The Environment for Application Software Integration and Execution (EASIE), version 1.0. Volume 2: Program integration guide

The Environment for Application Software Integration and Execution, EASIE, provides a methodology and a set of software utility programs to ease the task of coordinating engineering design and analysis codes. EASIE was designed to meet the needs of conceptual design engineers that face the task of integrating many stand-alone engineering analysis programs. Using EASIE, programs are integrated through a relational data base management system. In volume 2, the use of a SYSTEM LIBRARY PROCESSOR is used to construct a DATA DICTIONARY describing all relations defined in the data base, and a TEMPLATE LIBRARY. A TEMPLATE is a description of all subsets of relations (including conditional selection criteria and sorting specifications) to be accessed as input or output for a given application. Together, these form the SYSTEM LIBRARY which is used to automatically produce the data base schema, FORTRAN subroutines to retrieve/store data from/to the data base, and instructions to a generic REVIEWER program providing review/modification of data for a given template. Automation of these functions eliminates much of the tedious, error prone work required by the usual approach to data base integration

Surrogate models for precessing binary black hole simulations with unequal masses

Only numerical relativity simulations can capture the full complexities of binary black hole mergers. These simulations, however, are prohibitively expensive for direct data analysis applications such as parameter estimation. We present two new fast and accurate surrogate models for the outputs of these simulations: the first model, NRSur7dq4, predicts the gravitational waveform and the second model, \RemnantModel, predicts the properties of the remnant black hole. These models extend previous 7-dimensional, non-eccentric precessing models to higher mass ratios, and have been trained against 1528 simulations with mass ratios $q\leq4$ and spin magnitudes $\chi_1,\chi_2 \leq 0.8$, with generic spin directions. The waveform model, NRSur7dq4, which begins about 20 orbits before merger, includes all $\ell \leq 4$ spin-weighted spherical harmonic modes, as well as the precession frame dynamics and spin evolution of the black holes. The final black hole model, \RemnantModel, models the mass, spin, and recoil kick velocity of the remnant black hole. In their training parameter range, both models are shown to be more accurate than existing models by at least an order of magnitude, with errors comparable to the estimated errors in the numerical relativity simulations. We also show that the surrogate models work well even when extrapolated outside their training parameter space range, up to mass ratios $q=6$.Comment: Matches published version. Models publicly available at https://zenodo.org/record/3455886#.XZ9s1-dKjBI and https://pypi.org/project/surfinB

Interkingdom Gene Transfer of a Hybrid NPS/PKS from Bacteria to Filamentous Ascomycota

Nonribosomal peptides (NRPs) and polyketides (PKs) are ecologically important secondary metabolites produced by bacteria and fungi using multidomain enzymes called nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), respectively. Previous phylogenetic analyses of fungal NRPSs and PKSs have suggested that a few of these genes were acquired by fungi via horizontal gene transfer (HGT) from bacteria, including a hybrid NPS/PKS found in Cochliobolus heterostrophus (Dothideomycetes, Ascomycota). Here, we identify this hybrid gene in fungi representing two additional classes of Ascomycota (Aspergillus spp., Microsporum canis, Arthroderma spp., and Trichophyton spp., Eurotiomycetes; Chaetomium spp. and Metarhizium spp., Sordariomycetes) and use phylogenetic analyses of the most highly conserved domains from NRPSs (adenylation (A) domain) and PKSs (ketoacyl synthase (KS) domain) to examine the hypothesis that the hybrid NPS7/PKS24 was acquired by fungi from bacteria via HGT relatively early in the evolution of the Pezizomycotina. Our results reveal a unique ancestry of the A domain and KS domain in the hybrid gene relative to known fungal NRPSs and PKSs, provide strong evidence for HGT of the hybrid gene from a putative bacterial donor in the Burkholderiales, and suggest the HGT event occurred early in the evolution of the filamentous Ascomycota

Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4.

While it is recognized that aquaporin-4 (AQP4)-specific T cells and antibodies participate in the pathogenesis of neuromyelitis optica (NMO), a human central nervous system (CNS) autoimmune demyelinating disease, creation of an AQP4-targeted model with both clinical and histologic manifestations of CNS autoimmunity has proven challenging. Immunization of wild-type (WT) mice with AQP4 peptides elicited T cell proliferation, although those T cells could not transfer disease to naïve recipient mice. Recently, two novel AQP4 T cell epitopes, peptide (p) 135-153 and p201-220, were identified when studying immune responses to AQP4 in AQP4-deficient (AQP4-/-) mice, suggesting T cell reactivity to these epitopes is normally controlled by thymic negative selection. AQP4-/- Th17 polarized T cells primed to either p135-153 or p201-220 induced paralysis in recipient WT mice, that was associated with predominantly leptomeningeal inflammation of the spinal cord and optic nerves. Inflammation surrounding optic nerves and involvement of the inner retinal layers (IRL) were manifested by changes in serial optical coherence tomography (OCT). Here, we illustrate the approaches used to create this new in vivo model of AQP4-targeted CNS autoimmunity (ATCA), which can now be employed to study mechanisms that permit development of pathogenic AQP4-specific T cells and how they may cooperate with B cells in NMO pathogenesis

A Numerical Relativity Waveform Surrogate Model for Generically Precessing Binary Black Hole Mergers

