1,233 research outputs found

    Development of a simple information pump.

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    The Information Pump (IP) is a methodology that aims to counter the problems arising from traditional subjective product data collection. The IP is a game theory based process that aims to maximise information extracted from a panel of subjects, while maintaining their interest in the process through a continuous panelist scoring method. The challenge with implementing this arises from the difficulty in executing the 'game'. In its original format, there is an assumption that the game is played with each player using their own PC to interact with the process. While this in theory allows information and scores to flow in a controlled manner between the players, it actually provides a major barrier to the wider adoption of the IP method. This barrier is two-fold: it is costly and complex, and it is not a natural manner for exchanging information. The core objective is to develop a low cost version of the IP method. This will use the game theory approach to maintain interest among participants and maximise information extraction, but remove the need for each participant to have their own PC interface to the game. This will require replacing both the inter-player communication method and the score keeping/reporting

    Deciphering c-MYC-regulated genes in two distinct tissues.

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    BACKGROUND: The transcription factor MYC is a critical regulator of diverse cellular processes, including both replication and apoptosis. Differences in MYC-regulated gene expression responsible for such opposing outcomes in vivo remain obscure. To address this we have examined time-dependent changes in global gene expression in two transgenic mouse models in which MYC activation, in either skin suprabasal keratinocytes or pancreatic islet β-cells, promotes tissue expansion or involution, respectively. RESULTS: Consistent with observed phenotypes, expression of cell cycle genes is increased in both models (albeit enriched in β-cells), as are those involved in cell growth and metabolism, while expression of genes involved in cell differentiation is down-regulated. However, in β-cells, which unlike suprabasal keratinocytes undergo prominent apoptosis from 24 hours, there is up-regulation of genes associated with DNA-damage response and intrinsic apoptotic pathways, including Atr, Arf, Bax and Cycs. In striking contrast, this is not the case for suprabasal keratinocytes, where pro-apoptotic genes such as Noxa are down-regulated and key anti-apoptotic pathways (such as Igf1-Akt) and those promoting angiogenesis are up-regulated. Moreover, dramatic up-regulation of steroid hormone-regulated Kallikrein serine protease family members in suprabasal keratinocytes alone could further enhance local Igf1 actions, such as through proteolysis of Igf1 binding proteins. CONCLUSIONS: Activation of MYC causes cell growth, loss of differentiation and cell cycle entry in both β-cells and suprabasal keratinocytes in vivo. Apoptosis, which is confined to β-cells, may involve a combination of a DNA-damage response and downstream activation of pro-apoptotic signalling pathways, including Cdc2a and p19(Arf)/p53, and downstream targets. Conversely, avoidance of apoptosis in suprabasal keratinocytes may result primarily from the activation of key anti-apoptotic signalling pathways, particularly Igf1-Akt, and induction of an angiogenic response, though intrinsic resistance to induction of p19(Arf) by MYC in suprabasal keratinocytes may contribute.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    Phonon bottleneck in GaAs/AlxGa1-xAs quantum dots

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    We report low-temperature photoluminescence measurements on highly-uniform GaAs/AlxGa1-xAs quantum dots grown by droplet epitaxy. Recombination between confined electrons and holes bound to carbon acceptors in the dots allow us to determine the energies of the confined states in the system, as confirmed by effective mass calculations. The presence of acceptor-bound holes in the quantum dots gives rise to a striking observation of the phonon-bottleneck effect

    Acute changes in liver tumour perfusion measured non-invasively with arterial spin labelling

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    BACKGROUND: Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting (or modifying) therapies. In this study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was investigated to measure acute changes in perfusion of colorectal cancer in the liver, in response to vascular disruption therapy with OXi4503. METHODS: SW1222 and LS174T tumours were established in the liver of MF1 nu/nu mice via intrasplenic injection. Perfusion and R2(*) MRI measurements were acquired with an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg(-1) OXi4503. RESULTS: A significant decrease in SW1222 tumour perfusion was observed (-43±33%, P<0.005). LS174T tumours had a significantly lower baseline level of perfusion. Intrinsic susceptibility MRI showed a significant increase in R2(*) in LS174T tumours (28±25%, P<0.05). An association was found between the change in tumour perfusion and the proximity to large vessels, with pre-treatment blood flow predictive of subsequent response. Histological evaluation confirmed the onset of necrosis and evidence of heterogeneous response between tumour deposits. CONCLUSIONS: Hepatic ASL-MRI can detect acute response to targeted tumour vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has potential for use in a clinical setting

