Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2012-2013. / Le récepteur activé par les proliférateurs de peroxysomes de type y (PPARy) est un puissant régulateur des gènes impliqués dans le métabolisme du tissu adipeux et l'adipogenèse. Son activation pharmacologique, par des ligands de type thiazolidinedione (TZD), diminue la résistance à l'insuline et est utilisée en clinique dans le traitement du diabète de Type 2. Les agonistes de PPARy exercent leurs effets bénéfiques en favorisant la séquestration des lipides et leur entreposage dans les tissus adipeux périphériques métaboliquement plus sûrs, en stimulant la production adipocytaire d'adipokines telles l'adiponectine et en réduisant l'infiltration de macrophages dans les réserves de graisses. En détournant les lipides des organes tels que le muscle squelettique et le foie, les TZD préviennent la lipotoxicité. Bien que l'élucidation des mécanismes par lesquels PPARy contrôle l'entreposage des lipides dans le tissu adipeux progresse, les connaissances en ce domaine demeurent imcomplètes. Les travaux décrits dans cette thèse montrent que les agonistes de PPARy favorisent l'entreposage des graisses en périphérie en modulant de façon dépôt-spécifique et coordonnée la lipase lipoprotéique et les protéines impliquées dans sa maturation, les transporteurs d'acides gras et les enzymes lipogènes. Les résultats présentés dans cette thèse mettent également en évidence le rôle de la cible de la rapamycine chez les mammifères (mTOR, mammalian target of rapamycin) dans le contrôle de la lipogenèse exercé par PPARy in vivo. Lorsque cette protéine au coeur d'un réseau de signalisation contrôlant le métabolisme cellulaire est inactivée, l'activité transcriptionnelle de PPARy est significativement réduite et les TZD perdent leur capacité à stimuler l'entreposage des lipides circulants. Finalement, les études décrites dans cet ouvrage montrent que l'activation de PPARy peut à son tour influencer le sentier métabolique de mTOR en stimulant le catabolisme des acides aminés à chaîne ramifiée, l'un de ses principaux activateurs, dans les tissus adipeux blanc et brun. L'étude des interactions complexes entre ces deux systèmes a le potentiel de contribuer au développement de nouvelles avenues thérapeutiques pour prévenir et guérir l'obésité et le diabète.

samples were irradiated for approximately 45 minutes to allow for the saturation of fission products. The first method used the beam port shutter and allowed for longer counting and irradiation times, but was unsuitable for examining fission products with half-lives below 10 seconds. The on/off method used a cycle of equal irradiation and counting times of one minute. The second method is able to measure track the production of fission products with half-lives of less than 10 seconds. This method used a borated aluminum wheel beam chopper to stop the irradiation of the sample during counting. The beam chopper was set to cycle for approximately one second of counting following half a second of irradiation. The spectra from both methods were analyzed and the peaks were assigned to the appropriate fission products. The majority of the peaks were composed of gamma-rays from multiple nuclides. The peaks created by gamma-rays from decays of a single nuclide were used to calculate the detection limits of the system. Using the beam chopper system, 21 peaks would be above the detection limits of our system 95% of the time for uranium samples of less than one kilogram. / text

Gamma-ray bursts (GRBs) are the mysterious, short and intense flashes of gamma-rays in the space, and are believed to originate from the rare, explosively devastating, stellar events that happens at cosmological distances. Enormous progress has been made from four decades of GRB research endeavor but the ultimate understanding of their origins has yet to arrive. Recently revealed features in their early afterglows broadened the opportunity space for exploration. We have carried out extensive studies on various physical processes in GRBs. We showed that the distribution of electrons' energy spectral index in GRBs and other relativistic sources is inconsistent with the prediction from the first-order Fermi theory of the shock particle acceleration. We investigated the photon scattering processes within the relativistic outflow that produces the GRB and calculated the resultant emission flux from it. We showed the scattering of the GRB prompt photons by the circum-burst dust, although an attractive possibility, can not explain the puzzling plateau component in the GRB afterglow light curve. We made meaningful constraint on the GRB prompt emission radius, R [greater-than or equal to] 10¹⁴, by studying the synchrotron self absorption for a small sample of bursts with good data. We showed that a late jet, which is thought to be producing the late X-ray flares in GRB afterglows, will produce detectable emissions from its interactions with other components in the explosive event of GRB, and identification of these emissions could verify the existence of the late jet and further prove the massive star origin of long-duration GRBs. / text

This project is to search for Very High Energy (VHE) (10¹¹ eV to 10¹⁴ eV) gamma rays from the Crab nebula and pulsar using the atmospheric Cherenkov imaging technique. The technique uses an array of 37 photomultiplier tubes to record the images of the Cherenkov light pulses generated by energetic particles in the air showers initiated by VHE gamma rays or charged cosmic rays. Gamma-ray-like events are selected from numerous cosmic-ray events based on the predicted properties of the image, such as the size, shape, and orientation with respect to the axis of the detector. A steady weak flux of VHE gamma rays from the Crab is detected at high statistical significance (9 sigma), which is not usually achieved in VHE gamma-ray astronomy. No strong evidence of pulsed emission is found when the same data is folded at the Crab pulsar's radio ephemeris. The angular resolution of the technique cannot separate the emission coming from the nebula from that from the pulsar. Although it is generally believed that the unpulsed emission is coming from the nebula, there may be an unpulsed component coming at only a couple of light cylinder radii away from the pulsar too. Using the outer gap model of pulsar, the spectrum is derived and is found to be compatible with the observations.

