Power Line Foundation Design Using the Pressuremeter

During the design phase of a 2000-towers electric power transmission line, a load test program was undertaken to evaluate the accuracy of new design methods for uplift and lateral capacity of drilled shafts. Seven uplift tests and six lateral load tests were performed in three different soil deposits: a medium clay, a very hard clay and a sand. The shafts were 2 ft in diameter and either 10 or 15 ft long. The pressuremeter test results are used together with existing methods to predict the behavior of the shafts

The Star Formation Rate Function for Redshift z~4-7 Galaxies: Evidence for a Uniform Build-Up of Star-Forming Galaxies During the First 3 Gyr of Cosmic Time

We combine recent estimates of dust extinction at z~4-7 with UV luminosity function (LF) determinations to derive star formation rate (SFR) functions at z~4, 5, 6 and 7. SFR functions provide a more physical description of galaxy build-up at high redshift and allow for direct comparisons to SFRs at lower redshifts determined by a variety of techniques. Our SFR functions are derived from well-established z~4-7 UV LFs, UV-continuum slope trends with redshift and luminosity, and IRX-beta relations. They are well-described by Schechter relations. We extend the comparison baseline for SFR functions to z~2 by considering recent determinations of the H{\alpha} and mid-IR luminosity functions. The low-end slopes of the SFR functions are flatter than for the UV LFs, \Delta\alpha\sim+0.13, and show no clear evolution with cosmic time (z~0-7). In addition, we find that the characteristic value SFR* from the Schechter fit to SFR function exhibits consistent, and substantial, linear growth as a function of redshift from ~5 M_sun/yr at z~8, 650 Myr after the Big Bang, to ~100 M_sun/yr at z~2, ~2.5 Gyr later. Recent results at z~10, close to the onset of galaxy formation, are consistent with this trend. The uniformity of this evolution is even greater than seen in the UV LF over the redshift range z~2-8, providing validation for our dust corrections. These results provide strong evidence that galaxies build up uniformly over the first 3 Gyr of cosmic time.Comment: Added an appendix, 1 figure and 3 tables: 9 pages, 5 figures, 4 tables, ApJ, in pres

Noninvasive, In Vivo Assessment of Mouse Retinal Structure Using Optical Coherence Tomography

BACKGROUND: Optical coherence tomography (OCT) is a novel method of retinal in vivo imaging. In this study, we assessed the potential of OCT to yield histology-analogue sections in mouse models of retinal degeneration. METHODOLOGY/PRINCIPAL FINDINGS: We achieved to adapt a commercial 3(rd) generation OCT system to obtain and quantify high-resolution morphological sections of the mouse retina which so far required in vitro histology. OCT and histology were compared in models with developmental defects, light damage, and inherited retinal degenerations. In conditional knockout mice deficient in retinal retinoblastoma protein Rb, the gradient of Cre expression from center to periphery, leading to a gradual reduction of retinal thickness, was clearly visible and well topographically quantifiable. In Nrl knockout mice, the layer involvement in the formation of rosette-like structures was similarly clear as in histology. OCT examination of focal light damage, well demarcated by the autofluorescence pattern, revealed a practically complete loss of photoreceptors with preservation of inner retinal layers, but also more subtle changes like edema formation. In Crb1 knockout mice (a model for Leber's congenital amaurosis), retinal vessels slipping through the outer nuclear layer towards the retinal pigment epithelium (RPE) due to the lack of adhesion in the subapical region of the photoreceptor inner segments could be well identified. CONCLUSIONS/SIGNIFICANCE: We found that with the OCT we were able to detect and analyze a wide range of mouse retinal pathology, and the results compared well to histological sections. In addition, the technique allows to follow individual animals over time, thereby reducing the numbers of study animals needed, and to assess dynamic processes like edema formation. The results clearly indicate that OCT has the potential to revolutionize the future design of respective short- and long-term studies, as well as the preclinical assessment of therapeutic strategies

Two human cDNAs, including a homolog of Arabidopsis FUS6 (COP11), suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction in yeast and mammalian cells.

