579 research outputs found

    The proapoptotic dp5 gene is a direct target of the MLK-JNK-c-Jun pathway in sympathetic neurons

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    The death of sympathetic neurons after nerve growth factor (NGF) withdrawal requires de novo gene expression. Dp5 was one of the first NGF withdrawal-induced genes to be identified and it encodes a proapoptotic BH3-only member of the Bcl-2 family. To study how dp5 transcription is regulated by NGF withdrawal we cloned the regulatory regions of the rat dp5 gene and constructed a series of dp5-luciferase reporter plasmids. In microinjection experiments with sympathetic neurons we found that three regions of dp5 contribute to its induction after NGF withdrawal: the promoter, a conserved region in the single intron, and sequences in the 3′ untranslated region of the dp5 mRNA. A construct containing all three regions is efficiently activated by NGF withdrawal and, like the endogenous dp5, its induction requires mixed-lineage kinase (MLK) and c-Jun N-terminal kinase (JNK) activity. JNKs phosphorylate the AP-1 transcription factor c-Jun, and thereby increase its activity. We identified a conserved ATF site in the dp5 promoter that binds c-Jun and ATF2, which is critical for dp5 promoter induction after NGF withdrawal. These results suggest that part of the mechanism by which the MLK-JNK-c-Jun pathway promotes neuronal apoptosis is by activating the transcription of the dp5 gene

    The acceptability and feasibility of a brief psychosocial intervention to reduce blood-borne virus risk behaviours among people who inject drugs: A randomised control feasibility trial of a psychosocial intervention (the PROTECT study) versus treatment as usual

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    Background: While opiate substitution therapy and injecting equipment provision (IEP) have reduced blood-borne viruses (BBV) among people who inject drugs (PWID), some PWID continue to share injecting equipment and acquire BBV. Psychosocial interventions that address risk behaviours could reduce BBV transmission among PWID.Methods: A pragmatic, two-armed randomised controlled, open feasibility study of PWID attending drug treatment or IEP in four UK regions. Ninety-nine PWID were randomly allocated to receive a three-session manualised psychosocial group intervention and BBV transmission information booklet plus treatment as usual (TAU) (n = 52) or information booklet plus TAU (n = 47). The intervention was developed from evidence-based literature, qualitative interviews with PWID, key stakeholder consultations, and expert opinion. Recruitment rates, retention in treatment, follow-up completion rates and health economic data completion measured feasibility.Results: Fifty-six percent (99/176) of eligible PWID were recruited. More participants attended at least one intervention session in London (10/16; 63%) and North Wales (7/13; 54%) than in Glasgow (3/12; 25%) and York (0/11). Participants who attended no sessions (n = 32) compared to those attending at least one (n = 20) session were more likely to be homeless (56 vs 25%, p = 0.044), injected drugs for a greater number of days (median 25 vs 6.5, p = 0.019) and used a greater number of needles from an IEP in the last month (median 31 vs 20, p = 0.056). No adverse events were reported. 45.5% (45/99) were followed up 1 month post-intervention. Feedback forms confirmed that the intervention was acceptable to both intervention facilitators and participants who attended it. Follow-up attendance was associated with fewer days of injecting in the last month (median 14 vs 27, p = 0.030) and fewer injections of cocaine (13 vs 30%, p = 0.063). Analysis of the questionnaires identified several service use questionnaire categories that could be excluded from the assessment battery in a full-randomised controlled trial.Conclusions: Findings should be interpreted with caution due to small sample sizes. A future definitive RCT of the psychosocial intervention is not feasible. The complex needs of some PWID may have limited their engagement in the intervention. More flexible delivery methods may have greater reach

    Search for Higgs Bosons in e+e- Collisions at 183 GeV

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    The data collected by the OPAL experiment at sqrts=183 GeV were used to search for Higgs bosons which are predicted by the Standard Model and various extensions, such as general models with two Higgs field doublets and the Minimal Supersymmetric Standard Model (MSSM). The data correspond to an integrated luminosity of approximately 54pb-1. None of the searches for neutral and charged Higgs bosons have revealed an excess of events beyond the expected background. This negative outcome, in combination with similar results from searches at lower energies, leads to new limits for the Higgs boson masses and other model parameters. In particular, the 95% confidence level lower limit for the mass of the Standard Model Higgs boson is 88.3 GeV. Charged Higgs bosons can be excluded for masses up to 59.5 GeV. In the MSSM, mh > 70.5 GeV and mA > 72.0 GeV are obtained for tan{beta}>1, no and maximal scalar top mixing and soft SUSY-breaking masses of 1 TeV. The range 0.8 < tanb < 1.9 is excluded for minimal scalar top mixing and m{top} < 175 GeV. More general scans of the MSSM parameter space are also considered.Comment: 49 pages. LaTeX, including 33 eps figures, submitted to European Physical Journal

