General CMB bispectrum analysis using wavelets and separable modes

In this paper we combine partial-wave (`modal') methods with a wavelet analysis of the CMB bispectrum. Our implementation exploits the advantages of both approaches to produce robust, reliable and efficient estimators which can constrain the amplitude of arbitrary primordial bispectra. This will be particularly important for upcoming surveys such as \emph{Planck}. A key advantage is the computational efficiency of calculating the inverse covariance matrix in wavelet space, producing an error bar which is close to optimal. We verify the efficacy and robustness of the method by applying it to WMAP7 data, finding \fnllocal=38.4 \pm 23.6 and \fnlequil=-119.2 \pm 123.6

Central Star Formation in Pseudobulges and Classical Bulges

I use Spitzer 3.6-8.0 \mu m color profiles to compare the radial structure of star formation in pseudobulges and classical bulges. Pseudobulges are ``bulges'' which form through secular evolution, rather than mergers. In this study, pseudobulges are identified using the presence of disk-like structure in the center of the galaxy (nuclear spiral, nuclear bar, and/or high ellipticity in bulge); classical bulges are those galaxy bulges with smooth isophotes which are round compared to the outer disk, and show no disky structure in their bulge. I show that galaxies structurally identified as having pseudobulges have higher central star formation rates than those of classical bulges. Further, I also show that galaxies identified as having classical bulges have remarkably regular star formation profiles. The color profiles of galaxies with classical bulges show a star forming outer disk with a sharp change, consistent with a decline in star formation rates, toward the center of the galaxy. Classical bulges have a nearly constant inner profile (r < 1.5 kpc) that is similar to elliptical galaxies. Pseudobulges in general show no such transition in star formation properties from the outer disk to the central pseudobulge. Thus I conclude that pseudobulges and classical bulges do in fact form their stars via different mechanisms. Further, this adds to the evidence that classical bulges form most of their stars in fast episodic bursts, in a similar fashion to elliptical galaxies; whereas, pseudobulges form stars from longer lasting secular processes.Comment: accepted to ApJ Letter

NMR DIFFUSION MEASUREMENTS OF COMPARTMENTALIZED AND MULTICOMPONENT BIOLOGICAL SYSTEMS: Studies of Tropoelastin, the Self Association of N Methylacetamide, and q-Space Analysis of Real and Model Cell Suspensions

Molecular diffusion is an inherent feature of all fluid systems. The processes and interactions that characterize these systems are in some way dependent upon the mobility of the component molecules. Pulsed field-gradient spin-echo nuclear magnetic resonance (PGSE NMR) is a powerful tool for the study of molecular diffusion; for heterogeneous systems, such as those typically found in biology, this technique is unsurpassed in the diversity of systems that yield to its probing. The aim of the work presented in this thesis was to use an integrated NMR-based approach, in conjunction with computer modeling, for the study of molecular diffusion in compartmentalized and multicomponent biological systems. Erythrocyte suspensions provided an ideal experimental system for the study of compartmentalized diffusion in cells. Water exchanges rapidly between the intra- and extracellular regions and, as the major constituent of the cell, provides a strong and predominant proton NMR signal. In addition, the cells are known to align in the strong static magnetic field of the spectrometer. As a consequence of these two properties, the signal intensity from a suitably designed series of PGSE NMR experiments exhibits a series of maxima and minima when graphed as a function of the magnitude of the spatial wave number vector q. The apparently periodic phenomenon is mathematically analogous to optical diffraction and interference and is referred to here as diffusion-coherence. It is the characterization of this phenomenon, with the aid of computer-based models, which was the focus of a major section of the work described herein. Two quite distinct molecular systems formed the basis of the work in which I investigated diffusion in multicomponent systems. Both systems involved molecules that undergo self-association such that at equilibrium a population distribution of different oligomeric species is present. The first of these was tropoelastin, the monomeric subunit of elastin, which under certain conditions aggregates to form a coacervate. The second system was N-methylacetamide (NMA) which also undergoes extensive self-association. NMA oligomers have previously been studied as peptide analogues due to the presence in the monomer of a peptide linkage. In this work the aim was to use PGSE NMR diffusion measurements, in a manner that is in many ways analogous to analytical ultracentrifugation, to obtain estimates of hydrodynamic and thermodynamic parameters. Computer modeling was also used extensively in this section of work for the interpretation of the experimental data

NMR DIFFUSION MEASUREMENTS OF COMPARTMENTALIZED AND MULTICOMPONENT BIOLOGICAL SYSTEMS: Studies of Tropoelastin, the Self Association of N Methylacetamide, and q-Space Analysis of Real and Model Cell Suspensions

