Towards Massively Parallel Computations in Algebraic Geometry

Foundations of Computational Mathematics - Introducing parallelism and exploring its use is still a fundamental challenge for the computer algebra community. In high-performance numerical...     

Fluorescent small molecule probe to modulate and explore α2β1 integrin function

Collagen binding integrins are an important family of cell surface receptors that mediate bidirectionally signals between the interior of the cell and the extracellular matrix. The protein-protein interactions between cells and collagen are necessary for many physiological functions, but also promote diseases. For example, the interaction of α2β1 integrin and collagen has been shown to have an important role in thrombus formation and cancer spread. The fact that the discovery of small molecules that can block such protein-protein interactions is highly challenging has significantly hindered the discovery of pharmaceutical agents to treat these diseases. Here, we present a rationally designed novel fluorescent molecule that can be synthesized in just a few minutes from commercially available starting materials. This molecule blocks the protein-protein interaction between α2β1 integrin and collagen, and due to its fluorescent properties, it can be employed in wide variety of biological applications.     

Low-temperature neutron diffraction structures of N-glycoprotein linkage models and analogues: structure refinement and trifurcated hydrogen bonds

The biological addition of oligosaccharide moieties to asparagine residues of N-glycoproteins influences the properties and bioactivities of these macromolecules. The low-temperature neutron crystal structures of three N-glycoprotein linkage models and analogues provide accurate characterization of the three-dimensional structure of the conserved GlcNAc-Asn linkage. These first crystal structures of N-acetylated carbohydrates obtained by neutron diffraction provide high-resolution geometrical parameters that can be used for force-field parametrization and subsequent molecular dynamics simulation of N-glycoproteins. The correct localization of hydrogen atoms demonstrates the occurrence of trifurcated hydrogen bonds and hydrophobic contacts.     

Preparation of Benz[b]Indeno[1,2-e]Pyran-11(6H)-Ones and Benz[b]Indeno[1,2-e]Thiopyran-11(6H)-One from Dilithiated 2-Indanone and Lithiated Methyl Salicylates or Lithiated Methyl Thiosalicylate

Dilithiated 2-indanone was prepared with excess lithium diisopropylamide, and the resulting intermediate was condensed with several lithiated methyl salicylates or lithiated methyl thiosalicylate, which was followed by acid cyclization to benz[b]indeno[1,2-e]pyran-11(6H)-ones 3--9 or benz[b]indeno[1,2-e]thiopyran-11(6H)-one 10, which are rare fused-ring indeno-chromones and a new indeno-thiochromone, respectively.     

High-pressure crystallization of isotactic polypropylene droplets

Dispersions of isotactic polypropylene (PP) particles in polystyrene (PS) were produced by interfacially driven breakup of nanolayers in multilayered systems that were fabricated by means of layer-multiplying coextrusion. The droplet size was controlled by the individual PP layer thickness ranging from 12 to 200?nm. In addition, PP was melt blended with PS to produce PP droplets larger than those formed by breakup of nanolayers. The dispersions of PP particles in the PS matrix were melted and annealed under high pressure of 200?MPa. Only the largest PP droplets, with average sizes of 170?μm, crystallized predominantly in the γ form. In the 42-μm droplets obtained by breakup of 200?nm layers, a minor content of the γ form was found whereas the smaller droplets obtained by breakup of the thinner nanolayers contained the α form and/or the mesophase. The results showed that the γ phase formed only in the droplets sufficiently large to contain the most active heterogeneities nucleating PP crystallization under atmospheric pressure. It is concluded that the presence of nucleating heterogeneities is necessary for crystallization of PP in the γ form under high pressure.     

Microchip integrating magnetic nanoparticles for allergy diagnosis

We report on the development of a simple and easy to use microchip dedicated to allergy diagnosis. This microchip combines both the advantages of homogeneous immunoassays i.e. species diffusion and heterogeneous immunoassays i.e. easy separation and preconcentration steps. In vitro allergy diagnosis is based on specific Immunoglobulin E (IgE) quantitation, in that way we have developed and integrated magnetic core-shell nanoparticles (MCSNPs) as an IgE capture nanoplatform in a microdevice taking benefit from both their magnetic and colloidal properties. Integrating such immunosupport allows to perform the target analyte (IgE) capture in the colloidal phase thus increasing the analyte capture kinetics since both immunological partners are diffusing during the immune reaction. This colloidal approach improves 1000 times the analyte capture kinetics compared to conventional methods. Moreover, based on the MCSNPs' magnetic properties and on the magnetic chamber we have previously developed the MCSNPs and therefore the target can be confined and preconcentrated within the microdevice prior to the detection step. The MCSNPs preconcentration factor achieved was about 35,000 and allows to reach high sensitivity thus avoiding catalytic amplification during the detection step. The developed microchip offers many advantages: the analytical procedure was fully integrated on-chip, analyses were performed in short assay time (20 min), the sample and reagents consumption was reduced to few microlitres (5 μL) while a low limit of detection can be achieved (about 1 ng mL(-1)).     

Design of multitarget activity landscapes that capture hierarchical activity cliff distributions

An activity landscape model of a compound data set can be rationalized as a graphical representation that integrates molecular similarity and potency relationships. Activity landscape representations of different design are utilized to aid in the analysis of structure-activity relationships and the selection of informative compounds. Activity landscape models reported thus far focus on a single target (i.e., a single biological activity) or at most two targets, giving rise to selectivity landscapes. For compounds active against more than two targets, landscapes representing multitarget activities are difficult to conceptualize and have not yet been reported. Herein, we present a first activity landscape design that integrates compound potency relationships across multiple targets in a formally consistent manner. These multitarget activity landscapes are based on a general activity cliff classification scheme and are visualized in graph representations, where activity cliffs are represented as edges. Furthermore, the contributions of individual compounds to structure-activity relationship discontinuity across multiple targets are monitored. The methodology has been applied to derive multitarget activity landscapes for compound data sets active against different target families. The resulting landscapes identify single-, dual-, and triple-target activity cliffs and reveal the presence of hierarchical cliff distributions. From these multitarget activity landscapes, compounds forming complex activity cliffs can be readily selected.     

Preparation and characterization of pore-wall modification gradients generated on porous silicon photonic crystals using diazonium salts

One-dimensional photonic crystals (rugate filters) constructed from porous silicon were modified by the chemical hydrosilylation of terminal alkenes (decyl, 10-carboxydecyl, and 10-hydroxydecyl) in the presence of a concentration gradient of diazonium salt initiators. The concentration gradient was generated by vertically orienting the Si wafer containing the porous Si layer in an alkene solution and then introducing the diazonium salt at the bottom edge of the wafer. Slow diffusion of the salt led to a varying density of grafted alkene across the surface of the porous layer. The modified surfaces were end-capped with methyl groups by electrochemical grafting to impart improved stability and greater hydrophobicity. The surface modified with 10-carboxydecyl species was ionized by deprotonation of the carboxy groups to increase the hydrophilicity of this porous silicon surface. The pore-wall modification gradients were characterized using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS). The more hydrophilic portion of the gradient changes color when water infiltrates the porous nanostructure because of a shift in the stop band of the photonic crystal. The more hydrophobic portion of the gradient excludes water, although mixtures of water and ethanol will infiltrate this region, depending on the concentration of ethanol in the mixture. A simple visual sensor for small quantities of ethanol in water, capable of detecting ethanol concentrations of between 0 and 8% with a resolution of 1% is demonstrated.     

Bifunctional rhenium complexes for the catalytic transfer-hydrogenation reactions of ketones and imines

The silyloxycyclopentadienyl hydride complexes [Re(H)(NO)(PR(3))(C(5)H(4)OSiMe(2)tBu)] (R=iPr (3 a), Cy (3 b)) were obtained by the reaction of [Re(H)(Br)(NO)(PR(3))(2)] (R=iPr, Cy) with Li[C(5)H(4)OSiMe(2)tBu]. The ligand-metal bifunctional rhenium catalysts [Re(H)(NO)(PR(3))(C(5)H(4)OH)] (R=iPr (5 a), Cy (5 b)) were prepared from compounds 3 a and 3 b by silyl deprotection with TBAF and subsequent acidification of the intermediate salts [Re(H)(NO)(PR(3))(C(5)H(4)O)][NBu(4)] (R=iPr (4 a), Cy (4 b)) with NH(4)Br. In nonpolar solvents, compounds 5 a and 5 b formed an equilibrium with the isomerized trans-dihydride cyclopentadienone species [Re(H)(2)(NO)(PR(3))(C(5)H(4)O)] (6 a,b). Deuterium-labeling studies of compounds 5 a and 5 b with D(2) and D(2)O showed H/D exchange at the H(Re) and H(O) positions. Compounds 5 a and 5 b were active catalysts in the transfer hydrogenation reactions of ketones and imines with 2-propanol as both the solvent and H(2) source. The mechanism of the transfer hydrogenation and isomerization reactions was supported by DFT calculations, which suggested a secondary-coordination-sphere mechanism for the transfer hydrogenation of ketones.