    A Measurement of the Product Branching Ratio f(b->Lambda_b).BR(Lambda_b->Lambda X) in Z0 Decays

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    The product branching ratio, f(b->Lambda_b).BR(Lambda_b->Lambda X), where Lambda_b denotes any weakly-decaying b-baryon, has been measured using the OPAL detector at LEP. Lambda_b are selected by the presence of energetic Lambda particles in bottom events tagged by the presence of displaced secondary vertices. A fit to the momenta of the Lambda particles separates signal from B meson and fragmentation backgrounds. The measured product branching ratio is f(b->Lambda_b).BR(Lambda_b->Lambda X) = (2.67+-0.38(stat)+0.67-0.60(sys))% Combined with a previous OPAL measurement, one obtains f(b->Lambda_b).BR(Lambda_b->Lambda X) = (3.50+-0.32(stat)+-0.35(sys))%.Comment: 16 pages, LaTeX, 3 eps figs included, submitted to the European Physical Journal

    A measurement of the tau mass and the first CPT test with tau leptons

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    We measure the mass of the tau lepton to be 1775.1+-1.6(stat)+-1.0(syst.) MeV using tau pairs from Z0 decays. To test CPT invariance we compare the masses of the positively and negatively charged tau leptons. The relative mass difference is found to be smaller than 3.0 10^-3 at the 90% confidence level.Comment: 10 pages, 4 figures, Submitted to Phys. Letts.

    A Measurement of Rb using a Double Tagging Method

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    The fraction of Z to bbbar events in hadronic Z decays has been measured by the OPAL experiment using the data collected at LEP between 1992 and 1995. The Z to bbbar decays were tagged using displaced secondary vertices, and high momentum electrons and muons. Systematic uncertainties were reduced by measuring the b-tagging efficiency using a double tagging technique. Efficiency correlations between opposite hemispheres of an event are small, and are well understood through comparisons between real and simulated data samples. A value of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is statistical and the second systematic. The uncertainty on Rc, the fraction of Z to ccbar events in hadronic Z decays, is not included in the errors. The dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the deviation of Rc from the value 0.172 predicted by the Standard Model. The result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European Physical Journal

    First Measurement of Z/gamma* Production in Compton Scattering of Quasi-real Photons

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    We report the first observation of Z/gamma* production in Compton scattering of quasi-real photons. This is a subprocess of the reaction e+e- to e+e-Z/gamma*, where one of the final state electrons is undetected. Approximately 55 pb-1 of data collected in the year 1997 at an e+e- centre-of-mass energy of 183 GeV with the OPAL detector at LEP have been analysed. The Z/gamma* from Compton scattering has been detected in the hadronic decay channel. Within well defined kinematic bounds, we measure the product of cross-section and Z/gamma* branching ratio to hadrons to be (0.9+-0.3+-0.1) pb for events with a hadronic mass larger than 60 GeV, dominated by (e)eZ production. In the hadronic mass region between 5 GeV and 60 GeV, dominated by (e)egamma* production, this product is found to be (4.1+-1.6+-0.6) pb. Our results agree with the predictions of two Monte Carlo event generators, grc4f and PYTHIA.Comment: 18 pages, LaTeX, 5 eps figures included, submitted to Physics Letters

    Measurement of the B0 Lifetime and Oscillation Frequency using B0->D*+l-v decays

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    The lifetime and oscillation frequency of the B0 meson has been measured using B0->D*+l-v decays recorded on the Z0 peak with the OPAL detector at LEP. The D*+ -> D0pi+ decays were reconstructed using an inclusive technique and the production flavour of the B0 mesons was determined using a combination of tags from the rest of the event. The results t_B0 = 1.541 +- 0.028 +- 0.023 ps, Dm_d = 0.497 +- 0.024 +- 0.025 ps-1 were obtained, where in each case the first error is statistical and the second systematic.Comment: 17 pages, 4 figures, submitted to Phys. Lett.

    Measurement of the Michel Parameters in Leptonic Tau Decays

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    The Michel parameters of the leptonic tau decays are measured using the OPAL detector at LEP. The Michel parameters are extracted from the energy spectra of the charged decay leptons and from their energy-energy correlations. A new method involving a global likelihood fit of Monte Carlo generated events with complete detector simulation and background treatment has been applied to the data recorded at center-of-mass energies close to sqrt(s) = M(Z) corresponding to an integrated luminosity of 155 pb-1 during the years 1990 to 1995. If e-mu universality is assumed and inferring the tau polarization from neutral current data, the measured Michel parameters are extracted. Limits on non-standard coupling constants and on the masses of new gauge bosons are obtained. The results are in agreement with the V-A prediction of the Standard Model.Comment: 32 pages, LaTeX, 9 eps figures included, submitted to the European Physical Journal
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