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

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.     

The X-prolyl dipeptidyl-peptidase PepX of Streptococcus thermophilus initially described as intracellular is also responsible for peptidase extracellular activity

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.     

An evidential approach for detection of abnormal behaviour in the presence of unreliable sensors

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.     

Improvement of fermentative biohydrogen production by Clostridium butyricum CWBI1009 in sequenced-batch,horizontal fixed bed and biodisc-like anaerobic reactors with biomass retention

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.     

Anisotropic loss of toughness with physical aging of work toughened polycarbonate

We have studied the response of mechanically toughened and physically aged polycarbonate primarily using Charpy impact and ultrasonic wave speed measurements. The toughening was conducted through plastic compression on as‐received PC. The Charpy impact tests showed anisotropic toughening, both in the absorbed energy and in the mode of fracture. The amount of toughening with plastic compression, even though anisotropic, is centered around the response of annealed and quenched samples, which represent the response of an unaged PC. There was an anisotropic drop in the toughness of some samples with aging. The time of this drop was uncorrelated in the different directions and disappeared for the highly toughened samples. This transition was bimodal and statistically distributed between either a fully ductile or a fully brittle failure. As the samples were prepared in a manner to remove induced residual stresses, this drop in toughening may be associated with an intrinsic anisotropic thermal aging of the deformed material. POLYM. ENG. SCI., 54:794–804, 2014. © 2013 Society of Plastics Engineers