Formal Verification of Astronaut-Rover Teams for Planetary Surface Operations

This paper describes an approach to assuring the reliability of autonomous systems for Astronaut-Rover (ASRO) teams using the formal verification of models in the Brahms multi-agent modelling language. Planetary surface rovers have proven essential to several manned and unmanned missions to the moon and Mars. The first rovers were tele- or manuallyoperated, but autonomous systems are increasingly being used to increase the effectiveness and range of rover operations on missions such as the NASA Mars Science Laboratory. It is anticipated that future manned missions to the moon and Mars will use autonomous rovers to assist astronauts during extravehicular activity (EVA), including science, technical and construction operations. These ASRO teams have the potential to significantly increase the safety and efficiency of surface operations. We describe a new Brahms model in which an autonomous rover may perform several different activities including assisting an astronaut during EVA. These activities compete for the autonomous rovers “attention’ and therefore the rover must decide which activity is currently the most important and engage in that activity. The Brahms model also includes an astronaut agent, which models an astronauts predicted behaviour during an EVA. The rover must also respond to the astronauts activities. We show how this Brahms model can be simulated using the Brahms integrated development environment. The model can then also be formally verified with respect to system requirements using the SPIN model checker, through automatic translation from Brahms to PROMELA (the input language for SPIN). We show that such formal verification can be used to determine that mission- and safety critical operations are conducted correctly, and therefore increase the reliability of autonomous systems for planetary rovers in ASRO teams

Assessing Retinal Structure In Complete Congenital Stationary Night Blindness and Oguchi Disease

Purpose To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. Design Prospective, observational case series. Methods We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. Results Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. Conclusions The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus

Verifiable self-certifying autonomous systems

Autonomous systems are increasingly being used in safety-and mission-critical domains, including aviation, manufacturing, healthcare and the automotive industry. Systems for such domains are often verified with respect to essential requirements set by a regulator, as part of a process called certification. In principle, autonomous systems can be deployed if they can be certified for use. However, certification is especially challenging as the condition of both the system and its environment will surely change, limiting the effective use of the system. In this paper we discuss the technological and regulatory background for such systems, and introduce an architectural framework that supports verifiably-correct dynamic self-certification by the system, potentially allowing deployed systems to operate more safely and effectively

Evaluating Large Spontaneous Deletions in a Bovine Cell Line Selected for Bovine Viral Diarrhea Virus Resistance

Bovine viral diarrhea virus’s (BVDV) entry into bovine cells involves attachment of virions to cellular receptors, internalization, and pH-dependent fusion with endosomal membranes. The primary host receptor for BVDV is CD46; however, the complete set of host factors required for virus entry is unknown. The Madin-Darby bovine kidney (MDBK) cell line is susceptible to BVDV infection, while a derivative cell line (CRIB) is resistant at the level of virus entry. We performed complete genome sequencing of each to identify genomic variation underlying the resistant phenotype with the aim of identifying host factors essential for BVDV entry. Three large compound deletions in the BVDV-resistant CRIB cell line were identified and predicted to disrupt the function or expression of the genes PTPN12, GRID2, and RABGAP1L. However, CRISPR/Cas9 mediated knockout of these genes, individually or in combination, in the parental MDBK cell line did not impact virus entry or replication. Therefore, resistance to BVDV in the CRIB cell line is not due to the apparent spontaneous loss of PTPN12, GRID2, or RABGAP1L gene function. Identifying the functional cause of BVDV resistance in the CRIB cell line may require more detailed comparisons of the genomes and epigenomes

A Review of Verification and Validation for Space Autonomous Systems

From Springer Nature via Jisc Publications RouterHistory: registration 2021-05-13, accepted 2021-05-13, online 2021-06-18, pub-electronic 2021-06-18, pub-print 2021-09Publication status: PublishedFunder: Engineering and Physical Sciences Research Council; doi: https://doi.org/10.13039/501100000266; Grant(s): EP/R026092/1Abstract: Purpose of Review: The deployment of hardware (e.g., robots, satellites, etc.) to space is a costly and complex endeavor. It is of extreme importance that on-board systems are verified and validated through a variety of verification and validation techniques, especially in the case of autonomous systems. In this paper, we discuss a number of approaches from the literature that are relevant or directly applied to the verification and validation of systems in space, with an emphasis on autonomy. Recent Findings: Despite advances in individual verification and validation techniques, there is still a lack of approaches that aim to combine different forms of verification in order to obtain system-wide verification of modular autonomous systems. Summary: This systematic review of the literature includes the current advances in the latest approaches using formal methods for static verification (model checking and theorem proving) and runtime verification, the progress achieved so far in the verification of machine learning, an overview of the landscape in software testing, and the importance of performing compositional verification in modular systems. In particular, we focus on reporting the use of these techniques for the verification and validation of systems in space with an emphasis on autonomy, as well as more general techniques (such as in the aeronautical domain) that have been shown to have potential value in the verification and validation of autonomous systems in space

