Breed-Specific Hematological Phenotypes in the Dog: A Natural Resource for the Genetic Dissection of Hematological Parameters in a Mammalian Species

Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval. Seventy-five pure breeds plus a mixed breed control group were represented by 10 or more dogs. All measured parameters except mean corpuscular hemoglobin concentration (MCHC) varied with age. Concentrations of white blood cells (WBCs), neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood cell parameters, all varied with sex. Neutering status had an impact on hemoglobin concentration, mean corpuscular hemoglobin (MCH), MCHC, and concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets. Principal component analysis of hematological data revealed 37 pure breeds with distinctive phenotypes. Furthermore, all hematological parameters except MCHC showed significant differences between specific individual breeds and the mixed breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this way, of which 19 had already been identified by principal component analysis. Tentative breed-specific reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis. This study represents the first large-scale analysis of hematological phenotypes in the dog and underlines the important potential of this species in the elucidation of genetic determinants of hematological traits, triangulating phenotype, breed and genetic predisposition

Cell Lineage Identification and Stem Cell Culture in a Porcine Model for the Study of Intestinal Epithelial Regeneration

Significant advances in intestinal stem cell biology have been made in murine models; however, anatomical and physiological differences between mice and humans limit mice as a translational model for stem cell based research. The pig has been an effective translational model, and represents a candidate species to study intestinal epithelial stem cell (IESC) driven regeneration. The lack of validated reagents and epithelial culture methods is an obstacle to investigating IESC driven regeneration in a pig model. In this study, antibodies against Epithelial Adhesion Molecule 1 (EpCAM) and Villin marked cells of epithelial origin. Antibodies against Proliferative Cell Nuclear Antigen (PCNA), Minichromosome Maintenance Complex 2 (MCM2), Bromodeoxyuridine (BrdU) and phosphorylated Histone H3 (pH3) distinguished proliferating cells at various stages of the cell cycle. SOX9, localized to the stem/progenitor cells zone, while HOPX was restricted to the +4/‘reserve’ stem cell zone. Immunostaining also identified major differentiated lineages. Goblet cells were identified by Mucin 2 (MUC2); enteroendocrine cells by Chromogranin A (CGA), Gastrin and Somatostatin; and absorptive enterocytes by carbonic anhydrase II (CAII) and sucrase isomaltase (SIM). Transmission electron microscopy demonstrated morphologic and sub-cellular characteristics of stem cell and differentiated intestinal epithelial cell types. Quantitative PCR gene expression analysis enabled identification of stem/progenitor cells, post mitotic cell lineages, and important growth and differentiation pathways. Additionally, a method for long-term culture of porcine crypts was developed. Biomarker characterization and development of IESC culture in the porcine model represents a foundation for translational studies of IESC-driven regeneration of the intestinal epithelium in physiology and disease

The Pierre Auger Observatory I: The Cosmic Ray Energy Spectrum and Related Measurements

Studies of the cosmic ray energy spectrum at the highest energies with the Pierre Auger Observator

The Pierre Auger Observatory scaler mode for the study of solar activity modulation of galactic cosmic rays

