Biological/Biomedical Accelerator Mass Spectrometry Targets. 1. Optimizing the CO₂ Reduction Step Using Zinc Dust

Biological and biomedical applications of accelerator mass spectrometry (AMS) use isotope ratio mass spectrometry to quantify minute amounts of long-lived radioisotopes such as ¹⁴C. AMS target preparation involves first the oxidation of carbon (in sample of interest) to CO₂ and second the reduction of CO₂ to filamentous, fluffy, fuzzy, or firm graphite-like substances that coat a −400-mesh spherical iron powder (−400MSIP) catalyst. Until now, the quality of AMS targets has been variable; consequently, they often failed to produce robust ion currents that are required for reliable, accurate, precise, and high-throughput AMS for biological/biomedical applications. Therefore, we described our optimized method for reduction of CO₂ to high-quality uniform AMS targets whose morphology we visualized using scanning electron microscope pictures. Key features of our optimized method were to reduce CO₂ (from a sample of interest that provided 1 mg of C) using 100 ± 1.3 mg of Zn dust, 5 ± 0.4 mg of −400MSIP, and a reduction temperature of 500 °C for 3 h. The thermodynamics of our optimized method were more favorable for production of graphite-coated iron powders (GCIP) than those of previous methods. All AMS targets from our optimized method were of 100% GCIP, the graphitization yield exceeded 90%, and δ¹³C was −17.9 ± 0.3‰. The GCIP reliably produced strong ¹²C⁻ currents and accurate and precise <i>F</i>_m values. The observed <i>F</i>_m value for oxalic acid II NIST SRM deviated from its accepted <i>F</i>_m value of 1.3407 by only 0.0003 ± 0.0027 (mean ± SE, <i>n</i> = 32), limit of detection of ¹⁴C was 0.04 amol, and limit of quantification was 0.07 amol, and a skilled analyst can prepare as many as 270 AMS targets per day. More information on the physical (hardness/color), morphological (SEMs), and structural (FT-IR, Raman, XRD spectra) characteristics of our AMS targets that determine accurate, precise, and high-hroughput AMS measurement are in the companion paper

Accelerator Mass Spectrometry Targets of Submilligram Carbonaceous Samples Using the High-Throughput Zn Reduction Method

The high-throughput Zn reduction method was developed and optimized for various biological/biomedical accelerator mass spectrometry (AMS) applications of mg of C size samples. However, high levels of background carbon from the high-throughput Zn reduction method were not suitable for sub-mg of C size samples in environmental, geochronology, and biological/biomedical AMS applications. This study investigated the effect of background carbon mass (<i>m</i>_c) and background ¹⁴C level (<i>F</i>_c) from the high-throughput Zn reduction method. Background <i>m</i>_c was 0.011 mg of C and background <i>F</i>_c was 1.5445. Background subtraction, two-component mixing, and expanded formulas were used for background correction. All three formulas accurately corrected for backgrounds to 0.025 mg of C in the aerosol standard (NIST SRM 1648a). Only the background subtraction and the two-component mixing formulas accurately corrected for backgrounds to 0.1 mg of C in the IAEA-C6 and -C7 standards. After the background corrections, our high-throughput Zn reduction method was suitable for biological (diet)/biomedical (drug) and environmental (fine particulate matter) applications of sub-mg of C samples (≥ 0.1 mg of C) in keeping with a balance between throughput (270 samples/day/analyst) and sensitivity/accuracy/precision of AMS measurement. The development of a high-throughput method for examination of ≥ 0.1 mg of C size samples opens up a range of applications for ¹⁴C AMS studies. While other methods do exist for ≥ 0.1 mg of C size samples, the low throughput has made them cost prohibitive for many applications

Calculating Radiation Exposures during Use of ¹⁴C-Labeled Nutrients, Food Components, and Biopharmaceuticals To Quantify Metabolic Behavior in Humans

¹⁴C has long been used as a tracer for quantifying the in vivo human metabolism of food components, biopharmaceuticals, and nutrients. Minute amounts (≤1 × 10 ⁻¹⁸ mol) of ¹⁴C can be measured with high-throughput ¹⁴C-accelerator mass spectrometry (HT ¹⁴C-AMS) in isolated chemical extracts of biological, biomedical, and environmental samples. Availability of in vivo human data sets using a ¹⁴C tracer would enable current concepts of the metabolic behavior of food components, biopharmaceuticals, or nutrients to be organized into models suitable for quantitative hypothesis testing and determination of metabolic parameters. In vivo models are important for specification of intake levels for food components, biopharmaceuticals, and nutrients. Accurate estimation of the radiation exposure from ingested ¹⁴C is an essential component of the experimental design. Therefore, this paper illustrates the calculation involved in determining the radiation exposure from a minute dose of orally administered ¹⁴C-β-carotene, ¹⁴C-α-tocopherol, ¹⁴C-lutein, and ¹⁴C-folic acid from four prior experiments. The administered doses ranged from 36 to 100 nCi, and radiation exposure ranged from 0.12 to 5.2 μSv to whole body and from 0.2 to 3.4 μSv to liver with consideration of tissue weighting factor and fractional nutrient. In comparison, radiation exposure experienced during a 4 h airline flight across the United States at 37000 ft was 20 μSv

Review of population-based studies of risk factors associated with esodeviation and exodeviation in children.

