Superconductivity fluctuations in Bi(Pb) based granular ceramics superconductors: evidence for fractal behavior

We report precise measurements of the electrical resistivity in three different Bi(Pb) based granular ceramics superconductors. We show that a single critical exponent (5/6) describes the superconductivity fluctuations. Such a critical exponent indicates a fractal behavior of the superconducting path. Our results thus indicate a strict two dimensional fluctuation percolation set (below the superconductivity onset temperature 195 K down toT _c), and provide some proof for Tarascon et al. shell conductivity path hypothesis. We estimate the shell thickness to be of the order of 10 Å.     

Comparison between the growth of gold particles onto MgO and amorphous carbon substrates by in situ electrical conductance measurements

The sheet conductance of gold condensates on MgO anda-C is expressed in terms of granulometric quantities. This expression enables us to follow the evolution of metal repartition on its substrate during the gold evaporation. The difference between the growth modes of these gold layers on MgO and ona-C is explained by the predominance of respectively nucleation and coalescence phenomena     

Structure investigation of multiply — twinned Ni particles by electron investigation

Nickel particles are prepared by reducing NiBr₂ in organic solvent. These Ni particles are investigated by electron diffraction. Some of them are icosahedral or decahedral. We have compared the experimental results and the theoretical patterns obtained with models composed of units with a fcc structure or with either rhombohedral or orthorhombic structure for icosahedral or decahedral particles respectively. The results show that the particles are composed of units with fcc structure.     

Similarity searching using reduced graphs

Reduced graphs provide summary representations of chemical structures. In this work, the effectiveness of reduced graphs for similarity searching is investigated. Different types of reduced graphs are introduced that aim to summarize features of structures that have the potential to form interactions with receptors while retaining the topology between the features. Similarity searches have been carried out across a variety of different activity classes. The effectiveness of the reduced graphs at retrieving compounds with the same activity as known target compounds is compared with searching using Daylight fingerprints. The reduced graphs are shown to be effective for similarity searching and to retrieve more diverse active compounds than those found using Daylight fingerprints; they thus represent a complementary similarity searching tool.     

Amyloid binding and beyond: a new approach for Alzheimer's disease drug discovery targeting Aβo–PrPC binding and downstream pathways

Amyloid β oligomers (Aβo) are the main toxic species in Alzheimer''s disease, which have been targeted for single drug treatment with very little success. In this work we report a new approach for identifying functional Aβo binding compounds. A tailored library of 971 fluorine containing compounds was selected by a computational method, developed to generate molecular diversity. These compounds were screened for Aβo binding by a combined ¹⁹F and STD NMR technique. Six hits were evaluated in three parallel biochemical and functional assays. Two compounds disrupted Aβo binding to its receptor PrP^C in HEK293 cells. They reduced the pFyn levels triggered by Aβo treatment in neuroprogenitor cells derived from human induced pluripotent stem cells (hiPSC). Inhibitory effects on pTau production in cortical neurons derived from hiPSC were also observed. These drug-like compounds connect three of the pillars in Alzheimer''s disease pathology, i.e. prion, Aβ and Tau, affecting three different pathways through specific binding to Aβo and are, indeed, promising candidates for further development.

A new approach combining virtual screening, ¹⁹F and STD NMR, and biochemical assays using hiPSC and targetting multiple pathways involving Aβ, PrP^C and Tau provides a more effective strategy for Alzheimer''s disease drug discovery than Aβ only approach.     

Analysis of data fusion methods in virtual screening: theoretical model

This paper presents a theoretical model of how data fusion can be used to combine the results of multiple similarity searches of chemical databases. The model is based on frequency distributions of similarity values that are fused using a multiple integration over regions defined by the particular fusion rule that is being applied. For pairwise fusion, the resulting double integrals are straightforward to evaluate for simple model distributions. Similarity values for recovered-active and recovered-nonactive frequency distributions are independently modeled using a constant background, linearly biased terms, and a first-order correlated term. The model shows that two standard fusion rules can give performance enhancements in some cases but that the results of fusion are dependent on many factors that, taken together, can lead to seemingly inconsistent levels of enhancement.     

Spontaneous association of hydrophobized dextran and poly-beta-cyclodextrin into nanoassemblies. Formation and interaction with a hydrophobic drug

New nanoassemblies were instantaneously prepared by mixing two aqueous solutions, one containing a beta-cyclodextrin polymer (pbetaCD), and the other a hydrophobically modified by alkyl chains dextran (MD). The formation mechanism and the inner structure of these nanoassemblies were analysed using surface tension measurements and (1)H NMR spectroscopy. The effect of a hydrophobic guest molecule, such as benzophenone (BZ), on the formation and stability of the nanoassemblies was also evaluated. MD exhibited the typical behaviour of a soluble amphiphilic molecule and adsorbed at the air/water interface. Whereas the injection of native beta-CDs in the solution beneath the adsorbed MD monolayer did not produce any change in the surface tension, that of the pbetaCD resulted in an increase in the surface tension, indicating the desorption of the polymer from the interface. This result accounts for a cooperative effect of beta-CDs linked together in the pbetaCD polymer on dextran desorption. The presence of benzophenone in the system hindered the sequestration of dextran alkyl moieties by beta-CD in the polymer without impeding the formation of associative nanoassemblies of 100-200 nm. (1)H NMR investigations demonstrated that, in the BZ-loaded nanoassemblies, the hydrophobic molecule was mainly located into the cyclodextrin cavities.