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Synthesis of poly (2-hydroxyethyl ethyleneimine) and its mucoadhesive film formulations when blended with chitosan for buccal delivery of haloperidol
Get PDFMucoadhesive films are attractive for buccal drug delivery because of their extended retention on the mucosal surface, enabling sustained drug delivery to and across the tissue. In this study, poly(2-hydroxyethyl ethyleneimine) (P2HEEI) was synthesized by reacting linear polyethyleneimine (L-PEI) with 2-bromoethanol and combined with chitosan to formulate mucoadhesive films for buccal delivery of haloperidol. The polymer displayed excellent solubility in water, a low glass transition temperature (−31.6 °C) and low toxicity in human dermal skin fibroblast cells. This polymer was then blended with chitosan before films were formed by a casting technique. Differential scanning calorimetry and scanning electron microscopy confirmed that chitosan and P2HEEI were fully miscible in the blends. The films based on chitosan-P2HEEI blends were more elastic and had enhanced mechanical properties. Films containing haloperidol were also formulated. The release of haloperidol from the films increased as the P2HEEI content in the blends was raised. Mucoadhesion of these films on ex vivo sheep buccal mucosal tissues was evaluated using a tensile method. All films were mucoadhesive but increasing P2HEEI content in the blend gradually reduced adhesion to the buccal mucosa
Evaluation and verification of new UK air temperature extremes during the July 2022 heatwave: part 1, maximum temperatures
Get PDFThe brief but intense heatwave which affected all areas of the British Isles during the third week of July 2022 was particularly noteworthy as being the first occasion on which screen temperatures exceeded 40 °C anywhere in the United Kingdom. The event resulted in widespread new records for high air temperatures, both day maximum and night minimum, many by surprisingly wide margins relative to existing climatology. This two-part analysis examines the causes and distribution of resulting extremes of air temperature, specifically the validity of new UK air temperature records: Part 1 considers daytime maximum temperatures, and Part 2 minimum temperatures
Marine data assimilation in the UK: the past, the present and the vision for the future
Get PDFIn the last 2 decades, UK research institutes have led a wide range of developments in marine data assimilation (MDA), covering areas from operational applications in physics and biogeochemistry to fundamental theory. We highlight the emergence of strong collaboration in the UK MDA community over this period and the increasing unification of its tools. We focus on identifying the MDA stakeholder community and current/future areas of impact, as well as current trends and future opportunities. This includes the rapid growth of machine learning (ML)/artificial intelligence (AI) and digital-twin applications. We articulate a vision for the future, including the need for future types of observational data (whether planned missions or hypothetical) and how the community should respond to increases in computational power and new computer architectures (e.g. exascale computing). We contrast the requirements of different MDA areas, including physics, biogeochemistry, and coupled data assimilation (DA). Although the specifics of the vision depend on each area, common themes emerge. We advocate for balanced redistribution of new computational capability among increased model resolution, model complexity, more sophisticated DA algorithms, and uncertainty representation (e.g. ensembles). We also advocate for integrated approaches, such as strongly coupled DA (ocean–atmosphere, physics–biogeochemistry, and ocean–sea ice) and the use of ML/AI components (e.g. for multivariate increment balancing, bias correction, model emulation, observation re-gridding, or fusion)
A sucrose‐utilisation gene cluster contributes to colonisation of horse chestnut by Pseudomonas syringae pv. aesculi
Get PDFPseudomonas syringae pathovar aesculi (E-Pae) causes bleeding canker disease in the woody tissue of European horse chestnut (HC). Comparative genomic analysis of E-Pae with a related leaf-infecting strain (I-Pae) and other P. syringae strains identified candidate virulence genes for colonisation of woody tissue, including a sucrose uptake and utilisation system (scrYABCDBR cluster) found in 162 of 206 P. syringae strains spanning the pangenome. Growth analysis using sucrose as sole carbon source showed that I-Pae (lacking the gene cluster) was unable to grow whereas E-Pae could grow. P. savastanoi pv. phaseolicola 1448A and P. syringae pv. morsprunorum R15244 were compromised in growth despite the presence of the gene cluster. Sucrose utilisation assays using scrB and scrY mutants and complemented strains confirmed the importance of the cluster for sucrose metabolism in vitro. Pathogenicity assays in HC revealed the sucrose gene cluster is important for symptom development in the woody tissue. While the scr genes contribute to disease causation, they were not essential for pathogen fitness when compared to hrpL and hopAB1 mutants. E-Pae caused disease symptoms in HC leaves, suggesting the strain has the potential to infect leaves as well. However, it was notable that the scrB mutant of E-Pae caused increased disease symptoms, possibly highlighting a niche adaptation strategy for I-Pae to cause leaf spots in HC as well as constraining E-Pae to predominantly infect the woody tissue
The role of internal variability in seasonal hindcast trend errors
