Cell decomposition of almost smooth real algebraic surfaces

Let Z be a two dimensional irreducible complex component of the solution set of a system of polynomial equations with real coefficients in N complex variables. This work presents a new numerical algorithm, based on homotopy continuation methods, that begins with a numerical witness set for Z and produces a decomposition into 2-cells of any almost smooth real algebraic surface contained in Z. Each 2-cell (a face) has a generic interior point and a boundary consisting of 1-cells (edges). Similarly, the 1-cells have a generic interior point and a vertex at each end. Each 1-cell and each 2-cell has an associated homotopy for moving the generic interior point to any other point in the interior of the cell, defining an invertible map from the parameter space of the homotopy to the cell. This work draws on previous results for the curve case. Once the cell decomposition is in hand, one can sample the 2-cells and 1-cells to any resolution, limited only by the computational resources available.     

Delocalization-to-localization charge transition in diferrocenyl-oligothienylene-vinylene molecular wires as a function of the size by Raman spectroscopy

In going from short to large size thienylene-vinylene diferrocenyl cations, the transition from a charge delocalized to a localized state is addressed by resonance Raman spectroscopy and supported by theoretical model chemistry. The shorter members, dimer and tetramer, display conjugated structures near the cyanine limit of bond length equalization as a result of the strong interferrocene charge resonance, producing a full charge delocalized mixed valence system. In the longest octamer, charge resonance vanishes and the cation is localized at the bridge center (the mixed valence property disappears). The hexamer is at the delocalized-to-localized turning point. Solvent and variable-temperature Raman measurements highlight this borderline property. A detailed structure-property correlation of bond length alternation data and Raman frequencies is proposed to account for the whole set of spectroscopic properties, with emphasis on the changes observed with the size of the molecular wire.     

Merochlorins A-D, cyclic meroterpenoid antibiotics biosynthesized in divergent pathways with vanadium-dependent chloroperoxidases

Meroterpenoids are mixed polyketide-terpenoid natural products with a broad range of biological activities. Herein, we present the structures of four new meroterpenoid antibiotics, merochlorins A-D, produced by the marine bacterium Streptomyces sp. strain CNH-189, which possess novel chemical skeletons unrelated to known bacterial agents. Draft genome sequencing, mutagenesis, and heterologous biosynthesis in the genome-minimized model actinomycete Streptomyces coelicolor provided the 57.6 kb merochlorin gene cluster that contains two genes encoding rare bacterial vanadium-dependent haloperoxidase (VHPO) genes. Pathway expression of two different fosmid clones that differ largely by the presence or absence of the VHPO gene mcl40 resulted in the differential biosynthesis of merochlorin C, suggesting that Mcl40 catalyzes an unprecedented 15-membered chloronium-induced macrocyclization reaction converting merochlorin D to merochlorin C.     

Age-related changes in talker recognition with reduced spectral cues

Temporal information provided by cochlear implants enables successful speech perception in quiet, but limited spectral information precludes comparable success in voice perception. Talker identification and speech decoding by young hearing children (5-7 yr), older hearing children (10-12 yr), and hearing adults were examined by means of vocoder simulations of cochlear implant processing. In Experiment 1, listeners heard vocoder simulations of sentences from a man, woman, and girl and were required to identify the talker from a closed set. Younger children identified talkers more poorly than older listeners, but all age groups showed similar benefit from increased spectral information. In Experiment 2, children and adults provided verbatim repetition of vocoded sentences from the same talkers. The youngest children had more difficulty than older listeners, but all age groups showed comparable benefit from increasing spectral resolution. At comparable levels of spectral degradation, performance on the open-set task of speech decoding was considerably more accurate than on the closed-set task of talker identification. Hearing children's ability to identify talkers and decode speech from spectrally degraded material sheds light on the difficulty of these domains for child implant users.     

Logarithmic mean oscillation on the polydisc,endpoint results for multi-parameter paraproducts,and commutators on BMO

We study boundedness properties of a class ofmultiparameter paraproducts on the dual space of the dyadic Hardy space H _d ¹ (T ^N ), the dyadic product BMO space BMO ^d (T ^N ). For this, we introduce a notion of logarithmic mean oscillation on the polydisc. We also obtain a result on the boundedness of iterated commutators on BMO [0, 1] ^N ).     

Construction of a Microstructured Collagen Membrane Mimicking the Papillary Dermis Architecture and Guiding Keratinocyte Morphology and Gene Expression

A papillary‐structured collagen fibril membrane is created, mimicking the 3D‐architecture of the human papillary dermis. Primary human keratinocytes cultured to confluency on papillar‐structured films are compared to keratinocytes cultured on flat membranes. Microscopical evaluation reveals the presence of morphologically distinct cells at the base of the papillar structures that are not observed on flat membranes. Gene expression microarrays and RT‐qPCR indicate that these cells are in a more proliferative/migrational state, whereas cells on flat membranes have a more differentiated expression profile. Immunohistochemical stainings confirm these results. In conclusion, specific collagen architecture can direct keratinocyte behavior, and this may be used to further improve skin regeneration.

     

Understanding the inhibitory effect of highly potent and selective archazolides binding to the vacuolar ATPase

Vacuolar ATPases are a potential therapeutic target because of their involvement in a variety of severe diseases such as osteoporosis or cancer. Archazolide A (1) and related analogs have been previously identified as selective inhibitors of V-ATPases with potency down to the subnanomolar range. Herein we report on the determination of the ligand binding mode by a combination of molecular docking, molecular dynamics simulations, and biochemical experiments, resulting in a sound model for the inhibitory mechanism of this class of putative anticancer agents. The binding site of archazolides was confirmed to be located in the equatorial region of the membrane-embedded V(O)-rotor, as recently proposed on the basis of site-directed mutagenesis. Quantification of the bioactivity of a series of archazolide derivatives, together with the docking-derived binding mode of archazolides to the V-ATPase, revealed favorable ligand profiles, which can guide the development of a simplified archazolide analog with potential therapeutic relevance.