Enhanced 3-epi-25-hydroxyvitamin D3 signal leads to overestimation of its concentration and amplifies interference in 25-hydroxyvitamin D LC-MS/MS assays

Background 3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3) interferes in most liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for 25-hydroxyvitamin D (25OHD). The clinical significance of this is unclear, with concentrations from undetectable to 230 nmol/L reported. Many studies have quantified 3-epi-25OHD3 based on 25OHD3 calibrators or other indirect methods, and we speculated that this contributes to the observed variability in reported 3-epi-25OHD3 concentrations. Methods We compared continuous MS/MS infusions of 3-epi-25OHD3 and 25OHD3 solutions, spiked both analytes into the same serum matrix and analysed patient samples to assess the effect of three different quantitation methods on 3-epi-25OHD3 concentration. Experiments were performed on an LC-MS/MS system using a phenyl column which does not resolve 3-epi-25OHD3, and a modified method utilizing a Zorbax SB-CN column that chromatographically resolves 3-epi-25OHD3 from 25OHD3. Results A greater 3-epi-25OHD3 signal, compared with 25OHD3, was observed during equimolar post-column continuous infusion of analyte solutions, and following analysis of a serum pool spiked with both analytes. 3-epi-25OHD3 signal enhancement was dependent on mobile phase composition. Compared with 3-epi-25OHD3 calibrators, indirect quantitation methods resulted in up to 10 times as many samples having 3-epi-25OHD3 concentrations ≥ 10 nmol/L, and an approximately fourfold increase in the maximum observed 3-epi-25OHD3 concentration to 95 nmol/L. Conclusions Enhanced 3-epi-25OHD3 signal leads to overestimation of its concentrations in the indirect quantitation methods used in many previous studies. The enhanced signal may contribute to greater interference in some 25OHD LC-MS/MS assays than others. We highlight that equimolar responses cannot be assumed in LC-MS/MS systems, even if two molecules are structurally similar

The arithmetic of hyperelliptic curves

We summarise recent advances in techniques for solving Diophantine problems on hyperelliptic curves; in particular, those for finding the rank of the Jacobian, and the set of rational points on the curve

K dwarfs and the chemical evolution of the Solar cylinder

K-dwarfs have life-times older than the present age of the Galactic disc, and are thus ideal stars to investigate the disc's chemical evolution. We have developed several photometric metallicity indicators for K dwarfs, based an a sample of accurate spectroscopic metallicities for 34 disc and halo G and K dwarfs. The photometric metallicities lead us to develop a metallicity index for K dwarfs based only on their position in the colour absolute-magnitude diagram. Metallicities have been determined for 431 single K dwarfs drawn from the Hipparcos catalog, selecting the stars by absolute magnitude and removing multiple systems. The sample is essentially a complete reckoning of the metal content in nearby K dwarfs. We use stellar isochrones to mark the stars by mass, and select a subset of 220 of the stars which is complete in a narrow mass interval. We fit the data with a model of the chemical evolution of the Solar cylinder. We find that only a modest cosmic scatter is required to fit our age metallicity relation. The model assumes two main infall episodes for the formation of the halo-thick disc and thin disc respectively. The new data confirms that the solar neighbourhood formed on a long timescale of order 7 Gyr.Comment: 14 pages, 15 figures, accepted by MNRA

Design of testbed and emulation tools

The research summarized was concerned with the design of testbed and emulation tools suitable to assist in projecting, with reasonable accuracy, the expected performance of highly concurrent computing systems on large, complete applications. Such testbed and emulation tools are intended for the eventual use of those exploring new concurrent system architectures and organizations, either as users or as designers of such systems. While a range of alternatives was considered, a software based set of hierarchical tools was chosen to provide maximum flexibility, to ease in moving to new computers as technology improves and to take advantage of the inherent reliability and availability of commercially available computing systems

Cycles of Quadratic Polynomials and Rational Points on a Genus-Two Curve

It has been conjectured that for $N$ sufficiently large, there are no quadratic polynomials in $\bold Q[z]$ with rational periodic points of period $N$. Morton proved there were none with $N=4$, by showing that the genus~$2$ algebraic curve that classifies periodic points of period~4 is birational to $X_1(16)$, whose rational points had been previously computed. We prove there are none with $N=5$. Here the relevant curve has genus~$14$, but it has a genus~$2$ quotient, whose rational points we compute by performing a~$2$-descent on its Jacobian and applying a refinement of the method of Chabauty and Coleman. We hope that our computation will serve as a model for others who need to compute rational points on hyperelliptic curves. We also describe the three possible Gal$_{\bold Q}$-stable $5$-cycles, and show that there exist Gal$_{\bold Q}$-stable $N$-cycles for infinitely many $N$. Furthermore, we answer a question of Morton by showing that the genus~$14$ curve and its quotient are not modular. Finally, we mention some partial results for $N=6$

Researching the Researchers by Edward F. Flynn, UND Summer Commencement: August 2, 1945

Text of speech delivered by Edward Flynn at the UND Summer Commencement on August 2, 1945. Flynn was the Assistant to the Vice President and General Counsel for the Great Northern Railway Company. He entitled his remarks: Researching the Researchers