Asymmetrical booster ascent guidance and control system design study. Volume 2: SSFS math models - Ascent

The engineering equations and mathematical models developed for use in the space shuttle functional simulator (SSFS) are presented, and include extensive revisions and additions to earlier documentation. Definitions of coordinate systems used by the SSFS models and coordinate tranformations are given, along with documentation of the flexible body mathematical models. The models were incorporated in the SSFS and are in the checkout stage

redstarts (Setophaga ruticilla)

Breeding dispersions and site fidelity of America

Asymmetrical booster guidance and control system design study. Volume 3: Space shuttle vehicle SRB actuator failure study

The investigation of single actuator failures on the space shuttle solid rocket booster required the analysis of both square pattern and diamond pattern actuator configurations. It was determined that for failures occuring near or prior to the region of maximum dynamic pressure, control gain adjustments can be used to achieve virtually nominal mid-boost vehicle behavior. A distinct worst case failure condition was established near staging that could significantly delay staging. It is recommended that the square pattern be retained as a viable alternative to the baseline diamond pattern because the staging transient is better controlled resulting in earlier staging

Asymmetrical booster ascent guidance and control system design study. Volume 1: Summary

Dynamics and control, stability, and guidance analyses are summarized for the asymmetrical booster ascent guidance and control system design studies, performed in conjunction with space shuttle planning. The mathematical models developed for use in rigid body and flexible body versions of the NASA JSC space shuttle functional simulator are briefly discussed, along with information on the following: (1) space shuttle stability analysis using equations of motion for both pitch and lateral axes; (2) the computer program used to obtain stability margin; and (3) the guidance equations developed for the space shuttle powered flight phases

Different contributions of primary motor cortex, reticular formation, and spinal cord to fractionated muscle activation

Coordinated movement requires patterned activation of muscles. In this study, we examined differences in selective activation of primate upper limb muscles by cortical and subcortical regions. Five macaque monkeys were trained to perform a reach and grasp task, and electromyogram (EMG) was recorded from 10 to 24 muscles while weak single-pulse stimuli were delivered through microelectrodes inserted in the motor cortex (M1), reticular formation (RF), or cervical spinal cord (SC). Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked effects were assessed from averages of rectified EMG. M1, RF, and SC activated 1.5 ± 0.9, 1.9 ± 0.8, and 2.5 ± 1.6 muscles per site (means ± SD); only M1 and SC differed significantly. In between recording sessions, natural muscle activity in the home cage was recorded using a miniature data logger. A novel analysis assessed how well natural activity could be reconstructed by stimulus-evoked responses. This provided two measures: normalized vector length L, reflecting how closely aligned natural and stimulus-evoked activity were, and normalized residual R, measuring the fraction of natural activity not reachable using stimulus-evoked patterns. Average values for M1, RF, and SC were L = 119.1 ± 9.6, 105.9 ± 6.2, and 109.3 ± 8.4% and R = 50.3 ± 4.9, 56.4 ± 3.5, and 51.5 ± 4.8%, respectively. RF was significantly different from M1 and SC on both measurements. RF is thus able to generate an approximation to the motor output with less activation than required by M1 and SC, but M1 and SC are more precise in reaching the exact activation pattern required. Cortical, brainstem, and spinal centers likely play distinct roles, as they cooperate to generate voluntary movements. NEW & NOTEWORTHY Brainstem reticular formation, primary motor cortex, and cervical spinal cord intermediate zone can all activate primate upper limb muscles. However, brainstem output is more efficient but less precise in producing natural patterns of motor output than motor cortex or spinal cord. We suggest that gross muscle synergies from the reticular formation are sculpted and refined by motor cortex and spinal circuits to reach the finely fractionated output characteristic of dexterous primate upper limb movements

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

HOLISMOKES -- II. Identifying galaxy-scale strong gravitational lenses in Pan-STARRS using convolutional neural networks

We present a systematic search for wide-separation (Einstein radius >1.5"), galaxy-scale strong lenses in the 30 000 sq.deg of the Pan-STARRS 3pi survey on the Northern sky. With long time delays of a few days to weeks, such systems are particularly well suited for catching strongly lensed supernovae with spatially-resolved multiple images and open new perspectives on early-phase supernova spectroscopy and cosmography. We produce a set of realistic simulations by painting lensed COSMOS sources on Pan-STARRS image cutouts of lens luminous red galaxies with known redshift and velocity dispersion from SDSS. First of all, we compute the photometry of mock lenses in gri bands and apply a simple catalog-level neural network to identify a sample of 1050207 galaxies with similar colors and magnitudes as the mocks. Secondly, we train a convolutional neural network (CNN) on Pan-STARRS gri image cutouts to classify this sample and obtain sets of 105760 and 12382 lens candidates with scores pCNN>0.5 and >0.9, respectively. Extensive tests show that CNN performances rely heavily on the design of lens simulations and choice of negative examples for training, but little on the network architecture. Finally, we visually inspect all galaxies with pCNN>0.9 to assemble a final set of 330 high-quality newly-discovered lens candidates while recovering 23 published systems. For a subset, SDSS spectroscopy on the lens central regions proves our method correctly identifies lens LRGs at z~0.1-0.7. Five spectra also show robust signatures of high-redshift background sources and Pan-STARRS imaging confirms one of them as a quadruply-imaged red source at z_s = 1.185 strongly lensed by a foreground LRG at z_d = 0.3155. In the future, we expect that the efficient and automated two-step classification method presented in this paper will be applicable to the deeper gri stacks from the LSST with minor adjustments.Comment: 18 pages and 11 figures (plus appendix), submitted to A&

