Analysis of β-globin chromatin micro-environment using a novel 3C variant, 4Cv

Copyright: © 2010 Pink et al.Higher order chromatin folding is critical to a number of developmental processes, including the regulation of gene expression. Recently developed biochemical techniques such as RNA TRAP and chromosome conformation capture (3C) have provided us with the tools to probe chromosomal structures. These techniques have been applied to the β-globin locus, revealing a complex pattern of interactions with regions along the chromosome that the gene resides on. However, biochemical and microscopy data on the nature of β-globin interactions with other chromosomes is contradictory. Therefore we developed a novel 4C variant, Complete-genome 3C by vectorette amplification (4Cv), which allows an unbiased and quantitative method to examine chromosomal structure. We have used 4Cv to study the microenvironment of the β-globin locus in mice and show that a significant proportion of the interactions of β-globin are inter-chromosomal. Furthermore, our data show that in the liver, where the gene is active, β-globin is more likely to interact with other chromosomes, compared to the brain where the gene is silent and is more likely to interact with other regions along the same chromosome. Our data suggest that transcriptional activation of the β-globin locus leads to a change in nuclear position relative to the chromosome territory.Ryan Pink is supported by a grant from Action Medical Research; Daniel Caley is supported by a grant from The Dunhill Medical Trust; David Carter is supported by a grant from the British Society for Haematology

Constants of Geodesic Motion in Higher-Dimensional Black-Hole Spacetimes

In [arXiv:hep-th/0611083] we announced the complete integrability of geodesic motion in the general higher-dimensional rotating black-hole spacetimes. In the present paper we prove all the necessary steps leading to this conclusion. In particular, we demonstrate the independence of the constants of motion and the fact that they Poisson commute. The relation to a different set of constants of motion constructed in [arXiv:hep-th/0612029] is also briefly discussed.Comment: 8 pages, no figure

Complete Integrability of Geodesic Motion in General Kerr-NUT-AdS Spacetimes

We explicitly exhibit n-1 constants of motion for geodesics in the general D-dimensional Kerr-NUT-AdS rotating black hole spacetime, arising from contractions of even powers of the 2-form obtained by contracting the geodesic velocity with the dual of the contraction of the velocity with the (D-2)-dimensional Killing-Yano tensor. These constants of motion are functionally independent of each other and of the D-n+1 constants of motion that arise from the metric and the D-n = [(D+1)/2] Killing vectors, making a total of D independent constants of motion in all dimensions D. The Poisson brackets of all pairs of these D constants are zero, so geodesic motion in these spacetimes is completely integrable.Comment: 4 pages. We have now found that the geodesic motion is not just integrable, but completely integrabl

Invited Article: First flight in space of a wide-field-of-view soft x-ray imager using lobster-eye optics: Instrument description and initial flight results

We describe the development, launch into space, and initial results from a prototype wide field-of-view soft X-ray imager that employs lobster-eye optics and targets heliophysics, planetary, and astrophysics science. The sheath transport observer for the redistribution of mass is the first instrument using this type of optics launched into space and provides proof-of-concept for future flight instruments capable of imaging structures such as the terrestrial cusp, the entire dayside magnetosheath from outside the magnetosphere, comets, the Moon, and the solar wind interaction with planetary bodies like Venus and Mars [Kuntz et al., Astrophys. J. (in press)]

The structure of blocks with a Klein four defect group

We prove Erdmann’s conjecture [16] stating that every block with a Klein four defect group has a simple module with trivial source, and deduce from this that Puig’s finiteness conjecture holds for source algebras of blocks with a Klein four defect group. The proof uses the classification of finite simple groups

A First Comparison of Kepler Planet Candidates in Single and Multiple Systems

In this letter we present an overview of the rich population of systems with multiple candidate transiting planets found in the first four months of Kepler data. The census of multiples includes 115 targets that show 2 candidate planets, 45 with 3, 8 with 4, and 1 each with 5 and 6, for a total of 170 systems with 408 candidates. When compared to the 827 systems with only one candidate, the multiples account for 17 percent of the total number of systems, and a third of all the planet candidates. We compare the characteristics of candidates found in multiples with those found in singles. False positives due to eclipsing binaries are much less common for the multiples, as expected. Singles and multiples are both dominated by planets smaller than Neptune; 69 +2/-3 percent for singles and 86 +2/-5 percent for multiples. This result, that systems with multiple transiting planets are less likely to include a transiting giant planet, suggests that close-in giant planets tend to disrupt the orbital inclinations of small planets in flat systems, or maybe even to prevent the formation of such systems in the first place.Comment: 13 pages, 13 figures, submitted to ApJ Letter

Sosa on Knowledge, Judgment and Guessing

In Chapter 3 of Judgment and Agency, Sosa (Judgment and Agency, 2015) explicates the concept of a fully apt performance. In the course of doing so, he draws from illustrative examples of practical performances and applies lessons drawn to the case of cognitive performances, and in particular, to the cognitive performance of judging. Sosa’s examples in the practical sphere are rich and instructive. But there is, I will argue, an interesting disanalogy between the practical and cognitive examples he relies on. Ultimately, I think the source of the disanalogy is a problematic picture of the cognitive performance of guessing and its connection to knowledge and defeat. Once this critical line of argument is advanced, an alternative picture of guessing, qua cognitive performance, is articulated, one which avoids the problems discussed, and yet remains compatible with Sosa’s broader framework

Challenges and directions in studying cell-cell communication by extracellular vesicles

Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. They have important roles in numerous physiological and pathological processes, and show considerable promise as novel biomarkers of disease, as therapeutic agents and as drug delivery vehicles. Intriguingly, however, understanding of the cellular and molecular mechanisms that govern the many observed functions of EVs remains far from comprehensive, at least partly due to technical challenges in working with these small messengers. Here, we highlight areas of consensus as well as contentious issues in our understanding of the intracellular and intercellular journey of EVs: from biogenesis, release and dynamics in the extracellular space, to interaction with and uptake by recipient cells. We define knowledge gaps, identify key questions and challenges, and make recommendations on how to address these

Kepler constraints on planets near hot Jupiters

We present the results of a search for planetary companions orbiting near hot Jupiter planet candidates (Jupiter-size candidates with orbital periods near 3 d) identified in the Kepler data through its sixth quarter of science operations. Special emphasis is given to companions between the 2∶1 interior and exterior mean-motion resonances. A photometric transit search excludes companions with sizes ranging from roughly two-thirds to five times the size of the Earth, depending upon the noise properties of the target star. A search for dynamically induced deviations from a constant period (transit timing variations) also shows no significant signals. In contrast, comparison studies of warm Jupiters (with slightly larger orbits) and hot Neptune-size candidates do exhibit signatures of additional companions with these same tests. These differences between hot Jupiters and other planetary systems denote a distinctly different formation or dynamical history