Scaffolding School Pupils’ Scientific Argumentation with Evidence-Based Dialogue Maps

This chapter reports pilot work investigating the potential of Evidence-based Dialogue Mapping to scaffold young teenagers’ scientific argumentation. Our research objective is to better understand pupils’ usage of dialogue maps created in Compendium to write scientific ex-planations. The participants were 20 pupils, 12-13 years old, in a summer science course for “gifted and talented” children in the UK. Through qualitative analysis of three case studies, we investigate the value of dialogue mapping as a mediating tool in the scientific reasoning process during a set of learning activities. These activities were published in an online learning envi-ronment to foster collaborative learning. Pupils mapped their discussions in pairs, shared maps via the online forum and in plenary discussions, and wrote essays based on their dialogue maps. This study draws on these multiple data sources: pupils’ maps in Compendium, writings in science and reflective comments about the uses of mapping for writing. Our analysis highlights the diversity of ways, both successful and unsuccessful, in which dialogue mapping was used by these young teenagers

A study to develop a mechanized welding procedure to join thick-gage aluminum alloy plate using narrow-gap techniques Final report

Narrow-gap welding procedures for joining thick gauge aluminum alloy plat

Engineered G protein coupled receptors reveal independent regulation of internalization, desensitization and acute signaling

BACKGROUND: The physiological regulation of G protein-coupled receptors, through desensitization and internalization, modulates the length of the receptor signal and may influence the development of tolerance and dependence in response to chronic drug treatment. To explore the importance of receptor regulation, we engineered a series of G(i)-coupled receptors that differ in signal length, degree of agonist-induced internalization, and ability to induce adenylyl cyclase superactivation. All of these receptors, based on the kappa opioid receptor, were modified to be receptors activated solely by synthetic ligands (RASSLs). This modification allows us to compare receptors that have the same ligands and effectors, but differ only in desensitization and internalization. RESULTS: Removal of phosphorylation sites in the C-terminus of the RASSL resulted in a mutant that was resistant to internalization and less prone to desensitization. Replacement of the C-terminus of the RASSL with the corresponding portion of the mu opioid receptor eliminated the induction of AC superactivation, without disrupting agonist-induced desensitization or internalization. Surprisingly, removal of phosphorylation sites from this chimera resulted in a receptor that is constitutively internalized, even in the absence of agonist. However, the receptor still signals and desensitizes in response to agonist, indicating normal G-protein coupling and partial membrane expression. CONCLUSIONS: These studies reveal that internalization, desensitization and adenylyl cyclase superactivation, all processes that decrease chronic G(i)-receptor signals, are independently regulated. Furthermore, specific mutations can radically alter superactivation or internalization without affecting the efficacy of acute G(i )signaling. These mutant RASSLs will be useful for further elucidating the temporal dynamics of the signaling of G protein-coupled receptors in vitro and in vivo

Regression Approaches for Microarray Data Analysis

A variety of new procedures have been devised to handle the two sample comparison (e.g., tumor versus normal tissue) of gene expression values as measured with microarrays. Such new methods are required in part because of some defining characteristics of microarray-based studies: (i) the very large number of genes contributing expression measures which far exceeds the number of samples (observations) available, and (ii) the fact that by virtue of pathway/network relationships, the gene expression measures tend to be highly correlated. These concerns are exacerbated in the regression setting, where the objective is to relate gene expression, simultaneously for multiple genes, to some external outcome or phenotype. Correspondingly, several methods have been recently proposed for addressing these issues. We briefly critique some of these methods prior to a detailed evaluation of gene harvesting. This reveals that gene harvesting, without additional constraints, can yield artifactual solutions. Results obtained employing such constraints motivate the use of regularized regression procedures such as the lasso, least angle regression, and support vector machines. Model selection and solution multiplicity issues are also discussed. The methods are evaluated using a microarraybased study of cardiomyopathy in transgenic mice

MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data

MAPPFinder is a tool that creates a global gene-expression profile across all areas of biology by integrating the annotations of the Gene Ontology (GO) Project with the free software package GenMAPP . The results are displayed in a searchable browser, allowing the user to rapidly identify GO terms with over-represented numbers of gene-expression changes. Clicking on GO terms generates GenMAPP graphical files where gene relationships can be explored, annotated, and files can be freely exchanged

Cardiomyocyte-restricted overexpression of extracellular superoxide dismutase increases nitric oxide bioavailability and reduces infarct size after ischemia/reperfusion

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