Medium frequency (800-1600Hz) geoacoustic inversions with drifting sparse arrays during the MREA BP07 experiment

In order to evaluate properly the acoustic propagation characteristics in shallow water environments, it is well established that appropriate knowledge of the acoustic properties of the seabottom is required. In the last decade, full-field geoacoustic inversion techniques have been demonstrated to provide adequate methodologies to assess those properties. However, several of the developed techniques may suffer a lack of adequacy to the design of low-frequency active sonar systems (LFAS) for which the assessment of seabottom characteristics are drawn. For instance most matched-field inversion techniques demonstrated so far use acoustical signals at much lower frequencies than those of the sonar (few tens to hundreds Hertz to be compared to the 1-2 kHz range of standard LFAS). Furthermore, some of the techniques may be difficult to be handled in an â€oeoperationally relevant context― since they are based on relatively complex designed systems such as highly instrumented vertical line arrays spanning the whole water column. In this paper, we investigate the potentialities of medium frequency acoustical signals (800-1600 Hz) received at several ranges (from 1 km to 10 km) along a field of drifting sparse arrays eventually reduced to a couple of hydrophones or even a single one for spatial coherent geoacoustic inversion purposes. The experimental datasets of the Maritime Rapid Environmental Assessment BP’07 seatrials South of Elba Island in the Mediterranean Sea are used to support this study.FC

A buoy network system for acoustic monitoring

Continuous evolution of both methodologies and required technologies for REA; support of sea-based operations as demonstrated through MREA-BP-RADAR acoustic/oceanic model integration; spatially coherent processed buoys/sparse arraysinclude adaptive geoacoustic estimationPOSI; POCTI; FCT Portugal; Royal Netherlands Navy

Intermittent preventive treatment with dihydroartemisinin-piperaquine in Ugandan schoolchildren selects for Plasmodium falciparum transporter polymorphisms that modify drug sensitivity.

Dihydroartemisinin-piperaquine (DP) offers prolonged protection against malaria, but its impact on Plasmodium falciparum drug sensitivity is uncertain. In a trial of intermittent preventive treatment in schoolchildren in Tororo, Uganda, in 2011 to 2012, monthly DP for 1 year decreased the incidence of malaria by 96% compared to placebo; DP once per school term offered protection primarily during the first month after therapy. To assess the impact of DP on selection of drug resistance, we compared the prevalence of key polymorphisms in isolates that emerged at different intervals after treatment with DP. Blood obtained monthly and at each episode of fever was assessed for P. falciparum parasitemia by microscopy. Samples from 160 symptomatic and 650 asymptomatic episodes of parasitemia were assessed at 4 loci (N86Y, Y184F, and D1246Y in pfmdr1 and K76T in pfcrt) that modulate sensitivity to aminoquinoline antimalarials, utilizing a ligase detection reaction-fluorescent microsphere assay. For pfmdr1 N86Y and pfcrt K76T, but not the other studied polymorphisms, the prevalences of mutant genotypes were significantly greater in children who had received DP within the past 30 days than in those not treated within 60 days (86Y, 18.0% versus 8.3% [P = 0.03]; 76T, 96.0% versus 86.1% [P = 0.05]), suggesting selective pressure of DP. Full sequencing of pfcrt in a subset of samples did not identify additional polymorphisms selected by DP. In summary, parasites that emerged soon after treatment with DP were more likely than parasites not under drug pressure to harbor pfmdr1 and pfcrt polymorphisms associated with decreased sensitivity to aminoquinoline antimalarials. (This study has been registered at ClinicalTrials.gov under no. NCT01231880.)

A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue.

Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC50 32 nM), Ugandan field isolates (mean ex vivo IC50 64 nM), and murine P. berghei and P. falciparum infections (day 4 ED90 0.34 and 0.57 mg kg-1, respectively). Multiple P. falciparum lines selected in vitro for resistance to AN3661 harboured point mutations in pfcpsf3, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of pfcpsf3 mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these mutations in the active site, where AN3661 is predicted to bind. Transcripts for three trophozoite-expressed genes were lost in AN3661-treated trophozoites, which was not observed in parasites selected or engineered for AN3661 resistance. Our results identify the pre-mRNA processing factor PfCPSF3 as a promising antimalarial drug target

