Galileo mission planning for Low Gain Antenna based operations

The Galileo mission operations concept is undergoing substantial redesign, necessitated by the deployment failure of the High Gain Antenna, while the spacecraft is on its way to Jupiter. The new design applies state-of-the-art technology and processes to increase the telemetry rate available through the Low Gain Antenna and to increase the information density of the telemetry. This paper describes the mission planning process being developed as part of this redesign. Principal topics include a brief description of the new mission concept and anticipated science return (these have been covered more extensively in earlier papers), identification of key drivers on the mission planning process, a description of the process and its implementation schedule, a discussion of the application of automated mission planning tool to the process, and a status report on mission planning work to date. Galileo enhancements include extensive reprogramming of on-board computers and substantial hard ware and software upgrades for the Deep Space Network (DSN). The principal mode of operation will be onboard recording of science data followed by extended playback periods. A variety of techniques will be used to compress and edit the data both before recording and during playback. A highly-compressed real-time science data stream will also be important. The telemetry rate will be increased using advanced coding techniques and advanced receivers. Galileo mission planning for orbital operations now involves partitioning of several scarce resources. Particularly difficult are division of the telemetry among the many users (eleven instruments, radio science, engineering monitoring, and navigation) and allocation of space on the tape recorder at each of the ten satellite encounters. The planning process is complicated by uncertainty in forecast performance of the DSN modifications and the non-deterministic nature of the new data compression schemes. Key mission planning steps include quantifying resource or capabilities to be allocated, prioritizing science observations and estimating resource needs for each, working inter-and intra-orbit trades of these resources among the Project elements, and planning real-time science activity. The first major mission planning activity, a high level, orbit-by-orbit allocation of resources among science objectives, has already been completed; and results are illustrated in the paper. To make efficient use of limited resources, Galileo mission planning will rely on automated mission planning tools capable of dealing with interactions among time-varying downlink capability, real-time science and engineering data transmission, and playback of recorded data. A new generic mission planning tool is being adapted for this purpose

The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa

Transthyretin (TTR) pV142I (rs76992529-A) is one of the 113 variants in the human TTR gene associated with systemic amyloidosis. It results from a G to A transition at a CG dinucleotide in the codon for amino acid 122 of the mature protein (TTR V122I). The allele frequency is 0.0173 in African Americans

Is it possible to separate the graft-versus-leukemia (GVL) effect against B cell acute lymphoblastic leukemia from graft-versus-host disease (GVHD) after hematopoietic cell transplant?

Hematopoietic cell transplant is a curative therapy for many pediatric patients with high risk acute lymphoblastic leukemia. Its therapeutic mechanism is primarily based on the generation of an alloreactive graft-versus-leukemia effect that can eliminate residual leukemia cells thus preventing relapse. However its efficacy is diminished by the concurrent emergence of harmful graft-versus-host disease disease which affects healthly tissue leading to significant morbidity and mortality. The purpose of this review is to describe the interventions that have been trialed in order to augment the beneficial graft-versus leukemia effect post-hematopoietic cell transplant while limiting the harmful consequences of graft-versus-host disease. This includes many emerging and promising strategies such a

Highly conserved molecular pathways, including Wnt signaling, promote functional recovery from spinal cord injury in lampreys

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 8 (2018): 742, doi:10.1038/s41598-017-18757-1.In mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and synaptic connections, and consequently function. Unlike mammals, lampreys are vertebrates that undergo spontaneous regeneration and achieve functional recovery after SCI. Therefore our goal was to determine the complete transcriptional responses that occur after SCI in lampreys and to identify deeply conserved pathways that promote regeneration. We performed RNA-Seq on lamprey spinal cord and brain throughout the course of functional recovery. We describe complex transcriptional responses in the injured spinal cord, and somewhat surprisingly, also in the brain. Transcriptional responses to SCI in lampreys included transcription factor networks that promote peripheral nerve regeneration in mammals such as Atf3 and Jun. Furthermore, a number of highly conserved axon guidance, extracellular matrix, and proliferation genes were also differentially expressed after SCI in lampreys. Strikingly, ~3% of differentially expressed transcripts belonged to the Wnt pathways. These included members of the Wnt and Frizzled gene families, and genes involved in downstream signaling. Pharmacological inhibition of Wnt signaling inhibited functional recovery, confirming a critical role for this pathway. These data indicate that molecular signals present in mammals are also involved in regeneration in lampreys, supporting translational relevance of the model.We gratefully acknowledge support from the National Institutes of Health (R03NS078519 to OB; R01GM104123 to JJS; R01NS078165 to JRM), The Feinstein Institute for Medical Research and The Marine Biological Laboratory, including the Charles Evans Foundation Research Award, the Albert and Ellen Grass Foundation Faculty Research Award, and The Eugene and Millicent Bell Fellowship Fund in Tissue Engineering

Apraxia and motor dysfunction in corticobasal syndrome

Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS.   Methods: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM.   Results: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/2 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices.   Conclusions: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C

The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

Evolutionary autonomous agents and the nature of apraxia

BACKGROUND: Evolutionary autonomous agents are robots or robot simulations whose controller is a dynamical neural network and whose evolution occurs autonomously under the guidance of a fitness function without the detailed or explicit direction of an external programmer. They are embodied agents with a simple neural network controller and as such they provide the optimal forum by which sensorimotor interactions in a specified environment can be studied without the computational assumptions inherent in standard neuroscience. METHODS: Evolutionary autonomous agents were evolved that were able to perform identical movements under two different contexts, one which represented an automatic movement and one which had a symbolic context. In an attempt to model the automatic-voluntary dissociation frequently seen in ideomotor apraxia, lesions were introduced into the neural network controllers resulting in a behavioral dissociation with loss of the ability to perform the movement which had a symbolic context and preservation of the simpler, automatic movement. RESULTS: Analysis of the changes in the hierarchical organization of the networks in the apractic EAAs demonstrated consistent changes in the network dynamics across all agents with loss of longer duration time scales in the network dynamics. CONCLUSION: The concepts of determinate motor programs and perceptual representations that are implicit in the present day understanding of ideomotor apraxia are assumptions inherent in the computational understanding of brain function. The strength of the present study using EAAs to model one aspect of ideomotor apraxia is the absence of these assumptions and a grounding of all sensorimotor interactions in an embodied, autonomous agent. The consistency of the hierarchical changes in the network dynamics across all apractic agents demonstrates that this technique is tenable and will be a valuable adjunct to a computational formalism in the understanding of the physical basis of neurological disorders