Molecular diffusion is an inherent feature of all fluid systems. The processes and interactions that characterize these systems are in some way dependent upon the mobility of the component molecules. Pulsed field-gradient spin-echo nuclear magnetic resonance (PGSE NMR) is a powerful tool for the study of molecular diffusion; for heterogeneous systems, such as those typically found in biology, this technique is unsurpassed in the diversity of systems that yield to its probing. The aim of the work presented in this thesis was to use an integrated NMR-based approach, in conjunction with computer modeling, for the study of molecular diffusion in compartmentalized and multicomponent biological systems. Erythrocyte suspensions provided an ideal experimental system for the study of compartmentalized diffusion in cells. Water exchanges rapidly between the intra- and extracellular regions and, as the major constituent of the cell, provides a strong and predominant proton NMR signal. In addition, the cells are known to align in the strong static magnetic field of the spectrometer. As a consequence of these two properties, the signal intensity from a suitably designed series of PGSE NMR experiments exhibits a series of maxima and minima when graphed as a function of the magnitude of the spatial wave number vector q. The apparently periodic phenomenon is mathematically analogous to optical diffraction and interference and is referred to here as diffusion-coherence. It is the characterization of this phenomenon, with the aid of computer-based models, which was the focus of a major section of the work described herein. Two quite distinct molecular systems formed the basis of the work in which I investigated diffusion in multicomponent systems. Both systems involved molecules that undergo self-association such that at equilibrium a population distribution of different oligomeric species is present. The first of these was tropoelastin, the monomeric subunit of elastin, which under certain conditions aggregates to form a coacervate. The second system was N-methylacetamide (NMA) which also undergoes extensive self-association. NMA oligomers have previously been studied as peptide analogues due to the presence in the monomer of a peptide linkage. In this work the aim was to use PGSE NMR diffusion measurements, in a manner that is in many ways analogous to analytical ultracentrifugation, to obtain estimates of hydrodynamic and thermodynamic parameters. Computer modeling was also used extensively in this section of work for the interpretation of the experimental data

Mechanisms of glucocorticoid programmed disease

Substantial epidemiological evidence correlates low weight or thinness at birth with increased risk of disease in later life; notably insulin resistance, hypertension and ischaemic heart disease. This concept of intrauterine life events having permanent influences upon later health has been termed 'programming'. Whilst the molecular mechanisms linking these effects are unknown, overexposure of the foetus to glucocorticoids has been implicated. Treating pregnant rats with dexamethasone (DEX), a synthetic glucocorticoid commonly used in obstetric practice, results in offspring born of low weight, who subsequently develop adulthood hypertension, glucose intolerance and insulin resistance. Whilst prenatal DEX-programmed glucose intolerance is associated with permanently increased hepatic activity of a key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK), mechanisms underlying the programming of hypertension remain unidentified. DEX-programmed hypertension occurs in both sexes, whilst hyperglycaemia/hyperinsulinaemia has only been demonstrated in male offspring. Principally, this thesis investigates the role of the renin-angiotensin (RAS), and sympathetic nervous systems (SNS) in determining programmed hypertension, and seeks to determine whether programming effects are sexually dimoiphic. ft further examines the impact of dietary manipulations, and environmental noise stress, on prenatally-treated offspring phenotypes.DEX administration in the last week of gestation reduces offspring birth weight and programmes adult cardiovascular and metabolic physiology in a sex specific manner. In male offspring, prenatal glucocorticoid exposure programmes elevated basal circulating corticosterone, elevated PEPCK activity, and produces adulthood post-glucose hyperglycaemia and hyperinsulinaemia. Whilst in female offspring, prenatal DEX programmes elevated hepatic angiotensinogen mRNA expression, elevated plasma angiotensinogen and renin activity, and produces hypertension, when measured by tail-cuff plethysmography.A 4-fold reduction in dietary sodium intensifies this RAS dysregulation in female DEX-treated offspring; however this does not exacerbate their programmed blood pressure phenotype. Conversely, the lower sodium diet results in hypertension in prenatally vehicle treated animals, and supports a role for both the HPA and RAS in mediating this. Furthermore, acute exposure to the lower sodium diet is sufficient to cause glucose intolerance and insulin resistance in female adult rats, irrespective of their prenatal treatment.Unlike previous studies, offspring blood pressure was subsequently assessed with radiotelemetry, which is unmarred by any stress artefact. We now show that prenatal DEX-treated male and female offspring actually display lower basal blood pressure in adulthood; with the commonly expected hypertensive phenotype only being noted when these offspring are subjected to any stressor, regardless of its apparent banality. Moreover, DEX-treated offspring sustain this stress-induced hypertension for longer. These hypertensive responses are mediated by alterations in the responsivity of the sympathetic nervous system, being ameliorated by the inhibition of catecholamine synthesis, and further exaggerated by the promotion of systemic catecholamine release. Additionally, we demonstrate that DEX-treated offspring display greater sensitivity to various vasoconstrictors in the isolated mesenteric vasculature.Finally, perinatal exposure of pregnant rats to environmental noise pollution results in vehicle-treated offspring with a phenotype analogous to prenatal DEXtreated offspring i.e. lower birth weight, hypercorticosteronaemia, hypertension, and features of the insulin resistance syndrome. Conversely, exposure of DEX-treated offspring to the same perinatal noise stressors does not appear to further influence their phenotype. Therefore, perinatal stress produces a similar phenotype to prenatal glucocorticoid over-exposure.These findings demonstrate that in utero over-exposure to glucocorticoids actually results in stress-induced hypertension, and support a role for both RAS and SNS in mediating this. Furthermore, it appears that the programming of cardiovascular physiology may reflect distinct processes in each gender, whilst the programming of metabolic physiology is male specific