEFF Research Database (Denmark)

    Rask, Morten

    2005-01-01

    for digital product providers. However, other types of entry modes like what we call direct digital export with F2F-sales, direct digital export with F2F-support, and virtual sales subsidiary are entry modes that respond to a higher degree of pre- and postsales complexity.......When the product is digital, it will most often be distributed directly to the customer through the Internet, and therefore, the entry modes, considered in this paper, are different flavors of the entry mode called direct export: virtual export channel is generally understood as the entry mode...

  8. Exporting Complex Digital Products: Motives and Entry Modes

    DEFF Research Database (Denmark)

    Rask, Morten

    for digital product providers. However other types of entry modes like what wee call direct digital export with F2F-sales, direct digital export with F2F-support and virtual sales subsidiary are entry modes that respond to a higher degree of pre- and after-sales complexity.......When the product is digital, it will most often be distributed directly to the customer through the Internet, and therefore the entry modes, considered in this paper, are different flavors of the entry mode called direct export: Virtual export channel are generally understood as the entry mode...

  9. Exporting Complex Digital Products: Motives and Entry Modes

    DEFF Research Database (Denmark)

    Rask, Morten

    When the product is digital, it will most often be distributed directly to the customer through the Internet, and therefore the entry modes, considered in this paper, are different flavors of the entry mode called direct export: Virtual export channel are generally understood as the entry mode...... for digital product providers. However other types of entry modes like what wee call direct digital export with F2F-sales, direct digital export with F2F-support and virtual sales subsidiary are entry modes that respond to a higher degree of pre- and after-sales complexity....

  10. Exporting Complex Digital Products: Motives and Entry Modes

    DEFF Research Database (Denmark)

    Rask, Morten

    2005-01-01

    When the product is digital, it will most often be distributed directly to the customer through the Internet, and therefore, the entry modes, considered in this paper, are different flavors of the entry mode called direct export: virtual export channel is generally understood as the entry mode...... for digital product providers. However, other types of entry modes like what we call direct digital export with F2F-sales, direct digital export with F2F-support, and virtual sales subsidiary are entry modes that respond to a higher degree of pre- and postsales complexity....

  11. Registration Delay and Student Performance

    Science.gov (United States)

    Siefken, Jason

    2017-01-01

    Tracking the difference between the time a first-year student is allowed to register for a course and the time he or she does register for a course (a student's registration delay), we notice a negative correlation between registration delay and final grade in a course. The difference between a student who registers within the first two minutes…

  12. 78 FR 59422 - Delayed Applications

    Science.gov (United States)

    2013-09-26

    ... Pipeline and Hazardous Materials Safety Administration Delayed Applications AGENCY: Office of Hazardous... applications delayed more than 180 days. SUMMARY: In accordance with the requirements of 49 U.S.C. 5117(c), PHMSA is publishing the following list of special permit applications that have been in process for 180...

  13. High resolution digital delay timer

    Science.gov (United States)

    Martin, Albert D.

    1988-01-01

    Method and apparatus are provided for generating an output pulse following a trigger pulse at a time delay interval preset with a resolution which is high relative to a low resolution available from supplied clock pulses. A first lumped constant delay (20) provides a first output signal (24) at predetermined interpolation intervals corresponding to the desired high resolution time interval. Latching circuits (26, 28) latch the high resolution data (24) to form a first synchronizing data set (60). A selected time interval has been preset to internal counters (142, 146, 154) and corrected for circuit propagation delay times having the same order of magnitude as the desired high resolution. Internal system clock pulses (32, 34) count down the counters to generate an internal pulse delayed by an interval which is functionally related to the preset time interval. A second LCD (184) corrects the internal signal with the high resolution time delay. A second internal pulse is then applied to a third LCD (74) to generate a second set of synchronizing data (76) which is complementary with the first set of synchronizing data (60) for presentation to logic circuits (64). The logic circuits (64) further delay the internal output signal (72) to obtain a proper phase relationship of an output signal (80) with the internal pulses (32, 34). The final delayed output signal (80) thereafter enables the output pulse generator (82) to produce the desired output pulse (84) at the preset time delay interval following input of the trigger pulse (10, 12).

  14. Calibrating for Ionospheric Phase Delays

    Science.gov (United States)

    Macdoran, P. F.

    1985-01-01

    Technique determines ionospheric phase delay on real-time universally applicable basis in terms of electrons per meter squared by coherently modulating two L-band carrier frequencies received from two Global Positioning System satelites. Two pseudorandom number sequences cross-correlated to derive delay time.

  15. #FakeNobelDelayReasons

    CERN Multimedia

    2013-01-01

    Tuesday’s hour-long delay of the Nobel Prize in Physics announcement was (and still is) quite the cause for speculation. But on the Twittersphere, it was simply the catalyst for some fantastic puns, so-bad-they're-good physics jokes and other shenanigans. Here are some of our favourite #FakeNobelDelayReasons.    

  16. Imitation dynamics with time delay.

    Science.gov (United States)

    Wang, Shi-Chang; Yu, Jie-Ru; Kurokawa, Shun; Tao, Yi

    2017-05-07

    Based on the classic imitation dynamics (Hofbauer and Sigmund, 1998, Evolutionary Games and Population Dynamics, Cambridge University Press), the imitation dynamics with time delay is investigated, where the probability that an individual will imitate its opponent's own strategy is assumed to depend on the comparison between the past expected payoff of this individual's own strategy and the past expected payoff of its opponent's own strategy, i.e. there is a time delay effect. For the two-phenotype model, we show that if the system has an interior equilibrium and this interior equilibrium is stable when there is no time delay, then there must be a critical value of time delay such that the system tends to a stable periodic solution when the time delay is larger than the critical value. On the other hand, for three-phenotype (rock-scissors-paper) model, the numerical analysis shows that for the stable periodic solution induced by the time delay, the amplitude and the period will increase with the increase of the time delay. These results should help to understand the evolution of behavior based on the imitation dynamics with time delay. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Magnetic bearing optical delay line

    NARCIS (Netherlands)

    Dool, T.C. van den; Kamphues, F.G.; Fouss, B.; Henrioulle, K.; Hogenhuis, H.

    2004-01-01

    TNO TPD, in close cooperation with Micromega-Dynamics and Dutch Space, has developed an advanced Optical Delay Line (ODL) for use in PRIMA, GENIE and other ground based interferometers. The delay line design is modular and flexible, which makes scaling for other applications a relatively easy task.

  18. Microperforated hymen: a case of delayed diagnosis.

    Science.gov (United States)

    Ferrarini, Olívia Maria Ferraz; Munhoz, Lívia Oliveira; Simões, Ricardo Santos; Cezarino, Pérsio Yvon Adri; Mieli, Mauricio Paulo Ângelo; Margarido, Paulo Francisco Ramos; Guida, Fábio José; Baracat, Edmund Chada

    2014-01-01

    Although the incidence of microperforated hymen (MH) is unclear, this hymenal subocclusive anomaly is considered a rare entity. Differently from imperforated hymen, MH may be asymptomatic until puberty when the women's quality of life is jeopardized. Depending on the size of the microperforation, MH's clinical features me be very similar to those found in imperforated hymen cases. However, MH may present infectious complications since the accumulated secretion retained in the vaginal canal has contact with the external environment and therefore represents a source of entry for infectious agents. The authors report a case of a 28-year-old woman who sought the gynecologist complaining of inability to have vaginal intercourse. She referred normal menses, but in fact, although regular, bleeding was filiform and was exteriorized only through the right side of the vagina. Physical examination and imaging disclosed a microperforation of the hymenal membrane at 10 o'clock position. Hymenotomy under general anesthesia was undertaken. Outcome was favorable and the patient could thenceforth have a normal life. We conclude that this anomaly may be overlooked, interfering on its incidence determination. The delayed onset of symptoms and psychological embarrassing aspects, which postpone gynecological consultation, may contribute for misdiagnoses. We call attention to a mandatory detailed anamnesis and thorough physical examination to diagnose this anomaly before the puberty, when complications are less frequent and treatment is advisable.

  19. Microperforated hymen: a case of delayed diagnosis

    Directory of Open Access Journals (Sweden)

    Olívia Maria Ferraz Ferrarini

    2014-09-01

    Full Text Available Although the incidence of microperforated hymen (MH is unclear, this hymenal subocclusive anomaly is considered a rare entity. Differently from imperforated hymen, MH may be asymptomatic until puberty when the women’s quality of life is jeopardized. Depending on the size of the microperforation, MH’s clinical features me be very similar to those found in imperforated hymen cases. However, MH may present infectious complications since the accumulated secretion retained in the vaginal canal has contact with the external environment and therefore represents a source of entry for infectious agents. The authors report a case of a 28-year-old woman who sought the gynecologist complaining of inability to have vaginal intercourse. She referred normal menses, but in fact, although regular, bleeding was filiform and was exteriorized only through the right side of the vagina. Physical examination and imaging disclosed a microperforation of the hymenal membrane at 10 o’clock position. Hymenotomy under general anesthesia was undertaken. Outcome was favorable and the patient could thenceforth have a normal life. We conclude that this anomaly may be overlooked, interfering on its incidence determination. The delayed onset of symptoms and psychological embarrassing aspects, which postpone gynecological consultation, may contribute for misdiagnoses. We call attention to a mandatory detailed anamnesis and thorough physical examination to diagnose this anomaly before the puberty, when complications are less frequent and treatment is advisable.

  20. Ekspresi COX-2 setelah pemberian ekstrak etanolik kulit manggis (Garcinia mangostana Linn pada tikus wistar (COX-2 expression after mangosteen rind (Garcinia mangostana Linn etanolic extract administration in wistar rats

    Directory of Open Access Journals (Sweden)

    Rendra Chriestedy Prasetya

    2013-12-01

    Full Text Available Background: Cyclooxygenase is an enzyme for prostaglandins (PGs synthesis from arachidonic acid. Cyclooxygenase have been characterized and named as COX-1 and COX-2. COX-1 is responsible for constitutive PGs production under physiological condition and maintains normal function. On the other hand, while COX-2 expression is inducible by cytokines and endotoxin. Periodontitis is a chronic inflammatory disease caused by anaerobic bacteria especially gram negative bacteria. The periodontitis occurrence is followed by increased of COX-2 expression. Mangosteen rind (Garcinia mangostana Linn contains gamma mangostin which inhibits the synthesis of PGE2 through inhibition of COX-2 expression. Purpose: This research was aimed to study COX-2 expression in experimental-induced periodontitis in wistar rats after mangosteen rind etanolic extract administration. Methods: Forty eight male wistar rats were induced periodontitis by putting silk ligature subgingivally around the cervical of the anterior lower teeth for 7 days. After the ligation was taken out, the rats were divided into 4 groups, and treated orally with mangosteen rind extract 60 mg/kg BB, 30 mg/kg BB, ibuprofen and saline respectively. The rats were sacrificed on the 1st, 3rd, 4th, 7th day after the treatment. The rats’ anterior lower jaws were processed for paraffin embedded tissue, cut serially and stained with immunohistochemistry. COX-2 expression were observed and counted under the microscope (400x. The data were analyzed using kruskall wallis test. Results: Kruskal wallis test showed a significant difference COX-2 expression among group indicating that mangosteen rind etanolic extract affected COX-2 expression. Conclusion: Mangosteen rind etanolic extract reduced COX-2 expression in periodontitis rats.Latar belakang: Siklooksigenase adalah enzim yang mensintesis prostaglandin (PG dari asam arakhidonat. Siklooksigenase dibagi menjadi 2 yaitu COX-1 dan COX-2. COX-1 bertanggung jawab pada

  1. Interaction of apoptotic cells with macrophages upregulates COX-2/PGE2 and HGF expression via a positive feedback loop.

