Tortoise: Interactive System Configuration Repair

System configuration languages provide powerful abstractions that simplify managing large-scale, networked systems. Thousands of organizations now use configuration languages, such as Puppet. However, specifications written in configuration languages can have bugs and the shell remains the simplest way to debug a misconfigured system. Unfortunately, it is unsafe to use the shell to fix problems when a system configuration language is in use: a fix applied from the shell may cause the system to drift from the state specified by the configuration language. Thus, despite their advantages, configuration languages force system administrators to give up the simplicity and familiarity of the shell. This paper presents a synthesis-based technique that allows administrators to use configuration languages and the shell in harmony. Administrators can fix errors using the shell and the technique automatically repairs the higher-level specification written in the configuration language. The approach (1) produces repairs that are consistent with the fix made using the shell; (2) produces repairs that are maintainable by minimizing edits made to the original specification; (3) ranks and presents multiple repairs when relevant; and (4) supports all shells the administrator may wish to use. We implement our technique for Puppet, a widely used system configuration language, and evaluate it on a suite of benchmarks under 42 repair scenarios. The top-ranked repair is selected by humans 76% of the time and the human-equivalent repair is ranked 1.31 on average.Comment: Published version in proceedings of IEEE/ACM International Conference on Automated Software Engineering (ASE) 201

Magnetic Fields Recorded by Chondrules Formed in Nebular Shocks

Recent laboratory efforts (Fu et al., 2014) have constrained the remanent magnetizations of chondrules and the magnetic field strengths at which the chondrules were exposed to as they cooled below their Curie points. An outstanding question is whether the inferred paleofields represent the background magnetic field of the solar nebula or were unique to the chondrule-forming environment. We investigate the amplification of the magnetic field above background values for two proposed chondrule formation mechanisms, large-scale nebular shocks and planetary bow shocks. Behind large-scale shocks, the magnetic field parallel to the shock front is amplified by factors $\sim 10-30$, regardless of the magnetic diffusivity. Therefore, chondrules melted in these shocks probably recorded an amplified magnetic field. Behind planetary bow shocks, the field amplification is sensitive to the magnetic diffusivity. We compute the gas properties behind a bow shock around a 3000 km-radius planetary embryo, with and without atmospheres, using hydrodynamics models. We calculate the ionization state of the hot, shocked gas, including thermionic emission from dust, and thermal ionization of gas-phase potassium atoms, and the magnetic diffusivity due to Ohmic dissipation and ambipolar diffusion. We find that the diffusivity is sufficiently large that magnetic fields have already relaxed to background values in the shock downstream where chondrules acquire magnetizations, and that these locations are sufficiently far from the planetary embryos that chondrules should not have recorded a significant putative dynamo field generated on these bodies. We conclude that, if melted in planetary bow shocks, chondrules probably recorded the background nebular field.Comment: 17 pages, 11 figures, accepted for publication in Ap

A Method for Fast, High-Precision Characterization of Synthetic Biology Devices

Engineering biological systems with predictable behavior is a foundational goal of synthetic biology. To accomplish this, it is important to accurately characterize the behavior of biological devices. Prior characterization efforts, however, have generally not yielded enough high-quality information to enable compositional design. In the TASBE (A Tool-Chain to Accelerate Synthetic Biological Engineering) project we have developed a new characterization technique capable of producing such data. This document describes the techniques we have developed, along with examples of their application, so that the techniques can be accurately used by others

First measurements of high frequency cross-spectra from a pair of large Michelson interferometers

Measurements are reported of the cross-correlation of spectra of differential position signals from the Fermilab Holometer, a pair of co-located 39 m long, high power Michelson interferometers with flat, broadband frequency response in the MHz range. The instrument obtains sensitivity to high frequency correlated signals far exceeding any previous measurement in a broad frequency band extending beyond the 3.8 MHz inverse light crossing time of the apparatus. The dominant but uncorrelated shot noise is averaged down over $2\times 10^8$ independent spectral measurements with 381 Hz frequency resolution to obtain $2.1\times 10^{-20} \ \mathrm{m}/\sqrt{\mathrm{Hz}}$ sensitivity to stationary signals. For signal bandwidths $\Delta f > 11$ kHz, the sensitivity to strain $h$ or shear power spectral density of classical or exotic origin surpasses a milestone $PSD_{\delta h} < t_p$ where $t_p= 5.39\times 10^{-44}/\mathrm{Hz}$ is the Planck time.Comment: 5 pages, 3 figure

