771 resultados para TRANSCRIPTIONAL CONTROL


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Objective: We hypothesize that chondrocytes from distinct zones of articular cartilage respond differently to compressive loading, and that zonal chondrocytes from osteoarthritis (OA) patients can benefit from optimized compressive stimulation. Therefore, we aimed to determine the transcriptional response of superficial (S) and middle/deep (MD) zone chondrocytes to varying dynamic compressive strain and loading duration. To confirm effects of compressive stimulation on overall matrix production, we subjected zonal chondrocytes to compression for 2 weeks. Design: Human S and MD chondrocytes from osteoarthritic joints were encapsulated in 2% alginate, pre-cultured, and subjected to compression with varying dynamic strain (5, 15, 50% at 1 Hz) and loading duration (1, 3, 12 h). Temporal changes in cartilage-specific, zonal, and dedifferentiation genes following compression were evaluated using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). The benefits of long-term compression (50% strain, 3 h/day, for 2 weeks) were assessed by measuring construct glycosaminoglycan (GAG) content and compressive moduli, as well as immunostaining. Results: Compressive stimulation significantly induced aggrecan (ACAN), COL2A1, COL1A1, proteoglycan 4 (PRG4), and COL10A1 gene expression after 2 h of unloading, in a zone-dependent manner (P < 0.05). ACAN and PRG4 mRNA levels depended on strain and load duration, with 50% and 3 h loading resulting in highest levels (P < 0.05). Long-term compression increased collagen type II and ACAN immunostaining and total GAG (P < 0.05), but only S constructs showed more PRG4 stain, retained more GAG (P < 0.01), and developed higher compressive moduli than non-loaded controls. Conclusions: The biosynthetic activity of zonal chondrocytes from osteoarthritis joints can be enhanced with selected compression regimes, indicating the potential for cartilage tissue engineering applications. © 2012 Osteoarthritis Research Society International.

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A physiological control system was developed for a rotary left ventricular assist device (LVAD) in which the target pump flow rate (LVADQ) was set as a function of left atrial pressure (LAP), mimicking the Frank-Starling mechanism. The control strategy was implemented using linear PID control and was evaluated in a pulsatile mock circulation loop using a prototyped centrifugal pump by varying pulmonary vascular resistance to alter venous return. The control strategy automatically varied pump speed (2460 to 1740 to 2700 RPM) in response to a decrease and subsequent increase in venous return. In contrast, a fixed-speed pump caused a simulated ventricular suction event during low venous return and higher ventricular volumes during high venous return. The preload sensitivity was increased from 0.011 L/min/mmHg in fixed speed mode to 0.47L/min/mmHg, a value similar to that of the native healthy heart. The sensitivity varied automatically to maintain the LAP and LVADQ within a predefined zone. This control strategy requires the implantation of a pressure sensor in the left atrium and a flow sensor around the outflow cannula of the LVAD. However, appropriate pressure sensor technology is not yet commercially available and so an alternative measure of preload such as pulsatility of pump signals should be investigated.

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An important issue facing Canadians today is crime control and prevention. Research done in the late 1980s and early 1990s by three sociologists shows that Canadian federal criminal justice policies and practices adopted by the Mulroney government from 1984 to 1990 were inconsistent with US ‘law and order’ models in place at that time. However, since the mid‐1990s, Canadian federal and provincial governments have mimicked some US authoritarian and gender‐blind means of curbing crime. The main objective of this paper is to provide some key examples of criminal justice policy transfer from the USA in Canada. At first glance, Canada may appear to be a ‘kinder, gentler nation,’ but not to the extent assumed by many, if not most, outside observers.

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The concept of globalization has gradually permeated criminology, but more so as applied to transnational organized crime, international terrorism and policing than in addressing processes of criminal justice reform. Based on a wide range of bibliographic and web resources, this article assesses the extent to which a combination of neo-liberal assaults on the social logics of the welfare state and public provision, widespread experimentation with restorative justice and the prospect of rehabilitation through mediation and widely ratified international directives, epitomized by the United Nations Convention on the Rights of the Child, have now made it possible to talk of a global juvenile/youth justice. Conversely it also reflects on how persistent national and local divergences, together with the contradictions of contemporary reform, may preclude any aspiration for the delivery of a universal and consensual product

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Separate systems of justice for children and young people have always been beset by issues of contradiction and compromise. There is compelling evidence that such ambiguity is currently being `resolved' by a greater governmental resort to neo-conservative punitive and correctional interventions and a neo-liberal responsibilizing mentality in which the protection historically afforded to children is rapidly dissolving. This resurgent authoritarianism appears all the more anachronistic when it is set against the widely held commitment to act within the guidelines established by various children's rights conventions. Of note is the United Nations Convention on the Rights of the Child, frequently described as the most ratified human rights convention in the world, but lamentably also the most violated. Based on international research on juvenile custody rates and children's rights compliance in the USA and Western Europe, this article examines why and to what extent `American exceptionalism' might be permeating European nation states.