    Higher self-reported physical activity Is associated with lower systolic blood pressure: The Dietary Intervention Study in Childhood (DISC)

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    Objective: Children participating in a dietary clinical trial were studied to assess physical activity patterns in boys and girls longitudinally from late childhood through puberty; and to determine the association of level of physical activity on systolic blood pressure (SBP), low density lipoprotein (LDL) cholesterol, and body mass index (BMI). Patients and Methods: In the Dietary Intervention Study in Childhood (DISC), a randomized clinical trial of a reduced saturated fat and cholesterol diet in 8-10 year olds with elevated LDL, a questionnaire that determined time spent in five intensity levels of physical activity was completed at baseline and at 1 and 3 years. A MET score was calculated for weekly activity; hours per week were calculated for intense activities. We hypothesized that weekly self-reported physical activity would be associated with lower SBP, LDL, and BMI over three years. Longitudinal data analyses were performed for each outcome (SBP, LDL, and BMI) using generalized estimating equations with MET score per week as the independent variable adjusted for visit, gender, and Tanner stage (BMI was included in models for SBP and LDL). Results: The initial study cohort comprised 663 youths (362 male; age 9.7 years, 301 female; age 9.0 years) of whom 623 (94%) completed the 3-year visit. For every 100 MET-hours of physical activity, there was a decrease of 1.15 mmHg of SBP (p=0.0038). There was a 1.28 mg/dl decline in LDL (p=0.10) for a similar energy expenditure. For BMI, an analysis of intense physical activity showed that for every 10 hours of intense activity, there was a trend toward significance with a 0.2 kg/m2 decrease (p=0.06). Conclusion: Children with elevated cholesterol who lead a more physically active lifestyle have lower SBP and a trend toward lower LDL over a 3-year interval. Long-term participation in intense physical activity may reduce BMI as well

    Life or cell death: identifying c-Myc regulated genes in two distinct tissues

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    The c-myc oncogene is over-expressed or deregulated in many human cancers. c-myc encodes a transcription factor, the oncoprotein c-Myc (Myc), which acts as a master regulator of genes involved in such diverse cellular processes as replication and growth, loss of differentiation, invasion, and angiogenesis. Myc can also act as its own tumour suppressor by promoting cell death in the form of apoptosis. Thus, for putative cancer cells to arise, apoptosis must be blocked. Conditional MycERTAM transgenic mice allow regulated activation of Myc in distinct cell populations (skin suprabasal keratinocytes and pancreatic islet β-cells) and have highlighted contrasting behaviour between these two adult tissues in vivo: proliferation in the skin, and apoptosis in the pancreas. Given the crucial dependence on tissue location in vivo, we still do not know enough about the key divergence in Myc-regulated genes and proteins under conditions favouring opposing outcomes. To address this, we performed high-throughput transcriptome analysis using oligonucleotide microarrays. The in vivo transcriptional response to deregulated Myc was analysed for skin keratinocytes and laser-captured pancreatic islets following a time-course of MycERTAM activation. Due to the multi-factorial nature of the experimental design, novel statistical tools were developed allowing the use of linear models for inference of changes in gene-expression based on multiple experimental variables. Comparison of the transcriptional response between the two tissues identified potential signalling pathways which may promote apoptosis of β-cells or survival of skin keratinocytes: the DNA damage response pathway, and the Insulin-like growth factor 1 (Igf1) signalling pathway respectively. In addition, a marked change in expression was detected in members of the steroid hormone-regulated Kallikrein serine protease family in suprabasal keratinocytes but not for β-cells. These have been found to play an important role in regulating Igf1/Igf1-receptor ligation through proteolysis of the Igf1 binding proteins, are previously categorised markers for several human cancers, and may indicate a tissue-specific regulatory mechanism for determining ultimate Myc function in vivo

    Crise sócioeconômica e processo de trabalho : à busca de uma relação teórica

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    Acesso ao livro na íntegra no endereço: http://acesso.mte.gov.br/data/files/8A7C816A2E7311D1012FEAA3403E09B2/TrabalhonaCapital.pdf.Este capítulo propõe-se a explorar questões como estas e suscitar hipóteses sobre a relação teórica das crises capitalistas com mudanças na organização do processo de trabalho, entendidas como tentativas de reorganizar o trabalho em função da crise, estratégias que permitam ao capital contornar a crise e voltar a trilhar os caminhos da acumulação, conduzindo possivelmente a novas formas de exploração do trabalho e de produção da mais-valia absoluta e relativa

    Characteristics of outdoor falls among older people: A qualitative study

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    Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people
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