PEO-PPO block copolymer vectors do not interact directly with DNA but with lipid membranes

Small angle neutron (SANS) and light scattering was used to study the interaction between fragments of double stranded deoxyribonucleic acid (DNA) and a synthetic triblock [poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)] amphiphilic polymer, known as L64, a potential vector for gene therapy. The mechanism of action of this vector is yet unknown. The contrast variation method was used to separate the partial structure factors of the different components in mixtures of triblock and DNA. It has been found that the copolymer and DNA molecules exhibit repulsive interactions. Further, the interaction between the copolymer and a model lipid membrane was investigated in order to explain the action of the vector. Electrical measurements on black lipid membranes indicated that the main effect of L64 as a vector is to permeabilize the cell's membrane.     

5a-Carba-β-D-, 5a-Carba-β-L- and 5-Thio-β-L-xylopyranosides as New Orally Active Venous Antithrombotic Agents

Mitsunobu displacement of (−)-(1S,4R,5S,6S)-4,5,6-tris{[(tert-butyl)dimethylsilyl]oxy}cyclohex-2-en-1-ol ((−)- 12 ; a (−)-conduritol-F derivative) with 4-ethyl-7-hydroxy-2H-1-benzopyran-2-one ( 16 ) provided a 5a-carba-β-D -pyranoside (+)- 17 that was converted into (+)-4-ethyl-7-[(1′R,4′R,5′S,6′R)-4′,5′,6′-trihydroxycyclohex-2′-en-1′-yloxy]-2H-1-benzopyran-2-one ((+)- 5 ) and (+)-4-ethyl-7-[(1′R,2′R,3′S,4′R)-2′,3′,4′-trihydroxycyclohexyloxy]-2H-1-benzopyran-2-one ((+)- 6 ). The 5a-carba-β-D -xyloside (+)- 6 was an orally active antithrombotic agent in the rat (venous Wessler's test), but less active than racemic carba-β-xylosides (±)- 5 and (±)- 6 . The 5a-carba-β-L -xyloside (−)- 6 was derived from the enantiomer (+)- 12 and found to be at least 4 times as active as (+)- 6 . (+)-4-Cyanophenyl 5-thio-β-L -xylopyranoside ((+)- 3 ) was synthesized from L -xylose and found to maintain ca. 50% of the antithrombotic activity of its D -enantiomer. Compounds (±)- 5 , (±)- 6 , and (−)- 6 are in vitro substrates for galactosyltransferase 1.     

Photopatterning of multilayer n-alkylsilane films

Surface photopatterning of organosilane self-assembled monolayers (SAM) has received increasing attention since its introduction 20 years ago. Herein we report for the first time a cost-efficient soft photopatterning technique affording amplified 3D multilayer structures. The essential chemistry relies on a spatially controlled photoacid-catalyzed hydrolysis and polycondensation of n-alkyltrimethoxysilane precursors (n-C(12)H(25)Si(OCH(3))(3),). Amphiphilic siloxane species are photogenerated locally and are able to self-assemble spontaneously into a long-range-ordered lamellar mesostructure.     

Axon diodes for the reconstruction of oriented neuronal networks in microfluidic chambers

Various experimental models are used to study brain development and degeneration. They range from whole animal models, which preserve anatomical structures but strongly limit investigations at the cellular level, to dissociated cell culture systems that allow detailed observation of cell phenotypes but lack the highly ordered physiological neuron connection architecture. We describe here a platform comprising independent cell culture chambers separated by an array of "axonal diodes". This array involves asymmetric micro-channels, imposing unidirectional axon connectivity with 97% selectivity. It allows the construction of complex, oriented neuronal networks not feasible with earlier platforms. Different neuronal subtypes could be co-cultivated for weeks, and sequential seeding of different cell populations reproduced physiological network development. To illustrate possible applications, we created and characterized a cortico-striatal oriented network. Functional synaptic connections were established. The activation of striatal differentiation by cortical axons, and the synchronization of neural activity were demonstrated. Each neuronal population and subcompartment could be chemically addressed individually. The directionality of neural pathways being a key feature of the nervous system organization, the axon diode concept brings in a paradigmatic change in neuronal culture platforms, with potential applications for studying neuronal development, synaptic transmission and neurodegenerative disorder such as Alzheimer and Parkinson diseases at the sub-cellular, cellular and network levels.     

Evaluation of Doppler shifts to improve the accuracy of primary atomic fountain clocks

We demonstrate agreement between measurements and ab initio calculations of the frequency shifts caused by distributed cavity phase variations in the microwave cavity of a primary atomic fountain clock. Experimental verification of the finite element models of the cavities gives the first quantitative evaluation of this leading uncertainty and allows it to be reduced to δν/ν=±8.4×10(-17). Applying these experimental techniques to clocks with improved microwave cavities will yield negligible distributed cavity phase uncertainties, less than ±1×10(-17).     

