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Uncovering the unusual inhibition mechanism of a trypanosome alternative oxidase inhibitor displaying broad-spectrum activity against African animal trypanosomes
Get PDFThe glucose-dependent respiration of bloodstream forms of the parasite Trypanosoma brucei depends on an unusual and essential mitochondrial electron-transport system, consisting of glycerol-3-phosphate dehydrogenase and the trypanosome alternative oxidase (TAO). We report here the discovery of an allosteric inhibitor of TAO that displays highly potent activity (EC50 values in the range 1–20 nM) against the important veterinary pathogens T. b. brucei, Trypanosoma evansi, Trypanosoma equiperdum, and Trypanosoma congolense, i.e., >5-fold greater potency than the standard drugs. The methylene-linked 2-methyl-4-hydroxybenzoate 2-pyridinyldiphenylphosphonium derivative (1) was the best inhibitor of recombinant TAO (IC50 = 1.3 nM) via a noncompetitive/allosteric mechanism (Ki = 3.46 nM). Remarkably, X-ray crystallography showed that 1 was bound to a site of TAO ∼25 Å from the catalytic pocket. Although 1 demonstrated good safety toward mammalian cells in vitro (selectivity index >2300), it did not fully clear parasitemia in experimental animals, attributable to a high hepatic clearance
Ultrasound synthetic aperture non-line-of-sight imaging
Get PDFNon-line-of-sight (NLOS) imaging typically relies on the use of ultrashort laser pulses and timeresolved detection to then reconstruct 3D environments that are hidden from the direct line-of-sight. However, the same scattering mechanism and wall-reflections that allow light to propagate into the hidden environment and back again ultimately limit both resolution and imaging distances even at high laser powers. Non-optical, such as acoustic and radio-wave approaches promise to solve some of these issues but have yet to achieve results comparable to optical systems. We present an ultrasound based NLOS imaging system based on a scanning ultrasound emitter and receiver operating in a frequency range similar to common bats that demonstrates high-resolution 3D reconstruction of hidden scenes. We successfully image multiple targets and complex scenes with ~ cm depth resolution at distances up to 2m away from the scattering surface. Measurements of the NLOS modulation transfer function quantify the spatial resolution to also be ~ 1 cm, which is comparable to traditional optical NLOS techniques
Podcasts as pedagogy in higher education: a scoping review to map and advance the field
Get PDFPodcasts are now one of the most ubiquitous forms of digital engagement and entertainment. Their increasing global impact also extends to higher education (HE), where they serve a variety of pedagogical purposes despite limited conceptual clarity. This paper reports on a scoping review exploring the concept and role of podcasts in HE teaching and learning. Based on a review of 91 publications, the paper maps definitions, taxonomies and pedagogical uses of podcasts, leading to a working definition of the concept ‘educational podcasts’. This conceptualisation seeks to capture the many types of pedagogical work for which podcasts are used in contemporary HE, which are explored in an adapted taxonomy based on the scoping review. The paper then points to four key areas for future research. Together, the paper thinks productively and creatively toward further development in researching and teaching of, with and through podcasts
Podcasting comparative and international education: reflecting, reframing, or reorienting the field?
Get PDFThe contribution of VET to resilience and the possibilities for decolonisation: exploring the Palestinian case
No full textDrawing on existing academic literature, institutional accounts and
agency reports on Palestinian VET, we explore the question of how
VET can support resilience, a neglected topic in the international
VET literature. In spite of the horrendous current situation, we
suggest that there are signs of hope and possibilities for new
developments in the Palestinian VET context. Beyond presenting
the Palestinian situation to an international audience, we argue that
the paper also contributes to wider trends in the VET for development literature due to the extremity of the case, which provides
unique insights into current debates. We show how the Palestinian
case can contribute to the growing move towards a post-political
economy of skills and particularly to the small but crucially important literature on the coloniality of VET and possibilities for
decolonisation
Crisis and urban research: preliminary reflections
Get PDFIn this paper, we reflect on the threads that connect and distinguish our collected essays on cities and crisis. We pull out four themes for further consideration: the (urban) crisis of knowledge; the global/local dimensions of crisis; temporalities; and the connections between democracy and urban crisis. These reflections constitute an invitation for further conversations, both within the pages of the journal and beyond
Inclusive B-meson flavour-tagging algorithm at LHCb
Get PDFA new algorithm is developed to identify the flavour of neutral B mesons at production in pp collisions by utilising all tracks from the hadronisation process. The algorithm is calibrated separately for B0 and Bs0 mesons using B0 → J/ψK+π− and Bs0→Ds−π+ decays from pp collision data collected by the LHCb experiment at a centre-of-mass energy of 13 TeV. This new algorithm improves the tagging power by 35% for B0 mesons and 20% for Bs0 mesons when compared to the combined performance of the existing LHCb flavour-tagging algorithms
Roadmap of exploring self-assembly and the self-organization of nanoscale polyoxometalate clusters
No full textPolyoxometalates (POMs) have undergone rapid development over the past decade, emerging as one of the most versatile classes of inorganic molecular clusters with broad applications in catalysis, energy conversion, nanotechnology, and biomedicine. This chapter highlights several fast-evolving areas in POM research, with a focus on the self-assembly and self-organisation of novel structures and composites. Particular emphasis is placed on innovative synthetic methodologies, unprecedented structural diversity, and controlled self-assembly processes at the nanoscale. We showcase groundbreaking advances in giant molybdenum blue/red systems, high-nuclearity polyoxoniobate clusters, non-classical POMs, atomically precise silver-POM hybrids, and mixed-metal architectures. This chapter provides an in-depth analysis of organic ligand-directed assembly strategies that have enabled the construction of new classes of POM-based cages and metal-organic frameworks. Special attention is given to emerging research directions, including supramolecular assembly, nanoscale POM materials, and bio-inspired POM systems. The structure-property relationships that underpin POM functionality in catalysis, energy storage, and biomedical applications are briefly evaluated. Finally, we present a forward-looking perspective on the challenges and opportunities in the field, including AI-guided molecular design, simulation of reaction mechanisms and assembly process, and the integration of POMs into functional materials. With over 160 references to the most impactful studies of the past decade, this chapter serves as a comprehensive roadmap to future developments in POM self-assembly and self-organization
The hybrid renewable energy forecasting and trading competition 2024
No full textThe Hybrid Energy Forecasting and Trading Competition challenged participants to forecast and trade electricity generation from a 3.6 GW portfolio of wind and solar farms in Great Britain for three months in 2024. The competition mimicked operational practice, with participants required to submit genuine forecasts and market bids for the day ahead on a daily basis. Prizes were awarded for forecasting performance measured by the pinball score, trading performance measured by total revenue, and combined performance based on rank in the other two tracks. Here, we present an analysis of the participants’ performance and the lessons learned from the competition. The forecasting track reaffirmed the competitiveness of popular gradient boosted tree algorithms for day-ahead wind and solar power forecasting, though other methods also yielded strong results, with performance in all cases highly dependent on implementation. The trading track offers insight into the relationship between forecast skill and value, with trading strategy and underlying forecasts influencing performance. All competition data, including power production, weather forecasts, electricity market data, and participants’ submissions, are shared for further analysis and benchmarking
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