One-step Metabolomics: Carbohydrates, Organic and Amino Acids Quantified in a Single Procedure

Every infant born in the US is now screened for up to 42 rare genetic disorders called "inborn errors of metabolism". The screening method is based on tandem mass spectrometry and quantifies acylcarnitines as a screen for organic acidemias and also measures amino acids. All states also perform enzymatic testing for carbohydrate disorders such as galactosemia. Because the results can be non-specific, follow-up testing of positive results is required using a more definitive method. The present report describes the "urease" method of sample preparation for inborn error screening. Crystalline urease enzyme is used to remove urea from body fluids which permits most other water-soluble metabolites to be dehydrated and derivatized for gas chromatography in a single procedure. Dehydration by evaporation in a nitrogen stream is facilitated by adding acetonitrile and methylene chloride. Then, trimethylsilylation takes place in the presence of a unique catalyst, triethylammonium trifluoroacetate. Automated injection and chromatography is followed by macro-driven custom quantification of 192 metabolites and semi-quantification of every major component using specialized libraries of mass spectra of TMS derivatized biological compounds. The analysis may be performed on the widely-used Chemstation platform using the macros and libraries available from the author. In our laboratory, over 16,000 patient samples have been analyzed using the method with a diagnostic yield of about 17%--that is, 17% of the samples results reveal findings that should be acted upon by the ordering physician. Included in these are over 180 confirmed inborn errors, of which about 38% could not have been diagnosed using previous methods

Mechanistic influence of sub-micrometer porosity on the hydrogen environment-assisted cracking behavior of additively manufactured 17-4PH steel

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Superkicks in Hyperbolic Encounters of Binary Black Holes

Generic inspirals and mergers of binary black holes produce beamed emission of gravitational radiation that can lead to a gravitational recoil or kick of the final black hole. The kick velocity depends on the mass ratio and spins of the binary as well as on the dynamics of the binary configuration. Studies have focused so far on the most astrophysically relevant configuration of quasi-circular inspirals, for which kicks as large as 3,300 km/s have been found. We present the first study of gravitational recoil in hyperbolic encounters. Contrary to quasi-circular configurations, in which the beamed radiation tends to average during the inspiral, radiation from hyperbolic encounters is plunge dominated, resulting in an enhancement of preferential beaming. As a consequence, it is possible to achieve kick velocities as large as 10,000 km/s.Comment: 4 pages, 5 figures, 1 tabl

Hard and soft news: A review of concepts, operationalizations and key findings

Over 30 years, a large body of research on what is often called ‘hard’ and ‘soft news’ has accumulated in communication studies. However, there is no consensus about what hard and soft news exactly is, or how it should be defined or measured. Moreover, the concept has not been clearly differentiated from or systematically related to concepts addressing very similar phenomena – tabloidization and ‘infotainment’. Consequently, the results of various studies are hard to compare and different scientific discourses on related issues remain unconnected. Against this backdrop, this article offers a conceptual analysis of the concept based on studies in English and other languages. We identify key dimensions of the concept and make suggestions for a standardized definition and multi-dimensional measurement of harder and softer news. In doing so, we propose to distinguish thematic, focus and style features as basic dimensions that – in their combination – make up harder and softer types of news

Thermal performance of diamond field-effect transistors

In this report, the thermal performance of a hydrogen (H)-terminated diamond field-effect transistor (FET) is investigated using Raman spectroscopy and electrothermal device modeling. First, the thermal conductivity (κdiamond) of the active diamond channel was determined by measuring the temperature rise of transmission line measurement structures under various heat flux conditions using nanoparticle-assisted Raman thermometry. Using this approach, κdiamond was estimated to be 1860 W/m K with a 95% confidence interval ranging from 1610 to 2120 W/m K. In conjunction with measured electrical output characteristics, this κ was used as an input parameter for an electrothermal device model of an H-terminated diamond FET. The simulated thermal response showed good agreement with surface temperature measurements acquired using nanoparticle-assisted Raman thermometry. These diamond-based structures were highly efficient at dissipating heat from the active device channel with measured device thermal resistances as low as ∼1 mm K/W. Using the calibrated electrothermal device model, the diamond FET was able to operate at a very high power density of 40 W/mm with a simulated temperature rise of ∼33 K. Finally, the thermal resistance of these lateral diamond FETs was compared to lateral transistor structures based on other ultrawide bandgap materials (Al0.70Ga0.30N, β-Ga2O3) and wide bandgap GaN for benchmarking. These results indicate that the thermal resistance of diamond-based lateral transistors can be up to ∼10× lower than GaN-based devices and ∼50× lower than other UWBG devices

