26 research outputs found

    Search for spontaneous muon emission from lead nuclei

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    We describe a possible search for muonic radioactivity from lead nuclei using the base elements ("bricks" composed by lead and nuclear emulsion sheets) of the long-baseline OPERA neutrino experiment. We present the results of a Monte Carlo simulation concerning the expected event topologies and estimates of the background events. Using few bricks, we could reach a good sensitivity level.Comment: 12 pages, 4 figure

    Studying general multivariate dependence using associated copulas with applications to financial time series

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    In this thesis we study the general multivariate dependence of a random vector using associated copulas. The analysis of multivariate tail dependence has been centered in the positive case. To address this issue, we define the concept of gen- eral dependence and its corresponding probability functions. We prove a version of Sklar's Theorem that links these probability functions with its marginals using the associated copulas. We extend definitions and results from positive to the general dependence case. This includes associated tail dependence functions and associated tail dependence coefficients. We derive the relationships among associated copulas and obtain sev- eral results involving these copulas. We study the associated copulas of several copula models. This includes the perfect dependence cases, elliptical copulas, cop- ula models based on Laplace transforms, vine copulas and Marshall-Olkin copulas. For all these examples we analyse their tail dependence and obtain the correspond- ing tail dependence functions. We then extend several nonparametric estimators to the tail dependence func- tion in the general dependence case, and, using the results obtained in this work, we introudce new estimators. We use two optimisation methods for these esti- mators and run a simulation study to assess their performance for three levels of tail dependence and three sample sizes. With this simulation study we obtain an optimal estimator for each level of tail dependence. We use these estimators in two financial time series examples. In the first example we study the tail depen- dence structure between volatility indices and their corresponding stock market indices. In the second one between gold and other financial indices. With the results obtained in this thesis, it was possible to determine the existence of asym- metric negative tail dependence for both examples. Overlooking this feature can have undesirable consequences when modelling this data.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    SHP-1 Tyrosine phosphatase in human erythrocytes

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    Abstract: SHP-1 is a SH2-domain containing protein Tyr-phosphatase expressed in hematopoietic cell lines, which is hypothesized to play a negative role in signal transduction. In human erythrocytes, the phospho-Tyr level of proteins, mainly transmembrane band 3, is closely controlled by the antithetic activity of Tyr-protein kinases and phosphatases, resulting in a dephosphorylated state. Only after particular stimuli, as with oxidizing agents, diamide or pervanadate, or thiol alkylating compound, N-ethyl maleimide (NEM), Tyr-phosphorylation of band 3 can be triggered, inhibiting Tyr-phosphatase action and inducing erythrocyte membrane reorganization. We demonstrate that, in human erythrocytes, SHP-1 is present in membranes from resting cells, but in 5% of the protein amount. Interestingly, this amount increases up to threefold following NEM treatment of intact cells, whereas diamide and pervanadate do not alter the normal protein location. In addition, SHP-1 translocation from cytosol to membrane is not affected by band 3 P-Tyr level, because it is not mediated by the SH2-P-Tyr recruitment mechanism, and localizes into the cytoskeletal compartment. Band 3 is the target of SHP-1, which dephosphorylates Tyr8, 21, and 904. These findings support the idea that, in human erythrocytes, the normal level of Tyr-phosphorylation of membrane protein, mainly band 3, must be downregulated. We hypothesize that the presence of both SHP-2 and SHP-1 ensures band 3 dephosphorylation in different conditions: SHP-2, through interaction of its SH2 domain/s to P-Tyr protein, is regulated by the band 3 Tyr-phosphorylation level; SHP-1 may be involved by simple membrane rearrangement

    Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function.