    Science.gov (United States)

    Byun, Ji Yeon; Youn, Young-So; Lee, Ye-Ji; Choi, Youn-Hee; Woo, So-Yeon; Kang, Jihee Lee

    2014-01-01

    Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and hepatocyte growth factor (HGF) play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2 expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cells in vitro and in vivo orchestrate the interaction between COX-2/PGE2 and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2 production. Both NS-398 and COX-2-siRNA, as well as the PGE2 receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2 induction. The in vivo relevance of the interaction between the COX-2/PGE2 and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages following in vivo exposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE2 and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition.

  2. Interaction of Apoptotic Cells with Macrophages Upregulates COX-2/PGE2 and HGF Expression via a Positive Feedback Loop

    Directory of Open Access Journals (Sweden)

    Ji Yeon Byun

    2014-01-01

    Full Text Available Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2/prostaglandin E2 (PGE2 and hepatocyte growth factor (HGF play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2 expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cells in vitro and in vivo orchestrate the interaction between COX-2/PGE2 and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2 production. Both NS-398 and COX-2-siRNA, as well as the PGE2 receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2 induction. The in vivo relevance of the interaction between the COX-2/PGE2 and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages following in vivo exposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE2 and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition.

  3. COX-2 Induces Breast Cancer Stem Cells via EP4/PI3K/AKT/NOTCH/WNT Axis.

    Science.gov (United States)

    Majumder, Mousumi; Xin, Xiping; Liu, Ling; Tutunea-Fatan, Elena; Rodriguez-Torres, Mauricio; Vincent, Krista; Postovit, Lynne-Marie; Hess, David; Lala, Peeyush K

    2016-09-01

    Cancer stem-like cells (SLC) resist conventional therapies, necessitating searches for SLC-specific targets. We established that cyclo-oxygenase(COX)-2 expression promotes human breast cancer progression by activation of the prostaglandin(PG)E-2 receptor EP4. Present study revealed that COX-2 induces SLCs by EP4-mediated NOTCH/WNT signaling. Ectopic COX-2 over-expression in MCF-7 and SKBR-3 cell lines resulted in: increased migration/invasion/proliferation, epithelial-mesenchymal transition (EMT), elevated SLCs (spheroid formation), increased ALDH activity and colocalization of COX-2 and SLC markers (ALDH1A, CD44, β-Catenin, NANOG, OCT3/4, SOX-2) in spheroids. These changes were reversed with COX-2-inhibitor or EP4-antagonist (EP4A), indicating dependence on COX-2/EP4 activities. COX-2 over-expression or EP4-agonist treatments of COX-2-low cells caused up-regulation of NOTCH/WNT genes, blocked with PI3K/AKT inhibitors. NOTCH/WNT inhibitors also blocked COX-2/EP4 induced SLC induction. Microarray analysis showed up-regulation of numerous SLC-regulatory and EMT-associated genes. MCF-7-COX-2 cells showed increased mammary tumorigenicity and spontaneous multiorgan metastases in NOD/SCID/IL-2Rγ-null mice for successive generations with limiting cell inocula. These tumors showed up-regulation of VEGF-A/C/D, Vimentin and phospho-AKT, down-regulation of E-Cadherin and enrichment of SLC marker positive and spheroid forming cells. MCF-7-COX-2 cells also showed increased lung colonization in NOD/SCID/GUSB-null mice, an effect reversed with EP4-knockdown or EP4A treatment of the MCF-7-COX-2 cells. COX-2/EP4/ALDH1A mRNA expression in human breast cancer tissues were highly correlated with one other, more marked in progressive stage of disease. In situ immunostaining of human breast tumor tissues revealed co-localization of SLC markers with COX-2, supporting COX-2 inducing SLCs. High COX-2/EP4 mRNA expression was linked with reduced survival. Thus, EP4 represents a novel SLC

  4. Time-delay damping theory

    Institute of Scientific and Technical Information of China (English)

    洪峰

    2002-01-01

    In this paper, existing damping theories are briefly reviewed. On the basis of the existing damping theories, a new kind of damping theory, i.e., the time-delay damping theory, is developed. In the time-delay damping theory, the damping force is considered to be directly proportional to the increment of displacement. The response analysis of an SDOF time-delay damping system is carried out, and the methods for obtaining the solution for a time-delay damping system in the time domain as well as the frequency domain are given. The comparison between results from different damping theories shows that the time-delay damping theory is both reasonable and convenient.

  5. Asynchronous Bounded Expected Delay Networks

    CERN Document Server

    Bakhshi, Rena; Fokkink, Wan; Pang, Jun

    2010-01-01

    The commonly used asynchronous bounded delay (ABD) network models assume a fixed bound on message delay. We propose a probabilistic network model, called asynchronous bounded expected delay (ABE) model. Instead of a strict bound, the ABE model requires only a bound on the expected message delay. While the conditions of ABD networks restrict the set of possible executions, in ABE networks all asynchronous executions are possible, but executions with extremely long delays are less probable. In contrast to ABD networks, ABE networks cannot be synchronised efficiently. At the example of an election algorithm, we show that the minimal assumptions of ABE networks are sufficient for the development of efficient algorithms. For anonymous, unidirectional ABE rings of known size N we devise a probabilistic leader election algorithm having average message and time complexity O(N).

  6. Phil Cox Takes on APPA Presidency with Energy, Experience, and Commitment.

    Science.gov (United States)

    Thaler-Carter, Ruth E.

    2002-01-01

    Describes the background, experience, and goals of Philip L. Cox, the new president of APPA, the Association of Higher Education Facilities Officers, who currently serves as director of facilities management for Cornell University in Ithaca, New York. Explores his vision for APPA. (EV)

  7. Dual inhibitory effect of Glycyrrhiza glabra (GutGard™) on COX and LOX products.

    Science.gov (United States)

    Chandrasekaran, C V; Deepak, H B; Thiyagarajan, P; Kathiresan, S; Sangli, Gopal Krishna; Deepak, M; Agarwal, Amit

    2011-02-15

    Glycyrrhiza glabra and its phytoconstituents have been known to possess widespread pharmacological properties as an anti-inflammatory, anti-viral, antitumour and hepatoprotective drug. In this study, we examined the inhibitory potential of extract of G. glabra (GutGard™) root and its phytoconstituents (glabridin, glycyrrhizin, and isoliquiritigenin) on both cyclooxygenase (COX) and lipoxygenase (LOX) products in order to understand the mechanism of its anti-inflammatory action. Inhibitory effect of GutGard™ and its phytoconstituents on lipopolysaccharide (LPS) induced prostaglandin E(2) (PGE(2)), calcimycin (A23187) induced thromboxane (TXB(2)), and leukotriene (LTB(4)) release was studied using murine macrophages (J774A.1) and human neutrophil (HL-60) cells. Results revealed that, G. glabra and glabridin significantly inhibited PGE(2), TXB(2) (COX) and LTB(4) (LOX), while, isoliquiritigenin exerted inhibitory effect only against COX products but failed to suppress LOX product. However, glycyrrhizin at the tested concentrations failed to exhibit inhibitory effect on both COX and LOX products. Here, we report for the first time that G. glabra (almost devoid of glycyrrhizin) exhibits anti-inflammatory property likely through the inhibition of PGE(2), TXB(2) and LTB(4) in mammalian cell assay system, which could be influenced in part by glabridin and isoliquiritigenin.

  8. A COX-2 inhibitor combined with chemoradiation of locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Mortensen, John Pløen; Bisgaard, Claus;

    2008-01-01

    BACKGROUND AND AIM: The aim of this study was to investigate the possible effect of a COX-2 inhibitor in addition to chemoradiation of locally advanced rectal cancer. MATERIALS AND METHODS: The study included 35 patients with rectal adenocarcinoma. All patients had a tumor localised....

  9. Elevated COX2 expression and PGE2 production by downregulation of RXRα in senescent macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Huimin, E-mail: huiminchen.jq@gmail.com [Department of Geratology, Liaoning Jinqiu Hospital, Shenyang 110015 (China); Ma, Feng [Institute of Immunology, Zhejiang University of Medicine, Hangzhou 310058 (China); Hu, Xiaona; Jin, Ting; Xiong, Chuhui [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China); Teng, Xiaochun, E-mail: tengxiaochun@126.com [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China)

    2013-10-11

    Highlights: •Downregulation of RXRα in senescent macrophage. •RXRα suppresses NF-κB activity and COX2 expression. •Increased PGE2 production due to downregulation of RXRα. -- Abstract: Increased systemic level of inflammatory cytokines leads to numerous age-related diseases. In senescent macrophages, elevated prostaglandin E2 (PGE2) production contributes to the suppression of T cell function with aging, which increases the susceptibility to infections. However, the regulation of these inflammatory cytokines and PGE2 with aging still remains unclear. We have verified that cyclooxygenase (COX)-2 expression and PGE2 production are higher in LPS-stimulated macrophages from old mice than that from young mice. Downregulation of RXRα, a nuclear receptor that can suppress NF-κB activity, mediates the elevation of COX2 expression and PGE2 production in senescent macrophages. We also have found less induction of ABCA1 and ABCG1 by RXRα agonist in senescent macrophages, which partially accounts for high risk of atherosclerosis in aged population. Systemic treatment with RXRα antagonist HX531 in young mice increases COX2, TNF-α, and IL-6 expression in splenocytes. Our study not only has outlined a mechanism of elevated NF-κB activity and PGE2 production in senescent macrophages, but also provides RXRα as a potential therapeutic target for treating the age-related diseases.

  10. Cyclooxygenase 1 (COX1 expression in Type 2 diabetes mellitus: A preliminary study from north India

    Directory of Open Access Journals (Sweden)

    Sushma Verma

    2016-01-01

    Conclusion: Although COX1 is known to be a “housekeeping” gene, our study showed that its expression can be correlated with the disease condition and be used as a marker. However, further studies are required in more number of samples from other ethnic populations to confirm the findings.

  11. Analysis of multi-species point patterns using multivariate log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus; Guan, Yongtao; Jalilian, Abdollah;

    Multivariate log Gaussian Cox processes are flexible models for multivariate point patterns. However, they have so far only been applied in bivariate cases. In this paper we move beyond the bivariate case in order to model multi-species point patterns of tree locations. In particular we address...

  12. Prognostic significance of COX-2 and β-catenin in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Amani Kazem

    2014-09-01

    Conclusion: Both β-catenin and COX-2 expression may play an important role in the evolution of colon carcinogenesis. Increased expression of both could be used as a marker of tumor progression and poor prognosis. This might be of therapeutic value for allocating patients with colorectal carcinoma to different treatment modalities.

  13. Isoorientin, a Selective Inhibitor of Cyclooxygenase-2 (COX-2) from the Tubers of Pueraria tuberosa.

    Science.gov (United States)

    Sumalatha, Manne; Munikishore, Rachakunta; Rammohan, Aluru; Gunasekar, Duvvuru; Kumar, Kotha Anil; Reddy, Kakularam Kumar; Azad, Rajaram; Reddanna, Pallu; Bodo, Bernard

    2015-10-01

    Bioassay-guided fraction of the methanol extract of the roots of Pueraria tuberose DC yielded puerarin, an isoflavone C-glycoside (PT-1), isoorientin, a flavone C-glycoside (PT-2) and mangiferin, a xanthone C-glycoside (PT-3). The extracts and the isolated compounds were screened for potent anti-inflammatory components inhibiting the cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX), the target enzymes of inflammation, by employing spectroscopic/polorographic methods. Among these, isoorientin was found to be a potent inhibitor of COX-2with an IC50 value of 39 μM. Docking studies were carried out to understand the interactions of isorientin (PT-2) with COX-2.The structures of the isolates were determined by mass spectrometry and 2D-NMR techniques including HSQC, HMBC, NOESY and 1H-1H COSY experiments. Although isoorientin and mangiferin have been reported from several plant sources, this is the first report of their isolation from a Pueraria species.

