Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides.

Framingham score and LV mass predict events in young adults: CARDIA study.

Background: Framingham risk score (FRS) underestimates risk in young adults. Left ventricular mass (LVM) relates to cardiovascular disease (CVD), with unclear value in youth. In a young biracial cohort, we investigate how FRS predicts CVD over 20 years and the incremental value of LVM.

Depression and risk of incident asthma in adults. The CARDIA study.

Rationale: Asthma is associated with depression, but the temporality of the association has not been established.

Objectives: To examine the association between prevalent elevated depressive symptoms and incident asthma, and between prevalent asthma and incident elevated depressive symptoms in a cohort of young and middle-aged adults.

Methods: We examined the longitudinal association between asthma and depressive symptoms bidirectionally in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort.

Functionalization of homodiamantane: oxygen insertion reactions without rearrangement with dimethyldioxirane.

Homodiamantane bromination and nitroxylation are accompanied by contraction of the seven-membered ring to give the corresponding substituted 1-diamantylmethyl derivatives. In contrast, CH-bond hydroxylations with dimethyldioxirane retain the cage and give both apically and medially substituted homodiamantanes. The product ratios are in accord with the barriers for the oxygen insertion computed with density functional theory methods only if solvation is included through a polarizable continuum model.

Polytwistane.

Twistane, C10H16, is a classic D2-symmetric chiral hydrocarbon that has been studied for decades due to its fascinating stereochemical and thermodynamic properties. Here we propose and analyze in detail the contiguous linear extension of twistane with ethano (ethane-1,2-diyl) bridges to create a new chiral, C2-symmetric hydrocarbon nanotube called polytwistane. Polytwistane, (CH)n, has the same molecular formula as polyacetylene but is composed purely of C(sp(3))-H units, all of which are chemically equivalent.

Physical environment may modify the association between depressive symptoms and change in waist circumference: the multi-ethnic study of atherosclerosis.

Background: Although the bidirectional association between depressive symptoms and adiposity has been recognized, the contribution of neighborhood factors to this relationship has not been assessed.

Objective: This study evaluates whether physical and social neighborhood environments modify the bidirectional relationship between depressive symptoms and adiposity (measured by waist circumference and body mass index).

Methods: Using data on 5,122 men and women (ages 45 to 84 years) from the Multi-Ethnic Study of Atherosclerosis (MESA) we investigated whether neighborhood physical (i.

Changes in procoagulants track longitudinally with insulin resistance: findings from the coronary artery risk development in young adults (CARDIA) study.

Aims: To examine the association between changes in procoagulants (fibrinogen factors VII and VIII and von Willebrand factor) and the risk of insulin resistance.

Methods: Using data from the Coronary Artery Risk Development in Young Adults study, we followed 2398 black and white adults without diabetes, aged 25-37 years at year 7, to year 20. Levels of fibrinogen factors VII and VIII and von Willebrand factor were divided in tertiles (low/middle/high) at years 7 and 20 and four groups reflecting changes were defined: 'low' (low at years 7 and 20), 'stable' (low/middle at years 7 and 20, but not both low at years 7 and 20), 'high' (high at year 7 and low/middle at year 20; or low/middle at year 7 and high at year 20) and 'highest' (high at years 7 and 20).

En route to multicatalysis: kinetic resolution of trans-cycloalkane-1,2-diols via oxidative esterification.

We demonstrate the application of a multicatalyst to the oxidation of a broad variety of aldehydes and subsequent enantioselective esterification of the incipient acids with (±)-trans-cycloalkane-1,2-diols. This reaction operates well with a multicatalyst bearing two independent catalytic moieties that provide monoprotected 1,2-diols in one pot.

Relation of left ventricular mass at age 23 to 35 years to global left ventricular systolic function 20 years later (from the Coronary Artery Risk Development in Young Adults study).

Left ventricular (LV) mass and the LV ejection fraction (LVEF) are major independent predictors of future cardiovascular disease. The association of LV mass with the future LVEF in younger populations has not been studied. The aim of this study was to investigate the relation of LV mass index (LVMI) at ages 23 to 35 years to LV function after 20 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Fine Mapping and Identification of BMI Loci in African Americans.

Genome-wide association studies (GWASs) primarily performed in European-ancestry (EA) populations have identified numerous loci associated with body mass index (BMI). However, it is still unclear whether these GWAS loci can be generalized to other ethnic groups, such as African Americans (AAs). Furthermore, the putative functional variant or variants in these loci mostly remain under investigation.

Matrix isolation and spectroscopic properties of the methylsulfinyl radical CH3(O)S˙.

