4,864 research outputs found

    An exploratory study of the types and roles of skincare advertising visuals in magazines

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    Despite the observations that visuals are almost always present in skincare ads, and that they are noticed to a greater extent than the text in these ads, there appears to be virtually no publicly available research that has analysed the visual content of skincare ads. As visuals might be useful to consumers in assessing the effectiveness of skincare products, their role in influencing consumer behaviour needs to be researched. Before such research is undertaken, it is necessary to investigate visuals that are actually employed by skincare marketers given the large number of products and varied visual cues or stimuli that seem to exist. The purpose of this research is to identify some of the types (or elements) and roles (or functions) of skincare advertising visuals and examine the extent to which they are evident in ads selected from the April through August 2005 issues of four popular womens magazines in Australia. 24 elements and five functions of skincare advertising visuals were identified, and their presence or absence was assessed in a sample of 52 ads. Due to the exploratory and time-specific nature of this study, future research that audits the visual content of magazine advertisements in the skincare market over a longer period could facilitate an extensive investigation of its impact on consumer attitudes and behaviour

    The immunopathogenesis and treatment of chronic allergic eye disease

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    The pathogenesis of the potentially blinding chronic ocular allergies is poorly understood, and current therapy relies on topical steroids which have vision-reducing side-effects. This thesis aimed to elucidate this pathogenesis, particularly of sight-damaging corneal involvement, and to evaluate therapeutic topical cyclosporin A in atopic keratoconjunctivitis (AKC). The techniques employed were conjunctival biopsy, immunohistochemistry, in situ hybridisation and a randomised, placebo-controlled clinical trial. An initial examination of normal conjunctival leukocytes showed the relative frequencies of different leukocytes and that lymphocytes had features of mucosal-associated lymphoid tissue but organised conjunctival-associated lymphoid tissue was infrequent. An examination of T cells, eosinophils and epithelial cells was conducted. Vernal keratoconjunctivitis and giant papillary conjunctivitis had predominantly Th2-like cells (resembling asthma) but AKC resembled atopic dermatitis with a shift towards a Th1-pattern. There was greater expression of eosinophil surface antigens (and possibly activation) associated with corneal disease and variations in patterns of eosinophil-cytokine localisation occurred between individual disorders. Epithelial cell expression of pro-inflammatory surface antigens was particularly upregulated in disorders with keratopathy and there were different patterns of cytokine co-localisation in the various diseases. A trial of topical cyclosporin A demonstrated clinical improvement and reduced steroid requirement in AKC associated with reductions in leukocyte numbers and T cell cytokine expression not seen with placebo. The drops were difficult to tolerate. These results show a complex pathogenesis of cellular and cytokine interactions underlying chronic allergic eye disease with certain parallels to systemic allergic disorders. These results may allow future therapeutic developments with greater specificity and fewer side-effects than topical steroids

    Preformulation Characterization And Formulation Development of Δ9-Tetrahydrocannabinol Prodrugs For Potential Treatment Of Glacuoma

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    Relationship between smoking marihuana and a drop in intraocular pressure (IOP) was first reported in 1971. Research efforts since then have identified a number of constituents that could be linked to this observation. Delta-9-Tetrahydrocannabinol (THC) was one of the ingredients identified. However, four decades and numerous research efforts since the first observation, it has still not been concluded whether THC is effective in the treatment of glaucoma or not. Current therapy for IOP control in glaucoma, though effective, cannot prevent vision loss completely. Thus, identification of agents that can lower IOP as well as protect the retinal ganglion cells from apoptosis could yield a new class of anti-glaucoma molecules. Protection of retinal ganglion cells against apoptosis could yield a new class of antiglaucoma agents. Numerous investigations have demonstrated that THC also acts as a neuroprotective agent making it a very promising lead compound. However noninvasive delivery of THC to the targeted intraocular tissues is challenging due to its poor physiochemical properties. The aim of the current project was to effectively deliver THC to the intraocular tissues. THC prodrugs were synthesized to improve physicochemical properties. Preformulation characterization and formulation development for the THC prodrugs was undertaken. A high throughput in vitro model to screen the various formulations for transcorneal permeability was also developed. Promising formulations were instilled in vivo in anesthetized rabbit model and tissue concentrations were determined. Earlier formulations reported in the literature, used for determining efficacy were not observed to deliver THC to the targeted intraocular tissues. The formulations developed in this study were able to deliver significantly higher concentrations to the intraocular tissues. Future studies need to investigate if these improved formulations of THC demonstrate pharmacological activity against glaucoma

