Qualitative Evaluation of Associations by the Transitivity of the Association Signs

We say that the signs of association measures among three variables {X, Y, Z} are transitive if a positive association measure between the variable X and the intermediate variable Y and further a positive association measure between Y and the endpoint variable Z imply a positive association measure between X and Z. We introduce four association measures with different stringencies, and discuss conditions for the transitivity of the signs of these association measures. When the variables follow exponential family distributions, the conditions become simpler and more interpretable. Applying our results to two data sets from an observational study and a randomized experiment, we demonstrate that the results can help us to draw conclusions about the signs of the association measures between X and Z based only on two separate studies about {X, Y} and {Y, Z}.Comment: Statistica Sinica 201

Principal causal effect identification and surrogate endpoint evaluation by multiple trials

Principal stratification is a causal framework to analyze randomized experiments with a post-treatment variable between the treatment and endpoint variables. Because the principal strata defined by the potential outcomes of the post-treatment variable are not observable, we generally cannot identify the causal effects within principal strata. Motivated by a real data set of phase III adjuvant colon clinical trials, we propose approaches to identifying and estimating the principal causal effects via multiple trials. For the identifiability, we remove the commonly-used exclusion restriction assumption by stipulating that the principal causal effects are homogeneous across these trials. To remove another commonly-used monotonicity assumption, we give a necessary condition for the local identifiability, which requires at least three trials. Applying our approaches to the data from adjuvant colon clinical trials, we find that the commonly-used monotonicity assumption is untenable, and disease-free survival with three-year follow-up is a valid surrogate endpoint for overall survival with five-year follow-up, which satisfies both the causal necessity and the causal sufficiency. We also propose a sensitivity analysis approach based on Bayesian hierarchical models to investigate the impact of the deviation from the homogeneity assumption

The contribution of Alu exons to the human proteome.

BackgroundAlu elements are major contributors to lineage-specific new exons in primate and human genomes. Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. However, the contribution of Alu exons to the human proteome remains unclear and controversial. The prevailing view is that exons derived from young repetitive elements, such as Alu elements, are restricted to regulatory functions and have not had adequate evolutionary time to be incorporated into stable, functional proteins.ResultsWe adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. Using RNA sequencing, ribosome profiling, and proteomics data from human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. These Alu exon peptides represent species-specific protein differences between primates and other mammals, and in certain instances between humans and closely related primates. In the case of the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA sequencing analyses of A-to-I editing demonstrate that both the Alu exon skipping and inclusion isoforms encode active enzymes. The Alu exon derived peptide may fine tune the overall editing activity and, in limited cases, the site selectivity of ADARB1 protein products.ConclusionsOur data indicate that Alu elements have contributed to the acquisition of novel protein sequences during primate and human evolution

Synthesis and antiviral activity of a series of novel N-phenylbenzamide and N-phenylacetophenone compounds as anti-HCV and anti-EV71 agents

AbstractA series of novel N-phenylbenzamide and N-phenylacetophenone compounds were synthesized and evaluated for their antiviral activity against HCV and EV71 (strain SZ-98). The biological results showed that three compounds (23, 25 and 41) exhibited considerable anti-HCV activity (IC50=0.57–7.12μmol/L) and several compounds (23, 28, 29, 30, 31 and 42) displayed potent activity against EV71 with the IC50 values lower than 5.00μmol/L. The potency of compound 23 (IC50=0.57μmol/L) was superior to that of reported compounds IMB-1f (IC50=1.90μmol/L) and IMB-1g (IC50=1.00μmol/L) as anti-HCV agents, and compound 29 possessed the highest anti-EV71 activity, comparable to the comparator drug pirodavir. The efficacy in vivo and antiviral mechanism of these compounds warrant further investigations