Association Between Homocysteine and Vascular Calcification Incidence, Prevalence, and Progression in the MESA Cohort.

Background While elevated homocysteine has been associated with calcification in several studies, its importance as a cardiovascular risk factor remains unclear. This study examines the relationship between homocysteine and vascular and valve calcification in the MESA (Multi-ethnic Study of Atherosclerosis) cohort. Methods and Results MESA participants with baseline homocysteine measurements and cardiac computed tomography scans were included (N=6789). Baseline and follow-up assessment of vascular (coronary artery [CAC], descending thoracic aorta [DTAC]) and valve (aortic valve [AVC], mitral annular [MAC]) calcification was performed. Prevalence ratio/relative risk regression was used to assess the relationship of homocysteine with prevalent and incident calcification, and multivariable logistic regression was used to assess associations between homocysteine and calcification progression. Elevated homocysteine was associated with greater relative risk of prevalent and incident CAC and incident DTAC. We also identified a strong association between elevated homocysteine and CAC and DTAC progression. Elevated homocysteine was found to confer a >2-fold increased risk of severe CAC progression (defined as ΔCAC ≥100/year) and an ≈1.5-fold increased risk for severe DTAC progression (defined as ΔDTAC ≥100/year). Conclusions To our knowledge, this is the first study demonstrating an association between elevated homocysteine and both incidence and progression of coronary and extra-coronary vascular calcification. Our findings suggest a potential role for elevated homocysteine as a risk factor for severe vascular calcification progression. Future studies are warranted to further assess the utility of homocysteine as a biomarker for vascular calcification incidence and progression. Clinical Trial Registration https://www.clinicaltrials.gov/. Unique identifier: NCT00005487

Casting inorganic structures with DNA molds

We report a general strategy for designing and synthesizing inorganic nanostructures with arbitrarily prescribed three-dimensional shapes. Computationally designed DNA strands self-assemble into a stiff “nanomold” that contains a user-specified three-dimensional cavity and encloses a nucleating gold “seed.” Under mild conditions, this seed grows into a larger cast structure that fills and thus replicates the cavity. We synthesized a variety of nanoparticles with 3-nanometer resolution: three distinct silver cuboids with three independently tunable dimensions, silver and gold nanoparticles with diverse cross sections, and composite structures with homo- and heterogeneous components. The designer equilateral silver triangular and spherical nanoparticles exhibited plasmonic properties consistent with electromagnetism-based simulations. Our framework is generalizable to more complex geometries and diverse inorganic materials, offering a range of applications in biosensing, photonics, and nanoelectronics.United States. Air Force Office of Scientific Research. Defense University Research Instrumentation Program (Grant N000141310664)United States. Air Force Office of Scientific Research. Defense University Research Instrumentation Program (Grant N000141210621)National Science Foundation (U.S.). Designing Materials to Revolutionize and Engineer our Future Program (Grant CMMI1334109

Electron Microprobe/SIMS Determinations of Al in Olivine: Applications to Solar Wind, Pallasites and Trace Element Measurements

Electron probe microanalyser measurements of trace elements with high accuracy are challenging. Accurate Al measurements in olivine are required to calibrate SIMS implant reference materials for measurement of Al in the solar wind. We adopt a combined EPMA/SIMS approach that is useful for producing SIMS reference materials as well as for EPMA at the ~100 µg g⁻¹ level. Even for mounts not polished with alumina photoelectron spectroscopy shows high levels of Al surface contamination. In order to minimise electron beam current density, a rastered 50 × 100 µm electron beam was adequate and minimised sensitivity to small Al‐rich contaminants. Reproducible analyses of eleven SIMS cleaned spots on San Carlos olivine agreed at 69.3 ± 1.0 µg g⁻¹. The known Al mass fraction was used to calibrate an Al implant into San Carlos. Accurate measurements of Al were made for olivines in the pallasites: Imilac, Eagle Station and Springwater. Our focus was on Al in olivine; but our technique could be refined to give accurate electron probe measurements for other contamination‐sensitive trace elements. For solar wind it is projected that the Al/Mg abundance ratio can be determined to 6%, a factor of 2 more precise than the solar spectroscopic ratio

Electron Microprobe/SIMS Determinations of Al in Olivine: Applications to Solar Wind, Pallasites and Trace Element Measurements

Electron probe microanalyser measurements of trace elements with high accuracy are challenging. Accurate Al measurements in olivine are required to calibrate SIMS implant reference materials for measurement of Al in the solar wind. We adopt a combined EPMA/SIMS approach that is useful for producing SIMS reference materials as well as for EPMA at the ~100 µg g⁻¹ level. Even for mounts not polished with alumina photoelectron spectroscopy shows high levels of Al surface contamination. In order to minimise electron beam current density, a rastered 50 × 100 µm electron beam was adequate and minimised sensitivity to small Al‐rich contaminants. Reproducible analyses of eleven SIMS cleaned spots on San Carlos olivine agreed at 69.3 ± 1.0 µg g⁻¹. The known Al mass fraction was used to calibrate an Al implant into San Carlos. Accurate measurements of Al were made for olivines in the pallasites: Imilac, Eagle Station and Springwater. Our focus was on Al in olivine; but our technique could be refined to give accurate electron probe measurements for other contamination‐sensitive trace elements. For solar wind it is projected that the Al/Mg abundance ratio can be determined to 6%, a factor of 2 more precise than the solar spectroscopic ratio

Analysis of the Potential for Delay Propagation in Passenger Airline Networks

In this paper, we analyze the potential for delays to propagate in passenger airline networks. The motivation for this research is the need to better understand the relationship between the scheduling of aircraft and crew members, and the operational performance of such schedules. In particular, when carriers decide how to schedule these costly resources, the focus is primarily on achieving high levels of utilization. The resulting plans, however, often have little slack, limiting the schedule's ability to absorb disruption; instead, initial flight delays may propagate to delay subsequent flights as well. Understanding the relationship between planned schedules and delay propagation is a requisite precursor to developing tools for building more robust airline plans. In this paper, we investigate this relationship using flight data provided by two major U.S. carriers, one traditional hub-and-spoke and one “low-fare” carrier

Elemental abundances of major elements in the solar wind as measured in Genesis targets and implications on solar wind fractionation

The UCLA ion microprobe facility is partially supported by a grant from the NSF Instrumentation and Facilities program. V. S. Heber thanks NASA for financial support. This work was supported by grants from the NASA Laboratory Analysis of Returned Samples (LARS) program (NASA LARS 80NSSC17K0025 to D. S. Burnett and A. J. G. Jurewicz). R. Wieler acknowledges the hospitality of Caltech's Division of Geologial and Planetary Sciences during his stay in Pasadena.We present elemental abundance data of C, N, O, Na, Mg, Al, Ca, and Cr in Genesis silicon targets. For Na, Mg, Al, and Ca, data from three different SW regimes are also presented. Data were obtained by backside depth profiling using Secondary Ion Mass Spectrometry. The accuracy of these measurements exceeds those obtained by in-situ observations; therefore the Genesis data provide new insights into elemental fractionation between Sun and solar wind, including differences between solar wind regimes. We integrate previously published noble gas and hydrogen elemental abundances from Genesis targets, as well as preliminary values for K and Fe. The abundances of the solar wind elements measured display the well-known fractionation pattern that correlates with each element's First Ionization Potential (FIP). When normalized either to spectroscopic photospheric solar abundances or to those derived from CI-chondritic meteorites, the fractionation factors of low-FIP elements (K, Na, Al, Ca, Cr, Mg, Fe) are essentially identical within uncertainties, but the data are equally consistent with an increasing fractionation with decreasing FIP. The elements with higher FIPs between ~11 and ~16 eV (C, N, O, H, Ar, Kr, Xe) display a relatively well-defined trend of increasing fractionation with decreasing FIP, if normalized to modern 3D photospheric model abundances. Among the three Genesis regimes, the Fast SW displays the least elemental fractionation for almost all elements (including the noble gases) but differences are modest: for low-FIP elements the precisely measured Fast-Slow SW variations are less than 3%.PostprintPeer reviewe

Full-length isoform transcriptome of the developing human brain provides further insights into autism.

Alternative splicing plays an important role in brain development, but its global contribution to human neurodevelopmental diseases (NDDs) requires further investigation. Here we examine the relationships between splicing isoform expression in the brain and de novo loss-of-function mutations from individuals with NDDs. We analyze the full-length isoform transcriptome of the developing human brain and observe differentially expressed isoforms and isoform co-expression modules undetectable by gene-level analyses. These isoforms are enriched in loss-of-function mutations and microexons, are co-expressed with a unique set of partners, and have higher prenatal expression. We experimentally test the effect of splice-site mutations and demonstrate exon skipping in five NDD risk genes, including SCN2A, DYRK1A, and BTRC. Our results suggest that the splice site mutation in BTRC reduces translational efficiency, likely affecting Wnt signaling through impaired degradation of β-catenin. We propose that functional effects of mutations should be investigated at the isoform- rather than gene-level resolution

Genetic deletion of skeletal muscle iPLA2γ results in mitochondrial dysfunction, muscle atrophy and alterations in whole-body energy metabolism

Skeletal muscle is the major site of glucose utilization in mammals integrating serum glucose clearance with mitochondrial respiration. To mechanistically elucidate the roles of iPL