B 0 field inhomogeneity considerations in pseudo‐continuous arterial spin labeling (pCASL): effects on tagging efficiency and correction strategy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89456/1/nbm1675.pd

Interaction of Aspirin (Acetylsalicylic Acid) with Lipid Membranes

We studied the interaction of Aspirin (acetylsalicylic acid) with lipid membranes using x-ray diffraction for bilayers containing up to 50 mol% of aspirin. From 2D x-ray intensity maps that cover large areas of reciprocal space we determined the position of the ASA molecules in the phospholipid bilayers and the molecular arrangement of the molecules in the plane of the membranes. We present direct experimental evidence that ASA molecules participate in saturated lipid bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and preferably reside in the head group region of the membrane. Up to 50 mol% ASA molecules can be dissolved in this type of bilayer before the lateral membrane organization is disturbed and the membranes are found to form an ordered, 2D crystal-like structure. Furthermore, ASA and cholesterol were found to co-exist in saturated lipid bilayers, with the ASA molecules residing in the head group region and the cholesterol molecules participating in the hydrophobic membrane core

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Eye-to-eye with a mega-sheath fold: A case study from Wadi Mayh, northern Oman Mountains

Sheath folds are highly curvilinear folds, typically considered to develop by hinge rotation toward the transport direction during intense deformation. Most sheath folds are recognized on the centimeter to meter scale, with very few detailed studies of larger kilometer-scale structures. We here present evidence for a megascale sheath fold superbly exposed in the northern Oman Mountains. The Saih Hatat culmination consists of an exhumed high-pressure subduction zone with deep-level eclogites and garnet blueschists (As Sifah unit), epidote blueschists (Hulw unit) and carpholite-bearing metasediments (part of the "Upperplate"). Sheath folds are present at a variety of scales throughout the As Sifah, Hulw, and Upper plate tectonic packages. Curvilinear fold hinges along a 15-km-long profile outline the Wadi Mayh mega-sheath fold, which closes to the SSW and faces to the NNE. It consists of at least four secondary sheath folds with cross-sectional (y-z) eye folds measuring 200 m stacked on top of one another within Permian and Triassic shelf carbonates. These eye folds display highly elliptical geometries (Ryz > 5) and cat's-eye fold patterns consistent with simple/general shear. The sheath fold is enveloped by Ordovician and older rocks that do not show equal amounts of internal deformation. The upper bounding envelope is a detachment that has been subsequently sheath folded. The lower boundary of the sheath fold is the Upper plate-Lower plate detachment, which forms a major high-strain shear zone showing little vertical displacement but significant horizontal displacement. The sheath fold displays a SSW elongation (x axis) of at least 15 km and possibly up to 25 km, coupled with significant amounts of vertical flattening and WNW-ESE shortening. © 2007 The Geological Society of America

The evolution and significance of microfracturing within feldspars in low-grade granitic mylonites: A case study from the Eastern Ghats Mobile Belt, India

Patterns of microfracturing are investigated in plagioclase and K-feldspar porphyroclasts formed within granitic mylonites along the boundary of the Eastern Ghats Mobile Belt, India. The mineral assemblage comprising quartz, feldspar, biotite and hornblende suggests lower greenschist facies conditions during mylonitisation, with the contrasting ductile behaviour of quartz and brittle fracturing of feldspars restricting the temperature range during deformation to 300-350 degrees C. Microfracturing of feldspars takes place by concentration of pure shear within the feldspar-rich layers. This may reflect strain partitioning into dominantly pure and simple shear due to the competency contrasts between the two major constituent minerals (quartz and feldspar). The microfractures occur in conjugates (here designated T(1) and T(2)) with T(1) inclined in the same direction as the S-fabric and showing an antithetic sense to the NW verging shear, while T(2) is inclined in an opposite sense to the S-fabric and displays synthetic shear. The direction of maximum compression occurs at high angles to the C-fabric, and the T(1) and T(2) fractures are the result of pure shear localized into brittle layers within the mylonite. With progressive shear, the fractures along with their host feldspar grains are rotated. Theoretical graphs are plotted between bulk shear (gamma) and the angle of initiation (alpha) of T(1) and T(2) with respect to C-planes, for fractures hosted in a circular or elliptical objects. The kinematics of these fractures are also analyzed with regard to variations in shear strain and sense of shear along them. The sense of shear may vary or remain stable within fractures, depending on their initial angle of inclination with respect to the C-fabric. As T(1) is inclined at low angles to the XY plane and in the same direction as the S-fabric, it undergoes maximum shear strain compared to T(2) and may even exceed the bulk shear. This facilitates breakdown of feldspar porphyroclasts during progressive deformation. The T(1) set maintains an antithetic sense of shear even at low angles with the C-fabric, while T(2) displays a synthetic sense in spite of being at high angles to C. The T(1) and T(2) fractures therefore differ significantly from the classic Riedel, P and Y shears where low angle fractures display synthetic shear and high angle ones (R') show antithetic displacement with respect to the bulk shear sense