Learning About New Demands in Schools: Considering Algebra Policy Environments (LANDSCAPE)

The past three decades in mathematics education policy and research have seen a considerable focus on algebra and its place in secondary schools. Access to and success in the first high school course, most often termed Algebra I, has been framed as a civil rights issue, a harbinger of college success, and a lynchpin to global competitiveness. Policymakers have targeted access to Algebra I through universal enrollment policies at specific grade levels, while educational researchers and policy analysts have investigated the efficacy of such policies in improving student outcomes

5.5-7.5 MeV Proton generation by a moderate intensity ultra-short laser interaction with H2O nano-wire targets

We report on the first generation of 5.5-7.5 MeV protons by a moderate intensity short-pulse laser (4.5 \times 1017 W/cm^2, 50 fsec) interacting with H2O nano-wires (snow) deposited on a Sapphire substrate. In this setup, the laser intensity is locally enhanced by the tip of the snow nano-wire, leading to high spatial gradients. Accordingly, the plasma near the tip is subject to enhanced ponderomotive potential, and confined charge separation is obtained. Electrostatic fields of extremely high intensities are produced over the short scale length, and protons are accelerated to MeV-level energies.Comment: submitted to PRL, under press embargo. 6 figure

A Paradigmatic Analysis of Digital Application Marketplaces

This paper offers a paradigmatic analysis of digital application marketplaces for advancing information systems (IS) research on digital platforms and ecosystems. We refer to the notion of digital application marketplace, colloquially called “appstores,” as a platform component that offers a venue for exchanging applications between developers and end-users belonging to a single or multiple ecosystems. Such marketplaces exhibit diversity in features and assumptions, and we propose that examining this diversity, and its ideal types, will help us to further understand the relationship between application marketplaces, platforms, and platform ecosystems. To this end, we generate a typology that distinguishes four kinds of digital application marketplaces: closed, censored, focused, and open marketplaces. The paper also offers implications for actors wishing to make informed decisions about their relationship to a particular digital application marketplace

Loss of RhoB Expression Enhances the Myelodysplastic Phenotype of Mammalian Diaphanous-Related Formin mDia1 Knockout Mice

Myelodysplastic syndrome (MDS) is characterized by ineffective hematopoiesis and hyperplastic bone marrow. Complete loss or interstitial deletions of the long arm of chromosome 5 occur frequently in MDS. One candidate tumor suppressor on 5q is the mammalian Diaphanous (mDia)-related formin mDia1, encoded by DIAPH1 (5q31.3). mDia-family formins act as effectors for Rho-family small GTP-binding proteins including RhoB, which has also been shown to possess tumor suppressor activity. Mice lacking the Drf1 gene that encodes mDia1 develop age-dependent myelodysplastic features. We crossed mDia1 and RhoB knockout mice to test whether the additional loss of RhoB expression would compound the myelodysplastic phenotype. Drf1−/−RhoB−/− mice are fertile and develop normally. Relative to age-matched Drf1−/−RhoB+/− mice, the age of myelodysplasia onset was earlier in Drf1−/−RhoB−/− animals—including abnormally shaped erythrocytes, splenomegaly, and extramedullary hematopoiesis. In addition, we observed a statistically significant increase in the number of activated monocytes/macrophages in both the spleen and bone marrow of Drf1−/−RhoB−/− mice relative to Drf1−/−RhoB+/− mice. These data suggest a role for RhoB-regulated mDia1 in the regulation of hematopoietic progenitor cells

Darolutamide does not interfere with OATP-mediated uptake of docetaxel

The addition of darolutamide, an androgen receptor signalling inhibitor, to therapy with docetaxel has recently been approved as a strategy to treat metastatic prostate cancer. OATP1B3 is an SLC transporter that is highly expressed in prostate cancer and is responsible for the accumulation of substrates, including docetaxel, into tumours. Given that darolutamide inhibits OATP1B3 in vitro, we sought to characterise the impact of darolutamide on docetaxel pharmacokinetics. We investigated the influence of darolutamide on OATP1B3 transport using in vitro and in vivo models. We assessed the impact of darolutamide on the tumour accumulation of docetaxel in a patient-derived xenograft (PDX) model and on an OATP1B biomarker in patients. Darolutamide inhibited OATP1B3 in vitro at concentrations higher than the reported Cmax. Consistent with these findings, in vivo studies revealed that darolutamide does not influence the pharmacokinetics of Oatp1b substrates, including docetaxel. Docetaxel accumulation in PDX tumours was not decreased in the presence of darolutamide. Metastatic prostate cancer patients had similar levels of OATP1B biomarkers, regardless of treatment with darolutamide. Consistent with a low potential to inhibit OATP1B3-mediated transport in vitro, darolutamide does not significantly impede the transport of Oatp1b substrates in vivo or in patients. Our findings support combined treatment with docetaxel and darolutamide, as no OATP1B3 transporter based drug–drug interaction was identified

Darolutamide does not interfere with OATP-mediated uptake of docetaxel

The addition of darolutamide, an androgen receptor signalling inhibitor, to therapy with docetaxel has recently been approved as a strategy to treat metastatic prostate cancer. OATP1B3 is an SLC transporter that is highly expressed in prostate cancer and is responsible for the accumulation of substrates, including docetaxel, into tumours. Given that darolutamide inhibits OATP1B3 in vitro, we sought to characterise the impact of darolutamide on docetaxel pharmacokinetics. We investigated the influence of darolutamide on OATP1B3 transport using in vitro and in vivo models. We assessed the impact of darolutamide on the tumour accumulation of docetaxel in a patient-derived xenograft (PDX) model and on an OATP1B biomarker in patients. Darolutamide inhibited OATP1B3 in vitro at concentrations higher than the reported Cmax. Consistent with these findings, in vivo studies revealed that darolutamide does not influence the pharmacokinetics of Oatp1b substrates, including docetaxel. Docetaxel accumulation in PDX tumours was not decreased in the presence of darolutamide. Metastatic prostate cancer patients had similar levels of OATP1B biomarkers, regardless of treatment with darolutamide. Consistent with a low potential to inhibit OATP1B3-mediated transport in vitro, darolutamide does not significantly impede the transport of Oatp1b substrates in vivo or in patients. Our findings support combined treatment with docetaxel and darolutamide, as no OATP1B3 transporter based drug–drug interaction was identified

