Quantum interference enhances the performance of single-molecule transistors.

Quantum effects in nanoscale electronic devices promise to lead to new types of functionality not achievable using classical electronic components. However, quantum behaviour also presents an unresolved challenge facing electronics at the few-nanometre scale: resistive channels start leaking owing to quantum tunnelling. This affects the performance of nanoscale transistors, with direct source-drain tunnelling degrading switching ratios and subthreshold swings, and ultimately limiting operating frequency due to increased static power dissipation. The usual strategy to mitigate quantum effects has been to increase device complexity, but theory shows that if quantum effects can be exploited in molecular-scale electronics, this could provide a route to lower energy consumption and boost device performance. Here we demonstrate these effects experimentally, showing how the performance of molecular transistors is improved when the resistive channel contains two destructively interfering waves. We use a zinc-porphyrin coupled to graphene electrodes in a three-terminal transistor to demonstrate a >104 conductance-switching ratio, a subthreshold swing at the thermionic limit, a >7 kHz operating frequency and stability over >105 cycles. We fully map the anti-resonance interference features in conductance, reproduce the behaviour by density functional theory calculations and trace back the high performance to the coupling between molecular orbitals and graphene edge states. These results demonstrate how the quantum nature of electron transmission at the nanoscale can enhance, rather than degrade, device performance, and highlight directions for future development of miniaturized electronics

Catalan Teenagers’ Identity, Literacy and Language Practices on YouTube

This chapter addresses the interconnection between identity building and the use and learning of language and literacy online. We will do so through a case study that investigates the specifics of three Catalan teenage language users and learners who use YouTube as a multimodal space of confluence for making meaning. We will particularly address three research questions: 1. How do teenage language users and learners in Catalonia appropriate YouTube? 2. What means of performing identity do teenagers in Catalonia employ on YouTube? 3. How do teenagers in Catalonia as youtubers develop such means of identity representation and performance in relation to language and literacy practices?This research was supported in part by a postdoctoral grant from the autonomous government of Galicia (Xunta de Galicia, Spain) awarded to Boris Vazquez-Calvo (ED481B 2017/007). This research was also supported by the research project ForVid (Ministry of Science, Innovation and Universities—National Research Agency, Spain: Video as a language learning format in and outside schools, RTI2018-100790-B-I00). There is also collaboration with the research project CDEPI (FEDER/Ministry of Science, Innovation and Universities—National Research Agency, Spain: Competencia digital y e-inclusión del alumnado de educación primaria de Galicia: el papel de la escuela, la familia y el entorno próximo, EDU2015-67975-C3-1-P)

Heregulin β1 drives gefitinib-resistant growth and invasion in tamoxifen-resistant MCF-7 breast cancer cells

Introduction Resistance to anti-epidermal growth factor receptor (anti-EGFR) therapies is an emerging clinical problem. The efficacy of anti-EGFR therapies can be influenced by the presence of heregulins (HRGs), which can bind erbB3/4 receptors and can activate alternative signalling pathways. In the present study we have examined whether HRG signalling can circumvent EGFR blockade in an EGFR-positive tamoxifen-resistant MCF-7 (Tam-R) breast cancer cell line. Methods Tam-R cells, incubated with the selective EGFR tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839), were exposed to HRGβ1 and the effects on erbB receptor dimerization profiles and on activation of associated downstream signalling components were assessed by immunoprecipitation, western blotting and immunocytochemistry. The effects of HRGβ1 on gefitinib-treated Tam-R cell growth and invasion were also examined, and HRGβ1 expression levels were assessed in breast cancer tissue by immunohistochemistry to address the potential clinical relevance of such a resistance mechanism. Results In Tam-R cells, HRGβ1 promoted erbB3/erbB2 and erbB3/EGFR heterodimerization, promoted ERK1/2 and AKT pathway activation and increased cell proliferation and invasion. Gefitinib prevented HRGβ1-driven erbB3/EGFR heterodimerization, ERK1/2 activation and Tam-R cell proliferation, but HRGβ1-driven erbB3/erbB2 heterodimerization, AKT activation and Tam-R cell invasion were maintained. A combination of gefitinib and the phosphatidylinositol 3-kinase inhibitor LY294002 effectively blocked HRGβ1-mediated intracellular signalling activity, growth and invasion in Tam-R cells. Similarly, targeting erbB2 with trastuzumab in combination with gefitinib in Tam-R cells reduced HRGβ1-induced erbB2 and ERK1/2 activity; however, HRGβ1-driven AKT activity and cell growth were maintained while cell invasion was significantly enhanced with this combination. In clinical tissue all samples demonstrated cytoplasmic tumour epithelial HRGβ1 protein staining, with expression correlating with EGFR positivity and activation of both AKT and ERK1/2. Conclusion HRGβ1 can overcome the inhibitory effects of gefitinib on cell growth and invasion in Tam-R cells through promotion of erbB3/erbB2 heterodimerization and activation of the phosphatidylinositol 3-kinase/AKT signalling pathway. This may have implications for the effectiveness of anti-EGFR therapies in breast cancer as HRGβ1 is enriched in many EGFR-positive breast tumours

ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.

