Formation of the pro-apoptotic death-inducing signaling complex (DISC) can be initiated in cancer cells via binding of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to its two pro-apoptotic receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2. Primary components of the DISC are trimerized TRAIL-R1/-R2, FADD, caspase 8 and caspase 10. The anti-apoptotic protein FLIP can also be recruited to the DISC to replace caspase 8 and form an inactive complex. Caspase 8/10 processing at the DISC triggers the caspase cascade, which eventually leads to apoptotic cell death. Besides TRAIL, TRAIL-R1- or TRAIL-R2-selective variants of TRAIL and agonistic antibodies have been designed. These ligands are of interest as anti-cancer agents since they selectively kill tumor cells. To increase tumor sensitivity to TRAIL death receptor-mediated apoptosis and to overcome drug resistance, TRAIL receptor ligands have already been combined with various therapies in preclinical models. In this review, we discuss factors influencing the initial steps of the TRAIL apoptosis signaling pathway, focusing on mechanisms modulating DISC assembly and caspase activation at the DISC. These insights will direct rational design of drug combinations with TRAIL receptor ligands to maximize DISC signaling. © 2009 Elsevier B.V. All rights reserved.
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Individual and unorganized sports with a health-related focus, such as recreational running, have grown extensively in the last decade. Consistent with this development, there has been an exponential increase in the availability and use of electronic monitoring devices such as smartphone applications (apps) and sports watches. These electronic devices could provide support and monitoring for unorganized runners, who have no access to professional trainers and coaches. The purpose of this paper is to gain insight into the characteristics of event runners who use running-related apps and sports watches. This knowledge is useful from research, design, and marketing perspectives to adequately address unorganized runners’ needs, and to support them in healthy and sustainable running through personalized technology. Data used in this study are drawn from the standardized online Eindhoven Running Survey 2014 (ERS14). In total, 2,172 participants in the Half Marathon Eindhoven 2014 completed the questionnaire (a response rate of 40.0%). Binary logistic regressions were used to analyze the impact of socio-demographic variables, running-related variables, and psychographic characteristics on the use of running-related apps and sports watches. Next, consumer profiles were identified. The results indicate that the use of monitoring devices is affected by socio-demographics as well as sports-related and psychographic variables, and this relationship depends on the type of monitoring device. Therefore, distinctive consumer profiles have been developed to provide a tool for designers and manufacturers of electronic running-related devices to better target (unorganized) runners’ needs through personalized and differentiated approaches. Apps are more likely to be used by younger, less experienced and involved runners. Hence, apps have the potential to target this group of novice, less trained, and unorganized runners. In contrast, sports watches are more likely to be used by a different group of runners, older and more experienced runners with higher involvement. Although apps and sports watches may potentially promote and stimulate sports participation, these electronic devices do require a more differentiated approach to target specific needs of runners. Considerable efforts in terms of personalization and tailoring have to be made to develop the full potential of these electronic devices as drivers for healthy and sustainable sports participation.
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Er is recent veel zorg over de zgn. ‘zorgkinderen’ in de reguliere Nederlandse kinderopvang, omdat hun aantal is gestegen en ook hun problematiek ernstiger lijkt te zijn. In een sequentiële mixed-methods-aanpak is een kwantitatieve vragenlijststudie uitgevoerd onder pedagogisch medewerkers, gevolgd door een kwalitatieve analyse van focusgroepen met kinderopvangprofessionals.In Studie 1 zijn, aansluitend op het ‘Job Demands en Resources’-model, in een vragenlijstonderzoek (N= 446) risicofactoren en protectieve factoren in kaart gebracht voor pedagogisch medewerkers. Een ‘moderated mediation’-model voor welbevinden en voor burnout liet zien dat het aandeel zorgkinderen op de groep, gemedieerd via ervaren werkbelasting en handelingsverlegenheid, een voorspeller is van lager welbevinden en gevoelens van emotionele uitputting van deze professionals. Steun vanuit team en organisatie blijkt een protectieve factor.Aansluitend bij de gevonden relaties uit Studie 1, is in Studie 2 verkend in zes focusgroepen (N= 20) welke concrete ervaringen van pedagogisch medewerkers en staf hebben op hun werk met kinderen met een extra zorgbehoefte. De uitkomsten uit beide deelstudies zijn ten slotte in een breder kader geplaatst met aandacht voor implicaties voor de praktijk.
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