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

Neuroadaptations in Human Chronic Alcoholics: Dysregulation of the NF-κB System

Anna Ökvist is with Karolinska Institute, Sofia Johansson is with Karolinska Institute, Alexander Kuzmin is with Karolinska Institute, Igor Bazov is with Karolinska Institute, Roxana Merino-Martinez is with Karolinska Institute, Igor Ponomarev is with UT Austin, R. Dayne Mayfield is with UT Austin, R. Adron Harris is with UT Austin, Donna Sheedy is with University of Sydney, Therese Garrick is with University of Sydney, Clive Harper is with University of Sydney, Yasmin L. Hurd is with Mount Sinai School of Medicine, Lars Terenius is with Karolinska Institute, Tomas J. Ekström is with Karolinska Institute, Georgy Bakalkin is with Karolinska Institute and Uppsala University, Tatjana Yakovleva is with Karolinska Institute and Uppsala University.Background -- Alcohol dependence and associated cognitive impairments apparently result from neuroadaptations to chronic alcohol consumption involving changes in expression of multiple genes. Here we investigated whether transcription factors of Nuclear Factor-kappaB (NF-κB) family, controlling neuronal plasticity and neurodegeneration, are involved in these adaptations in human chronic alcoholics. Methods and Findings -- Analysis of DNA-binding of NF-κB (p65/p50 heterodimer) and the p50 homodimer as well as NF-κB proteins and mRNAs was performed in postmortem human brain samples from 15 chronic alcoholics and 15 control subjects. The prefrontal cortex involved in alcohol dependence and cognition was analyzed and the motor cortex was studied for comparison. The p50 homodimer was identified as dominant κB binding factor in analyzed tissues. NF-κB and p50 homodimer DNA-binding was downregulated, levels of p65 (RELA) mRNA were attenuated, and the stoichiometry of p65/p50 proteins and respective mRNAs was altered in the prefrontal cortex of alcoholics. Comparison of a number of p50 homodimer/NF-κB target DNA sites, κB elements in 479 genes, down- or upregulated in alcoholics demonstrated that genes with κB elements were generally upregulated in alcoholics. No significant differences between alcoholics and controls were observed in the motor cortex. Conclusions -- We suggest that cycles of alcohol intoxication/withdrawal, which may initially activate NF-κB, when repeated over years downregulate RELA expression and NF-κB and p50 homodimer DNA-binding. Downregulation of the dominant p50 homodimer, a potent inhibitor of gene transcription apparently resulted in derepression of κB regulated genes. Alterations in expression of p50 homodimer/NF-κB regulated genes may contribute to neuroplastic adaptation underlying alcoholism.This work was supported by grants from the AFA Forsäkring to AK, YLH, TJE and GB, the Research Foundation of the Swedish Alcohol Retail Monopoly (SRA) and Karolinska Institutet to AK, TJE and GB, and the Swedish Science Research Council and the Swedish National Drug Policy Coordinator to GB. The Australian Brain Donor Programs NSW Tissue Resource Centre was supported by The University of Sydney, National Health and Medical Research Council of Australia, Neuroscience Institute of Schizophrenia and Allied Disorders, National Institute of Alcohol Abuse and Alcoholism and NSW Department of Health.Waggoner Center for Alcohol and Addiction Researc

Super Tuesday and the "primary" education of the electorate: Political learning and the news media.

This thesis details how individuals learn about candidates during a presidential nominating campaign. An "indirect effects and individual-level conditions" model of political learning is developed to explain changes in how much individuals learn about candidates during the campaign. According to this model, how much a person learns about a candidate depends on the amount of information made available about the candidate in the news. The impact of this news coverage is hypothesized not to be direct but rather to be conditioned by the predispositions to learn about politics that individuals bring with them into the campaign. The research design developed to test this model relies on two complementary data sets, both of which were gathered during the 1988 Democratic and Republican presidential nomination campaigns. One set consists of original data detailing the amount of news coverage provided about the candidates in the sixteen states which held presidential primaries on March 8, 1988, "Super Tuesday." A second consists of American National Election Studies data drawn from a representative sample of citizens living in these same sixteen states; these data made it possible to assess how the nature of candidate awareness in the Super Tuesday electorate changed during the course of the campaign. In order to test the model, the content data on variations in the nature of candidate news coverage across campaign active states were merged with the survey data on citizens' knowledge of candidates and their individual-level predispositions to learn. The findings demonstrate that news coverage matters but that the ultimate power of news coverage on knowledge about the candidates depends on three important considerations: (1) the amount of news coverage devoted to a candidate during the campaign; (2) the predispositions to learn that citizens bring with them into the campaign, including their news use habits, political involvement, political interest, cognitive capabilities, partisan motivations, and news use habits; and (3) levels of public awareness of the candidates at the start of the campaign.Ph.D.University of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/104719/1/9542981.pdfDescription of 9542981.pdf : Restricted to UM users only

Effect of morning exercise on counterregulatory responses to subsequent, afternoon exercise

Les effets d'un exercice physique réalisé le matin sur l'altération des réponses métaboliques et neuro-endocriniennes de sujets masculins et féminins réalisant le même exercice l'après midi. Mesure et analys

Delivery and Impact of a Motivational Intervention for Smoking Cessation: A PROS Study

OBJECTIVES: We tested a Public Health Service 5As-based clinician-delivered smoking cessation counseling intervention with adolescent smokers in pediatric primary care practice. METHODS: We enrolled clinicians from 120 practices and recruited youth (age \u3e /=14) from the American Academy of Pediatrics Pediatric Research in Office Settings practice-based research network. Practices were randomly assigned to training in smoking cessation (intervention) or social media counseling (attentional control). Youth recruited during clinical visits completed confidential screening forms. All self-reported smokers and a random sample of nonsmokers were offered enrollment and interviewed by phone at 4 to 6 weeks, 6 months, and 12 months after visits. Measures included adolescents\u27 report of clinicians\u27 delivery of screening and counseling, current tobacco use, and cessation behaviors and intentions. Analysis assessed receipt of screening and counseling, predictors of receiving 5As counseling, and effects of interventions on smoking behaviors and cessation at 6 and 12 months. RESULTS: Clinicians trained in the 5As intervention delivered more screening (beta = 1.0605, P \u3c .0001) and counseling (beta = 0.4354, P \u3c .0001). In both arms, clinicians more often screened smokers than nonsmokers. At 6 months, study arm was not significantly associated with successful cessation; however, smokers in the 5As group were more likely to have quit at 12 months. Addicted smokers more often were counseled, regardless of study arm, but were less likely to successfully quit smoking. CONCLUSIONS: Adolescent smokers whose clinicians were trained in 5As were more likely to receive smoking screening and counseling than controls, but the ability of this intervention to help adolescents quit smoking was limited