The Low-Resolution Structure of Nascent High Density Lipoprotein Reconstituted with DMPC With and Without Cholesterol Reveals A Mechanism for Particle Expansion

High density lipoproteins (HDL) are athero-protective particles under investigation as potential therapeutic agents for cardiovascular disease. We applied small angle neutron scattering (SANS) with contrast variation to obtain the low resolution structure of nascent HDL (nHDL) reconstituted with dimyristoyl phosphatidyl choline (DMPC), apoA1:DMPC (1:80, mol:mol). The overall shape of the entire particle is discoidal, with low resolution architecture of apoA1 visualized as an open, contorted, and slightly out of plane structure with three arms, while the low resolution shape of the lipid phase is an oblate ellipsoid that fits well within the protein shape. Modeling studies incorporating the SANS data indicate that apoA1 within the lipoprotein is folded onto itself, making a hairpin, which was also confirmed independently by both cross-linking mass spectrometry and hydrogen-deuterium exchange mass spectrometry analyses. The open conformation of apoA1 observed coupled with the lipid shape indicate that the lipid is predominantly a bilayer with a small micelle domain between the open apoA1 arms. Collectively, these studies demonstrate that full length apoA1 retains an open architecture that is dictated by its lipid cargo. This configuration may help accommodate potential changing lipid cargo content of the particle by quantized expansion of hairpin structures in apoA

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

Variable Stars in Galactic Globular Clusters

Based on a search of the literature up to May 2001, the number of known variable stars in Galactic globular clusters is approximately 3000. Of these, more than 2200 have known periods and the majority (approximately 1800) are of the RR Lyrae type. In addition to the RR Lyrae population, there are approximately 100 eclipsing binaries, 120 SX Phe variables, 60 Cepheids (including population II Cepheids, anomalous Cepheids and RV Tauri) and 120 SR/red variables. The mean period of the fundamental mode RR Lyrae variables is 0.585, for the overtone variables it is 0.342 (0.349 for the first-overtone pulsators and 0.296 for the second-overtone pulsators) and approximately 30% are overtone pulsators. These numbers indicate that about 65% of RR Lyrae variables in Galactic globular clusters belong to Oosterhoff type I systems. The mean period of the RR Lyrae variables in the Oosterhoff type I clusters seems to be correlated with metal abundance in the sense that the periods are longer in the more metal poor clusters. Such a correlation does not exist for the Oosterhoff type II clusters. Most of the Cepheids are in clusters with blue horizontal branches.Comment: 45 pages, 10 figures, to be published in AJ November 200

Translating Marine Animal Tracking Data into Conservation Policy and Management

There have been efforts around the globe to track individuals of many marine species and assess their movements and distribution with the putative goal of supporting their conservation and management. Determining whether, and how, tracking data have been successfully applied to address real-world conservation issues is however difficult. Here, we compile a broad range of case studies from diverse marine taxa to show how tracking data have helped inform conservation policy and management, including reductions in fisheries bycatch and vessel strikes, and the design and administration of marine protected areas and important habitats. Using these examples, we highlight pathways through which the past and future investment in collecting animal tracking data might be better used to achieve tangible conservation benefits

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Calibration of the CMS hadron calorimeters using proton-proton collision data at root s=13 TeV

Methods are presented for calibrating the hadron calorimeter system of theCMSetector at the LHC. The hadron calorimeters of the CMS experiment are sampling calorimeters of brass and scintillator, and are in the form of one central detector and two endcaps. These calorimeters cover pseudorapidities vertical bar eta vertical bar ee data. The energy scale of the outer calorimeters has been determined with test beam data and is confirmed through data with high transverse momentum jets. In this paper, we present the details of the calibration methods and accuracy.Peer reviewe

Power of Maps : (Counter) Mapping for Conservation

This paper considers what is at stake in defining and mapping protected areas for conservation. We link issues of power in cartography to themes from political ecology, social natures, and conservation biology literatures to extend our understanding of maps as reflective of, and productive of, power. Reviewing insights from these literatures to consider power asymmetries common to conservation practice, we highlight ways that mapping practices and products reinforce and contribute to such dynamics. Doing so enriches consideration of the power geometries of conservation cartographies by inviting fuller consideration of diverse species and landscapes, as well as enabling discussion of other representational and productive effects of conservation mappings. Once determined, how might conservation maps serve to naturalize certain spaces or boundaries as fixed, or contribute to certain socio-psychological understandings of conservation possibilities or outcomes? In the closing sections, we invoke the idea of ‘counter-mapping’ to explore strategies that might redress these concerns. Possibilities range from efforts to adapt the form of protected areas to more critical approaches that question the appropriateness of territorial focus and mapping practices for conservation goals. In conclusion, we argue that theorizing power in human, other-than-human, and inter-species contexts is essential to understanding the power geometries of conservation mapping.Non UBCReviewedFacult