  14. Systematic revision of the mealybug genus Delottococcus Cox & Ben-Dov (Hemiptera: Pseudococcidae)

    Science.gov (United States)

    A systematic revision of the mealybug genus Delottococcus Cox & Ben-Dov is presented. Nine species are treated, including D. millari which is described as new. The 8 previously described species are: Delottococcus aberiae (De Lotto), D. confusus (De Lotto), D. elisabethae (Brain), D. euphorbiae (E...

  15. Measures to assess the prognostic ability of the stratified Cox proportional hazards model

    DEFF Research Database (Denmark)

    (Tybjaerg-Hansen, A.) The Fibrinogen Studies Collaboration.The Copenhagen City Heart Study; Tybjærg-Hansen, Anne

    2009-01-01

    Many measures have been proposed to summarize the prognostic ability of the Cox proportional hazards (CPH) survival model, although none is universally accepted for general use. By contrast, little work has been done to summarize the prognostic ability of the stratified CPH model; such measures w...

  16. Magnetic and transport properties of Fe1-xCoxSb2

    Science.gov (United States)

    Hu, Rongwei; Petrovic, Cedomir; Mitrovic, Vesna

    2006-03-01

    Anisotropic magnetic and electronic transport measurements were carried out on large single crystals of Fe1-xCoxSb2, grown by self flux method, in the temperature range 1.8-350K for 0Pnnm structure of FeSb2 to monoclinic P21/c structure of CoSb2. Large magnetoresistance and anisotropy in electronic transport were observed.

  17. High-Dimensional Cox Regression Analysis in Genetic Studies with Censored Survival Outcomes

    Directory of Open Access Journals (Sweden)

    Jinfeng Xu

    2012-01-01

    Full Text Available With the advancement of high-throughput technologies, nowadays high-dimensional genomic and proteomic data are easy to obtain and have become ever increasingly important in unveiling the complex etiology of many diseases. While relating a large number of factors to a survival outcome through the Cox relative risk model, various techniques have been proposed in the literature. We review some recently developed methods for such analysis. For high-dimensional variable selection in the Cox model with parametric relative risk, we consider the univariate shrinkage method (US using the lasso penalty and the penalized partial likelihood method using the folded penalties (PPL. The penalization methods are not restricted to the finite-dimensional case. For the high-dimensional (p→∞, p≪n or ultrahigh-dimensional case (n→∞, n≪p, both the sure independence screening (SIS method and the extended Bayesian information criterion (EBIC can be further incorporated into the penalization methods for variable selection. We also consider the penalization method for the Cox model with semiparametric relative risk, and the modified partial least squares method for the Cox model. The comparison of different methods is discussed and numerical examples are provided for the illustration. Finally, areas of further research are presented.

  18. Survival prediction based on compound covariate under Cox proportional hazard models.

    Directory of Open Access Journals (Sweden)

    Takeshi Emura

    Full Text Available Survival prediction from a large number of covariates is a current focus of statistical and medical research. In this paper, we study a methodology known as the compound covariate prediction performed under univariate Cox proportional hazard models. We demonstrate via simulations and real data analysis that the compound covariate method generally competes well with ridge regression and Lasso methods, both already well-studied methods for predicting survival outcomes with a large number of covariates. Furthermore, we develop a refinement of the compound covariate method by incorporating likelihood information from multivariate Cox models. The new proposal is an adaptive method that borrows information contained in both the univariate and multivariate Cox regression estimators. We show that the new proposal has a theoretical justification from a statistical large sample theory and is naturally interpreted as a shrinkage-type estimator, a popular class of estimators in statistical literature. Two datasets, the primary biliary cirrhosis of the liver data and the non-small-cell lung cancer data, are used for illustration. The proposed method is implemented in R package "compound.Cox" available in CRAN at http://cran.r-project.org/.

  19. Ruin Probabilities and Aggregrate Claims Distributions for Shot Noise Cox Processes

    DEFF Research Database (Denmark)

    Albrecher, H.; Asmussen, Søren

    We consider a risk process Rt where the claim arrival process is a superposition of a homogeneous Poisson process and a Cox process with a Poisson shot noise intensity process, capturing the effect of sudden increases of the claim intensity due to external events. The distribution of the aggregate...

  20. [Effect of COX-2 inhibitor celecoxib on proliferation, apoptosis of HL-60 cells and its mechanism].

    Science.gov (United States)

    Xie, Xia; Li, Jie; Wang, Rui-Cang; Geng, Rui-Li; Wang, Su-Yun; Wang, Chao; Zhao, Xiao-Yun; Hao, Hong-Ling

    2014-06-01

    This study was aimed to investigate the effect of COX-2 inhibitor celecoxib on proliferation, apoptosis of human acute myeloid leukemia cell line HL-60 and its mechanism. HL-60 cells were cultured with different concentrations of celecoxib for 24 h. Cell proliferation was analyzed by CCK-8 assay, cell apoptosis and cell cycle distribution were detected by flow cytometry. Cyclin D1, cyclin E1 and COX-2 mRNA expressions were determined by RT-PCR. The results showed that after the HL-60 cells were treated with different concentrations of celecoxib for 24 h, the cell growth was significantly inhibited in a dose-dependent manner(r = 0.955), IC50 was 63.037 µmol/L of celecoxib. Celecoxib could effectively induce apoptosis in HL-60 cells also in dose-dependent manner(r = 0.988), blocked the HL-60 cells in the G0/G1 phase. The expression of cyclin D1, cyclin E1 and COX-2 mRNA were downregulated. It is concluded that celecoxib can inhibit the proliferation of HL-60 cells in dose-dependent manner, celecoxib causes cell G0/G1 arrest and induces cell apoptosis possibly through down-regulation of the cyclin D1 and cyclin E1 expression, and down-regulation of COX-2 expression respectively.

  1. Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up-regulation

    Institute of Scientific and Technical Information of China (English)

    Ananya Chatterjee; Sirshendu Chatterjee; Smita Das; Arpita Saha; Subrata Chattopadhyay; Sandip K. Bandyopadhyay

    2012-01-01

    The mechanism of indomethacin-induced gastric ulcer healing by ellagic acid (EA) in experimental mice model is described in our study.Ulcer index (UI) and myeloperoxidase (MPO) activity of the stomach tissues showed maximum ulceration on the third day after indomethacin (18 mg/kg,single dose) administration.Preliminary observation of UI and MPO activity suggests that EA possesses ulcer-healing activity.Other anti-ulcer parameters such as the levels of prostaglandin E2,cyclooxygenase (COX) 1 and 2 enzymes,anti-inflammatory cytokines [interleukin (IL)-4 and -5J,pro-angiogenic factors,e.g.vascular endothelial growth factor,hepatocyte growth factor (HGF),and endothelial growth factor (EGF) were down-regulated by indomethacin.EA (7 mg/kg/day) treatment for 3 days shifted the indomethacin-induced pro-inflammatory biochemical parameters to the healing side.These activities were correlated with the ability of EA to alter the COX-2-dependent healing pathways.The ulcer-healing activity of EA was,however,compromised by pre-administration of the specific COX-2 inhibitor,celecoxib,and NS-398.Taken together,these results suggested that the EA treatment accelerates ulcer healing by inducing IL-4,EGF/HGF levds and enhances COX-2 expression.

  2. Global Stability of an HIV-1 Infection Model with General Incidence Rate and Distributed Delays.

    Science.gov (United States)

    Ndongo, Abdoul Samba; Talibi Alaoui, Hamad

    2014-01-01

    In this work an HIV-1 infection model with nonlinear incidence rate and distributed intracellular delays and with humoral immunity is investigated. The disease transmission function is assumed to be governed by general incidence rate f(T, V)V. The intracellular delays describe the time between viral entry into a target cell and the production of new virus particles and the time between infection of a cell and the emission of viral particle. Lyapunov functionals are constructed and LaSalle invariant principle for delay differential equation is used to establish the global asymptotic stability of the infection-free equilibrium, infected equilibrium without B cells response, and infected equilibrium with B cells response. The results obtained show that the global dynamics of the system depend on both the properties of the general incidence function and the value of certain threshold parameters R 0 and R 1 which depends on the delays.

  3. Global Stability of an HIV-1 Infection Model with General Incidence Rate and Distributed Delays

    Science.gov (United States)

    2014-01-01

    In this work an HIV-1 infection model with nonlinear incidence rate and distributed intracellular delays and with humoral immunity is investigated. The disease transmission function is assumed to be governed by general incidence rate f(T, V)V. The intracellular delays describe the time between viral entry into a target cell and the production of new virus particles and the time between infection of a cell and the emission of viral particle. Lyapunov functionals are constructed and LaSalle invariant principle for delay differential equation is used to establish the global asymptotic stability of the infection-free equilibrium, infected equilibrium without B cells response, and infected equilibrium with B cells response. The results obtained show that the global dynamics of the system depend on both the properties of the general incidence function and the value of certain threshold parameters R 0 and R 1 which depends on the delays. PMID:27355007

  4. Assessment of the ATV-1 Re-Entry Observation Campaign for Future Re-Entry Missions

    Science.gov (United States)

    Lips, T.; Lohle, S.; Marynowsky, T.; Rees, D.; Stenbeak-Nielsen, H. C.; Beks, M. L.; Hatton, J.

    2010-09-01

    This paper summarizes the midterm results of the currently ongoing ESA study “Assessment of the ATV-1 Reentry Observation Campaign for Future Re-entry Missions”. The primary objective of this study is to investigate the data obtained during a joint ESA/NASA airborne observation campaign of the destructive re-entry of ATV-1 Jules Verne which occurred on September 29, 2008. The presented results are focused on spectroscopic fragment characterization(material identification), frame-by-frame fragment tracking(manual and automatic) for various video recordings, 3D triangulation of the tracked fragments, and fragment propagation until complete demise or ground impact, including the actual size and location of the ATV-1 debris footprint. Fragment propagation analyses comprise also the derivation of aerodynamic fragment properties and potential delta velocities. These parameters are of high importance for the re-entry safety analysis for ATV-2 Johannes Kepler.

  5. Delayed radiation neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Nagashima, T.; Miyamoto, K.; Beppu, H.; Hirose, K.; Yamada, K. (Tokyo Metropolitan Neurological Hospital (Japan))

    1981-07-01

    A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author).

  6. CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

    Directory of Open Access Journals (Sweden)

    Marianne Houssier

    2008-02-01

    Full Text Available BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD. Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS phagocytosis by the retinal pigment epithelium (RPE in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR and CD36-/- mice. Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

  7. Design and synthesis of benzimidazole analogs endowed with oxadiazole as selective COX-2 inhibitor.

    Science.gov (United States)

    Rathore, Ankita; Rahman, Mujeeb Ur; Siddiqui, Anees Ahamad; Ali, Abuzer; Shaharyar, Mohammad

    2014-12-01

    New molecules of benzimidazole endowed with oxadiazole were designed and synthesized from 2-(2-((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazol-1-yl)acetohydrazide as 1-((5-substituted alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl)-2-((pyrimidin-2-ylthio)methyl)-1H-benzimidazoles (5a-r) with the aim to acquire selective cyclooxygenase (COX-2) inhibitor activity. The synthesized compounds were screened by in vitro cyclooxygenase assays to determine COX-1 and COX-2 inhibitory potency and the results showed that they had good-to-remarkable activity with an IC50 range of 11.6-56.1 µM. The most active compounds were further screened for their in vivo anti-inflammatory activity by using the carrageenan-induced rat paw edema model. In vitro anticancer activities of the hybrid compounds were assessed by the National Cancer Institute (NCI), USA, against 60 human cell lines, and the results showed a good spectrum. Compound 5l exhibited significant COX-2 inhibition with an IC50 value of 8.2 µM and a percent protection of 68.4%. Compound 5b evinced moderate cytotoxicity toward the UO-31 cell line of renal cancer. A docking study was performed using Maestro 9.0, to provide the binding mode into the binding sites of the cyclooxygenase enzyme. Hopefully, in the future, compound 5l could serve as a lead compound for developing new COX-2 inhibitors.

  8. COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease.

    Science.gov (United States)

    Oliveira-Filho, Jamary; Ornellas, Ana C P; Zhang, Cathy R; Oliveira, Luciana M B; Araújo-Santos, Théo; Borges, Valeria M; Ventura, Laís M G B; Reis, Francisco J F B; Aras, Roque; Fernandes, André M; Rosand, Jonathan; Greenberg, Steven M; Furie, Karen L; Rost, Natalia S

    2015-08-01

    To investigate the effect of COX-2 polymorphism and its product, prostaglandin E2 (PGE2), on stroke risk in an endemic area for Chagas disease. In a separate cohort, to investigate the effect of COX-2 polymorphisms on the total burden of cerebral white matter disease. Cases were outpatients with ischemic stroke; controls were stroke-free subjects from 2 outpatient clinics (heart failure and caregivers of a movement disorders clinic). We extracted DNA from total blood to investigate the rs20417 COX-2 polymorphism. Serologic tests (Enzime-linked immunosorbent assay) were performed to confirm Trypanosoma cruzi infection and to quantify PGE2 levels. In the Boston cohort, white matter hyperintensity volume (WMHv) was quantified on the admission brain magnetic resonance images of subjects with ischemic stroke, who also donated DNA for the COX-2 gene region analysis. We studied 44 patients with stroke and 96 controls (46 with heart failure and 50 caregivers) in the Brazilian cohort; and 788 stroke patients (302 cardioembolic and 486 noncardioembolic) in the Boston cohort. In the Brazilian cohort, rs20417 polymorphism was associated with both stroke (P = 5 × 10(-6)) and decreased PGE2 levels (P = 4 × 10(-5)); similarly, Chagas was associated with stroke (P = 4 × 10(-3)) and decreased PGE2 levels (P = 7 × 10(-3)). In the Boston cohort, rs20417 polymorphism was associated with increased WMHv among noncardioembolic (P = .037), but not among cardioembolic stroke patients. Variation in COX-2 gene is associated with both symptomatic and silent brain cerebrovascular disease. This candidate gene region should be tested in population-based samples. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  9. The David Y. Graham lecture: use of nonsteroidal antiinflammatory drugs in a COX-2 restricted environment.

    Science.gov (United States)

    Chan, Francis K L

    2008-01-01

    Recent evidence suggests that both cyclooxygenase-2 (COX-2) inhibitors and nonselective NSAIDs, with the possible exception of naproxen, increase cardiovascular (CV) hazard. Clinicians should assess not only patients' GI risk but also their CV risk before prescribing these drugs. Patients with low CV risk can be managed according to their GI risk-low-risk patients (without risk factors) receive nonselective NSAIDs, medium risk patients (1-2 risk factors) receive COX-2 inhibitors or nonselective NSAIDs plus a proton pump inhibitor (PPI) or misoprostol, whereas high-risk patients (multiple risk factors, previous ulcer complications, or concomitant anticoagulants) receive a COX-2 inhibitor plus a PPI or misoprostol. Among patients with high CV risk (e.g., prior cardiothrombotic events) who require NSAIDs, naproxen is preferred. These patients should receive a prophylactic PPI or misoprostol because the risk of ulcer bleeding is substantially increased with concomitant use of naproxen and low-dose aspirin. Substitution of clopidogrel for aspirin is not recommended in patients at risk for upper GI bleeding who require antiplatelet therapy. Patients with high GI and high CV risk should avoid NSAIDs and COX-2 inhibitors. If antiinflammatory analgesics are required, the choice of therapy depends on the relative importance of GI and CV risks of individual patients. Combination of naproxen, low-dose aspirin, and a PPI or misoprostol is recommended if CV risk is the major concern (e.g., recent myocardial infarction). In contrast, combination of low-dose COX-2 inhibitor, low-dose aspirin, and a PPI or misoprostol is preferred if GI risk outweighs CV risk (e.g., recent ulcer bleeding and stable CV disease).

  10. MEK1 inactivates Myt1 to regulate Golgi membrane fragmentation and mitotic entry in mammalian cells.

    Science.gov (United States)

    Villeneuve, Julien; Scarpa, Margherita; Ortega-Bellido, Maria; Malhotra, Vivek

    2013-01-01

    The pericentriolar stacks of Golgi cisternae are separated from each other in G2 and fragmented extensively during mitosis. MEK1 is required for Golgi fragmentation in G2 and for the entry of cells into mitosis. We now report that Myt1 mediates MEK1's effects on the Golgi complex. Knockdown of Myt1 by siRNA increased the efficiency of Golgi complex fragmentation by mitotic cytosol in permeabilized and intact HeLa cells. Myt1 knockdown eliminated the requirement of MEK1 in Golgi fragmentation and alleviated the delay in mitotic entry due to MEK1 inhibition. The phosphorylation of Myt1 by MEK1 requires another kinase but is independent of RSK, Plk, and CDK1. Altogether our findings reveal that Myt1 is inactivated by MEK1 mediated phosphorylation to fragment the Golgi complex in G2 and for the entry of cells into mitosis. It is known that Myt1 inactivation is required for CDK1 activation. Myt1 therefore is an important link by which MEK1 dependent fragmentation of the Golgi complex in G2 is connected to the CDK1 mediated breakdown of Golgi into tubules and vesicles in mitosis.

  11. Entry properties and entry inhibitors of a human H7N9 influenza virus.

    Directory of Open Access Journals (Sweden)

    Youhui Si

    Full Text Available The recently identified human infections with a novel avian influenza H7N9 virus in China raise important questions regarding possible risk to humans. However, the entry properties and tropism of this H7N9 virus were poorly understood. Moreover, neuraminidase inhibitor resistant H7N9 isolates were recently observed in two patients and correlated with poor clinical outcomes. In this study, we aimed to elucidate the entry properties of H7N9 virus, design and evaluate inhibitors for H7N9 virus entry. We optimized and developed an H7N9-pseudotyped particle system (H7N9pp that could be neutralized by anti-H7 antibodies and closely mimicked the entry process of the H7N9 virus. Avian, human and mouse-derived cultured cells showed high, moderate and low permissiveness to H7N9pp, respectively. Based on influenza virus membrane fusion mechanisms, a potent anti-H7N9 peptide (P155-185-chol corresponding to the C-terminal ectodomain of the H7N9 hemagglutinin protein was successfully identified. P155-185-chol demonstrated H7N9pp-specific inhibition of infection with IC50 of 0.19 µM. Importantly, P155-185-chol showed significant suppression of A/Anhui/1/2013 H7N9 live virus propagation in MDCK cells and additive effects with NA inhibitors Oseltamivir and Zanamivir. These findings expand our knowledge of the entry properties of the novel H7N9 viruses, and they highlight the potential for developing a new class of inhibitors targeting viral entry for use in the next pandemic.

  12. APC/C and SCFcyclin F Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry

    Directory of Open Access Journals (Sweden)

    Rajarshi Choudhury

    2016-09-01

    Full Text Available The anaphase promoting complex/cyclosome (APC/C is an ubiquitin ligase and core component of the cell-cycle oscillator. During G1 phase, APC/C binds to its substrate receptor Cdh1 and APC/CCdh1 plays an important role in restricting S-phase entry and maintaining genome integrity. We describe a reciprocal feedback circuit between APC/C and a second ubiquitin ligase, the SCF (Skp1-Cul1-F box. We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCFcyclin F. Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1. These data indicate that the coordinated, temporal ordering of cyclin F and Cdh1 degradation, organized in a double-negative feedback loop, represents a fundamental aspect of cell-cycle control. This mutual antagonism could be a feature of other oscillating systems.

  13. Entry Properties and Entry Inhibitors of a Human H7N9 Influenza Virus

    OpenAIRE

    Youhui Si; Jianguo Li; Yuqiang Niu; Xiuying Liu; Lili Ren; Li Guo; Min Cheng; Hongli Zhou; Jianwei Wang; Qi Jin; Wei Yang

    2014-01-01

    The recently identified human infections with a novel avian influenza H7N9 virus in China raise important questions regarding possible risk to humans. However, the entry properties and tropism of this H7N9 virus were poorly understood. Moreover, neuraminidase inhibitor resistant H7N9 isolates were recently observed in two patients and correlated with poor clinical outcomes. In this study, we aimed to elucidate the entry properties of H7N9 virus, design and evaluate inhibitors for H7N9 virus e...

  14. IL-1β stimulates COX-2 dependent PGE₂ synthesis and CGRP release in rat trigeminal ganglia cells.

    Directory of Open Access Journals (Sweden)

    Lars Neeb

    Full Text Available OBJECTIVE: Pro-inflammatory cytokines like Interleukin-1 beta (IL-1β have been implicated in the pathophysiology of migraine and inflammatory pain. The trigeminal ganglion and calcitonin gene-related peptide (CGRP are crucial components in the pathophysiology of primary headaches. 5-HT1B/D receptor agonists, which reduce CGRP release, and cyclooxygenase (COX inhibitors can abort trigeminally mediated pain. However, the cellular source of COX and the interplay between COX and CGRP within the trigeminal ganglion have not been clearly identified. METHODS AND RESULTS: 1. We used primary cultured rat trigeminal ganglia cells to assess whether IL-1β can induce the expression of COX-2 and which cells express COX-2. Stimulation with IL-1β caused a dose and time dependent induction of COX-2 but not COX-1 mRNA. Immunohistochemistry revealed expression of COX-2 protein in neuronal and glial cells. 2. Functional significance was demonstrated by prostaglandin E2 (PGE(2 release 4 hours after stimulation with IL-1β, which could be aborted by a selective COX-2 (parecoxib and a non-selective COX-inhibitor (indomethacin. 3. Induction of CGRP release, indicating functional neuronal activation, was seen 1 hour after PGE(2 and 24 hours after IL-1β stimulation. Immunohistochemistry showed trigeminal neurons as the source of CGRP. IL-1β induced CGRP release was blocked by parecoxib and indomethacin, but the 5-HT1B/D receptor agonist sumatriptan had no effect. CONCLUSION: We identified a COX-2 dependent pathway of cytokine induced CGRP release in trigeminal ganglia neurons that is not affected by 5-HT1B/D receptor activation. Activation of neuronal and glial cells in the trigeminal ganglion by IL-β leads to an elevated expression of COX-2 in these cells. Newly synthesized PGE(2 (by COX-2 in turn activates trigeminal neurons to release CGRP. These findings support a glia-neuron interaction in the trigeminal ganglion and demonstrate a sequential link between COX-2

  15. Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-{alpha}-treated A549 cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Lixin; Zhang, Shuang; Jiang, Zhenzhou; Huang, Xin; Wang, Tao; Huang, Xiao; Li, Han [Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn [Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Triptolide inhibited COX-2 expression and the half-life of COX-2 mRNA is decreased. Black-Right-Pointing-Pointer The HuR protein shuttling from nucleus to cytoplasm is inhibited by triptolide. Black-Right-Pointing-Pointer Triptolide inhibited 3 Prime -UTR fluorescence reporter gene activity. Black-Right-Pointing-Pointer COX-2 mRNA binding to HuR is decreased by triptolide in pull-down experiments. -- Abstract: Cyclooxygenase-2 (COX-2) over-expression is frequently associated with human non-small-cell lung cancer (NSCLC) and involved in tumor proliferation, invasion, angiogenesis and resistance to apoptosis. In the present study, the effects of triptolide on COX-2 expression in A549 cells were investigated and triptolide was found to inhibit TNF-{alpha}-induced COX-2 expression. In our further studies, it was found that triptolide decreased the half-life of COX-2 mRNA dramatically and that it inhibited 3 Prime -untranslated region (3 Prime -UTR) fluorescence reporter gene activity. Meanwhile, triptolide inhibited the HuR shuttling from nucleus to cytoplasm. After triptolide treatment, decreased COX-2 mRNA in pull-down experiments with anti-HuR antibodies was observed, indicating that the decreased cytoplasmic HuR is responsible for the decreased COX-2 mRNA. Taken together, our results provided evidence for the first time that triptolide inhibited COX-2 expression by COX-2 mRNA stability modulation and post-transcriptional regulation. These results provide a novel mechanism of action for triptolide which may be important in the treatment of lung cancer.

  16. Pulmonary and Cardiorenal Cyclooxygenase-1 (COX-1, -2 (COX-2, and Microsomal Prostaglandin E Synthase-1 (mPGES-1 and -2 (mPGES-2 Expression in a Hypertension Model

    Directory of Open Access Journals (Sweden)

    Zaher A. Radi

    2007-01-01

    Our work suggests that in hypertensive mice, there are (a significant microanatomic variations in the pulmonary, renal, and cardiac distribution and cellular localization of COX-1, COX-2, mPGES-1, and mPGES-2, and (b no differences in expression between genders.

  17. Access, entry and researcher-participant position

    DEFF Research Database (Denmark)

    Louw, Arnt Vestergaard

    2015-01-01

    it deals with the research findings that such a research design produced. As well as the methodological issues of researcher access, entry and participant position in the field, this article reports on the following questions: What kinds of implicit expectations of the students are embedded in the way...... the school introduces and initiates the programme? What kinds of effects does this have on the motivation of the students? How do the terms and professional language of the profession work on the individual students in including and excluding ways? These specific descriptions of classroom pedagogy, inspired...

  18. Radiation Database for Earth and Mars Entry

    Science.gov (United States)

    2008-11-17

    d3Πg − a3Πu (0:18;0:33) Fox- Herzberg e3Πg − a3Πu (0:15;0:35) Radiation Database for Earth and Mars Entry RTO-EN-AVT-162 8 - 15 affect a few J...structures of the spectra, namely in lines. This motivates the development of approximate models which do not have the high resolution structures but provide...Dec 1996. [2] L.C. Hartung. Predicting radiative heat transfer in thermo-chemical non-equilibrium flow- fields: theory and user’s manual for the

  19. Evolved Acceleration Guidance for Planetary Entry

    Science.gov (United States)

    Mease, K. D.; Leavitt, J. A.; Ferch, M.

    The U.S. Apollo and Shuttle programs have proven the viability and effectiveness of acceleration guidance. New capabilities have been developed to augment this basic concept. Algorithms have been designed for low lift to drag ratio vehicles and for mid to high lift to drag ratio vehicles. These algorithms have been tested for Mars landing and for earth entry of reusable launch vehicles and have performed well in both cases. Also the trajectory planner has been incorporated into a landing footprint generator that is designed for on-board use.

  20. Reference pricing with endogenous generic entry.

    OpenAIRE

    Kurt R. Brekke; Canta, Chiara; Straume, Odd Rune

    2015-01-01

    In this paper we study the effect of reference pricing on pharmaceutical prices and ex-penditures when generic entry is endogenously determined. We develop a Salop-type model where a brand-name producer competes with generic producers in terms of prices. In the market there are two types of consumers: (i) brand biased consumers who choose between brand-name and generic drugs, and (ii) brand neutral consumers who choose between the different generic drugs. We find that, for a given number of ...

  1. Female entrepreneurial networks and foreign market entry

    DEFF Research Database (Denmark)

    Rosenbaum, Gitte Ohrt

    2017-01-01

    The purpose of this paper is to explore the role of networks in the 116 foreign market entries (FMEs) of women-owned small businesses. A multiple case study based on semi-structured interviews with eight female entrepreneurs in the Danish fashion design industry. The results show that contrary to...... entrepreneurial ventures....... or compromising their work-life balance. The present study’s findings suggest that ICT has a much stronger role in the FME of firms than previously envisioned. The study’s findings also have important implications for policymakers and practitioners charged with promoting the international growth of female...

  2. Time Delay in Molecular Photoionization

    CERN Document Server

    Hockett, P; Villeneuve, D M; Corkum, P B

    2015-01-01

    Time-delays in the photoionization of molecules are investigated. As compared to atomic ionization, the time-delays expected from molecular ionization present a much richer phenomenon, with a strong spatial dependence due to the anisotropic nature of the molecular scattering potential. We investigate this from a scattering theory perspective, and make use of molecular photoionization calculations to examine this effect in representative homonuclear and hetronuclear diatomic molecules, nitrogen and carbon monoxide. We present energy and angle-resolved maps of the Wigner delay time for single-photon valence ionization, and discuss the possibilities for experimental measurements.

  3. Genomic,Lipidomic,and Metabolomic Analysis ®CrossMark of Cyclooxygenase-null Cells:Eicosanoid Storm, Cross Talk, and Compensation by COX-1

    Institute of Scientific and Technical Information of China (English)

    Abul BMMK Islam; Mandar Dave; Sonia Amin; oderick V Jensen; Ashok R Amin

    2016-01-01

    The constitutively-expressed cyclooxygenase 1 (COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA) to prostaglandins (PGs). However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT) mice and COX-2"^' or COX-1'^" mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2-" > COX-1"^' > WT + IL-lp. COX-l /_ or COX-2'^" cells shared about 50% of the induced transcripts with WT cells treated with IL-lp, respectively. An interactive 4"anti-inflammatory, proinflammatory, and redox-activated” signature in the protein—protein interactome map was observed in COX-2'^' cells. The augmented COX-1 mRNA (in COX-2cells) was associated with the upregulation of mRNAs for glutathione 5-transferase (GST), superoxide dismutase (SOD), NAD(P)H dehydrogenase quinone 1 (NQOl),aryl hydrocarbon receptor (AhR), peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4), PGF1a, thromboxane B2 (TXB2), and PGF2a. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2-/- cells generated an ‘‘eicosanoid storm”. The genomic characteristics of COX-2-/- is similar to that of proinflammatory cells as observed in IL-1b induced WT cells. COX-1-/- and COX-2-/- cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

  4. A comparative immunohistochemical analysis of COX-2, p53, and Ki-67 expression in keratocystic odontogenic tumors

    NARCIS (Netherlands)

    Mendes, R.A.; Carvalho, J.F.C.; van der Waal, I.

    2011-01-01

    Objective. The aim of the present study was to investigate the association between the expression of cyclooxygenase-2 (COX-2) in keratocystic odontogenic tumors (KCOT) and more commonly used markers, such as p53 and Ki-67. Study design. Expression of cyclooxygenase-2 (COX-2) in 20 biopsy specimens o

  5. Deep RNA sequencing reveals the smallest known mitochondrial micro exon in animals: The placozoan cox1 single base pair exon.

    Science.gov (United States)

    Osigus, Hans-Jürgen; Eitel, Michael; Schierwater, Bernd

    2017-01-01

    The phylum Placozoa holds a key position for our understanding of the evolution of mitochondrial genomes in Metazoa. Placozoans possess large mitochondrial genomes which harbor several remarkable characteristics such as a fragmented cox1 gene and trans-splicing cox1 introns. A previous study also suggested the existence of cox1 mRNA editing in Trichoplax adhaerens, yet the only formally described species in the phylum Placozoa. We have analyzed RNA-seq data of the undescribed sister species, Placozoa sp. H2 ("Panama" clone), with special focus on the mitochondrial mRNA. While we did not find support for a previously postulated cox1 mRNA editing mechanism, we surprisingly found two independent transcripts representing intermediate cox1 mRNA splicing stages. Both transcripts consist of partial cox1 exon as well as overlapping intron fragments. The data suggest that the cox1 gene harbors a single base pair (cytosine) micro exon. Furthermore, conserved group I intron structures flank this unique micro exon also in other placozoans. We discuss the evolutionary origin of this micro exon in the context of a self-splicing intron gain in the cox1 gene of the last common ancestor of extant placozoans.

  6. 77 FR 72715 - Informal Entry Limit and Removal of a Formal Entry Requirement

    Science.gov (United States)

    2012-12-06

    ... increase of the informal entry limit is also consistent with one of the goals of the Beyond the Border... the policy seemed inconsistent with the recent Congressional decision to increase the ad valorem MPFs... this analysis, CBP cannot ascertain with any degree of certainty the specific monetary impacts...

  7. Entry, Descent, and Landing Operations Analysis for the Genesis Entry Capsule

    Science.gov (United States)

    Desai, Prasun N.; Lyons, Daniel T.

    2007-01-01

    On September 8, 2004, the Genesis spacecraft returned to Earth after spending 29 months about the sun-Earth libration point (L1) collecting solar wind particles. Four hours prior to Earth arrival, the sample return capsule containing the samples was released for entry and subsequent landing at the Utah Test and Training Range. This paper provides an overview of the entry, descent, and landing trajectory analysis that was performed during the mission operations phase leading up to final approach to Earth. The final orbit determination solution produced an inertial entry flight-path angle of -8.002 deg (which was the desired nominal value) with a 3-sigma error of +/-0.0274 deg (a third of the requirement). The operations effort accurately delivered the entry capsule to the desired landing site. The final landing location was 8.3 km from the target, and was well within the allowable landing area. Overall, the Earth approach operation procedures worked well and there were no issues (logistically or performance based) that arose. As a result, the process of targeting a capsule from deep space and accurately landing it on Earth was successfully demonstrated.

  8. The Hera Saturn Entry Probe Mission

    CERN Document Server

    Mousis, O; Spilker, T; Venkatapathy, E; Poncy, J; Frampton, R; Coustenis, A; Reh, K; Lebreton, J -P; Fletcher, L N; Hueso, R; Amato, M J; Colaprete, A; Ferri, F; Stam, D; Wurz, P; Atreya, S; Aslam, S; Banfield, D J; Calcutt, S; Fischer, G; Holland, A; Keller, C; Kessler, E; Leese, M; Levacher, P; Morse, A; Munoz, O; Renard, J -B; Sheridan, S; Schmider, F -X; Snik, F; Waite, J H; Bird, M; Cavalié, T; Deleuil, M; Fortney, J; Gautier, D; Guillot, T; Lunine, J I; Marty, B; Nixon, C; Orton, G S; Sanchez-Lavega, A

    2015-01-01

    The Hera Saturn entry probe mission is proposed as an M--class mission led by ESA with a contribution from NASA. It consists of one atmospheric probe to be sent into the atmosphere of Saturn, and a Carrier-Relay spacecraft. In this concept, the Hera probe is composed of ESA and NASA elements, and the Carrier-Relay Spacecraft is delivered by ESA. The probe is powered by batteries, and the Carrier-Relay Spacecraft is powered by solar panels and batteries. We anticipate two major subsystems to be supplied by the United States, either by direct procurement by ESA or by contribution from NASA: the solar electric power system (including solar arrays and the power management and distribution system), and the probe entry system (including the thermal protection shield and aeroshell). Hera is designed to perform in situ measurements of the chemical and isotopic compositions as well as the dynamics of Saturn's atmosphere using a single probe, with the goal of improving our understanding of the origin, formation, and ev...