During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angiogenesis, and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis. Myeloid-derived suppressor cells, a group of immature neutrophils recently identified as mediators of vasculogenesis and metastasis, were recruited to the tumor in response to ELF5. Depletion of these cells using specific Ly6G antibodies prevented ELF5 from driving vasculogenesis and metastasis. Expression signatures in luminal A breast cancers indicated that increased myeloid cell invasion and inflammation were correlated with ELF5 expression, and increased ELF5 immunohistochemical staining predicted much shorter metastasis-free and overall survival of luminal A patients, defining a group who experienced unexpectedly early disease progression. Thus, in the MMTV-PyMT mouse mammary model, increased ELF5 levels drive metastasis by co-opting the innate immune system. As ELF5 has been previously implicated in the development of antiestrogen resistance, this finding implicates ELF5 as a defining factor in the acquisition of the key aspects of the lethal phenotype in luminal A breast cancer

Loss of Pluripotency in Human Embryonic Stem Cells Directly Correlates with an Increase in Nuclear Zinc

The pluripotency of human embryonic stem cells (hESCs) is important to investigations of early development and to cell replacement therapy, but the mechanism behind pluripotency is incompletely understood. Zinc has been shown to play a key role in differentiation of non-pluripotent cell types, but here its role in hESCs is directly examined. By mapping the distribution of metals in hESCs at high resolution by x-ray fluorescence microprobe (XFM) and by analyzing subcellular metal content, we have found evidence that loss of pluripotency is directly correlated with an increase in nuclear zinc. Zinc elevation not only redefines our understanding of the mechanisms that support pluripotency, but also may act as a biomarker and an intervention point for stem cell differentiation

How do NHS organisations plan research capacity development? Strategies, strengths, and opportunities for improvement

Research that is integral into a 'learning healthcare system' can promote cost effective services and knowledge creation. As such, research is defined as a 'core function' in UK health service organisations, and is often planned through research and development (R&D) strategies that aim to promote research activity and research capacity development (RCD). The discussion focuses around the content of ten R&D strategies for healthcare organisations in England and Scotland, with respect to RCD. These organisations were engaged with a research interest network called ACORN (Addressing Organisational Capacity to do Research Network) that included two Scottish Health Boards, four community and mental health trusts, two provincial district hospitals, and two teaching hospitals. We undertook a thematic documentary analysis of the R&D strategies which identified 11 'core activities' of RCD. The potential for building research capacity in these 'core activities' was established by reviewing them through the lens of a RCD framework. Core activities aimed to 'hard wire' RCD into health organisations. They demonstrated a complex interplay between developing a strong internal organisational infrastructure, and supporting individual career planning and skills development, in turn enabled by organisational processes. They also included activities to build stronger inter-organisational relationships and networks. Practitioner, manager and patient involvement was a cross cutting theme. The potential to demonstrate progress was included in plans through monitoring activity across all RCD principles. Strategies were primarily aimed at research production rather than research use. Developing 'actionable dissemination' was poorly addressed in the strategies, and represents an area for improvement. We describe strengths of RCD planning activities, and opportunities for improvement. We explore how national policy and research funders can influence health systems' engagement in research

Creating symbolic cultures of consumption: an analysis of the content of sports wagering advertisements in Australia

Background: Since 2008, Australia has seen the rapid emergence of marketing for online and mobile sports wagering. Previous research from other areas of public health, such as tobacco and alcohol, has identified the range of appeal strategies these industries used to align their products with culturally valued symbols. However, there is very limited research that has investigated the tactics the sports wagering industry uses within marketing to influence the consumption of its products and services. Method: This study consisted of a mixed method interpretive content analysis of 85 sports wagering advertisements from 11 Australian and multinational wagering companies. Advertisements were identified via internet searches and industry websites. A coding framework was applied to investigate the extent and nature of symbolic appeal strategies within advertisements. Results: Ten major appeal strategies emerged from this analysis. These included sports fan rituals and behaviours; mateship; gender stereotypes; winning; social status; adventure, thrill and risk; happiness; sexualised imagery; power and control; and patriotism. Symbols relating to sports fan rituals and behaviours, and mateship, were the most common strategies used within the advertisements. Discussion/Conclusions: This research suggests that the appeal strategies used by the sports wagering industry are similar to those strategies adopted by other unhealthy commodity industries. With respect to gambling, analysis revealed that strategies are clearly targeted to young male sports fans. Researchers and public health practitioners should seek to better understand the impact of marketing on the normalisation of sports wagering for this audience segment, and implement strategies to prevent gambling harm

The DRUID study: racism and self-assessed health status in an indigenous population

BackgroundThere is now considerable evidence from around the world that racism is associated with both mental and physical ill-health. However, little is known about the mediating factors between racism and ill-health. This paper investigates relationships between racism and self-assessed mental and physical health among Indigenous Australians as well as potential mediators of these relationships.MethodsA total of 164 adults in the Darwin Region Urban Indigenous Diabetes (DRUID) study completed a validated instrument assessing interpersonal racism and a separate item on discrimination-related stress. Self-assessed health status was measured using the SF-12. Stress, optimism, lack of control, social connections, cultural identity and reactions/responses to interpersonal racism were considered as mediators and moderators of the relationship between racism/discrimination and self-assessed health status.ResultsAfter adjusting for socio-demographic factors, interpersonal racism was significantly associated with the SF-12 mental (but not the physical) health component. Stress, lack of control and feeling powerless as a reaction to racism emerged as significant mediators of the relationship between racism and general mental health. Similar findings emerged for discrimination-related stress.ConclusionsRacism/discrimination is significantly associated with poor general mental health among this indigenous population. The mediating factors between racism and mental health identified in this study suggest new approaches to ameliorating the detrimental effects of racism on health. In particular, the importance of reducing racism-related stress, enhancing general levels of mastery, and minimising negative social connections in order to ameliorate the negative consequences of racism

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration