Étude de la dynamique multiélectronique de BeH₂ en présence d'un champ laser intense

Face au besoin de simulation de la dynamique multiélectronique en champ intense, en particulier de la dynamique d'ionisation en champ fort, un algorithme de calcul quanto-chimique au niveau multiconfigurationel, avec des partitions de Feshbach de l'espace d'états à N électrons, a été développé dans notre laboratoire. Cet algorithme résoud l'équation de Schrödinger dépendante du temps pour le système à N électrons forcé par un champ intense de façon non perturbative. Les partitions de Feshbach permettent de séparer la simulation de la dynamique fortement corrélée des électrons liés de celle des électrons libres engendrés par ionisation en champ fort. Les éléments de cette approche multiconfigurationelle avec lses partitions de Feshbach, en particulier les emprunts des méthodes de calculs de la structure électronique post-SCF, sont présentés et illustrés avec des calculs effectués pour un modèle de la molécule BeH₂ soumise à un champ laser intense.To meet the need for simulations of laser-driven multi-electron dynamics and, in particular of strong-field ionization, a multi-configuration quantum chemical algorithm combined with Feshbach partitioning techniques, had been developed in our laboratory. This algorithm solves non-perturbatively the time dependent Schrödinger equation for an N electron system driven by an intense field. The Feshbach partitions allow one to separate highly correlated dynamics of the molecular bound electrons from that of the free electrons arising from the strong-field ionisation of the molecule. The approach, and elements it borrows from Quantum Chemistry's post-SCF ab-initio methodology, are illustrated by calculations on a model of the BeH₂ molecule driven by an intense laser field

Intronic small nucleolar RNAs regulate host gene splicing through base pairing with their adjacent intronic sequences

Background Small nucleolar RNAs (snoRNAs) are abundant noncoding RNAs best known for their involvement in ribosomal RNA maturation. In mammals, most expressed snoRNAs are embedded in introns of longer genes and produced through transcription and splicing of their host. Intronic snoRNAs were long viewed as inert passengers with little effect on host expression. However, a recent study reported a snoRNA influencing the splicing and ultimate output of its host gene. Overall, the general contribution of intronic snoRNAs to host expression remains unclear. Results Computational analysis of large-scale human RNA-RNA interaction datasets indicates that 30% of detected snoRNAs interact with their host transcripts. Many snoRNA-host duplexes are located near alternatively spliced exons and display high sequence conservation suggesting a possible role in splicing regulation. The study of the model SNORD2-EIF4A2 duplex indicates that the snoRNA interaction with the host intronic sequence conceals the branch point leading to decreased inclusion of the adjacent alternative exon. Extended SNORD2 sequence containing the interacting intronic region accumulates in sequencing datasets in a cell-type-specific manner. Antisense oligonucleotides and mutations that disrupt the formation of the snoRNA-intron structure promote the splicing of the alternative exon, shifting the EIF4A2 transcript ratio away from nonsense-mediated decay. Conclusions Many snoRNAs form RNA duplexes near alternative exons of their host transcripts, placing them in optimal positions to control host output as shown for the SNORD2-EIF4A2 model system. Overall, our study supports a more widespread role for intronic snoRNAs in the regulation of their host transcript maturation

Platelet quiescence in patients with acute coronary syndrome undergoing coronary artery bypass graft surgery

BACKGROUND: The optimal antiplatelet strategy for patients with acute coronary syndromes who require coronary artery bypass surgery remains unclear. While a more potent antiplatelet regimen will predispose to perioperative bleeding, it is hypothesized that through “platelet quiescence,” ischemic protection conferred by such therapy may provide a net clinical benefit. METHODS AND RESULTS: We compared patients undergoing coronary artery bypass surgery who were treated with a more potent antiplatelet inhibition strategy with those with a less potent inhibition through a meta-analysis. The primary outcome was all-cause mortality after bypass surgery. The analysis identified 4 studies in which the antiplatelet regimen was randomized and 6 studies that were nonrandomized. Combining all studies, there was an overall higher mortality with weaker strategies compared with more potent strategies (odds ratio, 1.38; 95% CI, 1.03–1.85; P=0.03). CONCLUSIONS: Our findings support the concept of platelet quiescence, in reducing mortality for patients with acute coronary syndrome requiring coronary artery bypass surgery. This suggests the routine up-front use of potent antiplatelet regimens in acute coronary syndrome, irrespective of likelihood of coronary artery bypass graft

Rugged Single Domain Antibody Detection Elements for Bacillus anthracis Spores and Vegetative Cells

Significant efforts to develop both laboratory and field-based detection assays for an array of potential biological threats started well before the anthrax attacks of 2001 and have continued with renewed urgency following. While numerous assays and methods have been explored that are suitable for laboratory utilization, detection in the field is often complicated by requirements for functionality in austere environments, where limited cold-chain facilities exist. In an effort to overcome these assay limitations for Bacillus anthracis, one of the most recognizable threats, a series of single domain antibodies (sdAbs) were isolated from a phage display library prepared from immunized llamas. Characterization of target specificity, affinity, and thermal stability was conducted for six sdAb families isolated from rounds of selection against the bacterial spore. The protein target for all six sdAb families was determined to be the S-layer protein EA1, which is present in both vegetative cells and bacterial spores. All of the sdAbs examined exhibited a high degree of specificity for the target bacterium and its spore, with affinities in the nanomolar range, and the ability to refold into functional antigen-binding molecules following several rounds of thermal denaturation and refolding. This research demonstrates the capabilities of these sdAbs and their potential for integration into current and developing assays and biosensors

Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

La qualité des soins, les guides de pratique et les modalités d’organisation

Laflamme Brigitte, Fervers Béatrice, Couture Félix, Minvielle Étienne. La qualité des soins, les guides de pratique et les modalités d’organisation. In: Santé, Société et Solidarité, n°1, 2010. Le cancer au quotidien. pp. 77-86

Impact of Processed Electroencephalography in Cardiac Surgery: A Retrospective Analysis

The use of brain function monitoring with processed electroencephalography (pEEG) during cardiac surgery is gaining interest for the optimization of hypnotic agent delivery during the maintenance of anesthesia. The authors sought to determine whether the routine use of pEEG-guided anesthesia is associated with a reduction of hemodynamic instability during cardiopulmonary bypass (CPB) separation and subsequently reduces vasoactive and inotropic requirements in the intensive care unit