Self-trapping dynamics in a 2D optical lattice

We describe theoretical models for the recent experimental observation of Macroscopic Quantum Self-Trapping (MQST) in the transverse dynamics of an ultracold bosonic gas in a 2D lattice. The pure mean-field model based on the solution of coupled nonlinear equations fails to reproduce the experimental observations. It greatly overestimates the initial expansion rates at short times and predicts a slower expansion rate of the cloud at longer times. It also predicts the formation of a hole surrounded by a steep square fort-like barrier which was not observed in the experiment. An improved theoretical description based on a simplified Truncated Wigner Approximation (TWA), which adds phase and number fluctuations in the initial conditions, pushes the theoretical results closer to the experimental observations but fails to quantitatively reproduce them. An explanation of the delayed expansion as a consequence of a new type of self-trapping mechanism, where quantum correlations suppress tunneling even when there are no density gradients, is discussed and supported by numerical time-dependent Density Matrix Renormalization Group (t-DMRG) calculations performed in a simplified two coupled tubes set-up

Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer.

Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC

High-throughput smFRET analysis of freely diffusing nucleic acid molecules and associated proteins

Single-molecule Förster resonance energy transfer (smFRET) is a powerful technique for nanometer-scale studies of single molecules. Solution-based smFRET, in particular, can be used to study equilibrium intra- and intermolecular conformations, binding/unbinding events and conformational changes under biologically relevant conditions without ensemble averaging. However, single-spot smFRET measurements in solution are slow. Here, we detail a high-throughput smFRET approach that extends the traditional single-spot confocal geometry to a multispot one. The excitation spots are optically conjugated to two custom silicon single photon avalanche diode (SPAD) arrays. Two-color excitation is implemented using a periodic acceptor excitation (PAX), allowing distinguishing between singly- and doubly-labeled molecules. We demonstrate the ability of this setup to rapidly and accurately determine FRET efficiencies and population stoichiometries by pooling the data collected independently from the multiple spots. We also show how the high throughput of this approach can be used o increase the temporal resolution of single-molecule FRET population characterization from minutes to seconds. Combined with microfluidics, this high-throughput approach will enable simple real-time kinetic studies as well as powerful molecular screening applications

(Correcting) misdiagnoses of asthma: A cost effectiveness analysis

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The prevalence of physician-diagnosed-asthma has risen over the past three decades and misdiagnosis of asthma is potentially common. Objective: to determine whether a secondary-screening-program to establish a correct diagnosis of asthma in those who report a physician diagnosis of asthma is cost effective.Method: Randomly selected physician-diagnosed-asthmatic subjects from 8 Canadian cities were studied with an extensive diagnostic algorithm to rule-in, or rule-out, a correct diagnosis of asthma. Subjects in whom the diagnosis of asthma was excluded were followed up for 6-months and data on asthma medications and heath care utilization was obtained. Economic analysis was performed to estimate the incremental lifetime costs associated with secondary screening of previously diagnosed asthmatic subjects. Analysis was from the perspective of the Canadian healthcare system and is reported in Canadian dollars.Results: Of 540 randomly selected patients with physician diagnosed asthma 150 (28%; 95%CI 19-37%) did not have asthma when objectively studied. 71% of these misdiagnosed patients were on some asthma medications. Incorporating the incremental cost of secondary-screening for the diagnosis of asthma, we found that the average cost savings per 100 individuals screened was $35,141 (95$4,588-$69,278).Conclusion: Cost savings primarily resulted from lifetime costs of medication use averted in those who had been misdiagnosed.This work was funded by the Canadian Institute of Health Research, Canada and the University Of Ottawa Division Of Respiratory Medicine