Inverse Simulation as a Tool for Fault Detection and Isolation in Planetary Rovers

With manned expeditions to planetary bodies beyond our own and the Moon currently intractable, the onus falls upon robotic systems to explore and analyse extraterrestrial environments such as Mars. These systems typically take the form of wheeled rovers, designed to navigate the difficult terrain of other worlds. Rovers have been used in this role since Lunokhod 1 landed on the Moon in 1970. While early rovers were remote controlled, communication latency with bodies beyond the Moon and the desire to improve mission effectiveness have resulted in increasing autonomy in planetary rovers. With an increase in autonomy, however, comes an increase in complexity. This can have a negative impact on the reliability of the rover system. With a fault-free system an unlikely prospect and human assistance millions of miles away, the rover must have a robust fault detection, isolation and recovery (FDIR) system. The need for comprehensive FDIR is demonstrated by the recent Chinese lunar rover, Yutu (or “Jade Rabbit”). Yutu was rendered immobile 42 days after landing and remained so for the duration of its operational life: 31 months. While its lifespan far exceeded its expected value, Yutu's inability to move severely impaired its ability to perform its mission. This clearly highlights the need for robust FDIR. A common approach to FDIR is through the generation and analysis of residuals. Output residuals may be obtained by comparing the outputs of the system with predictions of those outputs, obtained from a mathematical model of the system which is supplied with the system inputs. Output residuals allow simple detection and isolation of faults at the output of the system. Faults in earlier stages of the system, however, propagate through the system dynamics and can disperse amongst several of the outputs. This problem is exemplified by faults at the input, which can potentially excite every system state and thus manifest in every output residual. Methods exist for decoupling and analysing output residuals such that input faults may be isolated, however, these methods are complex and require comprehensive development and testing. A conceptually simpler approach is presented in this paper. Inverse simulation (InvSim) is a numerical method by which the inputs of a system are obtained for a desired output. It does so by using a Newton-Raphson algorithm to solve a non-linear model of the system for the input. When supplied with the outputs of a fault-afflicted system, InvSim produces the input required to drive a fault-free system to this output. The fault therefore manifests itself in this generated input signal. The InvSim-generated input may then be compared to the true system input to generate input residuals. Just as a fault at an output manifests itself in the residual for that output alone, a fault at an input similarly manifests itself only in the residual for that input. InvSim may also be used to generate residuals at other locations in the system, by considering distinct subsystems with their own inputs and outputs. This ability is tested comprehensively in this paper. Faults are applied to a simulated rover at a variety of locations within the system structure and residuals generated using both InvSim and conventional forward simulation. Residuals generated using InvSim are shown to facilitate detection and isolation of faults in several locations using simple analyses. By contrast, forward simulation requires the use of complex analytical methods such as structured residuals or adaptive thresholds

A Comparison of Forward and Inverse Simulation Methods for Fault Detection on a Rover

Fault tolerant design is hugely important for autonomous mobile robots such as planetary exploration rovers (PERs), as they are required to be both robust and reliable in extremely harsh environments. One of the main principles of fault tolerance is the detection and diagnosis of any faults afflicting the system. A model-based fault detection procedure is presented using forward and inverse simulation methods. The results of each method are compared for faults in different system locations to display the differences and advantages of both methods. It is shown by this comparison that the methods complement each other and can be used concurrently to diagnose output and input faults

Reversible linkage of two distinct small molecule inhibitors of myc generates a dimeric inhibitor with improved potency that is active in myc over-expressing cancer cell lines

We describe the successful application of a novel approach for generating dimeric Myc inhibitors by modifying and reversibly linking two previously described small molecules.We synthesized two directed libraries of monomers, each comprised of a ligand, a connector, and a bioorthogonal linker element, to identify the optimal dimer configuration required to inhibit Myc. We identified combinations of monomers, termed self-assembling dimeric inhibitors, which displayed synergistic inhibition of Myc-dependent cell growth. We confirmed that these dimeric inhibitors directly bind to Myc blocking its interaction with Max and affect transcription of MYC dependent genes. Control combinations that are unable to form a dimer do not show any synergistic effects in these assays. Collectively, these data validate our new approach to generate more potent and selective inhibitors of Myc by self-assembly from smaller, lower affinity components. This approach provides an opportunity for developing novel therapeutics against Myc and other challenging protein:protein interaction (PPI) target classes. © 2015 Wanner et al

The challenges of intersectionality: Researching difference in physical education

