Synthesis of some 3-alkenyl-4-oxo-6,7-dihydro-4H-pyrano[3,4-d]isoxazoles

A series of 3-alkenyl-4-oxo-6,7-dihydro-4H-pyrano[3,4-d]isoxazole derivatives was prepared by reaction of hydroxylamine with 4,5-dioxo-2,3,7,8-tetrahydro-4H,5H-pyrano[4,3-b]pyran derivatives.     

Exact convergence rates for the bounded law of the iterated logarithm in Hilbert space

Summary In a previous paper we obtained upper and lower class type results refining the bounded LIL for sums of iid Hilbert space valued mean zero random variables, whose covariance operators satisfy certain regularity assumptions. We now establish precise convergence rates for the bounded LIL in the non-regular case. It turns out that the almost sure behavior in this case is entirely different from the behavior in the previous situation.Supported in part by NSF Grant DMS 90-05804     

Rethinking ramoplanin: the role of substrate binding in inhibition of peptidoglycan biosynthesis

Ramoplanin is a cyclicdepsipeptide antibiotic that inhibits peptidoglycan biosynthesis. It was proposed in 1990 to block the MurG step of peptidoglycan synthesis by binding to the substrate of MurG, Lipid I. The proposed mechanism of MurG inhibition has become widely accepted even though it was never directly tested. In this paper, we disprove the accepted mechanism for how ramoplanin functions, and we present an alternative mechanism. This work has implications for the design of ramoplanin derivatives and may influence how other proposed substrate binding antibiotics are studied.     

Octasubstituted metal-free phthalocyanine as core of phosphorus dendrimers: a probe for the properties of the internal structure

The synthesis of a new family of phosphorus dendrimers built from an octasubstituted metal-free phthalocyanine core is described up to generation 5. This core is used as a sensor and a probe for analyzing the properties of the internal structure and the influence of each structural part (core, branches, surface) upon the whole structure. UV-visible spectra show both a hyperchromic and bathochromic effect on the Q-bands with increasing generation, indicating that the chromophore is more isolated, and that the dendritic shell mimics a highly polar solvent. There is no evidence for aggregation, except for generation 0, showing again the isolation of the core. However, the dendritic shell is permeable to aqueous acids and bases, as demonstrated by the reversible splitting of the Q-band in an acidic medium (neutral form of the phthalocyanine) and the single Q-band in a basic medium (dianionic form), even for generation 4. The fluorescence quantum yield for the neutral form increases with increasing generation. The dianionic form of generation 0 is poorly fluorescent, whereas generations 3 and 4 (G3 and G4) exhibit better fluorescence. The cores of G3 and G4 are highly sensitive optical sensors for H3O+ and OH-. These experiments are carried out in THF/water mixtures, and the influence of water on the structure has been checked. The hydrodynamic radius of generation 4 is measured by NMR diffusion (pulse gradient spin-echo) experiments. R(H) varies from 35.4 A at 4 mol % of water to 32.5 A at 64 mol % of water in THF, indicating the hydrophobic nature of these dendrimers.     

Synthesis of some 4-carboxy-3- and 5-(2-hydroxyalkyl)pyrazole lactone derivatives

The synthesis and biological activities of some 4-oxo-1-or-2-substituted 1H-or-2H-pyrano[4,3-c]pyrazole derivatives are described.     

Chip-based nLC-TOF-MS is a highly stable technology for large-scale high-throughput analyses

Many studies focused on the discovery of novel biomarkers for the diagnosis and treatment of disease states are facilitated by mass spectrometry-based technology. HPLC coupled to mass spectrometry is widely used; miniaturization of this technique using nano-liquid chromatography (LC)-mass spectrometry (MS) usually results in better sensitivity, but is associated with limited repeatability. The recent introduction of chip-based technology has significantly improved the stability of nano-LC-MS, but no substantial studies to verify this have been performed. To evaluate the temporal repeatability of chip-based nano-LC-MS analyses, N-glycans released from a serum sample were repeatedly analyzed using nLC-PGC-chip-TOF-MS on three non-consecutive days. With an average inter-day coefficient of variation of 4 %, determined on log₁₀-transformed integrals, the repeatability of the system is very high. Overall, chip-based nano-LC-MS appears to be a highly stable technology, which is suitable for the profiling of large numbers of clinical samples for biomarker discovery.     

A continuous updating weighted least squares estimator of tail dependence in high dimensions

Likelihood-based procedures are a common way to estimate tail dependence parameters. They are not applicable, however, in non-differentiable models such as those arising from recent max-linear structural equation models. Moreover, they can be hard to compute in higher dimensions. An adaptive weighted least-squares procedure matching nonparametric estimates of the stable tail dependence function with the corresponding values of a parametrically specified proposal yields a novel minimum-distance estimator. The estimator is easy to calculate and applies to a wide range of sampling schemes and tail dependence models. In large samples, it is asymptotically normal with an explicit and estimable covariance matrix. The minimum distance obtained forms the basis of a goodness-of-fit statistic whose asymptotic distribution is chi-square. Extensive Monte Carlo simulations confirm the excellent finite-sample performance of the estimator and demonstrate that it is a strong competitor to currently available methods. The estimator is then applied to disentangle sources of tail dependence in European stock markets.     

Adaptation of a load-inject valve for a flow injection chemiluminescence system enabling dual-reagent injection enhances understanding of environmental Fenton chemistry

Environmental Fenton chemistry has been poorly constrained within the marine environment at a multi-component level. A simple, unique, reconfiguration of a flow-injection analytical system combined with luminol chemiluminescence allows quasi-simultaneously the measurement, using a single load-inject valve and a single photon multiplier tube, of reduced iron, Fe(II), and hydrogen peroxide. The system enables rapid, every 22 s, measurements with good accuracy at environmentally relevant concentrations, less than 5% relative standard deviations on both a 5 nM Fe(II) standard and a 60 nM hydrogen peroxide standard. Limits of detection were as low as 40 pM Fe(II) and 100 pM hydrogen peroxide. The system showed excellent capability by measuring from within an organic rich seawater the photochemically induced production of Fe(II) and hydrogen peroxide and their subsequent cycling and Fenton like interactions.