SRMS Assisted Docking and Undocking for the Orbiter Repair Maneuver

As part of the Orbiter Repair Maneuver (ORM) planned for Return to Flight (RTF) operations, the Shuttle Remote Manipulator System (SRMS) must undock the Orbiter, maneuver it through a complex trajectory at extremely low rates, present it to an EVA crewman at the end of the Space Station Remote Manipulator System to perform the Thermal Protection System (TPS) repair, and then retrace back through the trajectory to dock the Orbiter with the Orbiter Docking System (ODs). The initial and final segments of this operation involve the interaction between the SRMS, ISS, Orbiter and ODs. This paper first provides an overview of the Monte-Carlo screening analysis for the installation (both nominal and contingency), including the variation of separation distance, misalignment conditions, SRMS joint/brake parameter characteristics, and PRCS jet combinations and corresponding thrust durations. The resulting 'optimum' solution is presented based on trade studies between predicted capture success and integrated system loads. This paper then discusses the upgrades to the APAS math model associated with the new SRMS assisted undocking technique and reviews simulation results for various options investigated for either the active and passive separation of the ISS from the Orbiter

Conceptual Design of Beryllium Target for the KLF Project

The Kaon Production Target (KPT) is an important component of the proposed K-Long facility which will be operated in JLab Hall~D, targeting strange baryon and meson spectroscopy. In this note we present a conceptual design for the Be-target assembly for the planned K-Long beam line, which will be used along with the GlueX spectrometer in its standard configuration for the proposed experiments. The high quality 12-GeV CEBAF electron beam enables production of a K$_L$ flux at the GlueX target on the order of $1\times 10^4 K_L/sec$, which exceeds the K$_L$ flux previously attained at SLAC by three orders of magnitude. An intense K$_L$ beam would open a new window of opportunity not only to locate "missing resonances" in the strange hadron spectrum, but also to establish their properties by studying different decay channels systematically. The most important and radiation damaging background in K$_L$ production is due to neutrons. The Monte Carlo simulations for the proposed conceptual design of KPT show that the resulting neutron and gamma flux lead to a prompt radiation dose rate for the KLF experiment that is below the JLab Radiation Control Department radiation dose rate limits in the experimental hall and at the site boundary, and will not substantially affect the performance of the spectrometer.Comment: 9 pages, 9 figure

Detecting modification of biomedical events using a deep parsing approach

<p>Abstract</p> <p>Background</p> <p>This work describes a system for identifying event mentions in bio-molecular research abstracts that are either speculative (e.g. <it>analysis of IkappaBalpha phosphorylation</it>, where it is not specified whether phosphorylation did or did not occur) or negated (e.g. <it>inhibition of IkappaBalpha phosphorylation</it>, where phosphorylation did <it>not </it>occur). The data comes from a standard dataset created for the BioNLP 2009 Shared Task. The system uses a machine-learning approach, where the features used for classification are a combination of shallow features derived from the words of the sentences and more complex features based on the semantic outputs produced by a deep parser.</p> <p>Method</p> <p>To detect event modification, we use a Maximum Entropy learner with features extracted from the data relative to the trigger words of the events. The shallow features are bag-of-words features based on a small sliding context window of 3-4 tokens on either side of the trigger word. The deep parser features are derived from parses produced by the English Resource Grammar and the <it>RASP </it>parser. The outputs of these parsers are converted into the Minimal Recursion Semantics formalism, and from this, we extract features motivated by linguistics and the data itself. All of these features are combined to create training or test data for the machine learning algorithm.</p> <p>Results</p> <p>Over the test data, our methods produce approximately a 4% absolute increase in F-score for detection of event modification compared to a baseline based only on the shallow bag-of-words features.</p> <p>Conclusions</p> <p>Our results indicate that grammar-based techniques can enhance the accuracy of methods for detecting event modification.</p

Integrated Approach Reveals Role of Mitochondrial Germ-Line Mutation F18L in Respiratory Chain, Oxidative Alterations, Drug Sensitivity, and Patient Prognosis in Glioblastoma

Glioblastoma is the most common and malignant primary brain tumour in adults, with a dismal prognosis. This is partly due to considerable inter- and intra-tumour heterogeneity. Changes in the cellular energy-producing mitochondrial respiratory chain complex (MRC) activities are a hallmark of glioblastoma relative to the normal brain, and associate with differential survival outcomes. Targeting MRC complexes with drugs can also facilitate anti-glioblastoma activity. Whether mutations in the mitochondrial DNA (mtDNA) that encode several components of the MRC contribute to these phenomena remains underexplored. We identified a germ-line mtDNA mutation (m. 14798T &gt; C), enriched in glioblastoma relative to healthy controls, that causes an amino acid substitution F18L within the core mtDNA-encoded cytochrome b subunit of MRC complex III. F18L is predicted to alter corresponding complex III activity, and sensitivity to complex III-targeting drugs. This could in turn alter reactive oxygen species (ROS) production, cell behaviour and, consequently, patient outcomes. Here we show that, despite a heterogeneous mitochondrial background in adult glioblastoma patient biopsy-derived cell cultures, the F18L substitution associates with alterations in individual MRC complex activities, in particular a 75% increase in MRC complex II_III activity, and a 34% reduction in CoQ10, the natural substrate for MRC complex III, levels. Downstream characterisation of an F18L-carrier revealed an 87% increase in intra-cellular ROS, an altered cellular distribution of mitochondrial-specific ROS, and a 64% increased sensitivity to clomipramine, a repurposed MRC complex III-targeting drug. In patients, F18L-carriers that received the current standard of care treatment had a poorer prognosis than non-carriers (373 days vs. 415 days, respectively). Single germ-line mitochondrial mutations could predispose individuals to differential prognoses, and sensitivity to mitochondrial targeted drugs. Thus, F18L, which is present in blood could serve as a useful non-invasive biomarker for the stratification of patients into prognostically relevant groups, one of which requires a lower dose of clomipramine to achieve clinical effect, thus minimising side-effects

Language development after cochlear implantation: an epigenetic model

Growing evidence supports the notion that dynamic gene expression, subject to epigenetic control, organizes multiple influences to enable a child to learn to listen and to talk. Here, we review neurobiological and genetic influences on spoken language development in the context of results of a longitudinal trial of cochlear implantation of young children with severe to profound sensorineural hearing loss in the Childhood Development after Cochlear Implantation study. We specifically examine the results of cochlear implantation in participants who were congenitally deaf (N = 116). Prior to intervention, these participants were subject to naturally imposed constraints in sensory (acoustic–phonologic) inputs during critical phases of development when spoken language skills are typically achieved rapidly. Their candidacy for a cochlear implant was prompted by delays (n = 20) or an essential absence of spoken language acquisition (n = 96). Observations thus present an opportunity to evaluate the impact of factors that influence the emergence of spoken language, particularly in the context of hearing restoration in sensitive periods for language acquisition. Outcomes demonstrate considerable variation in spoken language learning, although significant advantages exist for the congenitally deaf children implanted prior to 18 months of age. While age at implantation carries high predictive value in forecasting performance on measures of spoken language, several factors show significant association, particularly those related to parent–child interactions. Importantly, the significance of environmental variables in their predictive value for language development varies with age at implantation. These observations are considered in the context of an epigenetic model in which dynamic genomic expression can modulate aspects of auditory learning, offering insights into factors that can influence a child’s acquisition of spoken language after cochlear implantation. Increased understanding of these interactions could lead to targeted interventions that interact with the epigenome to influence language outcomes with intervention, particularly in periods in which development is subject to time-sensitive experience