  9. Mycobacteria entry and trafficking into endothelial cells.

    Science.gov (United States)

    Baltierra-Uribe, Shantal Lizbeth; García-Vásquez, Manuel de Jesús; Castrejón-Jiménez, Nayeli Shantal; Estrella-Piñón, Mayra Patricia; Luna-Herrera, Julieta; García-Pérez, Blanca Estela

    2014-09-01

    Endothelial cells are susceptible to infection by mycobacteria, but the endocytic mechanisms that mycobacteria exploit to enter host cells and their mechanisms of intracellular transport are completely unknown. Using pharmacological inhibitors, we determined that the internalization of Mycobacterium tuberculosis (MTB), Mycobacterium smegmatis (MSM), and Mycobacterium abscessus (MAB) is dependent on the cytoskeleton and is differentially inhibited by cytochalasin D, nocodazole, cycloheximide, wortmannin, and amiloride. Using confocal microscopy, we investigated their endosomal trafficking by analyzing Rab5, Rab7, LAMP-1, and cathepsin D. Our results suggest that MSM exploits macropinocytosis to enter endothelial cells and that the vacuoles containing these bacteria fuse with lysosomes. Conversely, the entry of MTB seems to depend on more than one endocytic route, and the observation that only a subset of the intracellular bacilli was associated with phagolysosomes suggests that these bacteria are able to inhibit endosomal maturation to persist intracellularly. The route of entry for MAB depends mainly on microtubules, which suggests that MAB uses a different trafficking pathway. However, MAB is also able to inhibit endosomal maturation and can replicate intracellularly. Together, these findings provide the first evidence that mycobacteria modulate proteins of host endothelial cells to enter and persist within these cells.

  10. Text Entry by Gazing and Smiling

    Directory of Open Access Journals (Sweden)

    Outi Tuisku

    2013-01-01

    Full Text Available Face Interface is a wearable prototype that combines the use of voluntary gaze direction and facial activations, for pointing and selecting objects on a computer screen, respectively. The aim was to investigate the functionality of the prototype for entering text. First, three on-screen keyboard layout designs were developed and tested (n=10 to find a layout that would be more suitable for text entry with the prototype than traditional QWERTY layout. The task was to enter one word ten times with each of the layouts by pointing letters with gaze and select them by smiling. Subjective ratings showed that a layout with large keys on the edge and small keys near the center of the keyboard was rated as the most enjoyable, clearest, and most functional. Second, using this layout, the aim of the second experiment (n=12 was to compare entering text with Face Interface to entering text with mouse. The results showed that text entry rate for Face Interface was 20 characters per minute (cpm and 27 cpm for the mouse. For Face Interface, keystrokes per character (KSPC value was 1.1 and minimum string distance (MSD error rate was 0.12. These values compare especially well with other similar techniques.

  11. Structural correlates of rotavirus cell entry.

    Directory of Open Access Journals (Sweden)

    Aliaa H Abdelhakim

    2014-09-01

    Full Text Available Cell entry by non-enveloped viruses requires translocation into the cytosol of a macromolecular complex--for double-strand RNA viruses, a complete subviral particle. We have used live-cell fluorescence imaging to follow rotavirus entry and penetration into the cytosol of its ∼ 700 Å inner capsid particle ("double-layered particle", DLP. We label with distinct fluorescent tags the DLP and each of the two outer-layer proteins and track the fates of each species as the particles bind and enter BSC-1 cells. Virions attach to their glycolipid receptors in the host cell membrane and rapidly become inaccessible to externally added agents; most particles that release their DLP into the cytosol have done so by ∼ 10 minutes, as detected by rapid diffusional motion of the DLP away from residual outer-layer proteins. Electron microscopy shows images of particles at various stages of engulfment into tightly fitting membrane invaginations, consistent with the interpretation that rotavirus particles drive their own uptake. Electron cryotomography of membrane-bound virions also shows closely wrapped membrane. Combined with high resolution structural information about the viral components, these observations suggest a molecular model for membrane disruption and DLP penetration.

  12. Imaging single retrovirus entry through alternative receptor isoforms and intermediates of virus-endosome fusion.

    Directory of Open Access Journals (Sweden)

    Naveen K Jha

    Full Text Available A large group of viruses rely on low pH to activate their fusion proteins that merge the viral envelope with an endosomal membrane, releasing the viral nucleocapsid. A critical barrier to understanding these events has been the lack of approaches to study virus-cell membrane fusion within acidic endosomes, the natural sites of virus nucleocapsid capsid entry into the cytosol. Here we have investigated these events using the highly tractable subgroup A avian sarcoma and leukosis virus envelope glycoprotein (EnvA-TVA receptor system. Through labeling EnvA pseudotyped viruses with a pH-sensitive fluorescent marker, we imaged their entry into mildly acidic compartments. We found that cells expressing the transmembrane receptor (TVA950 internalized the virus much faster than those expressing the GPI-anchored receptor isoform (TVA800. Surprisingly, TVA800 did not accelerate virus uptake compared to cells lacking the receptor. Subsequent steps of virus entry were visualized by incorporating a small viral content marker that was released into the cytosol as a result of fusion. EnvA-dependent fusion with TVA800-expressing cells occurred shortly after endocytosis and delivery into acidic endosomes, whereas fusion of viruses internalized through TVA950 was delayed. In the latter case, a relatively stable hemifusion-like intermediate preceded the fusion pore opening. The apparent size and stability of nascent fusion pores depended on the TVA isoforms and their expression levels, with TVA950 supporting more robust pores and a higher efficiency of infection compared to TVA800. These results demonstrate that surface receptor density and the intracellular trafficking pathway used are important determinants of efficient EnvA-mediated membrane fusion, and suggest that early fusion intermediates play a critical role in establishing low pH-dependent virus entry from within acidic endosomes.

  13. Leibniz Dynamics with Time Delay

    OpenAIRE

    Albu, I. D.; Opris, D.

    2005-01-01

    In this paper we show that several dynamical systems with time delay can be described as vector fields associated to smooth functions via a bracket of Leibniz structure. Some examples illustrate the theoretical considerations.

  14. Delays and networked control systems

    CERN Document Server

    Hetel, Laurentiu; Daafouz, Jamal; Johansson, Karl

    2016-01-01

    This edited monograph includes state-of-the-art contributions on continuous time dynamical networks with delays. The book is divided into four parts. The first part presents tools and methods for the analysis of time-delay systems with a particular attention on control problems of large scale or infinite-dimensional systems with delays. The second part of the book is dedicated to the use of time-delay models for the analysis and design of Networked Control Systems. The third part of the book focuses on the analysis and design of systems with asynchronous sampling intervals which occur in Networked Control Systems. The last part of the book exposes several contributions dealing with the design of cooperative control and observation laws for networked control systems. The target audience primarily comprises researchers and experts in the field of control theory, but the book may also be beneficial for graduate students. .

  15. A Kac CROW Delay Line

    CERN Document Server

    Sumetsky, M

    2013-01-01

    A low-loss CROW delay line with a weak inter-resonator coupling determined by the Kac matrix is dispersionless and can be easily impedance-matched by adjusting the coupling to the input/output waveguide.

  16. Analytic Development of a Reference Profile for the First Entry in a Skip Atmospheric Entry

    Science.gov (United States)

    Garcia-Llama, Eduardo

    2010-01-01

    This note shows that a feasible reference drag profile for the first entry portion of a skip entry can be generated as a polynomial expression of the velocity. The coefficients of that polynomial are found through the resolution of a system composed of m + 1 equations, where m is the degree of the drag polynomial. It has been shown that a minimum of five equations (m = 4) are required to establish the range and the initial and final conditions on velocity and flight path angle. It has been shown that at least one constraint on the trajectory can be imposed through the addition of one extra equation in the system, which must be accompanied by the increase in the degree of the drag polynomial. In order to simplify the resolution of the system of equations, the drag was considered as being a probability density function of the velocity, with the velocity as a distribution function of the drag. Combining this notion with the introduction of empirically derived constants, it has been shown that the system of equations required to generate the drag profile can be successfully reduced to a system of linear algebraic equations. For completeness, the resulting drag profiles have been flown using the feedback linearization method of differential geometric control as a guidance law with the error dynamics of a second order homogeneous equation in the form of a damped oscillator. Satisfactory results were achieved when the gains in the error dynamics were changed at a certain point along the trajectory that is dependent on the velocity and the curvature of the drag as a function of the velocity. Future work should study the capacity to update the drag profile in flight when dispersions are introduced. Also, future studies should attempt to link the first entry, as presented and controlled in this note, with a more standard control concept for the second entry, such as the Apollo entry guidance, to try to assess the overall skip entry performance. A guidance law that includes

  17. Systematics in delayed neutron yields

    Energy Technology Data Exchange (ETDEWEB)

    Ohsawa, Takaaki [Kinki Univ., Higashi-Osaka, Osaka (Japan). Atomic Energy Research Inst.

    1998-03-01

    An attempt was made to reproduce the systematic trend observed in the delayed neutron yields for actinides on the basis of the five-Gaussian representation of the fission yield together with available data sets for delayed neutron emission probability. It was found that systematic decrease in DNY for heavier actinides is mainly due to decrease of fission yields of precursors in the lighter side of the light fragment region. (author)

  18. Time Delay in Molecular Photoionization

    OpenAIRE

    Hockett, P.; Frumker, E.; Villeneuve, D M; Corkum, P. B.

    2015-01-01

    Time-delays in the photoionization of molecules are investigated. As compared to atomic ionization, the time-delays expected from molecular ionization present a much richer phenomenon, with a strong spatial dependence due to the anisotropic nature of the molecular scattering potential. We investigate this from a scattering theory perspective, and make use of molecular photoionization calculations to examine this effect in representative homonuclear and hetronuclear diatomic molecules, nitroge...

  19. Measuring information-transfer delays.

    Directory of Open Access Journals (Sweden)

    Michael Wibral

    Full Text Available In complex networks such as gene networks, traffic systems or brain circuits it is important to understand how long it takes for the different parts of the network to effectively influence one another. In the brain, for example, axonal delays between brain areas can amount to several tens of milliseconds, adding an intrinsic component to any timing-based processing of information. Inferring neural interaction delays is thus needed to interpret the information transfer revealed by any analysis of directed interactions across brain structures. However, a robust estimation of interaction delays from neural activity faces several challenges if modeling assumptions on interaction mechanisms are wrong or cannot be made. Here, we propose a robust estimator for neuronal interaction delays rooted in an information-theoretic framework, which allows a model-free exploration of interactions. In particular, we extend transfer entropy to account for delayed source-target interactions, while crucially retaining the conditioning on the embedded target state at the immediately previous time step. We prove that this particular extension is indeed guaranteed to identify interaction delays between two coupled systems and is the only relevant option in keeping with Wiener's principle of causality. We demonstrate the performance of our approach in detecting interaction delays on finite data by numerical simulations of stochastic and deterministic processes, as well as on local field potential recordings. We also show the ability of the extended transfer entropy to detect the presence of multiple delays, as well as feedback loops. While evaluated on neuroscience data, we expect the estimator to be useful in other fields dealing with network dynamics.

