1,773 research outputs found

    Preparando estudantes da Pós-Graduação para a indústria e aprendizado para a vida: uma abordagem baseada em projeto

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    Este estudo de caso baseia-se em projetos que têm uma dimensão de mundo real, em que os alunos estão mais propensos a adquirir as competências e habilidades que a indústria exige. Informações de base são apresenta- das, relacionando vínculos entre a academia, a indústria e o papel dos projetos dos estudantes. Os dados são provenien- tes de programas de computação em nível de mestrado, da Universidade de Sunderland, e dos projetos desenvolvidos por cada um dos estudantes. Uma abordagem específica permitiu que centenas de projetos bem sucedidos, realiza- dos anualmente com o setor da indústria, fossem descritos juntamente com a avaliação de sua eficácia em dar aos alunos uma formação de competência para a vida

    Systemic Administration of Tolerogenic Dendritic Cells Ameliorates Murine Inflammatory Arthritis

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    The expression of various cell surface molecules and the production of certain cytokines are important mechanisms by which dendritic cells (DC) are able to bias immune responses. This paper describes the effects of the inflammatory cytokine tumor necrosis factor (TNF)-α on DC phenotype and function. TNF-α treatment resulted in upregulation of MHC class II and CD86 in the absence of increased cell surface CD40 and CD80 or the production of IL-12. Additionally TNF-α treated cells were able to bias T cell responses towards an anti-inflammatory profile. On a note of caution this tolerogenic phenotype of the DC was not stable upon subsequent TLR-4 ligation as a 4 hour pulse of the TNF-α treated DC with lipopolysaccharide (LPS) resulted in the restoration of IL-12 production and an enhancement of their T cell stimulatory capacity which resulted in an increased IFN-γ production. However, TNF-α treated DC, when administered in vivo, were shown to ameliorate disease in collagen induced arthritis, an experimental model of inflammatory joint disease. Mice receiving TNF-α treated DC but not LPS matured DC had a delayed onset, and significantly reduced severity, of arthritis. Disease suppression was associated with reduced levels of collagen specific IgG2a and decreased inflammatory cell infiltration into affected joints. In summary the treatment of DC with TNF-α generates an antigen presenting cell with a phenotype that can reduce the pro-inflammatory response and direct the immune system towards a disease modifying, anti-inflammatory state

    Curriculum Alignment After Reforms: A Systematic Review with Considerations for Queensland Pre- and In-service Teachers

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    This systematic review synthesises research on curriculum alignment to suggest considerations for the implementation of the Senior secondary curriculum reform in Queensland, Australia. It focuses on the coherence of cognitive skills in the prescribed and enacted curriculum as these are typically the least aligned curriculum components. Search methods, which followed the PRISMA model, resulted in 108 relevant articles for qualitative synthesis. Results show that alignment after curriculum reforms is typically low. The use of educational taxonomies can support curriculum alignment. Marzano and Kendall’s (2007) New Taxonomy of Educational Objectives underpins the new Queensland Senior secondary syllabi which, in line with other Australian policy, encourage the explicit teaching of cognitive skills. Research is needed on the enacted cognitive skills curriculum in Queensland and its alignment with the reformed prescribed curriculum. To promote the successful implementation of the new Queensland Senior system, pre- and in-service teachers could engage with the New Taxonomy and best practice for teaching cognitive skills

    Curriculum alignment after reforms: a systematic review with considerations for Queensland pre- and in-service teachers

    Get PDF
    This systematic review synthesises research on curriculum alignment to suggest considerations for the implementation of the Senior secondary curriculum reform in Queensland, Australia. It focuses on the coherence of cognitive skills in the prescribed and enacted curriculum as these are typically the least aligned curriculum components. Search methods, which followed the PRISMA model, resulted in 108 relevant articles for qualitative synthesis. Results show that alignment after curriculum reforms is typically low. The use of educational taxonomies can support curriculum alignment. Marzano and Kendall’s (2007) New Taxonomy of Educational Objectives underpins the new Queensland Senior secondary syllabi which, in line with other Australian policy, encourage the explicit teaching of cognitive skills. Research is needed on the enacted cognitive skills curriculum in Queensland and its alignment with the reformed prescribed curriculum. To promote the successful implementation of the new Queensland Senior system, pre- and in-service teachers could engage with the New Taxonomy and best practice for teaching cognitive skills

    Differential Hox expression in murine embryonic stem cell models of normal and malignant hematopoiesis

