Restructuring the Energy System in Germany since 1973.

The Shell Lecture 1984

Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies

SLC4A11, a member of the SLC4 family of bicarbonate transporters, is a widely expressed integral membrane protein, abundant in kidney and cornea. Mutations of SLC4A11 cause some cases of the blinding corneal dystrophies, congenital hereditary endothelial dystrophy, and Fuchs endothelial corneal dystrophy. These diseases are marked by fluid accumulation in the corneal stroma, secondary to defective fluid reabsorption by the corneal endothelium. The role of SLC4A11 in these corneal dystrophies is not firmly established, as SLC4A11 function remains unclear. To clarify the normal function(s) of SLC4A11, we characterized the protein following expression in the simple, low-background expression system Xenopus laevis oocytes. Since plant and fungal SLC4A11 orthologs transport borate, we measured cell swelling associated with accumulation of solute borate. The plant water/borate transporter NIP5;1 manifested borate transport, whereas human SLC4A11 did not. SLC4A11 supported osmotically driven water accumulation that was electroneutral and Na⁺ independent. Studies in oocytes and HEK293 cells could not detect Na⁺⁻ coupled HCO3⁻ transport or Cl⁻/HCO3⁻ exchange by SLC4A11. SLC4A11 mediated electroneutral NH3 transport in oocytes. Voltagedependent OH⁻ or H⁺ movement was not measurable in SLC4A11- expressing oocytes, but SLC4A11-expressing HEK293 cells manifested low-level cytosolic acidification at baseline. In mammalian cells, but not oocytes, OH⁻/H⁺ conductance may arise when SLC4A11 activates another protein or itself is activated by another protein. These data argue against a role of human SLC4A11 in bicarbonate or borate transport. This work provides additional support for water and ammonia transport by SLC4A11. When expressed in oocytes, SLC4A11 transported NH3, not NH3/H⁺.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare

Sagittarius Tidal Debris 90 kpc from the Galactic Center

A new overdensity of A-colored stars in distant parts of the Milky Way's stellar halo, at a dereddened SDSS magnitude of g_0 = 20.3, is presented. Identification of associated variable RR Lyrae candidates supports the claim that these are blue horizontal branch stars. The inferred distance of these stars from the Galactic center is 90 kpc, assuming the absolute magnitude of these stars is M_g_0 = 0.7 and that the Sun is 8.5 kpc from the Galactic center. The new tidal debris is within 10 kpc of same plane as other confirmed tidal debris from the disruption of the Sagittarius dwarf galaxy, and could be associated with the trailing tidal arm. Distances to the Sagittarius stream estimated from M stars are about 13% smaller than our inferred distances. The tidal debris has a width of at least 10 degrees, and is traced for more than 20 degrees across the sky. The globular cluster NGC 2419 is located within the detected tidal debris, and may also have once been associated with the Sagittarius dwarf galaxy.Comment: 4 figures, ApJL in pres

On the effects of microstructural orientation on fracture toughness in (V,Al)-nitride and -oxynitride thin films

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Inflammatory bowel disease addressed by Caco-2 and monocyte-derived macrophages : an opportunity for an in vitro drug screening assay

Infammatory bowel disease (IBD) is a widespread disease, afecting a growing demographic. The treatment of chronic infammation located in the GI-tract is dependent on the severity; therefore, the IBD treatment pyramid is commonly applied. Animal experimentation plays a key role for novel IBD drug development; nevertheless, it is ethically questionable and limited in its throughput. Reliable and valid in vitro assays ofer the opportunity to overcome these limitations. We combined Caco-2 with monocyte-derived macrophages and exposed them to known drugs, targeting an in vitro-in vivo correlation (IVIVC) with a focus on the severity level and its related drug candidate. This co-culture assay addresses namely the intestinal barrier and the immune response in IBD. The drug efcacy was analyzed by an LPS-infammation of the co-culture and drug exposure according to the IBD treatment pyramid. Efcacy was defned as the range between LPS control (0%) and untreated co-culture (100%) independent of the investigated read-out (TEER, Papp, cytokine release: IL-6, IL-8, IL-10, TNF-α). The release of IL-6, IL-8, and TNF-α was identifed as an appropriate readout for a fast drug screening (“yes–no response”). TEER showed a remarkable IVIVC correlation to the human treatment pyramid (5-ASA, Prednisolone, 6-mercaptopurine, and infiximab) with an R2 of 0.68. Similar to the description of an adverse outcome pathway (AOP) framework, we advocate establishing an “Efcacy Outcome Pathways (EOPs)” framework for drug efcacy assays. The in vitro assay ofers an easy and scalable method for IBD drug screening with a focus on human data, which requires further validation

