Molecular models of human P-glycoprotein in two different catalytic states

P-glycoprotein belongs to the family of ATP-binding cassette proteins which hydrolyze ATP to catalyse the translocation of their substrates through membranes. This protein extrudes a large range of components out of cells, especially therapeutic agents causing a phenomenon known as multidrug resistance. Because of its clinical interest, its activity and transport function have been largely characterized by various biochemical studies. In the absence of a high-resolution structure of P-glycoprotein, homology modeling is a useful tool to help interpretation of experimental data and potentially guide experimental studies.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Reliability of mantle tomography models assessed by spectral element simulation

Global tomographic models collected in the Seismic wave Propagation and Imaging in Complex (SPICE media: a European network) model library (http://www.spicertn.org/research/planetaryscale/tomography/) share a similar pattern of long, spatial wavelength heterogeneity, but are not consistent at shorter spatial wavelengths. Here, we assess the performance of global tomographic models by comparing how well they fit seismic waveform observations, in particular Love and Rayleigh wave overtones and fundamental modes. We first used the coupled spectral element method (CSEM) to calculate long-period (>100 s) synthetic seismograms for different global tomography models. The CSEM can incorporate the effect of three-dimensional (3-D) variations in velocity, anisotropy, density and attenuation with very little numerical dispersion. We then compared quantitatively synthetic seismograms and real data. To restrict ourselves to high-quality overtone data, and to minimize the effects of the finite extent of seismic sources and of crustal heterogeneity, we favour deep (>500 km) earthquakes of intermediate magnitude (Mw ∼ 7). Our comparisons reveal that: (1) The 3-D global tomographic models explain the data much better than the one-dimensional (1-D) anisotropic Preliminary Reference Earth Model (PREM). The current 3-D tomographic models have captured the large-scale features of upper-mantle heterogeneities, but there is still some room for the improvement of large-scale features of global tomographic models. (2) The average correlation coefficients for deep events are higher than those for shallow events, because crustal structure is too complex to be completely incorporated into CSEM simulations. (3) The average correlation coefficient (or the time lag) for the major-arc wave trains is lower (or higher) than that for the minor-arc wave trains. Therefore, the current tomographic models could be much improved by including the major-arc wave trains in the inversion. (4) The shallow-layer crustal correction has more effects on the fundamental surface waves than on the overtone

Investigation and modelling of the progression of zinc leaching from large sphalerite ore particles

X-ray Computed Tomography (CT) was used to follow the progression of Zn leaching in a number of individual sphalerite ore particles, which were subjected to a long-term simulated heap bioleaching environment. The ore was prepared by two different modes of comminution – HPGR at 90 bar and cone crusher – and individual particles were selected from three different size fractions. Investigation of the reacted fraction of Zn vs distance from the centre of each particle indicated that leaching from large particles leads to near complete conversion near the surface, but only partial conversion in the zones that are closer to the centre of particles. The cores of the cone-crushed particles show hardly any conversion at all, especially in the larger particle sizes. Mathematical analysis shows that leaching from the large particle does not follow the shrinking core model. It is shown that the progression can rather be described by a combined reaction-diffusion process progressing through the network of cracks and pores closer to the particle surface. Extent and depth of this network are a function of particle size and comminution method. A simplified rate model is proposed that describes the extent of leaching as a function of time in terms of a set of parameters that can all be related to just particle size and crushing mode

Simultaneous X-ray radiography and diffraction topography imaging applied to silicon for defect analysis during melting and crystallization

International audienceSynopsis A setup for simultaneous, time-resolved X-ray radiography and diffraction topography imaging is presented. It is used to study defect generation and growth mechanisms during heating, solidification and cooling of a silicon crystal. Abstract One of the key issues to be resolved to improve the performance of silicon solar cells is to reduce crystalline defect formation and propagation during the growth process fabrication step. For this purpose, the generation of structural defects such as grain boundaries and dislocations in silicon must be understood and characterised. We combine in situ X-ray diffraction imaging, historically named topography, with radiography imaging to analyse the development of crystal defects before, during and after crystallisation. Two individual indirect detector systems are implemented to record simultaneously the crystal structure (topographs) and the solid-liquid morphology evolution (radiographs) at high temperature. This allows for a complete synchronisation of the images and for an increased image acquisition rate compared to previous studies that used X-ray sensitive films to record the topographs. The experiments are performed with X-ray synchrotron radiation at beamline ID19 at the European Synchrotron Radiation Facility (ESRF). We present in situ observations of the heating, melting, solidification and holding stages of silicon samples to demonstrate that with the upgraded setup detailed investigations of time-dependent phenomena are now possible. The motion of dislocations is recorded during the entire experiment, so that their interaction with grain boundaries and their multiplication through the activation of Frank-Read sources can be observed. Moreover, the capability to record with two camera-based detectors allows for the study of the relationship between strain distribution, twinning and nucleation events. In conclusion, the simultaneous recording of topographs and radiographs has great potential for further detailed investigations of the interaction and generation of grains and defects that influence the growth process and the final crystalline structure in silicon and other crystalline materials

