6,725 research outputs found

    What do error patterns tell us about Hong Kong Chinese and Australian studentsā€™ understanding of decimal numbers?

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    Mathematics educators have had a long standing interest in studentsā€™ understanding of decimal numbers. Most studies of studentsā€™ understanding of decimals have been conducted within Western cultural settings. The present study sought to gain insight into Chinese Hong Kong studentsā€™ and regional Australian studentsā€™ general performance on a variety of decimals tasks and to investigate studentsā€™ error patterns

    Teaching with procedural variation: A Chinese way of promoting deep understanding of mathematics

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    In mathematics education, there has been tension between deep learning and repetitive learning. Western educators often emphasize the need for students to construct a conceptual understanding of mathematical symbols and rules before they practise the rules (Li, 2006). On the other hand, Chinese learners tend to be oriented towards rote learning and memorization (Marton, Watkins & Tang, 1997). One aspect of the criticism is that rote learning is known to lead to poor learning outcomes (Watkins & Biggs, 2001). However, Chinese students consistently outperform their Western counterparts in many international comparative studies on mathematics achievement such as TIMSS (Beaton, Mullis, Martin, Gonzalez, Kelly & Smith, 1997; Mullis, Martin, & Foy, 2008) and PISA (OECD, 2004; OECD, 2010). This paper aims to contribute to an understanding of the ā€œparadox of the Chinese learnersā€ (Marton, Dallā€Ÿ Alba & Lai, 1993) by exploring the procedural variation and its place in the development of mathematical understanding

    HONG KONG GRADE 6 STUDENTSā€™ PERFORMANCE AND MATHEMATICAL REASONING IN DECIMALS TASKS: PROCEDURALLY BASED OR CONCEPTUALLY BASED?

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    Ā© 2014, National Science Council, Taiwan. Most studies of studentsā€™ understanding of decimals have been conducted within Western cultural settings. The broad aim of the present research was to gain insight into Chinese Hong Kong grade 6 studentsā€™ general performance on a variety of decimals tasks. More specifically, the study aimed to explore studentsā€™ mathematical reasoning for their use of ā€˜rulesā€™ and algorithms and to determine whether connections exist between studentsā€™ conceptual and procedural knowledge when completing decimals tasks. Results indicated that conceptual understanding for rules and procedures were built into the studentsā€™ knowledge system for most of the items concerned with place value in decimalsā€”ordering decimals, translating fractions into decimals, the representation of place value in decimals, the concept of place value in decimals on number line and the concept of continuous quantity in decimals. However, the students were not able to provide such clear explanations for the use of algorithms for the multiplication and division items. The findings are discussed in the light of Chinese perspectives on procedural and conceptual understanding

    Methylation of CENP-A/Cse4 on arginine 143 and lysine 131 regulates kinetochore stability in yeast

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    Post-translational modifications on histones are well known to regulate chromatin structure and function, but much less information is available on modifications of the centromeric histone H3 variant and their effect at the kinetochore. Here, we report two modifications on the centromeric histone H3 variant CENP-A/Cse4 in the yeast Saccharomyces cerevisiae, methylation at arginine 143 (R143me) and lysine 131 (K131me), that affect centromere stability and kinetochore function. Both R143me and K131me lie in the core region of the centromeric nucleosome, near the entry/exit sites of the DNA from the nucleosome. Unexpectedly, mutation of Cse4-R143 (cse4-R143A) exacerbated the kinetochore defect of mutations in components of the NDC80 complex of the outer kinetochore (spc25-1) and the MIND complex (dsn1-7). The analysis of suppressor mutations of the spc25-1 cse4-R143A growth defect highlighted residues in Spc24, Ndc80, and Spc25 that localize to the tetramerization domain of the NDC80 complex and the Spc24-Spc25 stalk, suggesting that the mutations enhance interactions among NDC80 complex components and thus stabilize the complex. Furthermore, the Set2 histone methyltransferase inhibited kinetochore function in spc25-1 cse4-R143A cells, possibly by methylating Cse4-K131. Taken together, our data suggest that Cse4-R143 methylation and Cse4-K131 methylation affect the stability of the centromeric nucleosome, which is detrimental in the context of defective NDC80 tetramerization and can be compensated for by strengthening interactions among NDC80 complex components.Peer Reviewe

