Ocular Gene Transfer with Self-Complementary AAV Vectors

PURPOSE. Self-complementary AAV (scAAV) vectors have been developed to circumvent rate-limiting second-strand synthesis in single-stranded AAV vector genomes and to facilitate robust transgene expression at a minimal dose. In this study, the authors investigated the effects of intraocular injections of type 2 scAAV.GFP in mice. METHODS. Dose-response experiments were performed to compare conventional single-strand AAV type 2 (ssAAV2) vectors with scAAV2 vectors encoding an identical expression cassette. RESULTS. Subretinal injection of 5 X 108viral particles (vp) of scAAV.CMV-GFP resulted in green fluorescent protein (GFP) expression in almost all retinal pigment epithelial (RPE) cells within the area of the small detachment caused by the injection by 3 days and strong, diffuse expression by 7 days. Expression was strong in all retinal cell layers by days 14 and 28. In contrast, 3 days after subretinal injection of 5 X 108vp of ssAAV.CMV-GFP, GFP expression was detectable in few RPE cells. Moreover, the ssAAV vector required 14 days for the attainment of expression levels comparable to those observed using scAAV at day 3. Expression in photoreceptors was not detectable until day 28. Dose-response experiments confirmed that onset of GFP expression was more rapid and robust after subretinal injection of scAAV.CMV-GFP than of ssAAV.CMV-GFP, resulting in pronounced expression in photoreceptors and other retinal neurons. Similar results were obtained for intravitreous injections. CONCLUSIONS. These data suggest that scAAV vectors may be advantageous for ocular gene therapy, particularly in retinal diseases that require rapid and robust transgene expression in photoreceptor cells

Overexpression of SOD in retina: Need for increase in H2O2-detoxifying enzyme in same cellular compartment

In retinitis pigmentosa (RP), various mutations cause rod photoreceptor cell death leading to increased oxygen levels in the outer retina, progressive oxidative damage to cones, and gradual loss of cone cell function. We have been exploring the potential of overexpressing components of the endogenous antioxidant defense system to preserve cone cell function in rd10+/+ mice, a model of RP. Rd10+/+ mice deficient in superoxide dismutase 1 (SOD1) showed increased levels of superoxide radicals and carbonyl adducts (a marker of oxidative damage) in the retina, and more rapid loss of cone function than rd10+/+ mice with normal levels of SOD1. This suggests that SOD1 is an important component of the antioxidant defense system of cones, but increased expression of SOD1 in rd10+/+ mice increased oxidative damage and accelerated the loss of cone function. Co-expression of SOD1 with glutathione peroxidase 4 (Gpx4), which like SOD1 is localized in the cytoplasm, but not with catalase targeted to the mitochondria, reduced oxidative damage in the retina and significantly slowed the loss of cone cell function in rd10+/+ mice. Gene transfer resulting in increased expression of SOD2, but not co-expression of SOD2 and mitochondrial Gpx4, resulted in high levels of H2O2 in the retina. These data suggest that in order to provide benefit in RP, over-expression of a SOD must be combined with expression of a peroxide detoxifying enzyme in the same cellular compartment

KELT-17B: A HOT-JUPITER TRANSITING AN A-STAR IN A MISALIGNED ORBIT DETECTED WITH DOPPLER TOMOGRAPHY

We present the discovery of a hot-Jupiter transiting the V=9.23 mag main-sequence A-star KELT-17 (BD+14 1881). KELT-17b is a 1.31 -0.29/+0.28 Mj, 1.525 -0.060/+0.065 Rj hot-Jupiter in a 3.08 day period orbit misaligned at -115.9 +/- 4.1 deg to the rotation axis of the star. The planet is confirmed via both the detection of the radial velocity orbit, and the Doppler tomographic detection of the shadow of the planet over two transits. The nature of the spin-orbit misaligned transit geometry allows us to place a constraint on the level of differential rotation in the host star; we find that KELT-17 is consistent with both rigid-body rotation and solar differential rotation rates (alpha < 0.30 at 2 sigma significance). KELT-17 is only the fourth A-star with a confirmed transiting planet, and with a mass of 1.635 -0.061/+0.066 Msun, effective temperature of 7454 +/- 49 K, and projected rotational velocity v sin I_* = 44.2 -1.3/+1.5 km/s; it is amongst the most massive, hottest, and most rapidly rotating of known planet hosts.Comment: 15 pages, 9 figures, accepted for publication in A

German bibliographical services

117-131<span style="font-size:10.0pt;line-height: 115%;font-family:" calibri","sans-serif";mso-fareast-font-family:"times="" new="" roman";="" mso-bidi-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="" lang="EN-US">This contribution presents an annotated listing of some important German bibliographies, both retrospective and current. They are listed under 14 main heads like, General bibliographies, National bibliographies, Bibliographies of incunabula, Bibliographies of theses and dissertations, Book trade bibliographies, Bibliographies of government publications, etc. A few sample pages of some of the well known bibliographies are also reproduced.</span

Optimizing use of multiple stars for near-infrared tip-tilt compensation at the W. M. Keck Observatory

The implementation of a near-infrared tip-tilt sensor in the Keck I adaptive optics (AO) system is the first of its kind, and represents a substantial step forward in AO technology. Enhanced-TRICK (Tilt Removal with IR Compensation at Keck) is a project built off this implementation which will further improve performance and versatility. Currently the system is capable of using a single star for measuring image motion, but in the off-axis case this may cause elongation in the science image due to tilt anisoplanatism. The near-infrared tip-tilt sensor (NIRTTS) has been designed with the capability of using up to three stars from around the field to correct for elongation. In order for the science object correction to be optimized, the measurements from each star must be weighted based on magnitude and separation from the science object. When weighted optimally the tip-tilt error at the science object will be a minimum. The process for assigning weights is described, and results of performance modeling of the actual systems having multiple tip-tilt stars are presented

Optimizing use of multiple stars for near-infrared tip-tilt compensation at the W. M. Keck Observatory

The implementation of a near-infrared tip-tilt sensor in the Keck I adaptive optics (AO) system is the first of its kind, and represents a substantial step forward in AO technology. Enhanced-TRICK (Tilt Removal with IR Compensation at Keck) is a project built off this implementation which will further improve performance and versatility. Currently the system is capable of using a single star for measuring image motion, but in the off-axis case this may cause elongation in the science image due to tilt anisoplanatism. The near-infrared tip-tilt sensor (NIRTTS) has been designed with the capability of using up to three stars from around the field to correct for elongation. In order for the science object correction to be optimized, the measurements from each star must be weighted based on magnitude and separation from the science object. When weighted optimally the tip-tilt error at the science object will be a minimum. The process for assigning weights is described, and results of performance modeling of the actual systems having multiple tip-tilt stars are presented