Digital Platforms in the Global South: Foundations and Research Agenda

Digital platforms have become integral to many of the everyday activities that people across the globe encounter in areas like transportation, commerce and social interactions. Research on the topic has largely concentrated on the general functioning of these platforms in terms of platform governance, business strategies and consumer behaviour. Despite their significant presence in the global South, the developmental implications of digital platforms remain largely understudied. In part, this is because digital platforms are a challenging research object due to their lack of conceptual definition, their spread across different regions and industries, and their intertwined nature with institutions, actors and digital technologies. The aim of this paper is therefore twofold: to provide a conceptual definition of digital platforms, and to identify research strands in international development contexts. To do so, we draw from digital platforms literature, differentiate between transaction and innovation platforms and expose their main characteristics. We the present four strands in the form of research questions, illustrated with concrete examples, that can assist to pursue relevant studies on digital platforms and international development in the future

The Relationship between the Level of Fatness and Fitness during Adolescence and the Risk Factors of Metabolic Disorders in Adulthood

BACKGROUND: The purpose of the current study was to investigate the association between the level of obesity and physical fitness (PF) during adolescence and the risk factors of metabolic disorders during adulthood. METHODS: In the current analysis, 3,993 Korean adults (mean age, 38.70 +/- 1.69 years) were recruited. The level of body index (BI) and PF were examined during adolescence through high school record, and their health examination data, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose (FG), total cholesterol (TC), and current body mass index (BMI) were obtained from National Health Insurance Corporation Data. Gender-specific analyses were administered to compare health exam data across the level of BI, the level of PF, and a mixed level of BI and PF. RESULTS: Most obese males during high school had statistically higher SBP, DBP, FG, and BMI in adulthood, and most obese females had higher BMI, as compared to most lean males or females. Least fit males during high school had statistically higher BMI in adulthood, and least fit females had statistically higher SBP, DBP, FG, TC, and BMI, as compared to most fit males or females. There was a significant relationship between the mixed level of BI and PF and SBP, DBP, TC and current BMI in both genders. CONCLUSION: Maintaining a healthy level of body weight and PF during adolescence is recommended to prevent the development of metabolic diseases in adulthood.ope

Understanding signaling cascades in melanoma

Understanding regulatory pathways involved in melanoma development and progression has advanced significantly in recent years. It is now appreciated that melanoma is the result of complex changes in multiple signaling pathways that affect growth control, metabolism, motility and the ability to escape cell death programs. Here we review the major signaling pathways currently known to be deregulated in melanoma with an implication to its development and progression. Among these pathways are Ras, B-Raf, MEK, PTEN, phosphatidylinositol-3 kinase (PI3Ks) and Akt which are constitutively activated in a significant number of melanoma tumors, in most cases due to genomic change. Other pathways discussed in this review include the [Janus kinase/signal transducer and activator of transcription (JAK/STAT), transforming growth factor-beta pathways which are also activated in melanoma, although the underlying mechanism is not yet clear. As a paradigm for remodeled signaling pathways, melanoma also offers a unique opportunity for targeted drug development.Fil: Lopez Bergami, Pablo Roberto. Sanford-burnham Medical Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fitchmann, B. Sanford-burnham Medical Research Institute; Estados UnidosFil: Ronai, Ze´ev. Sanford-burnham Medical Research Institute; Estados Unido

Percentile reference values for anthropometric body composition indices in European children from the IDEFICS study

INTRODUCTION: To characterise the nutritional status in children with obesity or wasting conditions, European anthropometric reference values for body composition measures beyond the body mass index (BMI) are needed. Differentiated assessment of body composition in children has long been hampered by the lack of appropriate references. OBJECTIVES: The aim of our study is to provide percentiles for body composition indices in normal weight European children, based on the IDEFICS cohort (Identification and prevention of Dietary-and lifestyle-induced health Effects in Children and infantS). METHODS: Overall 18 745 2.0-10.9-year-old children from eight countries participated in the study. Children classified as overweight/obese or underweight according to IOTF (N = 5915) were excluded from the analysis. Anthropometric measurements (BMI (N = 12 830); triceps, subscapular, fat mass and fat mass index (N = 11 845-11 901); biceps, suprailiac skinfolds, sum of skinfolds calculated from skinfold thicknesses (N = 8129-8205), neck circumference (N = 12 241); waist circumference and waist-to-height ratio (N = 12 381)) were analysed stratified by sex and smoothed 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th and 99th percentile curves were calculated using GAMLSS. RESULTS: Percentile values of the most important anthropometric measures related to the degree of adiposity are depicted for European girls and boys. Age-and sex-specific differences were investigated for all measures. As an example, the 50th and 99th percentile values of waist circumference ranged from 50.7-59.2 cm and from 51.3-58.7 cm in 4.5-to < 5.0-year-old girls and boys, respectively, to 60.6-74.5 cm in girls and to 59.9-76.7 cm in boys at the age of 10.5-10.9 years. CONCLUSION: The presented percentile curves may aid a differentiated assessment of total and abdominal adiposity in European children