Conducting A/B Experiments with a Scalable Architecture

A/B experiments are commonly used in research to compare the effects of changing one or more variables in two different experimental groups - a control group and a treatment group. While the benefits of using A/B experiments are widely known and accepted, there is less agreement on a principled approach to creating software infrastructure systems to assist in rapidly conducting such experiments. We propose a four-principle approach for developing a software architecture to support A/B experiments that is domain agnostic and can help alleviate some of the resource constraints currently needed to successfully implement these experiments: the software architecture (i) must retain the typical properties of A/B experiments, (ii) capture problem solving activities and outcomes, (iii) allow researchers to understand the behavior and outcomes of participants in the experiment, and (iv) must enable automated analysis. We successfully developed a software system to encapsulate these principles and implement it in a real-world A/B experiment

Ekiden: A Platform for Confidentiality-Preserving, Trustworthy, and Performant Smart Contract Execution

Smart contracts are applications that execute on blockchains. Today they manage billions of dollars in value and motivate visionary plans for pervasive blockchain deployment. While smart contracts inherit the availability and other security assurances of blockchains, however, they are impeded by blockchains' lack of confidentiality and poor performance. We present Ekiden, a system that addresses these critical gaps by combining blockchains with Trusted Execution Environments (TEEs). Ekiden leverages a novel architecture that separates consensus from execution, enabling efficient TEE-backed confidentiality-preserving smart-contracts and high scalability. Our prototype (with Tendermint as the consensus layer) achieves example performance of 600x more throughput and 400x less latency at 1000x less cost than the Ethereum mainnet. Another contribution of this paper is that we systematically identify and treat the pitfalls arising from harmonizing TEEs and blockchains. Treated separately, both TEEs and blockchains provide powerful guarantees, but hybridized, though, they engender new attacks. For example, in naive designs, privacy in TEE-backed contracts can be jeopardized by forgery of blocks, a seemingly unrelated attack vector. We believe the insights learned from Ekiden will prove to be of broad importance in hybridized TEE-blockchain systems

Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction

Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5 million people, our approach is statistically more powerful than single-trait analyses and identifies more than 500 genetic loci. The loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results predicts a range of behavioral and medical outcomes that were not part of genome-wide analyses, including traits that until now lacked well-performing polygenic scores, such as opioid use disorder, suicide, HIV infections, criminal convictions and unemployment. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental trait with complex and far-reaching social and health correlates

Genes Contributing to Staphylococcus aureus Fitness in Abscess- and Infection-Related Ecologies

ABSTRACT Staphylococcus aureus is a leading cause of both community- and hospital-acquired infections that are increasingly antibiotic resistant. The emergence of S. aureus resistance to even last-line antibiotics heightens the need for the development of new drugs with novel targets. We generated a highly saturated transposon insertion mutant library in the genome of S. aureus and used Tn-seq analysis to probe the entire genome, with unprecedented resolution and sensitivity, for genes of importance in infection. We further identified genes contributing to fitness in various infected compartments (blood and ocular fluids) and compared them to genes required for growth in rich medium. This resulted in the identification of 426 genes that were important for S. aureus fitness during growth in infection models, including 71 genes that could be considered essential for survival specifically during infection. These findings highlight novel as well as previously known genes encoding virulence traits and metabolic pathways important for S. aureus proliferation at sites of infection, which may represent new therapeutic targets

Holistic spectroscopy: complete reconstruction of a wide-field, multiobject spectroscopic image using a photonic comb

The primary goal of Galactic archaeology is to learn about the origin of the Milky Way from the detailed chemistry and kinematics of millions of stars. Wide-field multifibre spectrographs are increasingly used to obtain spectral information for huge samples of stars. Some surveys (e.g. GALAH) are attempting to measure up to 30 separate elements per star. Stellar abundance spectroscopy is a subtle art that requires a very high degree of spectral uniformity across each of the fibres. However, wide-field spectrographs are notoriously non-uniform due to the fast output optics necessary to image many fibre outputs on to the detector. We show that precise spectroscopy is possible with such instruments across all fibres by employing a photonic comb – a device that produces uniformly spaced spots of light on the CCD to precisely map complex aberrations. Aberrations are parametrized by a set of orthogonal moments with ∼100 independent parameters. We then reproduce the observed image by convolving high-resolution spectral templates with measured aberrations as opposed to extracting the spectra from the observed image. Such a forward modelling approach also trivializes some spectroscopic reduction problems like fibre cross-talk, and reliably extracts spectra with a resolution ∼2.3 times above the nominal resolution of the instrument. Our rigorous treatment of optical aberrations also encourages a less conservative spectrograph design in the future

