NIA Long Life Family Study: Objectives, design, and heritability of cross-sectional and longitudinal phenotypes

The NIA Long Life Family Study (LLFS) is a longitudinal, multicenter, multinational, population-based multigenerational family study of the genetic and nongenetic determinants of exceptional longevity and healthy aging. The Visit 1 in-person evaluation (2006-2009) recruited 4 953 individuals from 539 two-generation families, selected from the upper 1% tail of the Family Longevity Selection Score (FLoSS, which quantifies the degree of familial clustering of longevity). Demographic, anthropometric, cognitive, activities of daily living, ankle-brachial index, blood pressure, physical performance, and pulmonary function, along with serum, plasma, lymphocytes, red cells, and DNA, were collected. A Genome Wide Association Scan (GWAS) (Ilumina Omni 2.5M chip) followed by imputation was conducted. Visit 2 (2014-2017) repeated all Visit 1 protocols and added carotid ultrasonography of atherosclerotic plaque and wall thickness, additional cognitive testing, and perceived fatigability. On average, LLFS families show healthier aging profiles than reference populations, such as the Framingham Heart Study, at all age/sex groups, for many critical healthy aging phenotypes. However, participants are not uniformly protected. There is considerable heterogeneity among the pedigrees, with some showing exceptional cognition, others showing exceptional grip strength, others exceptional pulmonary function, etc. with little overlap in these families. There is strong heritability for key healthy aging phenotypes, both cross-sectionally and longitudinally, suggesting that at least some of this protection may be genetic. Little of the variance in these heritable phenotypes is explained by the common genome (GWAS + Imputation), which may indicate that rare protective variants for specific phenotypes may be running in selected families

Neurotrophic Effect of Citrus 5-Hydroxy-3,6,7,8,3′,4′-Hexamethoxyflavone: Promotion of Neurite Outgrowth via cAMP/PKA/CREB Pathway in PC12 Cells

5-Hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone (5-OH-HxMF), a hydroxylated polymethoxyflavone, is found exclusively in the Citrus genus, particularly in the peels of sweet orange. In this research, we report the first investigation of the neurotrophic effects and mechanism of 5-OH-HxMF in PC12 pheochromocytoma cells. We found that 5-OH-HxMF can effectively induce PC12 neurite outgrowth accompanied with the expression of neuronal differentiation marker protein growth-associated protein-43(GAP-43). 5-OH-HxMF caused the enhancement of cyclic AMP response element binding protein (CREB) phosphorylation, c-fos gene expression and CRE-mediated transcription, which was inhibited by 2-naphthol AS-E phosphate (KG-501), a specific antagonist for the CREB-CBP complex formation. Moreover, 5-OH-HxMF-induced both CRE transcription activity and neurite outgrowth were inhibited by adenylate cyclase and protein kinase A (PKA) inhibitor, but not MEK1/2, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K) or calcium/calmodulin-dependent protein kinase (CaMK) inhibitor. Consistently, 5-OH-HxMF treatment increased the intracellular cAMP level and downstream component, PKA activity. We also found that addition of K252a, a TrKA antagonist, significantly inhibited NGF- but not 5-OH-HxMF-induced neurite outgrowth. These results reveal for the first time that 5-OH-HxMF is an effective neurotrophic agent and its effect is mainly through a cAMP/PKA-dependent, but TrKA-independent, signaling pathway coupling with CRE-mediated gene transcription. A PKC-dependent and CREB-independent pathway was also involved in its neurotrophic action

MODELING U.S. BUTTER CONSUMPTION WITH ZERO OBSERVATIONS

A heteroscedastic double-hurdle model is used to investigate household butter consumption in the United States. Results suggest that failure to incorporate heteroscedastic errors may lead to unreliable elasticity estimates. Decomposition of the effects of variables leads to insightful information and makes the double-hurdle model a more useful tool in micro demand analysis. Larger and higher-income households are more likely to consume butter than others and also consume more, but income elasticity is very small. Age, region, and seasonality are among the other significant determinants of household butter consumption

A censored system of cigarette and alcohol consumption

Many previous studies of US cigarette and alcohol consumption have focused on single equations. However, the addictive nature of consumption suggests that it is more appropriate to model these products as a system. We propose a two-step estimation procedure and apply the procedure to a system of equations for cigarette, beer and wine consumption. Results differ from those derived from an existing two-step procedure. Findings suggest that consumption of cigarettes, beer and wine is responsive to income changes but the elasticities are rather small. Personal physiques, education, age, race, ethnicity, health, gender, employment status, and regions also play significant roles in consumption.

Study of the transverse beam motion in the DARHT Phase II accelerator

The accelerator for the second-axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT) facility will accelerate a 4-kA, 3-MeV, 2--µs long electron current pulse to 20 MeV. The energy variation of the beam within the flat-top portion of the current pulse is (plus or equal to) 0.5%. The performance of the DARHT Phase II radiographic machine requires the transverse beam motion to be much less than the beam spot size which is about 1.5 mm diameter on the x-ray converter. In general, the leading causes of the transverse beam motion in an accelerator are the beam breakup instability (BBU) and the corkscrew motion. We have modeled the transverse beam motion in the DARHT Phase II accelerator with various magnetic tunes and accelerator cell configurations by using the BREAKUP code. The predicted sensitivity of corkscrew motion and BBU growth to different tuning algorithms will be presented

Household demand for fats and oils: two-step estimation of a censored demand system

A censored system of household fat and oil demand equations is estimated with a two-step procedure, using cross-sectional data from the 1987–1988 US Nationwide Food Consumption Survey. Own price and total expenditure elasticities are close to unity and there is no evidence of gross substitutability. Compensated elasticities suggest net substitution among the products considered.