467 research outputs found

    Collecting Data from Children Ages 9-13

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    Provides a summary of literature on common methods used to collect data, such as diaries, interviews, observational methods, and surveys. Analyzes age group-specific considerations, advantages, and drawbacks, with tips for improving data quality

    Method for Alleviating Side Effects of Retinoic Acid Therapy and/or Improving Efficacy without Interfering with Efficacy

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    The invention relates to the use of nicotinic acid alkyl esters, especially myristyl nicotinate, to inhibit side effects associated with retinoic acid therapy. Also a part of the invention is a method for improving skin cell differentiation by administering the nicotinic acid alkyl ester in an amount sufficient to increase expression of caspase 14 and filaggrin. Deficiencies in expression of these molecules can be treated in this way as well

    Nicotinic Acid Receptor Abnormalities in Human Skin Cancer: Implications for a Role in Epidermal Differentiation

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    Chronic UV skin exposure leads to epidermal differentiation defects in humans that can be largely restored by pharmacological doses of nicotinic acid. Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through G(i)-mediated inhibition of adenylyl cyclase. We have examined the expression, cellular distribution, and functionality of GPR109A/B in human skin and skin derived epidermal cells.Nicotinic acid increases epidermal differentiation in photodamaged human skin as judged by the terminal differentiation markers caspase 14 and filaggrin. Both GPR109A and GPR109B genes are transcribed in human skin and in epidermal keratinocytes, but expression in dermal fibroblasts is below limits of detection. Receptor transcripts are greatly over-expressed in squamous cell cancers. Receptor protein in normal skin is prominent from the basal through granular layers of the epidermis, with cellular localization more dispersive in the basal layer but predominantly localized at the plasma membrane in more differentiated epidermal layers. In normal human primary and immortalized keratinocytes, nicotinic acid receptors show plasma membrane localization and functional G(i)-mediated signaling. In contrast, in a squamous cell carcinoma derived cell line, receptor protein shows a more diffuse cellular localization and the receptors are nearly non-functional.The results of these studies justify future genetic and pharmacological intervention studies to define possible specific role(s) of nicotinic acid receptors in human skin homeostasis

    Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors

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    The Notch protein is one of the most mechanistically direct transmembrane receptors—the intracellular domain contains a transcriptional regulator that is released from the membrane when engagement of the cognate extracellular ligand induces intramembrane proteolysis. We find that chimeric forms of Notch, in which both the extracellular sensor module and the intracellular transcriptional module are replaced with heterologous protein domains, can serve as a general platform for generating novel cell-cell contact signaling pathways. Synthetic Notch (synNotch) pathways can drive user-defined functional responses in diverse mammalian cell types. Because individual synNotch pathways do not share common signaling intermediates, the pathways are functionally orthogonal. Thus, multiple synNotch receptors can be used in the same cell to achieve combinatorial integration of environmental cues, including Boolean response programs, multi-cellular signaling cascades, and self-organized cellular patterns. SynNotch receptors provide extraordinary flexibility in engineering cells with customized sensing/response behaviors to user-specified extracellular cues

    Promoting ethical behaviour and preventing wrongdoing in organisations: A rapid evidence assessment

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    This Rapid Evidence Assessment (REA), based on 57 studies carried out in policing and other professions, aimed to identify interventions, mechanisms and levers that might encourage ethical behaviour and prevent wrongdoing in organisations. Taken together, the evidence raises a number of possibilities for organisations for action, though no readymade single solution was identified. The importance of strong and effective leadership – such as leaders being open, acting as role models, and also being ‘firm’ in terms of setting and enforcing standards – was highlighted as encouraging ethical behaviour, as well as being an essential ingredient for the successful implementation of interventions. Promising interventions tended to be broadly preventive or remedial in their approach, rather than focused on apprehending and disciplining those responsible for wrongdoing

    The Northeast Pacific GLOBEC Program: Coastal Gulf of Alaska

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    (First Paragraph) The Gulf of Alaska (GOA) continental shelf encompasses approximately 370,000 km2, or about 13% of the U.S. continental shell and supports a rich and diverse marine ecosystem including some of the largest commercial fisheries in the U.S. Exclusive Economic Zone. Of particular economic importance is the salmon fishery, which was worth on the order of $170 million (landed value) in 2000 accrued from a catch of over 100 million fish. However, there is considerable variability on both interannual and longer time scales in harvest and recruitment success to this and other GOA fisheries. Of recent interest are compelling indications that abundances of salmon, other fish species, and zooplankton vary on decadal scales in association with North Pacific basin-scale climate changes (Beamish, 1995; Mantua et al., 1997; Roemmich and McGowan, 1995; Brodeur et al., 1996; Francis et al., 1998; Anderson and Piatt, 1999; Hollowed et al., 2001)

    The discrepancy between social isolation and loneliness as a clinically meaningful metric: findings from the Irish and English longitudinal studies of ageing (TILDA and ELSA)

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    Objective Scant evidence is available on the discordance between loneliness and social isolation among older adults. We aimed to investigate this discordance and any health implications that it may have. Method Using nationally representative datasets from ageing cohorts in Ireland (TILDA) and England (ELSA), we created a metric of discordance between loneliness and social isolation, to which we refer as Social Asymmetry. This metric was the categorised difference between standardised scores on a scale of loneliness and a scale of social isolation, giving categories of: Concordantly Lonely and Isolated, Discordant: Robust to Loneliness, or Discordant: Susceptible to Loneliness. We used regression and multilevel modelling to identify potential relationships between Social Asymmetry and cognitive outcomes. Results Social Asymmetry predicted cognitive outcomes cross-sectionally and at a two-year follow-up, such that Discordant: Robust to Loneliness individuals were superior performers, but we failed to find evidence for Social Asymmetry as a predictor of cognitive trajectory over time. Conclusions We present a new metric and preliminary evidence of a relationship with clinical outcomes. Further research validating this metric in different populations, and evaluating its relationship with other outcomes, is warranted
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