Extreme scattering events and Galactic dark matter

Extreme Scattering Events (ESEs) are attributed to radio-wave refraction by a cloud of free-electrons crossing the line-of-sight. We present a new model in which these electrons form the photo-ionized 'skin' of an underlying cool, self-gravitating cloud in the Galactic halo. In this way we avoid the severe over-pressure problem which afflicts other models. The UV flux in the Galactic halo naturally generates electron densities of the right order. We demonstrate, for the first time, a good reproduction of the prototypical ESE in the quasar 0954+658. The neutral clouds are a few AU in radius and have masses less than about 10^{-3} solar. The observed rate of ESEs implies that a large fraction of the mass of the Galaxy is in this form.Comment: 5 pp incl 3 figs, LaTeX, uses aas2pp4.sty. Minor revisions. ApJ Letters in pres

Rewriteability in Finite Groups

What\u27s the probability that two elements in a finite group commute? A formal answer, Pr2(G) = {(x, y) [element of] G2 |xy = yx}| / |G|2 begs our next question. How many ordered pairs of elements of a finite group commute

Rewriteability in Finite Groups

What\u27s the probability that two elements in a finite group commute? A formal answer, Pr2(G) = {(x, y) [element of] G2 |xy = yx}| / |G|2 begs our next question. How many ordered pairs of elements of a finite group commute

Peripartum cardiomyopathy: diagnosis and management

No abstract available

Structural discordance between neogene detachments and frontal sevier thrusts, central Mormon Mountains, southern Nevada

This is the published version. Copyright 1985 American Geophysical Union. All Rights Reserved.Detailed geologic mapping in the Mormon Mountains of southern Nevada provides significant insight into processes of extensional tectonics developed within older compressional orogens. A newly discovered, WSW-directed low-angle normal fault, the Mormon Peak detachment, juxtaposes the highest levels of the frontal most part of the east-vergent, Mesozoic Sevier thrust belt with autochthonous crystalline basement. Palinspastic analysis suggests that the detachment initially dipped 20–25° to the west and cut discordantly across thrust faults. Nearly complete lateral removal of the hanging wall from the area has exposed a 5 km thick longitudinal cross-section through the thrust belt in the footwall, while highly attenuated remnants of the hanging wall (nowhere more than a few hundred meters thick) structurally veneer the range. The present arched configuration of the detachment resulted in part from progressive “domino-style” rotation of a few degrees while it was active, but is largely due to rotation on younger, structurally lower, basement-penetrating normal faults that initiated at high-angle. The geometry and kinematics of normal faulting in the Mormon Mountains suggest that pre-existing thrust planes are not required for the initiation of low-angle normal faults, and even where closely overlapped by extensional tectonism, need not function as a primary control of detachment geometry. Caution must thus be exercised in interpreting low-angle normal faults of uncertain tectonic heritage such as those seen in the COCORP west-central Utah and BIRP's MOIST deep-reflection profiles. Although thrust fault reactivation has reasonably been shown to be the origin of a very few low-angle normal faults, our results indicate that it may not be as fundamental a component of orogenic architecture as it is now widely perceived to be. We conclude that while in many instances thrust fault reactivation may be both a plausible and attractive hypothesis, it may never be assumed

Antibody-based detection of protein phosphorylation status to track the efficacy of novel therapies using nanogram protein quantities from stem cells and cell lines

This protocol describes a highly reproducible antibody-based method that provides protein level and phosphorylation status information from nanogram quantities of protein cell lysate. Nanocapillary isoelectric focusing (cIEF) combines with UV-activated linking chemistry to detect changes in phosphorylation status. As an example application, we describe how to detect changes in response to tyrosine kinase inhibitors (TKIs) in the phosphorylation status of the adaptor protein ​CrkL, a major substrate of the oncogenic tyrosine kinase ​BCR-​ABL in chronic myeloid leukemia (CML), using highly enriched CML stem cells and mature cell populations in vitro. This protocol provides a 2.5 pg/nl limit of protein detection (<0.2% of a stem cell sample containing <104 cells). Additional assays are described for phosphorylated tyrosine 207 (pTyr207)-​CrkL and the protein tyrosine phosphatase ​PTPRC/​CD45; these assays were developed using this protocol and applied to CML patient samples. This method is of high throughput, and it can act as a screen for in vitro cancer stem cell response to drugs and novel agents

Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes.

Neutrophils release free zinc to eliminate the phagocytosed bacterial pathogen Streptococcus pyogenes (Group A Streptococcus; GAS). In this study, we investigated the mechanisms underpinning zinc toxicity towards this human pathogen, responsible for diseases ranging from pharyngitis and impetigo, to severe invasive infections. Using the globally-disseminated M1T1 GAS strain, we demonstrate that zinc stress impairs glucose metabolism through the inhibition of the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. In the presence of zinc, a metabolic shift to the tagatose-6-phosphate pathway allows conversion of D-galactose to dihydroxyacetone phosphate and glyceraldehyde phosphate, partially bypassing impaired glycolytic enzymes to generate pyruvate. Additionally, zinc inhibition of phosphoglucomutase results in decreased capsule biosynthesis. These data indicate that zinc exerts it toxicity via mechanisms that inhibit both GAS central carbon metabolism and virulence pathways

TPL-2 restricts Ccl24-dependent immunity to Heligmosomoides polygyrus

Funding: This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001220), the UK Medical Research Council (FC001220), and the Wellcome Trust (FC001200). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We are indebted to The Francis Crick Institute Flow Cytometry facility, and in particular Bhavik Patel, Graham Preece, Wayne Turnbull and Phil Hobson. We would also like to thank The Francis Crick Institute Procedural Service Section for production of GA lines and Biological Services, especially Trisha Norton, Keith Williams and Adebambo Adekoya for animal husbandry and technical support; to Riccardo Guidi for constructive discussions and technical assistance. We would like to thank Gitta Stockinger and AhR Immunity Laboratory for providing technical support and reagents throughout this study. We also thank Richard Rance and the Wellcome Trust Sanger Institute’s 454 pyrosequencing team for generating 16S rRNA gene data.Peer reviewedPublisher PD