Exploring the use of game making across the school curriculum

Computer games as part of education is a well-established topic for research, suggesting that creating games is linked to a range of cognitive and behavioural outcomes. Creating games in all subject disciplines is becoming increasingly possible due to the increasingly higher status of computing in schools across Europe and the prevalence of visual programming languages such as Scratch and Pocket Code. The use of games within education is not new; in a systematic review of 129 papers [1] found that playing games impacts across a range of areas including engagement, cognitive ability and, most commonly, knowledge acquisition and content understanding. However, while research has thus far examined game play and game based learning in education there is limited work focussing on the process of game creation as a method of classroom teaching. This is a prospect which is increasingly possible with the introduction of visual programming languages such as Scratch [2] and Pocket Code. It is suggested that playful learning through computer games could stimulate students’ intrinsic motivation ([3] and that knowledge creation can emerge through the construction of artefacts in a playful learning environment via the co-creation of games [4]. The research presented in this paper is from a pilot study examining the impact of game making in traditional primary and secondary school classrooms (5-18 years) in the United Kingdom (UK). The research, funded by Horizon 2020, is part of a wider European project; No-one Left Behind. In the UK the project has introduced game making into disciplines such as Religious Education, Science and History. Data indicates that although not all students found this a positive experience, computational thinking skills have increased, and students, disaffected with their learning, have re-engaged with learning, increasing their persistence and resulting in a deeper understanding of subject knowledge. In addition initial results suggest that game making has the potential to increase engagement with classroom learning and lead to increased learner satisfaction within lessons. Non-computing teachers have gained in confidence in developing game creation in their subject discipline, increasing their awareness of computational thinking. Barriers identified include teacher familiarity with programming as a means to teach non-STEM subject knowledge, a potential to decrease knowledge acquisition during the process of familiarisation with the teaching tool and a need for software developers to consider design for children with SEND. The project is changing the learning environment and emerging pedagogy has been identified which will be shared in this paper. As a result of the study lesson resources have been created for teachers to use across disciplines which are now available via the project URL; these will be shared in this paper

Reprogramming epigenetic silencing: artificial transcription factors synergize with chromatin remodeling drugs to reactivate the tumor suppressor mammary serine protease inhibitor

Mammary serine protease inhibitor (maspin) is an important tumor suppressor gene whose expression is associated not only with tumor growth inhibition but also with decreased angiogenesis and metastasis. Maspin expression is down-regulated in metastatic tumors by epigenetic mechanisms, including aberrant promoter hypermethylation. We have constructed artificial transcription factors (ATFs) as novel therapeutic effectors able to bind 18-bp sites in the maspin promoter and reactivate maspin expression in cell lines that harbor an epigenetically silenced promoter. In this article, we have investigated the influence of epigenetic modifications on ATF-mediated regulation of maspin by challenging MDA-MB-231 breast cancer cells, comprising a methylated maspin promoter, with different doses of ATFs and chromatin remodeling drugs: the methyltransferase inhibitor 5-aza-2′-deoxycytidine and the histone deacetylase inhibitor suberoylanilide hydroxamic acid. We found that the ATFs synergized with both inhibitors in reactivating endogenous maspin expression. The strongest synergy was observed with the triple treatment ATF-126 + 5-aza-2′-deoxycytidine + suberoylanilide hydroxamic acid, in which the tumor suppressor was reactivated by 600-fold. Furthermore, this combination inhibited tumor cell proliferation by 95%. Our data suggest that ATFs enhance the efficiency of chromatin remodeling drugs in reactivating silenced tumor suppressors. Our results document the power of a novel therapeutic approach that combines both epigenetic and genetic (sequence-specific ATFs) strategies to reactivate specifically silenced regions of the genome and reprogram cellular phenotypes

Predicting worsted spinning performance with an artificial neural network model

For a given fiber spun to pre-determined yarn specifications, the spinning performance of the yarn usually varies from mill to mill. For this reason, it is necessary to develop an empirical model that can encompass all known processing variables that exist in different spinning mills, and then generalize this information and be able to accurately predict yarn quality for an individual mill. This paper reports a method for predicting worsted spinning performance with an artificial neural network (ANN) trained with backpropagation. The applicability of artificial neural networks for predicting spinning performance is first evaluated against a well established prediction and benchmarking tool (Sirolan YarnspecTM). The ANN is then subsequently trained with commercial mill data to assess the feasibility of the method as a mill-specific performance prediction tool. Incorporating mill-specific data results in an improved fit to the commercial mill data set, suggesting that the proposed method has the ability to predict the spinning performance of a specific mill accurately. <br /

