The Killing of African Trypanosomes by Ethidium Bromide

Introduced in the 1950s, ethidium bromide (EB) is still used as an anti-trypanosomal drug for African cattle although its mechanism of killing has been unclear and controversial. EB has long been known to cause loss of the mitochondrial genome, named kinetoplast DNA (kDNA), a giant network of interlocked minicircles and maxicircles. However, the existence of viable parasites lacking kDNA (dyskinetoplastic) led many to think that kDNA loss could not be the mechanism of killing. When recent studies indicated that kDNA is indeed essential in bloodstream trypanosomes and that dyskinetoplastic cells survive only if they have a compensating mutation in the nuclear genome, we investigated the effect of EB on kDNA and its replication. We here report some remarkable effects of EB. Using EM and other techniques, we found that binding of EB to network minicircles is low, probably because of their association with proteins that prevent helix unwinding. In contrast, covalently-closed minicircles that had been released from the network for replication bind EB extensively, causing them, after isolation, to become highly supertwisted and to develop regions of left-handed Z-DNA (without EB, these circles are fully relaxed). In vivo, EB causes helix distortion of free minicircles, preventing replication initiation and resulting in kDNA loss and cell death. Unexpectedly, EB also kills dyskinetoplastic trypanosomes, lacking kDNA, by inhibiting nuclear replication. Since the effect on kDNA occurs at a >10-fold lower EB concentration than that on nuclear DNA, we conclude that minicircle replication initiation is likely EB's most vulnerable target, but the effect on nuclear replication may also contribute to cell killing

Associated Charm Production in Neutrino-Nucleus Interactions

In this paper a search for associated charm production both in neutral and charged current $\nu$-nucleus interactions is presented. The improvement of automatic scanning systems in the {CHORUS} experiment allows an efficient search to be performed in emulsion for short-lived particles. Hence a search for rare processes, like the associated charm production, becomes possible through the observation of the double charm-decay topology with a very low background. About 130,000 $\nu$ interactions located in the emulsion target have been analysed. Three events with two charm decays have been observed in the neutral-current sample with an estimated background of 0.18$\pm$0.05. The relative rate of the associated charm cross-section in deep inelastic $\nu$ interactions, $\sigma(c\bar{c}\nu)/\sigma_\mathrm{NC}^\mathrm{DIS}= (3.62^{+2.95}_{-2.42}({stat})\pm 0.54({syst}))\times 10^{-3}$ has been measured. One event with two charm decays has been observed in charged-current $\nu_\mu$ interactions with an estimated background of 0.18$\pm$0.06 and the upper limit on associated charm production in charged-current interactions at 90% C.L. has been found to be $\sigma (c\bar{c} \mu^-)/\sigma_\mathrm{CC} < 9.69 \times 10^{-4}$.Comment: 10 pages, 4 figure

The detection of neutrino interactions in the emulsion/lead target of the OPERA experiment

The OPERA neutrino detector in the underground Gran Sasso Laboratory (LNGS) was designed to perform the first detection of neutrino oscillations in appearance mode through the study of $\nu_\mu\to\nu_\tau$ oscillations. The apparatus consists of an emulsion/lead target complemented by electronic detectors and it is placed in the high energy long-baseline CERN to LNGS beam (CNGS) 730 km away from the neutrino source. Runs with CNGS neutrinos were successfully carried out in 2007 and 2008 with the detector fully operational with its related facilities for the emulsion handling and analysis. After a brief description of the beam and of the experimental setup we report on the collection, reconstruction and analysis procedures of first samples of neutrino interaction events

Emulsion sheet doublets as interface trackers for the OPERA experiment

New methods for efficient and unambiguous interconnection between electronic counters and target units based on nuclear photographic emulsion films have been developed. The application to the OPERA experiment, that aims at detecting oscillations between mu neutrino and tau neutrino in the CNGS neutrino beam, is reported in this paper. In order to reduce background due to latent tracks collected before installation in the detector, on-site large-scale treatments of the emulsions ("refreshing") have been applied. Changeable Sheet (CSd) packages, each made of a doublet of emulsion films, have been designed, assembled and coupled to the OPERA target units ("ECC bricks"). A device has been built to print X-ray spots for accurate interconnection both within the CSd and between the CSd and the related ECC brick. Sample emulsion films have been extensively scanned with state-of-the-art automated optical microscopes. Efficient track-matching and powerful background rejection have been achieved in tests with electronically tagged penetrating muons. Further improvement of in-doublet film alignment was obtained by matching the pattern of low-energy electron tracks. The commissioning of the overall OPERA alignment procedure is in progress.Comment: 19 pages, 19 figure