Calcul de lʼespérance de la solution dʼune EDP stochastique unidimensionnelle à lʼaide dʼune base réduite

In this Note, we present an efficient method to approximate the expectation of the response of a one-dimensional elliptic problem with stochastic inputs. In conventional methods, the computational effort and cost of the approximation of the response can be dramatic. Our method presented here is based on the Karhunen–Loève (K-L) expansion of the inverse of the diffusion parameter, allowing us to build a base of random variables in reduced numbers, from which we construct a projected solution. We show that the expectation of this projected solution is a good approximation, and give an a priori error estimate. A numerical example is presented to show the efficiency of this approach.     

Masker location uncertainty reveals evidence for suppression of maskers in two-talker contexts

In many natural settings, spatial release from masking aids speech intelligibility, especially when there are competing talkers. This paper describes a series of three experiments that investigate the role of prior knowledge of masker location on phoneme identification and spatial release from masking. In contrast to previous work, these experiments use initial stop-consonant identification as a test of target intelligibility to ensure that listeners had little time to switch the focus of spatial attention during the task. The first experiment shows that target phoneme identification was worse when a masker played from an unexpected location (increasing the consonant identification threshold by 2.6 dB) compared to when an energetically very similar and symmetrically located masker came from an expected location. In the second and third experiments, target phoneme identification was worse (increasing target threshold levels by 2.0 and 2.6 dB, respectively) when the target was played unexpectedly on the side from which the masker was expected compared to when the target came from an unexpected, symmetrical location in the hemifield opposite the expected location of the masker. These results support the idea that listeners modulate spatial attention by both focusing resources on the expected target location and withdrawing attentional resources from expected locations of interfering sources.     

Alternatively linking fullerene and conjugated polymers

The stereo‐electronic control over bisadditions of conjugated polymers to fullerene (C₆₀) is explored in the formation of alternating copolymers. The chemistry, resulting configuration, and properties of poly(3‐hexylthiophene)‐alt‐C₆₀ copolymers prepared by either classic pyrrolidine ring formation or an atom transfer radical addition are compared. Both routes result in controlled additions of polymers to C₆₀. Extensive macromolecular modeling through PM6 methods indicate that there is no conjugation between P3HT and C₆₀ in the systems studied. This along with 2D‐NMR, AFM, and photovoltaic characterizations of the materials indicate the importance of the structure of the modified C₆₀ and the nature of the linking group between C₆₀ and P3HT segments in determining the morphology of the copolymers in the solid state. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2304–2317, 2009     

Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene,as evaluated by varied 1H‐NMR approaches

This study focused on the use of NMR techniques as a tool for the investigation of complex formation between proparacaine and cyclodextrins (CDs) or p‐sulfonic acid calix[6]arene. The pH dependence of the complexation of proparacaine with β‐CD and p‐sulfonic acid calix[6]arene was studied and binding constants were determined by ¹H NMR spectroscopy [diffusion‐ordered spectroscopy (DOSY)] for the charged and uncharged forms of the local anesthetic in β‐CD and p‐sulfonic acid calix[6]arene. The stoichiometries of the complexes was determined and rotating frame Overhauser enhancement spectroscopy (ROESY) 1D experiments revealed details of the molecular insertion of proparacaine into the β‐CD and p‐sulfonic acid calix[6]arene cavities. The results unambiguously demonstrate that pH is an important factor for the development of supramolecular architectures based on β‐CD and p‐sulfonic acid calix[6]arene as the host molecules. Such host–guest complexes were investigated in view of their potential use as new therapeutic formulations, designed to increase the bioavailability and/or to decrease the systemic toxicity of proparacaine in anesthesia procedures. Copyright © 2009 John Wiley & Sons, Ltd.     

Preparation of novel methyl methacrylate/fluorinated silsesquioxane copolymer film with low surface energy

Random copolymers of methyl methacrylate and fluorinated polyhedral oligomeric silsesquioxane (F-POSS) were synthesized and the corresponding thin films were prepared from solvent casting. Their microstructure was confirmed by ¹H NMR, elemental analysis and GPC. Separation occurs in the bulk of the film during solvent evaporation which can be evidenced by Transmission Electron Microscopy, TEM, with POSS-rich nanophase sizes from 20 to 50 nm. Nanostructuration is attributed to the self-assembly of F-POSS due to the cluster-cluster interactions resulting from the nature of their ligands, i.e., cycloaliphatic ligands and perfluorinated chains. Thermogravimetric analysis was used to investigate the thermal degradation temperature. It was shown that when F-POSS content is higher than 2.8 mol%, the incorporation of F-POSS could improve the thermal stability of PMMA significantly. In addition, it was shown that these fluorinated POSS-based copolymer surfaces could reduce the surface energy and could be used to design water-repellant nanocomposite coatings.