Mineralisation of surfactants using ultrasound and the Advanced Fenton Process

The destruction of the surfactants, sodium dodecylbenzene sulfonate (DBS) and dodecyl pyridinium chloride (DPC), using an advanced oxidation process is described. The use of zero valent iron (ZVI) and hydrogen peroxide at pH = 2.5 (the advanced Fenton process), with and without, the application of 20 kHz ultrasound leads to extensive mineralisation of both materials as determined by total organic carbon (TOC)measurements. For DBS, merely stirring with ZVI and H2O2 at 20°C leads to a 51% decrease in TOC, but using 20 kHz ultrasound at 40°C, maintaining the pH at 2.5 throughout and adding extra amounts of ZVI and H2O2 during the degradation, then the extent of mineralisation of DBS is substantially increased to 93%. A similar result is seen for DPC where virtually no degradation occurs at 20°C, but if extra amounts of both ZVI and hydrogen peroxide are introduced during the reaction at 40°C and the pH is maintained at 2.5, then an 87% mineralisation of DPC is obtained. The slow latent remediation of both surfactants and the mechanism of degradation are also discussed

Curvaton Dynamics and the Non-Linearity Parameters in Curvaton Model

We investigate the curvaton dynamics and the non-linearity parameters in curvaton model with potential slightly deviating from the quadratic form in detail. The non-linearity parameter $g_{NL}$ will show up due to the curvaton self-interaction. We also point out that the leading order of non-quadratic term in the curvaton potential can be negative, for example in the axion-type curvaton model. If a large positive $g_{NL}$ is detected, the axion-type curvaton model will be preferred.Comment: 14 pages, 4 figures; refs adde

The most effective but largely ignored target for prostate cancer early detection and intervention

Over the past two decades, the global efforts for the early detection and intervention of prostate cancer seem to have made significant progresses in the basic researches, but the clinic outcomes have been disappointing: (1) prostate cancer is still the most common non-cutaneous cancer in Europe in men, (2) the age-standardized prostate cancer rate has increased in nearly all Asian and African countries, (3) the proportion of advanced cancers at the diagnosis has increased to 8.2% from 3.9% in the USA, (4) the worldwide use of PSA testing and digital rectal examination have failed to reduce the prostate cancer mortality, and (5) there is still no effective preventive method to significantly reduce the development, invasion, and metastasis of prostate cancer… Together, these facts strongly suggest that the global efforts during the past appear to be not in a correlated target with markedly inconsistent basic research and clinic outcomes. The most likely cause for the inconsistence appears due to the fact that basic scientific studies are traditionally conducted on the cell lines and animal models, where it is impossible to completely reflect or replicate the in vivo status. Thus, we would like to propose the human prostate basal cell layer (PBCL) as “the most effective target for the early detection and intervention of prostate cancer”. Our proposal is based on the morphologic, immunohistochemical and molecular evidence from our recent studies of normal and cancerous human prostate tissues with detailed clinic follow-up data. We believe that the human tissue-derived basic research data may provide a more realistic roadmap to guide the clinic practice and to avoid the potential misleading from in vitro and animal studies

4-Deoxyphorbol inhibits HIV-1 infection in synergism with antiretroviral drugs and reactivates viral reservoirs through PKC/MEK activation synergizing with vorinostat.