Measurement of the lifetime of the B+c meson using the B+c→J/ψπ+ decay mode

See paper for full list of authors - 19 pages, 3 figuresInternational audienceThe difference in total widths between the B+c and B+ mesons is measured using 3.0fb−1 of data collected by the LHCb experiment in 7 and 8 TeV centre-of-mass energy proton-proton collisions at the LHC. Through the study of the time evolution of B+c→J/ψπ+ and B+→J/ψK+ decays, the width difference is measured to beΔΓ≡ΓB+c−ΓB+=4.46±0.14±0.07mm−1c,where the first uncertainty is statistical and the second systematic. The known lifetime of the B+ meson is used to convert this to a precise measurement of the B+c lifetime,τB+c=513.4±11.0±5.7fs,where the first uncertainty is statistical and the second systematic

Determination of gamma and -2beta_s from charmless two-body decays of beauty mesons

See paper for full list of authorsInternational audienceUsing the latest LHCb measurements of time-dependent CP violation in the B^0_s -> K^+K^- decay, a U-spin relation between the decay amplitudes of B^0_s -> K^+K^- and B^0 -> \pi^+\pi^- decay processes allows constraints to be placed on the angle gamma of the unitarity triangle and on the B^0_s mixing phase -2\beta_s. Results from an extended approach, which uses additional inputs on B^0 -> \pi^0\pi^0 and B^+ -> \pi^+\pi^0 decays from other experiments and exploits isospin symmetry, are also presented. The dependence of the results on the maximum allowed amount of U-spin breaking is studied. At 68% probability, the value \gamma = ( 63.5 +7.2 -6.7 ) degrees modulo 180 degrees is determined. In an alternative analysis, the value -2\beta_s = -0.12 +0.14 -0.16 rad is found. In both measurements, the uncertainties due to U-spin breaking effects up to 50% are included

Measurement of the CP-violating phase β in B0→J/ψπ+π− decays and limits on penguin effects

18 pages, 6 figures - See paper for full list of authorsInternational audienceTime-dependent CP violation is measured in the B0→J/ψπ+π− channel for each π+π− resonant final state using data collected with an integrated luminosity of 3.0 fb−1 in pp collisions using the LHCb detector. The final state with the largest rate, J/ψρ0(770), is used to measure the CP-violating angle 2βeff to be (41.7±9.6+2.8−6.3)∘. This result can be used to limit the size of penguin amplitude contributions to CP violation measurements in, for example, B0s→J/ψϕ decays. Assuming approximate SU(3) flavour symmetry and neglecting higher order diagrams, the shift in the CP-violating phase ϕs is limited to be within the interval [−1.05∘, +1.18∘] at 95% confidence level. Changes to the limit due to SU(3) symmetry breaking effects are also discussed

Study of the rare B0s and B0 decays into the π+π−μ+μ− final state

See paper for full list of authors - Submitted to Phys. Lett. BInternational audienceA search for the rare decays B0s→π+π−μ+μ− and B0→π+π−μ+μ− is performed in a data set corresponding to an integrated luminosity of 3.0 fb−1 collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3 GeV/c2 and with muon pairs that do not originate from a resonance are considered. The first observation of the decay B0s→π+π−μ+μ− and the first evidence of the decay B0→π+π−μ+μ− are obtained and the branching fractions are measured to be B(B0s→π+π−μ+μ−)=(8.6±1.5(stat)±0.7(syst)±0.7(norm))×10−8 and B(B0→π+π−μ+μ−)=(2.11±0.51(stat)±0.15(syst)±0.16(norm))×10−8, where the third uncertainty is due to the branching fraction of the decay B0→J/ψ(→μ+μ−)K∗(890)0(→K+π−), used as a normalisation

Mining a Cathepsin Inhibitor Library for New Antiparasitic Drug Leads

The targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, Chagas' disease, and malaria. The homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. We describe here the screening of a unique ∼2,100-member cathepsin inhibitor library against five parasite cysteine proteases thought to be relevant in tropical parasitic diseases. Compounds active against parasite enzymes were subsequently screened against cultured Plasmodium falciparum, Trypanosoma brucei brucei and/or Trypanosoma cruzi parasites and evaluated for cytotoxicity to mammalian cells. The end products of this effort include the identification of sub-micromolar cell-active leads as well as the elucidation of structure-activity trends that can guide further optimization efforts