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In models which allow for random jumps, statistical tests for jumps are typically non-standard and nuisance parameter-dependent. To handle these problems, we combine bounds and MonteCarlo (MC) simulation techniques to derive nuisance-parameter-free bounds and obtain level-exact p-values for a wide class of processes with random jumps and time varying heteroskedasticity. When identified nuisance parameters are absent under the null, we show that MC p-values are finite sample, level-exact. To illustrate this easy-to-implement approach, we analyze the spot prices of four commodities (aluminium, copper, gold and lead) and the closing prices of four technology stocks (Intel, Microsoft, Oracle and Sun). We find significant jumps in these time series. Our approach can easily be extended to other nuisance-parameter dependent tests. (C) 2003 Elsevier B.V. All rights reserved.

In order to adequately simulate the behavior of a Hall-Heroult electrolysis ceil a finite element model must take into account the properties of each material forming the cell structure and those contained in it. However, there is some lack of full knowledge of the mechanical behavior of these materials, e.g., the long term viscoelastic (creep/relaxation) behavior of the carbon cathode. In this present paper, a three-dimensional viscoelastic model is devised and proposed, being ready to be implemented in a finite element code. This 3D viscoelastic model was developed from the thermodynamics of irreversible processes, where the selection of the model's internal variables was based on a phenomenological approach. The model has been developed at a particular reference state; therefore, the model parameters are represented by constant constitutive tensors. The model's particular parameters were identified for three different types of cathode carbon, i.e., semigraphitic, graphitic, and graphitized. Keywords: graphite, cathodes, rheology, mechanical properties, viscoelasticity

Vasoactive eicosanoids such as thromboxane (TX) A 2 and F 2 -isoprostanes (F 2 -isoPs) were shown to be increased in the preeclamptic placenta. Only one of the 64 possible isomers of F 2 -isoPs derived from the oxidation of arachidonic acid was investigated in the placenta so far. F 2 -isoPs are released from membrane phospholipids by phospholipases A 2 (PLA 2 ) and were shown to act on the TXA 2 receptor (TBXA2R). However, the PLA 2 deregulated in preeclampsia (PE) remains to be determined. In this study, we analyzed the concentrations of six isomers of F 2 -isoPs; 8-iso-PGF 2α , 8-iso-15(R)-PGF 2α , 15(R)-PGF 2α , iPF 2α -IV, iPF 2α -VI, 5-iPF 2α -VI and the concentrations of the stable metabolites of TXA 2 , TXB 2, by high performance liquid chromatography coupled with tandem mass spectrometry in placentas of PE (n = 17) and normotensive (n = 15) pregnancies according to the biopsy site: peri-insertion or periphery. In the same biopsies, relative mRNA expression of PLA2G2A, PLA2G4A, PLA2G5, PLA2G7, the PLA2 receptor (PLA2R1), the TXA 2 synthase and TBXAR2 were measured by quantitative RT-PCR. We observed similar concentrations of total F 2 -isoP isomers between groups whereas higher concentrations (>40%) of free F 2 -isoP were observed for all isomers (p ≤ 0.033) in PE than normotensive controls. As expected, we also observed higher placental concentrations of TXB 2 in PE (p = 0.005). Interestingly, we concomitantly found higher mRNA expression of secretory PLA2G2A (p = 0.010), PLA2G5 (p = 0.038) and TBXA2R (p = 0.023) in PE than normotensive placentas. In sum, deregulated PLA 2 could potentially be implicated in freeing F 2 -isoP which could participate in local hypertension observed in the PE placenta through the TX pathway., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Preeclampsia (PE) was shown to affect the placental content and the transfer of polyunsaturated fatty acids (PUFA) to the fetus. Plasmalogens, a type of phospholipids with a vinyl-ether link at the sn-1 position, play an antioxidant role and are specifically enriched in PUFA at the sn-2 position. In this study, we characterized plasmalogen-derived dimethyl acetal (DMA) fatty acid derivatives, 16:0 DMA, 18:0 DMA, 9c-/11c-18:1 DMA and PUFA in the placenta of normotensive (n = 20) and PE (n = 20) pregnancies, according to the sampling site: peri-insertion or periphery. Phospholipid fatty acids from the placenta and maternal erythrocytes were identified by gas chromatography mass spectrometry and quantified by flame ionization detection. We found elevated total DMA in the PE placenta by 18% when compared to normotensive controls (p = 0.026). Moreover, the 16:0 DMA account for more than 55% of DMA fatty acids measured in the placenta, and its level is significantly higher in PE than controls (p = 0.018). Also, we found elevated placental PUFA, 20:5(n-3), 22:5(n-3) and a low level of 20:4(n-3) in PE compared to controls. Placental DMA was highly correlated with n-6 and n-3 PUFA in both, normotensive and PE pregnancies. In sum, elevated DMA fatty acids in the PE placenta could be an indirect defensive mechanism against oxidative stress and poor placental fatty acid transfer in PE., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Antioxidants may be beneficial additives to synthetic culture media because these well defined media lack serum or other macromolecules that serve as reactive oxygen species scavengers. In this study, three separate experiments were performed to determine the effects of antioxidants on the development of oocytes to the morula and blastocyst stage when added during in vitro maturation (IVM) of bovine oocytes, during in vitro fertilization (IVF), and during embryo culture for the first 72 h of the development period. Bovine oocytes were matured, fertilized (under 20% O(2)), and embryos were cultured (under 7% O(2)) in defined conditioned medium in vitro with or without supplementation with the antioxidant cysteine, N-acetyl-L-cysteine (NAC), catalase and superoxide dismutase (SOD). Significant improvements in the proportion of oocytes undergoing morula and blastocyst development (33.3% versus 20.3%, P<0.05) were achieved when cysteine (0.6 mM) was added to the maturation medium as compared to control medium without antioxidant supplementation. However, the addition of NAC (0.6mM), catalase (5 or 127 U/ml) or SOD (10 or 1000 U/ml) to the maturation medium did not improve the proportion of oocytes undergoing morula and blastocyst development. During the IVF period, addition of antioxidants (cysteine or NAC 0.6mM, catalase 127U/ml, SOD 100U/ml) significantly reduced the subsequent rate of bovine embryo development to the morula and blastocyst stage (P<0.05). In a defined medium for embryo culture (7% O(2)), the addition of cysteine improved the development of bovine embryos while NAC, catalase and SOD had no positive effect on embryonic development. Our study showed that medium supplementation with cysteine during IVM and in vitro culture (IVC) improved the rate of bovine embryo development, in contrast to extracellular antioxidants like catalase and SOD that caused no improvement.