<p>Review of population-based studies of risk factors associated with esodeviation and exodeviation in children.</p

Clinical characteristics of subjects for association analysis (n = 5,935).

<p>Clinical characteristics of subjects for association analysis (n = 5,935).</p

A flowchart showing study participants for final analysis.

<p>A flowchart showing study participants for final analysis.</p

Quality of Graphite Target for Biological/Biomedical/Environmental Applications of ¹⁴C-Accelerator Mass Spectrometry

Catalytic graphitization for ¹⁴C-accelerator mass spectrometry (¹⁴C-AMS) produced various forms of elemental carbon. Our high-throughput Zn reduction method (C/Fe = 1:5, 500 °C, 3 h) produced the AMS target of graphite-coated iron powder (GCIP), a mix of nongraphitic carbon and Fe₃C. Crystallinity of the AMS targets of GCIP (nongraphitic carbon) was increased to turbostratic carbon by raising the C/Fe ratio from 1:5 to 1:1 and the graphitization temperature from 500 to 585 °C. The AMS target of GCIP containing turbostratic carbon had a large isotopic fractionation and a low AMS ion current. The AMS target of GCIP containing turbostratic carbon also yielded less accurate/precise ¹⁴C-AMS measurements because of the lower graphitization yield and lower thermal conductivity that were caused by the higher C/Fe ratio of 1:1. On the other hand, the AMS target of GCIP containing nongraphitic carbon had higher graphitization yield and better thermal conductivity over the AMS target of GCIP containing turbostratic carbon due to optimal surface area provided by the iron powder. Finally, graphitization yield and thermal conductivity were stronger determinants (over graphite crystallinity) for accurate/precise/high-throughput biological, biomedical, and environmental¹⁴C-AMS applications such as absorption, distribution, metabolism, elimination (ADME), and physiologically based pharmacokinetics (PBPK) of nutrients, drugs, phytochemicals, and environmental chemicals

The SNP rs3128965 of HLA-DPB1 as a Genetic Marker of the AERD Phenotype

<div><p>Background</p><p>Two common clinical syndromes of acetylsalicylic acid (aspirin) hypersensitivity, aspirin-exacerbated respiratory disease (AERD) and aspirin-exacerbated cutaneous disease (AECD), were subjected to a genome-wide association study to identify strong genetic markers for aspirin hypersensitivity in a Korean population.</p><p>Methods</p><p>A comparison of SNP genotype frequencies on an Affymetrix Genome-Wide Human SNP array of 179 AERD patients and 1989 healthy normal control subjects (NC) revealed SNPs on chromosome 6 that were associated with AERD, but not AECD. To validate the association, we enrolled a second cohort comprising AERD (n = 264), NC (n = 238) and disease-control (aspirin tolerant asthma; ATA, n = 387) groups.</p><p>Results</p><p>The minor genotype frequency (AG or AA) of a particular SNP, rs3128965, in the HLA-DPB1 region was higher in the AERD group compared to the ATA or NC group (<i>P</i> = 0.001, <i>P</i> = 0.002, in a co-dominant analysis model, respectively). Comparison of rs3128965 alleles with the clinical features of asthmatics revealed that patients harboring the A allele had increased bronchial hyperresponsiveness to inhaled aspirin and methacholine, and higher 15-HETE levels, than those without the A allele (<i>P</i> = 0.039, 0.037, and 0.004, respectively).</p><p>Conclusions</p><p>This implies the potential of rs3128965 as a genetic marker for diagnosis and prediction of the AERD phenotype.</p></div

Synthesis and Assembly of Colloidal Particles with Sticky Dimples

The preparation of anisotropic colloidal particles by a simple yet versatile temperature-controlled swelling process is described. The resulting polymeric particles feature a surface dimple, the size and shape of which were determined by the amount of oil captured in particles and the interfacial tension between the three phases: polystyrene (PS), decane, and the suspending medium. Following the removal of free or physically adsorbed surfactant from the swollen particles, hydrophobic dimples were produced upon evaporation of the oil phase. We demonstrate the spontaneous assembly of these ‘dimpled particles’ into dumbbell shapes or trimers through a site-selective hydrophobic interaction

Inverse Photonic Glasses by Packing Bidisperse Hollow Microspheres with Uniform Cores

A major fabrication challenge is producing disordered photonic materials with an angle-independent structural red color. Theoretical work has shown that such a color can be produced by fabricating inverse photonic glasses with monodisperse, nontouching voids in a silica matrix. Here, we demonstrate a route toward such materials and show that they have an angle-independent red color. We first synthesize monodisperse hollow silica particles with precisely controlled shell thickness and then make glassy colloidal structures by mixing two types of hollow particles with the same core size and different shell thicknesses. We then infiltrate the interstices with index-matched polymers, producing disordered porous materials with uniform, nontouching air voids. This procedure allows us to control the light-scattering form factor and structure factor of these porous materials independently, which is not possible to do in photonic glasses consisting of packed solid particles. The structure factor can be controlled by the shell thickness, which sets the distance between pores, whereas the pore size determines the peak wave vector of the form factor, which can be set below the visible range to keep the main structural color pure. By using a binary mixture of 246 and 268 nm hollow silica particles with 180 nm cores in an index-matched polymer matrix, we achieve angle-independent red color that can be tuned by controlling the shell thickness. Importantly, the width of the reflection peak can be kept constant, even for larger interparticle distances