Boosted Off-Policy Learning

We investigate boosted ensemble models for off-policy learning from logged bandit feedback. Toward this goal, we propose a new boosting algorithm that directly optimizes an estimate of the policy's expected reward. We analyze this algorithm and prove that the empirical risk decreases (possibly exponentially fast) with each round of boosting, provided a "weak" learning condition is satisfied. We further show how the base learner reduces to standard supervised learning problems. Experiments indicate that our algorithm can outperform deep off-policy learning and methods that simply regress on the observed rewards, thereby demonstrating the benefits of both boosting and choosing the right learning objective

Pre-Steady-State Decoding of the Bicoid Morphogen Gradient

Morphogen gradients are established by the localized production and subsequent diffusion of signaling molecules. It is generally assumed that cell fates are induced only after morphogen profiles have reached their steady state. Yet, patterning processes during early development occur rapidly, and tissue patterning may precede the convergence of the gradient to its steady state. Here we consider the implications of pre-steady-state decoding of the Bicoid morphogen gradient for patterning of the anterior–posterior axis of the Drosophila embryo. Quantitative analysis of the shift in the expression domains of several Bicoid targets (gap genes) upon alteration of bcd dosage, as well as a temporal analysis of a reporter for Bicoid activity, suggest that a transient decoding mechanism is employed in this setting. We show that decoding the pre-steady-state morphogen profile can reduce patterning errors caused by fluctuations in the rate of morphogen production. This can explain the surprisingly small shifts in gap and pair-rule gene expression domains observed in response to alterations in bcd dosage

An Analysis of Fundamental Waffle Mode in Early AEOS Adaptive Optics Images

Adaptive optics (AO) systems have significantly improved astronomical imaging capabilities over the last decade, and are revolutionizing the kinds of science possible with 4-5m class ground-based telescopes. A thorough understanding of AO system performance at the telescope can enable new frontiers of science as observations push AO systems to their performance limits. We look at recent advances with wave front reconstruction (WFR) on the Advanced Electro-Optical System (AEOS) 3.6 m telescope to show how progress made in improving WFR can be measured directly in improved science images. We describe how a "waffle mode" wave front error (which is not sensed by a Fried geometry Shack-Hartmann wave front sensor) affects the AO point-spread function (PSF). We model details of AEOS AO to simulate a PSF which matches the actual AO PSF in the I-band, and show that while the older observed AEOS PSF contained several times more waffle error than expected, improved WFR techniques noticeably improve AEOS AO performance. We estimate the impact of these improved WFRs on H-band imaging at AEOS, chosen based on the optimization of the Lyot Project near-infrared coronagraph at this bandpass.Comment: 15 pages, 11 figures, 1 table; to appear in PASP, August 200

Analysis and Exploitation of Musician Social Networks for Recommendation and Discovery

This paper presents an extensive analysis of a sample of a social network of musicians. The network sample is first analyzed using standard complex network techniques to verify that it has similar properties to other web-derived complex networks. Content-based pairwise dissimilarity values between the musical data associated with the network sample are computed, and the relationship between those content-based distances and distances from network theory explored. Following this exploration, hybrid graphs and distance measures are constructed, and used to examine the community structure of the artist network. Finally, results of these investigations are presented and considered in the light of recommendation and discovery applications with these hybrid measures as their basis