Little is known about cell-cycle checkpoint activation by oxidative stress in mammalian cells. The effects of hyperoxia on cell-cycle progression were investigated in asynchronous human T47D-H3 cells, which contain mutated p53 and fail to arrest at G1/S in response to DNA damage. Hyperoxic exposure (95% O(2), 40-64 h) induced an S-phase arrest associated with acute inhibition of Cdk2 activity and DNA synthesis. In contrast, exit from G2/M was not inhibited in these cells. After 40 h of hyperoxia, these effects were partially reversible during recovery under normoxic conditions. The inhibition of Cdk2 activity was not due to degradation of Cdk2, cyclin E or A, nor impairment of Cdk2 complex formation with cyclin A or E and p21(Cip1). The loss of Cdk2 activity occurred in the absence of induction and recruitment of cdk inhibitor p21(Cip1) or p27(Kip1) in cyclin A/Cdk2 or cyclin E/Cdk2 complexes. In contrast, Cdk2 inhibition was associated with increased Cdk2-Tyr15 phosphorylation, increased E2F-1 recruitment, and decreased PCNA contents in Cdk2 complexes. The latter results indicate a p21(Cip1)/p27(Kip1)-independent mechanism of S-phase checkpoint activation in the hyperoxic T47D cell model investigated., (Copyright 2000 Academic Press.)

Growing evidence suggests that the generation of reactive oxygen species (ROS) and their detoxification by antioxidants plays a very important role in fertility. However, the relationship between the level of antioxidants in spermatozoa and the decreased fecundity following a freeze/thaw cycle remains poorly understood. We assessed the activities of antioxidant enzymes such as catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD), and levels of reduced/oxidized glutathione (GSH/GSSG) in bovine semen. Sperm cells were isolated using a Percoll gradient to avoid contamination from seminal plasma, cellular debris, and other cell types. We found that bovine spermatozoa are poorly adapted to metabolize the toxic hydrogen peroxide (H(2)O(2)). Indeed, very low levels of GPx and an absence of catalase were observed. We also studied the effect of freezing and thawing bovine spermatozoa in a egg yolk-Tris-glycerol extender (EYTG). Cryopreservation significantly reduced sperm GSH levels by 78% and SOD activity by 50%. We also investigated whether the decrease in GSH level could be linked to oxidative metabolism and found that a greater reduction in intracellular GSH level occurred when fresh sperm cells were incubated in EYTG for 6 hr at 38.5 degrees C under aerobic conditions than when incubated under restricted oxygen availability. Our results strongly suggest the involvement of an oxidative stress during a freeze/thaw cycle and are consistent with the hypothesis that ROS generated during such a cycle are detrimental to sperm function., (Copyright 2000 Wiley-Liss, Inc.)

Reactive oxygen species formation is strongly suspected to play a role in multistep carcinogenesis, notably in tumor promotion. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces peroxide production, oxidative damage to DNA and inflammation in mouse skin. TPA is also known to cause a decrease in the activity of several antioxidant enzymes including glutathione peroxidases (GPx). The observation that several anti-oxidants can inhibit TPA-mediated tumor promotion suggests that a decline in GPx activity could contribute to tumor promotion. We report here the effects of TPA on GPx activity in the skin of transgenic GPx mice that contain human GPx-1 transgenes under the regulation of a metallothionein IIA promoter. As expected, no significant difference in basal level of skin GPx activity was detected in the 3 lines of tg-MT-GPx mice investigated compared with non-transgenic controls. A single topical application of TPA induced gradually, over 20 hr, a small but detectable increase in GPx mRNA and protein levels in skin of non-transgenic mice and a contrasting decrease in both selenium-dependent and selenium-independent GPx activity. The extent of GPx induction was more pronounced in transgenic mice, and in contrast with non-transgenic mice, no significant loss of GPx activity was observed in the TPA-treated skin of these mice. Transgenic mice may, therefore, offer a novel model suitable to assess the role of GPx-1 in skin carcinogenesis, without the potential disadvantage of abnormally high levels of GPx activity produced constitutively in other transgenic models.