Efficient transplacental IgG transfer in women infected with Zika virus during pregnancy

Zika virus (ZIKV) is a newly-identified infectious cause of congenital disease. Transplacental transfer of maternal IgG to the fetus plays an important role in preventing many neonatal infections. However, antibody transfer may also have negative consequences, such as mediating enhancement of flavivirus infections in early life, or trafficking of virus immune complexes to the fetal compartment. ZIKV infection produces placental pathology which could lead to impaired IgG transfer efficiency as occurs in other maternal infections, such as HIV-1 and malaria. In this study, we asked whether ZIKV infection during pregnancy impairs transplacental transfer of IgG. We enrolled pregnant women with fever or rash in a prospective cohort in Vitoria, Brazil during the recent ZIKV epidemic. ZIKV and dengue virus (DENV)-specific IgG, ZIKV and DENV neutralizing antibodies, and routine vaccine antigenspecific IgG were measured in maternal samples collected around delivery and 20 paired cord blood samples. We concluded that 8 of these mothers were infected with ZIKV during pregnancy and 12 were ZIKV-uninfected. The magnitude of flavivirus-specific IgG, neutralizing antibody, and vaccine-elicited IgG were highly correlated between maternal plasma and infant cord blood in both ZIKV-infected and -uninfected mother-infant pairs. Moreover, there was no difference in the magnitude of plasma flavivirus-specific IgG levels between mothers and infants regardless of ZIKV infection status. Our data suggests that maternal ZIKV infection during pregnancy does not impair the efficiency of placental transfer of flavivirus-specific, functional, and vaccine-elicited IgG. These findings have implications for the neonatal outomes of maternal ZIKV infection and optimal administration of antibody-based ZIKV vaccines and therapeutics

Efficient nonmeiotic allele introgression in livestock using custom endonucleases

We have expanded the livestock gene editing toolbox to include transcription activator-like (TAL) effector nuclease (TALEN)- and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-stimulated homology-directed repair (HDR) using plasmid, rAAV, and oligonucleotide templates. Toward the genetic dehorning of dairy cattle, we introgressed a bovine POLLED allele into horned bull fibroblasts. Single nucleotide alterations or small indels were introduced into 14 additional genes in pig, goat, and cattle fibroblasts using TALEN mRNA and oligonucleotide transfection with efficiencies of 10–50% in populations. Several of the chosen edits mimic naturally occurring performance-enhancing or disease- resistance alleles, including alteration of single base pairs. Up to 70% of the fibroblast colonies propagated without selection harbored the intended edits, of which more than one-half were homozygous. Edited fibroblasts were used to generate pigs with knockout alleles in the DAZL and APC genes to model infertility and colon cancer. Our methods enable unprecedented meiosis-free intraspecific and interspecific introgression of select alleles in livestock for agricultural and biomedical applications

First gene-edited calf with reduced susceptibility to a major viral pathogen

Bovine viral diarrhea virus (BVDV) is one of the most important viruses affecting the health and well-being of bovine species throughout the world. Here, we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with a six amino acid substitution in the BVDV binding domain of bovine CD46. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by reduced clinical signs and the lack of viral infection in white blood cells. The edited calf has no off-target edits and appears normal and healthy at 20 months of age without obvious adverse effects from the on-target edit. This precision bred, proof-of-concept animal provides the first evidence that intentional genome alterations in the CD46 gene may reduce the burden of BVDV-associated diseases in cattle and is consistent with our stepwise, in vitro and ex vivo experiments with cell lines and matched fetal clones

People and Things on the Move: Domestic Material Culture, Poverty and Mobility in Victorian London

© 2016, The Author(s). The development of what Mayne and Lawrence (Urban History 26: 325–48, 1999) termed “ethnographic” approaches to studying nineteenth-century households and urban communities has gathered momentum in recent years. As such research agendas have taken hold and been applied to new contexts, so critiques, methodological developments, and new intellectual and theoretical currents, have provided opportunities to enhance and develop approaches. This article contributes to this on-going process. Drawing upon household archaeological research on Limehouse, a poor neighborhood in Victorian London, and inspired by the theoretical insights provided by the “new mobilities paradigm,” it aims to place “mobility” as a central and enabling intellectual framework for understanding the relationships between people, place, and poverty. Poor communities in nineteenth-century cities were undeniably mobile and transient. Historians and archaeologists have often regarded this mobility as an obstacle to studying everyday life in such contexts. However, examining temporal routines and geographical movements across a variety of time frames and geographical scales, this article argues that mobility is actually key to understanding urban life and an important mechanism for interpreting the fragmented material and documentary traces left by poor households in the nineteenth-century metropolis.We are grateful to the UK’s Arts and Humanities Research Council who funded the research upon which this paper is based (Grant Reference AH/E002285/1): ‘Living in Victorian London: Towards a Material History of Everyday Domestic Life in the Nineteenth-Century Metropolis