Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype phenotype correlations

We have generated a mouse carrying the human G551D mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR) by a one-step gene targeting procedure. These mutant mice show cystic fibrosis pathology but have a reduced risk of fatal intestinal blockage compared with 'null' mutants, in keeping with the reduced incidence of meconium ileus in G551D patients. The G551D mutant mice show greatly reduced CFTR-related chloride transport, displaying activity intermediate between that of cftr(mlUNC) replacement ('null') and cftr(mlHGU) insertional (residual activity) mutants and equivalent to approximately 4% of wild-type CFTR activity. The long-term survival of these animals should provide an excellent model with which to study cystic fibrosis, and they illustrate the value of mouse models carrying relevant mutations for examining genotype-phenotype correlations

Freshly Formed Dust in the Cassiopeia A Supernova Remnant as Revealed by the Spitzer Space Telescope

We performed Spitzer Infrared Spectrograph mapping observations covering nearly the entire extent of the Cassiopeia A supernova remnant (SNR), producing mid-infrared (5.5-35 micron) spectra every 5-10". Gas lines of Ar, Ne, O, Si, S and Fe, and dust continua were strong for most positions. We identify three distinct ejecta dust populations based on their continuum shapes. The dominant dust continuum shape exhibits a strong peak at 21 micron. A line-free map of 21 micron-peak dust made from the 19-23 micron range closely resembles the [Ar II], [O IV], and [Ne II] ejecta-line maps implying that dust is freshly formed in the ejecta. Spectral fitting implies the presence of SiO2, Mg protosilicates, and FeO grains in these regions. The second dust type exhibits a rising continuum up to 21 micron and then flattens thereafter. This ``weak 21 micron'' dust is likely composed of Al2O3 and C grains. The third dust continuum shape is featureless with a gently rising spectrum and is likely composed of MgSiO3 and either Al2O3 or Fe grains. Using the least massive composition for each of the three dust classes yields a total mass of 0.02 Msun. Using the most-massive composition yields a total mass of 0.054 Msun. The primary uncertainty in the total dust mass stems from the selection of the dust composition necessary for fitting the featureless dust as well as 70 micron flux. The freshly formed dust mass derived from Cas A is sufficient from SNe to explain the lower limit on the dust masses in high redshift galaxies.Comment: 8 figures: Accepted for the publication in Ap

RISK-RETURN ANALYSIS OF INCORPORATING ANNUAL LEGUMES AND LAMB GRAZING WITH DRYLAND CROP ROTATIONS

Profitability and risk, 1988-2001, are examined for lamb-grazed field pea as a fallow alternative with wheat, or an extended wheat-sunflower-millet rotation. Switching from conventional wheat-fallow to an extended rotation with grazed-peas increases profitability (2.3% to 7.3%), and reduces risk (below 0% target in only 2 versus 7 of 14 years).Crop Production/Industries,

The Three-Dimensional Structure of Interior Ejecta in Cassiopeia A at High Spectral Resolution

We used the Spitzer Space Telescope's Infrared Spectrograph to create a high resolution spectral map of the central region of the Cassiopeia A supernova remnant, allowing us to make a Doppler reconstruction of its 3D structure. The ejecta responsible for this emission have not yet encountered the remnant's reverse shock or the circumstellar medium, making it an ideal laboratory for exploring the dynamics of the supernova explosion itself. We observe that the O, Si, and S ejecta can form both sheet-like structures as well as filaments. Si and O, which come from different nucleosynthetic layers of the star, are observed to be coincident in velocity space in some regions, and separated by 500 km/s or more in others. Ejecta traveling toward us are, on average, ~900 km/s slower than the material traveling away from us. We compare our observations to recent supernova explosion models and find that no single model can simultaneously reproduce all the observed features. However, models of different supernova explosions can collectively produce the observed geometries and structures of the interior emission. We use the results from the models to address the conditions during the supernova explosion, concentrating on asymmetries in the shock structure. We also predict that the back surface of Cassiopeia A will begin brightening in ~30 years, and the front surface in ~100 years.Comment: 35 pages, 16 figures, accepted to Ap

Particle Impact Analysis of Bulk Powder During Pneumatic Conveyance

Fragmentation of powders during transportation is a common problem for manufacturers of food and pharmaceutical products. We illustrate that the primary cause of breakage is due to inter-particle collisions, rather than particle-wall impacts, and provide a statistical mechanics model giving the number of collisions resulting in fragmentation