Investigation of particles with high crack density produced by HPGR and its effect on the redistribution of the particle size fraction in heaps

The application of comminution technology such as the High-pressure grinding rolls (HPGR), which is able to generate a high density of cracks in the ore particles, is favourable for leaching processes. Extraction of metallic values by the heap leach process, can take place on the particles with partial exposure of mineral grains, if it can provide sufficient surface front for chemical attack by leaching solution. The aim of this study was to assess the benefits of high crack density in the ore particles produced using the HPGR and how it could diminish due to inadequate percolation of the leaching agent. A zinc ore was comminuted using HPGR at three different pressure settings and with a cone crusher for the control experiment. Subsamples from the (+23/-25, +14/-16, +5.25/-6.75 mm) size fractions were characterized and packed into leach reactors. The reactors were stopped from time to time to investigate the progress of crack and micro-crack growth and its effect on metal extraction using the X-ray computed tomography (CT). The results are validated with those obtained using traditional techniques such as SEM and QEMSCAN. Investigation of the leach reactors residue indicated significant changes in the particle size distribution (PSD) of initial feed toward the fine size fraction. The residues from the reactors leaching the material prepared using the HPGR product contained more fine particles than the reactors, which were fed by cone crusher product. These differences were up to 10.3%

Approaches for the optimization of MR protocols in clinical hybrid PET/MRI studies

Magnetic resonance imaging (MRI) is the examination method of choice for the diagnosis of a variety of diseases. MRI allows us to obtain not only anatomical information but also identification of physiological and functional parameters such as networks in the brain and tumor cellularity, which plays an increasing role in oncologic imaging, as well as blood flow and tissue perfusion. However, in many cases such as in epilepsy, degenerative neurological diseases and oncological processes, additional metabolic and molecular information obtained by PET can provide essential complementary information for better diagnosis. The combined information obtained from MRI and PET acquired in a single imaging session allows a more accurate localization of pathological findings and better assessment of the underlying physiopathology, thus providing a more powerful diagnostic tool. Two hundred and twenty-one patients were scanned from April 2011 to January 2012 on a Philips Ingenuity TF PET/MRI system. The purpose of this review article is to provide an overview of the techniques used for the optimization of different protocols performed in our hospital by specialists in the following fields: neuroradiology, head and neck, breast, and prostate imaging. This paper also discusses the different problems encountered, such as the length of studies, motion artifacts, and accuracy of image fusion including physical and technical aspects, and the proposed solution

The Hyper Suprime-Cam Software Pipeline

In this paper, we describe the optical imaging data processing pipeline developed for the Subaru Telescope's Hyper Suprime-Cam (HSC) instrument. The HSC Pipeline builds on the prototype pipeline being developed by the Large Synoptic Survey Telescope's Data Management system, adding customizations for HSC, large-scale processing capabilities, and novel algorithms that have since been reincorporated into the LSST codebase. While designed primarily to reduce HSC Subaru Strategic Program (SSP) data, it is also the recommended pipeline for reducing general-observer HSC data. The HSC pipeline includes high level processing steps that generate coadded images and science-ready catalogs as well as low-level detrending and image characterizations.Comment: 39 pages, 21 figures, 2 tables. Submitted to Publications of the Astronomical Society of Japa

Delivery of Dark Material to Vesta via Carbonaceous Chondritic Impacts

NASA's Dawn spacecraft observations of asteroid (4) Vesta reveal a surface with the highest albedo and color variation of any asteroid we have observed so far. Terrains rich in low albedo dark material (DM) have been identified using Dawn Framing Camera (FC) 0.75 {\mu}m filter images in several geologic settings: associated with impact craters (in the ejecta blanket material and/or on the crater walls and rims); as flow-like deposits or rays commonly associated with topographic highs; and as dark spots (likely secondary impacts) nearby impact craters. This DM could be a relic of ancient volcanic activity or exogenic in origin. We report that the majority of the spectra of DM are similar to carbonaceous chondrite meteorites mixed with materials indigenous to Vesta. Using high-resolution seven color images we compared DM color properties (albedo, band depth) with laboratory measurements of possible analog materials. Band depth and albedo of DM are identical to those of carbonaceous chondrite xenolith-rich howardite Mt. Pratt (PRA) 04401. Laboratory mixtures of Murchison CM2 carbonaceous chondrite and basaltic eucrite Millbillillie also show band depth and albedo affinity to DM. Modeling of carbonaceous chondrite abundance in DM (1-6 vol%) is consistent with howardite meteorites. We find no evidence for large-scale volcanism (exposed dikes/pyroclastic falls) as the source of DM. Our modeling efforts using impact crater scaling laws and numerical models of ejecta reaccretion suggest the delivery and emplacement of this DM on Vesta during the formation of the ~400 km Veneneia basin by a low-velocity (<2 km/sec) carbonaceous impactor. This discovery is important because it strengthens the long-held idea that primitive bodies are the source of carbon and probably volatiles in the early Solar System.Comment: Icarus (Accepted) Pages: 58 Figures: 15 Tables: