658 research outputs found

    Fibroblast migration and collagen deposition during dermal wound healing: mathematical modelling and clinical implications,

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    The extent to which collagen alignment occurs during dermal wound healing determines the severity of scar tissue formation. We have modelled this using a multiscale approach, in which extracellular materials, for example collagen and fibrin, are modelled as continua, while fibroblasts are considered as discrete units. Within this model framework, we have explored the effects that different parameters have on the alignment process, and we have used the model to investigate how manipulation of transforming growth factor-β levels can reduce scar tissue formation. We briefly review this body of work, then extend the modelling framework to investigate the role played by leucocyte signalling in wound repair. To this end, fibroblast migration and collagen deposition within both the wound region and healthy peripheral tissue are considered. Trajectories of individual fibroblasts are determined as they migrate towards the wound region under the combined influence of collagen/fibrin alignment and gradients in a paracrine chemoattractant produced by leucocytes. The effects of a number of different physiological and cellular parameters upon the collagen alignment and repair integrity are assessed. These parameters include fibroblast concentration, cellular speed, fibroblast sensitivity to chemoattractant concentration and chemoattractant diffusion coefficient. Our results show that chemoattractant gradients lead to increased collagen alignment at the interface between the wound and the healthy tissue. Results show that there is a trade-off between wound integrity and the degree of scarring. The former is found to be optimized under conditions of a large chemoattractant diffusion coefficient, while the latter can be minimized when repair takes place in the presence of a competitive inhibitor to chemoattractants

    Polyurea-Functionalized Multiwalled Carbon Nanotubes

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    An in situ polycondensation approach was applied to functionalize multiwalled carbon nanotubes (MWNTs), resulting in various linear or hyperbranched polycondensed polymers [e.g., polyureas, polyurethanes, and poly(urea-urethane)-bonded carbon nanotubes]. The quantity of the grafted polymer can be easily controlled by the feed ratio of monomers. As a typical example, the polyurea-functionalized MWNTs were measured and characterized in detail. The oxidized MWNTs (MWNT-COOH) were converted into acyl chloride-functionalized MWNTs (MWNT-COCl) by reaction with neat thionyl chloride (SOCl2). MWNT-COCl was reacted with excess 1,6-diaminohexane, affording amino-functionalized MWNTs (MWNT-NH2). In the presence of MWNT-NH2, the polyurea was covalently coated onto the surfaces of the nanotube by in situ polycondensation of diisocyanate [e.g., 4,4‘-methylenebis(phenylisocyanate)] and 1,6-diaminohexane, followed by the removal of free polymer via repeated filtering and solvent washing. The coated polyurea content can be controlled to some extent by adjusting the feed ratio of the isocyanato and amino groups. The structure and morphology of the resulting nanocomposites were characterized by FTIR, NMR, Raman, confocal Raman, TEM, EDS, and SEM measurements. The polyurea-coated MWNTs showed interesting self-assembled flat- or flowerlike morphologies in the solid state. The signals corresponding to that of the D and G bands of the carbon nanotubes were strongly attenuated after polyurea was chemically tethered to the MWNT surfaces. Comparative experiments showed that the grafted polymer species and structures have a strong effect on the Raman signals of polymer-functionalized MWNTs

    Robot rights? Towards a social-relational justification of moral consideration \ud

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    Should we grant rights to artificially intelligent robots? Most current and near-future robots do not meet the hard criteria set by deontological and utilitarian theory. Virtue ethics can avoid this problem with its indirect approach. However, both direct and indirect arguments for moral consideration rest on ontological features of entities, an approach which incurs several problems. In response to these difficulties, this paper taps into a different conceptual resource in order to be able to grant some degree of moral consideration to some intelligent social robots: it sketches a novel argument for moral consideration based on social relations. It is shown that to further develop this argument we need to revise our existing ontological and social-political frameworks. It is suggested that we need a social ecology, which may be developed by engaging with Western ecology and Eastern worldviews. Although this relational turn raises many difficult issues and requires more work, this paper provides a rough outline of an alternative approach to moral consideration that can assist us in shaping our relations to intelligent robots and, by extension, to all artificial and biological entities that appear to us as more than instruments for our human purpose

    ruvA Mutants that resolve Holliday junctions but do not reverse replication forks

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    RuvAB and RuvABC complexes catalyze branch migration and resolution of Holliday junctions (HJs) respectively. In addition to their action in the last steps of homologous recombination, they process HJs made by replication fork reversal, a reaction which occurs at inactivated replication forks by the annealing of blocked leading and lagging strand ends. RuvAB was recently proposed to bind replication forks and directly catalyze their conversion into HJs. We report here the isolation and characterization of two separation-of-function ruvA mutants that resolve HJs, based on their capacity to promote conjugational recombination and recombinational repair of UV and mitomycin C lesions, but have lost the capacity to reverse forks. In vivo and in vitro evidence indicate that the ruvA mutations affect DNA binding and the stimulation of RuvB helicase activity. This work shows that RuvA's actions at forks and at HJs can be genetically separated, and that RuvA mutants compromised for fork reversal remain fully capable of homologous recombination

    Delayed-type hypersensitivity in classic Kaposi sarcoma patients and controls

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    BACKGROUND: Immune perturbation likely affects the development of Kaposi sarcoma (KS) among people infected with the KS-associated herpesvirus (KSHV). We tested whether KSHV-seropositive individuals or cases of classic KS (cKS), which typically originates in the leg, had differing delayed-type hypersensitivity (DTH) in the forearm or leg. METHODS: Mantoux DTH with three antigens (Candida, tetanus, PPD) was performed on the forearm and leg of 15 cKS cases, 14 KSHV-positives without KS, and 15 KSHV-negative controls. The diameters of induration responses were compared by group and body site. RESULTS: Leg DTH was greater than forearm DTH among controls (mean difference 5.6 mm, P\ubc0.0004), whereas this was not observed in cKS cases ( 2.2 mm, P\ubc0.32) or KSHV-positives (0.5 mm, P\ubc0.56). Leg-minus-forearm DTH difference was greater in controls compared with cKS cases (P\ubc0.004) and KSHV-positives (P\ubc0.002). Leg-plus-forearm DTH was similar in controls (mean 28.2 mm) and cKS cases (24.5 mm, P\ubc0.60), but it was reduced in KSHV-positives (11.8 mm, P\ubc0.02), particularly in the leg (P\ubc0.004) and marginally in the forearm (P\ubc0.07). CONCLUSION: KS cases had weaker DTH only in the leg, whereas both body sites appeared weaker in KSHV-positives without KS. Both systemic and regional immune alterations may influence the development of this malignancy

    Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

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    Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

    Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections

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    Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr Virus (EBV) establish life-long infections and are associated with malignancies. Striking geographic variation in incidence and the fact that virus alone is insufficient to cause disease, suggests other co-factors are involved. Here we present epidemiological analysis and genome-wide association study (GWAS) in 4365 individuals from an African population cohort, to assess the influence of host genetic and non-genetic factors on virus antibody responses. EBV/KSHV co-infection (OR = 5.71(1.58–7.12)), HIV positivity (OR = 2.22(1.32–3.73)) and living in a more rural area (OR = 1.38(1.01–1.89)) are strongly associated with immunogenicity. GWAS reveals associations with KSHV antibody response in the HLA-B/C region (p = 6.64 × 10−09). For EBV, associations are identified for VCA (rs71542439, p = 1.15 × 10−12). Human leucocyte antigen (HLA) and trans-ancestry fine-mapping substantiate that distinct variants in HLA-DQA1 (p = 5.24 × 10−44) are driving associations for EBNA-1 in Africa. This study highlights complex interactions between KSHV and EBV, in addition to distinct genetic architectures resulting in important differences in pathogenesis and transmission
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