Trimethylsilyl chloride promoted synthesis of a-branched amines by nucleophilic addition of organozinc halides to nitrones

A general procedure for the nucleophilic addition of organo-zinc halides with nitrones in the presence of trimethylsilyl chloride has been developed. Trimethylsilyl chloride was found to be both an indispensable reaction promoter and a ready hydroxylamine protective agent in these reactions. The produced O-(trimethylsilyl)hydroxylamines can be easily reduced into corresponding amines just by a zinc-copper couple in saturated aqueous NH4Cl solutio

Lattice dynamics of mixed semiconductors (Be,Zn)Se from first-principles calculations

Vibration properties of Zn(1-x)Be(x)Se, a mixed II-VI semiconductor haracterized by a high contrast in elastic properties of its pure constituents, ZnSe and BeSe, are simulated by first-principles calculations of electronic structure, lattice relaxation and frozen phonons. The calculations within the local density approximation has been done with the Siesta method, using norm-conserving pseudopotentials and localized basis functions; the benchmark calculations for pure endsystems were moreover done also by all-electron WIEN2k code. An immediate motivation for the study was to analyze, at the microscopic level, the appearance of anomalous phonon modes early detected in Raman spectra in the intermediate region (20 to 80%) of ZnBe concentration. This was early discussed on the basis of a percolation phenomenon, i.e., the result of the formation of wall-to-wall --Be--Se-- chains throughout the crystal. The presence of such chains was explicitly allowed in our simulation and indeed brought about a softening and splitting off of particular modes, in accordance with experimental observation, due to a relative elongation of Be--Se bonds along the chain as compared to those involving isolated Be atoms. The variation of force constants with interatomic distances shows common trends in relative independence on the short-range order.Comment: 11 pages, 10 figures, to be published in Phys. Rev.

Molecular characterization of signalling pathways in cancer stem cells

To avoid artefacts introduced by culturing cells for extended periods of time, it is crucial to use low-passage patient-derived tumour cells. The ability to enrich, isolate and assay sub-populations of cells that behave as cancer stem cells (CSCs) from these primary cell lines is essential before performing characterizations such as gene-expression profiling. We have isolated cells from glioblastomas which show characteristics of CSCs. Although glioblastomas contain only a relatively small amount of putative CSCs, these cells express many genes which seem to be worthy targets for future therapies

Alternative synthesis of the anti-baldness compound RU58841

RU58841 is active against baldness and is commercially available. The previously reported synthesis uses phosgene, three discrete inert atmosphere steps and three steps that require flash chromatography. Our synthesis uses no phosgene, only one inert atmosphere step and does not require flash chromatography. This is achieved by stepwise construction of the hydantoin moiety around the amino group of 3- trifluoromethyl-4-cyanoaniline and ring closure to give a 2-nitropropane leaving group. On a small scale we achieved an overall yield of 33%

Implementation of the Projector Augmented Wave LDA+U Method: Application to the Electronic Structure of NiO

The so-called local density approximation plus the multi-orbital mean-field Hubbard model (LDA+U) has been implemented within the all-electron projector augmented-wave method (PAW), and then used to compute the insulating antiferromagnetic ground state of NiO and its optical properties. The electronic and optical properties have been investigated as a function of the Coulomb repulsion parameter U. We find that the value obtained from constrained LDA (U=8 eV) is not the best possible choice, whereas an intermediate value (U=5 eV) reproduces the experimental magnetic moment and optical properties satisfactorily. At intermediate U, the nature of the band gap is a mixture of charge transfer and Mott-Hubbard type, and becomes almost purely of the charge-transfer type at higher values of U. This is due to the enhancement of the oxygen 2p states near the top of the valence states with increasing U value.Comment: 23 pages, 6 figures, submitted to Phys. Rev.

The Persistence Length of a Strongly Charged, Rod-like, Polyelectrolyte in the Presence of Salt

The persistence length of a single, intrinsically rigid polyelectrolyte chain, above the Manning condensation threshold is investigated theoretically in presence of added salt. Using a loop expansion method, the partition function is consistently calculated, taking into account corrections to mean-field theory. Within a mean-field approximation, the well-known results of Odijk, Skolnick and Fixman are reproduced. Beyond mean-field, it is found that density correlations between counterions and thermal fluctuations reduce the stiffness of the chain, indicating an effective attraction between monomers for highly charged chains and multivalent counterions. This attraction results in a possible mechanical instability (collapse), alluding to the phenomenon of DNA condensation. In addition, we find that more counterions condense on slightly bent conformations of the chain than predicted by the Manning model for the case of an infinite cylinder. Finally, our results are compared with previous models and experiments.Comment: 13 pages, 2 ps figure

Predicting where a radiation will occur: Acoustic and molecular surveys reveal overlooked diversity in Indian Ocean Island crickets (Mogoplistinae: Ornebius)

Recent theory suggests that the geographic location of island radiations (local accumulation of species diversity due to cladogenesis) can be predicted based on island area and isolation. Crickets are a suitable group for testing these predictions, as they show both the ability to reach some of the most isolated islands in the world, and to speciate at small spatial scales. Despite substantial song variation between closely related species in many island cricket lineages worldwide, to date this characteristic has not received attention in the western Indian Ocean islands; existing species descriptions are based on morphology alone. Here we use a combination of acoustics and DNA sequencing to survey these islands for Ornebius crickets. We uncover a small but previously unknown radiation in the Mascarenes, constituting a three-fold increase in the Ornebius species diversity of this archipelago (from two to six species). A further new species is detected in the Comoros. Although double archipelago colonisation is the best explanation for species diversity in the Seychelles, in situ cladogenesis is the best explanation for the six species in the Mascarenes and two species of the Comoros. Whether the radiation of Mascarene Ornebius results from intra- or purely inter- island speciation cannot be determined on the basis of the phylogenetic data alone. However, the existence of genetic, song and ecological divergence at the intra-island scale is suggestive of an intra-island speciation scenario in which ecological and mating traits diverge hand-in-hand. Our results suggest that the geographic location of Ornebius radiations is partially but not fully explained by island area and isolation. A notable anomaly is Madagascar, where our surveys are consistent with existing accounts in finding no Ornebius species present. Possible explanations are discussed, invoking ecological differences between species and differences in environmental history between islands. (Résumé d'auteur

Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

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