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"Noble, Richard"
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Designing the Next Generation of Chemical Separation Membranes
New materials can be prepared as membranes that may allow their performance to beat long-standing limits.
Synthetic membranes are used in many separation processes, from industrial-scale ones—such as separating atmospheric gases for medical and industrial use, and removing salt from seawater—to smaller-scale processes in chemical synthesis and purification. Membranes are commonly solid materials, such as polymers, that have good mechanical stability and can be readily processed into high–surface area, defect-free, thin films. These features are critical for obtaining not only good chemical separation but also high throughput. Membrane-based chemical separations can have advantages over other methods—they can take less energy than distillation or liquefaction, use less space than absorbent materials, and operate in a continuous mode. In some cases, such as CO2 separations for CO
2
capture, their performance must be improved. We discuss how membranes work, and some notable new approaches for improving their performance.
Journal Article
An Analysis and Theological Critique of Education
When we ask the question, \"what is the purpose of education?\" we are asking, \"what is the purpose of educating human beings?\" and any sincere answer to this question can only be advanced following our reflections upon the interrelated question, \"what do we mean by being human?\" This 'Who are We?\" question is embedded, though usually not explicitly, in school inspection regimes, in day-to-day teaching practice, and in all educational dialogue and policy. It affects the wellbeing of those on the frontline of education. But it is possible for staff, policy makers and academics to uncover these hidden assumptions, explore counter-narratives, and transform school curricula in the light of these reformed narratives. The author approaches these questions from a Christian Contemplative standpoint, via Radical Orthodoxy (RO) - an academic, persuasive and polemical sensibility - and through the prayerful and relational aspiration of the contemplative tradition. It takes as a central case study the inspection of a school by the UK Government inspection body, Ofsted, the Office for Standards in Education.
eBook
Simultaneous targeting of glycolysis and oxidative phosphorylation as a therapeutic strategy to treat diffuse large B-cell lymphoma
BackgroundWe evaluated the therapeutic potential of combining the monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 with the mitochondrial respiratory Complex I inhibitor IACS-010759, for the treatment of diffuse large B-cell lymphoma (DLBCL), a potential clinically actionable strategy to target tumour metabolism.MethodsAZD3965 and IACS-010759 sensitivity were determined in DLBCL cell lines and tumour xenograft models. Lactate concentrations, oxygen consumption rate and metabolomics were examined as mechanistic endpoints. In vivo plasma concentrations of IACS-010759 in mice were determined by LC-MS to select a dose that reflected clinically attainable concentrations.ResultsIn vitro, the combination of AZD3965 and IACS-010759 is synergistic and induces DLBCL cell death, whereas monotherapy treatments induce a cytostatic response. Significant anti-tumour activity was evident in Toledo and Farage models when the two inhibitors were administered concurrently despite limited or no effect on the growth of DLBCL xenografts as monotherapies.ConclusionsThis is the first study to examine a combination of two distinct approaches to targeting tumour metabolism in DLBCL xenografts. Whilst nanomolar concentrations of either AZD3965 or IACS-010759 monotherapy demonstrate anti-proliferative activity against DLBCL cell lines in vitro, appreciable clinical activity in DLBCL patients may only be realised through their combined use.
Journal Article
Factors influencing European river lamprey passage at a tidal river barrier
Understanding and improving passage by diadromous species at tidal barriers is less well advanced than that for non-tidal anthropogenic river barriers. This study assessed factors affecting upstream passage of anadromous river lamprey (Lampetra fluviatilis) at a tidal weir with pool-and-weir (PAW) and bypass (BP) fishways. A Continuous Time Markov Model (CTMM) was used to analyse migration behaviours of 120 acoustic- and PIT-tagged lamprey across 2 years. The weir was a major barrier to upstream migration with a mean time of 31.0 days taken to pass the weir compared to 2.5 days for the unobstructed reach immediately downstream. River stage was the most important variable associated with weir passage, with a 5.68 (CI = 3.95, 8.17) increase in passage probability for every 1 m river stage increase. Passage was predominately over the weir directly rather than by the fishways. Monitoring the fishways using additional PIT-tagged lamprey (n = 2814) suggested poor entrance efficiency (BP2018, 28.6%; BP2019, 53.1%; PAW2018, 37.0%). Successful fishway passage was estimated as 5.4% (BP2019)–9.0% (PAW2018) of lamprey that entered. Effective fishway entrance for lamprey is probably facilitated by high fishway discharge, yet high-velocity areas may have made it difficult for river lamprey to successfully ascend the fishways.
