Variance decomposition of protein profiles from antibody arrays using a longitudinal twin model

<p>Abstract</p> <p>Background</p> <p>The advent of affinity-based proteomics technologies for global protein profiling provides the prospect of finding new molecular biomarkers for common, multifactorial disorders. The molecular phenotypes obtained from studies on such platforms are driven by multiple sources, including genetic, environmental, and experimental components. In characterizing the contribution of different sources of variation to the measured phenotypes, the aim is to facilitate the design and interpretation of future biomedical studies employing exploratory and multiplexed technologies. Thus, biometrical genetic modelling of twin or other family data can be used to decompose the variation underlying a phenotype into biological and experimental components.</p> <p>Results</p> <p>Using antibody suspension bead arrays and antibodies from the Human Protein Atlas, we study unfractionated serum from a longitudinal study on 154 twins. In this study, we provide a detailed description of how the variation in a molecular phenotype in terms of protein profile can be decomposed into familial i.e. genetic and common environmental; individual environmental, short-term biological and experimental components. The results show that across 69 antibodies analyzed in the study, the median proportion of the total variation explained by familial sources is 12% (IQR 1-22%), and the median proportion of the total variation attributable to experimental sources is 63% (IQR 53-72%).</p> <p>Conclusion</p> <p>The variability analysis of antibody arrays highlights the importance to consider variability components and their relative contributions when designing and evaluating studies for biomarker discoveries with exploratory, high-throughput and multiplexed methods.</p

Serum Fatty Acid Binding Protein 4 (FABP4) Predicts Pre-eclampsia in Women with Type 1 Diabetes

OBJECTIVE To examine the association between fatty acid binding protein 4 (FABP4) and pre-eclampsia risk in women with type 1 diabetes. RESEARCH DESIGN AND METHODS Serum FABP4 was measured in 710 women from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT) in early pregnancy and in the second trimester (median 14 and 26 weeks’ gestation, respectively). RESULTS FABP4 was significantly elevated in early pregnancy (geometric mean 15.8 ng/mL [interquartile range 11.6–21.4] vs. 12.7 ng/mL [interquartile range 9.6–17]; P &amp;lt; 0.001) and the second trimester (18.8 ng/mL [interquartile range 13.6–25.8] vs. 14.6 ng/mL [interquartile range 10.8–19.7]; P &amp;lt; 0.001) in women in whom pre-eclampsia later developed. Elevated second-trimester FABP4 level was independently associated with pre-eclampsia (odds ratio 2.87 [95% CI 1.24–6.68], P = 0.03). The addition of FABP4 to established risk factors significantly improved net reclassification improvement at both time points and integrated discrimination improvement in the second trimester. CONCLUSIONS Increased second-trimester FABP4 independently predicted pre-eclampsia and significantly improved reclassification and discrimination. FABP4 shows potential as a novel biomarker for pre-eclampsia prediction in women with type 1 diabetes. </jats:sec

Lipoprotein-associated phospholipase A 2 , platelet-activating factor acetylhydrolase: a potential new risk factor for coronary artery disease

Abstract A specific and robust immunoassay for the lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), platelet-activating factor acetylhydrolase, is described for the first time. The immunoassay was used to evaluate possible links between plasma Lp-PLA 2 levels and atherosclerosis risk amongst susceptible individuals. Such an investigation was important because Lp-PLA 2 participates in the oxidative modification of low density lipoprotein by cleaving oxidised phosphatidylcholines, generating lysophosphatidylcholine and oxidised free fatty acids. The majority of Lp-PLA 2 was found associated with LDL (approximately 80%) and, as expected, enzyme levels were significantly positively correlated to LDL cholesterol. Plasma Lp-PLA 2 levels were significantly elevated in patients with angiographically proven coronary artery disease (CAD) when compared with age-matched controls, even though LDL cholesterol levels did not differ significantly. Indeed, when included in a general linear model with LDL cholesterol and other risk factors, Lp-PLA 2 appeared to be an independent predictor of disease status. We propose, therefore, that plasma Lp-PLA 2 mass should be viewed as a potential novel risk factor for CAD that provides information related to but additional to traditional lipoprotein measurements

Monolayer doping of silicon-germanium alloys: a balancing act between phosphorus incorporation and strain relaxation

This paper presents the application of monolayer doping (MLD) to silicon-germanium (SiGe). This study was carried out for phosphorus dopants on wafers of epitaxially grown thin films of strained SiGe on silicon with varying concentrations of Ge (18%, 30%, and 60%). The challenge presented here is achieving dopant incorporation while minimizing strain relaxation. The impact of high temperature annealing on the formation of defects due to strain relaxation of these layers was qualitatively monitored by cross-sectional transmission electron microscopy and atomic force microscopy prior to choosing an anneal temperature for the MLD drive-in. Though the bulk SiGe wafers provided are stated to have 18%, 30%, and 60% Ge in the epitaxial SiGe layers, it does not necessarily mean that the surface stoichiometry is the same, and this may impact the reaction conditions. X-ray photoelectron spectroscopy (XPS) and angle-resolved XPS were carried out to compare the bulk and surface stoichiometry of SiGe to allow tailoring of the reaction conditions for chemical functionalization. Finally, dopant profiling was carried out by secondary ion mass spectrometry to determine the impurity concentrations achieved by MLD. It is evident from the results that phosphorus incorporation decreases for increasing mole fraction of Ge, when the rapid thermal annealing temperature is a fixed amount below the melting temperature of each alloy

Globally Gridded Satellite (GridSat) Observations for Climate Studies

Geostationary satellites have provided routine, high temporal resolution Earth observations since the 1970s. Despite the long period of record, use of these data in climate studies has been limited for numerous reasons, among them: there is no central archive of geostationary data for all international satellites, full temporal and spatial resolution data are voluminous, and diverse calibration and navigation formats encumber the uniform processing needed for multi-satellite climate studies. The International Satellite Cloud Climatology Project set the stage for overcoming these issues by archiving a subset of the full resolution geostationary data at approx.10 km resolution at 3 hourly intervals since 1983. Recent efforts at NOAA s National Climatic Data Center to provide convenient access to these data include remapping the data to a standard map projection, recalibrating the data to optimize temporal homogeneity, extending the record of observations back to 1980, and reformatting the data for broad public distribution. The Gridded Satellite (GridSat) dataset includes observations from the visible, infrared window, and infrared water vapor channels. Data are stored in the netCDF format using standards that permit a wide variety of tools and libraries to quickly and easily process the data. A novel data layering approach, together with appropriate satellite and file metadata, allows users to access GridSat data at varying levels of complexity based on their needs. The result is a climate data record already in use by the meteorological community. Examples include reanalysis of tropical cyclones, studies of global precipitation, and detection and tracking of the intertropical convergence zone

Pre-sleep feeding, sleep quality, and markers of recovery in division I NCAA female soccer players

Pre-sleep nutrition habits in elite female athletes have yet to be evaluated. A retrospective analysis was performed with 14 NCAA Division I female soccer players who wore a WHOOP, Inc. band – a wearable device that quantifies recovery by measuring sleep, activity, and heart rate metrics through actigraphy and photoplethysmography, respectively – 24 h a day for an entire competitive season to measure sleep and recovery. Pre-sleep food consumption data were collected via surveys every 3 days. Average pre-sleep nutritional intake (mean ± sd: kcals 330 ± 284; cho 46.2 ± 40.5 g; pro 7.6 ± 7.3 g; fat 12 ± 10.5 g) was recorded. Macronutrients and kcals were grouped into high and low categories based upon the 50th percentile of the mean to compare the impact of a high versus low pre-sleep intake on sleep and recovery variables. Sleep duration (p = 0.10, 0.69, 0.16, 0.17) and sleep disturbances (p = 0.42, 0.65, 0.81, 0.81) were not affected by high versus low kcal, PRO, fat, CHO intake, respectively. Recovery (p = 0.81, 0.06, 0.81, 0.92), RHR (p = 0.84, 0.64, 0.26, 0.66), or HRV (p = 0.84, 0.70, 0.76, 0.93) were also not affected by high versus low kcal, PRO, fat, or CHO consumption, respectively. Consuming a small meal before bed may have no impact on sleep or recovery

Past and estimated future impact of invasive alien mammals on insular threatened vertebrate populations

Invasive mammals on islands pose severe, ongoing threats to global biodiversity. However, the severity of threats from different mammals, and the role of interacting biotic and abiotic factors in driving extinctions, remain poorly understood at a global scale. Here we model global extirpation patterns for island populations of threatened and extinct vertebrates. Extirpations are driven by interacting factors including invasive rats, cats, pigs, mustelids and mongooses, native species taxonomic class and volancy, island size, precipitation and human presence. We show that controlling or eradicating the relevant invasive mammals could prevent 41–75% of predicted future extirpations. The magnitude of benefits varies across species and environments; for example, managing invasive mammals on small, dry islands could halve the extirpation risk for highly threatened birds and mammals, while doing so on large, wet islands may have little benefit. Our results provide quantitative estimates of conservation benefits and, when combined with costs in a return-on-investment framework, can guide efficient conservation strategies

The Pan-STARRS Moving Object Processing System

We describe the Pan-STARRS Moving Object Processing System (MOPS), a modern software package that produces automatic asteroid discoveries and identifications from catalogs of transient detections from next-generation astronomical survey telescopes. MOPS achieves > 99.5% efficiency in producing orbits from a synthetic but realistic population of asteroids whose measurements were simulated for a Pan-STARRS4-class telescope. Additionally, using a non-physical grid population, we demonstrate that MOPS can detect populations of currently unknown objects such as interstellar asteroids. MOPS has been adapted successfully to the prototype Pan-STARRS1 telescope despite differences in expected false detection rates, fill-factor loss and relatively sparse observing cadence compared to a hypothetical Pan-STARRS4 telescope and survey. MOPS remains >99.5% efficient at detecting objects on a single night but drops to 80% efficiency at producing orbits for objects detected on multiple nights. This loss is primarily due to configurable MOPS processing limits that are not yet tuned for the Pan-STARRS1 mission. The core MOPS software package is the product of more than 15 person-years of software development and incorporates countless additional years of effort in third-party software to perform lower-level functions such as spatial searching or orbit determination. We describe the high-level design of MOPS and essential subcomponents, the suitability of MOPS for other survey programs, and suggest a road map for future MOPS development.Comment: 57 Pages, 26 Figures, 13 Table