The GALAH survey: accurate radial velocities and library of observed stellar template spectra

GALAH is a large-scale magnitude-limited southern stellar spectroscopic survey. Its second data release (GALAH DR2) provides values of stellar parameters and abundances of 23 elements for 342 682 stars (Buder et al.). Here we add a description of the public release of radial velocities with a typical accuracy of 0.1 km s−1 for 336 215 of these stars, achievable due to the large wavelength coverage, high resolving power, and good signal-to-noise ratio of the observed spectra, but also because convective motions in stellar atmosphere and gravitational redshift from the star to the observer are taken into account. In the process we derive medians of observed spectra that are nearly noiseless, as they are obtained from between 100 and 1116 observed spectra belonging to the same bin with a width of 50 K in temperature, 0.2 dex in gravity, and 0.1 dex in metallicity. Publicly released 1181 median spectra have a resolving power of 28 000 and trace the well-populated stellar types with metallicities between −0.6 and +0.3. Note that radial velocities from GALAH are an excellent match to the accuracy of velocity components along the sky plane derived by Gaia for the same stars. The level of accuracy achieved here is adequate for studies of dynamics within stellar clusters, associations, and streams in the Galaxy. So it may be relevant for studies of the distribution of dark matter.TZ, GT, and KC acknowledge financial support of ˇ the Slovenian Research Agency (research core funding No. P1-0188 and project N1-0040). TZ acknowledges the grant from the distinguished visitor programme of the RSAA at the Australian National University. JK is supported by a Discovery Project grant from the Australian Research Council (DP150104667) awarded to J. BlandHawthorn and T. Bedding. ARC acknowledges support through the Australian Research Council through grant DP160100637. LD, KF, and Y-ST are grateful for support from Australian Research Council grant DP160103747. SLM acknowledges support from the Australian Research Council through grant DE140100598. LC is the recipient of an ARC Future Fellowship (project number FT160100402). Parts of this research were conducted by the Australian Research Council Centre of Excellence for All Sky Astrophysics in 3 Dimensions (ASTRO 3D), through project number CE17010001

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

The GALAH survey: Co-orbiting stars and chemical tagging

We present a study using the second data release of the GALAH survey of stellar parameters and elemental abundances of 15 pairs of stars identified by Oh et al 2017. They identified these pairs as potentially co-moving pairs using proper motions and parallaxes from Gaia DR1. We find that 11 very wide (>1.7 pc) pairs of stars do in fact have similar Galactic orbits, while a further four claimed co-moving pairs are not truly co-orbiting. Eight of the 11 co-orbiting pairs have reliable stellar parameters and abundances, and we find that three of those are quite similar in their abundance patterns, while five have significant [Fe/H] differences. For the latter, this indicates that they could be co-orbiting because of the general dynamical coldness of the thin disc, or perhaps resonances induced by the Galaxy, rather than a shared formation site. Stars such as these, wide binaries, debris of past star formation episodes, and coincidental co-orbiters, are crucial for exploring the limits of chemical tagging in the Milky Way.Comment: 14 pages, 9 figures, submitted to MNRAS. Updated for Gaia DR2 value

The GALAH survey: Co-orbiting stars and chemical tagging

We present a study using the second data release of the GALAH survey of stellar parameters and elemental abundances of 15 pairs of stars identified by Oh et al 2017. They identified these pairs as potentially co-moving pairs using proper motions and parallaxes from Gaia DR1. We find that 11 very wide (>1.7 pc) pairs of stars do in fact have similar Galactic orbits, while a further four claimed co-moving pairs are not truly co-orbiting. Eight of the 11 co-orbiting pairs have reliable stellar parameters and abundances, and we find that three of those are quite similar in their abundance patterns, while five have significant [Fe/H] differences. For the latter, this indicates that they could be co-orbiting because of the general dynamical coldness of the thin disc, or perhaps resonances induced by the Galaxy, rather than a shared formation site. Stars such as these, wide binaries, debris of past star formation episodes, and coincidental co-orbiters, are crucial for exploring the limits of chemical tagging in the Milky Way.Comment: 14 pages, 9 figures, submitted to MNRAS. Updated for Gaia DR2 value