Conformational analysis, stereoelectronic interactions and NMR properties of 2-fluorobicyclo[2.2.1]heptan-7-ols

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Four diastereoisomers of 2-fluorobicyclo[2.2.1]heptan-7-ols were computationally investigated by using quantum-chemical calculations, and their relative energies were analyzed on the basis of stereoelectronic interactions, particularly the presence or otherwise of the F center dot center dot center dot HO intramolecular hydrogen bond in the syn-exo isomer. It was found through NBO and AIM analyses that such an interaction contributes to structural stabilization and that the (1h)J(F),(H(O)) coupling constant in the syn-exo isomer is modulated by the n(F)->sigma*(OH) interaction, i.e., the quantum nature of the F center dot center dot center dot HO hydrogen bond.812271232Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report

Insulin signalling pathways were investigated in a 33 year-old woman with immunologic insulin resistance. Her past medical history was remarkable for intermittent use of insulin and allergic reactions to several drugs, and measure of plasma anti-insulin antibodies level corroborated the clinical suspicion of immune mediated insulin resistance (8074 nU/ml - RIA - Ref value: <60). Treatment with several immunosuppressive regimens was tried, however the results were disappointing. Possible subcellular mechanisms of insulin resistance were investigated by performing analysis of insulin receptor and post receptor signaling in skeletal muscle biopsy. The expression of insulin receptor (IR), insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT-4) was evaluated in total extract from muscle tissue by Western blotting. Basal IR, IRS-1 and GLUT-4 expression was detected, however receptor autophosphorylation was not observed. A study of translocation of GLUT-4 to plasma membrane showed that tissue presented low levels of membrane-associated GLUT-4. When in vitro stimulation was undertaken, tissue was capable to be responsive to insulin. Our results suggest that even though IR expression was normally occurring, IR β-subunit tyrosine kinase activity in muscle was down-regulated leading to alterations in insulin post receptor signaling. Consistent with normal insulin receptor and post receptor signaling, our results were compatible with decreased insulin binding to IR probably due to neutralization by anti-insulin antibodies. In conclusion, this patient has immunologic insulin resistance and treatment should be based on immunosuppressive drugs as tolerated

Spectral Energy Distributions and Age Estimates of 172 Globular Clusters in M31

In this paper we present CCD multicolor photometry for 172 globular clusters (GCs), taken from the Bologna catalog (Battistini et al. 1987), in the nearby spiral galaxy M31. The observations were carried out by using the National Astronomical Observatories 60/90 cm Schmidt Telescope in 13 intermediate-band filters, which covered a range of wavelength from 3800 to 10000A. This provides a multicolor map of M31 in pixels of 1.7"*1.7". By aperture photometry, we obtain the spectral energy distributions (SEDs) for these GCs. Using the relationship between the BATC intermediate-band system used for the observations and the UBVRI broad-band system, the magnitudes in the B and V bands are derived. The computed V and B-V are in agreement with the values given by Battistini et al. (1987) and Barmby et al. (2000). Finally, by comparing the photometry of each GC with theoretical stellar population synthesis models, we estimate ages of the sample GCs for different metallicities. The results show that nearly all our sample GCs have ages more than 10^{9} years, and most of them are around 10^{10} years old. Also, we find that GCs fitted by the metal-poor model are generally older than ones fitted by the metal-rich model.Comment: 38 pages, 7 figures will appear in the February 2003 issue of A

Serious games for higher education: a framework for reducing design complexity

Westera, W., Nadolski, R., Hummel, H. G. K., & Wopereis, I. (2008). Serious games for higher education: a framework for reducing design complexity. Journal of Computer Assisted Learning, 24(5), 420-432.Serious games open up many new opportunities for complex skills learning in higher education. The inherent complexity of such games though, requires large efforts for their development. This paper presents a framework for serious game design, which aims to reduce the design complexity at both conceptual, technical and practical levels. The approach focuses on a relevant subset of serious games, labelled scenario-based games. At the conceptual level it identifies the basic elements that make up the static game configuration; it also describes the game dynamics, i.e. the state changes of the various game components in the course of time. At the technical level it presents a basic system architecture, which comprises various building tools. Various building tools will be explained and illustrated with technical implementations that are part of the Emergo toolkit for scenario-based game development. At the practical level, a set of design principles are presented for controlling and reducing game design complexity. The principles cover the topics of game structure, feedback and game representation, respectively. Practical application of the framework and the associated toolkit is briefly reported and evaluated

A protocol for developing, disseminating, and implementing a core outcome set for stress urinary incontinence.

INTRODUCTION: Randomized trials evaluating interventions for stress urinary incontinence (SUI) have been using variable outcome measures, reporting a variety of outcomes. Alongside this variation across studies, outcome-reporting flaws contribute to a limited use of research to inform clinical practice. The development and use of core outcome sets (COSs) in future trials would ensure that outcomes important to different stakeholders and primarily women with SUI are reported more consistently and comprehensively. METHODS: An international steering group including healthcare professionals, researchers, and women with urinary incontinence will guide the development of this COS. Potential outcomes will be identified through comprehensive literature reviews. These outcomes will be entered into an international, multiperspective online Delphi survey. All key stakeholders, including healthcare professionals, researchers, and women with urinary incontinence, will be invited to participate. The modified Delphi method encourages stakeholder group convergence toward collective agreement, also referred as consensus, core outcomes. DISCUSSION: Dissemination and implementation of the resulting COS within an international context will be promoted and reviewed. Embedding the COS for SUI within future clinical trials, systematic reviews and clinical practice guidelines could make a significant contribution to advancing the value of research in informing clinical practice, enhancing patient care and improving outcomes. The infrastructure created by developing a COS for SUI could be leveraged in other settings, for example, selecting research priorities and clinical practice guideline development

Movement, Memory and Mathematics: Henri Bergson and the Ontology of Learning

© 2014, Springer Science+Business Media Dordrecht. Using the work of philosopher Henri Bergson (1859–1941) to examine the nature of movement and memory, this article contributes to recent research on the role of the body in learning mathematics. Our aim in this paper is to introduce the ideas of Bergson and to show how these ideas shed light on mathematics classroom activity. Bergson’s monist philosophy provides a framework for understanding the materiality of both bodies and mathematical concepts. We discuss two case studies of classrooms to show how the mathematical concepts of number and function are themselves mobile and full of potentiality, open to deformation and the remapping of the (im)possible. Bergson helps us look differently at mathematical activity in the classroom, not as a closed set of distinct interacting bodies groping after abstract concepts, but as a dynamic relational assemblage