965 resultados para Backward linkage
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Funded by The Scottish Government
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Funded by The Scottish Government
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This research was funded by the Chief Scientists Office, Scotland (CZH/4/659).
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A planar reconfigurable linear (also rectilinear) rigid-body motion linkage (RLRBML) with two operation modes, that is, linear rigid-body motion mode and lockup mode, is presented using only R (revolute) joints. The RLRBML does not require disassembly and external intervention to implement multi-task requirements. It is created via combining a Robert’s linkage and a double parallelogram linkage (with equal lengths of rocker links) arranged in parallel, which can convert a limited circular motion to a linear rigid-body motion without any reference guide way. This linear rigid-body motion is achieved since the double parallelogram linkage can guarantee the translation of the motion stage, and Robert’s linkage ensures the approximate straight line motion of its pivot joint connecting to the double parallelogram linkage. This novel RLRBML is under the linear rigid-body motion mode if the four rocker links in the double parallelogram linkage are not parallel. The motion stage is in the lockup mode if all of the four rocker links in the double parallelogram linkage are kept parallel in a tilted position (but the inner/outer two rocker links are still parallel). In the lockup mode, the motion stage of the RLRBML is prohibited from moving even under power off, but the double parallelogram linkage is still moveable for its own rotation application. It is noted that further RLRBMLs can be obtained from the above RLRBML by replacing Robert’s linkage with any other straight line motion linkage (such as Watt’s linkage). Additionally, a compact RLRBML and two single-mode linear rigid-body motion linkages are presented.
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Oceanic dimethyl sulfide (DMS) is the enzymatic cleavage product of the algal metabolite dimethylsulfoniopropionate (DMSP) and is the most abundant form of sulfur released into the atmosphere. To investigate the effects of two emerging environmental threats (ocean acidification and warming) on marine DMS production, we performed a large-scale perturbation experiment in a coastal environment. At both ambient temperature and 2 °C warmer, an increase in partial pressure of carbon dioxide (pCO2) in seawater (160-830 ppmv pCO2) favored the growth of large diatoms, which outcompeted other phytoplankton species in a natural phytoplankton assemblage and reduced the growth rate of smaller, DMSP-rich phototrophic dinoflagellates. This decreased the grazing rate of heterotrophic dinoflagellates (ubiquitous micrograzers), resulting in reduced DMS production via grazing activity. Both the magnitude and sign of the effect of pCO2 on possible future oceanic DMS production were strongly linked to pCO2-induced alterations to the phytoplankton community and the cellular DMSP content of the dominant species and its association with micrograzers.
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In 2006 the Gowers Review of Intellectual Property made a series of recommendations for reforming the intellectual property regime to better serve the interests of both consumers and industry. Among the proposed recommendations was that an exception for parody be introduced within the Copyright Designs and Patents Act 1988. In January 2008 the Intellectual Property Office (the IPO) launched the first part of a two-stage consultation process on exceptions to copyright. As part of that consultation process, the IPO proposed a ‘fair dealing style exception’ for parody, and sought views on whether a new exception should be introduced as well as what form it might take. In December 2009 the IPO launched the second stage of this consultation process. The second consultation document rejected the case for a new parody exception. This article considers the place of parody within the copyright regime and the objections levelled against the introduction of an exception set out within the IPO's second consultation document. It invites the IPO to reconsider its decision not to recommend the introduction of a specific exception for parody within the UK.
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Background Understanding the causes of poor mental health in early childhood and adolescence is important as this can be a significant determinant of mental well-being in later years. One potential and relatively unexplored factor is residential mobility in formative years. Previous studies have been relatively small and potentially limited due to methodological issues. The main aim of this study was to investigate the relationship between early residential instability and poor mental health among adolescents and young adults in Northern Ireland.
Methods A Census-based record linkage study of 28% of children aged 0–8 years in 2001 in Northern Ireland (n=49 762) was conducted, with six monthly address change assessments from health registration data and self-reported mental health status from the 2011 Census. Logistic regression models were built adjusting for socioeconomic status (SES), household composition and marital dissolution.
Results There was a graded relationship between the number of address changes and mental ill-health (adjusted OR 3.67, 95% CIs 2.11 to 6.39 for 5 or more moves). This relationship was not modified by SES or household composition. Marital dissolution was associated with poor mental health but did not modify the relationship between address change and mental health (p=0.206). There was some indication that movement after the age of five was associated with an increased likelihood of poor mental health.
Conclusions This large study clearly confirms the close relationship between address change in early years and later poor mental health. Residential mobility may be a useful marker for children at risk of poorer mental health in adolescence and early adulthood
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Purpose: Educational attainment has been shown to be positively associated with mental health and a potential buffer to stressful events. One stressful life event likely to affect everyone in their lifetime is bereavement. This paper assesses the effect of educational attainment on mental health post bereavement.
