Threshold phenomena in erosion driven by subsurface flow

We study channelization and slope destabilization driven by subsurface (groundwater) flow in a laboratory experiment. The pressure of the water entering the sandpile from below as well as the slope of the sandpile are varied. We present quantitative understanding of the three modes of sediment mobilization in this experiment: surface erosion, fluidization, and slumping. The onset of erosion is controlled not only by shear stresses caused by surfical flows, but also hydrodynamic stresses deriving from subsurface flows. These additional forces require modification of the critical Shields criterion. Whereas surface flows alone can mobilize surface grains only when the water flux exceeds a threshold, subsurface flows cause this threshold to vanish at slopes steeper than a critical angle substantially smaller than the maximum angle of stability. Slopes above this critical angle are unstable to channelization by any amount of fluid reaching the surface.Comment: 9 pages, 11 figure

Progesterone receptor expression contributes to gemcitabine resistance at higher ECM stiffness in breast cancer cell lines

Chemoresistance poses a great barrier to breast cancer treatment and is thought to correlate with increased matrix stiffness. We developed two-dimensional (2D) polyacrylamide (PAA) and three-dimensional (3D) alginate in vitro models of tissue stiffness that mimic the stiffness of normal breast and breast cancer. We then used these to compare cell viability in response to chemotherapeutic treatment. In both 2D and 3D we observed that breast cancer cell growth and size was increased at a higher stiffness corresponding to tumours compared to normal tissue. When chemotherapeutic response was measured, a specific differential response in cell viability was observed for gemcitabine in 2 of the 7 breast cancer cell lines investigated. MCF7 and T-47D cell lines showed gemcitabine resistance at 4 kPa compared to 500 Pa. These cell lines share a common phenotype of progesterone receptor (PGR) expression and, indeed, pre-treatment with the selective progesterone receptor modulator (SPRM) mifepristone abolished resistance to gemcitabine at high stiffness. Our data reveals that combined treatment with SPRMs may therefore help in reducing resistance to gemcitabine in stiffer breast tumours which are PGR positive

An All-Sky 2MASS Mosaic Constructed on the TeraGrid

The Montage mosaic engine supplies on-request image mosaic services for the NVO astronomical community. A companion paper describes scientific applications of Montage. This paper describes one application in detail: the generation at SDSC of a mosaic of the 2MASS All-sky Image Atlas on the NSF TeraGrid. The goals of the project are: to provide a value-added 2MASS product that combines overlapping images to improve sensitivity; to demonstrate applicability of computing at-scale to astronomical missions and surveys, especially projects such as LSST; and to demonstrate the utility of the NVO Hyperatlas format. The numerical processing of an 8 TB, 32-bit survey to produce a 64-bit, 20 TB output atlas presented multiple scalability and operational challenges. An MPI Python module, MYMPI, was used to manage the alternately sequential and parallel steps of the Montage process. This allowed us to parallelize all steps of the mosaic process: that of many, sequential steps executing simultaneously for independent mosaics and that of a single MPI parallel job executing on many CPUs for a single mosaic. The Storage Resource Broker (SRB) was used to archive the output results in the Hyperatlas. The 2MASS mosaics are now being assessed for scientific quality. Around 130,000 CPU-hours were used to complete the mosaics. The output consists of 1734 plates spanning 6◦ for each of 3 bands. Each of the 5202 mosaics is roughly 4 GB in size, and each has been tiled into a 12×12 array of 26 MB files for ease of handling. The total size is about 20 TB in 750,000 tiles

