The genomics of neonatal abstinence syndrome

Significant variability has been observed in the development and severity of neonatal abstinence syndrome (NAS) among neonates exposed to prenatal opioids. Since maternal opioid dose does not appear to correlate directly with neonatal outcome, maternal, placental, and fetal genomic variants may play important roles in NAS. Previous studies in small cohorts have demonstrated associations of variants in maternal and infant genes that encode the μ-opioid receptor (OPRM1), catechol-O-methyltransferase (COMT), and prepronociceptin (PNOC) with a shorter length of hospital stay and less need for treatment in neonates exposed to opioids in utero. Consistently falling genomic sequencing costs and computational approaches to predict variant function will permit unbiased discovery of genomic variants and gene pathways associated with differences in maternal and fetal opioid pharmacokinetics and pharmacodynamics and with placental opioid transport and metabolism. Discovery of pathogenic variants should permit better delineation of the risk of developing more severe forms of NAS. This review provides a summary of the current role of genomic factors in the development of NAS and suggests strategies for further genomic discovery

Launching to the Moon and Beyond: Ares I and V Updates

This slide presentation reviews the progress made on the Ares I and Ares V launch vehicles. Slides reviewing NASA's Mission, timetable and the Launch Vehicle comparisons between the shuttle and the Saturn V vehicles and the Ares I and V launch vehicles are shown. The elements of the Ares I is reviewed in detail with a slide showing Ares I Lunar mission profile. The Ares I-X test flight is reviewed. The Ares V elements are reviewed in a slide and the Ares V lunar profile is also shown. The progress made in this project is reviewed. Charts diagramming the production facilities at the Michoud Assembly Facility, and the manufacturing flow are displayed

Space Operations for a New Era of Exploration Launch Vehicles

Since 2005, Ares has made substantial progress on designing, developing, and testing the Ares I crew launch vehicle and has continued its in-depth studies of the Ares V cargo launch vehicles. The combined Ares I/Ares V architecture was designed to reduce the complexity and labor intensity of ground operations for America s next journeys beyond low-Earth orbit (LEO). The Ares Projects goal is to instill operability as part of the vehicles requirements development, design, and operations. Since completing the Preliminary Design Review in 2008, work has continued to push the Ares I beyond the concept phase and into full vehicle development, while tackling fresh engineering challenges and performing pathfinding activities related to vehicle manufacturing and ground operations

Plasmonic edge states: an electrostatic eigenmode description

We consider periodic arrangements of metal nanostructures and study the effect of periodicity on the localised surface plasmon resonance of the structures within an electrostatic eigenmode approximation. We show that within this limit, the collective surface plasmon resonances of the periodic structures can be expressed in terms of superpositions of the eigenmodes of uncoupled nanostructures that exhibit a standing--wave character delocalised across the entire periodic structure. The formalism derived successfully enables the design and accounts for the observation of plasmonic edge-states in periodic structures

Effect of rotational disruption on the size-frequency distribution of the Main Belt asteroid population

The size distribution of small asteroids in the Main Belt is assumed to be determined by an equilibrium between the creation of new bodies out of the impact debris of larger asteroids and the destruction of small asteroids by collisions with smaller projectiles. However, for a diameter less than 6 km we find that YORP-induced rotational disruption significantly contributes to the erosion even exceeding the effects of collisional fragmentation. Including this additional grinding mechanism in a collision evolution model for the asteroid belt, we generate size-frequency distributions from either an accretional (Weidenschilling, 2011) or an "Asteroids were born big" (Morbidelli, 2009) initial size-frequency distribution that are consistent with observations reported in Gladman et al. (2009). Rotational disruption is a new mechanism that must be included in all future collisional evolution models of asteroids.Comment: 5 pages, 3 figures, accepted in MNRAS letter

Numerical algebraic geometry for model selection and its application to the life sciences

Researchers working with mathematical models are often confronted by the related problems of parameter estimation, model validation, and model selection. These are all optimization problems, well-known to be challenging due to non-linearity, non-convexity and multiple local optima. Furthermore, the challenges are compounded when only partial data is available. Here, we consider polynomial models (e.g., mass-action chemical reaction networks at steady state) and describe a framework for their analysis based on optimization using numerical algebraic geometry. Specifically, we use probability-one polynomial homotopy continuation methods to compute all critical points of the objective function, then filter to recover the global optima. Our approach exploits the geometric structures relating models and data, and we demonstrate its utility on examples from cell signaling, synthetic biology, and epidemiology.Comment: References added, additional clarification

Microbiota modulation of behavior and stress responses : implications for neuro-immune research in zebrafish

Dissertation supervisor: Dr. Catherine H. Gillespie.Includes vita.The gut microbiota (GM) consists of a large microbial community whose collective set of genes encodes a vast array of functions. These microbes play a major role in many physiological processes within the host and are essential for survival. Ongoing research suggests that the GM is not only involved in gut physiology but may also have significant effects on brain function and behavior. The gut-brain axis is a bidirectional route of communication between the gastrointestinal tract and the central nervous system via neural, hormonal, and immunological pathways. The influence of the GM on gut-brain signaling is not well characterized. This dissertation research is aimed at investigating the role of the GM on stress-related brain function and behavior, as well as developing unique approaches for neuroimmune research. My first project was to investigate the influence the GM has on behavior in genetically identical mice. First, I isolated a subset of bacteria that colonize the ileum of mice from a particular vendor that has been shown to produce mice with very diverse GM. Isogenic colonies of mice were then generated with and without this subset of microbes and subjected to stress testing and behavioral analysis. From this study we were able to determine that the GM does play a significant role in stress-related brain function and behavior. However, dissecting out individual microbes and mechanisms by which the GM uses to communicate through the gut-brain axis proves to be a challenging task. In order to address some of these questions we began to explore more basic model systems, such as zebrafish. Zebrafish are an emerging high-throughput model system that exhibit many behaviors that have been correlated with those seen in human neurological disorders. The ability to easily control and manipulate the microbial environment in developing zebrafish makes neuroimmune research in zebrafish advantageous over other model systems. This research characterizes the ability of the GM to alter stress- and anxiety-related behavior and to mitigate stress responses in zebrafish. Furthermore, this research investigates potential pathways of communication to provide insight for mechanisms by which the GM influences the gut-brain axis. Since neurobehavioral research in zebrafish is an evolving field, my initial zebrafish project was to determine an optimal euthanasia agent for use in stress studies. This was crucial for eliminating euthanasia-induced stress responses which could confound results in our experiments. My next project was to generate gnotobiotic zebrafish in order to examine the significance of the GM in anxiety-related behavior and stress responses. Lastly, through bacterial metabolite experiments and probiotic studies, we began to investigate mechanisms of communication through the GM-gut-brain axis. This research sets the foundation for using zebrafish for neuroimmune research and will help elucidate the role that the GM plays in modulating brain function and behavior. A better understanding of the influence microbes have on the gut-brain axis will facilitate the potential for probiotic therapeutics targeting neurological disorders.Includes bibliographical references (pages 114-126)

Phase Control and Eclipse Avoidance in Near Rectilinear Halo Orbits

The baseline trajectory proposed for the Gateway is a southern Earth-Moon L2 Near Rectilinear Halo Orbit (NRHO). Designed to avoid eclipses, the NRHO exhibits a resonance with the lunar synodic period. The current investigation details the eclipse behavior in the baseline NRHO. Then, phase control is added to the orbit maintenance algorithm to regulate perilune passage time and maintain the eclipse-free characteristics of the Gateway reference orbit. A targeting strategy is designed to periodically target back to the long-horizon virtual reference if the orbit diverges over time in the presence of additional perturbations