LE DIMENSIONI LINGUISTICHE IN TUTTE LE DISCIPLINE SCOLASTICHE. UNA GUIDA PER L’ELABORAZIONE DEI CURRICOLI E PER LA FORMAZIONE DEGLI INSEGNANTI

Nell’aprile del 2014 la Raccomandazione CM/ Rec(2014)5 del Comitato dei Ministri degli Stati membri del Consiglio d’Europa ha attirato l’attenzione “sull’importanza delle competenze nella(e) lingua(e) di scolarizzazione per l’equità e la qualità nell’educazione e per il successo scolastico”. Uno dei principi fondamentali posti in evidenza dalla Raccomandazione è l’importanza della lingua, non solo in quanto specifica materia di studio, ma anche in tutte le discipline del curricolo. È questo un aspetto dell’insegnamento linguistico che rappresenta una sfida particolare per i responsabili politici e per tutti coloro che svolgono la loro professione nel campo dell’educazione perché richiede nuove idee e una prospettiva globale e interdisciplinare. Per questa ragione la Guida che qui si presenta è stata redatta per facilitare l’attuazione dei principi e delle misure indicate dalla Raccomandazione. Ha lo scopo di mostrare perché la padronanza della lingua è importante in tutte le materie e quali ne sono le implicazioni per le politiche linguistiche e le pratiche d’insegnamento.The language dimension in all subjects. A Handbook for Curriculum development and teacher trainingIn April 2014 a Recommendation of the Committee of Ministers of the Council of Europe drew attention to ‘The importance of competences on the language(s) of schooling for equity and quality in education and for educational success' (Recommendation CM/Rec(2014)5. One of the key principles in the Recommendation highlights the importance of language not just as a separate subject in school but in all subjects across the curriculum. This is an aspect of language education that presents a particular challenge for policy-makers and practitioners, since it requires new insights and a whole-school, cross-curricular perspective. This Handbook has been written, therefore, in order to support the implementation of the principles and measures set out in the Recommendation. It aims to show why language in all subjects is important, and what the implications are for policy and practice

A compact model for magnetic tunnel junction (MTJ) switched by thermally assisted Spin transfer torque (TAS + STT)

Thermally assisted spin transfer torque [TAS + STT] is a new switching approach for magnetic tunnel junction [MTJ] nanopillars that represents the best trade-off between data reliability, power efficiency and density. In this paper, we present a compact model for MTJ switched by this approach, which integrates a number of physical models such as temperature evaluation and STT dynamic switching models. Many experimental parameters are included directly to improve the simulation accuracy. It is programmed in the Verilog-A language and compatible with the standard IC CAD tools, providing an easy parameter configuration interface and allowing high-speed co-simulation of hybrid MTJ/CMOS circuits

Conservation, Variability and the Modeling of Active Protein Kinases

The human proteome is rich with protein kinases, and this richness has made the kinase of crucial importance in initiating and maintaining cell behavior. Elucidating cell signaling networks and manipulating their components to understand and alter behavior require well designed inhibitors. These inhibitors are needed in culture to cause and study network perturbations, and the same compounds can be used as drugs to treat disease. Understanding the structural biology of protein kinases in detail, including their commonalities, differences and modes of substrate interaction, is necessary for designing high quality inhibitors that will be of true use for cell biology and disease therapy. To this end, we here report on a structural analysis of all available active-conformation protein kinases, discussing residue conservation, the novel features of such conservation, unique properties of atypical kinases and variability in the context of substrate binding. We also demonstrate how this information can be used for structure prediction. Our findings will be of use not only in understanding protein kinase function and evolution, but they highlight the flaws inherent in kinase drug design as commonly practiced and dictate an appropriate strategy for the sophisticated design of specific inhibitors for use in the laboratory and disease therapy

Reproductive profiles and risk of breast cancer subtypes : a multi-center case-only study

Background: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. Methods: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years. Results: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0. 030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p <0.0001), but this effect was not apparent at a later FFTP. Conclusions: Our main findings suggest that parity is associated with TNBC across all ages at BC diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC.Peer reviewe

Leaf Morphology, Taxonomy and Geometric Morphometrics: A Simplified Protocol for Beginners

Taxonomy relies greatly on morphology to discriminate groups. Computerized geometric morphometric methods for quantitative shape analysis measure, test and visualize differences in form in a highly effective, reproducible, accurate and statistically powerful way. Plant leaves are commonly used in taxonomic analyses and are particularly suitable to landmark based geometric morphometrics. However, botanists do not yet seem to have taken advantage of this set of methods in their studies as much as zoologists have done. Using free software and an example dataset from two geographical populations of sessile oak leaves, we describe in detailed but simple terms how to: a) compute size and shape variables using Procrustes methods; b) test measurement error and the main levels of variation (population and trees) using a hierachical design; c) estimate the accuracy of group discrimination; d) repeat this estimate after controlling for the effect of size differences on shape (i.e., allometry). Measurement error was completely negligible; individual variation in leaf morphology was large and differences between trees were generally bigger than within trees; differences between the two geographic populations were small in both size and shape; despite a weak allometric trend, controlling for the effect of size on shape slighly increased discrimination accuracy. Procrustes based methods for the analysis of landmarks were highly efficient in measuring the hierarchical structure of differences in leaves and in revealing very small-scale variation. In taxonomy and many other fields of botany and biology, the application of geometric morphometrics contributes to increase scientific rigour in the description of important aspects of the phenotypic dimension of biodiversity. Easy to follow but detailed step by step example studies can promote a more extensive use of these numerical methods, as they provide an introduction to the discipline which, for many biologists, is less intimidating than the often inaccessible specialistic literature

Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, $\textit{cis}$-acting variants represent an important source of phenotypic variation. Consequently, $\textit{cis}$-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, $\textit{P}$ = 5.6x10$^{-6}$). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, $\textit{HELQ}$, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, $\textit{MRPS18C}$ encoding the Mitochondrial Ribosomal Protein S18C and $\textit{FAM175A (ABRAXAS)}$, encoding a $\textit{BRCA1}$ BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with $\textit{HELQ }$ ($\textit{P}$ = 8.28x10$^{-14}$), $\textit{MRPS18C}$ ($\textit{P}$ = 1.94x10$^{-27}$) and $\textit{FAM175A }$ ($\textit{P}$ = 3.83x10$^{-3}$), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.Information regarding funding can be found in the published article or the publisher's website. Funders include Cancer Research UK and the National Institute for Health Research

RAD51B in Familial Breast Cancer.

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

A likelihood ratio approach for utilizing case-control data in the clinical classification of rare sequence variants: Application to BRCA1 and BRCA2

A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance