Differences in vision performance in different scenarios and implications for design.

To design accessibly, designers need good, relevant population data on visual abilities. However, currently available data often focuses on clinical vision measures that are not entirely relevant to everyday product use. This paper presents data from a pilot survey of 362 participants in the UK, covering a range of vision measures of particular relevance to product design. The results from the different measures are compared, and recommendations are given for relative text sizes to use in different situations. The results indicate that text needs to be 17-18% larger for comfortable rather than perceived threshold viewing, and a further 20% larger when users are expected to wear their everyday vision setup rather than specific reading aids.The survey was funded by the Engineering and Physical Sciences Research Council (EPSRC) through the i~design 3 grant (Award Number: RG45089). The survey itself was conducted by the National Centre for Social Research under the direction of the research team. As well as the authors of this paper, several others made substantial contributions to the design and analysis of this survey, including Felicia Huppert, Pat Langdon, Kai Ruggeri, Eddy Elton, Jose Liht and John Ryan. Further analysis was funded by EPSRC through the KT-EQUAL project (grant number EP/G030898/2).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.apergo.2016.02.00

Design and delivery of a national pilot survey of capabilities

Understanding the numbers of people with different levels of ability in the population is important for informing design decisions for mainstream products, but a survey dataset for this purpose does not exist. This paper describes a key step towards obtaining such data. It describes a pilot survey of 362 people across England and Wales in preparation for a full national survey. Information was gathered on vision, hearing, hand and arm function, mobility, cognitive function, product use, psychological characteristics, anthropometrics and demographics. An interesting finding is that of those participants who reported any limitations in daily activities due to capability loss, 44% reported limitations due to loss of more than one capability. This finding highlights the importance of measuring multiple capabilities in a single survey. Top-level lessons learnt include: simplifying vision tests; reducing exclusion criteria for some of the tests; adopting a stratified sampling approach; and allocating more training for interviewers.This research was funded by the Engineering and Physical Sciences Research Council grant (Award Number: RG45089).This is the accepted version of the article. The final version is available fro Inderscience at http://inderscience.metapress.com/content/fk41618325n25741/

Effect of a cluster on gas–solid drag from lattice Boltzmann simulations

Fast fluidization of fine particles leads to formation of particle clusters, which significantly affects the drag force between the phases. Existing gas–solid drag models, both empirical and theoretical, do not account for the effect of the clusters on the drag force, and as a result, the computational studies using them are unable to capture the inherent heterogeneity of fast fluidization beds. The limitation of the current drag models is generally attributed to poor understanding of the effect of the clusters. In this study, the effect of a single cluster on the drag force has been investigated by conducting lattice Boltzmann simulations of gas–particle flow under a wide range of the overall voidage and particle Reynolds numbers. It was observed that simulations with the particles in a cluster configuration gave considerably lower drag than those with particles in a random arrangement. Furthermore, for the cluster voidage between maximum to 0.7, a significant drag reduction was observed when the inter-particle distances within a cluster was decreased. The simulations with a constant cluster voidage of 0.7 showed that the drag force decreased on decreasing the overall voidage from the maximum voidage to approximately 0.96; however any further decrease in the overall voidage caused a steep increase in the drag force. The results of this study are important in quantifying the drag reduction due to the formation of clusters

Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) variants govern transmissibility, responsiveness to vaccination, and disease severity. In a screen for new models of SARS-CoV-2 infection, we identify human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of angiotensin-converting enzyme 2 (ACE2) expression. Remarkably, H522 infection requires the E484D S variant; viruses expressing wild-type S are not infectious. Anti-S monoclonal antibodies differentially neutralize SARS-CoV-2 E484D S in H522 cells as compared to ACE2-expressing cells. Sera from vaccinated individuals block this alternative entry mechanism, whereas convalescent sera are less effective. Although the H522 receptor remains unknown, depletion of surface heparan sulfates block H522 infection. Temporally resolved transcriptomic and proteomic profiling reveal alterations in cell cycle and the antiviral host cell response, including MDA5-dependent activation of type I interferon signaling. These findings establish an alternative SARS-CoV-2 host cell receptor for the E484D SARS-CoV-2 variant, which may impact tropism of SARS-CoV-2 and consequently human disease pathogenesis

Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer’s and Parkinson’s diseases

Normal mitochondrial dynamics consist of fission and fusion events giving rise to new mitochondria, a process termed mitochondrial biogenesis. However, several neurodegenerative disorders manifest aberrant mitochondrial dynamics, resulting in morphological abnormalities often associated with deficits in mitochondrial mobility and cell bioenergetics. Rarely, dysfunctional mitochondrial occur in a familial pattern due to genetic mutations, but much more commonly patients manifest sporadic forms of mitochondrial disability presumably related to a complex set of interactions of multiple genes (or their products) with environmental factors (G × E). Recent studies have shown that generation of excessive nitric oxide (NO), in part due to generation of oligomers of amyloid-β (Aβ) protein or overactivity of the NMDA-subtype of glutamate receptor, can augment mitochondrial fission, leading to frank fragmentation of the mitochondria. S-Nitrosylation, a covalent redox reaction of NO with specific protein thiol groups, represents one mechanism contributing to NO-induced mitochondrial fragmentation, bioenergetic failure, synaptic damage, and eventually neuronal apoptosis. Here, we summarize our evidence in Alzheimer’s disease (AD) patients and animal models showing that NO contributes to mitochondrial fragmentation via S-nitrosylation of dynamin-related protein 1 (Drp1), a protein involved in mitochondrial fission. These findings may provide a new target for drug development in AD. Additionally, we review emerging evidence that redox reactions triggered by excessive levels of NO can contribute to protein misfolding, the hallmark of a number of neurodegenerative disorders, including AD and Parkinson’s disease. For example, S-nitrosylation of parkin disrupts its E3 ubiquitin ligase activity, and thereby affects Lewy body formation and neuronal cell death