    The valuation tool user guide: monetizing Cradle to CradleÂź

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    This User Guide outlines the object, scope and expected deliverables from the Valuation Tool component of the Cradle to Cradle Âź C2C BIZZ project. It describes the compendium of subtools that have been developed comprising: i) overview of funding tools; ii) C2C investment appraisal tool; and iii) C2C value indexing tool. The underpinning methodologies, as well as their inherent strengths and limitations are also described. The C2C BIZZ project as a whole aims specifically to promote and enhance the implementation of C2C methods in business site development within North Western Europe (NWE) (PAD, p.14). It is intended to infuse C2C notions into conventional site development, restructuring and management. The primary focus of the project is on planning, building and managing of business sites with C2C credentials (PAD, p.18) using sites in Lille Metropole (La Lainiere), London (London Sustainable Industries Park) and Luxemburg (Ecoparc Windhof) as experimental fields. C2C BIZZ is not concerned with the internal operations and activities of occupiers or users of the developed site. Accordingly, the scope of the valuation tool is confined to the planning, building and management of C2C sites. The deliverable from this component is a compendium of subtools (see Figure 1 below) that may be used to analyse the financial performance of C2C credentials in business sites to aid the making of a business case for such developments and evaluating the financial incentives for particular C2C site development projects. This entire work is premised on the argument that the wider adoption of C2C principles within the built environment depends on the rate of uptake by the private sector. The private sector, being profit driven, are likely to engage in C2C site development if they are convinced of its capacity to contribute to their business goals which ultimately is a return on their investment. The tool development described in this document attempts to provide a framework for collating an evidence base that can assist in articulating the business case for C2C in business site developments

    Role of a Conserved Glutamate Residue in the \u3cem\u3eEscherichia coli\u3c/em\u3e SecA ATPase Mechanism

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    Escherichia coli SecA uses ATP to drive the transport of proteins across cell membranes. Glutamate 210 in the “DEVD” Walker B motif of the SecA ATP-binding site has been proposed as the catalytic base for ATP hydrolysis (Hunt, J. F., Weinkauf, S., Henry, L., Fak, J. J., McNicholas, P., Oliver, D. B., and Deisenhofer, J. (2002) Science 297, 2018–2026). Consistent with this hypothesis, we find that mutation of glutamate 210 to aspartate results in a 90-fold reduction of the ATP hydrolysis rate compared with wild type SecA, 0.3 s–1versus 27 s–1, respectively. SecA-E210D also releases ADP at a slower rate compared with wild type SecA, suggesting that in addition to serving as the catalytic base, glutamate 210 might aid turnover as well. Our results contradict an earlier report that proposed aspartate 133 as the catalytic base (Sato, K., Mori, H., Yoshida, M., and Mizushima, S. (1996) J. Biol. Chem. 271, 17439–17444). Re-evaluation of the SecA-D133N mutant used in that study confirms its loss of ATPase and membrane translocation activities, but surprisingly, the analogous SecA-D133A mutant retains full activity, revealing that this residue does not play a key role in catalysis

    Comparison of the spatial QRS-T angle derived from digital ECGs recorded using conventional electrode placement with that derived from Mason-Likar electrode position