A generic, non-eccentric binary black hole (BBH) system emits gravitational waves (GWs) that are completely described by 7 intrinsic parameters: the black hole spin vectors and the ratio of their masses. Simulating a BBH coalescence by solving Einstein's equations numerically is computationally expensive, requiring days to months of computing resources for a single set of parameter values. Since theoretical predictions of the GWs are often needed for many different source parameters, a fast and accurate model is essential. We present the first surrogate model for GWs from the coalescence of BBHs including all $7$ dimensions of the intrinsic non-eccentric parameter space. The surrogate model, which we call NRSur7dq2, is built from the results of $744$ numerical relativity simulations. NRSur7dq2 covers spin magnitudes up to $0.8$ and mass ratios up to $2$, includes all $\ell \leq 4$ modes, begins about $20$ orbits before merger, and can be evaluated in $\sim~50\,\mathrm{ms}$. We find the largest NRSur7dq2 errors to be comparable to the largest errors in the numerical relativity simulations, and more than an order of magnitude smaller than the errors of other waveform models. Our model, and more broadly the methods developed here, will enable studies that would otherwise require millions of numerical relativity waveforms, such as parameter inference and tests of general relativity with GW observations.Comment: 10 pages, 5 figures; Added report numbe

Overview of the spectrometer optical fiber feed for the Habitable-zone Planet Finder

The Habitable-zone Planet Finder (HPF) is a highly stabilized fiber fed precision radial velocity (RV) spectrograph working in the Near Infrared (NIR): 810 - 1280 nm . In this paper we present an overview of the preparation of the optical fibers for HPF. The entire fiber train from the telescope focus down to the cryostat is detailed. We also discuss the fiber polishing, splicing and its integration into the instrument using a fused silica puck. HPF was designed to be able to operate in two modes, High Resolution (HR- the only mode mode currently commissioned) and High Efficiency (HE). We discuss these fiber heads and the procedure we adopted to attach the slit on to the HR fibers.Comment: Presented at 2018 SPIE Astronomical Telescopes + Instrumentation, Austin, Texas, USA. 18 pages, 25 figures, and 2 table

HLA-DO modulates the diversity of the MHC-II self-peptidome

Presentation of antigenic peptides on MHC-II molecules is essential for tolerance to self and for initiation of immune responses against foreign antigens. DO (HLA-DO in humans, H2-O in mice) is a non-classical MHC-II protein that has been implicated in control of autoimmunity and regulation of neutralizing antibody responses to viruses. These effects likely are related to a role of DO in selecting MHC-II epitopes, but previous studies examining the effect of DO on presentation of selected CD4 T cell epitopes have been contradictory. To understand how DO modulates MHC-II antigen presentation, we characterized the full spectrum of peptides presented by MHC-II molecules expressed by DO-sufficient and DO-deficient antigen-presenting cells in vivo and in vitro using quantitative mass spectrometry approaches. We found that DO controlled the diversity of the presented peptide repertoire, with a subset of peptides presented only when DO was expressed. Antigen-presenting cells express another non-classical MHC-II protein, DM, which acts as a peptide editor by preferentially catalyzing the exchange of less stable MHC-II peptide complexes, and which is inhibited when bound to DO. Peptides presented uniquely in the presence of DO were sensitive to DM-mediated exchange, suggesting that decreased DM editing was responsible for the increased diversity. DO-deficient mice mounted CD4 T cell responses against wild-type antigen-presenting cells, but not vice versa, indicating that DO-dependent alterations in the MHC-II peptidome could be recognized by circulating T cells. These data suggest that cell-specific and regulated expression of HLA-DO serves to fine-tune MHC-II peptidomes, to enhance self-tolerance to a wide spectrum of epitopes while allowing focused presentation of immunodominant epitopes during an immune response

Surrogate model of hybridized numerical relativity binary black hole waveforms

Numerical relativity (NR) simulations provide the most accurate binary black hole gravitational waveforms, but are prohibitively expensive for applications such as parameter estimation. Surrogate models of NR waveforms have been shown to be both fast and accurate. However, NR-based surrogate models are limited by the training waveforms' length, which is typically about 20 orbits before merger. We remedy this by hybridizing the NR waveforms using both post-Newtonian and effective one body waveforms for the early inspiral. We present NRHybSur3dq8, a surrogate model for hybridized nonprecessing numerical relativity waveforms, that is valid for the entire LIGO band (starting at $20~\text{Hz}$) for stellar mass binaries with total masses as low as $2.25\,M_{\odot}$. We include the $\ell \leq 4$ and $(5,5)$ spin-weighted spherical harmonic modes but not the $(4,1)$ or $(4,0)$ modes. This model has been trained against hybridized waveforms based on 104 NR waveforms with mass ratios $q\leq8$, and $|\chi_{1z}|,|\chi_{2z}| \leq 0.8$, where $\chi_{1z}$ ($\chi_{2z}$) is the spin of the heavier (lighter) BH in the direction of orbital angular momentum. The surrogate reproduces the hybrid waveforms accurately, with mismatches $\lesssim 3\times10^{-4}$ over the mass range $2.25M_{\odot} \leq M \leq 300 M_{\odot}$. At high masses ($M\gtrsim40M_{\odot}$), where the merger and ringdown are more prominent, we show roughly two orders of magnitude improvement over existing waveform models. We also show that the surrogate works well even when extrapolated outside its training parameter space range, including at spins as large as 0.998. Finally, we show that this model accurately reproduces the spheroidal-spherical mode mixing present in the NR ringdown signal.Comment: Matches PRD version. Model publicly available at https://zenodo.org/record/2549618#.XJvMrutKii4. 18 pages, 12 figure