Inhibition of HIV-1 by a peptide ligand of the genomic RNA packaging signal Psi

The interaction of the nucleocapsid NCp7 of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein with the RNA packaging signal Psi ensures specific encapsidation of the dimeric full length viral genome into nascent virus particles. Being an essential step in the HIV-1 replication cycle, specific genome encapsidation represents a promising target for therapeutic intervention. We previously selected peptides binding to HIV-1 Psi-RNA or stem loops (SL) thereof by phage display. Herein, we describe synthesis of peptide variants of the consensus HWWPWW motif on membrane supports to optimize Psi-RNA binding. The optimized peptide, psi-pepB, was characterized in detail with respect to its conformation and binding properties for the SL3 of the Psi packaging signal by NMR and tryptophan fluorescence quenching. Functional analysis revealed that psi-pepB caused a strong reduction of virus release by infected cells as monitored by reduced transduction efficiencies, capsid p24 antigen levels, and electron microscopy. Thus, this peptide shows antiviral activity and could serve as a lead compound to develop new drugs targeting HIV-1.     

Modélisation de la cinétique de biodégradation de phénol par granules aérobies

This work describes a model of the biodegradation of phenol carried out by aerobic granules. These granules were obtained by culturing an activated sludge supernatant in a sequencing batch reactor fed with a synthetic waste water and subsequently, by acclimation to phenol (100 mg/L). The kinetics of phenol biodegradation by the aerobic granules was investigated over a wide range of initial phenol concentrations (40–1112 mg/L) in shake‐flask cultures. A Haldane‐type model was adjusted to the experimental results, which depicts successfully the phenol biodegradation profiles in the entire range of initial concentrations studied by using only one set of parameters. It is our view that the proposed model could contribute to the knowledge about the ability of aerobic granular systems to biodegrade toxic, inhibitory compounds such as phenol.     

Influence of epitaxial stress on spinodal decomposition in binary alloys with large size effects: application to the Au–Ni system

Within the framework of Cahn’s pioneering theory of spinodal decomposition, the effect of the epitaxial stress on the stability of a binary alloy solid solution against infinitesimal compositional fluctuations is revisited. It is shown that the elastic energy term due to a coherent lattice mismatch with a substrate modifies the linearised diffusion equation. This term is particularly high when size effects between the two constituents are strong. It is then necessary to take into account anharmonic terms in the expression of the elastic energy. From the modified diffusion equation, a new spinodal curve, called the epitaxial coherent spinodal, may be calculated for different substrate lattice parameters. The results of the model are compared with recent experiments on coherently grown (001) Au–Ni alloys. A modulated structure has been evidenced upon annealing which is in good agreement with our calculations.

Résumé

Dans le cadre de la théorie de la décomposition spinodale développèe par Cahn, nous présentons l’effet des contraintes épitaxiales sur la stabilitéd’une solution solide d’alliage binaire soumise ádes fluctuations de compostion infinitésimales. Les contraintes induites par l’épitaxie cohérente sur un substrat ayant un paramètre de maille différent de celui de la solution solide considérée sont àl’origine d’un terme d’énergie élastique dont il faut tenir compte dans l’équation de diffusion. Ce terme devient particulièrement important lorsque les effets de taille entre les deux constituants sont grands. Nous montrons qu’il est alors nécessaire de considérer dans l’expression de l’énergie élastique les termes anharmoniques. Une nouvelle spinodale, appelée spinodale cohérente épitaxiale, peut être calculée pour différentes valeurs du paramètre de maille du substrat. Les calculs sont comparés avec les résulats expérimentaux obtenus sur des alliages Au–Ni (001) élaborés de manière cohérente. Une structure modulée a étémise en evidence au cours de recuits, ce qui est en accord avec les résultats du modèle.     

INFLUENCE OF MODEL UNCERTAINTY ON THE DYNAMIC OPTIMAL CONTROL PERFORMANCE OF A BATCH CORN DRYING PROCESS

A semi-empirical nonlinear model of moisture content and wet-milling quality degradation in com drying is established. The model uncertainty is expressed as a relative error level which includes a pre-specified percentage of experimental data. An optimal control strategy for batch drying is determined which maximizes the dryer throughput, while simultaneously satisfying two quality constraints on the final state: achieving specified moisture content and wet-milling quality levels. Taking into account the model uncertainty results in a conservative but less efficient control strategy. The performance - robustness compromise is discussed.     

Zika Virus Growth in Human Kidney Cells Is Restricted by an Elevated Glucose Level

Mosquito-borne Zika virus (ZIKV) became a real threat to human health due to the lack of vaccine and effective antiviral treatment. The virus has recently been responsible for a global outbreak leading to millions of infected cases. ZIKV complications were highlighted in adults with Guillain–Barré syndrome and in newborns with increasing numbers of congenital disorders ranging from mild developmental delays to fatal conditions. The ability of ZIKV to establish a long-term infection in diverse organs including the kidneys has been recently documented but the consequences of such a viral infection are still debated. Our study aimed to determine whether the efficiency of ZIKV growth in kidney cells relates to glucose concentration. Human kidney HK-2 cells were infected with different ZIKV strains in presence of normal and high glucose concentrations. Virological assays showed a decrease in viral replication without modifying entry steps (viral binding, internalization, fusion) under high glucose conditions. This decrease replication was associated with a lower virus progeny and increased cell viability when compared to ZIKV-infected HK-2 cells in normal glucose concentration. In conclusion, we showed for the first time that an elevated glucose level influences ZIKV replication level with an effect on kidney cell survival.     

Association of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients

The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet FcγRIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet FcγRIIA actually binds monomeric IgG, we investigated the role of platelets and FcγRIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn’s disease. The influence of platelet count and FcγRIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from ≈20 days (RR) and ≈17 days (HR) at 150 × 10⁹/L, respectively, to ≈13 days (both HR and RR) at 350 × 10⁹/L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet FcγRIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet FcγRIIA, which is probably tuned by its affinity for IgG2.     

On Analyzing the Potential of a Layer-2 Multi-hop Authentication and Credential Delivery Scheme for Vehicular Communications

In this paper we introduce a new security architecture and security mechanisms for vehicular networks providing a layer-2 multi-hop authentication and credential delivery scheme between vehicles and the network operator authentication server. We present a performance analysis of the proposed solution under various vehicles and Access Points (APs) densities, showing the potential of our scheme in providing a more efficient, robust and scalable authentication and credential delivery to vehicles when compared against the classical single-hop scheme.     

New temperature dependent thermal conductivity data for water-based nanofluids

This paper presents effective thermal conductivity measurements of alumina/water and copper oxide/water nanofluids. The effects of particle volume fraction, temperature and particle size were investigated. Readings at ambient temperature as well as over a relatively large temperature range were made for various particle volume fractions up to 9%. Results clearly show the predicted overall effect of an increase in the effective thermal conductivity with an increase in particle volume fraction and with a decrease in particle size. Furthermore, the relative increase in thermal conductivity was found to be more important at higher temperatures. Obtained results compare favorably with certain data sets and theoretical models found in current literature.     

Synthesis and Biological Evaluation of Chromium Bioorganometallics Based on the Antibiotic Platensimycin Lead Structure

The recent discovery of the natural product platensimycin as a new antibiotic lead structure has triggered the synthesis of numerous organic derivatives for structure–activity relationship studies. Herein, we describe the synthesis, characterization and biological evaluation of the first organometallic antibiotic inspired by platensimycin. Two bioorganometallic compounds containing (η⁶‐pentamethylbenzene)Cr(CO)₃ ( 2 ) and (η⁶‐benzene)Cr(CO)₃ ( 3 ), linked by an amide bond to the aromatic part of platensimycin, were synthesized. Their antibiotic activities were tested against B. subtilis 168 (Gram positive) and E. coli W3110 (Gram negative) bacterial strains. Both compounds were found to be inactive against E. coli but derivative 2 inhibits B. subtilis growth at a moderate MIC value of 0.15 mM . To test the intrinsic toxicity of chromium, several chromium salts along with {η⁶‐(3‐pentamethylphenyl propionic acid)}Cr(CO)₃ ( 5 ) and {η⁶‐(3‐phenyl propionic acid)}Cr(CO)₃ ( 6 ) were tested against both bacterial strains. No activity was observed against E. coli for any of the compounds; B. subtilis growth was not inhibited by Cr(NO₃)₃ and only very weakly by 5 , K₂Cr₂O₇ and Na₂CrO₄ at MIC values of 0.5, 0.68 and 1.24 mM , respectively. Compounds 2 , 3 , 5 and 4 (the pure organic analogue of 2 ) show similar cytotoxicity against HeLa, HepG2 and HT‐29 mammalian cell lines. Furthermore, the cellular uptake and the intracellular distribution of compounds 2 , 3 and Cr(NO₃)₃ in B. subtilis were studied using atomic absorption spectroscopy to gain insight in to the possible cellular targets. Compound 2 was found to be readily taken up and distributed almost equally among cytosol, cell debris and cell membrane in B. subtilis.     

A system for automatic measurement of circadian activity deviations in telemedicine

A system for the automatic measurement of the circadian activity deviations in telemedicine has been developed within the framework of a "Health Integrated Smart Home Information System" (HIS2). HIS2 is an experimental platform for the evaluation and the development of technologies in order to ensure the security and quality of life for patients who need home based medical monitoring. Location sensors are placed in each room of the HIS2, allowing the monitoring of patient's successive activity phases within the patient's home environment. We proceeded with a sampling in an hourly schedule to detect weak rhythmic variations. Based on numerous measurements, we established a mean value with confidence limits. These also allowed us to define a zone within which the patient's activity is qualified to be "predictable." Alerts are set off if the patient's activity deviates from this zone.