Latent HIV reservoirs are the main obstacle to eradicate HIV infection. One strategy proposes to eliminate these viral reservoirs by pharmacologically reactivating the latently infected T cells. We show here that a 4-deoxyphorbol ester derivative isolated from Euphorbia amygdaloides ssp. semiperfoliata, 4β-dPE A, reactivates HIV-1 from latency and could potentially contribute to decrease the viral reservoir. 4β-dPE A shows two effects in the HIV replication cycle, infection inhibition and HIV transactivation, similarly to other phorboids PKC agonists such PMA and prostratin and to other diterpene esters such SJ23B. Our data suggest 4β-dPE A is non-tumorigenic, unlike the related compound PMA. As the compounds are highly similar, the lack of tumorigenicity by 4β-dPE A could be due to the lack of a long side lipophilic chain that is present in PMA. 4β-dPE activates HIV transcription at nanomolar concentrations, lower than the concentration needed by other latency reversing agents (LRAs) such as prostratin and similar to bryostatin. PKCθ/MEK activation is required for the transcriptional activity, and thus, anti-latency activity of 4β-dPE A. However, CD4, CXCR4 and CCR5 receptors down-regulation effect seems to be independent of PCK/MEK, suggesting the existence of at least two different targets for 4β-dPE A. Furthermore, NF-κb transcription factor is involved in 4β-dPE HIV reactivation, as previously shown for other PKCs agonists. We also studied the effects of 4β-dPE A in combination with other LRAs. When 4β-dPE A was combined with another PKC agonists such as prostratin an antagonic effect was achieved, while, when combined with an HDAC inhibitor such as vorinostat, a strong synergistic effect was obtained. Interestingly, the latency reversing effect of the combination was synergistically diminishing the EC50 value but also increasing the efficacy showed by the drugs alone. In addition, combinations of 4β-dPE A with antiretroviral drugs as CCR5 antagonist, NRTIs, NNRTIs and PIs, showed a consistent synergistic effect, suggesting that the combination would not interefer with antiretroviral therapy (ART). Finally, 4β-dPE A induced latent HIV reactivation in CD4 + T cells of infected patients under ART at similar levels than the tumorigenic phorbol derivative PMA, showing a clear reactivation effect. In summary, we describe here the mechanism of action of a new potent deoxyphorbol derivative as a latency reversing agent candidate to decrease the size of HIV reservoirs.This work was supported by Ministry of Education of the Peruvian government (PRONABEC), the Universidad Complutense de Madrid (UCM-Santander PR87/19), the Instituto de Salud Carlos III (ISCIII-FIS PI16CIII/00034) and the Spanish AIDS Research Network RD12/0017/0015 that is included in the Spanish I D I Plan and is co-financed by ISCIII-Subdirección General de Evaluación and European Funding for Regional Development (FEDER). This work has also benefited from an “Investissement d’Avenir” grant managed by Agence Nationale de la Recherche (CEBA, ANR- 10-LABX-25-01).S

The Origin of the Universe as Revealed Through the Polarization of the Cosmic Microwave Background

Modern cosmology has sharpened questions posed for millennia about the origin of our cosmic habitat. The age-old questions have been transformed into two pressing issues primed for attack in the coming decade: How did the Universe begin? and What physical laws govern the Universe at the highest energies? The clearest window onto these questions is the pattern of polarization in the Cosmic Microwave Background (CMB), which is uniquely sensitive to primordial gravity waves. A detection of the special pattern produced by gravity waves would be not only an unprecedented discovery, but also a direct probe of physics at the earliest observable instants of our Universe. Experiments which map CMB polarization over the coming decade will lead us on our first steps towards answering these age-old questions.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 212 author available at http://cmbpol.uchicago.ed

The Transcriptomic Landscape of Prostate Cancer Development and Progression: An Integrative Analysis

Next-generation sequencing of primary tumors is now standard for transcriptomic studies, but microarray-based data still constitute the majority of available information on other clinically valuable samples, including archive material. Using prostate cancer (PC) as a model, we developed a robust analytical framework to integrate data across different technical platforms and disease subtypes to connect distinct disease stages and reveal potentially relevant genes not identifiable from single studies alone. We reconstructed the molecular profile of PC to yield the first comprehensive insight into its development, by tracking changes in mRNA levels from normal prostate to high-grade prostatic intraepithelial neoplasia, and metastatic disease. A total of nine previously unreported stage-specific candidate genes with prognostic significance were also found. Here, we integrate gene expression data from disparate sample types, disease stages and technical platforms into one coherent whole, to give a global view of the expression changes associated with the development and progression of PC from normal tissue through to metastatic disease. Summary and individual data are available online at the Prostate Integrative Expression Database (PIXdb), a user-friendly interface designed for clinicians and laboratory researchers to facilitate translational research