Cross-coupling reactions of organosilicon compounds in the stereocontrolled synthesis of retinoids

This paper presents a full account of the use of Hiyama cross-coupling reactions in a highly convergent approach to retinoids in which the key step is construction of the central C10-C11 bond. Representatives of two families of oxygen-activated dienyl silanes (ethoxysilanes and silanols) and of all reported families of "safety-catch" silanols (siletanes, silyl hydrides, allyl-, benzyl-, aryl-, 2-pyridyl- and 2-thienylsilanes) were regio- and stereoselectively prepared and stereospecifically coupled to an appropriate electrophile by treatment with a palladium catalyst and a nucleophilic activator. Both all-trans and 11-cis-retinoids, and their chain-demethylated analogues, were obtained in good yields regardless of the geometry (E/Z) and of the steric congestion in each fragment. This comprehensive study conclusively establishes the Hiyama cross-coupling reaction, with its mild reaction conditions and stable, easily prepared, ecologically advantageous silicon-based coupling partners, as the most effective route to retinoids reported to date.     

Directed flow from global symmetry and initial state Fluctuations

Collective flow is studied in a 3+1D fluid dynamical model with globally symmetric, peripheral initial conditions, taking into account the shear flow. At $\sqrt {s_{NN} } $ = 2.76 TeV in semi-peripheral Pb+Pb collisions this leads to rotation, while at more peripheral collisions with high resolution and low numerical viscosity, the initial development of a Kelvin-Helmholz instability is observed. This effect provides a precision tool for studying the viscosity of Quark-Gluon Plasma.     

Evaluation of an hPXR reporter gene assay for the detection of aquatic emerging pollutants: screening of chemicals and application to water samples

Many environmental endocrine-disrupting compounds act as ligands for nuclear receptors. Among these receptors, the human pregnane X receptor (hPXR) is well described as a xenobiotic sensor to various classes of chemicals, including pharmaceuticals, pesticides, and steroids. To assess the potential use of PXR as a sensor for aquatic emerging pollutants, we employed an in vitro reporter gene assay (HG5LN-hPXR cells) to screen a panel of environmental chemicals and to assess PXR-active chemicals in (waste) water samples. Of the 57 compounds tested, 37 were active in the bioassay and 10 were identified as new PXR agonists: triazin pesticides (promethryn, terbuthryn, terbutylazine), pharmaceuticals (fenofibrate, bezafibrate, clonazepam, medazepam) and non co-planar polychlorobiphenyls (PCBs; PCB101, 138, 180). Furthermore, we detected potent PXR activity in two types of water samples: passive polar organic compounds integrative sampler (POCIS) extracts from a river moderately impacted by agricultural and urban inputs and three effluents from sewage treatment works (STW). Fractionation of POCIS samples showed the highest PXR activity in the less polar fraction, while in the effluents, PXR activity was mainly associated with the dissolved water phase. Chemical analyses quantified several PXR-active substances (i.e., alkylphenols, hormones, pharmaceuticals, pesticides, PCBs, bisphenol A) in POCIS fractions and effluent extracts. However, mass-balance calculations showed that the analyzed compounds explained only 0.03% and 1.4% of biological activity measured in POCIS and STW samples, respectively. In effluents, bisphenol A and 4-tert-octylphenol were identified as main contributors of instrumentally derived PXR activities. Finally, the PXR bioassay provided complementary information as compared to estrogenic, androgenic, and dioxin-like activity measured in these samples. This study shows the usefulness of HG5LN-hPXR cells to detect PXR-active compounds in water samples, and further investigation will be necessary to identify the detected active compounds.     

Shortest path poset of Bruhat intervals

We define the shortest path poset SP(u,v) of a Bruhat interval [u,v], by considering the shortest u–v paths in the Bruhat graph of a Coxeter group W, where u,v∈W. We consider the case of SP(u,v) having a unique rising chain under a reflection order and show that in this case SP(u,v) is a Gorenstein^? poset. This allows us to derive the nonnegativity of certain coefficients of the complete cd-index. We furthermore show that the shortest path poset of an irreducible, finite Coxeter group exhibits a symmetric chain decomposition.     

Extending the applicability of Newton’s method using nondiscrete induction

We extend the applicability of Newton’s method for approximating a solution of a nonlinear operator equation in a Banach space setting using nondiscrete mathematical induction concept introduced by Potra and Ptak. We obtain new sufficient convergence conditions for Newton’s method using Lipschitz and center-Lipschitz conditions instead of only the Lipschitz condition used in F.A.Potra, V.Ptak, Sharp error bounds for Newton’s process, Numer. Math., 34 (1980), 63–72, and F.A.Potra, V.Ptak, Nondiscrete Induction and Iterative Processes, Research Notes in Mathematics, 103. Pitman Advanced Publishing Program, Boston, 1984. Under the same computational cost as before, we provide: weaker sufficient convergence conditions; tighter error estimates on the distances involved and more precise information on the location of the solution. Numerical examples are also provided in this study.     

Breakdown Voltage Distributions in Ne-Filled Diode at 1.33 mbar with Corona Appearance in Pre-breakdown Regime

The electrical breakdown of a gas subject to an up-ramping external voltage is studied, experimentally and theoretically, under conditions leading to the appearance of a positive corona at the anode in the pre-breakdown regime. Experimentally, voltage ramps with various rates k in the interval ranging from 0.3 V/s to 26 kV/s are applied to the diode, with the histogram of breakdown voltages being recorded for each rate. The theoretical model gives attention to the pre-breakdown multiplication causing the corona, which tends to reduce the statistical time delay $t_{S}$ before the primary electron is released and hence to make $t_{S}$ comparable to the formative time $t_{F}$ . The multiplication being therefore expected to affect the voltage dependence of the electron yield, a nonlinear equation relating the yield to the overvoltage is introduced. The resulting theoretical expression for the breakdown voltage distribution agrees well with the experimental histograms. Especially noteworthy is the good agreement with the low-voltage tail of the distribution, a segment of the data that has challenged previous theoretical analyses of the problem.     

Structure-based design of imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase

A series of imidazole-containing peptidomimetic PFTase inhibitors and their co-crystal structures bound to PFTase and FPP are reported. The structures reveal that the peptidomimetics adopt a similar conformation to that of the extended CVIM tetrapeptide, with the imidazole group coordinating to the catalytic zinc ion. Both mono- and bis-imidazole-containing derivatives, 13 and 16, showed remarkably high enzyme inhibition activity against PFTase in vitro with IC50 values of 0.86 and 1.7 nM, respectively. The peptidomimetics were also highly selective for PFTase over PGGTase-I both in vitro and in intact cells. In addition, peptidomimetics and were found to suppress tumor growth in nude mouse xenograft models with no gross toxicity at a daily dose of 25 mg kg(-1).