4,134 research outputs found

    Metamaterial metal-based bolometers

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    We demonstrate metamaterial metal-based bolometers, which take advantage of resonant absorption in that a spectral and/or polarization filter can be built into the bolometer. Our proof-of-principle gold-nanostructure-based devices operate around 1.5 \mum wavelength and exhibit room-temperature time constants of about 134 \mus. The ultimate detectivity is limited by Johnson noise, enabling room-temperature detection of 1 nW light levels within 1 Hz bandwidth. Graded bolometer arrays might allow for integrated spectrometers with several octaves bandwidth without the need for gratings or prisms and for integrated polarization analysis without external polarization optics

    Temporal endogenous gene expression profiles in response to polymer-mediated transfection and profile comparison to lipid-mediated transfection

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    Background Design of efficient nonviral gene delivery systems is limited by the rudimentary understanding of specific molecules that facilitate transfection. Methods Polyplexes using 25-kDa polyethylenimine (PEI) and plasmid encoding green fluorescent protein (GFP) were delivered to HEK 293T cells. After treating cells with polyplexes, microarrays were used to identify endogenous genes differentially expressed between treated and untreated cells (2 h of exposure) or between flow-separated transfected cells (GFP+) and treated, untransfected cells (GFP–) at 8, 16 and 24 h after lipoplex treatment. Cell priming studies were conducted using pharmacologic agents to alter endogenous levels of the identified differentially expressed genes to determine effect on transfection levels. Differentially expressed genes in polyplex-mediated transfection were compared with those differentially expressed in lipoplex transfection to identify DNA carrier-dependent molecular factors. Results Differentially expressed genes were RGS1, ARHGAP24, PDZD2, SNX24, GSN and IGF2BP1 after 2 h; RAP1A and ACTA1 after 8 h; RAP1A, WDR78 and ACTA1 after 16 h; and RAP1A, SCG5, ATF3, IREB2 and ACTA1 after 24 h. Pharmacologic studies altering endogenous levels for ARHGAP24, GSN, IGF2BP1, PDZD2 and RGS1 were able to increase or decrease transgene production. Comparing differentially expressed genes for polyplexes and lipoplexes, no common genes were identified at the 2-h time point, whereas, after the 8-h time point, RAP1A, ATF3 and HSPA6 were similarly expressed. SCG5 and PGAP1 were only upregulated in polyplex-transfected cells. Conclusions The identified genes and pharmacologic agents provide targets for improving transfection systems, although polyplex or lipoplex dependencies must be considered. Includes supplementary materials

    Temporal endogenous gene expression profiles in response to lipid-mediated transfection

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    Background — Design of efficient nonviral gene delivery systems is limited as a result of the rudimentary understanding of the specific molecules and processes that facilitate DNA transfer. Methods — Lipoplexes formed with Lipofectamine 2000 (LF2000) and plasmid-encoding green fluorescent protein (GFP) were delivered to the HEK 293T cell line. After treating cells with lipoplexes, HG-U133 Affymetrix microarrays were used to identify endogenous genes differentially expressed between treated and untreated cells (2 h exposure) or between flow-separated transfected cells (GFP+) and treated, untransfected cells (GFP–) at 8, 16 and 24 h after lipoplex treatment. Cell priming studies were conducted using pharmacologic agents to alter endogenous levels of the identified differentially expressed genes to determine effect on transfection levels. Results — Relative to untreated cells 2 h after lipoplex treatment, only downregulated genes were identified ≥ 30-fold: ALMS1, ITGB1, FCGR3A, DOCK10 and ZDDHC13. Subsequently, relative to GFP– cells, the GFP+ cell population showed at least a five-fold upregulation of RAP1A and PACSIN3 (8 h) or HSPA6 and RAP1A (16 and 24 h). Pharmacologic studies altering endogenous levels for ALMS1, FCGR3A, and DOCK10 (involved in filopodia protrusions), ITGB1 (integrin signaling), ZDDHC13 (membrane trafficking) and PACSIN3 (proteolytic shedding of membrane receptors) were able to increase or decrease transgene production. Conclusions — RAP1A, PACSIN3 and HSPA6 may help lipoplex-treated cells overcome a transcriptional shutdown due to treatment with lipoplexes and provide new targets for investigating molecular mechanisms of transfection or for enhancing transfection through cell priming or engineering of the nonviral gene delivery system. Includes supporting materials

