293 research outputs found

    A design framework for the mass customisation of custom-fit bicycle helmet models

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    Mass customisation (MC) can provide significant benefits to the customers. For example, custom-fit design approaches can improve the users’ perceived comfort of products where the fit is an important feature. MC can also bring major value to the producers, where for instance, premium prices can be implemented to the products. Research show that MC can bring competitive advantages especially when the system is new. It is therefore surprising that MC of helmets has not been studied more extensively, especially given the advances in 3D scanning, computational analyses, parametric design, and additive manufacturing techniques. The purpose of this study was to present a novel MC framework for the design of custom-fit bicycle helmet models. In the proposed design framework, we first categorized a subset of the Australian population into four groups of individuals based on their similar head shapes. New customers were then classified inside one of these groups. The customisation took place inside these groups to ensure that only small variations of the helmet liner were implemented. During the design process, the inside surfaces of a generic helmet model was modified to match the customer's head shape. We demonstrated that all the customized models created complied with the relevant drop impact test standard if their liner thickness was between the worst and best case helmets of each group. Fit accuracy was verified using an objective evaluation method. Future work should include detailed description of the manufacturing methods engaged in our MC framework

    Transmural Ultrasound-based Visualization of Patterns of Action Potential Wave Propagation in Cardiac Tissue

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    The pattern of action potential propagation during various tachyarrhythmias is strongly suspected to be composed of multiple re-entrant waves, but has never been imaged in detail deep within myocardial tissue. An understanding of the nature and dynamics of these waves is important in the development of appropriate electrical or pharmacological treatments for these pathological conditions. We propose a new imaging modality that uses ultrasound to visualize the patterns of propagation of these waves through the mechanical deformations they induce. The new method would have the distinct advantage of being able to visualize these waves deep within cardiac tissue. In this article, we describe one step that would be necessary in this imaging processβ€”the conversion of these deformations into the action potential induced active stresses that produced them. We demonstrate that, because the active stress induced by an action potential is, to a good approximation, only nonzero along the local fiber direction, the problem in our case is actually overdetermined, allowing us to obtain a complete solution. Use of two- rather than three-dimensional displacement data, noise in these displacements, and/or errors in the measurements of the fiber orientations all produce substantial but acceptable errors in the solution. We conclude that the reconstruction of action potential-induced active stress from the deformation it causes appears possible, and that, therefore, the path is open to the development of the new imaging modality

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Cognitive Bias in Ambiguity Judgements:Using Computational Models to Dissect the Effects of Mild Mood Manipulation in Humans

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    Positive and negative moods can be treated as prior expectations over future delivery of rewards and punishments. This provides an inferential foundation for the cognitive (judgement) bias task, now widely-used for assessing affective states in non-human animals. In the task, information about affect is extracted from the optimistic or pessimistic manner in which participants resolve ambiguities in sensory input. Here, we report a novel variant of the task aimed at dissecting the effects of affect manipulations on perceptual and value computations for decision-making under ambiguity in humans. Participants were instructed to judge which way a Gabor patch (250ms presentation) was leaning. If the stimulus leant one way (e.g. left), pressing the REWard key yielded a monetary WIN whilst pressing the SAFE key failed to acquire the WIN. If it leant the other way (e.g. right), pressing the SAFE key avoided a LOSS whilst pressing the REWard key incurred the LOSS. The size (0-100 UK pence) of the offered WIN and threatened LOSS, and the ambiguity of the stimulus (vertical being completely ambiguous) were varied on a trial-by-trial basis, allowing us to investigate how decisions were affected by differing combinations of these factors. Half the subjects performed the task in a 'Pleasantly' decorated room and were given a gift (bag of sweets) prior to starting, whilst the other half were in a bare 'Unpleasant' room and were not given anything. Although these treatments had little effect on self-reported mood, they did lead to differences in decision-making. All subjects were risk averse under ambiguity, consistent with the notion of loss aversion. Analysis using a Bayesian decision model indicated that Unpleasant Room subjects were ('pessimistically') biased towards choosing the SAFE key under ambiguity, but also weighed WINS more heavily than LOSSes compared to Pleasant Room subjects. These apparently contradictory findings may be explained by the influence of affect on different processes underlying decision-making, and the task presented here offers opportunities for further dissecting such processes

