There is a significant drive to identify alternative materials that exhibit room temperature phosphorescence for technologies including bio-imaging, photodynamic therapy and organic light-emitting ...diodes. Ideally, these materials should be non-toxic and cheap, and it will be possible to control their photoluminescent properties. This was achieved here by embedding carbon nanodots within crystalline particles of alkaline earth carbonates, sulphates and oxalates. The resultant nanocomposites are luminescent and exhibit a bright, sub-second lifetime afterglow. Importantly, the excited state lifetimes, and steady-state and afterglow colours can all be systematically controlled by varying the cations and anions in the host inorganic phase, due to the influence of the cation size and material density on emissive and non-emissive electronic transitions. This simple strategy provides a flexible route for generating materials with specific, phosphorescent properties and is an exciting alternative to approaches relying on the synthesis of custom-made luminescent organic molecules.
In chemical kinetics research, kinetic models containing hundreds of species and tens of thousands of elementary reactions are commonly used to understand and predict the behavior of reactive ...chemical systems. Reaction Mechanism Generator (RMG) is a software suite developed to automatically generate such models by incorporating and extrapolating from a database of known thermochemical and kinetic parameters. Here, we present the recent version 3 release of RMG and highlight improvements since the previously published description of RMG v1.0. Most notably, RMG can now generate heterogeneous catalysis models in addition to the previously available gas- and liquid-phase capabilities. For model analysis, new methods for local and global uncertainty analysis have been implemented to supplement first-order sensitivity analysis. The RMG database of thermochemical and kinetic parameters has been significantly expanded to cover more types of chemistry. The present release includes parallelization for faster model generation and a new molecule isomorphism approach to improve computational performance. RMG has also been updated to use Python 3, ensuring compatibility with the latest cheminformatics and machine learning packages. Overall, RMG v3.0 includes many changes which improve the accuracy of the generated chemical mechanisms and allow for exploration of a wider range of chemical systems.
On the metal: Open metal sites within isostructural M2(DHTP) metal–organic frameworks (M=Co2+, Mn2+, Mg2+, and Zn2+; DHTP=2,5‐dihydroxyterephthalate) exhibit differential molecular recognition with ...acetylene. The extremely strong interaction of Co2+ with acetylene (see structure) makes Co2(DHTP) the highest volumetric acetylene storage material with a capacity of 230 cm3 cm−3 at 295 K and 1 atm.
Exposure to loud sound damages the postsynaptic terminals of spiral ganglion neurons (SGNs) on cochlear inner hair cells (IHCs), resulting in loss of synapses, a process termed synaptopathy. ...Glutamatergic neurotransmission via α-amino-3-hydroxy-5- methylisoxazole-4-propionic acid (AMPA)-type receptors is required for synaptopathy, and here we identify a possible involvement of GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) using IEM-1460, which has been shown to block GluA2-lacking AMPARs. In CBA/CaJ mice, a 2-h exposure to 100-dB sound pressure level octave band (8 to 16 kHz) noise results in no permanent threshold shift but does cause significant synaptopathy and a reduction in auditory brainstem response (ABR) wave-I amplitude. Chronic intracochlear perfusion of IEM-1460 in artificial perilymph (AP) into adult CBA/CaJ mice prevented the decrease in ABR wave-I amplitude and the synaptopathy relative to intracochlear perfusion of AP alone. Interestingly, IEM-1460 itself did not affect the ABR threshold, presumably because GluA2-containing AMPARs can sustain sufficient synaptic transmission to evoke low-threshold responses during blockade of GluA2-lacking AMPARs. On individual postsynaptic densities, we observed GluA2-lacking nanodomains alongside regions with robust GluA2 expression, consistent with the idea that individual synapses have both CP-AMPARs and Ca2+-impermeable AMPARs. SGNs innervating the same IHC differ in their relative vulnerability to noise. We found local heterogeneity among synapses in the relative abundance of GluA2 subunits that may underlie such differences in vulnerability. We propose a role for GluA2-lacking CP-AMPARs in noise-induced cochlear synaptopathy whereby differences among synapses account for differences in excitotoxic susceptibility. These data suggest a means of maintaining normal hearing thresholds while protecting against noise-induced synaptopathy, via selective blockade of CP-AMPARs.