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    The Hox family are master transcriptional regulators of developmental processes, including hematopoiesis. The Hox regulators, caudal homeobox factors (Cdx1-4), and Meis1, along with several individual Hox proteins, are implicated in stem cell expansion during embryonic development, with gene dosage playing a significant role in the overall function of the integrated Hox network. To investigate the role of this network in normal and aberrant, early hematopoiesis, we employed an in vitro embryonic stem cell differentiation system, which recapitulates mouse developmental hematopoiesis. Expression profiles of Hox, Pbx1, and Meis1 genes were quantified at distinct stages during the hematopoietic differentiation process and compared with the effects of expressing the leukemic oncogene Tel/PDGFR;2. During normal differentiation the Hoxa cluster, Pbx1 and Meis1 predominated, with a marked reduction in the majority of Hox genes (27/39) and Meis1 occurring during hematopoietic commitment. Only the posterior Hoxa cluster genes (a9, a10, a11, and a13) maintained or increased expression at the hematopoietic colony stage. Cdx4, Meis1, and a subset of Hox genes, including a7 and a9, were differentially expressed after short-term oncogenic (Tel/PDGFR;2) induction. Whereas Hoxa4-10, b1, b2, b4, and b9 were upregulated during oncogenic driven myelomonocytic differentiation. Heterodimers between Hoxa7/Hoxa9, Meis1, and Pbx have previously been implicated in regulating target genes involved in hematopoietic stem cell (HSC) expansion and leukemic progression. These results provide direct evidence that transcriptional flux through the Hox network occurs at very early stages during hematopoietic differentiation and validates embryonic stem cell models for gaining insights into the genetic regulation of normal and malignant hematopoiesis

    Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

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    The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses

    A target-cell limited model can reproduce influenza infection dynamics in hosts with differing immune responses

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    We consider a hierarchy of ordinary differential equation models that describe the within-host viral kinetics of influenza infections: the IR model explicitly accounts for an immune response to the virus, while the simpler, target-cell limited TEIV and TV models do not. We show that when the IR model is fitted to pooled experimental murine data of the viral load, fraction of dead cells, and immune response levels, its parameters values can be determined. However, if, as is common, only viral load data are available, we can estimate parameters of the TEIV and TV models but not the IR model. These results are substantiated by a structural and practical identifiability analysis. We then use the IR model to generate synthetic data representing infections in hosts whose immune responses differ. We fit the TV model to these synthetic datasets and show that it can reproduce the characteristic exponential increase and decay of viral load generated by the IR model. Furthermore, the values of the fitted parameters of the TV model can be mapped from the immune response parameters in the IR model. We conclude that, if only viral load data are available, a simple target-cell limited model can reproduce influenza infection dynamics and distinguish between hosts with differing immune responses

    The Development and Validation of a Mental Toughness Scale for Adolescents

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    The present study examined the validity of a newly developed instrument, the Mental Toughness Scale for Adolescents (MTS-A), which examines the attributes of challenge, commitment, confidence (abilities and interpersonal) and control (life and emotion). The six factor model was supporting using Exploratory Factor Analysis (EFA, n = 373) and Confirmatory Factor Analysis (CFA, n = 372). In addition, the mental toughness attributes correlated with adolescents’ academic motivation and engagement (n = 439), well-being (depression and anxiety) (n = 279) and test anxiety (n = 279), indicating relations with a number of affective, cognitive and behavioural dispositions, and demonstrating relevance in education and potentially mental health contexts

    Screening families of patients with premature coronary heart disease to identify avoidable cardiovascular risk: a cross-sectional study of family members and a general population comparison group

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    <b>Background:</b> Primary prevention should be targeted at individuals with high global cardiovascular risk, but research is lacking on how best to identify such individuals in the general population. Family history is a good proxy measure of global risk and may provide an efficient mechanism for identifying high risk individuals. The aim was to test the feasibility of using patients with premature cardiovascular disease to recruit family members as a means of identifying and screening high-risk individuals. <b>Findings:</b> We recruited family members of 50 patients attending a cardiology clinic for premature coronary heart disease (CHD). We compared their cardiovascular risk with a general population control group, and determined their perception of their risk and current level of screening. 103 (36%) family members attended screening (27 siblings, 48 adult offspring and 28 partners). Five (5%) had prevalent CHD. A significantly higher percentage had an ASSIGN risk score >20% compared with the general population (13% versus 2%, p < 0.001). Only 37% of family members were aware they were at increased risk and only 50% had had their blood pressure and serum cholesterol level checked in the previous three years. <b>Conclusions:</b> Patients attending hospital for premature CHD provide a mechanism to contact family members and this can identify individuals with a high global risk who are not currently screened
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