Hepatitis C Virus Indirectly Disrupts DNA Damage-Induced p53 Responses by Activating Protein Kinase R

ABSTRACT Many DNA tumor viruses promote cellular transformation by inactivating the critically important tumor suppressor protein p53. In contrast, it is not known whether p53 function is disrupted by hepatitis C virus (HCV), a unique, oncogenic RNA virus that is the leading infectious cause of liver cancer in many regions of the world. Here we show that HCV-permissive, liver-derived HepG2 cells engineered to constitutively express microRNA-122 (HepG2/miR-122 cells) have normal p53-mediated responses to DNA damage and that HCV replication in these cells potently suppresses p53 responses to etoposide, an inducer of DNA damage, or nutlin-3, an inhibitor of p53 degradation pathways. Upregulation of p53-dependent targets is consequently repressed within HCV-infected cells, with potential consequences for cell survival. Despite this, p53 function is not disrupted by overexpression of the complete HCV polyprotein, suggesting that altered p53 function may result from the host response to viral RNA replication intermediates. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated ablation of double-stranded RNA (dsRNA)-activated protein kinase R (PKR) restored p53 responses while boosting HCV replication, showing that p53 inhibition results directly from viral activation of PKR. The hepatocellular abundance of phosphorylated PKR is elevated in HCV-infected chimpanzees, suggesting that PKR activation and consequent p53 inhibition accompany HCV infection in vivo . These findings reveal a feature of the host response to HCV infection that may contribute to hepatocellular carcinogenesis. IMPORTANCE Chronic infection with hepatitis C virus (HCV) is the leading cause of liver cancer in most developed nations. However, the mechanisms whereby HCV infection promotes carcinogenesis remain unclear. Here, we demonstrate that HCV infection inhibits the activation of p53 following DNA damage. Contrary to previous reports, HCV protein expression is insufficient to inhibit p53. Rather, p53 inhibition is mediated by cellular protein kinase R (PKR), which is activated by HCV RNA replication and subsequently suppresses global protein synthesis. These results redefine our understanding of how HCV infection influences p53 function. We speculate that persistent disruption of p53-mediated DNA damage responses may contribute to hepatocellular carcinogenesis in chronically infected individuals

Some Remarks on the Question of Charge Densities in Stationary-Current-Carrying Conductors

Recently, some discussions arose as to the definition of charge and the value of the density of charge in stationary-current-carrying conductors. We stress that the problem of charge definition comes from a misunderstanding of the usual definition. We provide some theoretical elements which suggest that positive and negative charge densities are equal in the frame of the positive ions.Comment: 14 pages, TeX, macro newsym.tex include

Evolutionary pathways to NS5A inhibitor resistance in genotype 1 hepatitis C virus

Direct-acting antivirals (DAAs) targeting NS5A are broadly effective against hepatitis C virus (HCV) infections, but sustained virological response rates are generally lower in patients infected with genotype (gt)-1a than gt-1b viruses. The explanation for this remains uncertain. Here, we adopted a highly accurate, ultra-deep primer ID sequencing approach to intensively study serial changes in the NS5A-coding region of HCV in gt-1a- and gt-1b-infected subjects receiving a short course of monotherapy with the NS5A inhibitor, elbasvir. Low or undetectable levels of viremia precluded on-treatment analysis in gt-1b-infected subjects, but variants with the resistance-associated substitution (RAS) Y93H in NS5A dominated rebounding virus populations following cessation of treatment. These variants persisted until the end of the study, two months later. In contrast, while Y93H emerged in multiple lineages and became dominant in subjects with gt-1a virus, these haplotypes rapidly decreased in frequency off therapy. Substitutions at Q30 and L31 emerged in distinctly independent lineages at later time points, ultimately coming to dominate the virus population off therapy. Consistent with this, cell culture studies with gt-1a and gt-1b reporter viruses and replicons demonstrated that Y93H confers a much greater loss of replicative fitness in gt-1a than gt-1b virus, and that L31M/V both compensates for the loss of fitness associated with Q30R (but not Y93H) and also boosts drug resistance. These observations show how differences in the impact of RASs on drug resistance and replicative fitness influence the evolution of gt-1a and gt-1b viruses during monotherapy with an antiviral targeting NS5A. © 2018 Elsevier B.V