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91.
Discovery of Heterocyclic Nonacetamide Synaptic Vesicle Protein 2A (SV2A) Ligands with Single‐Digit Nanomolar Potency: Opening Avenues towards the First SV2A Positron Emission Tomography (PET) Ligands
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Joël Mercier Laurence Archen Véronique Bollu Stéphane Carré Yves Evrard Dr. Eric Jnoff Dr. Benoît Kenda Bénédicte Lallemand Dr. Philippe Michel Dr. Florian Montel Dr. Florence Moureau Nathalie Price Dr. Yannick Quesnel Dr. Xavier Sauvage Dr. Anne Valade Dr. Laurent Provins 《ChemMedChem》2014,9(4):693-698
The role of the synaptic vesicle protein 2A (SV2A) protein, target of the antiepileptic drug levetiracetam, is still mostly unknown. Considering its potential to provide in vivo functional insights into the role of SV2A in epileptic patients, the development of an SV2A positron emission tomography (PET) tracer has been undertaken. Using a 3D pharmacophore model based on close analogues of levetiracetam, we report the rationale design of three heterocyclic non‐acetamide lead compounds, UCB‐A, UCB‐H and UCB‐J, the first single‐digit nanomolar SV2A ligands with suitable properties for development as PET tracers. 相似文献
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Zeeshan Hafeez Céline Cakir-Kiefer Xavier Lecomte Laurent Miclo Annie Dary-Mourot 《Journal of dairy science》2019,102(1):113-123
This study addresses the hypothesis that the extracellular cell-associated X-prolyl dipeptidyl-peptidase activity initially described in Streptococcus thermophilus could be attributable to the intracellular X-prolyl dipeptidyl-peptidase PepX. For this purpose, a PepX-negative mutant of S. thermophilus LMD-9 was constructed by interrupting the pepX gene and named LMD-9-ΔpepX. When cultivated, the S. thermophilus LMD-9 wild type strain grew more rapidly than its ΔpepX mutant counterpart. Thus, the growth rate of the LMD-9-ΔpepX strain was reduced by a factor of 1.5 and 1.6 in milk and LM17 medium (M17 medium supplemented with 2% lactose), respectively. The negative effect of the PepX inactivation on the hydrolysis of β-casomorphin-7 was also observed. Indeed, when incubated with this peptide, the LMD-9-ΔpepX mutant cells were unable to hydrolyze it, whereas this peptide was completely degraded by the S. thermophilus LMD-9 wild type cells. This hydrolysis was not due to leakage of intracellular PepX, as no peptide hydrolysis was highlighted in cell-free filtrate of wild type strain. Therefore, based on these results, it can be presumed that though lacking an export signal, the intracellular PepX might have accessed the β-casomorphin-7 externally, perhaps via its galactose-binding domain-like fold, this domain being known to help enzymes bind to several proteins and substrates. Therefore, the identification of novel distinctive features of the proteolytic system of S. thermophilus will further enhance its credibility as a starter in milk fermentation. 相似文献
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International Journal of Fracture - 相似文献
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An evidential approach for detection of abnormal behaviour in the presence of unreliable sensors 总被引:1,自引:0,他引:1
Bruno Marhic Laurent DelahocheClément Solau Anne Marie Jolly-DesodtVincent Ricquebourg 《Information Fusion》2012,13(2):146-160
We address the problem of abnormal behaviour recognition of the inhabitant of a smart home in the presence of unreliable sensors. The corner stone of this work is a two-level architecture sensor fusion based on the Transferable Belief Model (TBM). The novelty of our work lies in the way we detect both unreliable sensors and abnormal behaviour within our architecture by using a temporal analysis of conflict resulting from the fusion of sensors. Detection of abnormal behaviour is based on a prediction/observation process and the influence of the faulty sources is discarded by discounting coefficients. Our architecture is tested in a real-life setting using three heterogeneous sensors enabling the detection of impossible transitions between three possible postures: Sitting, Standing and Lying. The impact of having a faulty sensor management is also tested in the real-life experiment for posture detection. 相似文献
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Serge Hiligsmann Laurent BeckersJulien Masset Christopher HamiltonPhilippe Thonart 《International Journal of Hydrogen Energy》2014
A horizontal tubular fixed bed bioreactor (HFBR) and an anaerobic biodisc-like reactor (AnBDR) were designed to both fix Clostridium biomass and enable rapid transfer of the hydrogen produced to gas phase in order to decrease the strong effect of H2 partial pressure and H2 supersaturation on the performances of Clostridium strains. The highest H2 production rate (703 mL H2/L h) and yield (302 mL/g glucose consumed i.e. 2.4 mol/mol) with the pure culture were recorded in the AnBDR with 300 mL culture medium (total volume 2.3 L) at pH 5.2 and a glucose loading rate of 2.87 g/L h. These results are about 2.3 and 1.3-fold higher than those achieved in the same bioreactor with 500 mL liquid medium and with the same glucose consumption rate. Therefore, our experimentations and a short review of the literature reported in this paper emphasize the relevance of performing bioreactors with high L/G transfer. 相似文献