No abstract

The simulation results imply that the control limits should vary based on the particular patient population of interest in order to control the in-control performance of the risk-adjusted Bernoulli CUSUM method.

A novel [4 + 3] annulation of indoline-based aza-dienes and crotonate-derived sulfur ylides is described. This method could be further expanded by using more efficient synthetic strategies, including three-component [3 + 1 + 3] cascade and the direct sulfide-catalyzed [4 + 3] cyclization. These protocols enable the rapid construction of azepino­[2,3-b]­indole cores, and a broad spectrum of the desired products with diverse substituents was facilely accessed in generally high yield.

Recent advances in high-throughput genotyping have inspired increasing research interests in genome-wide association study for diseases. To understand underlying biological mechanisms of many diseases, we need to consider simultaneously the genetic effects across multiple loci. The large number of SNPs often makes multilocus association study very computationally challenging because it needs to explicitly enumerate all possible SNP combinations at the genome-wide scale. Moreover, with the large number of SNPs correlated, permutation procedure is often needed for properly controlling family-wise error rates. This makes the problem even more computationally demanding, since the test procedure needs to be repeated for each permuted data. In this paper, we present FastChi, an exhaustive yet efficient algorithm for genome-wide two-locus chi-square test. FastChi utilizes an upper bound of the two-locus chi-square test, which can be expressed as the sum of two terms – both are efficient to compute: the first term is based on the single-locus chi-square test for the given phenotype; and the second term only depends on the genotypes and is independent of the phenotype. This upper bound enables the algorithm to only perform the two-locus chi-square test on a small number of candidate SNP pairs without the risk of missing any significant ones. Since the second part of the upper bound only needs to be precomputed once and stored for subsequence uses, the advantage is more prominent in large permutation tests. Extensive experimental results demonstrate that our method is an order of magnitude faster than the brute force alternative.

4-Aminopyridine is a clinically approved drug to improve motor symptoms in multiple sclerosis. A fluorine-18-labeled derivative of this drug, 3-[18F]fluoro-4-aminopyridine, is currently under investigation for positron emission tomography (PET) imaging of demyelination. Herein, the Yamada-Curtius reaction has been successfully applied for the preparation of this PET radioligand with a better radiochemical yield and improved specific activity. The overall radiochemical yield was 5 to 15% (n = 12, uncorrected) with a specific activity of 37 to 148 GBq/µmol (end of synthesis) in a 90 minute synthesis time. It is expected that this 1 pot Yamada-Curtius reaction can be used to prepare similar fluorine-18-labeled amino substituted heterocycles.