Since data-taking began in January 2004, the Pierre Auger Observatory has been recording the count rates of low energy secondary cosmic ray particles for the self-calibration of the ground detectors of its surface detector array. After correcting for atmospheric effects, modulations of galactic cosmic rays due to solar activity and transient events are observed. Temporal variations related with the activity of the heliosphere can be determined with high accuracy due to the high total count rates. In this study, the available data are presented together with an analysis focused on the observation of Forbush decreases, where a strong correlation with neutron monitor data is found.Comision Nacional de Energia Atomica, ArgentinaFundacion AntorchasGobierno De La Provincia de Mendoza, Municipalidad de Malargue, ArgentinaNDM HoldingsValle Las Lenas, ArgentinaAustralian Research Council (ARC)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financiadora de Estudos e Projetos (FINEP)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Ministério da Ciência, Tecnologia e Inovação do Brasil (MCTI)Academy of Sciences of the Czech Republic (AVCR) [AV0Z10100502] [AV0Z10100522] [GAAV KJB300100801] [KJB100100904] [MSMT-CR LA08016] [LC527] [1M06002] [MSM0021620859]Centre National de la Recherche Scientifique (CNRS), Centre de Calcul IN2P3/CNRSConseil Regional Ile-de-France, Departement Physique Nucleaire et Corpusculaire [PNC-IN2P3/CNRS]Departement Sciences de l`Univers (SDU-INSU/CNRS), FranceBundesministerium fur Bildung und Forschung (BMBF)Deutsche Forschungsgemeinschaft (DFG)Finanzministerium Baden-WurttembergHelmholtz-Gemeinschaft Deutscher Forschungszentren (HGF)Ministerium fur Wissenschaft und Forschung, Nordrhein-Westfalen, GermanyMinisterium fur Wissenschaft, Forschung und Kunst, Baden-Wurttemberg, GermanyIstituto Nazionale di Fisica Nucleare (INFN)Istituto Nazionale di Astrofisica (INAF)Ministero dell Istruzione, dell Universita e della Ricerca (MIUR), ItalyConsejo Nacional de Ciencia y Tecnologia (CONACYT), MexicoMinisterie van Onderwijs, Cultuur en Wetenschap, Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)Stichting voor Fundamenteel Onderzoek der Materie (FOM), NetherlandsMinistry of Science and Higher Education, Poland [1 P03 D 014 30] [N N202 207238]Fundacao para a Ciencia e a Tecnologia (FCT), PortugalMinistry for Higher Education, Science, and Technology, Slovenian Research Agency, SloveniaComunidad de Madrid, SpainConsejeria de Educacion de la Comunidad de Castilla La ManchaFondo Europeo de Desarrollo Regional (FEDER)Ministerio de Ciencia e Innovacion, Consolider-Ingenio, SpainGeneralitat ValencianaJunta de AndaluciaXunta de Galicia, SpainScience and Technology Facilities Council, United KingdomU.S. Department of Energy (DOE) [DE-AC02-07CH11359] [DE-FR02-04ER41300]National Science Foundation (NSF) [0450696]Grainger Foundation USAALFA-EC / HELENEuropean Union [MEIF-CT-2005-025057] [PIEF-GA-2008-220240]United Nations Educational, Scientific and Cultural Organization (UNESCO

The Rapid Atmospheric Monitoring System of the Pierre Auger Observatory

The Pierre Auger Observatory is a facility built to detect air showers produced by cosmic rays above 10^17 eV. During clear nights with a low illuminated moon fraction, the UV fluorescence light produced by air showers is recorded by optical telescopes at the Observatory. To correct the observations for variations in atmospheric conditions, atmospheric monitoring is performed at regular intervals ranging from several minutes (for cloud identification) to several hours (for aerosol conditions) to several days (for vertical profiles of temperature, pressure, and humidity). In 2009, the monitoring program was upgraded to allow for additional targeted measurements of atmospheric conditions shortly after the detection of air showers of special interest, e.g., showers produced by very high-energy cosmic rays or showers with atypical longitudinal profiles. The former events are of particular importance for the determination of the energy scale of the Observatory, and the latter are characteristic of unusual air shower physics or exotic primary particle types. The purpose of targeted (or "rapid") monitoring is to improve the resolution of the atmospheric measurements for such events. In this paper, we report on the implementation of the rapid monitoring program and its current status. The rapid monitoring data have been analyzed and applied to the reconstruction of air showers of high interest, and indicate that the air fluorescence measurements affected by clouds and aerosols are effectively corrected using measurements from the regular atmospheric monitoring program. We find that the rapid monitoring program has potential for supporting dedicated physics analyses beyond the standard event reconstruction

Injection techniques

International audienceIn this paper we introduce the concept of Lateral Trigger Probability (LTP) function, i.e., the probability for an extensive air shower (EAS) to trigger an individual detector of a ground based array as a function of distance to the shower axis, taking into account energy, mass and direction of the primary cosmic ray. We apply this concept to the surface array of the Pierre Auger Observatory consisting of a 1.5 km spaced grid of about 1600 water Cherenkov stations. Using Monte Carlo simulations of ultra-high energy showers the LTP functions are derived for energies in the range between 1017 and 1019 eV and zenith angles up to 65°. A parametrization combining a step function with an exponential is found to reproduce them very well in the considered range of energies and zenith angles. The LTP functions can also be obtained from data using events simultaneously observed by the fluorescence and the surface detector of the Pierre Auger Observatory (hybrid events). We validate the Monte-Carlo results showing how LTP functions from data are in good agreement with simulations

The Pierre Auger Observatory III: Other Astrophysical Observations

Astrophysical observations of ultra-high-energy cosmic rays with the Pierre Auger Observator