Analysis of Mathematical Models Produced when Solving Fermi Problems

[EN] In this paper, we present an analysis of written productions of 16 year-old students while solving Estimation Problems involving Big Numbers (EPiBN). This kind of problems is a particular type of Fermi problems and allows us to introduce modelling processes in Secondary school classrooms. Our analysis supports on the characterization of mathematical models developed by students based on the model definition of Lesh and Harel. The results show that, through the analysis of EPiBN resolutions, differentiating aspects can be distinguished between the models produced by students without modelling experience of those produced by students with prior experience, especially in the concepts and language used to shape the built mathematical models.[ES] En este trabajo presentamos un estudio en el que analizamos las producciones escritas de estudiantes de 16 años con diferentes niveles de experiencia en modelización al resolver Problemas de Estimación de Grandes Cantidades (PEGC). Estos problemas son un tipo concreto de los Problemas de Fermi y permiten introducir los procesos de modelización en las aulas de Educación Secundaria. Nuestro análisis se soporta en la caracterización de los modelos matemáticos que producen los alumnos, basada en la definición de modelo matemático propuesta por Lesh y Harel. Los resultados muestran que, a través del análisis de las resoluciones de PEGC, se pueden distinguir aspectos diferenciadores entre los modelos producidos por alumnos sin experiencia modelizadora de aquellos producidos por alumnos con experiencia previa, especialmente en los conceptos y lenguajes utilizados para dar forma a los modelos matemáticos construidos.Este trabajo es fruto de una investigación llevada a cabo en el marco de los proyectos de investigación EDU2012-35638 y EDU2013-4683-R que han recibido soporte económico del Ministerio de Economía y Competitividad español y de los Fondos FEDER, así como de la ayuda recibida por parte de la Conselleria de Educació de la Generalitat Valenciana (proyecto GV/2016/129) y la Direcció General de Recerca de la Generalitat de Catalunya (SGR2014-723).Ferrando Palomares, I.; Albarracín, L.; Gallart-Palau, C.; García-Raffi, LM.; Gorgorió, N. (2017). Análisis de los Modelos Matemáticos Producidos durante la Resolución de Problemas de Fermi. Bolema. 31(57):220-242. https://doi.org/10.1590/1980-4415v31n57a11S2202423157Albarracín, L., & Gorgorió, N. (2013). PROBLEMAS DE ESTIMACIÓN DE GRANDES CANTIDADES: MODELIZACIÓN E INFLUENCIA DEL CONTEXTO. Revista Latinoamericana de Investigación en Matemática Educativa, 16(3), 289-315. doi:10.12802/relime.13.1631Albarracín, L., & Gorgorió, N. (2014). Devising a plan to solve Fermi problems involving large numbers. Educational Studies in Mathematics, 86(1), 79-96. doi:10.1007/s10649-013-9528-9Blum, W. (2002). Educational Studies in Mathematics, 51(1/2), 149-171. doi:10.1023/a:1022435827400Ferri, R. B. (2006). Theoretical and empirical differentiations of phases in the modelling process. ZDM, 38(2), 86-95. doi:10.1007/bf02655883Carlson, J. E. (1997). Fermi problems on gasoline consumption. The Physics Teacher, 35(5), 308-309. doi:10.1119/1.2344696Efthimiou, C. J., & Llewellyn, R. A. (2007). Cinema, Fermi problems and general education. Physics Education, 42(3), 253-261. doi:10.1088/0031-9120/42/3/003Lesh, R., & Harel, G. (2003). Problem Solving, Modeling, and Local Conceptual Development. Mathematical Thinking and Learning, 5(2), 157-189. doi:10.1207/s15327833mtl0502&3_03Lester, F. K. (1994). Musings about Mathematical Problem-Solving Research: 1970-1994. Journal for Research in Mathematics Education, 25(6), 660. doi:10.2307/749578Schoenfeld, A. H. (2007). Problem solving in the United States, 1970–2008: research and theory, practice and politics. ZDM, 39(5-6), 537-551. doi:10.1007/s11858-007-0038-zCampos, I. da S., & Araújo, J. de L. (2015). Envolvimento dos Alunos em Atividades de Modelagem Matemática: relação com o saber e possibilidades de ação. Bolema: Boletim de Educação Matemática, 29(51), 167-182. doi:10.1590/1980-4415v29n51a09Sriraman, B., & Knott, L. (2009). The Mathematics of Estimation: Possibilities for Interdisciplinary Pedagogy and Social Consciousness. Interchange, 40(2), 205-223. doi:10.1007/s10780-009-9090-

E2F transcription factor-1 modulates expression of glutamine metabolic genes in mouse embryonic fibroblasts and uterine sarcoma cells

Metabolic reprogramming is considered as a hallmark of cancer and is clinically exploited as a novel target for therapy. The E2F transcription factor-1 (E2F1) regulates various cellular processes, including proliferative and metabolic pathways, and acts, depending on the cellular and molecular context, as an oncogene or tumor suppressor. The latter is evident by the observation that E2f1-knockout mice develop spontaneous tumors, including uterine sarcomas. This dual role warrants a detailed investigation of how E2F1 loss impacts metabolic pathways related to cancer progression. Our data indicate that E2F1 binds to the promoter of several glutamine metabolism-related genes. Interestingly, the expression of genes in the glutamine metabolic pathway were increased in mouse embryonic fibroblasts (MEFs) lacking E2F1. In addition, we confirm that E2f1 <sup>-/-</sup> MEFs are more efficient in metabolizing glutamine and producing glutamine-derived precursors for proliferation. Mechanistically, we observe a co-occupancy of E2F1 and MYC on glutamine metabolic promoters, increased MYC binding after E2F1 depletion and that silencing of MYC decreased the expression of glutamine-related genes in E2f1 <sup>-/-</sup> MEFs. Analyses of transcriptomic profiles in 29 different human cancers identified uterine sarcoma that showed a negative correlation between E2F1 and glutamine metabolic genes. CRISPR/Cas9 knockout of E2F1 in the uterine sarcoma cell line SK-UT-1 confirmed elevated glutamine metabolic gene expression, increased proliferation and increased MYC binding to glutamine-related promoters upon E2F1 loss. Together, our data suggest a crucial role of E2F1 in energy metabolism and metabolic adaptation in uterine sarcoma cells

Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

Background and Aims This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients. Methods The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses. Results As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, p = 0.01) remained significant. Conclusions In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism

Quantifying unpredictability: A multiple-model approach based on satellite imagery data from Mediterranean ponds.

Fluctuations in environmental parameters are increasingly being recognized as essential features of any habitat. The quantification of whether environmental fluctuations are prevalently predictable or unpredictable is remarkably relevant to understanding the evolutionary responses of organisms. However, when characterizing the relevant features of natural habitats, ecologists typically face two problems: (1) gathering long-term data and (2) handling the hard-won data. This paper takes advantage of the free access to long-term recordings of remote sensing data (27 years, Landsat TM/ETM+) to assess a set of environmental models for estimating environmental predictability. The case study included 20 Mediterranean saline ponds and lakes, and the focal variable was the water-surface area. This study first aimed to produce a method for accurately estimating the water-surface area from satellite images. Saline ponds can develop salt-crusted areas that make it difficult to distinguish between soil and water. This challenge was addressed using a novel pipeline that combines band ratio water indices and the short near-infrared band as a salt filter. The study then extracted the predictable and unpredictable components of variation in the water-surface area. Two different approaches, each showing variations in the parameters, were used to obtain the stochastic variation around a regular pattern with the objective of dissecting the effect of assumptions on predictability estimations. The first approach, which is based on Colwell's predictability metrics, transforms the focal variable into a nominal one. The resulting discrete categories define the relevant variations in the water-surface area. In the second approach, we introduced General Additive Model (GAM) fitting as a new metric for quantifying predictability. Both approaches produced a wide range of predictability for the studied ponds. Some model assumptions-which are considered very different a priori-had minor effects, whereas others produced predictability estimations that showed some degree of divergence. We hypothesize that these diverging estimations of predictability reflect the effect of fluctuations on different types of organisms. The fluctuation analysis described in this manuscript is applicable to a wide variety of systems, including both aquatic and nonaquatic systems, and will be valuable for quantifying and characterizing predictability, which is essential within the expected global increase in the unpredictability of environmental fluctuations. We advocate that a priori information for organisms of interest should be used to select the most suitable metrics estimating predictability, and we provide some guidelines for this approach

Bispectral index in hypercapnic encephalopathy associated with COPD exacerbation : a pilot study

Altres ajuts: We are thankful to Jonathan McFarland for his editing aid and to Mireia Admetllo and Camino Fernández for their help in collecting clinical data. This project was funded in part by SAF, CIBERES, BRN-Pla Armengol 2014, SEPAR 2015, and SEPAR Becario 2015.Hypercapnic encephalopathy is relatively frequent in severe exacerbations of COPD (ECOPDs), with its intensity usually being evaluated through clinical scales. Bispectral index (BIS) is a relatively new technique, based on the analysis of the electroencephalographic signal, which provides a good approximation to the level of consciousness, having already been validated in anesthesia. The objective of the study was to evaluate the utility of BIS in the assessment of the intensity of hypercapnic encephalopathy in ECOPD patients. A total of ten ECOPD patients were included, and the level of brain activity was assessed using BIS and different scales: Glasgow Coma Scale, Ramsay Sedation Scale (RSS), and Richmond Agitation-Sedation Scale. The evaluation was performed both in the acute phase and 3 months after discharge. BIS was recorded for a total of about 600 minutes. During ECOPD, BIS values ranged from 58.8 (95% CI: 48.6-69) for RSS score of 4 to 92.2 (95% CI: 90.1-94.3) for RSS score of 2. A significant correlation was observed between values obtained with BIS and those from the three scales, although the best fit was for RSS, followed by Glasgow and Richmond (r =−0.757, r =0.701, and r =0.615, respectively; P <0.001 for all). In the stable phase after discharge, BIS showed values considered as normal for a wake state (94.6; 95% CI: 91.7-97.9). BIS may be useful for the objective early detection and automatic monitoring of the intensity of hypercapnic encephalopathy in ECOPD, facilitating the early detection and follow-up of this condition, which may avoid management problems in these patients

CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse

Adenosine deaminase (ADA), a protein whose deficit leads to severe combined immunodeficiency, binds to the cell surface by means of either CD26, A(1) adenosine receptors, or A(2B) adenosine receptors. The physiological role of these interactions is not well understood. Our results show that by a 3-fold reduction in the EC(50) for the antigen, ADA potentiated T cell proliferation in autologous cocultures with antigen-pulsed immature or mature dendritic cells. Costimulation was not due to the enzymatic activity but to the interaction of ADA–CD26 complexes in T cells with an ADA-anchoring protein in dendritic cells. From colocalization studies, it is deduced that ADA colocalizing with adenosine receptors on dendritic cells interact with CD26 expressed on lymphocytes. This costimulatory signal in the immunological synapse leads to a marked increase (3- to 34-fold) in the production of the T helper 1 and proimmflamatory cytokines IFN-γ, TNF-α, and IL-6

Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

BACKGROUND AND AIMS:This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients. METHODS:The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses. RESULTS:As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, p = 0.01) remained significant. CONCLUSIONS:In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism