85 research outputs found

    Learning to learn in mathematics: Two Fulbright distinguished awards in teaching fellows’ narratives

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    Two middle school educators earned a Fulbright Distinguished Award in Teaching fellowship. A Fulbright Finland Foundation inter-country travel grant provided the grantees with a unique opportunity to connect and collaborate at the University of Helsinki. Within this research, they described their inquiry experiences. The research included examining authentic student-centered learning continuums and phenomenon-based learning in Finland and teachers’ adaptability in relation to meeting the needs of linguistically and culturally diverse math classrooms in the Netherlands. This paper summarizes how cross-cultural dialogues, classroom observations, and informal interviews with educators, students, and thought leaders informed each grantee’s discovery of how student-centered learning is structured, delivered, and valued in Finland and the Netherlands. This article (1) describes how communication empowers middle school mathematics students, (2) analyzes the learning-to-learn framework, and (3) provides insights into how to utilize language diversity in a mathematics classroom.Peer reviewe

    An integrated approach to supply chain risk analysis

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    Despite the increasing attention that supply chain risk management is receiving by both researchers and practitioners, companies still lack a risk culture. Moreover, risk management approaches are either too general or require pieces of information not regularly recorded by organisations. This work develops a risk identification and analysis methodology that integrates widely adopted supply chain and risk management tools. In particular, process analysis is performed by means of the standard framework provided by the Supply Chain Operations Reference Model, the risk identification and analysis tasks are accomplished by applying the Risk Breakdown Structure and the Risk Breakdown Matrix, and the effects of risk occurrence on activities are assessed by indicators that are already measured by companies in order to monitor their performances. In such a way, the framework contributes to increase companies' awareness and communication about risk, which are essential components of the management of modern supply chains. A base case has been developed by applying the proposed approach to a hypothetical manufacturing supply chain. An in-depth validation will be carried out to improve the methodology and further demonstrate its benefits and limitations. Future research will extend the framework to include the understanding of the multiple effects of risky events on different processe

    Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes

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    Death domain–associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3.3 deposition and transcriptional repression of cellular promoters. Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression. Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein–protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX. To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase. Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5. We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling

    Including metabolite concentrations into flux balance analysis: thermodynamic realizability as a constraint on flux distributions in metabolic networks

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    <p>Abstract</p> <p>Background</p> <p>In recent years, constrained optimization – usually referred to as flux balance analysis (FBA) – has become a widely applied method for the computation of stationary fluxes in large-scale metabolic networks. The striking advantage of FBA as compared to kinetic modeling is that it basically requires only knowledge of the stoichiometry of the network. On the other hand, results of FBA are to a large degree hypothetical because the method relies on plausible but hardly provable optimality principles that are thought to govern metabolic flux distributions.</p> <p>Results</p> <p>To augment the reliability of FBA-based flux calculations we propose an additional side constraint which assures thermodynamic realizability, i.e. that the flux directions are consistent with the corresponding changes of Gibb's free energies. The latter depend on metabolite levels for which plausible ranges can be inferred from experimental data. Computationally, our method results in the solution of a mixed integer linear optimization problem with quadratic scoring function. An optimal flux distribution together with a metabolite profile is determined which assures thermodynamic realizability with minimal deviations of metabolite levels from their expected values. We applied our novel approach to two exemplary metabolic networks of different complexity, the metabolic core network of erythrocytes (30 reactions) and the metabolic network iJR904 of <it>Escherichia coli </it>(931 reactions). Our calculations show that increasing network complexity entails increasing sensitivity of predicted flux distributions to variations of standard Gibb's free energy changes and metabolite concentration ranges. We demonstrate the usefulness of our method for assessing critical concentrations of external metabolites preventing attainment of a metabolic steady state.</p> <p>Conclusion</p> <p>Our method incorporates the thermodynamic link between flux directions and metabolite concentrations into a practical computational algorithm. The weakness of conventional FBA to rely on intuitive assumptions about the reversibility of biochemical reactions is overcome. This enables the computation of reliable flux distributions even under extreme conditions of the network (e.g. enzyme inhibition, depletion of substrates or accumulation of end products) where metabolite concentrations may be drastically altered.</p

    Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis

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    Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18) and one strain of Paracoccidioides lutzii (Pb01). These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic species of Onygenales to transfer from soil to animal hosts.National Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health. Department of Health and Human Services (contract HHSN266200400001C)National Institutes of Health. Department of Health and Human Services(contract HHSN2722009000018C)Brazil. National Council for Scientific and Technological Developmen

    The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

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    DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

    Dewey’s Ideas in Action! Continuing Professional Development in an International Community of Practice

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    Drawing on Dewey’s concepts and thinking, a middle school mathematics teacher at The School at Columbia University describes her teaching practice and role as a field-based teacher-educator and professional development leader during EdTech Summit Africa. Through a first-person account of her experiences in Cape Town, Johannesburg, and Pretoria, South Africa, the author reflects on how professional development with technology was embraced and illuminates why the development of an international community of practice with primary, secondary, and tertiary teachers is evolving. The article is divided into four sections
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