In situ nanocompression testing of irradiated copper.

Increasing demand for energy and reduction of carbon dioxide emissions has revived interest in nuclear energy. Designing materials for radiation environments necessitates a fundamental understanding of how radiation-induced defects alter mechanical properties. Ion beams create radiation damage efficiently without material activation, but their limited penetration depth requires small-scale testing. However, strength measurements of nanoscale irradiated specimens have not been previously performed. Here we show that yield strengths approaching macroscopic values are measured from irradiated ~400 nm-diameter copper specimens. Quantitative in situ nanocompression testing in a transmission electron microscope reveals that the strength of larger samples is controlled by dislocation-irradiation defect interactions, yielding size-independent strengths. Below ~400 nm, size-dependent strength results from dislocation source limitation. This transition length-scale should be universal, but depends on material and irradiation conditions. We conclude that for irradiated copper, and presumably related materials, nanoscale in situ testing can determine bulk-like yield strengths and simultaneously identify deformation mechanisms

Plasmonic lenses for tunable ultrafast electron emitters at the nanoscale

Simultaneous spatiotemporal confinement of energetic electron pulses to femtosecond and nanometer scales is a topic of great interest in the scientific community, given the potential impact of such developments across a wide spectrum of scientific and industrial applications. For example, in ultrafast electron scattering, nanoscale probes would enable accurate maps of structural dynamics in materials with nanoscale heterogeneity, thereby leading to an understanding of the role of boundaries and defects on macroscopic properties. On the other hand, advances in this field are mostly limited by the brightness and size of the electron source. We present the design, fabrication, and optical characterization of bullseye plasmonic lenses for next-generation ultrafast electron sources. Using electromagnetic simulations, we examine how the interplay between light-plasmon coupling, plasmon propagation, dispersion, and resonance governs the properties of the photoemitted electron pulse. We also illustrate how the pulse duration and strength can be tuned by geometric design and predict that sub-10-fs pulses with nanoscale diameter can be achieved. We then fabricate lenses in gold films and characterize their plasmonic properties using cathodoluminescence spectromicroscopy, demonstrating suitable plasmonic behavior for ultrafast nanoscale photoemission

Oligomeric Structure of the MALT1 Tandem Ig-Like Domains

Mucosa-associated lymphoid tissue 1 (MALT1) plays an important role in the adaptive immune program. During TCR- or BCR-induced NF-κB activation, MALT1 serves to mediate the activation of the IKK (IκB kinase) complex, which subsequently regulates the activation of NF-κB. Aggregation of MALT1 is important for E3 ligase activation and NF-κB signaling.Unlike the isolated CARD or paracaspase domains, which behave as monomers, the tandem Ig-like domains of MALT1 exists as a mixture of dimer and tetramer in solution. High-resolution structures reveals a protein-protein interface that is stabilized by a buried surface area of 1256 Å(2) and contains numerous hydrogen and salt bonds. In conjunction with a second interface, these interactions may represent the basis of MALT1 oligomerization.The crystal structure of the tandem Ig-like domains reveals the oligomerization potential of MALT1 and a potential intermediate in the activation of the adaptive inflammatory pathway.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

Approaching the ideal elastic limit of metallic glasses

The ideal elastic limit is the upper bound to the stress and elastic strain a material can withstand. This intrinsic property has been widely studied for crystalline metals, both theoretically and experimentally. For metallic glasses, however, the ideal elastic limit remains poorly characterized and understood. Here we show that the elastic strain limit and the corresponding strength of submicron-sized metallic glass specimens are about twice as high as the already impressive elastic limit observed in bulk metallic glass samples, in line with model predictions of the ideal elastic limit of metallic glasses. We achieve this by employing an in situ transmission electron microscope tensile deformation technique. Furthermore, we propose an alternative mechanism for the apparent 'work hardening' behaviour observed in the tensile stress–strain curves

Managing changes initiated by industrial big data technologies : a technochange management model

With the adoption of Internet of Things and advanced data analytical technologies in manufacturing firms, the industrial sector has launched an evolutionary journey toward the 4th industrial revolution, or so called Industry 4.0. Industrial big data is a core component to realize the vision of Industry 4.0. However, the implementation and usage of industrial big data tools in manufacturing firms will not merely be a technical endeavor, but can also lead to a thorough management reform. By means of a comprehensive review of literature related to Industry 4.0, smart manufacturing, industrial big data, information systems (IS) and technochange management, this paper aims to analyze potential changes triggered by the application of industrial big data in manufacturing firms, from technological, individual and organizational perspectives. Furthermore, in order to drive these changes more effectively and eliminate potential resistance, a conceptual technochange management model was developed and proposed. Drawn upon theories reported in literature of IS technochange management, this model proposed four types of interventions that can be used to copy with changes initiated by industrial big data technologies, including human process intervention, techno-structural intervention, human resources management intervention and strategic intervention. This model will be of interests and value to practitioners and researchers concerned with business reforms triggered by Industry 4.0 in general and by industrial big data technologies in particular

Selection of Inhibitor-Resistant Viral Potassium Channels Identifies a Selectivity Filter Site that Affects Barium and Amantadine Block

BACKGROUND:Understanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function and for the discovery and development of ion channel directed drugs. METHODOLOGY/PRINCIPAL FINDINGS:We used genetic selection methods to probe the interaction of two ion channel blockers, barium and amantadine, with the miniature viral potassium channel Kcv. Selection for Kcv mutants that were resistant to either blocker identified a mutant bearing multiple changes that was resistant to both. Implementation of a PCR shuffling and backcrossing procedure uncovered that the blocker resistance could be attributed to a single change, T63S, at a position that is likely to form the binding site for the inner ion in the selectivity filter (site 4). A combination of electrophysiological and biochemical assays revealed a distinct difference in the ability of the mutant channel to interact with the blockers. Studies of the analogous mutation in the mammalian inward rectifier Kir2.1 show that the T-->S mutation affects barium block as well as the stability of the conductive state. Comparison of the effects of similar barium resistant mutations in Kcv and Kir2.1 shows that neighboring amino acids in the Kcv selectivity filter affect blocker binding. CONCLUSIONS/SIGNIFICANCE:The data support the idea that permeant ions have an integral role in stabilizing potassium channel structure, suggest that both barium and amantadine act at a similar site, and demonstrate how genetic selections can be used to map blocker binding sites and reveal mechanistic features

Adaptation of High-Growth Influenza H5N1 Vaccine Virus in Vero Cells: Implications for Pandemic Preparedness

Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14), a reassortant virus between A/Vietnam/1194/2004 (H5N1) virus and egg-adapted high-growth A/PR/8/1934 virus, could grow efficiently in eggs and MDCK cells but not Vero cells which is the most popular cell line for manufacturing human vaccines. After serial passages and plaque purifications of the NIBRG-14 vaccine virus in Vero cells, one high-growth virus strain (Vero-15) was generated and can grow over 108 TCID50/ml. In conclusion, one high-growth H5N1 vaccine virus was generated in Vero cells, which can be used to manufacture influenza H5N1 vaccines and prepare reassortant vaccine viruses for other influenza A subtypes

Chemical Diversity and Complexity of Scotch Whisky as Revealed by High-Resolution Mass Spectrometry

Scotch Whisky is an important product, both culturally and economically. Chemically, Scotch Whisky is a complex mixture, which comprises thousands of compounds, the nature of which are largely unknown. Here, we present a thorough overview of the chemistry of Scotch Whisky as observed by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Eighty-five whiskies, representing the majority of Scotch Whisky produced and sold, were analyzed by untargeted high-resolution mass spectrometry. Thousands of chemical formulae were assigned for each sample based on parts-per-billion mass accuracy of FT-ICR MS spectra. For the first time, isotopic fine structure analysis was used to confirm the assignment of high molecular weight CHOS species in Scotch Whisky. The assigned spectra were compared using a number of visualization techniques, including van Krevelen diagrams, double bond equivalence (DBE) plots, as well as heteroatomic compound class distributions. Additionally, multivariate analysis, including PCA and OPLS-DA, was used to interpret the data, with key compounds identified for discriminating between types of whisky (blend or malt) or maturation wood type. FT-ICR MS analysis of Scotch Whisky was shown to be of significant potential in further understanding of the complexity of mature spirit drinks and as a tool for investigating the chemistry of the maturation processes. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13361-016-1513-y) contains supplementary material, which is available to authorized users

Structure of an Engineered β-Lactamase Maltose Binding Protein Fusion Protein: Insights into Heterotropic Allosteric Regulation

Engineering novel allostery into existing proteins is a challenging endeavor to obtain novel sensors, therapeutic proteins, or modulate metabolic and cellular processes. The RG13 protein achieves such allostery by inserting a circularly permuted TEM-1 β-lactamase gene into the maltose binding protein (MBP). RG13 is positively regulated by maltose yet is, serendipitously, inhibited by Zn2+ at low µM concentration. To probe the structure and allostery of RG13, we crystallized RG13 in the presence of mM Zn2+ concentration and determined its structure. The structure reveals that the MBP and TEM-1 domains are in close proximity connected via two linkers and a zinc ion bridging both domains. By bridging both TEM-1 and MBP, Zn2+ acts to “twist tie” the linkers thereby partially dislodging a linker between the two domains from its original catalytically productive position in TEM-1. This linker 1 contains residues normally part of the TEM-1 active site including the critical β3 and β4 strands important for activity. Mutagenesis of residues comprising the crystallographically observed Zn2+ site only slightly affected Zn2+ inhibition 2- to 4-fold. Combined with previous mutagenesis results we therefore hypothesize the presence of two or more inter-domain mutually exclusive inhibitory Zn2+ sites. Mutagenesis and molecular modeling of an intact TEM-1 domain near MBP within the RG13 framework indicated a close surface proximity of the two domains with maltose switching being critically dependent on MBP linker anchoring residues and linker length. Structural analysis indicated that the linker attachment sites on MBP are at a site that, upon maltose binding, harbors both the largest local Cα distance changes and displays surface curvature changes, from concave to relatively flat becoming thus less sterically intrusive. Maltose activation and zinc inhibition of RG13 are hypothesized to have opposite effects on productive relaxation of the TEM-1 β3 linker region via steric and/or linker juxtapositioning mechanisms