Thyroxine-thyroid hormone receptor interactions

ABSTRACTThyroid hormone (TH) actions are mediated by nuclear receptors (TRs α and β) that bind triiodothyronine (T3, 3,5,3′-triiodo-l-thyronine) with high affinity, and its precursor thyroxine (T4, 3,5,3′,5′-tetraiodo-l-thyronine) with lower affinity. T4 contains a bulky 5′ iodine group absent from T3. Because T3 is buried in the core of the ligand binding domain (LBD), we have predicted that TH analogues with 5′ substituents should fit poorly into the ligand binding pocket and perhaps behave as antagonists. We therefore examined how T4 affects TR activity and conformation. We obtained several lines of evidence (ligand dissociation kinetics, migration on hydrophobic interaction columns, and non-denaturing gels) that TR-T4 complexes adopt a conformation that differs from TR-T3 complexes in solution. Nonetheless, T4 behaves as an agonist in vitro (in effects on coregulator and DNA binding) and in cells, when conversion to T3 does not contribute to agonist activity. We determined x-ray crystal structures of the TRβ LBD in complex with T3 and T4 at 2.5-Å and 3.1-Å resolution. Comparison of the structures reveals that TRβ accommodates T4 through subtle alterations in the loop connecting helices 11 and 12 and amino acid side chains in the pocket, which, together, enlarge a niche that permits helix 12 to pack over the 5′ iodine and complete the coactivator binding surface. While T3 is the major active TH, our results suggest that T4 could activate nuclear TRs at appropriate concentrations. The ability of TR to adapt to the 5′ extension should be considered in TR ligand design

A systematic review and meta-analysis of the safety, feasibility and effect of exercise in women with stage II+ breast cancer

To systematically evaluate the safety, feasibility and effect of exercise among women with stage II+ breast cancer.CINAHL, Cochrane, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, Science Direct and SPORTDiscus were searched for articles published prior to March 1, 2017.Randomised, controlled, exercise trials involving at least 50% of women diagnosed with stage II+ breast cancer were included.Risk of bias was assessed and adverse event severity was classified using the Common Terminology Criteria. Feasibility was evaluated by computing median (range) recruitment, withdrawal and adherence rates. Meta-analyses were performed to evaluate exercise safety and effects on health outcomes only. The influence of intervention characteristics (mode, supervision, duration and timing) on exercise outcomes were also explored.There were no differences in adverse events between exercise and usual care (risk difference

Chiral patterns arising from electrostatic growth models

Recently, unusual and strikingly beautiful seahorse-like growth patterns have been observed under conditions of quasi-two-dimensional growth. These `S'-shaped patterns strongly break two-dimensional inversion symmetry; however such broken symmetry occurs only at the level of overall morphology, as the clusters are formed from achiral molecules with an achiral unit cell. Here we describe a mechanism which gives rise to chiral growth morphologies without invoking microscopic chirality. This mechanism involves trapped electrostatic charge on the growing cluster, and the enhancement of growth in regions of large electric field. We illustrate the mechanism with a tree growth model, with a continuum model for the motion of the one-dimensional boundary, and with microscopic Monte Carlo simulations. Our most dramatic results are found using the continuum model, which strongly exhibits spontaneous chiral symmetry breaking, and in particular finned `S' shapes like those seen in the experiments.Comment: RevTeX, 12 pages, 9 figure

Assessment of Serum Proteomics to Detect Large Colon Adenomas

A non-invasive blood test that could reliably detect early CRC or large adenomas would provide an important advance in colon cancer screening. The purpose of this study was to determine whether a serum proteomics assay could discriminate among persons with and without a large (≥1cm) colon adenoma. To avoid problems of ‘bias’ that have affected many studies about molecular markers for diagnosis, specimens were obtained from a previously-conducted study of CRC etiology in which bloods had been collected before the presence or absence of neoplasm had been determined by colonoscopy, helping to assure that biases related to differences in sample collection and handling would be avoided. Mass spectra of 65 unblinded serum samples were acquired using a nano-electrospray ionization source on a QSTAR-XL mass spectrometer. Classification patterns were developed using the ProteomeQuest® algorithm, performing measurements twice on each specimen, and then applied to a blinded validation set of 70 specimens. After removing 33 specimens that had discordant results, the “test group” comprised 37 specimens that had never been used in training. Although in the primary analysis no discrimination was found, a single post-hoc analysis, done after hemolyzed specimens had been removed, showed sensitivity of 78%, specificity of 53%, and an accuracy of 63% (95% CI: 53% to 72%). The results of this study, although preliminary, suggest that further study of serum proteomics, in a larger number of appropriate specimens, could be useful. They also highlight the importance of understanding sources of ‘noise’ and ‘bias’ in studies of proteomics assays