    Herpes Simplex Virus Dances with Amyloid Precursor Protein while Exiting the Cell

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    Herpes simplex type 1 (HSV1) replicates in epithelial cells and secondarily enters local sensory neuronal processes, traveling retrograde to the neuronal nucleus to enter latency. Upon reawakening newly synthesized viral particles travel anterograde back to the epithelial cells of the lip, causing the recurrent cold sore. HSV1 co-purifies with amyloid precursor protein (APP), a cellular transmembrane glycoprotein and receptor for anterograde transport machinery that when proteolyzed produces A-beta, the major component of senile plaques. Here we focus on transport inside epithelial cells of newly synthesized virus during its transit to the cell surface. We hypothesize that HSV1 recruits cellular APP during transport. We explore this with quantitative immuno-fluorescence, immuno-gold electron-microscopy and live cell confocal imaging. After synchronous infection most nascent VP26-GFP-labeled viral particles in the cytoplasm co-localize with APP (72.8+/βˆ’6.7%) and travel together with APP inside living cells (81.1+/βˆ’28.9%). This interaction has functional consequences: HSV1 infection decreases the average velocity of APP particles (from 1.1+/βˆ’0.2 to 0.3+/βˆ’0.1 Β΅m/s) and results in APP mal-distribution in infected cells, while interplay with APP-particles increases the frequency (from 10% to 81% motile) and velocity (from 0.3+/βˆ’0.1 to 0.4+/βˆ’0.1 Β΅m/s) of VP26-GFP transport. In cells infected with HSV1 lacking the viral Fc receptor, gE, an envelope glycoprotein also involved in viral axonal transport, APP-capsid interactions are preserved while the distribution and dynamics of dual-label particles differ from wild-type by both immuno-fluorescence and live imaging. Knock-down of APP with siRNA eliminates APP staining, confirming specificity. Our results indicate that most intracellular HSV1 particles undergo frequent dynamic interplay with APP in a manner that facilitates viral transport and interferes with normal APP transport and distribution. Such dynamic interactions between APP and HSV1 suggest a mechanistic basis for the observed clinical relationship between HSV1 seropositivity and risk of Alzheimer's disease

    Production of Biogenic Nanoparticles for the Reduction of 4-Nitrophenol and Oxidative Laccase-Like Reactions

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    <p>Biogenic nanoparticles present a wide range of possibilities for use in industrial applications, their production is greener, they can be manufactured using impure feedstocks, and often have different catalytic abilities compared to their chemically made analogs. Nanoparticles of Ag, Pd, Pt, and the bi-elemental PdPt were produced by Morganella psychrotolerans and Desulfovibrio alaskensis and were shown to be able to reduce 4-nitrophenol, an industrial and toxic pollutant. Nanoparticles were recovered post-reaction and then reused, thus demonstrating continued activity. Biogenic PdNPs were shown to have enhanced specificity in a wide pH activity range in the oxidation of the three common substrates used 2,2β€²-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 2,6-Dimethoxyphenol and (2,6-DMP) and 3,3β€²,5,5β€²-Tetramethylbenzidine (TMB) to determine oxidase-like activity. Overall Pd in a nanoparticle form exhibited higher oxidation activity than its ionic counterpart, highlighting the potential of biogenic nanoparticles over the use of ions or chemically made elemental forms.</p

    Identifying Low pH Active and Lactate-Utilizing Taxa within Oral Microbiome Communities from Healthy Children Using Stable Isotope Probing Techniques

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    <div><h3>Background</h3><p>Many human microbial infectious diseases including dental caries are polymicrobial in nature. How these complex multi-species communities evolve from a healthy to a diseased state is not well understood. Although many health- or disease-associated oral bacteria have been characterized <em>in vitro</em>, their physiology within the complex oral microbiome is difficult to determine with current approaches. In addition, about half of these species remain uncultivated to date with little known besides their 16S rRNA sequence. Lacking culture-based physiological analyses, the functional roles of uncultivated species will remain enigmatic despite their apparent disease correlation. To start addressing these knowledge gaps, we applied a combination of Magnetic Resonance Spectroscopy (MRS) with RNA and DNA based Stable Isotope Probing (SIP) to oral plaque communities from healthy children for <em>in vitro</em> temporal monitoring of metabolites and identification of metabolically active and inactive bacterial species.</p> <h3>Methodology/Principal Findings</h3><p>Supragingival plaque samples from caries-free children incubated with <sup>13</sup>C-substrates under imposed healthy (buffered, pH 7) and diseased states (pH 5.5 and pH 4.5) produced lactate as the dominant organic acid from glucose metabolism. Rapid lactate utilization upon glucose depletion was observed under pH 7 conditions. SIP analyses revealed a number of genera containing cultured and uncultivated taxa with metabolic capabilities at pH 5.5. The diversity of active species decreased significantly at pH 4.5 and was dominated by <em>Lactobacillus</em> and <em>Propionibacterium</em> species, both of which have been previously found within carious lesions from children.</p> <h3>Conclusions/Significance</h3><p>Our approach allowed for identification of species that metabolize carbohydrates under different pH conditions and supports the importance of Lactobacilli and Propionibacterium in the development of childhood caries. Identification of species within healthy subjects that are active at low pH can lead to a better understanding of oral caries onset and generate appropriate targets for preventative measures in the early stages.</p> </div

    Phenotypic and Genome-Wide Analysis of an Antibiotic-Resistant Small Colony Variant (SCV) of Pseudomonas aeruginosa

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    Small colony variants (SCVs) are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch.One SCV (termed PAO-SCV) was isolated, showing high resistance to gentamicin and to the cephalosporine cefotaxime. PAO-SCV was prone to reversion as evidenced by emergence of large colonies with a frequency of 10(-5) on media without antibiotics while it was stably maintained in presence of gentamicin. PAO-SCV showed a delayed growth, defective motility, and strongly reduced levels of the quorum sensing Pseudomonas quinolone signal (PQS). Whole genome expression analysis further suggested a multi-layered antibiotic resistance mechanism, including simultaneous over-expression of two drug efflux pumps (MexAB-OprM, MexXY-OprM), the LPS modification operon arnBCADTEF, and the PhoP-PhoQ two-component system. Conversely, the genes for the synthesis of PQS were strongly down-regulated in PAO-SCV. Finally, genomic analysis revealed the presence of mutations in phoP and phoQ genes as well as in the mexZ gene encoding a repressor of the mexXY and mexAB-oprM genes. Only one mutation occurred only in REV, at nucleotide 1020 of the tufA gene, a paralog of tufB, both encoding the elongation factor Tu, causing a change of the rarely used aspartic acid codon GAU to the more common GAC, possibly causing an increase of tufA mRNA translation. High expression of phoP and phoQ was confirmed for the SCV variant while the revertant showed expression levels reduced to wild-type levels.By combining data coming from phenotypic, gene expression and proteome analysis, we could demonstrate that resistance to aminoglycosides in one SCV mutant is multifactorial including overexpression of efflux mechanisms, LPS modification and is accompanied by a drastic down-regulation of the Pseudomonas quinolone signal quorum sensing system

    A Global Metabolic Shift Is Linked to Salmonella Multicellular Development

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    Bacteria can elaborate complex patterns of development that are dictated by temporally ordered patterns of gene expression, typically under the control of a master regulatory pathway. For some processes, such as biofilm development, regulators that initiate the process have been identified but subsequent phenotypic changes such as stress tolerance do not seem to be under the control of these same regulators. A hallmark feature of biofilms is growth within a self-produced extracellular matrix. In this study we used metabolomics to compare Salmonella cells in rdar colony biofilms to isogenic csgD deletion mutants that do not produce an extracellular matrix. The two populations show distinct metabolite profiles. Even though CsgD controls only extracellular matrix production, metabolite signatures associated with cellular adaptations associated with stress tolerances were present in the wild type but not the mutant cells. To further explore these differences we examine the temporal gene expression of genes implicated in biofilm development and stress adaptations. In wild type cells, genes involved in a metabolic shift to gluconeogenesis and various stress-resistance pathways exhibited an ordered expression profile timed with multicellular development even though they are not CsgD regulated. In csgD mutant cells, the ordered expression was lost. We conclude that the induction of these pathways results from production of, and growth within, a self produced matrix rather than elaboration of a defined genetic program. These results predict that common physiological properties of biofilms are induced independently of regulatory pathways that initiate biofilm formation
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