Emergence of phenotypic and genotypic antimicrobial resistance in Mycobacterium tuberculosis.

Concentration dependency of phenotypic and genotypic isoniazid-rifampicin resistance emergence was investigated to obtain a mechanistic understanding on how anti-mycobacterial drugs facilitate the emergence of bacterial populations that survive throughout treatment. Using static kill curve experiments, observing two evolution cycles, it was demonstrated that rifampicin resistance was the result of non-specific mechanisms and not associated with accumulation of drug resistance encoding SNPs. Whereas, part of isoniazid resistance could be accounted for by accumulation of specific SNPs, which was concentration dependent. Using a Hollow Fibre Infection Model it was demonstrated that emergence of resistance did not occur at concentration-time profiles mimicking the granuloma. This study showed that disentangling and quantifying concentration dependent emergence of resistance provides an improved rational for drug and dose selection although further work to understand the underlying mechanisms is needed to improve the drug development pipeline

Search for CP Violation in the Decay Z -> b (b bar) g

About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, ${\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab}$ and $h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}$, limits of \hat{h}_b < 0.59$and$h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st

Observation of charmless hadronic B decays

Four candidates for charmless hadronic B decay are observed in a data sample of four million hadronic Z decays recorded by the ALEPH detector at LEP. The probability that these events come from background sources is estimated to be less than 10(-6). The average branching of weakly decaying B hadrons (a mixture of B-d(0), B-s(0) and Lambda(b) weighted by their production The average branching ratio of weakly decaying B hadrons (a mixture of B-d(0) cross sections and lifetimes, here denoted B) into two long-lived charged hadrons (pions, kaons or protons) is measured to be Br(B-->h(+)h(-))=(1.7(-0.7)(+1.0)+/-0.2)x10(-5). The relative branching fraction Br(B-d(s)(0)-->pi(+)pi(-)(K-))/Br(B-d(s)(0)-->h(+)h(-)) is measured to be 1.0(-0.3-0.1)(+0.0+0.0). In addition, branching ratio upper limits are obtained for a variety of exclusive charmless hadronic two-body decays of B hadrons

Determination of sin2 θeff w using jet charge measurements in hadronic Z decays

The electroweak mixing angle is determined with high precision from measurements of the mean difference between forward and backward hemisphere charges in hadronic decays of the Z. A data sample of 2.5 million hadronic Z decays recorded over the period 1990 to 1994 in the ALEPH detector at LEP is used. The mean charge separation between event hemispheres containing the original quark and antiquark is measured for bb̄ and cc̄ events in subsamples selected by their long lifetimes or using fast D*'s. The corresponding average charge separation for light quarks is measured in an inclusive sample from the anticorrelation between charges of opposite hemispheres and agrees with predictions of hadronisation models with a precision of 2%. It is shown that differences between light quark charge separations and the measured average can be determined using hadronisation models, with systematic uncertainties constrained by measurements of inclusive production of kaons, protons and A's. The separations are used to measure the electroweak mixing angle precisely as sin2 θeff w = 0.2322 ± 0.0008(exp. stat.) ±0.0007(exp. syst.) ± 0.0008(sep.). The first two errors are due to purely experimental sources whereas the third stems from uncertainties in the quark charge separations

Search for Bs0B^{0}_{s} oscillations using inclusive lepton events

A search for Bs oscillations is performed using a sample of semileptonic b-hadron decays collected by the ALEPH experiment during 1991-1995. Compared to previous inclusive lepton analyses, the prop er time resolution and b-flavour mistag rate are significantly improved. Additional sensitivity to Bs mixing is obtained by identifying subsamples of events having a Bs purity which is higher than the average for the whole data sample. Unbinned maximum likelihood amplitude fits are performed to derive a lower limit of Dms>9.5 ps-1 at 95% CL. Combining with the ALEPH Ds based analyses yields Dms>9.6 ps-1 at 95% CL.A search for B0s oscillations is performed using a sample of semileptonic b-hadron decays collected by the ALEPH experiment during 1991-1995. Compared to previous inclusive lepton analyses, the proper time resolution and b-flavour mistag rate are significantly improved. Additional sensitivity to B0s mixing is obtained by identifying subsamples of events having a B0s purity which is higher than the average for the whole data sample. Unbinned maximum likelihood amplitude fits are performed to derive a lower limit of Deltam_s>9.5ps^-1 at 95% CL. Combining with the ALEPH D-s based analyses yields Deltam_s>9.6ps^-1 at 95% CL