Originating in black feminist scholarship, intersectionality theory is emerging as a corner-stone of sociological thought. It encourages us to consider the ways in which upstream social determinants ...such as racism, sexism and classism form interlocking systems of oppression that shape the experiences and life chances of individuals as a consequence of their multi-dimensional social identities. Contextual forces such as sexism or racism do not operate in isolation but interact with each other in the production of health inequalities. Intersectionality is being increasingly adopted in social epidemiology because it dovetails with the domain's focus on the underlying power structures that produce inequalities (rather than inequalities simply resulting from the accumulation of independent risk factors). There is growing interest in applying intersectional approaches in health inequalities research. While theoretically rich, intersectionality has yet to be sufficiently tested in the health domain and there is a need for greater evidence and debate for how it can contribute to current population health approaches.
The COVID-19 pandemic has reinforced, amplified and created new health inequalities. Examining how COVID-19 prevalence varies by measures of work and occupation may help to understand these ...inequalities. The aim of the study is to evaluate how occupational inequalities in the prevalence of COVID-19 varies across England and their possible explanatory factors. We used data for 363,651 individuals (2,178,835 observations) aged 18 years and over between 1st May 2020 and 31st January 2021 from the Office for National Statistics Covid Infection Survey, a representative longitudinal survey of individuals in England. We focus on two measures of work; employment status for all adults, and work sector of individuals currently working. Multi-level binomial regression models were used to estimate the likelihood of testing positive of COVID-19, adjusting for known explanatory covariates. 0.9% of participants tested positive for COVID-19 over the study period. COVID-19 prevalence was higher among adults who were students or furloughed (i.e., temporarily not working). Among adults currently working, COVID-19 prevalence was highest in adults employed in the hospitality sector, with higher prevalence for individuals employed in transport, social care, retail, health care and educational sectors. Inequalities by work were not consistent over time. We find an unequal distribution of infections relating to COVID-19 by work and employment status. While our findings demonstrate the need for greater workplace interventions to protect employees tailored to their specific work sector needs, focusing on employment alone ignores the importance of SARS-CoV-2 transmission outside of employed work (i.e., furloughed and student populations).
Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell ...manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50-100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry.
With an ageing population, dietary approaches to promote health and independence later in life are needed. In part, this can be achieved by maintaining muscle mass and strength as people age. New ...evidence suggests that current dietary recommendations for protein intake may be insufficient to achieve this goal and that individuals might benefit by increasing their intake and frequency of consumption of high-quality protein. However, the environmental effects of increasing animal-protein production are a concern, and alternative, more sustainable protein sources should be considered. Protein is known to be more satiating than other macronutrients, and it is unclear whether diets high in plant proteins affect the appetite of older adults as they should be recommended for individuals at risk of malnutrition. The review considers the protein needs of an ageing population (>40 years old), sustainable protein sources, appetite-related implications of diets high in plant proteins, and related areas for future research.
Endothelial dysfunction is now considered an important early event in the development of atherosclerosis, which precedes gross morphological signs and clinical symptoms. The assessment of ...flow-mediated dilation (FMD) was introduced almost 20 years ago as a noninvasive approach to examine vasodilator function in vivo. FMD is widely believed to reflect endothelium-dependent and largely nitric oxide-mediated arterial function and has been used as a surrogate marker of vascular health. This noninvasive technique has been used to compare groups of subjects and to evaluate the impact of interventions within individuals. Despite its widespread adoption, there is considerable variability between studies with respect to the protocols applied, methods of analysis, and interpretation of results. Moreover, differences in methodological approaches have important impacts on the response magnitude, can result in spurious data interpretation, and limit the comparability of outcomes between studies. This review results from a collegial discussion between physiologists with the purpose of developing considered guidelines. The contributors represent several distinct research groups that have independently worked to advance the evidence base for improvement of the technical approaches to FMD measurement and analysis. The outcome is a series of recommendations on the basis of review and critical appraisal of recent physiological studies, pertaining to the most appropriate methods to assess FMD in humans.
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