Using Galvanic Vestibular Stimulation to Induce Post-Roll Illusion in a Fixed-Base Flight Simulator

INTRODUCTION: The illusions of head motion induced by galvanic vestibular stimulation (GVS) can be used to compromise flight performance of pilots in fixed-base simulators. However, the stimuli used in the majority of studies fail to mimic disorientation in realistic flight because they are independent from the simulated aircraft motion. This study investigated the potential of bilateral-bipolar GVS coupled to aircraft roll in a fixed-base simulator to mimic vestibular spatial disorientation illusions, specifically the “post-roll illusion” observed during flight.METHODS: There were 14 nonpilot subjects exposed to roll stimuli in a flight simulator operating in a fixed-base mode. GVS was delivered via carbon rubber electrodes on the mastoid processes. The electrical stimulus was driven by the high-pass filtered aircraft roll rate to mimic the semicircular canals’ physiological response. The post-roll test scenarios excluded outside visual cues or instruments and required subjects to actively maintain a constant bank angle after an abrupt stop following a passive prolonged roll maneuver. The anticipated outcome was an overshot in roll elicited by the GVS signal. RESULTS: The responses across subjects showed large variability, with less than a third aligning with the post-roll illusion. Subjective ratings suggest that the high-pass filtered GVS stimuli were mild and did not induce a clear sense of roll direction. However, uncontrolled head movements during stimulation might have obscured the intended effects of GVS-evoked illusory head movements. CONCLUSION: The mild and transient GVS stimuli used in this study, together with the uncontrolled head movements, did not convincingly mimic the post-roll illusion.</p

Objective Evaluation of the Somatogravic Illusion from Flight Data of an Airplane Accident

(1) Background: It is difficult for accident investigators to objectively determine whether spatial disorientation may have contributed to a fatal airplane accident. In this paper, we evaluate three methods to reconstruct the possible occurrence of the somatogravic illusion based on flight data recordings from an airplane accident. (2) Methods: The outputs of two vestibular models were compared with the “standard” method, which uses the unprocessed gravito-inertial acceleration (GIA). (3) Results: All three methods predicted that the changing orientation of the GIA would lead to a somatogravic illusion when no visual references were available. However, the methods were not able to explain the first pitch-down control input by the pilot flying, which may have been triggered by the inadvertent activation of the go-around mode and a corresponding pitch-up moment. Both vestibular models predicted a few seconds delay in the illusory tilt from GIA due to central processing and sensory integration. (4) Conclusions: While it is difficult to determine which method best predicted the somatogravic illusion perceived during the accident without data on the pilot’s pitch perception, both vestibular models go beyond the GIA analysis in taking into account validated vestibular dynamics, and they also account for other vestibular illusions. In that respect, accident investigators would benefit from a unified and validated vestibular model to better explain pilot actions in accidents related to spatial disorientation

Testing the Applicability of a Checklist-Based Startle Management Method in the Simulator

Several checklist-based methods have been proposed to help pilots manage startle in unexpected situations. In the current experiment, we tested how pilots reacted to using such a method, which featured the mnemonic COOL: Calm down – Observe – Outline – Lead. Using a motion-based simulator outfitted with a non-linear aerodynamic model of a small twin-propeller aircraft, twelve pilots practiced using the COOL method before performing four test scenarios involving startling events. Application of the full method in the test scenarios was high (90-100%), and pilots rated the method on average as useful (4 on a 1-5 point Likert scale). The first two steps of the method were seen as the “core” of the method. However, pilots also displayed difficulty with prioritizing dealing with immediate threats over executing the method. The results are promising, but they also warn us to be cautious when introducing a startle management method

Ubiquinone Analogs: A Mitochondrial Permeability Transition Pore-Dependent Pathway to Selective Cell Death