Researching the intersection of class, race, gender, sexuality and disability raises many issues for educational research. Indeed, Maynard (2002, 33) has recently argued that ‘difference is one of the most significant, yet unresolved, issues for feminist and social thinking at the beginning of the twentieth century’. This paper reviews some of the key imperatives of working with ‘intersectional theory’ and explores the extent to these debates are informing research around difference in education and Physical Education (PE). The first part of the paper highlights some key issues in theorising and researching intersectionality before moving on to consider how difference has been addressed within PE. The paper then considers three ongoing challenges of intersectionality – bodies and embodiment, politics and practice and empirical research. The paper argues for a continued focus on the specific context of PE within education for its contribution to these questions

Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization†

We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2

Developing mobile applications for and with young people with long-term conditions learning to share their healthcare with professionals: a young person and family-led approach

Although young people are frequent users of mobile devices in day-to-day life, there is little reliable research that actually involves young people with long-term conditions as partners in the development and testing of mobile technology applications to support their health needs. However, the transition from child to adult health services means that young people need to develop their own clinical skills and knowledge so that they can manage their condition in a confident and competent manner. Therefore this area of research is ripe for development. A group involving a patient with juvenile idiopathic arthritis (JIA), a parent, doctors, nurses, researchers and technologists have established a Manchester-based research and development programme on mobile technologies for young people with long term conditions. We have fostered strong partnerships with other national groups to help us agree on research priorities in this important area, and a plan of work to help us achieve these. First we obtained valuable suggestions from a national group of children and young people with JIA on the types of information and tools they would like to see included in a JIA specific mobile application. Next we are reviewing the research evidence to help us in our future work, and working with young people, parents and health professionals to produce a detailed software specification for a prototype application to test with young people. This poster will explore and discuss the progress we have made, with a focus on the central role of young people and their families living with JIA in the project

DNA sequence level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders

Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes

MARIS: Method for Analyzing RNA following Intracellular Sorting

Transcriptional profiling is a key technique in the study of cell biology that is limited by the availability of reagents to uniquely identify specific cell types and isolate high quality RNA from them. We report a Method for Analyzing RNA following Intracellular Sorting (MARIS) that generates high quality RNA for transcriptome profiling following cellular fixation, intracellular immunofluorescent staining and FACS. MARIS can therefore be used to isolate high quality RNA from many otherwise inaccessible cell types simply based on immunofluorescent tagging of unique intracellular proteins. As proof of principle, we isolate RNA from sorted human embryonic stem cell-derived insulin-expressing cells as well as adult human β cells. MARIS is a basic molecular biology technique that could be used across several biological disciplines.Howard Hughes Medical InstituteHarvard Stem Cell InstituteNational Institutes of Health (U.S.) (grant 2U01DK07247307)National Institutes of Health (U.S.) (grant RL1DK081184)National Institutes of Health (U.S.) (grant 1U01HL10040804

The Global Magneto-Ionic Medium Survey: A Faraday Depth Survey of the Northern Sky Covering 1280-1750 MHz

The Galactic interstellar medium hosts a significant magnetic field, which can be probed through the synchrotron emission produced from its interaction with relativistic electrons. Linearly polarized synchrotron emission is generated throughout the Galaxy, and at longer wavelengths, modified along nearly every path by Faraday rotation in the intervening magneto-ionic medium. Full characterization of the polarized emission requires wideband observations with many frequency channels. We have surveyed polarized radio emission from the Northern sky over the the range 1280-1750 MHz, with channel width 236.8 kHz, using the John A. Galt Telescope (diameter 25.6 m) at the Dominion Radio Astrophysical Observatory, as part of the Global Magneto-Ionic Medium Survey. The survey covered 72% of the sky, declinations -30 to +87 degrees at all right ascensions. The intensity scale was absolutely calibrated, based on the flux density and spectral index of Cygnus A. Polarization angle was calibrated using the extended polarized emission of the Fan Region. Data are presented as brightness temperatures with angular resolution 40'. Sensitivity in Stokes Q and U is 45 mK rms in a 1.18 MHz band. We have applied rotation measure synthesis to the data to obtain a Faraday depth cube of resolution 150 radians per square metre and sensitivity 3 mK rms of polarized intensity. Features in Faraday depth up to a width of 110 radians per square metre are represented. The maximum detectable Faraday depth is +/- 20,000 radians per square metre. The survey data are available at the Canadian Astronomy Data Centre.Comment: Accepted for publication in the Astronomical Journa