  20. The pharmacologic inhibition of the xc- antioxidant system improves the antitumor efficacy of COX inhibitors in the in vivo model of 3-MCA tumorigenesis.

    Science.gov (United States)

    Balza, Enrica; Castellani, Patrizia; Delfino, Laura; Truini, Mauro; Rubartelli, Anna

    2013-03-01

    The chemopreventive and therapeutic efficacy of the cyclooxygenase (COX) inhibitor ibuprofen (IB) and of sulfasalazine (SASP), a drug that targets the antioxidant xc- system, were exploited in the experimental model of 3-methylcholantrene (3-MCA)-induced mouse sarcoma. The chemopreventive treatments gave unsatisfactory results because administration of IB one day after the 3-MCA injection only slightly delayed the tumor development, whereas SASP dispensed under the same conditions resulted in accelerated tumorigenesis. Similarly, the therapeutic treatment with either drug, administrated daily from the tumor detection, decreased the proliferation rate of tumor cells and increased the survival of treated mice only at a low extent. Remarkably, the combined chemopreventive treatment with IB and therapeutic treatment with SASP displayed a better efficacy, with strong delay of sarcoma growth, reduced tumor size and increased survival of treated mice. The two drugs target not only tumor cells but also tumor-associated macrophages that were dramatically decreased in the tumor infiltrate of mice subjected to the combined treatment. The synergistic effects of the association between a broad anti-inflammatory compound, such as IB, and a redox-directed drug, such as SASP, shed new light in the role of inflammation and of the redox response in chemical tumorigenesis and point to the combined chemopreventive plus therapeutic treatment with IB and SASP as a promising novel approach for antitumor therapy.

  1. Basin stability in delayed dynamics

    Science.gov (United States)

    Leng, Siyang; Lin, Wei; Kurths, Jürgen

    2016-02-01

    Basin stability (BS) is a universal concept for complex systems studies, which focuses on the volume of the basin of attraction instead of the traditional linearization-based approach. It has a lot of applications in real-world systems especially in dynamical systems with a phenomenon of multi-stability, which is even more ubiquitous in delayed dynamics such as the firing neurons, the climatological processes, and the power grids. Due to the infinite dimensional property of the space for the initial values, how to properly define the basin’s volume for delayed dynamics remains a fundamental problem. We propose here a technique which projects the infinite dimensional initial state space to a finite-dimensional Euclidean space by expanding the initial function along with different orthogonal or nonorthogonal basis. A generalized concept of basin’s volume in delayed dynamics and a highly practicable calculating algorithm with a cross-validation procedure are provided to numerically estimate the basin of attraction in delayed dynamics. We show potential applicabilities of this approach by applying it to study several representative systems of biological or/and physical significance, including the delayed Hopfield neuronal model with multistability and delayed complex networks with synchronization dynamics.

  2. Orthopoxvirus species and strain differences in cell entry

    Energy Technology Data Exchange (ETDEWEB)

    Bengali, Zain; Satheshkumar, P.S. [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3210 (United States); Moss, Bernard, E-mail: bmoss@nih.gov [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3210 (United States)

    2012-11-25

    Vaccinia virus (VACV) enters cells by a low pH endosomal route or by direct fusion with the plasma membrane. We previously found differences in entry properties of several VACV strains: entry of WR was enhanced by low pH, reduced by bafilomycin A1 and relatively unaffected by heparin, whereas entry of IHD-J, Copenhagen and Elstree were oppositely affected. Since binding and entry modes may have been selected by specific conditions of in vitro propagation, we now examined the properties of three distinct, recently isolated cowpox viruses and a monkeypox virus as well as additional VACV and cowpox virus strains. The recent isolates were more similar to WR than to other VACV strains, underscoring the biological importance of endosomal entry by orthopoxviruses. Sequence comparisons, gene deletions and gene swapping experiments indicated that viral determinants, other than or in addition to the A26 and A25 'fusion-suppressor' proteins, impact entry properties.

  3. Mid-L/D Lifting Body Entry Demise Analysis

    Science.gov (United States)

    Ling, Lisa

    2017-01-01

    The mid-lift-to-drag ratio (mid-L/D) lifting body is a fully autonomous spacecraft under design at NASA for enabling a rapid return of scientific payloads from the International Space Station (ISS). For contingency planning and risk assessment for the Earth-return trajectory, an entry demise analysis was performed to examine three potential failure scenarios: (1) nominal entry interface conditions with loss of control, (2) controlled entry at maximum flight path angle, and (3) controlled entry at minimum flight path angle. The objectives of the analysis were to predict the spacecraft breakup sequence and timeline, determine debris survival, and calculate the debris dispersion footprint. Sensitivity analysis was also performed to determine the effect of the initial pitch rate on the spacecraft stability and breakup during the entry. This report describes the mid-L/D lifting body and presents the results of the entry demise and sensitivity analyses.

  4. Effects of the estrous cycle, pregnancy and interferon tau on expression of cyclooxygenase two (COX-2 in ovine endometrium

    Directory of Open Access Journals (Sweden)

    Bazer Fuller W

    2003-08-01

    Full Text Available Abstract In sheep, the uterus produces luteolytic pulses of prostaglandin F2α (PGF on Days 15 to 16 of estrous cycle to regress the corpus luteum (CL. These PGF pulses are produced by the endometrial lumenal epithelium (LE and superficial ductal glandular epithelium (sGE in response to binding of pituitary and/or luteal oxytocin to oxytocin receptors (OTR and liberation of arachidonic acid, the precursor of PGF. Cyclooxygenase-one (COX-1 and COX-2 are rate-limiting enzymes in PGF synthesis, and COX-2 is the major form expressed in ovine endometrium. During pregnancy recognition, interferon tau (IFNτ, produced by the conceptus trophectoderm, acts in a paracrine manner to suppress development of the endometrial epithelial luteolytic mechanism by inhibiting transcription of estrogen receptor α (ERα (directly and OTR (indirectly genes. Conflicting studies indicate that IFNτ increases, decreases or has no effect on COX-2 expression in bovine and ovine endometrial cells. In Study One, COX-2 mRNA and protein were detected solely in endometrial LE and sGE of both cyclic and pregnant ewes. During the estrous cycle, COX-2 expression increased from Days 10 to 12 and then decreased to Day 16. During early pregnancy, COX-2 expression increased from Days 10 to 12 and remained higher than in cyclic ewes. In Study Two, intrauterine infusion of recombinant ovine IFNτ in cyclic ewes from Days 11 to 16 post-estrus did not affect COX-2 expression in the endometrial epithelium. These results clearly indicate that IFNτ has no effect on expression of the COX-2 gene in the ovine endometrium. Therefore, antiluteolytic effects of IFNτ are to inhibit ERα and OTR gene transcription, thereby preventing endometrial production of luteolytic pulses of PGF. Indeed, expression of COX-2 in the endometrial epithelia as well as conceptus is likely to have a beneficial regulatory role in implantation and development of the conceptus.

  5. The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2 with aspirin insensitivity: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhiyuan Weng

    Full Text Available OBJECTIVE: Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643 from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2 with aspirin insensitivity via a meta-analysis. METHODS AND RESULTS: In total, there were 4 (353/595, 6 (344/698, 10 (588/878 and 7 (209/676 articles (patients/controls qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2. The risk estimate was expressed as odds ratio (OR and 95% confidence interval (95% CI. Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44-2.41; <0.0005 and rs1126643 (2.37; 1.44-3.89; 0.001 with aspirin insensitivity under allelic model. In subgroup analyses, the risk estimate for rs1126643 was greatly potentiated among patients with aspirin semi-resistance relative to those with aspirin resistance, especially under dominant model (aspirin semi-resistance: 5.44; 1.42-20.83; 0.013 versus aspirin resistance: 1.96; 1.07-3.6; 0.03. Further grouping articles by ethnicity observed a stronger prediction of all, but rs20417, examined polymorphisms for aspirin insensitivity in Chinese than in Caucasians. Finally, meta-regression analyses observed that the differences in percentage of coronary artery disease (P = 0.034 and averaged platelet numbers (P = 0.012 between two groups explained a large part of heterogeneity for rs20417 and rs1126643, respectively. CONCLUSION: Our findings provide strong evidence that COX-2 and ITGA2 genetic defects might increase the risk of having aspirin insensitivity, especially for aspirin semi-resistance and in Chinese populations.

  6. Potential of a COX-2 inhibitor in lowering chemotherapy-induced neutropenia%Potential of a COX-2 inhibitor in lowering chemotherapy induced neutropenia

    Institute of Scientific and Technical Information of China (English)

    Louis Wing-Cheong Chow; Adrian Yun-San Yip; Eleanor Yuen-Yuen Ong; Chi-Kei Lam; Masakazu Toi

    2010-01-01

    Objective This study was initially designed to evaluate the effect of celecoxib on the regimen of 5 fluorouracil, epirubicin, and cyclophosphamide (FEC) combination, followed by docetaxel (T) in neoadjuvant setting. An unplanned preliminary review on safety was conducted after a halt of the study due to the concerned potential cardiovascular risk of using COX 2 inhibitors.Methods We studied 23 consecutive cases of operable breast cancer having received four cycles of FEC(500 mg/m2, 100 mg/m2, 500 mg/m2) followed by four cycles of T(100 mg/m2) with concurrent celecoxib (400 mg twice daily) (group A) or same chemotherapy regimen but without concurrent celecoxib (group B). These combined chemotherapies were administered every 3 weeks. The Chi square test or Fisher's exact test were used to assess the difference in incidence of limiting hematological toxicites between groups. Results 23 patients (group A: n=12; group B, n=11) received a total of 183 out of 184 planned treatment cycles; one (4%, 1/23) of them omitted the fourth cycle of FEC owing to repeated incidences of febrile neutropenia. Received dose intensity (RDI) for FEC in group A (90%±11%) was higher than that in group B (80%±8%) while RDI for T was similar between group A (93%±8%) and group B (96%±9%). Of the first 91 treatment cycles of FEC, limiting hematological toxicity, severe neutropenia including febrile neutropenia, was significantly different between group A and B [(10.4%, 5/48) vs.( 32.6%, 14/43), P=0.009]. Other toxicities commonly observed in chemotherapy receiving patients were manageable. Conclusions Neoadjuvant use of FEC followed by T with concurrent celecoxib appeared to be safe for treatment of operable invasive breast cancer. The observed lower incidence of chemotherapy induced neutropenia is possibly contributed by the administration of COX inhibitor. We believe that further investigation might provide more evidence on the use of COX 2 inhibitors in breast cancer.

  7. The measurement of radon working levels at a mineral separation pilot plant in Cox's Bazar, Bangladesh.

    Science.gov (United States)

    Hamid Khan, M A; Chowdhury, M S

    2003-10-01

    Beach Sand Exploitation Centre at Cox's Bazar, Bangladesh, produces commercial grade concentrations of magnetite, ilmenite, zircon, etc., from the high-grade accumulations available along the beach and foredune of Cox's Bazar. Solid state nuclear track detectors (CR-39 foils) were used to determine indoor radon concentration of radioactive mineral sands and the technologically enhanced radiation level inside the pilot plant of the Centre. It is found that the concentrations at processed mineral stock areas are high, and the maximum concentration was found to be 2,103 +/- 331 Bq m(-3) (0.23 +/- 0.03 WL). The indoor concentration of radon and its decay products in the raw sand stock area and at other locations was in the range of 116 +/- 27 Bq m(-3) (0.03 +/- 0.003 WL) to 2,042 +/- 233 Bq m(-3) (0.22 +/- 0.03 WL).

