Synthesis and Anti-Hepatitis B Activities of 3′-Fluoro-2′-Substituted Apionucleosides

Nucleoside analogues have excellent records as anti-HBV drugs. Chronic infections require long-term administration ultimately leading to drug resistance. Therefore, the search for nucleosides with novel scaffolds is of high importance. Here we report the synthesis of novel 2′-hydroxy- and 2′-hydroxymethyl-apionucleosides, 4 and 5, corresponding triphosphates and phosphoramidate prodrugs. Triphosphate 38 of 2′-hydroxymethyl-apionucleoside 5 exhibited potent inhibition of HBV polymerase with an IC₅₀ value of 120 nM. In an HBV cell-based assay, the phosphoramidate prodrug 39 demonstrated potent activity with an EC₅₀ value of 7.8 nM.     

A local spectral approach for assessing time series model misspecification

We consider band-limited frequency-domain goodness-of-fit testing for stationary time series, without smoothing or tapering the periodogram, while taking into account the effects of parameter uncertainty (from maximum-likelihood estimation). We are principally interested in modeling short econometric time series, typically with 100 to 150 observations, for which data-driven bandwidth selection procedures for kernel-smoothed spectral density estimates are unlikely to have adequate levels. Our mathematical results take parameter uncertainty directly into account, allowing us to obtain adequate level properties at small sample sizes. The main theorems provide very general results involving joint normality for linear functionals of powers of the periodogram, while accounting for parameter uncertainty, which can be used to determine the level and power of a wide array of statistics. We discuss several applications, such as spectral peak testing and testing for the inclusion of an Unobserved Component, and illustrate our methods on a time series from the Energy Information Administration.     

Unique crystalline structure and performance of poly(ethylene terephthalate) melt spun fibers

Modification of the threadline dynamics has effected significant alternations in the structure and improvements in the properties of high-speed melt spun poly(ethylene terephthalate) (PET) fibers. Key process parameters extant in the threadline dynamics, such as temperature, tensile stress, and deformation time, were independently controlled through proper implementation of on-line perturbations. The placement of a liquid isothermal bath in close proximity to the spinneret in the melt spinning threadline provided tremendous increase in the spinning stress while at the same time controlled the filament temperature corresponding to development of the desired fiber structure. Characterization of the fiber structure and physical properties has been carried out using birefringence measurements, density, shrinkage, x-ray diffraction, DSC, FTIR spectroscopy, and tensile tests. The results provided sufficient evidence to support the existence of a unique crystalline morphology that led to the significantly improved tensile properties and excellent dimensional stability of the resulting fibers. This unique crystalline morphology was typically characterized by the presence of a larger amount of extended chain segments and an enhanced molecular connectivity. ©1995 John Wiley & Sons, Inc.     

Temperature-dependent fourth moment of the relaxation function for cubic Heisenberg paramagnets

Useful expressions, solely in terms of appropriate lattice Green functions, are derived for the fourth moment of the relaxation function of a Heisenberg paramagnet having cubic symmetry (s.c., b.c.c. and f.c.c.) and nearest-neighbour exchange interactions. As is customary, the temperature dependence was estimated on the basis of the spherical model and with a simple random-phase type decoupling of the four-spin correlation functions.     

An improved HPLC method for the investigation of L‐selenomethionine metabolism in rat gut contents

Selenomethionine (SeMet) is a widely used nutritional supplement that has potential benefit for people living in selenium‐deficient areas. Previous research has shown that selenium administered as SeMet undergoes significant enterohepatic recycling which may involve the gut microflora. In order to investigate this we have developed a simple method for the quantitation of l ‐SeMet in rat gut content suspensions prepared from jejunum, ileum, caecum and colon. After incubation of l ‐SeMet with gut content suspensions, samples were deproteinized with sulfosalicylic acid and derivatized with o‐phthaldialdehyde (OPA) and N‐acetyl‐l ‐cysteine (NAC). Mass spectrometry confirmed the formation of a 1:1:1 derivative of l ‐SeMet with OPA and NAC. Samples were analysed by reversed‐phase high‐performance liquid chromatography with fluorescence detection. The assay was linear in the concentration range 0.5–100 µg/mL (r² = 0.9992) with a limit of detection of 0.025 µg/mL (signal‐to‐noise ratio of 5). Intra‐day and inter‐day accuracies were 91.1–92.8 and 91.7–95.5%, respectively with corresponding precisions as relative standard deviation of <5%. Incubation of l ‐SeMet with gut content suspensions from different parts of the rat intestine showed that l ‐SeMet metabolism occurs mainly in the caecum. Copyright © 2009 John Wiley & Sons, Ltd.     

Open- and closed-loop aberration correction by use of a quadrature interferometric wave-front sensor

Experimental results are presented for an adaptive optics system based on a quadrature Twyman-Green interferometric wave-front sensor. The system uses a circularly polarized reference beam to form two interferograms with a pi/2 phase shift. The experiments conducted used Kolmogorov phase screens to simulate atmospheric phase distortions. Strehl ratio improvements by a factor of 8, to an absolute value of 0.45, are demonstrated.     

Electron density characterization by use of a broadband x-ray-compatible wave-front sensor

The use of a Hartmann wave-front sensor to accurately measure the line-integrated electron density gradients formed in laser-produced and z-pinch plasma experiments is examined. This wave-front sensor may be used with a soft-x-ray laser as well as with incoherent line emission at multikilovolt x-ray energies. This diagnostic is significantly easier to use than interferometery and moiré deflectometry, both of which have been demonstrated with soft-x-ray lasers. This scheme is experimentally demonstrated in the visible region by use of a Shack-Hartmann wave-front sensor and a liquid-crystal spatial light modulator to simulate a phase profile that could occur when an x-ray probe passes through a plasma. The merits of using a Hartmann sensor include a wide dynamic range, broadband or low-coherence-length light capability, high x-ray efficiency, two-dimensional gradient determination, multiplexing capability, and experimental simplicity. Hartmann sensors could also be utilized for wavelength testing of extreme-ultraviolet lithography components and x-ray phase imaging of biological specimens.     

The sixth frequency moments for an anisotropic paramagnet with exchange-bond dilution

The sixth frequency moments of the spin correlation function for a bond-diluted anisotropic Heisenberg paramagnet in the high temperature limit are evaluated for arbitrary spin values. Results for both the transverse and longitudinal moments are presented for a model in which the transverse and longitudinal exchange bonds can fluctuate independently. The results are presented in a form which allows the moments for the undiluted, site diluted, and single-bond diluted moments to be also written down.     

An integral strong law of large numbers for processes with independent increments

For a stochastically continuous stochastic process with independent increments overD[0,T], letN(t,ε) be the number of smaple function jumps that occur in the interval [0,t] of sizes less than −ε or greater than ε, where ε>0. LetM(t,ε)=EN(t,ε), and assumeM(t,0+)=∞ for 0<t≦T. If lim_{ε ↓0}(M(t,ε)/M(T,ε)) exists and is positive for eacht∈(0,T], then lim_{ε ↓0}(N(t,ε)/M(T,ε)) for allt∈(0,T] with probability one. The research of Howard G. Tucker was supported in part by the National Science Foundation, Grant No. MCS76-03591A01.