The atmospherically highly relevant methylsulfinyl radical CH3(O)S˙ was generated thermally under flash pyrolysis conditions and isolated in Ar matrices at 10 K; the allyl radical is a byproduct. CH3(O)S˙ and its D3- and (13)C-isotopologues were characterized through the excellent agreement between experimental and computed IR and UV/Vis spectra.

Exploring covalently bonded diamondoid particles with valence photoelectron spectroscopy.

We investigated the valence electronic structure of diamondoid particles in the gas phase, utilizing valence photoelectron spectroscopy. The samples were singly or doubly covalently bonded dimers or trimers of the lower diamondoids. Both the bond type and the combination of bonding partners are shown to affect the overall electronic structure.

Associations of retrospective and concurrent lipid levels with subclinical atherosclerosis prediction after 20 years of follow-up: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Purpose: Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, we sought to determine how well lipids measured at baseline and at 20 years predict the presence of subclinical atherosclerosis.

Methods: Complete risk factor, coronary artery calcification (CAC), and carotid intima media thickness (CIMT) data were available for 2435 participants. Lipids were categorized into quartiles, CAC at Y20 was dichotomized as present/absent, and CIMT was dichotomized as ≥84 or <84th overall percentile.

Lipophilic oligopeptides for chemo- and enantioselective acyl transfer reactions onto alcohols.

Inspired by the extraordinary selectivities of acylases, we envisioned the use of lipophilic oligopeptidic organocatalysts for the acylative kinetic resolution/desymmetrization of rac- and meso-cycloalkane-1,2-diols. Here we describe in a full account the discovery and development process from the theoretical concept to the final catalyst, including scope and limitations. Competition experiments with various alcohols and electrophiles show the full potential of the employed oligopeptides.

Long-term change in alcohol-consumption status and variations in fibrinogen levels: the coronary artery risk development in young adults (CARDIA) study.

Objective: To examine long-term associations between change in alcohol-consumption status and cessation of alcohol use, and fibrinogen levels in a large, young, biracial cohort.

Design: Analysis of covariance models were used to analyse participants within the Coronary Artery Risk Development in Young Adults Study (CARDIA) cohort who had fibrinogen and alcohol use data at year 7 (1992-1993; ages 25-37) and year 20 examinations.

Setting: 4 urban US cities.

Measurement of neutrino and antineutrino oscillations using beam and atmospheric data in MINOS.

We report measurements of oscillation parameters from ν(μ) and ν(μ) disappearance using beam and atmospheric data from MINOS. The data comprise exposures of 10.71×10(20) protons on target in the ν(μ)-dominated beam, 3.

Assessing the utility of methods for menopausal transition classification in a population-based cohort: the CARDIA Study.

Objectives: Perimenopause significantly impacts women's health, but is under-researched due to challenges in assessing perimenopause status. Using CARDIA data, we compared the validity of six approaches for classifying perimenopause status in order to better understand the performance of classification techniques which can be applied to general cohort data. Specifically, we examined the validity of a self-reported question concerning changes in menstrual cycle length and two full prediction models using all available data concerning menstrual cycles as potential indicators of perimenopause.

Electron neutrino and antineutrino appearance in the full MINOS data sample.

We report on ν(e) and ν(e) appearance in ν(μ) and ν(μ) beams using the full MINOS data sample. The comparison of these ν(e) and ν(e) appearance data at a 735 km baseline with θ13 measurements by reactor experiments probes δ, the θ23 octant degeneracy, and the mass hierarchy. This analysis is the first use of this technique and includes the first accelerator long-baseline search for ν(μ) → ν(e).

A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry.

Antral follicle count predicts natural menopause in a population-based sample: the Coronary Artery Risk Development in Young Adults Women's Study.

Objective: The timing of menopause is associated with multiple chronic diseases. Tools that predict this milestone have relevance for clinical and research purposes. Among infertile women, a positive relationship exists between antral follicle count (AFC) and response to controlled ovarian hyperstimulation, a marker of ovarian reserve.

Electronic structure tuning of diamondoids through functionalization.

We investigated the changes in electronic structures induced by chemical functionalization of the five smallest diamondoids using valence photoelectron spectroscopy. Through the variation of three parameters, namely functional group (thiol, hydroxy, and amino), host cluster size (adamantane, diamantane, triamantane, [121]tetramantane, and [1(2,3)4]pentamantane), and functionalization site (apical and medial) we are able to determine to what degree these affect the electronic structures of the overall systems. We show that unlike, for example, in the case of halobenzenes, the ionization potential does not show a linear dependence on the electronegativity of the functional group.