15 research outputs found

    Systematic mapping of free energy landscapes of a growing filamin domain during biosynthesis

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    Cotranslational folding (CTF) is a fundamental molecular process that ensures efficient protein biosynthesis and minimizes the formation of misfolded states. However, the complexity of this process makes it extremely challenging to obtain structural characterizations of CTF pathways. Here, we correlate observations of translationally arrested nascent chains with those of a systematic C-terminal truncation strategy. We create a detailed description of chain length-dependent free energy landscapes associated with folding of the FLN5 filamin domain, in isolation and on the ribosome, and thus, quantify a substantial destabilization of the native structure on the ribosome. We identify and characterize two folding intermediates formed in isolation, including a partially folded intermediate associated with the isomerization of a conserved cis proline residue. The slow folding associated with this process raises the prospect that neighboring unfolded domains might accumulate and misfold during biosynthesis. We develop a simple model to quantify the risk of misfolding in this situation and show that catalysis of folding by peptidyl-prolyl isomerases is sufficient to eliminate this hazard. [Abstract copyright: Copyright © 2018 the Author(s). Published by PNAS.

    Evaluation of close range photogrammetric support for Pavescan

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    Pavescan is a low cost mobile system for road modelling survey. Because of the absence of navigation sensors it has several practical drawbacks compared to most of the other mobile mapping systems, but those sensors are very expensive and do not fulfil most of the accuracy requirements. Pavescan will be more attractive if some of the practical drawbacks are reduced. Pavescan measures road profiles across the road by laser scanning at a series of positions. The separate scans are linked via control points, which have to be measured in an additional survey. The accuracy in height of the scans is most important (e.g. for volume calculations) and has to be in the range of millimetres. It is evaluated if integrating close range photogrammetry can achieve millimeter accuracy of the scan and reduce the number of control points. A test survey was conducted with a downward looking camera, which was mounted close to the scanner at a height of around 3.6 metres above the road's surface. The position and orientation of the camera at each exposure is retrieved by bundle adjustment. The accuracy of the bundle adjustment depended strongly on the configuration of the control points. Due to the narrow shape of a strip of images, this configuration will always be weak. For a sequence of 28 images ( 43 metres), around five control points are needed to achieve sub-centimetre accuracy of the object points. If more than 36 images or fewer than four control points were used, the bundle adjustment diverged (i.e. no solution could be obtained). A reduction of control points is therefore not possible. The practical feasibility for integrating close range photogrammetry into Pavescan is low, since too many control points are needed that should spatially be well distributed and measured with tachymetry (or with similar accuracy). Therefore it is not recommended to integrate photogrammetry in Pavescan.Department of Optical and Laser Remote SensingAerospace Engineerin

    Design of a Human Reliability Assessment model for structural engineering

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    It is generally accepted that humans are the “weakest link” in structural design and construction processes. Despite this, few models are available to quantify human error within engineering processes. This paper demonstrates the use of a quantitative Human Reliability Assessment model within structural engineering. The model consists of four steps. In the first step the process and its boundary conditions are identified. In the second step, the effect of human error on a single task is defined. In the third step, these effects are combined into an overall effect on the engineered structure. Finally, the structural failure probability is estimated by combining the strength and loading conditions by means of a Monte Carlo simulation. The use of the model is demonstrated using a case study based on the design process of a frame structure. This case study shows that the model has the potential to quantify the effect of human errors within carefully defined boundary conditions.OTB ResearchOTB Research Institute for the Built Environmen

    A cross-layer approach in sensing and resource allocation for multimedia transmission over cognitive UWB Networks

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    We propose an MAC centric cross-layer approach to address the problem of multimedia transmission over cognitive Ultra Wideband (C-UWB) networks. Several fundamental design issues, which are related to application (APP), medium access control (MAC), and physical (PHY) layer, are discussed. Although substantial research has been carried out in the PHY layer perspective of cognitive radio system, this paper attempts to extend the existing research paradigm to MAC and APP layers, which can be considered as premature at this time. This paper proposed a cross-layer design that is aware of (a) UWB wireless channel conditions, (b) time slot allocations at the MAC layer, and (c) MPEG-4 video at the APP layer. Two cooperative sensing mechanisms, namely, AND and OR, are analyzed in terms of probability of detection (Pd), probability of false alarm (P f), and the required sensing period. Then, the impact of sensing scheduling to the MPEG-4 video transmission over wireless cognitive UWB networks is observed. In addition, we also proposed the packet reception rate- (PRR-) based resource allocation scheme that is aware of the channel condition, target PRR, and queue status

    Generation of genomic-integration-free human induced pluripotent stem cells and the derived cardiomyocytes of X-linked dilated cardiomyopathy from DMD gene mutation

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    We derived an integration-free induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a 23-year-old male patient. This patient carries a 5′ splice site point mutation in intron 1 (c.31+1G > A) of the dystrophin gene, a mutation associated with X-linked dilated cardiomyopathy (XLDCM). Sendai virus was used to reprogram the PBMCs and deliver OCT3/4, SOX2, c-MYC, and KLF4 factors. The iPSC line (HKUi002-A) generated preserved the mutation, expressed common pluripotency markers, differentiated into three germ layers in vivo, and exhibited a normal karyotype. Further differentiation into cardiomyocytes enables the study of the disease mechanisms of XLDCM

    A psychometric evaluation of the emotional intelligence ability construct among working adult Australians

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    The broad aim of the research reported here was to evaluate key psychometric issues identified in relation to ability measures of emotional intelligence (EI). To investigate these issues, three studies were conducted including only participants from business and organisational backgrounds. In Study 1, the responses of 231 participants were analysed through a series of confirmatory factor analysis models to evaluate the factor structure of an EI ability measure (MEIS). Results of these analyses were generally consistent with past research, including the observation of non-positive definite matrices for more complex models. Study 2 examined the discriminant validity of the MEIS by comparing the MEIS scores of 147 participants with their responses to the NEO PI-R. Consistent with past research minimal correlations were observed between MEIS scores and NEO PI-R factor scores, indicating that the two instruments measure distinct constructs. There was also good convergence between the two alternative scoring methods for the MEIS, expert- and consensus-based, suggesting that the two scoring methods are comparable when an Australian organisational consensus group is used. As others have suspected (e.g. Palmer, Gignac, Manocha & Stough, 2005) although not investigated, a significant gender by scoring method interaction was observed for the MEIS in Study 2. Study 3 investigated the convergent validity of the MEIS by comparing MEIS scores from 45 participants with their scores on a measure of verbal reasoning. Moderate yet significant correlations were observed indicating that the two measures were related but not to the extent that they were measuring the same construct
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