    Changing Climate for Quality Assured Regional Qualifications in the Pacific: An innovative collaboration (EU-PacTVET & EQAP)

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    The Pacific region embraces 22 countries and territories. With more than 7,500 islands over 30 million square kilometres, their combined land mass accounts for only two per cent of this area. Climate change and disasters threaten Pacific economies, livelihoods and cultures, and impact a range of sectors, including natural resources, agriculture, food security, education, public health and infrastructure. The Pacific leaders have continued to reaffirm the ongoing urgency of addressing the challenges posed by, and the impacts of, climate change as a regional priority.1 At the Forty-Sixth Pacific Islands Forum held in September 2015 the leaders of the Pacific small island states reiterated their concerns that climate change remains the single greatest threat to the livelihood, security and well-being of the people of the Pacific. Pacific Island Countries (PICs) recognise a commitment to sustainable development is a national responsibility but also realize that this cannot be achieved without a regional approach. The European Union Pacific Technical, Vocational Education and Training in Sustainable Energy (SE) and Climate Change Adaptation (CCA) Project (EU PacTVET) aims to develop a quality assured regional qualification and accreditation process. This paper reflects discussions, views and validations from members of government agencies, private industry, training providers, non-government organisations, community groups, donors, and industry associations surrounding a regional accreditation strategy

    Accurate measurement of 5-methylcytosine and 5-hydroxymethylcytosine in human cerebellum DNA by oxidative bisulfite on an array (OxBS-array).

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    The Infinium 450K Methylation array is an established tool for measuring methylation. However, the bisulfite (BS) reaction commonly used with the 450K array cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). The oxidative-bisulfite assay disambiguates 5mC and 5hmC. We describe the use of oxBS in conjunction with the 450K array (oxBS-array) to analyse 5hmC/5mC in cerebellum DNA. The "methylation" level derived by the BS reaction is the combined level of 5mC and 5hmC at a given base, while the oxBS reaction gives the level of 5mC alone. The level of 5hmC is derived by subtracting the oxBS level from the BS level. Here we present an analysis method that distinguishes genuine positive levels of 5hmC at levels as low as 3%. We performed four replicates of the same sample of cerebellum and found a high level of reproducibility (average r for BS = 98.3, and average r for oxBS = 96.8). In total, 114,734 probes showed a significant positive measurement for 5hmC. The range at which we were able to distinguish 5hmC occupancy was between 3% and 42%. In order to investigate the effects of multiple replicates on 5hmC detection we also simulated fewer replicates and found that decreasing the number of replicates to two reduced the number of positive probes identified by > 50%. We validated our results using qPCR in conjunction with glucosylation of 5hmC sites followed by MspI digestion and we found good concordance with the array estimates (r = 0.94). This experiment provides a map of 5hmC in the cerebellum and a robust dataset for use as a standard in future 5hmC analyses. We also provide a novel method for validating the presence of 5hmC at low levels, and highlight some of the pitfalls associated with measuring 5hmC and 5mC.S. Balasubramanian is a Senior Investigator of The Wellcome Trust and the Balasubramanian group is core-funded by Cancer Research UK. We would like to thank Tobias Ost and Christine Clark of Cambridge Epigenetix Ltd. for valuable discussions and development of the method.This article was originally published in PLOS ONE (Field SF, Beraldi D, Bachman M, Stewart SK, Beck S, Balasubramanian S, PLoS ONE 2015, 10(2): e0118202. doi:10.1371/journal.pone.0118202

    Applying the integrated trans-contextual model to mathematics activities in the classroom and homework behavior and attainment