The Three-Dimensional Structure of Cassiopeia A

We used the Spitzer Space Telescope's Infrared Spectrograph to map nearly the entire extent of Cassiopeia A between 5-40 micron. Using infrared and Chandra X-ray Doppler velocity measurements, along with the locations of optical ejecta beyond the forward shock, we constructed a 3-D model of the remnant. The structure of Cas A can be characterized into a spherical component, a tilted thick disk, and multiple ejecta jets/pistons and optical fast-moving knots all populating the thick disk plane. The Bright Ring in Cas A identifies the intersection between the thick plane/pistons and a roughly spherical reverse shock. The ejecta pistons indicate a radial velocity gradient in the explosion. Some ejecta pistons are bipolar with oppositely-directed flows about the expansion center while some ejecta pistons show no such symmetry. Some ejecta pistons appear to maintain the integrity of the nuclear burning layers while others appear to have punched through the outer layers. The ejecta pistons indicate a radial velocity gradient in the explosion. In 3-D, the Fe jet in the southeast occupies a "hole" in the Si-group emission and does not represent "overturning", as previously thought. Although interaction with the circumstellar medium affects the detailed appearance of the remnant and may affect the visibility of the southeast Fe jet, the bulk of the symmetries and asymmetries in Cas A are intrinsic to the explosion.Comment: Accepted to ApJ. 54 pages, 21 figures. For high resolution figures and associated mpeg movie and 3D PDF files, see http://homepages.spa.umn.edu/~tdelaney/pape

Triggering necroptosis in cisplatin and IAP antagonist-resistant ovarian carcinoma.

Ovarian cancer patients are typically treated with carboplatin and paclitaxel, but suffer a high rate of relapse with recalcitrant disease. This challenge has fostered the development of novel approaches to treatment, including antagonists of the 'inhibitor of apoptosis proteins' (IAPs), also called SMAC mimetics, as apoptosis-inducing agents whose action is opposed by caspase inhibitors. Surprisingly, IAP antagonist plus caspase inhibitor (IZ) treatment selectively induced a tumor necrosis factor-α (TNFα)-dependent death among several apoptosis-resistant cell lines and patient xenografts. The induction of necroptosis was common in ovarian cancer, with expression of catalytically active receptor-interacting protein kinase-3 (RIPK3) necessary for death, and in fact sufficient to compromise survival of RIPK3-negative, necroptosis-resistant ovarian cancer cells. The formation of a necrosome-like complex with a second critical effector, receptor-interacting serine-threonine kinase-1 (RIPK1), was observed. RIPK1, RIPK3 and TNFα were required for the induction of death, as agents that inhibit the function of any of these targets prevented cell death. Abundant RIPK3 transcript is common in serous ovarian cancers, suggesting that further evaluation and targeting of this RIPK3-dependent pathway may be of clinical benefit

Task 7: ADPAC User's Manual

The overall objective of this study was to develop a 3-D numerical analysis for compressor casing treatment flowfields. The current version of the computer code resulting from this study is referred to as ADPAC (Advanced Ducted Propfan Analysis Codes-Version 7). This report is intended to serve as a computer program user's manual for the ADPAC code developed under Tasks 6 and 7 of the NASA Contract. The ADPAC program is based on a flexible multiple- block grid discretization scheme permitting coupled 2-D/3-D mesh block solutions with application to a wide variety of geometries. Aerodynamic calculations are based on a four-stage Runge-Kutta time-marching finite volume solution technique with added numerical dissipation. Steady flow predictions are accelerated by a multigrid procedure. An iterative implicit algorithm is available for rapid time-dependent flow calculations, and an advanced two equation turbulence model is incorporated to predict complex turbulent flows. The consolidated code generated during this study is capable of executing in either a serial or parallel computing mode from a single source code. Numerous examples are given in the form of test cases to demonstrate the utility of this approach for predicting the aerodynamics of modem turbomachinery configurations

TB162: Red Maple and White Pine Litter Quality: Initial Changes with Decomposition

The specific objectives of this study were (a) to define the organic and inorganic composition of foliar litter from red maple (Acer rubrum L.) and white pine (Pinus strobus L.), and (b) to determine the shifts in the organic and inorganic composition of these two litter types during the initial stages of decomposition. These two species were chosen because of their prominence in the northeastern U.S. and the contrast they afforded in litter quality characteristics which have a strong influence on litter decomposition.https://digitalcommons.library.umaine.edu/aes_techbulletin/1038/thumbnail.jp