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    Background: The spatial QRS-T angle is ideally derived from orthogonal leads. We compared the spatial QRS-T angle derived from orthogonal leads reconstructed from digital 12-lead ECGs and from digital Holter ECGs recorded with the Mason-Likar (M-L) electrode positions. Methods and results: Orthogonal leads were constructed by the inverse Dower method and used to calculate spatial QRS-T angle by (1) a vector method and (2) a net amplitude method, in 100 volunteers. Spatial QRS-T angles from standard and M-L ECGs differed significantly (57° ± 18° vs 48° ± 20° respectively using net amplitude method and 53° ± 28° vs 48° ± 23° respectively by vector method; p < 0.001). Difference in amplitudes in leads V4–V6 was also observed between Holter and standard ECGs, probably due to a difference in electrical potential at the central terminal. Conclusion: Mean spatial QRS-T angles derived from standard and M-L lead systems differed by 5°–9°. Though statistically significant, these differences may not be clinically significant

    Asymmetric ATP Binding and Hydrolysis Activity of the \u3cem\u3eThermus aquaticus\u3c/em\u3e MutS Dimer Is Key to Modulation of Its Interactions with Mismatched DNA

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    Prokaryotic MutS and eukaryotic Msh proteins recognize base pair mismatches and insertions or deletions in DNA and initiate mismatch repair. These proteins function as dimers (and perhaps higher order oligomers) and possess an ATPase activity that is essential for DNA repair. Previous studies of Escherichia coli MutS and eukaryotic Msh2−Msh6 proteins have revealed asymmetry within the dimer with respect to both DNA binding and ATPase activities. We have found the Thermus aquaticus MutS protein amenable to detailed investigation of the nature and role of this asymmetry. Here, we show that (a) in a MutS dimer one subunit (S1) binds nucleotide with high affinity and the other (S2) with 10-fold weaker affinity, (b) S1 hydrolyzes ATP rapidly while S2 hydrolyzes ATP at a 30−50-fold slower rate, (c) mismatched DNA binding to MutS inhibits ATP hydrolysis at S1 but slow hydrolysis continues at S2, and (d) interaction between mismatched DNA and MutS is weakened when both subunits are occupied by ATP but remains stable when S1 is occupied by ATP and S2 by ADP. These results reveal key MutS species in the ATPase pathway; S1ADP−S2ATP is formed preferentially in the absence of DNA or in the presence of fully matched DNA, while S1ATP−S2ATP and S1ATP−S2ADP are formed preferentially in the presence of mismatched DNA. These MutS species exhibit differences in interaction with mismatched DNA that are likely important for the mechanism of MutS action in DNA repair

    Mismatch Recognition-Coupled Stabilization of Msh2-Msh6 in an ATP-Bound State at the Initiation of DNA Repair

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    Mismatch repair proteins correct errors in DNA via an ATP-driven process. In eukaryotes, the Msh2-Msh6 complex recognizes base pair mismatches and small insertion/deletions in DNA and initiates repair. Both Msh2 and Msh6 proteins contain Walker ATP-binding motifs that are necessary for repair activity. To understand how these proteins couple ATP binding and hydrolysis to DNA binding/mismatch recognition, the ATPase activity of Saccharomyces cerevisiae Msh2-Msh6 was examined under pre-steady-state conditions. Acid-quench experiments revealed that in the absence of DNA, Msh2-Msh6 hydrolyzes ATP rapidly (burst rate = 3 s-1 at 20 °C) and then undergoes a slow step in the pathway that limits catalytic turnover (kcat = 0.1 s-1). ATP is hydrolyzed similarly in the presence of fully matched duplex DNA; however, in the presence of a G:T mismatch or +T insertion-containing DNA, ATP hydrolysis is severely suppressed (rate = 0.1 s-1). Pulse-chase experiments revealed that Msh2-Msh6 binds ATP rapidly in the absence or in the presence of DNA (rate = 0.1 ΌM-1 s-1), indicating that for the Msh2-Msh6·mismatched DNA complex, a step after ATP binding but before or at ATP hydrolysis is the rate-limiting step in the pathway. Thus, mismatch recognition is coupled to a dramatic increase in the residence time of ATP on Msh2-Msh6. This mismatch-induced, stable ATP-bound state of Msh2-Msh6 likely signals downstream events in the repair pathway
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