High-throughput SNP discovery through deep resequencing of a reduced representation library to anchor and orient scaffolds in the soybean whole genome sequence

Background: The Soybean Consensus Map 4.0 facilitated the anchoring of 95.6% of the soybean whole genome sequence developed by the Joint Genome Institute, Department of Energy, but its marker density was only sufficient to properly orient 66% of the sequence scaffolds. The discovery and genetic mapping of more single nucleotide polymorphism (SNP) markers were needed to anchor and orient the remaining genome sequence. To that end, next generation sequencing and high-throughput genotyping were combined to obtain a much higher resolution genetic map that could be used to anchor and orient most of the remaining sequence and to help validate the integrity of the existing scaffold builds. Results: A total of 7,108 to 25,047 predicted SNPs were discovered using a reduced representation library that was subsequently sequenced by the Illumina sequence-by-synthesis method on the clonal single molecule array platform. Using multiple SNP prediction methods, the validation rate of these SNPs ranged from 79% to 92.5%. A high resolution genetic map using 444 recombinant inbred lines was created with 1,790 SNP markers. Of the 1,790 mapped SNP markers, 1,240 markers had been selectively chosen to target existing un-anchored or un-oriented sequence scaffolds, thereby increasing the amount of anchored sequence to 97%. Conclusion: We have demonstrated how next generation sequencing was combined with high-throughput SNP detection assays to quickly discover large numbers of SNPs. Those SNPs were then used to create a high resolution genetic map that assisted in the assembly of scaffolds from the 8× whole genome shotgun sequences into pseudomolecules corresponding to chromosomes of the organism

Comparisons of host mitochondrial, nuclear and endosymbiont bacterial genes reveal cryptic fig wasp species and the effects of Wolbachia on host mtDNA evolution and diversity

Background Figs and fig-pollinating wasp species usually display a highly specific one-to-one association. However, more and more studies have revealed that the "one-to-one" rule has been broken. Co-pollinators have been reported, but we do not yet know how they evolve. They may evolve from insect speciation induced or facilitated by Wolbachia which can manipulate host reproduction and induce reproductive isolation. In addition, Wolbachia can affect host mitochondrial DNA evolution, because of the linkage between Wolbachia and associated mitochondrial haplotypes, and thus confound host phylogeny based on mtDNA. Previous research has shown that fig wasps have the highest incidence of Wolbachia infection in all insect taxa, and Wolbachia may have great influence on fig wasp biology. Therefore, we look forward to understanding the influence of Wolbachia on mitochondrial DNA evolution and speciation in fig wasps. Results We surveyed 76 pollinator wasp specimens from nine Ficus microcarpa trees each growing at a different location in Hainan and Fujian Provinces, China. We found that all wasps were morphologically identified as Eupristina verticillata, but diverged into three clades with 4.22-5.28% mtDNA divergence and 2.29-20.72% nuclear gene divergence. We also found very strong concordance between E. verticillata clades and Wolbachia infection status, and the predicted effects of Wolbachia on both mtDNA diversity and evolution by decreasing mitochondrial haplotypes. Conclusions Our study reveals that the pollinating wasp E. verticillata on F. microcarpa has diverged into three cryptic species, and Wolbachia may have a role in this divergence. The results also indicate that Wolbachia strains infecting E. verticillata have likely resulted in selective sweeps on host mitochondrial DNA

Feeding \u3ci\u3eDrosophila\u3c/i\u3e a biotin-deficient diet for multiple generations increases stress resistance and lifespan and alters gene expression and histone biotinylation patterns

Caloric restriction increases stress resistance and lifespan in Drosophila melanogaster and other species. The roles of individual nutrients in stress resistance and longevity are largely unknown. The vitamin biotin is a potential candidate for mediating these effects, given its known roles in stress signaling and gene regulation by epigenetic mechanisms, i.e., biotinylation of histones. Here, we tested the hypothesis that prolonged culture of Drosophila on biotin-deficient medium increases stress resistance and lifespan. Flies were fed a biotin-deficient diet for multiple generations; controls were fed a biotin-normal diet. In some experiments, a third group of flies was fed a biotin-deficient diet for 12 generations and then switched to control diets for two generations to eliminate potential effects of short-term biotin deficiency. Flies fed a biotin-deficient diet exhibited a 30% increase in lifespan. This increase was associated with enhanced resistance to the DNA-damaging agent hydroxyurea and heat stress. Also, fertility increased significantly compared with biotin-normal controls. Biotinylation of histones was barely detectable in biotin-deprived flies, suggesting that epigenetic events might have contributed to effects of biotin deprivation