Operation Of The NuMi Beam Monitoring System

The NuMI (Neutrinos at the Main Injector) facility produces an intense neutrino beam for experiments. The NuMI Beam Monitoring system consists of four arrays of ion chambers that measure the intensity and distribution of the remnant hadron and tertiary muon beams produced in association with the neutrinos. The ion chambers operate in an environment of high particle fluxes and high radiation.Physic

Genetic Variation in the Platelet Endothelial Aggregation Receptor 1 Gene Results in Endothelial Dysfunction

We gratefully acknowledge our Amish liaisons and field workers and the extraordinary cooperation and support of the Amish community, without which these studies would not have been possible. We also acknowledge Dr. Alan Shuldiner for his impactful insights and guidance.Platelet Endothelial Aggregation Receptor 1 (PEAR1) is a newly identified membrane protein reported to be involved in multiple vascular and thrombotic processes. While most studies to date have focused on the effects of this receptor in platelets, PEAR1 is located in multiple tissues including the endothelium, where it is most highly expressed. Our first objective was to evaluate the role of PEAR1 in endothelial function by examining flow-mediated dilation of the brachial artery in 641 participants from the Heredity and Phenotype Intervention Heart Study. Our second objective was to further define the impact of PEAR1 on cardiovascular disease computationally through meta-analysis of 75,000 microarrays, yielding insights regarding PEAR1 function, and predictions of phenotypes and diseases affected by PEAR1 dysregulation. Based on the results of this meta-analysis we examined whether genetic variation in PEAR1 influences endothelial function using an ex vivo assay of endothelial cell migration. We observed a significant association between rs12041331 and flow-mediated dilation in participants of the Heredity and Phenotype Intervention Heart Study (P = 0.02). Meta-analysis results revealed that PEAR1 expression is highly correlated with several genes (e.g. ANG2, ACVRL1, ENG) and phenotypes (e.g. endothelial cell migration, angiogenesis) that are integral to endothelial function. Functional validation of these results revealed that PEAR1 rs12041331 is significantly associated with endothelial migration (P = 0.04). Our results suggest for the first time that genetic variation of PEAR1 is a significant determinant of endothelial function through pathways implicated in cardiovascular disease.Yeshttp://www.plosone.org/static/editorial#pee

Toxoplasma gondii Serointensity and Seropositivity: Heritability and Household-Related Associations in the Old Order Amish

Toxoplasma gondii (T. gondii) is an intracellular parasite infecting one third of the world’s population. Latent T. gondii infection has been associated with mental illness, including schizophrenia and suicidal behavior. T. gondii IgG antibody titers were measured via ELISA. The heritability of T. gondii IgG was estimated using a mixed model that included fixed effects for age and sex and random kinship effect. Of 2017 Old Order Amish participants, 1098 had positive titers (54.4%). The heritability for T. gondii serointensity was estimated to be 0.22 (p = 1.7 × 10−8 and for seropositivity, it was estimated to be 0.28 (p = 1.9 × 10−5). Shared household environmental effects (i.e., household effects) were also determined. Household effects, modeled as a random variable, were assessed as the phenotypic covariance between any two individuals who had the same current address (i.e., contemporaneous household), and nuclear household (i.e., the phenotypic covariance between parents and children only, not other siblings or spouses). Household effects did not account for a significant proportion of variance in either T. gondii serointensity or T. gondii seropositivity. Our results suggest a significant familial aggregation of T. gondii serointensity and seropositivity with significant heritability. The shared household does not contribute significantly to family aggregation with T. gondii, suggesting that there are possible unmeasured non-household shared and non-shared environmental factors that may play a significant role. Furthermore, the small but significant heritability effects justify the exploration of genetic vulnerability to T. gondii exposure, infection, virulence, and neurotropism

Characteristics of HAPI Heart Study Participants.

<p>Abbreviations: BMI, body mass index; HAPI, Heredity and Phenotype Intervention; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SD, standard deviation.</p><p>SI conversion factors: To convert HDL-cholesterol, LDL-cholesterol, and total cholesterol values to mmol/L, multiply by 0.0259; triglycerides to mmol/L, multiply by 0.0113.</p><p>^*Defined as systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg or taking prescription medication for previously diagnosed hypertension.</p><p>^†Logarithm-transformed for analysis and back-transformed for presentation.</p><p>^‡Defined as LDL-cholesterol greater than 160 mg/dl or taking prescription medication for previously diagnosed hypercholesterolemia.</p><p>^§Self-reported history of smoking cigarette, pipe, or cigar. Only men report smoking in the OOA community.</p><p>Characteristics of HAPI Heart Study Participants.</p

The Impact of <i>PEAR1</i> rs12041331 on Endothelial Cell Migration in Human Umbilical Vein Endothelial Cells (HUVECs).

<p>(A) Representative phase-contrast images of rs12041331-stratified HUVECs at 0 and 6 hours post-scratch generation during an <i>ex vivo</i> endothelial cell migration assay. Scale bar, 250 μm. (B) Quantitative depiction of mean HUVEC migration. Endothelial cell migration distance was calculated by dividing the area of the scratch by the height of the frame using ImageJ. Mean endothelial cell migration distance was calculated based on 72, 72, and 36 independent measurements for GG, GA, and AA genotypes, respectively, as described in the Materials and Methods section.</p

<i>PEAR1</i> Genetic Network.

<p>Genes highly correlated with <i>PEAR1</i> (green nodes) were evaluated for protein-protein interactions (gray nodes) that were shared by at least 2 of the 30 genes analyzed. Green lines indicate a co-expression relationship; black lines indicate a physical protein-protein interaction. Genetic neighborhoods of similar pathway or function have been highlighted and labeled.</p

Predictors of Variance in Flow-Mediated Dilation in HAPI Study Participants.

<p>Abbreviations: BMI, body mass index; HAPI, Heredity and Phenotype Intervention; HDL, high-density lipoprotein; LDL, low-density lipoprotein.</p><p>^*Observed using a sex-stratified analysis to account for the OOA community’s male-only smoking cohort.</p><p>Predictors of Variance in Flow-Mediated Dilation in HAPI Study Participants.</p