International audienceBACKGROUND: Prolonged opening of the mitochondrial permeability transition pore (PTP) leads to cell death. Various ubiquinone analogs have been shown to regulate PTP opening but the outcome of PTP regulation by ubiquinone analogs on cell fate has not been studied yet. METHODOLOGY/PRINCIPAL FINDINGS: The effects of ubiquinone 0 (Ub(0)), ubiquinone 5 (Ub(5)), ubiquinone 10 (Ub(10)) and decyl-ubiquinone (DUb) were studied in freshly isolated rat hepatocytes, cultured rat liver Clone-9 cells and cancerous rat liver MH1C1 cells. PTP regulation by ubiquinones differed significantly in permeabilized Clone-9 and MH1C1 cells from that previously reported in liver mitochondria. Ub(0) inhibited PTP opening in isolated hepatocytes and Clone-9 cells, whereas it induced PTP opening in MH1C1 cells. Ub(5) did not affect PTP opening in isolated hepatocytes and MH1C1 cells, but it induced PTP opening in Clone-9 cells. Ub(10) regulated PTP in isolated hepatocytes, whereas it did not affect PTP opening in Clone-9 and MH1C1 cells. Only DUb displayed the same effect on PTP regulation in the three hepatocyte lines tested. Despite such modifications in PTP regulation, competition between ubiquinones still occurred in Clone-9 and MH1C1 cells. As expected, Ub(5) induced a PTP-dependent cell death in Clone-9, while it did not affect MH1C1 cell viability. Ub(0) induced a PTP-dependent cell death in MH1C1 cells, but was also slightly cytotoxic in Clone-9 by an oxidative stress-dependent mechanism. CONCLUSIONS/SIGNIFICANCE: We found that various ubiquinone analogs regulate PTP in different ways depending on the cell studied. We took advantage of this unique property to develop a PTP opening-targeted strategy that leads to cell death specifically in cells where the ubiquinone analog used induces PTP opening, while sparing the cells in which it does not induce PTP opening

Self-oligomerization regulates stability of survival motor neuron protein isoforms by sequestering an SCF^Slmb degron

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCFSlmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and stabilizes SMNΔ7. SMA-causing missense mutations that block multimerization of full-length SMN are also stabilized in the degron mutant background. Overexpression of SMNΔ7S270A, but not wild-type (WT) SMNΔ7, provides a protective effect in SMA model mice and human motor neuron cell culture systems. Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered when SMN forms higher-order multimers

Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names

Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information’s (NCBI’s) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()////-], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Virus nomenclature below the species level : a standardized nomenclature for laboratory animal-adapted strains and variants of viruses assigned to the family Filoviridae

The International Committee on Taxonomy of Viruses (ICTV) organizes the classification of viruses into taxa, but is not responsible for the nomenclature for taxa members. International experts groups, such as the ICTV Study Groups, recommend the classification and naming of viruses and their strains, variants, and isolates. The ICTV Filoviridae Study Group has recently introduced an updated classification and nomenclature for filoviruses. Subsequently, and together with numerous other filovirus experts, a consistent nomenclature for their natural genetic variants and isolates was developed that aims at simplifying the retrieval of sequence data from electronic databases. This is a first important step toward a viral genome annotation standard as sought by the US National Center for Biotechnology Information (NCBI). Here, this work is extended to include filoviruses obtained in the laboratory by artificial selection through passage in laboratory hosts. The previously developed template for natural filovirus genetic variant naming ( //<year of sampling>/-) is retained, but it is proposed to adapt the type of information added to each field for laboratory animal-adapted variants. For instance, the full-length designation of an Ebola virus Mayinga variant adapted at the State Research Center for Virology and Biotechnology “Vector” to cause disease in guinea pigs after seven passages would be akin to “Ebola virus VECTOR/C.porcellus-lab/COD/1976/Mayinga- GPA-P7”. As was proposed for the names of natural filovirus variants, we suggest using the fulllength designation in databases, as well as in the method section of publications. Shortened designations (such as “EBOV VECTOR/C.por/COD/76/May-GPA-P7”) and abbreviations (such as “EBOV/May-GPA-P7”) could be used in the remainder of the text depending on how critical it is to convey information contained in the full-length name. “EBOV” would suffice if only one EBOV strain/variant/isolate is addressed.This work was funded in part by the Joint Science and Technology Office for Chem Bio Defense (proposal #TMTI0048_09_RD_T to SB).http://www.springerlink.com/content/0304-8608/hb2013ab201