Fermipy: An open-source Python package for analysis of Fermi-LAT Data

Fermipy is an open-source python framework that facilitates analysis of data collected by the Fermi Large Area Telescope (LAT). Fermipy is built on the Fermi Science Tools, the publicly available software suite provided by NASA for the LAT mission. Fermipy provides a high-level interface for analyzing LAT data in a simple and reproducible way. The current feature set includes methods for extracting spectral energy distributions and lightcurves, generating test statistic maps, finding new source candidates, and fitting source position and extension. Fermipy leverages functionality from other scientific python packages including NumPy, SciPy, Matplotlib, and Astropy and is organized as a community-developed package following an open-source development model. We review the current functionality of Fermipy and plans for future development.Comment: Proc. 35th ICRC, Busan, South Korea, PoS(ICRC2017)82

Probing the Nature of Radiative Processes within Radio Galaxies using the Fermi Gamma-Ray Large Area Telescope

Radio galaxies, active galactic nuclei with misaligned relativistic jets and large diffuse extended lobe structures, are home to radiative processes which are still not well understood. In this thesis, I describe my use of gamma-ray photon data from the Fermi Large Area Telescope to investigate these radiative processes in the case of two radio galaxies, Fornax A and Centaurus A. I describe my discovery of the spatially extended nature of the gamma-ray emission from Fornax A and my observation of a gamma-ray intensity which is not consistent with the predicted process of stray energetic electrons inverse-Compton scattering with extragalactic background light photons. I describe how I positively identified a new gamma-ray spectral component from the core region of Centaurus A jointly with data from the High Energy Stereoscopic System and how the spectral component can be explained by the addition of a second hidden zone of synchrotron self-Compton emission. I describe my discovery of fine filamentary sub-structures in the gamma-ray lobes of Centaurus A using a new imaging technique which I created, mapping out the unexpected gamma-ray emission farther from the assumed central engine than we have observed in radio. I discuss how my observations of the Centaurus A lobes suggest local re-acceleration or channels of negligible magnetic field allowing long distance high energy particle paths

Defining the role of corticotropin releasing factor binding protein in alcohol consumption

The corticotropin releasing factor (CRF) exerts its effects by acting on its receptors and on the binding protein (CRFBP), and has been implicated in alcohol use disorder (AUD). Therefore, identification of the exact contribution of each protein that mediates CRF effects is necessary to design effective therapeutic strategies for AUD. A series of in vitro/in vivo experiments across different species were performed to define the biological discrete role of CRFBP in AUD. First, to establish the CRFBP role in receptor signaling, we developed a novel chimeric cell-based assay and showed that CFRBP full length can stably be expressed on the plasma membrane. We discovered that only CRFBP(10 kD) fragment is able to potentiate CRF-intracellular Ca2+ release. We provide evidence that CRHBP gene loss increased ethanol consumption in mice. Then, we demonstrate that selective reduction of CRHBP expression in the center nucleus of the amygdala (CeA) decreases ethanol consumption in ethanol-dependent rats. CRFBP amygdalar downregulation, however, does not attenuate yohimbine-induced ethanol self-administration. This effect was associated with decreased hemodynamic brain activity in the CRFBP-downregulated CeA and increased hemodynamic activity in the caudate putamen during yohimbine administration. Finally, in alcohol-dependent patients, genetic variants related to the CRFBP(10 kD) fragment were associated with greater risk for alcoholism and anxiety, while other genetic variants were associated with reduced risk for anxiety. Taken together, our data provide evidence that CRFBP may possess both inhibitory and excitatory roles and may represent a novel pharmacological target for the treatment of AUD

Functional definition of seizure provides new insight into post-traumatic epileptogenesis

Experimental animals’ seizures are often defined arbitrarily based on duration, which may lead to misjudgement of the syndrome and failure to develop a cure. We employed a functional definition of seizures based on the clinical practice of observing epileptiform electrocorticography and simultaneous ictal behaviour, and examined post-traumatic epilepsy induced in rats by rostral parasagittal fluid percussion injury and epilepsy patients evaluated with invasive monitoring. We showed previously that rostral parasagittal fluid percussion injury induces different types of chronic recurrent spontaneous partial seizures that worsen in frequency and duration over the months post injury. However, a remarkable feature of rostral parasagittal fluid percussion injury is the occurrence, in the early months post injury, of brief (<2 s) focal, recurrent and spontaneous epileptiform electrocorticography events (EEEs) that are never observed in sham-injured animals and have electrographic appearance similar to the onset of obvious chronic recurrent spontaneous partial seizures. Simultaneous epidural-electrocorticography and scalp-electroencephalography recordings in the rat demonstrated that these short EEEs are undetectable by scalp electrocorticography. Behavioural analysis performed blinded to the electrocorticography revealed that (i) brief EEEs lasting 0.8–2 s occur simultaneously with behavioural arrest; and (ii) while behavioural arrest is part of the rat's behavioural repertoire, the probability of behavioural arrest is greatly elevated during EEEs. Moreover, spectral analysis showed that EEEs lasting 0.8–2 s occurring during periods of active behaviour with dominant theta activity are immediately followed by loss of such theta activity. We thus conclude that EEEs lasting 0.8–2 s are ictal in the rat. We demonstrate that the assessment of the time course of fluid percussion injury-induced epileptogenesis is dramatically biased by the definition of seizure employed, with common duration-based arbitrary definitions resulting in artificially prolonged latencies for epileptogenesis. Finally, we present four human examples of electrocorticography capturing short (<2 s), stereotyped, neocortically generated EEEs that occurred in the same ictal sites as obvious complex partial seizures, were electrographically similar to rat EEEs and were not noted during scalp electroencephalography. When occurring in the motor cortex, these short EEEs were accompanied by ictal behaviour detectable with simultaneous surface electromyography. These data demonstrate that short (<2 s) focal recurrent spontaneous EEEs are seizures in both rats and humans, that they are undetectable by scalp electroencephalography, and that they are typically associated with subtle and easily missed behavioural correlates. These findings define the earliest identifiable markers of progressive post-traumatic epilepsy in the rat, with implications for mechanistic and prophylactic studies, and should prompt a re-evaluation of the concept of post-traumatic silent period in both animals and humans

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Specifying and Verifying the Correctness of Dynamic Software Updates

Recently, there has been much interest in dynamic software updating (DSU) systems, which allow running programs to be patched on-the-fly to add features or fix bugs. Open-source and commercial products are now available to support dynamic updates to OS kernels, desktop applications, server programs, and embedded devices. However, despite the many recent advances in DSU mechanisms, techniques to reason that dynamic updates are correct have lagged behind, focusing largely on simple properties like type safety. In this paper, we present a more complete framework for specifying and verifying the correctness of dynamic updates. Our framework is capable of describing application-specific, behavioral notions of correctness. We use our framework to characterize several classes of program properties that arise in updatable software. To verify such properties in actual updatable programs, we develop a transformation that combines the old and new versions of a program into a single merged program. This merged program is provably equivalent to running the old and new programs in a DSU system, and, most importantly, the merged program can be analyzed by off-theshelf program analysis tools. We describe an implementation of a program merger we have developed for C, and we demonstrate its utility with several case studies. 1