    Data-driven neuropathological staging and subtyping of TDP-43 proteinopathies

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    TAR DNA-binding protein-43 (TDP-43) accumulation is the primary pathology underlying several neurodegenerative diseases. Charting the progression and heterogeneity of TDP-43 accumulation is necessary to better characterize TDP-43 proteinopathies, but current TDP-43 staging systems are heuristic and assume each syndrome is homogeneous. Here, we use data-driven disease progression modelling to derive a fine-grained empirical staging system for the classification and differentiation of frontotemporal lobar degeneration due to TDP-43 (FTLD-TDP, n = 126), amyotrophic lateral sclerosis (ALS, n = 141) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) with and without Alzheimerā€™s disease (n = 304). The data-driven staging of ALS and FTLD-TDP complement and extend previously described human-defined staging schema for ALS and behavioural variant frontotemporal dementia. In LATE-NC individuals, progression along data-driven stages was positively associated with age, but negatively associated with age in individuals with FTLD-TDP. Using only regional TDP-43 severity, our data driven model distinguished individuals diagnosed with ALS, FTLD-TDP or LATE-NC with a cross-validated accuracy of 85.9%, with misclassifications associated with mixed pathological diagnosis, age and genetic mutations. Adding age and SuStaIn stage to this model increased accuracy to 92.3%. Our model differentiates LATE-NC from FTLD-TDP, though some overlap was observed between late-stage LATE-NC and early-stage FTLD-TDP. We further tested for the presence of subtypes with distinct regional TDP-43 progression patterns within each diagnostic group, identifying two distinct cortical-predominant and brainstem-predominant subtypes within FTLD-TDP and a further two subcortical-predominant and corticolimbic-predominant subtypes within ALS. The FTLD-TDP subtypes exhibited differing proportions of TDP-43 type, while there was a trend for age differing between ALS subtypes. Interestingly, a negative relationship between age and SuStaIn stage was seen in the brainstem/subcortical-predominant subtype of each proteinopathy. No subtypes were observed for the LATE-NC group, despite aggregating individuals with and without Alzheimerā€™s disease and a larger sample size for this group. Overall, we provide an empirical pathological TDP-43 staging system for ALS, FTLD-TDP and LATE-NC, which yielded accurate classification. We further demonstrate that there is substantial heterogeneity amongst ALS and FTLD-TDP progression patterns that warrants further investigation in larger cross-cohort studies

    Pressure balance in the multiphase ISM of cosmologically simulated disc galaxies

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    Pressure balance plays a central role in models of the interstellar medium (ISM), but whether and how pressure balance is realized in a realistic multiphase ISM is not yet well understood. We address this question by using a set of FIRE-2 cosmological zoom-in simulations of Milky Way-mass disc galaxies, in which a multiphase ISM is self-consistently shaped by gravity, cooling, and stellar feedback. We analyse how gravity determines the vertical pressure profile as well as how the total ISM pressure is partitioned between different phases and components (thermal, dispersion/turbulence, and bulk flows). We show that, on average and consistent with previous more idealized simulations, the total ISM pressure balances the weight of the overlying gas. Deviations from vertical pressure balance increase with increasing galactocentric radius and with decreasing averaging scale. The different phases are in rough total pressure equilibrium with one another, but with large deviations from thermal pressure equilibrium owing to kinetic support in the cold and warm phases, which dominate the total pressure near the mid-plane. Bulk flows (e.g. inflows and fountains) are important at a few disc scale heights, while thermal pressure from hot gas dominates at larger heights. Overall, the total mid-plane pressure is well-predicted by the weight of the disc gas and we show that it also scales linearly with the star formation rate surface density (Ļ‚SFR). These results support the notion that the Kennicutt-Schmidt relation arises because Ļ‚SFR and the gas surface density (Ļ‚g) are connected via the ISM mid-plane pressure

    Intra-anal imiquimod cream against human papillomavirus infection in men who have sex with men living with hiv: A single-arm, open-label pilot study

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    Men who have sex with men (MSM) living with HIV have a high prevalence and incidence of anal high-risk human papillomavirus (hrHPV) and anal cancer. We conducted an open-label, single-arm pilot study to examine the tolerability of imiquimod cream among MSM aged ā‰„18 years, living with HIV, who tested positive for anal hrHPV at Melbourne Sexual Health Centre between April 2018 and June 2020. We instructed men to apply 6.25 mg imiquimod intra-anally and peri-anally 3 doses per week for 16 weeks (period 1) and then one dose per week for a further 48 weeks (period 2). Twenty-seven MSM enrolled in period 1 and 24 (86%) applied at least 50% of doses. All men reported adverse events (AEs), including 39.5% grade 1, 39.5% grade 2, and 21% grade 3 AEs on at least one occasion. Eighteen MSM (67%) temporarily stopped using imiquimod during period 1, most commonly due to local AEs (n = 11) such as irritation and itching. Eighteen MSM continued in period 2 and all applied at least 50% of doses with no treatment-limiting AEs reported. Imiquimod 3 doses per week caused local AEs in most men and was not well tolerated. In contrast, once-a-week application was well tolerated over 48-weeks with no treatment-limiting AEs

    NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

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    Transcription factor NRF2 is an important regulator of oxidative stress. It is involved in cancer progression, and has abnormal constitutive expression in acute myeloid leukaemia (AML). Posttranscriptional regulation by microRNAs (miRNAs) can affect the malignant phenotype of AML cells. In this study, we identified and characterised NRF2-regulated miRNAs in AML. An miRNA array identified miRNA expression level changes in response to NRF2 knockdown in AML cells. Further analysis of miRNAs concomitantly regulated by knockdown of the NRF2 inhibitor KEAP1 revealed the major candidate NRF2-mediated miRNAs in AML. We identified miR-125B to be upregulated and miR-29B to be downregulated by NRF2 in AML. Subsequent bioinformatic analysis identified putative NRF2 binding sites upstream of the miR-125B1 coding region and downstream of the mir-29B1 coding region. Chromatin immunoprecipitation analyses showed that NRF2 binds to these antioxidant response elements (AREs) located in the 5ā€² untranslated regions of miR-125B and miR-29B. Finally, primary AML samples transfected with anti-miR-125B antagomiR or miR-29B mimic showed increased cell death responsiveness either alone or co-treated with standard AML chemotherapy. In summary, we find that NRF2 regulation of miR-125B and miR-29B acts to promote leukaemic cell survival, and their manipulation enhances AML responsiveness towards cytotoxic chemotherapeutics
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