Measurement of the atmospheric muon charge ratio with the OPERA detector

The OPERA detector at the Gran Sasso underground laboratory (LNGS) was used to measure the atmospheric muon charge ratio in the TeV energy region. We analyzed 403069 atmospheric muons corresponding to 113.4 days of livetime during the 2008 CNGS run. We computed separately the muon charge ratio for single and for multiple muon events in order to select different energy regions of the primary cosmic ray spectrum and to test the charge ratio dependence on the primary composition. The measured charge ratio values were corrected taking into account the charge-misidentification errors. Data have also been grouped in five bins of the "vertical surface energy". A fit to a simplified model of muon production in the atmosphere allowed the determination of the pion and kaon charge ratios weighted by the cosmic ray energy spectrum.Comment: 14 pages, 10 figure

Fluoroquinolone-resistant Escherichia coli, Indonesia

High prevalence may be due to clonal spread and emergence of resistant strains

First events from the CNGS neutrino beam detected in the OPERA experiment

The OPERA neutrino detector at the underground Gran Sasso Laboratory (LNGS) was designed to perform the first detection of neutrino oscillations in appearance mode, through the study of nu_mu to nu_tau oscillations. The apparatus consists of a lead/emulsion-film target complemented by electronic detectors. It is placed in the high-energy, long-baseline CERN to LNGS beam (CNGS) 730 km away from the neutrino source. In August 2006 a first run with CNGS neutrinos was successfully conducted. A first sample of neutrino events was collected, statistically consistent with the integrated beam intensity. After a brief description of the beam and of the various sub-detectors, we report on the achievement of this milestone, presenting the first data and some analysis results.Comment: Submitted to the New Journal of Physic

Leading order analysis of neutrino induced dimuon events in the CHORUS experiment

We present a leading order QCD analysis of a sample of neutrino induced charged-current events with two muons in the final state originating in the lead-scintillating fibre calorimeter of the CHORUS detector. The results are based on a sample of 8910 neutrino and 430 antineutrino induced opposite-sign dimuon events collected during the exposure of the detector to the CERN Wide Band Neutrino Beam between 1995 and 1998. % with $E_{\mu 1},E_{\mu 2} > 5$ GeV and $Q^2 > 3$ GeV$^2$ collected %between 1995 and 1998. The analysis yields a value of the charm quark mass of \mc = (1.26\pm 0.16 \pm 0.09) \GeVcc and a value of the ratio of the strange to non-strange sea in the nucleon of $\kappa = 0.33 \pm 0.05 \pm 0.05$, improving the results obtained in similar analyses by previous experiments.Comment: Submitted to Nuclear Physics

Charged-Particle Multiplicities in Charged-Current Neutrino-- and Anti-Neutrino--Nucleus Interactions

The CHORUS experiment, designed to search for $\nu_{\mu}\to\nu_{\tau}$ oscillations, consists of a nuclear emulsion target and electronic detectors. In this paper, results on the production of charged particles in a small sample of charged-current neutrino-- and anti-neutrino--nucleus interactions at high energy are presented. For each event, the emission angle and the ionization features of the charged particles produced in the interaction are recorded, while the standard kinematic variables are reconstructed using the electronic detectors. The average multiplicities for charged tracks, the pseudo-rapidity distributions, the dispersion in the multiplicity of charged particles and the KNO scaling are studied in different kinematical regions. A study of quasi-elastic topologies performed for the first time in nuclear emulsions is also reported. The results are presented in a form suitable for use in the validation of Monte Carlo generators of neutrino--nucleus interactions.Comment: 17 pages, 5 figure