A Knowledge Gradient Policy for Sequencing Experiments to Identify the Structure of RNA Molecules Using a Sparse Additive Belief Model

We present a sparse knowledge gradient (SpKG) algorithm for adaptively selecting the targeted regions within a large RNA molecule to identify which regions are most amenable to interactions with other molecules. Experimentally, such regions can be inferred from fluorescence measurements obtained by binding a complementary probe with fluorescence markers to the targeted regions. We use a biophysical model which shows that the fluorescence ratio under the log scale has a sparse linear relationship with the coefficients describing the accessibility of each nucleotide, since not all sites are accessible (due to the folding of the molecule). The SpKG algorithm uniquely combines the Bayesian ranking and selection problem with the frequentist $\ell_1$ regularized regression approach Lasso. We use this algorithm to identify the sparsity pattern of the linear model as well as sequentially decide the best regions to test before experimental budget is exhausted. Besides, we also develop two other new algorithms: batch SpKG algorithm, which generates more suggestions sequentially to run parallel experiments; and batch SpKG with a procedure which we call length mutagenesis. It dynamically adds in new alternatives, in the form of types of probes, are created by inserting, deleting or mutating nucleotides within existing probes. In simulation, we demonstrate these algorithms on the Group I intron (a mid-size RNA molecule), showing that they efficiently learn the correct sparsity pattern, identify the most accessible region, and outperform several other policies

When Values and Ethics of Care Conflict: A Lived Experience in the Roman Catholic Church

This article investigates contemporary understandings of the ethics of care. While the ethics of care is predominantly known as showing empathy and support to others, analysing the complex relationship between institutional and personal values of clerical leaders and the congregation in the Roman Catholic Church in England reveals very different understandings. The sociological and psychological concepts of authority, pastoral care and identity are used to analyse the role of a female youth work leader in a Roman Catholic parish who is exposed to different (conservative and liberal) leadership approaches. She explains how her views on care, gender and participation differ from those of three clerical leaders and powerfully illustrates the resulting conflicts between the priests but also towards the congregation. This story shows that individual agency influences strong conservative institutional values and that leadership in faith-based organisations needs to embrace the complex interplay between institutional and personal dynamics