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    Cannabinoids and endocannabinoids negatively influence sperm functions. These substances have been demonstrated in many mammalian tissues, including male and female reproductive tracts, and previous studies have shown the presence of functional receptors for cannabinoids in human sperm. The present study, by means of RT-PCR and Western blot techniques, demonstrates that human sperm express the CB(1), but not CB(2), cannabinoid receptor (CB-R) subtype located in the head and middle piece of the sperm. The activation of this receptor by anandamide reduces sperm motility and inhibits capacitation-induced acrosome reaction. Activation of the CB(1)-R did not induce any variation in sperm intracellular calcium concentrations, but produced a rapid plasma membrane hyperpolarization that was reduced by the K(+) channel blocker tetraethylammonium. The effects of anandamide on human sperm motility were dependent on the reduction of sperm mitochondrial activity as determined by rhodamine 123 fluorescence. The specificity of anandamide effects in human sperm were confirmed by the effects of the CB(1)-R antagonist SR141716. These findings provide additional evidence that human sperm express functional CB(1)-R, the activation of which negatively influences important sperm functions, and suggest a possible role for the cannabinoid system in the pathogenesis of some forms of male infertility

    Band 3 tyr-phosphorylation in normal and glucose-6-dehydrogenase-defcient huamn erythrocytes

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    Abstract: Haemolysis is usually episodic in glucose-6-phosphate dehydrogenase (G6PD) deficiency, often triggered by a period of oxidative stress. In the present work, we investigate a possible biochemical mechanism underlying the enhanced susceptibility of G6PD deficient red blood cells (RBC) to oxidative stress. We analysed eight male subjects with Mediterranean glucose-6P-dehydrogenase deficiency (G6PDd), class II, for their ability in phosphorylating erythrocyte membrane band 3 following oxidative and osmotic stress. Our findings show that this sensitivity is connected to an early membrane band 3 Tyr-phosphorylation in the presence of diamide. However, since both Syk, and Lyn kinases, and SHP-2 phosphatase, mostly implicated in the band 3 P-Tyr level regulation, are alike in content and activity in normal and patient erythrocytes, an alteration in the membrane organization is likely the cause of the anomalous response to the oxidant. We report, in fact, that hypertonic-induced morphological change in G6PDd erythrocyte induces a higher membrane band 3 Tyr-phosphorylation, suggesting a pre-existing membrane alteration, likely due to the chronic lowering of the redox systems in patients. We also report that 1-chloro-2,4-dinitrobenzene-pre-treatment of normal red cells can alter the normal protein-protein and protein-membrane interaction under hypertonic rather than oxidative stress, thus partially resembling the response in patients, and that RBC may utilize a wider range of redox defence, under oxidative conditions, including, but not exclusively, NADPH and glutathione. On the whole, these results would encourage a different approach to the evaluation of the effects of pharmacological administration to patients, giving more attention to the possible drug-induced membrane alteration evidenced by the abnormal band 3 Tyr-phosphorylation

    Human Sperm Express Cannabinoid Receptor Cb 1

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    Effector-induced Syk-mediated phosphorylation in human erythrocytes

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    Abstract: Band 3 (AEI), the most prominent polypeptide of the human erythrocyte membrane, becomes heavily tyrosine phosphorylated following treatment of intact cells with protein tyrosine phosphatase inhibitors such as diamide, pervanadate, vanadate, or N-ethylmaleimide (NEM). The mechanism underlying this tyrosine phosphorylation is thought to involve the sequential action of two protein tyrosine kinases, Syk (p72(syk)) and Lyn (p53/56(lyn)). While Lyn catalysed phosphorylation appears to be strictly dependent on prior phosphorylation of Tyr8 and 21 of band 3 by Syk, little is known about the mechanism of induction of Syk phosphorylation. Data presented here show that both the fraction of Syk that associates with the membrane and the extent of phosphorylation of band 3 differ in response to the above inhibitors. While diamide and NEM stimulate syk translocation to the membrane during their induction of band 3 tyrosine phosphorylation, pervanadate and vanadate induce no change in kinase distribution. Moreover, diamide and NEM-induced Syk recruitment to the membrane are phosphotyrosine independent and involve their preferential association with Triton X-100-insoluble membrane skeletons. Together these data reveal a complex process controlling the association and catalytic activity of protein tyrosine kinases syk and lyn with the human erythrocyte membrane
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