Toward the first nonpeptidic molecular tong inhibitor of wild-type and mutated HIV-1 protease dimerization

Herein we describe the synthesis and HIV-1 protease (PR) inhibitory activity of 16 new peptidomimetic molecular tongs with a naphthalene scaffold. Their peptidic character was progressively decreased. Two of these molecules exhibited the best dimerization inhibition activity toward HIV-1 wild-type and multimutated ANAM-11 proteases obtained to date for this class of molecules (～40?nM for wild-type PR and 100?nM for ANAM-11 PR). Although the peptidic character of one molecular tong was completely suppressed, the mechanism of inhibition and inhibitory potency toward both proteases were maintained.     

Mechanisms of weight maintenance under high- and low-protein, low-glycaemic index diets

Scope: Weight maintenance after intended weight loss is a challenge in an obesogenic environment. In a large multicentre dietary intervention study (DiOGenes), it has recently been demonstrated that a high‐protein/low‐glycaemic index (HP/LGI) diet was slightly more efficient in maintaining weight loss than low‐protein/LGI or high‐GI (LP/LGI or HGI) diets. Here, we use a proteomic approach to assess the molecular mechanisms behind this positive effect. Methods and results: A subset of the most successful (weight loser, n=12) and unsuccessful (weight re‐gainer, n=12) individuals consuming the LGI diets with either high‐ or low‐protein content (HP or LP/LGI), following an initial calorie deficit run‐in weight loss phase, were analyzed at the plasma protein level. Proteomic analysis revealed 18 proteins regulated after 6 months of the dietary weight maintenance phase. Furthermore, 12 proteins were significantly regulated as a function of success rate under an HP diet, arising as candidate biomarkers of mechanisms of successful weight maintenance under an HP/LGI diet. Pregnancy‐zone protein (PZP) and protein S (PROS1) were revealed as novel biomarkers of weight maintenance showing opposite effects. Conclusion: Semantic network analysis of the 12 regulated proteins revealed that under an HP/LGI an anti‐atherogenic effect and alterations of fat metabolism were associated with the success of maintaining the initial weight loss.     

Proton-conducting ionic liquid-based Proton Exchange Membrane Fuel Cell membranes: The key role of ionomer-ionic liquid interaction

The paper deals with the synthesis and characterisation of proton-conducting ionic liquids (PCILs) and their polymer electrolytes obtained by blending modified Nafion membranes with different concentrations of PCILs. The PCILs are obtained by the neutralization of triethylamine with different organic acids. The first part of the paper studies the influence of acidity and acid structure on PCIL thermal and electrochemical performance, while the second part examines membrane conductivity and reveals it to depend more on PCIL structure than on its intrinsic conductivity. At 130 °C, conductivities exceeding 10 mS cm⁻¹ were obtained in fully anhydrous conditions.     

Beyond Intercalation‐Based Li‐Ion Batteries: The State of the Art and Challenges of Electrode Materials Reacting Through Conversion Reactions

Despite the imminent commercial introduction of Li‐ion batteries in electric drive vehicles and their proposed use as enablers of smart grids based on renewable energy technologies, an intensive quest for new electrode materials that bring about improvements in energy density, cycle life, cost, and safety is still underway. This Progress Report highlights the recent developments and the future prospects of the use of phases that react through conversion reactions as both positive and negative electrode materials in Li‐ion batteries. By moving beyond classical intercalation reactions, a variety of low cost compounds with gravimetric specific capacities that are two‐to‐five times larger than those attained with currently used materials, such as graphite and LiCoO₂, can be achieved. Nonetheless, several factors currently handicap the applicability of electrode materials entailing conversion reactions. These factors, together with the scientific breakthroughs that are necessary to fully assess the practicality of this concept, are reviewed in this report.     

Characterisation of hydrodynamics induced by air injection related to membrane fouling behaviour

The study focuses on fine bubble and spherical cap bubble injection in case of outside/in fibres immersed in a tank. The objectives are to quantify liquid circulations and shear stresses along the membrane and to understand their effects on the fouling resistance. Thus, both filtration experiments and hydrodynamic characterisation were performed in the same aeration conditions. Only particle cake deposit was studied as fouling mode and the hydrodynamics was characterized experimentally by 2-phase flow particle image velocimetry (PIV) and numerically with the CFD code FLUENT. Results presented in this paper are limited to tight hollow-fibres to well understand hydrodynamics without fibre motion. One important result is that mean values of wall shear stress are very low (maximum 0.25 Pa) eliminating the wall shear stress as a mechanism able to explain filtration performances for a non-confined aeration without fibre displacement. In addition, an analysis has been conducted in terms of horizontal liquid flow toward the membrane. The quantification of this flow allowed to conclude that i) for a given local bubble flow rate, there is no influence of the kind of aeration on this horizontal flow rate; and ii) the filtration performances can be correlated with this horizontal flow. The reason might be an over concentration of particles near the membrane surface induced by this flow.     

Silicon Vibrating Wires at Low Temperatures

Nowadays microfabrication techniques originating from micro-electro nics enable to create mechanical objects of micron-size. The field of Micro-Electro-Mechanical devices (MEMs) is continuously expanding, with an amazingly broad range of applications at room temperature. Vibrating objects (torsional oscillators, vibrating wires) widely used at low temperatures to study quantum fluids, can be replaced advantageously by Silicon MEMs. In this letter we report on the study of Silicon vibrating wire devices. A goal-post structure covered with a metal layer is driven at resonance by the Laplace force acting on a current in a magnetic field, while the induced voltage arising from the cut magnetic flux allows to detect the motion. The characteristics of the resonance have been studied from 10 mK to 30 K, in vacuum and in ⁴He gas. In this article, we focus on the results obtained above 1.5 K, in vacuum and gas, and introduce some features observed at lower temperatures. The resonant properties can be quantitatively understood by means of simple models, from the linear regime to a highly non-linear response at strong drives. We demonstrate that the non-linearity is mostly due to the geometry of the vibrators. We also show that in our device the friction mechanisms originate in the metallic layers, and can be fully characterized. The interaction with ⁴He gas is fit to theory without adjustable parameters.      

Effect of GABA,a Bacterial Metabolite,on Pseudomonas fluorescens Surface Properties and Cytotoxicity

Different bacterial species and, particularly Pseudomonas fluorescens, can produce gamma-aminobutyric acid (GABA) and express GABA-binding proteins. In this study, we investigated the effect of GABA on the virulence and biofilm formation activity of different strains of P. fluorescens. Exposure of a psychotropic strain of P. fluorescens (MF37) to GABA (10⁻⁵ M) increased its necrotic-like activity on eukaryotic (glial) cells, but reduced its apoptotic effect. Conversely, muscimol and bicuculline, the selective agonist and antagonist of eukaryote GABA_A receptors, respectively, were ineffective. P. fluorescens MF37 did not produce biosurfactants, and its caseinase, esterase, amylase, hemolytic activity or pyoverdine productions were unchanged. In contrast, the effect of GABA was associated to rearrangements of the lipopolysaccharide (LPS) structure, particularly in the lipid A region. The surface hydrophobicity of MF37 was marginally modified, and GABA reduced its biofilm formation activity on PVC, but not on glass, although the initial adhesion was increased. Five other P. fluorescens strains were studied, and only one, MFP05, a strain isolated from human skin, showed structural differences of biofilm maturation after exposure to GABA. These results reveal that GABA can regulate the LPS structure and cytotoxicity of P. fluorescens, but that this property is specific to some strains.     

Temperature Modulation Measurements of the Thermal Properties of Nanosystems at Low Temperatures

We report on the dynamic measurements of thermal properties of nanosystems at very low temperatures. These techniques are based on the modulation of the temperature and hence leads to highly sensitive measurements. We will discuss the intrinsic limitations of these methods when the thermal properties of nano-objects are studied at very low temperatures, much below 1 K. Firstly, we will present thermal conductance measurements using the 3ω method. This technique is limited at low temperatures due to the significant increase of the mean free path. Secondly, heat capacity measurements using ac calorimetry are outlined, and again restrictions occur due to the continuous temperature gradient inherent to that technique. Propositions are made in order to overcome these limitations.     

Measurements and simulation of the Zeeman splitting in NdOCl and Nd:LiYF4

Measurements and simulation of the Zeeman effect in NdOCl and 1%Nd³⁺:LiYF₄ single crystals were carried out. The rare earth local symmetries are C_4v and D_2d respectively. The isomorphism between these two point groups allows discussion on symmetry assignments. The attention is focused on the ⁴G_7/2 and ⁴G_9/2 levels for NdOCl and on the ⁴F_9/2 and ⁴G_7/2 levels for Nd³⁺:LiYF₄, because they are representative of the general splitting behaviour. We have first revisited the simulation of the energy level scheme in order to deal with confident wave functions. In the experimental magnetic field (B) range we have obtained linear, non-linear, undefined crossing and anti-crossing levels. These features depend on the orientation of B, on the irreducible representation and on the transition closeness. The line widths have been the main obstacle in confirming crossing regions, because their average values are 8 cm⁻¹ at liquid helium temperature. The simulations were performed by introducing the magnetic Hamiltonian μ_BB(L+g_eS) in the secular determinant before diagonalisation. A magnetic accidental degeneracy is considered when discussing the crossing and anti-crossing cases.