On the relevance of the mathematics curriculum to young people

In this paper we draw upon focus group data from a large study of learner trajectories through 14-19 mathematics education to think about the notion of relevance in the mathematics curriculum. Drawing on data from three socially distanced sites we explore how different emphases on what might be termed practical, process and/or professional forms of relevance affect the experiences and aspirations of learners of mathematics. We consider whether an emphasis on practical relevance in schools serving relatively disadvantaged communities might aid the reproduction of students’ social position. This leads us to suggest that a fourth category of curriculum relevance – political relevance – is largely missing from classrooms

ABCB1 inhibition provides a novel therapeutic target to block TWIST1-induced migration in medulloblastoma

Background: Therapeutic intervention in metastatic medulloblastoma is dependent upon elucidating the underlying metastatic mechanism. We investigated whether an epithelialmesenchymal transition (EMT)-like pathway could drive medulloblastoma metastasis. Methods: A 3D Basement Membrane Extract (3D-BME)-model was used to investigate medulloblastoma cell migration. Cell line growth was quantified with AlamarBlue metabolic assays and morphology assessed by time-lapse imaging. Gene expression was analysed by qRT-PCR and protein expression by immunohistochemistry of patient tissue microarrays and mouse orthotopic xenografts. Chromatin immunoprecipitation was used to determine whether the EMT transcription factor TWIST1 bound to the promoter of the multidrug pump ABCB1. TWIST1 was overexpressed in MED6 cells by lentiviral transduction (MED6-TWIST1). Inhibition of ABCB1 was mediated by vardenafil and TWIST1 expression was reduced by either Harmine or shRNA. Results: Metastatic cells migrated to form large metabolically active aggregates, whereas nontumorigenic/ non-metastatic cells formed small aggregates with decreasing metabolic activity. TWIST1 expression was upregulated in the 3D-BME model. TWIST1 and ABCB1 were significantly associated with metastasis in patients (p=0.041 and p=0.04 respectively). High nuclear TWIST1 expression was observed in the invasive edge of the MED1 orthotopic model, and TWIST1 knock-down in cell lines was associated with reduced cell migration (

Empowerment/sexism: Figuring female sexual agency in contemporary advertising

This paper argues that there has been a significant shift in advertising representations of women in recent years, such that rather than being presented as passive objects of the male gaze, young women in adverts are now frequently depicted as active, independent and sexually powerful. This analysis examines contemporary constructions of female sexual agency in advertisements examining three recognizable ‘figures’: the young, heterosexually desiring ‘midriff’, the vengeful woman set on punishing her partner or ex partner for his transgressions, and the ‘hot lesbian’, almost always entwined with her beautiful Other or double. Using recent examples of adverts the paper asks how this apparent ‘agency’ and ‘empowerment’ should be understood. Drawing on accounts of the incorporation or recuperation of feminist ideas in advertising the paper takes a critical approach to these representations, examining their exclusions, their constructions of gender relations and heteronormativity, and the way power is figured within them. A feminist poststructuralist approach is used to interrogate the way in which ‘sexual agency’ becomes a form of regulation in these adverts, that requires the re-moulding of feminine subjectivity to fit the current postfeminist, neoliberal moment in which young women should not only be beautiful but sexy, sexually knowledgeable/practised and always ‘up for it’. The paper makes an original contribution to debates about representations of gender in advertising, to poststructuralist analyses about the contemporary operation of power, and to writing about female ‘sexual agency’ by suggesting that ‘voice’ or ‘agency’ may not be the solution to the ‘missing discourse of female desire' but may in fact be a technology of discipline and regulation

Intracellular processing of silica-coated superparamagnetic iron nanoparticles in human mesenchymal stem cells

Silica-coated superparamagnetic iron nanoparticles (SiMAGs) are an exciting biomedical technology capable of targeted delivery of cell-based therapeutics and disease diagnosis. However, in order to realise their full clinical potential, their intracellular fate must be determined. The analytical techniques of super-resolution fluorescence microscopy, particle counting flow cytometry and pH-sensitive nanosensors were applied to elucidate mechanisms of intracellular SiMAG processing in human mesenchymal stem cell (hMSCs). Super-resolution microscopy showed SiMAG fluorescently-tagged nanoparticles are endocytosed and co-localised within lysosomes. When exposed to simulated lysosomal conditions SiMAGs were solubilised and exhibited diminishing fluorescence emission over 7 days. The in vitro intracellular metabolism of SiMAGs was monitored in hMSCs using flow cytometry and co-localised pH-sensitive nanosensors. A decrease in SiMAG fluorescence emission, which corresponded to a decrease in lysosomal pH was observed, mirroring ex vivo observations, suggesting SiMAG lysosomal exposure degrades fluorescent silica-coatings and iron cores. These findings indicate although there is a significant decrease in intracellular SiMAG loading, sufficient particles remain internalised (>50%) to render SiMAG treated cells amenable to long-term magnetic cell manipulation. Our analytical approach provides important insights into the understanding of the intracellular fate of SiMAG processing, which could be readily applied to other particle therapeutics, to advance their clinical translation

Democratizing production through open source knowledge: from open software to open hardware

The commercial success of open source software, along with a broader socio-cultural shift towards participation in media and cultural production, have inspired attempts to extend and expand open source practices. These include expansions from software into general culture through 'Free Culture' movements and, more recently, expansions from software into hardware and design. This article provides a critical perspective on the democratic potential of these broader 'open' contribution structures by examining how open source contributions to both software and hardware increase the opportunities for democratic participation in production, governance and knowledge exchange. By analysing attempts to 'open source' the sharing of hardware designs, it also notes the limitations of this democratization. The insights developed in the article nuance the relationship between open source cultures and commercial and market structures, identifying how the generative opportunities created by certain aspects of open source contribution structures increase the potential for democratizing production of communication tools, but also how incongruities across different open-source cultures and communities of practice limit the democratic potential of these processes

Increased IL-2 and reduced TGF-β upon T-cell stimulation are associated with GM-CSF upregulation in multiple immune cell types in multiple sclerosis

© 2020 by the authors. Granulocyte macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine produced by immune cells. Recent evidence suggests that GM-CSF plays an important role in multiple sclerosis (MS) pathogenesis. We investigated the expression and regulation of GM-CSF in different immune cells in MS. We also investigated the differentiation and frequency of GM-CSF-producing Th cells that do not co-express interferon (IFN)-γ or interleukin-17 (IL-17) (Th-GM cells) in MS. We found a significant increase in the percentage of GM-CSF-expressing Th cells, Th1 cells, Th-GM cells, cytotoxic T (Tc) cells, monocytes, natural killer (NK) cells, and B cells in PBMC from MS patients stimulated with T cell stimuli. Stimulated PBMC culture supernatants from MS patients contained significantly higher levels of IL-2, IL-12, IL-1β, and GM-CSF and significantly lower levels of transforming growth factor (TGF-)β. Blocking IL-2 reduced the frequency of Th-GM cells in PBMC from MS patients. The frequency of Th-GM cells differentiated in vitro from naive CD4+ T cells was significantly higher in MS patients and was further increased in MS with IL-2 stimulation. These findings suggest that all main immune cell subsets produce more GM-CSF in MS after in vitro stimulation, which is associated with defective TGF-β and increased IL-2 and IL-12 production. Th-GM cells are increased in MS. GM-CSF may be a potential therapeutic target in MS