In this paper we start by outlining the continued decline of the small shop in Britain. The decline is seen as especially severe in the truly independent/non-affiliated sector and we look at trends ...in decline but also the methodologies used to analyse this. Since a key current theme in European integration policy is for exchange of experience and best practise we then report on how an EU-funded (ESF) project is seeking lessons and parallels in the small shop sector in Britain and Spain. By examining official government statistics we see how the sector is monitored in Britain and Spain and then identify one clear one common factor in the rise of organised town centre management. We suggest that future research may usefully begin to develop a more euro-centric approach ensuring that the small shop sector EU-wide learns from transnational experiences. Accordingly, we also present the preliminary findings from a transnational survey of small retailers. The paper ends with a summary of ways in which we have sought to bring together the experiences of small retailers in both countries.
A 13-wavelength channel 10-GHz pulse source is demonstrated using a novel scheme incorporating a dispersion-imbalanced fiber loop mirror and an arrayed waveguide grating. The output high-quality ...pulses are 5 ps wide with the pedestal suppression in excess of 25 dB.
ABSTRACT In a large cohort of osteogenesis imperfecta type V (OI type V) patients (17 individuals from 12 families), we identified the same mutation in the 5′ untranslated region (5′UTR) of the ...interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.–14C > T) and provide a detailed description of their phenotype. This mutation leads to the creation of a novel start codon adding five residues to IFITM5 and was recently reported in several other OI type V families. The variability of the phenotype was quite large even within families. Whereas some patients presented with the typical calcification of the forearm interosseous membrane, radial head dislocation and hyperplastic callus (HPC) formation following fractures, others had only some of the typical OI type V findings. Thirteen had calcification of interosseous membranes, 14 had radial head dislocations, 10 had HPC, 9 had long bone bowing, 11 could ambulate without assistance, and 1 had mild unilateral mixed hearing loss. The bone mineral density varied greatly, even within families. Our study thus highlights the phenotypic variability of OI type V caused by the IFITM5 mutation.
Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean ...duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1-infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation.
Background and Objective: Human gingival fibroblasts exhibit proliferative responses following epidermal growth factor exposure, which are thought to enhance periodontal regeneration in the absence ...of bacterial products such as lipopolysacharide. However, lipopolysaccharide challenge activates human gingival fibroblasts to release several inflammatory mediators that contribute to the immune response associated with periodontitis and attenuate wound repair. We tested the hypothesis that Porphyromonas gingivalis lipopolysaccharide‐activated signaling pathways down‐regulate epidermal growth factor receptor‐dependent events.
Material and Methods: To study lipopolysaccharide/epidermal growth factor interactions in human gingival fibroblasts, we introduced the catalytic subunit of human telomerase into human gingival fibroblasts, thereby generating a more long‐lived cellular model. These cells were characterized and evaluated for lipopolysaccharide/epidermal growth factor responsiveness and regulation of epidermal growth factor‐dependent pathways.
Results: Comparison of human telomerase‐transduced gingival fibroblasts with human gingival fibroblasts revealed that both cell lines exhibit a spindle‐like morphology and express similar levels of epidermal growth factor receptor, CD14 and Toll‐like receptors 2 and 4. Importantly, human telomerase‐transduced gingival fibroblasts proliferation rates are increased 5–9 fold over human gingival fibroblasts and exhibit a longer life span in culture. In addition, human telomerase‐transduced gingival fibroblasts and human gingival fibroblasts exhibit comparable profiles of mitogen‐activated protein kinase kinase (extracellular signal‐regulated kinase 1/2) activation upon epidermal growth factor or P. gingivalis lipopolysaccharide administration. Interestingly, treatment with P. gingivalis lipopolysaccharide leads to a down‐regulation of epidermal growth factor‐dependent extracellular signal‐regulated kinase 1/2, p38 and cyclic‐AMP response element binding protein phosphorylation in both cell types.
Conclusion: These studies demonstrate that human telomerase‐transduced gingival fibroblasts exhibit an extended life span and recapitulate human gingival fibroblasts biology. Moreover, this system has allowed for the first demonstration of lipopolysaccharide down‐regulation of epidermal growth factor activated pathways in human gingival fibroblasts and should facilitate the analysis of signaling events relevant to the pathogenesis and treatment of periodontitis.
Abstract
Azotobacter vinelandii cydAB mutants lacking cytochrome bd lost viability in stationary phase, irrespective of temperature, but microaerobiosis or iron addition to stationary phase cultures ...prevented viability loss. Growth on solid medium was inhibited by a diffusible factor from neighbouring cells, and by iron chelators, In(III) or Ga(III); microaerobic growth overcame inhibition by the extracellular factor. Siderophore production and total Fe(III)-chelating activity were not markedly affected in Cyd− mutants, and remained responsive to iron repression. Cyd− mutants were hypersensitive to Cu(II), Zn(II), and compounds exerting oxidative stress. Failure to synthesise haemoproteins does not explain the complex phenotype since mutants retained significant catalase activity. We hypothesise that Cyd− mutants are defective in maintaining the near-anoxic cytoplasm required for reductive iron metabolism and nitrogenase activity.
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