Extending the applicability of the dose addition model to the assessment of chemical mixtures of partial agonists by using a novel toxic unit extrapolation method

This article has been made available through the Brunel Open Access Publishing Fund.Dose addition, a commonly used concept in toxicology for the prediction of chemical mixture effects, cannot readily be applied to mixtures of partial agonists with differing maximal effects. Due to its mathematical features, effect levels that exceed the maximal effect of the least efficacious compound present in the mixture, cannot be calculated. This poses problems when dealing with mixtures likely to be encountered in realistic assessment situations where chemicals often show differing maximal effects. To overcome this limitation, we developed a pragmatic solution that extrapolates the toxic units of partial agonists to effect levels beyond their maximal efficacy. We extrapolated different additivity expectations that reflect theoretically possible extremes and validated this approach with a mixture of 21 estrogenic chemicals in the E-Screen. This assay measures the proliferation of human epithelial breast cancers. We found that the dose-response curves of the estrogenic agents exhibited widely varying shapes, slopes and maximal effects, which made it necessary to extrapolate mixture responses above 14% proliferation. Our toxic unit extrapolation approach predicted all mixture responses accurately. It extends the applicability of dose addition to combinations of agents with differing saturating effects and removes an important bottleneck that has severely hampered the use of dose addition in the past. © 2014 Scholze et al

A Measurement of Rb using a Double Tagging Method

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

Measurement of the B+ and B-0 lifetimes and search for CP(T) violation using reconstructed secondary vertices

The lifetimes of the B+ and B-0 mesons, and their ratio, have been measured in the OPAL experiment using 2.4 million hadronic Z(0) decays recorded at LEP. Z(0) --> b (b) over bar decays were tagged using displaced secondary vertices and high momentum electrons and muons. The lifetimes were then measured using well-reconstructed charged and neutral secondary vertices selected in this tagged data sample. The results aretau(B+) = 1.643 +/- 0.037 +/- 0.025 pstau(Bo) = 1.523 +/- 0.057 +/- 0.053 pstau(B+)/tau(Bo) = 1.079 +/- 0.064 +/- 0.041,where in each case the first error is statistical and the second systematic.A larger data sample of 3.1 million hadronic Z(o) decays has been used to search for CP and CPT violating effects by comparison of inclusive b and (b) over bar hadron decays, No evidence fur such effects is seen. The CP violation parameter Re(epsilon(B)) is measured to be Re(epsilon(B)) = 0.001 +/- 0.014 +/- 0.003and the fractional difference between b and (b) over bar hadron lifetimes is measured to(Delta tau/tau)(b) = tau(b hadron) - tau((b) over bar hadron)/tau(average) = -0.001 +/- 0.012 +/- 0.008

Measurement of the W+W−γW^{+}W^{-} \gamma Cross-section and First direct Limits on Anomalous Electroweak Quartic Gauge Couplings

A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W + W − events accompanied by hard photon radiation produced in e + e − collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183 pb −1 of data recorded at s =189 GeV. From these data, 17 W + W − γ candidates are selected with photon energy greater than 10 GeV, consistent with the Standard Model expectation. These events are used to measure the e + e − →W + W − γ cross-section within a set of geometric and kinematic cuts, σ ̂ WW γ =136±37±8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the W + W − γγ and W + W − γ Z 0 vertices: −0.070 GeV −

Transverse and Longitudinal Bose Einstein Correlations in hadronic Z0Z^0 Decays

Bose-Einstein correlations in pairs of identical charged pions produced in asample of 4.3 million Z0 hadronic decays are studied as a function of the threecomponents of the momentum difference, transverse ("out" and "side") andlongitudinal with respect to the thrust direction of the event. A significantdifference between the transverse, r_t_side, and longitudinal, r_l, dimensionsis observed, indicating that the emitting source of identical pions, asobserved in the Longitudinally CoMoving System, has an elongated shape. This isobserved with a variety of selection techniques. Specifically, the values ofthe parameters obtained by fitting the extended Goldhaber parametrisation tothe correlation function C'= C^{DATA}}/C^{MC} for two-jet events, selected withthe Durham algorithm and resolution parameter ycut=0.04, arer_t_out=(0.647+-0.011(stat})+0.022-0.124(syst)) fm,r_t_side=(0.809+-0.009(stat)+0.019-0.032}(syst)) fm, r_l=(0.989+-0.011(stat)+0.030-0.015(syst})) fm andr_l/r_t_side=1.222+- 0.027(stat})+0.075-0.012(syst). The results are discussedin the context of a recent model of Bose-Einstein correlations based on stringfragmentation.Bose-Einstein correlations in pairs of identical charged pions produced in a sample of 4.3 million Z0 hadronic decays are studied as a function of the three components of the momentum difference, transverse ("out" and "side") and longitudinal with respect to the thrust direction of the event. A significant difference between the transverse, r_t_side, and longitudinal, r_l, dimensions is observed, indicating that the emitting source of identical pions, as observed in the Longitudinally CoMoving System, has an elongated shape. This is observed with a variety of selection techniques. Specifically, the values of the parameters obtained by fitting the extended Goldhaber parametrisation to the correlation function C'= C^{DATA}}/C^{MC} for two-jet events, selected with the Durham algorithm and resolution parameter ycut=0.04, are r_t_out=(0.647+-0.011(stat})+0.022-0.124(syst)) fm, r_t_side=(0.809+-0.009(stat)+0.019-0.032}(syst)) fm, r_l=(0.989+-0.011(stat)+0.030-0.015(syst})) fm and r_l/r_t_side=1.222+-0.027(stat})+0.075-0.012(syst). The results are discussed in the context of a recent model of Bose-Einstein correlations based on string fragmentation

