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

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations

Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p < 1.2E-7). The downstream pathways affected by DNA methylation included the identification of IFI16 and IRF7 CpG-gene transcript pairs which contributed to the innate immune response gene enrichment pathway along with NLRC5, NOD2, and AIM2. Gene enrichment analysis also identified the nuclear factor-kappaB transcription pathway. Using two-sample Mendelian randomization (MR) we inferred methylation at three CpG sites as causal for CRP levels using both White and Black or African American MR instrument variables. Overall, we identified novel CpG sites and gene transcripts that could be valuable in understanding the specific cellular processes and pathogenic mechanisms involved in inflammation

Richelia

Ri.che'li.a. N.L. fem. n. Richelia, named for the Danish admiral Andreas du Plessis de Richelieu (1852–1932).Cyanobacteria / Cyanobacteria / Cyanobacteriales / Nostocaceae / RicheliaFilamentous heterocyst-forming, Gram-stain-negative, aerobic, phototrophic, N2-fixing, and occurring either as free-living or most often associated with several marine diatom genera (Rhizosolenia, Hemiaulus, and Chaetoceros). Filaments (trichomes) contain variable numbers of sheathless vegetative cells and one terminal heterocyst. Filaments lack akinetes and have limited motility via gliding. Gas vesicles are absent. Cyanophycin granules can be present in vegetative cells and heterocysts. Glycogen appears as large deposits, and thylakoids are dispersed randomly. Reproduce by normal cell division and asynchronous with one host diatom Rhizosolenia. DNA G + C content (mol%) from draft genomes varies 33–39%; genome size varies 3.42–6.04 Mb. Reduces atmospheric N2 with nitrogenase. Known habitats are warm (24–27.5°C), marine, and oligotrophic seas with intermediate (32 PSU) to fully marine (36 PSU) salinities. Biogeochemically relevant as N2 fixers and drivers of carbon export. Have been reported in all major ocean basins (Atlantic, Pacific, and Indian) and smaller seas (Mediterranean Sea and Red Sea).DNA G + C content (mol%): 33–39 (genome sequence).Type species: Richelia intracellularis Schmidt in Ostenfeld and Schmidt 1901.</p

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE): Conceptual Design Report

This volume of the LBNF/DUNE Conceptual Design Report cover the Long-Baseline Neutrino Facility for DUNE and describes the LBNF Project, which includes design and construction of the beamline at Fermilab, the conventional facilities at both Fermilab and SURF, and the cryostat and cryogenics infrastructure required for the DUNE far detector.This volume of the LBNF/DUNE Conceptual Design Report cover the Long-Baseline Neutrino Facility for DUNE and describes the LBNF Project, which includes design and construction of the beamline at Fermilab, the conventional facilities at both Fermilab and SURF, and the cryostat and cryogenics infrastructure required for the DUNE far detector

Sequestration of Vascular Endothelial Growth Factor (VEGF) Induces Late Restrictive Lung Disease.

RATIONALE: Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF), which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function. OBJECTIVES: To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function. METHODS: Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1) were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model. MEASUREMENTS AND MAIN RESULTS: Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes. CONCLUSIONS: These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions