Synthesis and evaluation of sphinganine analogues of KRN7000 and OCH

[structures: see text] The phytosphingosine-containing alpha-galactosylceramides (alpha-GalCers), KRN7000 and OCH, have been shown to activate NKT cells via interaction with CD1d, a member of the CD1 family of antigen presenting proteins. Evidence from KRN7000 stimulation of NKT cells suggests that alpha-GalCers may have applications in the treatment or prevention of a range of viral, bacterial, and autoimmune conditions. Moreover, OCH, a truncated analogue of KRN7000, appears to induce a T(H)2 bias, which could have implications for the treatment of autoimmune and inflammatory conditions. We have prepared the direct sphinganine-containing analogues of KRN7000 and OCH, 1 and 2, and found them to be comparable in activity to the parent compounds in inducing the release of IL-2, IL-4, and IFNgamma. In addition, compound 2 leads to a cytokine bias similar to that seen with OCH. This is significant because sphinganines are more easily accessed than phytosphingosines, which should facilitate SAR studies.     

Vapor pressure and intramolecular hydrogen bonding in fluorotelomer alcohols

Vapor pressure and aqueous solubility are important parameters used to estimate the potential for transport of chemical substances in the atmosphere. For fluorotelomer alcohols (FTOHs), currently under scrutiny by environmental scientists as potential precursors of persistent perfluorocarboxylates (PFCAs), vapor pressure is the more significant property since these compounds are only very sparingly soluble in water. We have measured the vapor pressures of a homologous series of fluorotelomer alcohols, F(CF2CF2)nCH2CH2OH (n = 2-5), in the temperature range 21-250 degrees C by three independent methods: (a) a method suitable for very low vapor pressures at ambient temperatures (gas-saturation method), (b) an improved boiling point method at controlled pressures (Scott method), and (c) a novel method, requiring milligram quantities of substance, based on gas-phase NMR, a technique largely unfamiliar to chemists and holding promise for studies of relevance to environmental chemistry. The concordant values obtained indicate that recently published vapor pressure data overestimate the vapor pressure at ambient temperature, and therefore the volatility, of this series of fluorinated compounds. It was suggested that substantial intramolecular -O-H...F- hydrogen bonding between the hydroxylic proton and the two fluorines next to the ethanol moiety was responsible for their putative high volatility. Therefore, we have used gas-phase NMR, gas-phase FTIR, 2D NMR heteronuclear Overhauser effect measurements, and high-level ab initio computations to investigate the intramolecular hydrogen bonding in fluorotelomer alcohols. Our studies unequivocally show that hydrogen bonding of this type is not significant and cannot contribute to and cause unusual volatility. The substantially lower vapor pressure at ambient temperatures than previously reported resulting from our work is important in developing a valid understanding of the environmental transport behavior of this class of compounds.     

Direct femtosecond laser writing of waveguides in As2S3 thin films

Single-channel waveguides and Y couplers were fabricated in chalcogenide thin films by use of femtosecond laser pulses from a 25-MHz repetition rate Ti:sapphire laser. Refractive-index differentials (delta n > 10(-2)) were measured through interferometric microscopy and are higher than the typical values reported for oxide glasses. The dependence of the index differential on the peak intensity reveals the nonlinear nature of the photosensitivity in arsenic trisulfide below its bandgap energy, and the refractive-index change is correlated to the photoinduced structural changes inferred by Raman spectroscopy data. A free-electron model to predict the parametric dependence of delta n is proposed.     

ALS-associated mutant SOD1<Superscript>G93A</Superscript> causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes

Background  

Amyotrophic lateral sclerosis (ALS) is an age-dependent neurodegenerative disease that causes motor neuron degeneration, paralysis and death. Mutations in Cu, Zn superoxide dismutase (SOD1) are one cause for the familial form of this disease. Transgenic mice expressing mutant SOD1 develop age-dependent motor neuron degeneration, skeletal muscle weakness, paralysis and death similar to humans. The mechanism whereby mutant SOD1 induces motor neuron degeneration is not understood but widespread mitochondrial vacuolation has been observed during early phases of motor neuron degeneration. How this vacuolation develops is not clear, but could involve autophagic vacuolation, mitochondrial permeability transition (MPT) or uncharacterized mechanisms. To determine which of these possibilities are true, we examined the vacuolar patterns in detail in transgenic mice expressing mutant SOD1^G93A.     

Nonlinear femtosecond pulse compression at high average power levels by use of a large-mode-area holey fiber

We demonstrate that nonlinear fiber compression is possible at unprecedented average power levels by use of a large-mode-area holey (microstructured) fiber and a passively mode-locked thin disk Yb:YAG laser operating at 1030 nm. We broaden the optical spectrum of the 810-fs pump pulses by nonlinear propagation in the fiber and remove the resultant chirp with a dispersive prism pair to achieve 18 W of average power in 33-fs pulses with a peak power of 12 MW and a repetition rate of 34 MHz. The output beam is nearly diffraction limited and is linearly polarized.     

Tellurite glasses with peak absolute Raman gain coefficients up to 30 times that of fused silica

An experimental system has been assembled to measure the absolute values of the Raman gain spectrum for millimeter-thick glass samples. Results are reported for two new oxide glasses with Raman gain coefficients as much as 30 times larger than that of fused silica and more than twice its spectral coverage.     

Practical uses of femtosecond laser micro-materials processing

We describe several approaches to basic femtosecond machining and materials processing that should lead to practical applications. Included are results on high-throughput deep hole drilling in glasses in ambient air, and precision high-speed micron-scale surface modification of composite materials and chalcogenide glasses. Ablation of soda-lime silicate glass and PbO lead-silicate is studied under three different sets of exposure conditions, for which both the wavelength and pulse duration are varied. Ablation rates are measured below and above the air ionization threshold. The differences observed are explained in terms of self-channeling in the ablated hole. Fabrication of practical devices such as waveguides and gratings is demonstrated in chalcogenide glass. Received: 11 December 2002 / Accepted: 20 January 2003 / Published online: 28 May 2003 RID="*" ID="*"Corresponding author. Fax: +1-407/8233-570, E-mail: mrichard@mail.ucf.edu     

Studies of high-repetition-rate laser plasma EUV sources from droplet targets

The water droplet laser plasma source has been shown to have many attractive features as a continuous, almost debris-free source for extreme ultraviolet (EUV) and X-ray applications. Through a dual experimental and theoretical study, we analyze the interaction physics between the laser light and the target. The hydrodynamic laser plasma simulation code, Medusa103 is used to model the electron density distribution for comparison to electron density distributions obtained through Abel inversion of plasma interferograms. In addition, flat field EUV spectra are compared to synthetic spectra calculated with the atomic physics code RATION. Received: 31 October 2002 / Accepted: 8 February 2003 / Published online: 28 May 2003 RID="*" ID="*"Present address: Naval Reseach Laboratory, Washington D.C. RID="**" ID="**"Present address: Xtreme Technologies, G?ttingen, Germany. RID="***" ID="***"Corresponding author. Fax: +1-407/823-3570, E-mail: mrichard@mail.ucf.edu     

Influence of the glass transition on solvent loss from spin-cast glassy polymer thin films

The interdependence of solvent loss and vitrification in spin-cast poly(methyl methacrylate) thin films is explored. Fast measurements of decreases in film thickness, achieved with ellipsometry, indicate that the rate of solvent (toluene) loss decreases sharply when the solvent volume fraction phi(solv) falls below about 0.15 and the film vitrifies. Ellipsometry and microgravimetry show that solvent is lost from a glassy thin film (150 nm thick) over of a period of more than ten hours, which is much longer than would be required if it was limited by diffusion in the glass. These results support the recently-proposed idea that the compression of the glass creates an energy barrier that slows down solvent loss.     

Optical parametric oscillator with a pulse repetition rate of 39 GHz and 2.1-W signal average output power in the spectral region near 1.5 microm

We present a singly resonant, synchronously pumped optical parametric oscillator with a record-high repetition rate of 39 GHz. The transform-limited 2.2-ps pulses at 1570 nm have as much as 2.1-W average output power. The all-solid-state pump source is based on a diode-pumped passively mode-locked 39-GHz Nd:YVO4 laser and an efficient ytterbium-doped fiber amplifier.