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    The aim of the present study was to test hypotheses of the trans-contextual model. We predicted relations between perceived autonomy support, autonomous motivation toward mathematics learning activities in an educational context, autonomous motivation toward mathematics homework in an out-of-school context, social-cognitive variables and intentions for future engagement in mathematics homework, and mathematics homework outcomes. Secondary school students completed measures of perceived autonomy support from teachers and autonomous motivation for in-class mathematics activities; measures of autonomous motivation, social-cognitive variables, and intentions for out-of-school mathematics homework; and follow-up measures of students' mathematics homework outcomes: self-reported homework engagement and actual homework grades. Perceived autonomy support was related to autonomous motivation toward in-class mathematics activities. There were trans-contextual effects of autonomous motivation across educational and out-of-school contexts, and relations between out-of-school autonomous motivation, intentions, and mathematics homework outcomes. Findings support trans-contextual effects of autonomous motivation toward mathematics activities across educational and out-of-school contexts and homework outcomes

    GPs’ role in caring for children and young people with life-limiting conditions: a retrospective cohort study

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    Background: GPs are rarely actively involved in healthcare provision for children and young people (CYP) with life-limiting conditions (LLCs). This raises problems when these children develop minor illness or require management of other chronic diseases. Aim: To investigate the association between GP attendance patterns and hospital urgent and emergency care use. Design and setting: Retrospective cohort study using a primary care data source (Clinical Practice Research Datalink) in England. The cohort numbered 19 888. Method: CYP aged 0–25 years with an LLC were identified using Read codes (primary care) or International Classification of Diseases 10 th Revision (ICD-10) codes (secondary care). Emergency inpatient admissions and accident and emergency (A&E) attendances were separately analysed using multivariable, two-level random intercept negative binomial models with key variables of consistency and regularity of GP attendances. Results: Face-to-face GP surgery consultations reduced, from a mean of 7.12 per person year in 2000 to 4.43 in 2015. Those consulting the GP less regularly had 15% (95% confidence interval [CI] = 10% to 20%) more emergency admissions and 5% more A&E visits (95% CI = 1% to 10%) than those with more regular consultations. CYP who had greater consistency of GP seen had 10% (95% CI = 6% to 14%) fewer A&E attendances but no significant difference in emergency inpatient admissions than those with lower consistency. Conclusion: There is an association between GP attendance patterns and use of urgent secondary care for CYP with LLCs, with less regular GP attendance associated with higher urgent secondary healthcare use. This is an important area for further investigation and warrants the attention of policymakers and GPs, as the number of CYP with LLCs living in the community rises

    The Role of Distal Variables in Behavior Change: Effects of Adolescents\u27 Risk for Marijuana Use on Intention to Use Marijuana

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    This study uses an integrative model of behavioral prediction as an account of adolescents\u27 intention to use marijuana regularly. Adolescents\u27 risk for using marijuana regularly is examined to test the theoretical assumption that distal variables affect intention indirectly. Risk affects intention indirectly if low-risk and high-risk adolescents differ on the strength with which beliefs about marijuana are held, or if they differ on the relative importance of predictors of intention. A model test confirmed that the effect of risk on intention is primarily indirect. Adolescents at low and high risk particularly differed in beliefs concerning social costs and costs to self-esteem. Not surprisingly, at-risk adolescents took a far more positive stand toward using marijuana regularly than did low-risk adolescents. On a practical level, the integrative model proved to be an effective tool for predicting intention to use marijuana, identifying key variables for interventions, and discriminating between target populations in terms of determinants of marijuana use

    Sources of Sex Information Used by Young British Women Who Have Sex with Women (WSW) and Women Who Have Sex Exclusively with Men (WSEM): Evidence from the National Survey of Sexual Attitudes and Lifestyles

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    There is little consideration about the provision of information about sex to women who have sex with women (WSW). This study drew on data from the third National Survey of Sexual Attitudes and Lifestyle, a nationally representative survey of people in Great Britain. Logistic regression was undertaken to examine firstly the relationships between WSW and women who have sex exclusively with men (WSEM) and their main source of information about sex, and secondly between WSW/WSEM and unmet need for information about sex. Each source was included as the binary outcome indicating yes this was the main source, or no this was not the main source of information about sex. The results found that WSW had significantly lower odds of reporting lessons at schools as their main source of information, and significantly higher odds of reporting sources defined as ‘other’ (predominantly first girlfriend/boyfriend or sexual partner) as their main source of information. Reported levels of unmet need for information was also higher amongst young WSW compared with WSEM. This study provides new insights into the sex educational needs of young women and highlights the need for sex education in schools in Great Britain to include information on a full-range of sexual practices, including same-sex sexual relationships
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