We have isolated two novel human cDNAs, gps1-1 and gps2, that suppress lethal G-protein subunit-activating mutations in the pheromone response pathway of the yeast Saccharomyces cerevisiae. Suppression of other pathway-activating events was examined. In wild-type cells, expression of either gps1-1 or gps2 led to enhanced recovery from cell cycle arrest induced by pheromone. Sequence analysis indicated that gps1-1 contains only the carboxy-terminal half of the gps1 coding sequence. The predicted gene product of gps1 has striking similarity to the protein encoded by the Arabidopsis FUS6 (COP11) gene, a negative regulator of light-mediated signal transduction that is known to be essential for normal development. A chimeric construct containing gps1 and FUS6 sequences also suppressed the yeast pheromone pathway, indicating functional conservation between these human and plant genes. In addition, when overexpressed in mammalian cells, gps1 or gps2 potently suppressed a RAS- and mitogen-activated protein kinase-mediated signal and interfered with JNK activity, suggesting that signal repression is part of their normal function. For gps1, these results are consistent with the proposed function of FUS6 (COP11) as a signal transduction repressor in plants

Earth System Model Evaluation Tool (ESMValTool) v2.0-diagnostics for extreme events, regional and impact evaluation, and analysis of Earth system models in CMIP

This paper complements a series of now four publications that document the release of the Earth System Model Evaluation Tool (ESMValTool) v2.0. It describes new diagnostics on the hydrological cycle, extreme events, impact assessment, regional evaluations, and ensemble member selection. The diagnostics are developed by a large community of scientists aiming to facilitate the evaluation and comparison of Earth system models (ESMs) which are participating in the Coupled Model Intercomparison Project (CMIP). The second release of this tool aims to support the evaluation of ESMs participating in CMIP Phase 6 (CMIP6). Furthermore, datasets from other models and observations can be analysed. The diagnostics for the hydrological cycle include several precipitation and drought indices, as well as hydroclimatic intensity and indices from the Expert Team on Climate Change Detection and Indices (ETCCDI). The latter are also used for identification of extreme events, for impact assessment, and to project and characterize the risks and impacts of climate change for natural and socio-economic systems. Further impact assessment diagnostics are included to compute daily temperature ranges and capacity factors for wind and solar energy generation. Regional scales can be analysed with new diagnostics implemented for selected regions and stochastic downscaling. ESMValTool v2.0 also includes diagnostics to analyse large multi-model ensembles including grouping and selecting ensemble members by user-specified criteria. Here, we present examples for their capabilities based on the well-established CMIP Phase 5 (CMIP5) dataset

Rapid cohort generation and analysis of disease spectrum of large animal model of cone dystrophy.

Large animal models are an important resource for the understanding of human disease and for evaluating the applicability of new therapies to human patients. For many diseases, such as cone dystrophy, research effort is hampered by the lack of such models. Lentiviral transgenesis is a methodology broadly applicable to animals from many different species. When conjugated to the expression of a dominant mutant protein, this technology offers an attractive approach to generate new large animal models in a heterogeneous background. We adopted this strategy to mimic the phenotype diversity encounter in humans and generate a cohort of pigs for cone dystrophy by expressing a dominant mutant allele of the guanylate cyclase 2D (GUCY2D) gene. Sixty percent of the piglets were transgenic, with mutant GUCY2D mRNA detected in the retina of all animals tested. Functional impairment of vision was observed among the transgenic pigs at 3 months of age, with a follow-up at 1 year indicating a subsequent slower progression of phenotype. Abnormal retina morphology, notably among the cone photoreceptor cell population, was observed exclusively amongst the transgenic animals. Of particular note, these transgenic animals were characterized by a range in the severity of the phenotype, reflecting the human clinical situation. We demonstrate that a transgenic approach using lentiviral vectors offers a powerful tool for large animal model development. Not only is the efficiency of transgenesis higher than conventional transgenic methodology but this technique also produces a heterogeneous cohort of transgenic animals that mimics the genetic variation encountered in human patients