Journal Article
Two decades of body length measurements of larval and juvenile fish populations in English rivers
Long-term datasets provide context and understanding of complex ecological processes, including temporal variations in species diversity and ecosystem dynamics. This dataset is comprised of body length measurements (mm) of more than 380,000 larval or juvenile fish of 30 species from five English river catchments collected almost monthly over two decades. Such information can be used to determine growth rates, future recruitment success, population structure and compliance with monitoring protocols and conservation objectives. The dataset provides a baseline for analysing the impacts of anthropogenic disturbances such as climate change, pollution and habitat degradation, and, given that many fish populations are size structured with a positive relationship between fish body length and various biological attributes such as swimming ability, survival and fecundity, it will be invaluable for investigating natural and human- induced disturbances.
Journal Article
Single crystal texture by directed molecular self-assembly along dual axes
Creating well-defined single-crystal textures in materials requires the biaxial alignment of all grains into desired orientations, which is challenging to achieve in soft materials. Here we report the formation of single crystals with rigorously controlled texture over macroscopic areas (>1 cm2) in a soft mesophase of a columnar discotic liquid crystal. We use two modes of directed self-assembly, physical confinement and magnetic fields, to achieve control of the orientations of the columnar axes and the hexagonal lattice along orthogonal directions. Field control of the lattice orientation emerges in a low-temperature phase of tilted discogens that breaks the field degeneracy around the columnar axis present in non-tilted states. Conversely, column orientation is controlled by physical confinement and the resulting imposition of homeotropic anchoring at bounding surfaces. These results extend our understanding of molecular organization in tilted systems and may enable the development of a range of new materials for distinct applications.
Journal Article
Engagement in video and audio narratives: contrasting self-report and physiological measures
Stories play a fundamental role in human culture. They provide a mechanism for sharing cultural identity, imparting knowledge, revealing beliefs, reinforcing social bonds and providing entertainment that is central to all human societies. Here we investigated the extent to which the delivery medium of a story (audio or visual) affected self-reported and physiologically measured engagement with the narrative. Although participants self-reported greater involvement for watching video relative to listening to auditory scenes, stronger physiological responses were recorded for auditory stories. Sensors placed at their wrists showed higher and more variable heart rates, greater electrodermal activity, and even higher body temperatures. We interpret these findings as evidence that the stories were more cognitively and emotionally engaging at a physiological level when presented in an auditory format. This may be because listening to a story, rather than watching a video, is a more active process of co-creation, and that this imaginative process in the listener’s mind is detectable on the skin at their wrist.
Journal Article
Factors affecting irreversible inhibition of EGFR and influence of chirality on covalent binding
The discovery of targeted covalent inhibitors is of increasing importance in drug discovery. Finding efficient covalent binders requires modulation of warhead reactivity and optimisation of warhead geometry and non-covalent interactions. Uncoupling the contributions that these factors make to potency is difficult and best practice for a testing cascade that is pragmatic and informative is yet to be fully established. We studied the structure-reactivity-activity relationships of a series of analogues of the EGFR inhibitor poziotinib with point changes in two substructural regions as well as variations in warhead reactivity and geometry. This showed that a simple probe displacement assay that is appropriately tuned in respect of timing and reagent concentrations can reveal structural effects on all three factors: non-covalent affinity, warhead reactivity and geometry. These effects include the detection of potency differences between an enantiomeric pair that differ greatly in their activity and their capacity to form a covalent bond. This difference is rationalised by X-ray crystallography and computational studies and the effect translates quantitatively into cellular mechanistic and phenotypic effects.
Covalent inhibitors are a successful class of drugs, however, the optimization of targeted covalent inhibitors has challenges due to the need to increase non-covalent interactions and modulate reactivity. Here, the authors study the structure-reactivity-activity relationships of analogues of the EGFR inhibitor poziotinib, showing practical methods to characterize structure-activity relationships, providing insights into the origins of potency and highlighting the effect of chirality on covalent binding.
Journal Article