Nonproliferation Regime Compliance: Prediction and Measure Using UNSCR 1540

This dissertation investigates factors that predict compliance with international regimes, specifically the Non-Proliferation Regime. Generally accepted in international relations literature, is Krasner’s (1983) definition that regimes are “sets of implicit or explicit principles, norms, rules, and decision-making procedures around which actor expectations converge in a given [issue] area of international relations.” Using institutionalization as a framework, I hypothesize that compliance is a function of the respect for which a nation has for the rule of law. I investigate the NP regime through the lens of United Nations Security Council Resolution 1540, a mandate for member nations to enact domestic legislation criminalizing the proliferation of Weapons of Mass Destruction. Using NP regime compliance and implementation of UNSCR 1540’s mandates as dependent variables, I test the hypotheses with the following independent variables: rule of law, political competition, and regional compliance. I also present qualitative case studies on Argentina, South Africa, and Malaysia. The quantitative results of these analyses indicated a strong relationship between rule of law and regional compliance and a nation’s compliance with the overall NP regime and implementation of UNSCR 1540. These results indicate a nation will institutionalize the NP norms, and comply with the specifics of implementation. The results of in-depth analysis of Argentina, South Africa, and Malaysia showed that predicting an individual nation’s compliance is more complex than descriptions of government capacity or geography. Argentina and South Africa, expected by the hypotheses to exhibit low to medium compliance and implementation, scored high and well above their region for both measures. Malaysia, expected to score high in compliance, scored low. Findings thus reveal that rule of law is probably less influential on individual cases and regional compliance and cooperation better predictors of a nation’s compliance with a security regime

Drug-like antagonists of P2Y receptors — from lead identification to drug development

P2Y receptors are expressed in virtually all cells and tissue types and mediate an astonishing array of biological functions, including platelet aggregation, smooth muscle cell proliferation, and immune regulation. The P2Y receptors belong to the G protein-coupled receptor superfamily and are composed of eight members encoded by distinct genes that can be subdivided into two groups on the basis of their coupling to specific G-proteins. Extensive research has been undertaken to find modulators of P2Y receptors, although to date only a limited number of small-molecule P2Y receptor antagonists have been approved by drug/medicines agencies. This Perspective reviews the known P2Y receptor antagonists, highlighting oral drug-like receptor antagonists, and considers future opportunities for the development of small molecules for clinical evaluation

Drug-like antagonists of P2Y receptors — from lead identification to drug development

P2Y receptors are expressed in virtually all cells and tissue types and mediate an astonishing array of biological functions, including platelet aggregation, smooth muscle cell proliferation, and immune regulation. The P2Y receptors belong to the G protein-coupled receptor superfamily and are composed of eight members encoded by distinct genes that can be subdivided into two groups on the basis of their coupling to specific G-proteins. Extensive research has been undertaken to find modulators of P2Y receptors, although to date only a limited number of small-molecule P2Y receptor antagonists have been approved by drug/medicines agencies. This Perspective reviews the known P2Y receptor antagonists, highlighting oral drug-like receptor antagonists, and considers future opportunities for the development of small molecules for clinical evaluation

Synthesis and evaluation of the first fluorescent antagonists of the human P2Y2 receptor based on AR-C118925

The human P2Y2 receptor (hP2Y2R) is a G protein-coupled receptor that shows promise as a therapeutic target for many important conditions including anti-metastatic cancer therapy and more recently for the treatment of idiopathic pulmonary fibrosis. As such, there is a need for new hP2Y2R antagonists and molecular probes to study this receptor. Herein, we report the development of a new series of non-nucleotide hP2Y2R antagonists leading to the discovery of a series of fluorescent ligands containing different linkers and fluorophores based on the known, non-nucleotide hP2Y2R antagonist AR-C118925 (1). One of these conjugates 98 displayed micromolar affinity for the hP2Y2R (pKd = 6.32 ± 0.10; n=17) using a bioluminescence energy transfer (BRET) assay. Confocal microscopy with this ligand revealed displaceable membrane labeling of astrocytoma cells expressing un-tagged hP2Y2R. These properties, make 98 one of the first tools for studying hP2Y2R distribution and organization

The GALEX Arecibo SDSS survey: III. Evidence for the Inside-Out Formation of Galactic Disks

We analyze a sample of galaxies with stellar masses greater than $10^{10} M_{\odot}$ and with redshifts in the range $0.025<z<0.05$ for which HI mass measurements are available from the GALEX Arecibo SDSS Survey (GASS) or from the Arecibo Legacy Fast ALFA survey (ALFALFA). At a given value of $M_*$, our sample consists primarily of galaxies that are more HI-rich than average. We constructed a series of three control samples for comparison with these HI-rich galaxies. As expected, HI-rich galaxies differ strongly from galaxies of same stellar mass that are selected without regard to HI content. The majority of these differences are attributable to the fact that galaxies with more gas are bluer and more actively star-forming. In order to identify those galaxy properties that are causally connected with HI content, we compare results derived for the HI sample with those derived for galaxies matched in stellar mass, size and NUV-$r$ colour. The only photometric property that is clearly attributable to increasing HI content, is the colour gradient of the galaxy. Galaxies with larger HI fractions have bluer, more actively star-forming outer disks compared to the inner part of the galaxy. HI-rich galaxies also have larger $g$-band radii compared to $i$-band radii. Our results are consistent with the "inside-out" picture of disk galaxy formation, which has commonly served as a basis for semi-analytic models of the formation of disks in the context of Cold Dark Matter cosmologies. The lack of any intrinsic connection between HI fraction and galaxy asymmetry suggests that gas is accreted smoothly onto the outer disk.Comment: 18 pages, 20 figures. Accepted for publication in MNRAS. GASS publications and released data can be found at http://www.mpa-garching.mpg.de/GASS/index.ph

The global build-up to intrinsic edge localized mode bursts seen in divertor full flux loops in JET

A global signature of the build-up to an intrinsic edge localized mode (ELM) is found in the temporal analytic phase of signals measured in full flux azimuthal loops in the divertor region of JET. Toroidally integrating, full flux loop signals provide a global measurement proportional to the voltage induced by changes in poloidal magnetic flux; they are electromagnetically induced by the dynamics of spatially integrated current density. We perform direct time-domain analysis of the high time-resolution full flux loop signals VLD2 and VLD3. We analyze plasmas where a steady H-mode is sustained over several seconds during which all the observed ELMs are intrinsic; there is no deliberate intent to pace the ELMing process by external means. ELM occurrence times are determined from the Be II emission at the divertor. We previously [Chapman et al., Phys. Plasmas 21, 062302 (2014); Chapman et al., in 41st EPS Conference on Plasma Physics, Europhysics Conference Abstracts (European Physical Society, 2014), Vol. 38F, ISBN 2-914771-90-8] found that the occurrence times of intrinsic ELMs correlate with specific temporal analytic phases of the VLD2 and VLD3 signals. Here, we investigate how the VLD2 and VLD3 temporal analytic phases vary with time in advance of the ELM occurrence time. We identify a build-up to the ELM in which the VLD2 and VLD3 signals progressively align to the temporal analytic phase at which ELMs preferentially occur, on a ∼2−5ms timescale. At the same time, the VLD2 and VLD3 signals become temporally phase synchronized with each other, consistent with the emergence of coherent global dynamics in the integrated current density. In a plasma that remains close to a global magnetic equilibrium, this can reflect bulk displacement or motion of the plasma. This build-up signature to an intrinsic ELM can be extracted from a time interval of data that does not extend beyond the ELM occurrence time, so that these full flux loop signals could assist in ELM prediction or mitigation