The accretion origin of the Milky Way's stellar halo

We have used data from the Sloan Digital Sky Survey (SDSS) Data Release 5 to explore the overall structure and substructure of the stellar halo of the Milky Way using about 4 million color-selected main sequence turn-off stars. We fit oblate and triaxial broken power-law models to the data, and found a `best-fit' oblateness of the stellar halo 0.5<c/a<0.8, and halo stellar masses between Galactocentric radii of 1 and 40kpc of (3.7+/-1.2)x10^8 M_sun. The density profile of the stellar halo is approximately r^{-3}; it is possible that the power law slope is shallower inside 20kpc and steeper outside that radius. Yet, we found that all smooth and symmetric models were very poor fits to the distribution of stellar halo stars because the data exhibit a great deal of spatial substructure. We quantified deviations from a smooth oblate/triaxial model using the RMS of the data around the model profile on scales >~100pc, after accounting for the (known) contribution of Poisson uncertainties. The fractional RMS deviation of the actual stellar distribution from any smooth, parameterized halo model is >~40%: hence, the stellar halo is highly structured. We compared the observations with simulations of galactic stellar halos formed entirely from the accretion of satellites in a cosmological context by analysing the simulations in the same way as the data. While the masses, overall profiles, and degree of substructure in the simulated stellar halos show considerable scatter, the properties and degree of substructure in the Milky Way's halo match well the properties of a `typical' stellar halo built exclusively out of the debris from disrupted satellite galaxies. Our results therefore point towards a picture in which an important fraction of the Milky Way's stellar halo has been accreted from satellite galaxies.Comment: Submitted to the Astrophysical Journal. 14 pages; 11 figure

The C4 Clustering Algorithm: Clusters of Galaxies in the Sloan Digital Sky Survey

We present the "C4 Cluster Catalog", a new sample of 748 clusters of galaxies identified in the spectroscopic sample of the Second Data Release (DR2) of the Sloan Digital Sky Survey (SDSS). The C4 cluster--finding algorithm identifies clusters as overdensities in a seven-dimensional position and color space, thus minimizing projection effects which plagued previous optical clusters selection. The present C4 catalog covers ~2600 square degrees of sky with groups containing 10 members to massive clusters having over 200 cluster members with redshifts. We provide cluster properties like sky location, mean redshift, galaxy membership, summed r--band optical luminosity (L_r), velocity dispersion, and measures of substructure. We use new mock galaxy catalogs to investigate the sensitivity to the various algorithm parameters, as well as to quantify purity and completeness. These mock catalogs indicate that the C4 catalog is ~90% complete and 95% pure above M_200 = 1x10^14 solar masses and within 0.03 <=z <= 0.12. The C4 algorithm finds 98% of X-ray identified clusters and 90% of Abell clusters within 0.03 <= z <= 0.12. We show that the L_r of a cluster is a more robust estimator of the halo mass (M_200) than the line-of-sight velocity dispersion or the richness of the cluster. L_r. The final SDSS data will provide ~2500 C4 clusters and will represent one of the largest and most homogeneous samples of local clusters.Comment: 32 pages of figures and text accepted in AJ. Electronic version with additional tables, links, and figures is available at http://www.ctio.noao.edu/~chrism/c

The dynamical Green's function and an exact optical potential for electron-molecule scattering including nuclear dynamics

We derive a rigorous optical potential for electron-molecule scattering including the effects of nuclear dynamics by extending the common many-body Green's function approach to optical potentials beyond the fixed-nuclei limit for molecular targets. Our formalism treats the projectile electron and the nuclear motion of the target molecule on the same footing whereby the dynamical optical potential rigorously accounts for the complex many-body nature of the scattering target. One central result of the present work is that the common fixed-nuclei optical potential is a valid adiabatic approximation to the dynamical optical potential even when projectile and nuclear motion are (nonadiabatically) coupled as long as the scattering energy is well below the electronic excitation thresholds of the target. For extremely low projectile velocities, however, when the cross sections are most sensitive to the scattering potential, we expect the influences of the nuclear dynamics on the optical potential to become relevant. For these cases, a systematic way to improve the adiabatic approximation to the dynamical optical potential is presented that yields non-local operators with respect to the nuclear coordinates.Comment: 22 pages, no figures, accepted for publ., Phys. Rev.

Forward K+ production in subthreshold pA collisions at 1.0 GeV

K+ meson production in pA (A = C, Cu, Au) collisions has been studied using the ANKE spectrometer at an internal target position of the COSY-Juelich accelerator. The complete momentum spectrum of kaons emitted at forward angles, theta < 12 degrees, has been measured for a beam energy of T(p)=1.0 GeV, far below the free NN threshold of 1.58 GeV. The spectrum does not follow a thermal distribution at low kaon momenta and the larger momenta reflect a high degree of collectivity in the target nucleus.Comment: 4 pages, 3 figure