Experimental properties of gluon and quark jets from a point source

Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data

τ\tau decays with neutral kaons

The branching ratio of the tau lepton to a neutral K meson is measured from a sample of approximately 200,000 tau decays recorded by the OPAL detector at centre-of-mass energies near the Z0 resonance. The measurement is based on two samples which identify one-prong tau decays with KL and KS mesons. The combined branching ratios are measured to be B(tau- -->pi- K0bar nutau) = (9.33+-0.68+-0.49)x10^-3 B(tau- -->pi- K0bar [>=1pi0] nutau) = (3.24+-0.74+-0.66)x10^-3 B(tau- -->K- K0bar [>=0pi0] nutau) = (3.30+-0.55+-0.39)x10^-3 where the first error is statistical and the second systematic.The branching ratio of the tau lepton to a neutral K meson is measured from a sample of approximately 200,000 tau decays recorded by the OPAL detector at centre-of-mass energies near the Z0 resonance. The measurement is based on two samples which identify one-prong tau decays with KL and KS mesons. The combined branching ratios are measured to be B(tau- -->pi- K0bar nutau) = (9.33+-0.68+-0.49)x10^-3 B(tau- -->pi- K0bar [>=1pi0] nutau) = (3.24+-0.74+-0.66)x10^-3 B(tau- -->K- K0bar [>=0pi0] nutau) = (3.30+-0.55+-0.39)x10^-3 where the first error is statistical and the second systematic

Vector Transmission of Leishmania Abrogates Vaccine-Induced Protective Immunity

Numerous experimental vaccines have been developed to protect against the cutaneous and visceral forms of leishmaniasis caused by infection with the obligate intracellular protozoan Leishmania, but a human vaccine still does not exist. Remarkably, the efficacy of anti-Leishmania vaccines has never been fully evaluated under experimental conditions following natural vector transmission by infected sand fly bite. The only immunization strategy known to protect humans against natural exposure is “leishmanization,” in which viable L. major parasites are intentionally inoculated into a selected site in the skin. We employed mice with healed L. major infections to mimic leishmanization, and found tissue-seeking, cytokine-producing CD4+ T cells specific for Leishmania at the site of challenge by infected sand fly bite within 24 hours, and these mice were highly resistant to sand fly transmitted infection. In contrast, mice vaccinated with a killed vaccine comprised of autoclaved L. major antigen (ALM)+CpG oligodeoxynucleotides that protected against needle inoculation of parasites, showed delayed expression of protective immunity and failed to protect against infected sand fly challenge. Two-photon intra-vital microscopy and flow cytometric analysis revealed that sand fly, but not needle challenge, resulted in the maintenance of a localized neutrophilic response at the inoculation site, and removal of neutrophils following vector transmission led to increased parasite-specific immune responses and promoted the efficacy of the killed vaccine. These observations identify the critical immunological factors influencing vaccine efficacy following natural transmission of Leishmania

Presence of Avian Influenza Viruses in Waterfowl and Wetlands during Summer 2010 in California: Are Resident Birds a Potential Reservoir?

Although wild waterfowl are the main reservoir for low pathogenic avian influenza viruses (LPAIv), the environment plays a critical role for the circulation and persistence of AIv. LPAIv may persist for extended periods in cold environments, suggesting that waterfowl breeding areas in the northern hemisphere may be an important reservoir for AIv in contrast to the warmer southern wintering areas. We evaluated whether southern wetlands, with relatively small populations (thousands) of resident waterfowl, maintain AIv in the summer, prior to the arrival of millions of migratory birds. We collected water and fecal samples at ten wetlands in two regions (Yolo Bypass and Sacramento Valley) of the California Central Valley during three bi-weekly intervals beginning in late July, 2010. We detected AIv in 29/367 fecal samples (7.9%) and 12/597 water samples (2.0%) by matrix real time Reverse Transcription Polymerase Chain Reaction (rRT-PCR). We isolated two H3N8, two H2N3, and one H4N8 among rRT-PCR positive fecal samples but no live virus from water samples. Detection of AIv RNA in fecal samples was higher from wetlands in the Sacramento Valley (11.9%) than in the Yolo Bypass (0.0%), but no difference was found for water samples (2.7 vs. 1.7%, respectively). Our study showed that low densities of hosts and unfavorable environmental conditions did not prevent LPAIv circulation during summer in California wetlands. Our findings justify further investigations to understand AIv dynamics in resident waterfowl populations, compare AIv subtypes between migratory and resident waterfowl, and assess the importance of local AIv as a source of infection for migratory birds