482 research outputs found
Preliminary analysis of fuel tank impact
Following the accident involving the Air France Concorde in 2000 the effects of fluid structure interactions resulting from the impact of a fluid filled tank has become a cause for concern. The work reported here relates to the design of a series of experiments loosely based upon the Concorde incident which aimed to assess whether the probable failure mode in the Concorde accident could occur in land based vessels. Preliminary numerical analyses were undertaken for two of the nine cases that were investigated experimentally in which an empty tank was impacted by a projectile with a velocity of 14m/s and 21.9m/s Initial numerical results for the acceleration at two points on the tank surface and the deformation at the impact zone showed good agreement with test data. Future work is discussed including further numerical modelling incorporating fluid structure interactions for the analysis of the cases when the tank is partially full or completely full
CASTNet: Community-Attentive Spatio-Temporal Networks for Opioid Overdose Forecasting
Opioid overdose is a growing public health crisis in the United States. This
crisis, recognized as "opioid epidemic," has widespread societal consequences
including the degradation of health, and the increase in crime rates and family
problems. To improve the overdose surveillance and to identify the areas in
need of prevention effort, in this work, we focus on forecasting opioid
overdose using real-time crime dynamics. Previous work identified various types
of links between opioid use and criminal activities, such as financial motives
and common causes. Motivated by these observations, we propose a novel
spatio-temporal predictive model for opioid overdose forecasting by leveraging
the spatio-temporal patterns of crime incidents. Our proposed model
incorporates multi-head attentional networks to learn different representation
subspaces of features. Such deep learning architecture, called
"community-attentive" networks, allows the prediction of a given location to be
optimized by a mixture of groups (i.e., communities) of regions. In addition,
our proposed model allows for interpreting what features, from what
communities, have more contributions to predicting local incidents as well as
how these communities are captured through forecasting. Our results on two
real-world overdose datasets indicate that our model achieves superior
forecasting performance and provides meaningful interpretations in terms of
spatio-temporal relationships between the dynamics of crime and that of opioid
overdose.Comment: Accepted as conference paper at ECML-PKDD 201
Synthesis and structural characterization of a mimetic membrane-anchored prion protein
During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP
Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo
The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity
Observation of the Zero Doppler Effect
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.National Basic Research Program (973) of China (No. 2011CB922001), and National Natural Science Foundation of China (No. 11234010)
A method for detergent-free isolation of membrane proteins in their local lipid environment.
Despite the great importance of membrane proteins, structural and functional studies of these proteins present major challenges. A significant hurdle is the extraction of the functional protein from its natural lipid membrane. Traditionally achieved with detergents, purification procedures can be costly and time consuming. A critical flaw with detergent approaches is the removal of the protein from the native lipid environment required to maintain functionally stable protein. This protocol describes the preparation of styrene maleic acid (SMA) co-polymer to extract membrane proteins from prokaryotic and eukaryotic expression systems. Successful isolation of membrane proteins into SMA lipid particles (SMALPs) allows the proteins to remain with native lipid, surrounded by SMA. We detail procedures for obtaining 25 g of SMA (4 d); explain the preparation of protein-containing SMALPs using membranes isolated from Escherichia coli (2 d) and control protein-free SMALPS using E. coli polar lipid extract (1-2 h); investigate SMALP protein purity by SDS-PAGE analysis and estimate protein concentration (4 h); and detail biophysical methods such as circular dichroism (CD) spectroscopy and sedimentation velocity analytical ultracentrifugation (svAUC) to undertake initial structural studies to characterize SMALPs (∼2 d). Together, these methods provide a practical tool kit for those wanting to use SMALPs to study membrane proteins
A preliminary investigation of proximal effects of media multitasking on executive functioning
It has been suggested that media-multitasking may be cumulatively harmful to executive functions, but evidence mainly comes from cross-sectional investigations. If media-multitasking does cause harm, we might expect to observe a decline in executive performance in the immediate aftermath of media-multitasking, relative to sequential media engagement. This study examined proximal effects utilising a lab-based experiment where 76 young adults were randomised into either a media-multitasking group or a sequential media engagement group (both consuming media for 20 min). They completed a pre and post battery of executive function tasks measuring working memory, inhibition and cognitive flexibility. However, there were no interactions showing a greater change in performance for the multitasking group at the second time point. Mood became more negative over the study for both groups. Therefore, no evidence was found that executive functions were fatigued by media-multitasking, and the search for mechanisms of harm must continue
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Generation of an ultrabroadband supercontinuum in the mid-infrared region using dispersion-engineered GeAsSe photonic crystal fiber
An ultrabroadband mid-infrared (MIR) region supercontinuum (SC) is demonstrated numerically through dispersion-engineered traditional chalcogenide (ChG) photonic crystal fiber (PCF). By varying structural parameters pitch (hole to hole spacing) and air-hole diameter to pitch ratio, a number of 10-mm-long hexagonal PCFs made employing GeAsSe ChG glass as a core and air-holes of hexagonal lattice running through their lengths as a cladding are optimized to predict an efficient mid-infrared region SC spectral emission by pumping them using a tunable pump source between 2.9 and 3.3 µm. Simulations are carried out using an ultrashort pump pulse of 100-fs duration with a low pulse peak powers of between 3 and 4 kW into the optimized designs. It is found through numerical analysis that efficient SC spectral broadening with flattened output can be obtained by increasing the PCF pitch rather than increasing the PCF cladding containing air-hole diameter although a larger nonlinear coefficient could be obtained through increasing air-hole diameter of an optimized design. Simulation results show that the SC spectra can be broadened up to 12.2 µm for a certain design with a peak power of 3 kW. Using a peak power of 4 kW, it is possible to obtain SC spectral broadening beyond 14 µm with an optimized design spanning the wavelength range from 1.8 to 14 µm which covers the electromagnetic spectrum required for MIR molecular fingerprint region applications such as sensing and biological imaging
Research on information systems failures and successes: Status update and future directions
The final publication is available at Springer via http://dx.doi.org/10.1007/s10796-014-9500-yInformation systems success and failure are among the most prominent streams in IS research. Explanations of why some IS fulfill their expectations, whereas others fail, are complex and multi-factorial. Despite the efforts to understand the underlying factors, the IS failure rate remains stubbornly high. A Panel session was held at the IFIP Working Group 8.6 conference in Bangalore in 2013 which forms the subject of this Special Issue. Its aim was to reflect on the need for new perspectives and research directions, to provide insights and further guidance for managers on factors enabling IS success and avoiding IS failure. Several key issues emerged, such as the need to study problems from multiple perspectives, to move beyond narrow considerations of the IT artifact, and to venture into underexplored organizational contexts, such as the public sector. © 2014 Springer Science+Business Media New York
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