A robust characterization of retinoic acid response elements based on a comparison of sites in three species.

The availability of high-throughput genomic sequencing has allowed us to construct a more robust characterization of retinoic acid response elements than was possible in the past. We located human, mouse, and rat homologs for each of 51 well-documented, conserved retinoic acid response elements. Mathematical and statistical analyses of these 153 sites, 78 of which are new, shows that 92% of response elements have direct-repeat symmetry, but that only 76% exhibit canonical spacing attributes. While the familiar '(a/g)g(g/t)tca' hexamer motif is upheld, the more relaxed sequence, '(a/g)g(g/t)(g/t)(g/c)a', represents a 10% consensus. Sites are as likely to be on the coding strand as on the non-coding strand, and 86% of them are in upstream locations. From a statistical point of view, DR1 elements are fundamentally different from DR2 and DR5 elements, but this is only evident in the 5' hexamer. While there is considerable variation in core positions, and while no nucleotide can be considered forbidden at any position, variation among species at a fixed locus appears surprisingly constrained once a functional site has been attained.

Talbot array illuminator for single-shot measurements of laser-induced-damage thresholds of thin-film coatings.

A highly efficient Talbot array illuminator for single-shot, laser-induced-damage test measurements of optical thin-film coatings is proposed. With a periodic binary phase grating, a laser beam is transformed into an ensemble of Gaussian-like spots, which are known as the Fresnel image of the grating. For this purpose hexagonal phase gratings were fabricated and analyzed. With a peak fluence distribution of approximately 1 order of magnitude, the damage threshold of thin films can be deduced by use of the data from only a single shot.

Specific teratogenic effects of different retinoic acid isomers and analogs in the developing anterior central nervous system of zebrafish.

Vertebrate embryos are sensitive to retinoic acid, either in deficiency or in excess. Although all-trans retinoic acid (RA) and 9-cis RA are known to have distinct but overlapping activities in higher organisms, only the all-trans isomer has been investigated in detail as a teratogen in zebrafish. We have identified profound and specific effects of 9-cis RA when administered to zebrafish embryos, and have confirmed the results of prior studies on the teratogenic effects of exogenous all-trans RA. Moreover, we have identified a 1-hr period during gastrulation in which embryos are particularly sensitive to the teratogenic effects of RA. In the course of these investigations, we have also studied the effects of two synthetic retinoids-a 9-cis RA analog, SR11217, and an all-trans RA analog, TTAB. An application of all-trans RA to the early zebrafish gastrula leads to defects that are limited to the caudal midbrain and rostral hindbrain. Our experiments show that an application of exogenous 9-cis RA for a period as short as 1 hr and at a concentration as low as 0.1 mu M can block differentiation of the rostral CNS. We have observed abnormal phenotypes using DIC optics, and have demonstrated further abnormalities using whole-mount immunocytochemical staining with antibodies to HNK-1 and acetylated alpha-tubulin. Major axon tract formation in the anterior CNS is unambiguously disrupted by the administration of 9-cis RA but not all-trans RA. Furthermore, exogenous 9-cis RA produces a qualitative alteration in the multiple-site expression pattern of the hlx-1 gene within the rostral CNS, while treatment with all-trans RA leads only to a weakened expression signal. The administration of TTAB and SR11217 result in distinctive inhibitions of hlx-1 expression. Unlike all-trans RA, which causes premature par-2 expression in the posterior midbrains of a majority of embryos, 9-cis RA leads to a complete deletion of this domain throughout development. These results suggest that 9-cis RA is a more active teratogen than all-trans RA in rostral CNS structures of the zebrafish embryo.

1053-nm-wavelength selection in a diode-laser-pumped Nd:YLF laser.

We report on a Nd:YLF laser that operates at 1053 nm without optical intracavity elements for the suppression of the stronger 1047-nm transition. The Nd:YLF crystal is end pumped by a fiber optically coupled 10-W diode-laser bar. The different thermal-lensing focal lengths of the two main lasing wavelengths in a plane-parallel resonator were used to achieve the selection by tilting the end mirror slightly from its optimum position for maximum output power. With 9.8-W cw diode-laser-pumping power the 1053-nm Nd:YLF laser produces a maximum output power of 1.9 W in cw operation and nearly 1 W of average power at a Q-switch repetition rate of 15 kHz. The highest slope efficiency of 47% achieved in cw operation.

Pulsed optical damage threshold of potassium niobate.

We have determined the optical damage threshold of orthorhombic potassium niobate under pulsed laser irradiation for wavelengths of 1054 and 527 nm and pulse durations of 700 and 500 ps, respectively. Six uncoated crystals and two crystals with antireflection coating were tested. The single-shot damage thresholds varied between 4.1 J/cm(2) at 527 nm (lowest value observed) and 26.4 J/cm(2) at 1054 nm (the highest value observed). The threshold fluence was found to depend on the polarization direction of the incident radiation with respect to the crystal axes.

Q-switched Nd:YLF laser end pumped by a diode-laser bar.

We describe 20-kW operation of a Q-switched Nd:YLF laser end pumped by a 5-mJ, 25-W quasi-cw diode-laser bar. A fiber coupler was used to adapt the 1-cm-wide active area of the diode-laser bar to the circular shape of the TEM(00) mode. The maximum 1047-nm TEM(00) output energy was 0.5 mJ in a 22-nsec Q-switched pulse. This corresponds to a peak power in excess of 20 kW and was obtained at an optical slope efficiency of 13%.