Pharmacological characterisation of the hP2Y11 and xlP2Y11 receptors.

Extracellular nucleotides and nucleosides are important signalling molecules that exert a diverse range of physiological responses throughout the body. These chemical messengers often transduce their effects through interaction with specific cell surface receptors called purinoceptors. The P2Y purinoceptor family binds extracellular nucleotides, principally ATP, ADP, UTP and UDP. Conformational change of the P2Y purinoceptors upon ligand binding conveys a signal to intracellular heterotrimeric G proteins, which are activated, transducing the signal further downstream by acting at different effector enzymes to influence second messenger production. In this thesis I present the first pharmacological characterisation of a non-manurtalian P2Yn receptor orthologue, Xenopus laevis P2Yn (XlP2Yn), and extend the pharmacological profile of the human P2Yn receptor (hP2Yn). Second messenger assays were employed to record the intracellular cyclic AMP (cAMP) accumulation and Ca2+ mobilisation generated by both the human and Xenopus laevis P2Y receptors in response to various P2Y agonists and antagonists. In a manner similar to its human orthologue, I have shown that XlP2Yn is activated by nucleotides and nucleotide analogues, mobilising calcium from intracellular stores, and increasing cAMP production through the activation of adenylyl cyclase. When compared to previously published data, XlP2Yn exhibits a novel rank order of agonist and antagonist potency, revealing a receptor functionally similar but pharmacologically distinct from both the human and canine P2Yn receptor orthologues (hP2Yn and cP2Yn)

Hall effect in the marginal Fermi liquid regime of high-Tc superconductors

The detailed derivation of a theory for transport in quasi-two-dimensional metals, with small-angle elastic scattering and angle-independent inelastic scattering is presented. The transport equation is solved for a model Fermi surface representing a typical cuprate superconductor. Using the small-angle elastic and the inelastic scattering rates deduced from angle-resolved photoemission experiments, good quantitative agreement with the observed anomalous temperature dependence of the Hall angle in optimally doped cuprates is obtained, while the resistivity remains linear in temperature. The theory is also extended to the frequency-dependent complex Hall angle

Filling historical data gaps to foster solutions in marine conservation

Ecological data sets rarely extend back more than a few decades, limiting our understanding of environmental change and its drivers. Marine historical ecology has played a critical role in filling these data gaps by illuminating the magnitude and rate of ongoing changes in marine ecosystems. Yet despite a growing body of knowledge, historical insights are rarely explicitly incorporated in mainstream conservation and management efforts. Failing to consider historical change can have major implications for conservation, such as the ratcheting down of expectations of ecosystem quality over time, leading to less ambitious targets for recovery or restoration. We discuss several unconventional sources used by historical ecologists to fill data gaps - including menus, newspaper articles, cookbooks, museum collections, artwork, benthic sediment cores - and novel techniques for their analysis. We specify opportunities for the integration of historical data into conservation and management, and highlight the important role that these data can play in filling conservation data gaps and motivating conservation actions. As historical marine ecology research continues to grow as a multidisciplinary enterprise, great opportunities remain to foster direct linkages to conservation and improve the outlook for marine ecosystems

Constraining the Volume Density of Dusty Star-forming Galaxies through the First 3 mm Number Counts from ALMA

Large scale structure and cosmolog

Physical Characterization of an Unlensed, Dusty Star-forming Galaxy at z = 5.85

We present a physical characterization of MM J100026.36+021527.9 (a.k.a. "Mambo-9"), a dusty star-forming galaxy (DSFG) at z = 5.850 \ub1 0.001. This is the highest-redshift unlensed DSFG (and fourth most distant overall) found to date and is the first source identified in a new 2 mm blank-field map in the COSMOS field. Though identified in prior samples of DSFGs at 850 \u3bcm to 1.2 mm with unknown redshift, the detection at 2 mm prompted further follow-up as it indicated a much higher probability that the source was likely to sit at z > 4. Deep observations from the Atacama Large Millimeter and submillimeter Array (ALMA) presented here confirm the redshift through the secure detection of 12CO(J = 6\u21925) and p-H2O (21,1 \u2192 20,2). Mambo-9 is composed of a pair of galaxies separated by 6 kpc with corresponding star formation rates of 590 M o\u2d9 yr-1 and 220 M o\u2d9 yr-1, total molecular hydrogen gas mass of (1.7 \ub1 0.4) 7 1011 M o\u2d9, dust mass of (1.3 \ub1 0.3) 7 109 M o\u2d9, and stellar mass of (3.2-1.5+1.0) 7 109 M o\u2d9. The total halo mass, (3.3 \ub1 0.8) 7 1012 M o\u2d9, is predicted to exceed 1015 M o\u2d9 by z = 0. The system is undergoing a merger-driven starburst that will increase the stellar mass of the system tenfold in \u3c4 depl = 40-80 Myr, converting its large molecular gas reservoir (gas fraction of 96-2+1) into stars. Mambo-9 evaded firm spectroscopic identification for a decade, following a pattern that has emerged for some of the highest-redshift DSFGs found. And yet, the systematic identification of unlensed DSFGs like Mambo-9 is key to measuring the global contribution of obscured star formation to the star formation rate density at z \u2a86 4, the formation of the first massive galaxies, and the formation of interstellar dust at early times ( 721 Gyr)

Germinal Centers without T Cells

Germinal centers are critical for affinity maturation of antibody (Ab) responses. This process allows the production of high-efficiency neutralizing Ab that protects against virus infection and bacterial exotoxins. In germinal centers, responding B cells selectively mutate the genes that encode their receptors for antigen. This process can change Ab affinity and specificity. The mutated cells that produce high-affinity Ab are selected to become Ab-forming or memory B cells, whereas cells that have lost affinity or acquired autoreactivity are eliminated. Normally, T cells are critical for germinal center formation and subsequent B cell selection. Both processes involve engagement of CD40 on B cells by T cells. This report describes how high-affinity B cells can be induced to form large germinal centers in response to (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll in the absence of T cells or signaling through CD40 or CD28. This requires extensive cross-linking of the B cell receptors, and a frequency of antigen-specific B cells of at least 1 in 1,000. These germinal centers abort dramatically at the time when mutated high-affinity B cells are normally selected by T cells. Thus, there is a fail-safe mechanism against autoreactivity, even in the event of thymus-independent germinal center formation

Massive Star Formation

This chapter reviews progress in the field of massive star formation. It focuses on evidence for accretion and current models that invoke high accretion rates. In particular it is noted that high accretion rates will cause the massive young stellar object to have a radius much larger than its eventual main sequence radius throughout much of the accretion phase. This results in low effective temperatures which may provide the explanation as to why luminous young stellar objects do not ionized their surroundings to form ultra-compact H II regions. The transition to the ultra-compact H II region phase would then be associated with the termination of the high accretion rate phase. Objects thought to be in a transition phase are discussed and diagnostic diagrams to distinguish between massive young stellar objects and ultra-compact H II regions in terms of line widths and radio luminosity are presented.Comment: 21 pages, 6 figures, chapter in Diffuse Matter from Star Forming Regions to Active Galaxies - A Volume Honouring John Dyson, Edited by T.W. Hartquist, J. M. Pittard, and S. A. E. G. Falle. Series: Astrophysics and Space Science Proceedings. Springer Dordrecht, 2007, p.6

The landscape of cognitive neuroscience: challenges, rewards, and new perspectives

No abstract available

Characterization of two 2 mm detected optically obscured dusty star-forming galaxies

Galaxie