Methods: By utilising large administrative datasets, linking Census returns to death records and prescribed medication data, we analysed the bereavement exposure of 208,332 individuals aged 25-74 years. Two-level multi-level logistic regression models were constructed to determine the likelihood of antidepressant medication use (a proxy of mental ill-health) post bereavement given level of educational attainment.
Results: Individuals who are bereaved have greater antidepressant use than those who are not bereaved, with over a quarter (26.5%) of those bereaved by suicide in receipt of antidepressant medication compared to just 12.4% of those not bereaved. Within individuals bereaved by a sudden death those with a University Degree or higher qualifications are 73% less likely to be in receipt of antidepressant medication compared to those with no qualifications, after full adjustment for demographic, socio-economic and area factors (OR=0.27, 95% CI 0.09,0.75). Higher educational attainment and no qualifications have an equivalent effect for those bereaved by suicide.
Conclusions: Education may protect against poor mental health, as measured by the use of antidepressant medication, post bereavement, except in those bereaved by suicide. This is likely due to the improved cognitive, personal and psychological skills gained from time spent in education.
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Ubiquitylation or covalent attachment of ubiquitin (Ub) to a variety of substrate proteins in cells is a versatile post-translational modification involved in the regulation of numerous cellular processes. The distinct messages that polyubiquitylation encodes are attributed to the multitude of conformations possible through attachment of ubiquitin monomers within a polyubiquitin chain via a specific lysine residue. Thus the hypothesis is that linkage defines polyubiquitin conformation which in turn determines specific recognition by cellular receptors. Ubiquitylation of membrane surface receptor proteins plays a very important role in regulating receptor-mediated endocytosis as well as endosomal sorting for lysosomal degradation. Epsin1 is an endocytic adaptor protein with three tandem UIMs (Ubiquitin Interacting Motifs) which are responsible for the highly specific interaction between epsin and ubiquitylated receptors. Epsin1 is also an oncogenic protein and its expression is upregulated in some types of cancer. Recently it has been shown that novel K11 and K63 mixed-linkage polyubiquitin chains serve as internalization signal for MHC I (Major Histocompatibility Complex I) molecule through their association with the tUIMs of epsin1. However the molecular mode of action and structural details of the interaction between polyubiquitin chains on receptors and tUIMs of epsin1 is yet to be determined. This information is crucial for the development of anticancer therapeutics targeting epsin1. The molecular basis for the linkage-specific recognition of K11 and K63 mixed-linkage polyubiquitin chains by the tandem UIMs of the endocytic adaptor protein epsin1 is investigated using a combination of NMR methods.
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The delicate balance between the production and disposal of proteins is vital for the changes required in the cell to respond to given stimulus. Ubiquitination is a protein modification with a range of signaling outcomes when ubiquitin is attached to a protein through a highly ordered enzymatic cascade process. Understanding ubiquitination is a growing field and nowadays the application of chemical reactions allows the isolation of quantitative materials for structural studies. Therefore, in this dissertation it is described some of these suitable chemical methodologies to produce an isopeptide bond toward the polymerization of ubiquitin bypassing the enzymatic control with the purpose of showing if these chemical modifications have a direct impact on the structure of ubiquitin. First, the possibility of incorporating non-natural lysine analogs known as mercaptolysines into the polypeptide chain of Ubiquitin was explored when they were attached to ubiquitin by native chemical ligation at its C terminus. The sulfhydryl group was used for the attachment of a paramagnetic label to map the surface of ubiquitin. Second, the condensation catalyzed by silver nitrate was used for the dimer assembly. In particular, the main focus was on examining whether orthogonal protection and deprotection of each monomer have an impact on the reaction yield, since the synthetic strategy has been previously attempted successfully. Third, the formation of ubiquitin dimers was approached by building an inter-ubiquitin linkage mimicking the isopeptide bond with two approaches, the classic disulfide exchange as well as the thiol-ene click reaction by thermal initiation in aqueous conditions. After assembling the dimeric units, they were studied by Nuclear Magnetic Resonance, in order to establish a conformational state profile which depends on the pH conditions. The latter is a very important concept since some ligands have a preferred affinity when the protein-protein hydrophobic patches are in close proximity.
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126 p. El contenido del capítulo 3 está sujeto a confidencialidad.
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Doutoramento em Economia.
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The scientific production, in the field of education, constantly refers to linkage as a special condition to develop research. However, its meaning and the way to achieve that condition are not always clear, particularly for those who are in a training stage of research in education. Meanwhile, the academic production reviewers consider linkage as a very important aspect and essential characteristic of any research project. This paper suggests that linkage involves an epistemological discussion on the research factors in each one of the research stages, such as the construction of the object of study, the definition of methodology, and the data analysis and interpretation, among the most important stages. Linkage takes shape in a written product showing the results from an orderly construction and communication of thought, according to the rules established in a particular field of knowledge.
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2016