Direct measurement of single-molecule dynamics and reaction kinetics in confinement using time-resolved transmission electron microscopy

We report experimental methodologies utilising transmission electron microscopy (TEM) as an imaging tool for reaction kinetics at the single molecule level, in direct space and with spatiotemporal continuity. Using reactions of perchlorocoronene (PCC) in nanotubes of different diameters and at different temperatures, we found a period of molecular movement to precede the intermolecular addition of PCC, with a stronger dependence of the reaction rate on the nanotube diameter, controlling the local environments around molecules, than on the reaction temperature (−175, 23 or 400 °C). Once initiated, polymerisation of PCC follows zero-order reaction kinetics with the observed reaction cross section σobs of 1.13 × 10⁻⁹ nm2 (11.3 ± 0.6 barn), determined directly from time-resolved TEM image series acquired with a rate of 100 frames per second. Polymerisation was shown to proceed from a single point, with molecules reacting sequentially, as in a domino effect, due to the strict conformational requirement of the Diels–Alder cycloaddition creating the bottleneck for the reaction. The reaction mechanism was corroborated by correlating structures of reaction intermediates observed in TEM images, with molecular weights measured by using mass spectrometry (MS) when the same reaction was triggered by UV irradiation. The approaches developed in this study bring the imaging of chemical reactions at the single-molecule level closer to traditional concepts of chemistry

Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME): Study protocol for a randomised controlled trial

Background: Abdominal aortic aneurysm (AAA) is a slowly progressive destructive process of the main abdominal artery. Experimental studies indicate that fibrates exert beneficial effects on AAAs by mechanisms involving both serum lipid modification and favourable changes to the AAA wall. Methods/design: Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME) is a multicentre, randomised, double-blind, placebo-controlled clinical trial to assess the effect of orally administered therapy with fenofibrate on key pathological markers of AAA in patients undergoing open AAA repair. A total of 42 participants scheduled for an elective open AAA repair will be randomly assigned to either 145 mg of fenofibrate per day or identical placebo for a minimum period of 2 weeks prior to surgery. Primary outcome measures will be macrophage number and osteopontin (OPN) concentration within the AAA wall as well as serum concentrations of OPN. Secondary outcome measures will include levels of matrix metalloproteinases and proinflammatory cytokines within the AAA wall, periaortic fat and intramural thrombus and circulating concentrations of AAA biomarkers. Discussion: At present, there is no recognised medical therapy to limit AAA progression. The FAME trial aims to assess the ability of fenofibrate to alter tissue markers of AAA pathology. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12612001226897. Registered on 20 November 2012. © 2017 The Author(s)

Windows of opportunities for catching up: an analysis of ICT sector development in Ukraine

Following long-standing calls to investigate information and communication technology (ICT) sector development in lesser-developed economies, this study examines the sector’s rapid emergence in Ukraine utilizing a catch-up cycle conceptual framework. Ukraine is a unique case due to the country’s location in Eastern Europe, the sector’s explosive growth within an otherwise stagnant economy, and related disconnectedness to other economic sectors. This study finds that the confluence of several windows of opportunity spurred an entrepreneurial response among hundreds of firms. However, most of these firms focus on low value-added segments of the ICT global value chain and lack the managerial and technical capabilities to compete globally, much less develop new products and services. As the global ICT services sector evolves, multi-level interventions are required to maintain the sector’s growth trajectory and realize the economic and social benefits normally associated the development of a domestically inter-connected ICT sector. In order for Ukraine to secure its digital future, it must seize windows of opportunity in the global and European data economy

Palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl halides: scope of the three-component synthesis of N-aminosulfonamides.

By using DABCO·(SO(2))(2), DABSO, as a solid bench-stable SO(2)-equivalent, the palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl halides has been achieved. N,N-Dialkylhydrazines are employed as the N-nucleophiles and provide N-aminosulfonamides as the products in good to excellent yields. The reactions are operationally simple to perform, requiring only a slight excess of SO(2) (1.2-2.2 equiv.), and tolerate a variety of substituents on the halide coupling partner. Variation of the hydrazine component is also demonstrated. The use of N,N-dibenzylhydrazine as the N-nucleophile delivers N-aminosulfonamide products that can be converted into the corresponding primary sulfonamides using a high-yielding, telescoped, deprotection sequence. The ability to employ hydrazine·SO(2) complexes as both the N-nucleophile and SO(2) source is also illustrated