The LAEX and NASA portals for CoRoT public data

* Aims. We describe here the main functionalities of the LAEX (Laboratorio de Astrofisica Estelar y Exoplanetas/Laboratory for Stellar Astrophysics and Exoplanets) and NASA portals for CoRoT Public Data. The CoRoT archive at LAEX was opened to the community in January 2009 and is managed in the framework of the Spanish Virtual Observatory. NStED (NASA Star and Exoplanet Database) serves as the CoRoT portal for the US astronomical community. NStED is a general purpose stellar and exoplanet archive with the aim of providing support for NASA planet finding and characterisation goals, and the planning and support of NASA and other space missions. CoRoT data at LAEX and NStED can be accessed at http://sdc.laeff.inta.es/corotfa/ and http://nsted.ipac.caltech.edu,respectively. * Methods. Based on considerable experience with astronomical archives, the aforementioned archives are designed with the aim of delivering science-quality data in a simple and efficient way. * Results. LAEX and NStED not only provide access to CoRoT Public Data but furthermore serve a variety of observed and calculated astrophysical data. In particular, NStED provides scientifically validated information on stellar and planetary data related to the search for and characterization of extrasolar planets, and LAEX makes any information from Virtual Observatory services available to the astronomical community.Comment: Accepted for publication in Astronomy & Astrophysic

The NASA Exoplanet Archive: Data and Tools for Exoplanet Research

We describe the contents and functionality of the NASA Exoplanet Archive, a database and tool set funded by NASA to support astronomers in the exoplanet community. The current content of the database includes interactive tables containing properties of all published exoplanets, Kepler planet candidates, threshold-crossing events, data validation reports and target stellar parameters, light curves from the Kepler and CoRoT missions and from several ground-based surveys, and spectra and radial velocity measurements from the literature. Tools provided to work with these data include a transit ephemeris predictor, both for single planets and for observing locations, light curve viewing and normalization utilities, and a periodogram and phased light curve service. The archive can be accessed at http://exoplanetarchive.ipac.caltech.edu.Comment: Accepted for publication in the Publications of the Astronomical Society of the Pacific, 4 figure

Intercalated theophylline-smectite hybrid for pH-mediated delivery

On the basis of their large specific surface areas, high adsorption and cation exchange capacities, swelling potential and low toxicity, natural smectite clays are attractive substrates for the gastric protection of neutral and cationic drugs. Theophylline is an amphoteric xanthine derivative that is widely used as a bronchodilator in the treatment of asthma and chronic obstructive pulmonary disease. This study considers the in vitro uptake and release characteristics of the binary theophylline-smectite system. The cationic form of theophylline was readily ion exchanged into smectite clay at pH 1.2 with a maximum uptake of 67±2 mg g−1. Characterisation of the drug-clay hybrid system by powder X-ray diffraction analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy confirmed that the theophylline had been exclusively intercalated into the clay system in an amorphous form. The drug remained bound within the clay under simulated gastric conditions at pH 1.2; and the prolonged release of approximately 40% of the drug was observed in simulated intestinal fluid at pH 6.8 and 7.4 within a 2-h timeframe. The incomplete reversibility of the intercalation process was attributed to chemisorption of the drug within the clay lattice. These findings indicate that smectite clay is a potentially suitable vehicle for the safe passage of theophylline into the duodenum. Protection from absorption in the stomach and subsequent prolonged release in the small intestine are advantageous in reducing fluctuations in serum concentration which may impact therapeutic effect and toxicit

Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

Molecular cloning and expression analysis of a zebrafish novel zinc finger protein gene rnf141

ZNF230 is a novel zinc finger gene cloned by our laboratory. In order to understand the potential functions of this gene in vertebrate development, we cloned the zebrafish orthologue of human ZNF230, named rnf141. The cDNA fragment of rnf141 was obtained by rapid amplification of cDNA ends (RACE). The open reading frame (ORF) encodes a polypeptide of 222 amino acids which shares 75.65% identity with the human ZNF230. RT-PCR analysis in zebrafish embryo and adult tissues revealed that rnf141 transcripts are maternally derived and that rnf141 mRNA has a broad distribution. Zygotic rnf141 message is strongly localized in the central nervous system, as shown by whole-mount in situ hybridization. Knockdown and over expression of rnf141 can induce abnormal phenotypes, including abnormal development of brain, as well as yolk sac and axis extendsion. Marker gene analysis showed that rnf141 may play a role in normal dorsoventral patterning of zebrafish embryos, suggesting that rnf141 may have a broad function during early development of vertebrates