  8. INHOMOGENEITY IN SPATIAL COX POINT PROCESSES – LOCATION DEPENDENT THINNING IS NOT THE ONLY OPTION

    Directory of Open Access Journals (Sweden)

    Michaela Prokešová

    2010-11-01

    Full Text Available In the literature on point processes the by far most popular option for introducing inhomogeneity into a point process model is the location dependent thinning (resulting in a second-order intensity-reweighted stationary point process. This produces a very tractable model and there are several fast estimation procedures available. Nevertheless, this model dilutes the interaction (or the geometrical structure of the original homogeneous model in a special way. When concerning the Markov point processes several alternative inhomogeneous models were suggested and investigated in the literature. But it is not so for the Cox point processes, the canonical models for clustered point patterns. In the contribution we discuss several other options how to define inhomogeneous Cox point process models that result in point patterns with different types of geometric structure. We further investigate the possible parameter estimation procedures for such models.

  9. Analysis of a genetically structured variance heterogeneity model using the Box-Cox transformation

    DEFF Research Database (Denmark)

    Yang, Ye; Christensen, Ole Fredslund; Sorensen, Daniel

    2011-01-01

    of the marginal distribution of the data. To investigate how the scale of measurement affects inferences, the genetically structured heterogeneous variance model is extended to accommodate the family of Box–Cox transformations. Litter size data in rabbits and pigs that had previously been analysed...... in the untransformed scale were reanalysed in a scale equal to the mode of the marginal posterior distribution of the Box–Cox parameter. In the rabbit data, the statistical evidence for a genetic component at the level of the environmental variance is considerably weaker than that resulting from an analysis...... in the original metric. In the pig data, the statistical evidence is stronger, but the coefficient of correlation between additive genetic effects affecting mean and variance changes sign, compared to the results in the untransformed scale. The study confirms that inferences on variances can be strongly affected...

  10. Maximum Likelihood Inference for the Cox Regression Model with Applications to Missing Covariates.

    Science.gov (United States)

    Chen, Ming-Hui; Ibrahim, Joseph G; Shao, Qi-Man

    2009-10-01

    In this paper, we carry out an in-depth theoretical investigation for existence of maximum likelihood estimates for the Cox model (Cox, 1972, 1975) both in the full data setting as well as in the presence of missing covariate data. The main motivation for this work arises from missing data problems, where models can easily become difficult to estimate with certain missing data configurations or large missing data fractions. We establish necessary and sufficient conditions for existence of the maximum partial likelihood estimate (MPLE) for completely observed data (i.e., no missing data) settings as well as sufficient conditions for existence of the maximum likelihood estimate (MLE) for survival data with missing covariates via a profile likelihood method. Several theorems are given to establish these conditions. A real dataset from a cancer clinical trial is presented to further illustrate the proposed methodology.

  11. Skin tight: macrophage-specific COX-2 induction links salt handling in kidney and skin.

    Science.gov (United States)

    Stegbauer, Johannes; Coffman, Thomas M

    2015-11-02

    The relationship between dietary salt intake and the associated risk of hypertension and cardiovascular disease is an important public health concern. In this issue of the JCI, a study by Zhang and associates shows that consumption of a high-sodium diet induces expression of cyclooxygenase-2 (COX-2) in macrophages, resulting in enhanced levels of prostaglandin E2 (PGE2), autocrine activation of the macrophage E-prostanoid 4 (EP4) receptor, and subsequent triggering of parallel pathways in the kidney and in skin that help dispose of excess sodium. The authors found that blockade or genetic elimination of the COX-2/PGE2/EP4 receptor pathway in hematopoietic cells causes salt-sensitive hypertension in mice. These studies illuminate an unexpected central role for the macrophage in coordinating homeostatic responses to dietary salt intake and suggest a complex pathophysiology for hypertension associated with NSAID use.

  12. BFLCRM: A BAYESIAN FUNCTIONAL LINEAR COX REGRESSION MODEL FOR PREDICTING TIME TO CONVERSION TO ALZHEIMER'S DISEASE.

    Science.gov (United States)

    Lee, Eunjee; Zhu, Hongtu; Kong, Dehan; Wang, Yalin; Giovanello, Kelly Sullivan; Ibrahim, Joseph G

    2015-12-01

    The aim of this paper is to develop a Bayesian functional linear Cox regression model (BFLCRM) with both functional and scalar covariates. This new development is motivated by establishing the likelihood of conversion to Alzheimer's disease (AD) in 346 patients with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) and the early markers of conversion. These 346 MCI patients were followed over 48 months, with 161 MCI participants progressing to AD at 48 months. The functional linear Cox regression model was used to establish that functional covariates including hippocampus surface morphology and scalar covariates including brain MRI volumes, cognitive performance (ADAS-Cog), and APOE status can accurately predict time to onset of AD. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. A simulation study is performed to evaluate the finite sample performance of BFLCRM.

  13. Aerobic oxidation of hydroxymethylfurfural and furfural by using heterogeneous Cox Oy -N@C catalysts.

    Science.gov (United States)

    Deng, Jin; Song, Hai-Jie; Cui, Min-Shu; Du, Yi-Ping; Fu, Yao

    2014-12-01

    2,5-Furandicarboxylic acid (FDCA) is considered to be a promising replacement for terephthalic acid since they share similar structures and properties. In contrast to FDCA, 2,5-furandicarboxylic acid methyl (FDCAM) has properties that allow it to be easily purified. In this work, we reported an oxidative esterification of 5-hydroxymethylfurfural (HMF) and furfural to prepare corresponding esters over Cox Oy -N@C catalysts using O2 as benign oxidant. High yield and selectivity of FDCAM and methyl 2-furoate were obtained under optimized conditions. Factors which influenced the product distribution were examined thoroughly. The Cox Oy -N@C catalysts were recycled five times and no significant loss of activity was detected. Characterization of the catalysts could explain such phenomena. Using XPS and TGA, we made a thorough investigation of the effects of ligand and pyrolysis temperature on catalyst activity.

  14. Aspirin inhibits hepatitis C virus entry by downregulating claudin-1.

    Science.gov (United States)

    Yin, P; Zhang, L

    2016-01-01

    Aspirin has previously been reported to inhibit hepatitis C virus (HCV) replication. The aim of this study was to investigate whether aspirin is involved in blocking HCV entry. We found that aspirin inhibits the entry of HCVpp and infectious HCV. The level of claudin-1, an HCV receptor, is reduced by aspirin. Our results extend the anti-HCV effect of aspirin to the HCV entry step and further reinforce the anti-HCV role of aspirin.

  15. DWCox: A density-weighted Cox model for outlier-robust prediction of prostate cancer survival

    OpenAIRE

    Jinfeng Xiao; Sheng Wang; Jingbo Shang; Henry Lin; Doris Xin; Xiang Ren; Jiawei Han; Jian Peng

    2016-01-01

    Reliable predictions on the risk and survival time of prostate cancer patients based on their clinical records can help guide their treatment and provide hints about the disease mechanism. The Cox regression is currently a commonly accepted approach for such tasks in clinical applications. More complex methods, like ensemble approaches, have the potential of reaching better prediction accuracy at the cost of increased training difficulty and worse result interpretability. Better performance o...

  16. Reduction in cancer risk by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors

    OpenAIRE

    Harris, Randall; Beebe,; Alshafie,

    2012-01-01

    Randall E Harris,1 Joanne Beebe,1 Galal A Alshafie21College of Medicine and College of Public Health, 2College of Pharmacy, The Ohio State University, Columbus, Ohio, USAAbstract: We conducted a series of epidemiologic studies to evaluate the chemopreventive effects of aspirin, ibuprofen, and selective cyxlooxygenase-2 (COX-2) inhibitors (coxibs) against cancers of the breast, colon, prostate, and lung. Composite results across all four cancer sites revealed that regular intake of 325 mg aspi...

  17. Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity.

    Science.gov (United States)

    Willenberg, Ina; Meschede, Anna K; Gueler, Faikah; Jang, Mi-Sun; Shushakova, Nelli; Schebb, Nils Helge

    2015-01-01

    Epidemiologic studies show a correlation between the dietary intake of food polyphenols and beneficial health effects. Several in vitro studies indicate that the anti-inflammatory potential of polyphenols is, at least in part, mediated by a modulation of the enzymes of the arachidonic acid cascade, such as the prostaglandin forming cyclooxygenases (COXs). Evidence that this mode of action can be transferred to the situation in vivo is scarce. This study characterized effects of a subset of polyphenols on COX-2 expression and activity in vitro and compared the potency with known drugs. Next, the in vivo relevance of the observed in vitro effects was tested. Enzyme assays and incubations of polyphenols with the cancer cell line HCA-7 and lipopolysaccharide (LPS) stimulated primary monocytes support the hypothesis that polyphenols can effect COX-2 expression and activity in vitro. The effects were most pronounced in the monocyte assay for wogonin, apigenin, resveratrol and genistein with IC50 values of 1.5 μM, 2.6 μM, 2.8 μM and 7.4 μM. However, these values are 100- to 1000-fold higher in comparison to those of the known pharmaceuticals celecoxib, indomethacin and dexamethasone. In an animal model of LPS induced sepsis, pretreatment with polyphenols (i. p. 100 mg/kg bw) did not result in decreased plasma or tissue prostaglandin levels, whereas the positive control celecoxib effectively attenuated LPS induced prostaglandin formation. These data suggest that despite the moderate potency in vitro, an effect of polyphenols on COX-2 during acute inflammation is unlikely, even if a high dose of polyphenols is ingested.

  18. Skin tight: macrophage-specific COX-2 induction links salt handling in kidney and skin

    OpenAIRE

    Stegbauer, Johannes; Coffman, Thomas M.

    2015-01-01

    The relationship between dietary salt intake and the associated risk of hypertension and cardiovascular disease is an important public health concern. In this issue of the JCI, a study by Zhang and associates shows that consumption of a high-sodium diet induces expression of cyclooxygenase-2 (COX-2) in macrophages, resulting in enhanced levels of prostaglandin E2 (PGE2), autocrine activation of the macrophage E-prostanoid 4 (EP4) receptor, and subsequent triggering of parallel pathways in the...

  19. On Model Specification and Selection of the Cox Proportional Hazards Model*

    OpenAIRE

    Lin, Chen-Yen; Halabi, Susan

    2013-01-01

    Prognosis plays a pivotal role in patient management and trial design. A useful prognostic model should correctly identify important risk factors and estimate their effects. In this article, we discuss several challenges in selecting prognostic factors and estimating their effects using the Cox proportional hazards model. Although a flexible semiparametric form, the Cox’s model is not entirely exempt from model misspecification. To minimize possible misspecification, instead of imposing tradi...

  20. COxSwAIN: Compressive Sensing for Advanced Imaging and Navigation

    Science.gov (United States)

    Kurwitz, Richard; Pulley, Marina; LaFerney, Nathan; Munoz, Carlos

    2015-01-01

    The COxSwAIN project focuses on building an image and video compression scheme that can be implemented in a small or low-power satellite. To do this, we used Compressive Sensing, where the compression is performed by matrix multiplications on the satellite and reconstructed on the ground. Our paper explains our methodology and demonstrates the results of the scheme, being able to achieve high quality image compression that is robust to noise and corruption.