The Level-0 Muon Trigger for the LHCb Experiment

A very compact architecture has been developed for the first level Muon Trigger of the LHCb experiment that processes 40 millions of proton-proton collisions per second. For each collision, it receives 3.2 kBytes of data and it finds straight tracks within a 1.2 microseconds latency. The trigger implementation is massively parallel, pipelined and fully synchronous with the LHC clock. It relies on 248 high density Field Programable Gate arrays and on the massive use of multigigabit serial link transceivers embedded inside FPGAs.Comment: 33 pages, 16 figures, submitted to NIM

Réalités et enjeux de la participation des femmes dans les essais cliniques sur les antirétroviraux : expérience au Sénégal

De plus en plus d'essais cliniques se déroulent dans les pays du Sud. Contrairement aux pays du Nord, où dans les années 1990 les associations critiquaient l'absence de femmes dans les essais, les femmes sont quatre fois plus nombreuses que les hommes parmi les participants lors du dernier d'entre eux mené à Dakar. Cela rend particulièrement aiguë la question de la survenue de grossesses dans les essais. Ce chapitre analyse cette féminisation des participants aux essais, avec la question de savoir si celle-ci résulte des modalités d'inclusion. Le mode de prise en charge des femmes enceintes dans les essais sera présenté et discuté à partir de l'expérience des femmes, des soignants et des chercheurs. Les problèmes que pose la féminisation des participants aux essais cliniques seront discutés, notamment pour ce qui concerne les limites du dispositif de prise en charge en matière de contraception, les dispositions éthiques exigées et la possibilité de critères d'inclusion basés sur le sexe

Sonoprinting liposomes on tumor spheroids by microbubbles and ultrasound

Ultrasound-triggered drug-loaded microbubbles have great potential for drug delivery due to their ability to locally release drugs and simultaneously enhance their delivery into the target tissue. We have recently shown that upon applying ultrasound, nanoparticle-loaded microbubbles can deposit nanoparticles onto cells grown in 2D monolayers, through a process that we termed "sonoprinting". However, the rigid surfaces on which cell monolayers are typically growing might be a source of acoustic reflections and aspherical microbubble oscillations, which can influence microbubble-cell interactions. In the present study, we aim to reveal whether sonoprinting can also occur in more complex and physiologically relevant tissues, by using free-floating 3D tumor spheroids as a tissue model. We show that both monospheroids (consisting of tumor cells alone) and cospheroids (consisting of tumor cells and fibroblasts, which produce an extracellular matrix) can be sonoprinted. Using doxorubicin-liposome-loaded microbubbles, we show that sonoprinting allows to deposit large amounts of doxorubicin-containing liposomes to the outer cell layers of the spheroids, followed by doxorubicin release into the deeper layers of the spheroids, resulting in a significant reduction in cell viability. Sonoprinting may become an attractive approach to deposit drug patches at the surface of tissues, thereby promoting the delivery of drugs into target tissues

Kinetics of error generation in homologous B-family DNA polymerases

The kinetics of forming a proper Watson–Crick base pair as well incorporating bases opposite furan, an abasic site analog, have been well characterized for the B Family replicative DNA polymerase from bacteriophage T4. Structural studies of these reactions, however, have only been performed with the homologous enzyme from bacteriophage RB69. In this work, the homologous enzymes from RB69 and T4 were compared in parallel reactions to determine the relative abilities of the two polymerases to incorporate correct nucleotides as well as to form improper pairings. The kinetic rates for three different exonuclease mutants for each enzyme were measured for incorporation of an A opposite T and an A opposite furan as well as for the formation of A:C and T:T mismatches. The T4 exonuclease mutants were all ∼2- to 7-fold more efficient than the corresponding RB69 exonuclease mutants depending on whether a T or furan was in the templating position and which exonuclease mutant was used. The rates for mismatch formation by T4 were significantly reduced compared with incorporation opposite furan, much more so than the corresponding RB69 mutant. These results show that there are kinetic differences between the two enzymes but they are not large enough to preclude structural assumptions for T4 DNA polymerase based on the known structure of the RB69 DNA polymerase

Prevalence of H63D, S65C and C282Y hereditary hemochromatosis gene mutations in Slovenian population by an improved high-throughput genotyping assay

<p>Abstract</p> <p>Background</p> <p>Hereditary hemochromatosis (HH) is a common genetic disease characterized by excessive iron overload that leads to multi-organ failure. Although the most prevalent genotype in HH is homozygosity for C282Y mutation of the <it>HFE </it>gene, two additional mutations, H63D and S65C, appear to be associated with a milder form of HH. The aim of this study was to develop a high-throughput assay for <it>HFE </it>mutations screening based on TaqMan technology and to determine the frequencies of <it>HFE </it>mutations in the Slovenian population.</p> <p>Methods</p> <p>Altogether, 1282 randomly selected blood donors from different Slovenian regions and 21 HH patients were analyzed for the presence of <it>HFE </it>mutations by an in-house developed real-time PCR assay based on TaqMan technology using shorter non-interfering fluorescent single nucleotide polymorphism (SNP)-specific MGB probes. The assay was validated by RFLP analysis and DNA sequencing.</p> <p>Results</p> <p>The genotyping assay of the H63D, S65C and C282Y mutations in the <it>HFE </it>gene, based on TaqMan technology proved to be fast, reliable, with a high-throughput capability and 100% concordant with genotypes obtained by RFLP and DNA sequencing. The observed frequency of C282Y homozygotes in the group of HH patients was only 48%, others were of the heterogeneous <it>HFE </it>genotype. Among 1282 blood donors tested, the observed H63D, S65C and C282Y allele frequency were 12.8% (95% confidence interval (CI) 11.5 – 14.2%), 1.8% (95% CI 1.4 – 2.5%) and 3.6% (95% CI 3.0 – 4.5%), respectively. Approximately 33% of the tested subjects had at least one of the three HH mutations, and 1% of them were C282Y homozygotes or compound heterozygotes C282Y/H63D or C282Y/S65C, presenting an increased risk for iron overload disease. A significant variation in H63D allele frequency was observed for one of the Slovenian regions.</p> <p>Conclusion</p> <p>The improved real-time PCR assay for H63D, S65C and C282Y mutations detection is accurate, fast, cost-efficient and ready for routine screening and diagnostic procedures. The genotype frequencies in the Slovenian population agree with those reported for the Central European populations although some deviations where observed in comparison with other populations of Slavic origin. Regional distribution of the mutations should be considered when planning population screening.</p

Test of CPT Symmetry and Quantum Mechanics with Experimental data from CPLEAR

We use fits to recent published CPLEAR data on neutral kaon decays to $\pi^+\pi^-$ and $\pi e\nu$ to constrain the CPT--violation parameters appearing in a formulation of the neutral kaon system as an open quantum-mechanical system. The obtained upper limits of the CPT--violation parameters are approaching the range suggested by certain ideas concerning quantum gravity.Comment: 9 pages of uuencoded postscript (includes 3 figures