163 research outputs found

    Intellectual need and problem-free activity in the mathematics classroom

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    Intellectual need, a key part of the DNR theoretical framework, is posited to be necessary for significant learning to occur. This paper provides a theoretical examination of intellectual need and its absence in mathematics classrooms. Although this is not an empirical study, we use data from observed high school algebra classrooms to illustrate four categories of activity students engage in while feeling little or no intellectual need. We present multiple examples for each category in order to draw out different nuances of the activity, and we contrast the observed situations with ones that would provide various types of intellectual need. Finally, we offer general suggestions for teaching with intellectual need

    Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy.

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    Inadequate oxygen supply, or hypoxia, is characteristic of the tumor microenvironment and correlates with poor prognosis and therapeutic resistance. Hypoxia leads to the activation of the hypoxia-inducible factor (HIF) signaling pathway and stabilization of the HIF-α subunit, driving tumor progression. The homologous alpha subunits, HIF-1α and HIF-2α, are responsible for mediating the transcription of a multitude of critical proteins that control proliferation, angiogenic signaling, metastasis, and other oncogenic factors, both differentially and sequentially regulating the hypoxic response. Post-translational modifications of HIF play a central role in its behavior as a mediator of transcription, as well as the temporal transition from HIF-1α to HIF-2α that occurs in response to chronic hypoxia. While it is evident that HIF-α is highly dynamic, HIF-2α remains vastly under-considered. HIF-2α can intensify the behaviors of the most aggressive tumors by adapting the cell to oxidative stress, thereby promoting metastasis, tissue remodeling, angiogenesis, and upregulating cancer stem cell factors. The structure, function, hypoxic response, spatiotemporal dynamics, and roles in the progression and persistence of cancer of this HIF-2α molecule and it

    Aromatase Is a Direct Target of FOXL2: C134W in Granulosa Cell Tumors via a Single Highly Conserved Binding Site in the Ovarian Specific Promoter

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    BACKGROUND: Granulosa cell tumors (GCT) of the ovary often express aromatase and synthesize estrogen, which in turn may influence their progression. Recently a specific point mutation (C134W) in the FOXL2 protein was identified in >94% of adult-type GCT and it is likely to contribute to their development. A number of genes are known to be regulated by FOXL2, including aromatase/CYP19A1, but it is unclear which are direct targets and whether the C134W mutation alters their regulation. Recently, it has been reported that FOXL2 forms a complex with steroidogenic factor 1 (SF-1) which is a known regulator of aromatase in granulosa cells. METHODOLOGY/PRINCIPAL FINDINGS: In this work, the human GCT-derived cell lines KGN and COV434 were heterozygous and wildtype for the FOXL2:C134W mutation, respectively. KGN had abundant FOXL2 mRNA expression but it was not expressed in COV434. Expression of exogenous FOXL2:C134W in COV434 cells induced higher expression of a luciferase reporter for the ovarian specific aromatase promoter, promoter II (PII) (-516bp) than expression of wildtype FOXL2, but did not alter induction of a similar reporter for the steroidogenic acute regulatory protein (StAR) promoter (-1300bp). Co-immunoprecipitation confirmed that FOXL2 bound SF-1 and that it also bound its homologue, liver receptor homologue 1 (LRH-1), however, the C134W mutation did not alter these interactions or induce a selective binding of the proteins. A highly conserved putative binding site for FOXL2 was identified in PII. FOXL2 was demonstrated to bind the site by electrophoretic mobility shift assays (EMSA) and site-directed mutagenesis of this element blocked its differential induction by wildtype FOXL2 and FOXL2:C134W. CONCLUSIONS/SIGNIFICANCE: These findings suggest that aromatase is a direct target of FOXL2:C134W in adult-type GCT via a single distinctive and highly conserved binding site in PII and therefore provide insight into the pathogenic mechanism of this mutation

    The first ever anti-football painting: A consideration of the soccer match in John Singer Sargent’s "Gassed"

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    The paper presents a discussion of Gassed, a large oil painting by John Singer Sargent displayed at the Imperial War Museum in London. Completed in 1919, Gassed is the major achievement from Sargent’s commission as an official war artist at the appointment of the British War Memorials Committee during the latter period of World War I. Prominent in the painting is a group of soldiers, blinded by a mustard gas attack, being lead to a casualty clearing station tent. In the distant background of the painting, another group of soldiers can be seen kitted out in football attire playing a match. The significance of this football imagery is our point of enquiry. As our title suggests, some recent interpretations regard the painting as offering critical reflection, from the time, about the symbolic links between sport and war. However, while the painting may certainly be left open to this type of viewer interpretation, archival and secondary resource material research does not support such a critical intention by the artist. Yet, nor is there evidence that Sargent’s intention was the projection of war-heroism. Rather, Sargent’s endeavour to faithfully represent what he observed allows Gassed to be regarded as a visual record of routine activity behind the lines and of football as an aspect of the daily life of British soldiers during the Great War

    A new class of large-amplitude radial-mode hot subdwarf pulsators

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    Using high-cadence observations from the Zwicky Transient Facility at low Galactic latitudes, we have discovered a new class of pulsating, hot compact stars. We have found four candidates, exhibiting blue colors (g − r ≤ −0.1 mag), pulsation amplitudes of >5%, and pulsation periods of 200–475 s. Fourier transforms of the light curves show only one dominant frequency. Phase-resolved spectroscopy for three objects reveals significant radial velocity, T eff, and log(g) variations over the pulsation cycle, which are consistent with large-amplitude radial oscillations. The mean T eff and log(g) for these stars are consistent with hot subdwarf B (sdB) effective temperatures and surface gravities. We calculate evolutionary tracks using MESA and adiabatic pulsations using GYRE for low-mass, helium-core pre-white dwarfs (pre-WDs) and low-mass helium-burning stars. Comparison of low-order radial oscillation mode periods with the observed pulsation periods show better agreement with the pre-WD models. Therefore, we suggest that these new pulsators and blue large-amplitude pulsators (BLAPs) could be members of the same class of pulsators, composed of young ≈0.25–0.35 M ⊙ helium-core pre-WDs.Published versio

    The biocultural origins and dispersal of domestic chickens

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    SignificanceChickens are the world's most numerous domestic animal. In order to understand when, where, and how they first became associated with human societies, we critically assessed the domestic status of chicken remains described in >600 sites in 89 countries, and evaluated zoogeographic, morphological, osteometric, stratigraphic, contextual, iconographic, and textual data. Although previous studies have made claims for an early origin of chickens, our results suggest that unambiguous chickens were not present until ∼1650 to 1250 BCE in central Thailand. A correlation between early chickens and the first appearance of rice and millet cultivation suggests that the production and storage of these cereals may have acted as a magnet, thus initiating the chicken domestication process

    Football: a counterpoint to the procession of pain on the Western Front, 1914-1918?

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    In this article, three artworks of the First World War containing images of recreational football are analysed. These three images, In the Wings of the Theatre of War, Artillery Men at Football and Gassed, span the war from its beginning to its conclusion and are discussed in relationship to the development of recreational football in the front-line area, the evolving policies of censorship and propaganda and in consideration of the national mood in Britain. The paper shows how football went from being a spontaneous and improvised pastime in the early stages of the war to a well organized entertainment by war’s end. The images demonstrate how the war was portrayed as a temporary affair by a confident nation in 1914 to a more resigned acceptance of a semi-permanent event to be endured by 1918; however, all three artworks show that the sporting spirit, and hence the fighting spirit, of the British soldier was intact
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