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The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR < 0.1) and six others met our ‘suggestive’ criterion (FDR <0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.
Patterns in radar-detected internal layers in glaciers and ice streams can be tracked hundreds of kilometers downstream. We use distinctive patterns to delineate flowbands of Thwaites Glacier in the Amundsen Sea sector of West Antarctica. Flowbands contain information for the past century to millennium, the approximate time for ice to flow through the study region. GPS-detected flow directions (acquired in 2007/08) agree within uncertainty (~4°) with the radar-detected flowlines, indicating that the flow direction has not changed significantly in recent centuries. In contrast, InSAR-detected directions (from 1996) differ from the radar- and GPS-detected flowlines in all but the middle tributary, indicating caution is needed when using InSAR velocities to define flow directions. There is agreement between all three datasets in the middle tributary. We use two radar-detected flowlines to define a 95 km long flowband and perform a flux balance analysis using InSAR-derived velocities, radar-detected ice thickness, and estimates of the accumulation rate. Inferred thinning of 0.49 ± 0.34 m a–1 is consistent with satellite altimetry measurements, but has higher uncertainty due mainly to the velocity uncertainty. The uncertainty is underestimated because InSAR velocities often differ from GPS velocities by more than the stated uncertainties.
The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene–environment–development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the National Institute on Drug Abuse-funded Gene-Environment-Development Initiative, our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used of which common characteristics include (1) general population samples, including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol, and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene–environment analyses, of alcohol misuse and stressful life events, some significant gene–environment and gene–development effects were identified. We conclude that in some circumstances, already collected data sets can be combined for gene–environment and gene–development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables.
Information about glacier volume and ice thickness distribution is essential for many glaciological applications, but direct measurements of ice thickness can be difficult and costly. We present a new method that calculates ice thickness via an estimate of ice flux. We solve the familiar continuity equation between adjacent flowlines, which decreases the computational time required compared to a solution on the whole grid. We test the method on Columbia Glacier, a large tidewater glacier in Alaska, USA, and compare calculated and measured ice thicknesses, with favorable results. This shows the potential of this method for estimating ice thickness distribution of glaciers for which only surface data are available. We find that both the mean thickness and volume of Columbia Glacier were approximately halved over the period 1957–2007, from 281 m to 143 m, and from 294 km3 to 134 km3, respectively. Using bedrock slope and considering how waves of thickness change propagate through the glacier, we conduct a brief analysis of the instability of Columbia Glacier, which leads us to conclude that the rapid portion of the retreat may be nearing an end.
The two theories that revolutionized physics in the twentieth century, relativity and quantum mechanics, are full of predictions that defy common sense. Recently, we used three such paradoxical ideas to prove “The Free Will Theorem” (strengthened here), which is the culmination of a series of theorems about quantum mechanics that began in the 1960s. It asserts, roughly, that if indeed we humans have free will, then elementary particles already have their own small share of this valuable commodity. More precisely, if the experimenter can freely choose the directions in which to orient his apparatus in a certain measurement, then the particle's response (to be pedantic—the universe's response near the particle) is not determined by the entire previous history of the universe.
Our argument combines the well-known consequence of relativity theory, that the time order of spacelike separated events is not absolute, with the EPR paradox discovered by Einstein, Podolsky, and Rosen in 1935 and the Kochen–Specker Paradox of 1967 (see ). We follow Bohm in using a spin version of EPR and Peres in using his set of thirty-three directions, rather than the original configuration used by Kochen and Specker. More contentiously, the argument also involves the notion of free will, but we postpone further discussion of this to the last section of the chapter.
A mass-balance model using upper-air meteorological data for input was calibrated with surface mass balance measured mainly during 1977–78 at 67 sites on Columbia Glacier, Alaska, between 135 and 2645 m a.s.l. Root-mean-square error, model vs measured, is 1.0 m w.e. a−1, with r2 = 0.88. A remarkable result of the analysis was that both precipitation and the factor in the positive degree-day model used to estimate surface ablation were constant with altitude. The model was applied to reconstruct glacier-wide components of surface mass balance over 1948–2007. Surface ablation, 4 km3 ice eq. a−1 (ice equivalent), has changed little throughout the period. From 1948 until about 1981, when drastic retreat began, the surface mass balance was positive but changes in glacier geometry were small, so the positive balance was offset by calving, ∼0.9 km3 ice eq. a−1 . During retreat, volume loss of the glacier accounted for 92% of the iceberg production. Calving increased to ∼4.3 km3 ice eq. a−1 from 1982 to 1995, and after that until 2007 to ∼8.0 km3 ice eq. a−1, which was about twice the loss by surface ablation, whereas prior to retreat it was only about a quarter as much. Calving is calculated as the difference between glacier-wide surface mass balance and geodetically determined volume change.
We report a novel method of growing silver nanostructures by cathodic sputtering onto an ionic liquid (IL) and our visualization by transmission cryo-electron microscopy to avoid beam-induced motion of the nanoparticles. By freezing the IL suspension and controlling electron dose, we can assess properties of particle size, morphology, crystallinity, and aggregation in situ and at high detail. We observed round silver nanoparticles with a well-defined diameter of 7.0 ± 1.5 nm that are faceted with crystalline cubic structures and ˜80% of the particles have multiply twinned faults. We also applied cryo-electron tomography to investigate the structure of the nanoparticles and to directly visualize the IL wetting around them. In addition to particles, we observed nanorods that appear to have assembled from individual nanoparticles. Reexamination of the samples after 4–5 days from initial preparation showed significant changes in morphology, and potential mechanisms for this are discussed.
Strains of Salmonella enteritidis belonging to phage type 4 (SE4) were grown in the peritoneal cavities of chickens, and without subculture on laboratory media examined for inducible in vivo phenotypic characteristics. These bacteria expressed three major outer membrane proteins (OMPs) of 33, 35 and 36 kilodaltons (kDa), and iron regulated OMPs of 74, 78 and 81 kDa. Bacteria growing in vivo did not express flagella, or fimbriae with a subunit molecular mass of 14 kDa (14 kDa fimbriae). Two OMPs of 55 and 23 kDa, expressed during culture in nutrient broth, were repressed during growth in chickens. Possession of a 38 MDa ‘mouse virulence’ plasmid did not influence the expression of OMPs, flagella or fimbriae. It was concluded that strains of SE4 growing in chicken tissues, use an enterobactin mediated iron uptake system to obtain ferric ions, do not express flagella or 14 kDa fimbriae and appear not to express novel OMPs involved in survival in vivo.
A model using upper-air meteorological variables in the US National Centers for Environmental Prediction and US National Center for Atmospheric Research (NCEP/NCAR) re-analysis database is used to extend net balance bn back to 1948 for seven glaciers in southern Norway. The observational record of another glacier, Storbreen, began in 1948. Over the observational record of each of the seven glaciers, correlation with Storbreen estimates bn more accurately than the upper-air model does for four of them and less accurately for three. In all seven cases, however, an average of the model and the Storbreen correlation is more accurate than either alone, so the average is used to reconstruct bn for years when it was not observed. For the seven glaciers other than Storbreen, a combined series is formed from observations during their period of record and from reconstructed values prior to then back to 1948. There are three distinct sections in all eight bn series: prior to 1989; 1989–1995, when the North Atlantic Oscillation index was strongly positive; and after 1995. The 1989–95 mean bn was anomalously positive because of both decreased ablation and especially increased accumulation. The mean bn since 1995 has been anomalously negative because of increased ablation, whilst accumulation has been nearly the same as over 1948–88. The first principal component of the eight 1949–2005 bn series explains 78% of the total variance, and the second explains 12%. Over 1949–88 there were no substantial shifts in bn or in either winter balance bw or summer balance bs at any of the seven glaciers where observations began after 1948, nor were there in the Storbreen record. There is a distinction between the three glaciers that gained mass over 1948–2005 and the five that lost mass. Each of the three that gained had accumulation-area ratio AAR ≥ 0.64 and <0.7% of its area δS in the lowest tenth of its altitude range, while the five that lost had AAR ≤ 0.46 and 1.9 ≤ δS ≤ 4.4%. Because of these hypsometries, the five glaciers that lost mass now have an especially large ablation area.