We present the second multi-frequency radio detection of a reverse shock in a gamma-ray burst. By combining our extensive radio observations of the Fermi-Large Area Telescope gamma-ray burst 160509A at z - 1.17 up to 20 days after the burst with Swift X-ray observations and ground-based optical and near-infrared data, we show that the afterglow emission comprises distinct reverse shock and forward shock contributions: the reverse shock emission dominates in the radio band at. less than or similar to 10 days, while the forward shock emission dominates in the X-ray, optical, and near-infrared bands. Through multi-wavelength modeling, we determine a circumburst density of n(0) approximate to 10(-3) cm(-3), supporting our previous suggestion that a low- density circumburst environment is conducive to the production of long-lasting reverse shock radiation in the radio band. We infer the presence of a large excess X-ray absorption column, N-H approximate to 1.5. x 10(22) cm(-2), and a high rest-frame optical extinction, A(V) approximate to 3.4 mag. We identify a jet break in the X-ray light curve at t(jet) approximate to 6 days, and thus derive a jet opening angle of theta(jet) approximate to 4 degrees, yielding a beaming-corrected kinetic energy and radiated gamma-ray energy of E-K approximate to 4 x 10(50) erg and E-gamma approximate to 1.3 x 10(51) erg ( 1-10(4) keV, rest frame), respectively. Consistency arguments connecting the forward shocks and reverse shocks suggest a deceleration time of t(dec) approximate to 460 s approximate to T-90, a Lorentz factor of Gamma( t(dec)) approximate to 330, and a reverse-shock-to-forward-shock fractional magnetic energy density ratio of R-B equivalent to is an element of(B, RS)/is an element of(B, FS) approximate to 8. Our study highlights the power of rapid-response radio observations in the study of the properties and dynamics of gamma-ray burst ejecta.

In this thesis, we explore and improve on the science of gamma-ray bursts with particular attention to the very-high-energy regime. We begin by discussing Imaging Atmospheric Cherenkov Telescope Arrays (IACTs), which are the primary instruments of observation at very-high-energy gamma rays. We focus on a particular, state-of-the-art IACT array in southern Arizona: Very Energetic Radiation Imaging Telescope Array System (VERITAS). We then discuss the science of gamma-ray bursts and what can be learned from IACT observations. We follow with a couple of technical improvements, allowing one to better search for and characterize gamma-ray bursts with IACTs. The techniques focus on statistical methods for detection of transient sources, as well as angular reconstruction at arbitrary zenith angles of observation. We then use one of our new statistical methods to search for a signal in VERITAS observations of gamma-ray burst locations, with tests designed to search for particular bursts as well as for hints of emission in the entire sample of observations. We conclude that there is no evidence for a signal and follow with a discussion of the particularly interesting non-detection of GRB 150323A. We discuss the implications of this non-detection on the energetics and ambient environment of this burst. We conclude that the VERITAS observations might indicate gamma-ray bursts taking place in the dense wind of Wolf-Rayet stars.

The processing of amyloid precursor protein (APP) by - and -secretases produces amyloid (A) peptide, the principal component of the neuritic plaques found in Alzheimers disease (AD) pathology. The enzyme -secretase is a multimeric protein consisting of presenilins-1/2 (PS1/PS2), nicastrin, anterior pharynx defective 1 (APH-1) and presenilin enhancer-2 (PEN-2). Recently it was discovered that p23, a transmembrane protein involved in intracellular protein trafficking, negatively regulates -secretase activity. In the present study, I evaluated the levels/expression of the nicastrin and p23 and their possible colocalization with PS1 in normal adult and developing brains. Additionally, I have studied the alterations of p23 levels in both animal model of neurodegeneration and in postmortem AD brains. Nicastrin and p23 were widely distributed throughout the brain and colocalized in all brain regions with PS1. The levels of nicastrin and p23 were relatively high at the early stages of postnatal development and then declined gradually as age increased. Interestingly, p23 level/expression was found to be altered following kainic acid-induced neurodegeneration in the adult rat brain. Additionally, p23 levels were reduced in the brains of individuals with AD. These results, taken together, suggest that both nicastrin and p23 are expressed in neurons throughout the brain and their levels decline gradually during development to reach an adult profile. Additionally, my results indicate that a decreased level of p23 may contribute to AD pathogenesis by increasing the production of A-related peptides.

Thesis (Ph. D.)--University of Chicago, Dept. of Physics, June 1997. / Includes bibliographical references. Also available on the Internet.

A new gamma imaging method, Neutron Stimulated Emission Computed Tomography (NSECT), is being developed to non-invasively and non-destructively measure and image elemental concentrations in vivo. In NSECT a beam of fast neutrons (3 - 5 MeV) bombards a target, inelastically scattering with target nuclei and exciting them. Decay from this excited state produces characteristic gamma emissions. Collecting the resulting gamma energy spectrum allows identification of elements present in the target. As these gamma rays range in energy from 0.3 - 1.5 MeV, outside the useable energy range for existing gamma cameras (0.1 - .511 MeV), a new gamma imaging method must be developed. The purpose of this dissertation is to design and develop a near-field (less then 0.5 m) high-energy (0.3 - 1.5 MeV) gamma camera to facilitate planar NSECT imaging. Modifying a design implemented in space-based imaging (focus of infinity), a prototype camera was built. Experimental testing showed that the far-field space-based assumptions were inapplicable in the near-field. A new mathematical model was developed to describe the modulation behavior in the near-field. Additionally, a Monte Carlo simulation of the camera and imaging environment was developed. These two tools were used to facilitate optimization of the camera parameters. Simulated data was then used to reconstruct images for both small animal and human fields of view. Limitations of the camera design were identified and quantified. Image analysis demonstrated that the camera has the potential to identify regions of interest in a human field of view. / Dissertation

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