Get PDFInitialised hindcasts inherit knowledge of the observed climate state, so studies of multidecadal trends in seasonal and decadal hindcast models have focused on the ensemble-mean when benchmarking against observed trends. However, this neglects the role of short-timescale variability in contributing to longer-term trends, and hence trend errors. Using a single-model coupled hindcast ensemble, we generate a distribution of 10,000 hindcast trends over 1981-2022 by randomly sampling a single ensemble member in each year. We find that the hindcast model supports a wide range of trends in various features of the large-scale climate, even when sampled at leads of just 1-3 months following initialisation. The spread in hindcast global surface temperature trends is equivalent to approximately a sixth of the total observed warming over the same period, driven by large seasonal variability of temperatures over land. The hindcasts also lend support for observed poleward jet shifts, but the magnitude of the shifts varies widely across the ensemble. Our results show that a fair comparison of hindcast trends to observations should consider the full range of model trends, not only the ensemble mean. More broadly, we argue that the hindcast trend distribution offers a largely untapped tool for studying multidecadal climate trends in a very large ensemble, through exploiting existing hindcast data
Alpha oscillatory current application impacts prospective remembering through strategic monitoring
Get PDFProspective memory (PM) is the ability to remember to execute future intentions. PM requires engagement of attentional networks, in which oscillatory activity in the alpha frequency range has been implicated. The left dorsolateral prefrontal cortex (DLPFC) and inferior parietal cortex are assumed to be engaged during PM tasks. We hypothesized that the selective application of transcranial alternating current stimulation (tACS) at alpha frequency to these areas can modulate PM‐associated event‐related potentials. Participants were assigned to alpha‐tACS, theta‐tACS, or Sham stimulation. They performed a working memory task (OGT), with a PM component, pre‐, during, and post‐stimulation. EEG was recorded post‐stimulation. Accuracy and reaction times (RTs) were computed. Following EEG source reconstruction of mean amplitude, source activity was contrasted between conditions in which performance was modulated by tACS using cluster‐based permutation tests. RTs were slower on introducing the PM task, consistent with strategic monitoring. PM accuracy improved in the alpha‐tACS group only. During PM trials, source activity in the posterior cingulate cortex (PCC) was lower following alpha‐tACS than after Sham stimulation. Source activity in the DLPFC following alpha‐tACS was lower during PM than in OGT trials following alpha‐tACS. Performance modulation through alpha‐tACS, and the lower DLPFC activity in PM than in OGT trials provide evidence of a role for alpha oscillations during strategic monitoring for a PM cue. Lower PCC activity in the alpha‐tACS than Sham group is consistent with facilitation of disengagement of the default mode network, supporting re‐direction of attention from the OGT to the PM task and task‐switching
Sub‐auroral heating at Jupiter following a solar wind compression
Get PDFJupiter's polar aurorae deliver significant heating at the poles, thought to spread across the planet through atmospheric winds. Additionally, ground-based Keck observations have revealed a large-scale high-temperature region, spatially distinct from the aurorae. Here, we investigate the origins and characteristics of the feature using Keck data, in-situ Juno spacecraft measurements, and solar wind modeling. Juno exited the magnetosphere on approach to Jupiter, coinciding with modeled high-speed solar wind impact that compressed the magnetosphere. This hot feature may be dynamic, transported equatorward by winds following auroral activity enhancements from magnetospheric compression akin to a large-scale traveling ionospheric disturbance on Earth, or driven by the inner magnetosphere particle precipitation. Exploring the dynamic case, we calculated equatorward velocities ranging from 0.46 to 2.02 km, similar to those seen at Earth. Our study underscores the importance of the solar wind at all planets, exemplified by its ability to alter Jupiter's upper-atmospheric energy balance globally
The effect of increasing model resolution on the Northern Hemisphere winter mid-latitude storm track: an equatorward shift due to contraction of the Hadley cell
Get PDFWe examine how changes in horizontal resolution impact the Northern Hemisphere winter mid-latitude climatological storm track position using the historical runs of six fully coupled climate models from the HighResMIP project. Each model has a low- and high-resolution version, with atmospheric resolutions of ~100–200 to ∼25–50 km respectively, and four of the six models also increase oceanic resolution from 1o to 0.25o. In all models the storm track position is more equatorward as resolution increases. This is associated with an intensification and narrowing of precipitation around the equator and contraction of the Hadley cell. This shifts the subtropical jet equatorwards, increasing the baroclinicity at lower latitudes, leading to more favourable conditions for storm genesis at these latitudes. The contraction of the Hadley cell with resolution is similar to that caused by El Niño on interannual timescales. Four of the six models, including those which increase atmospheric resolution only, show a corresponding El Niño like sea-surface temperature signature at high resolution. The Hadley cell contraction with resolution increase is not seen in models with prescribed sea surface temperatures. The increase in oceanic resolution drives the Hadley Cell contraction in some models. In others, the increase in atmospheric resolution is the dominant driver, but only when the atmosphere is dynamically coupled with the ocean. These results show that increasing resolution alone could exacerbate the existing equatorward storm track bias seen in CMIP6 models, although it is possible this could be mitigated by optimisation of parametrisation settings