101 research outputs found

    Time for action! ICT integration in formal education : key findings from a region-wide follow-up monitor

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    This paper is a report on the key findings of a region-wide monitoring study conducted in Dutch-speaking schools in Belgium. First, we elaborate on the building blocks of the instrument, which has been updated and improved since its first deployment in 2007. In particular we focus on the core indicators, along with the multi-actor approach, the sample design and the ways in which new phenomena such as media literacy and gaming have been operationalized. Secondly, we highlight the main trends and patterns within pre-school, primary and secondary education. The first descriptive analyses show quite disappointing results with regard to ICT use at the micro level and the available infrastructure, while headmasters, teachers and pupils reported positive perceptions of different aspects of ICT integration. These results indicate an urgent need to take appropriate action. Therefore, the final part of the paper examines how ICT integration could be improved via structural changes and appropriate policymaking with regard to budgeting, teacher training and the particular role of ICT coordinators in schools

    Monitor for ICT Integration in Flemish Education (MICTIVO) : research set-up and some preliminaries

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    MICTIVO is a monitoring tool to evaluate ICT integration in the formal Flemish education. It was first conducted in 2008, based on a literature review of several European monitors for mapping the adoption and diffusion of technology for teaching and learning purposes to evaluate the return on investment and effects of ICT on educational practice. The tool consists of different aspects concerning ICT: infrastructure and policy, perceptions, competences and integration at micro-level. In 2008, MICTIVO was tested a first time, the indicators for the different components were validated and empirically tested. In 2013 and 2018 a follow up study was conducted to monitor the current state of ICT integration. The scale and breadth of MICTIVO makes it possible to get representative information on the status of ICT integration in Flanders and the evolution of trends through time

    Betrokken, voorbeeldig, proactief: ICT-integratie in de lerarenopleiding

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    Naar aanleiding van een evaluatie van ICT-integratie in Vlaanderen waaruit blijkt dat er meer dan dringend nood is aan professionalisering van leraren, worden drie benaderingen geschetst. Elke benadering reflecteert een eigen visie op de (toekomstige) rol van ICT in het onderwijs

    Synthesis and biological evaluation of cyclopropyl analogues of fosmidomycin as potent Plasmodium falciparum growth inhibitors

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    A series of fosmidomycin analogues featuring restricted conformational mobility has been synthesized and evaluated as inhibitors of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase and as growth inhibitors of P. falciparum. The enantiomerically pure trans-cyclopropyl N-acetyl analogue 3b showed comparable inhibitory activity as fosmidomycin toward E. coli DOXP reductoisomerase and proved equally active when tested in vitro for P. falciparum growth inhibition. Conversely, the alpha-phenyl cis-cyclopropyl analogue 4 showed virtually no inhibition of the enzyme

    Elaboration of a proprietary thymidylate kinase inhibitor motif towards anti-tuberculosis agents

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    International audienceWe report the design and synthesis of a series of non-nucleoside MtbTMPK inhibitors (1-14) based on the gram-positive bacterial TMPK inhibitor hit compound 1. A practical synthesis was developed to access these analogues. Several compounds show promising MtbTMPK inhibitory potency and allow the establishment of a structure-activity relationship, which is helpful for further optimization

    Depression in Mild Cognitive Impairment is associated with Progression to Alzheimer's Disease:A Longitudinal Study

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    Background: Behavioral and psychological signs and symptoms of dementia (BPSD) belong to the core symptoms of dementia and are also common in mild cognitive impairment (MCI).Objective: This study would like to contribute to the understanding of the prognostic role of BPSD in MCI for the progression to dementia due to Alzheimer's disease (AD).Methods: Data were generated through an ongoing prospective longitudinal study on BPSD. Assessment was performed by means of the Middelheim Frontality Score, Behave-AD, Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia (CSDD), and Geriatric Depression Scale 30-questions (GDS-30). Cox proportional hazard models were used to test the hypothesis that certain BPSD in MCI are predictors of developing AD.Results: The study population consisted of 183 MCI patients at baseline. At follow-up, 74 patients were stable and 109 patients progressed to AD. The presence of significant depressive symptoms in MCI as measured by the CSDD (HR: 2.06; 95% CI: 1.23-3.44; p = 0.011) and the GDS-30 (HR: 1.77; 95% CI: 1.10-2.85; p = 0.025) were associated with progression to AD. The severity of depressive symptoms as measured by the GDS-30 was a predictor for progression too (HR: 1.06; 95% CI: 1.01-1.11; p = 0.020). Furthermore, the severity of agitated behavior, especially verbal agitation and the presence of purposeless activity, was also associated with progression, whereas diurnal rhythm disturbances were associated with no progression to AD.Conclusion: Depressive symptoms in MCI appear to be predictors for progression to AD.</p

    New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma

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    Abstract The use of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) as a positron emission tomography (PET) tracer for brain tumor imaging might have some limitations because of the relatively low affinity for the L-type amino acid transporter 1 (LAT1). To assess the stereospecificity and evaluate the influence of aromatic ring modification of phenylalanine LAT1 targeting tracers, six different fluoroalkylated phenylalanine analogues were synthesized. After in vitro Ki determination, the most promising compound, 2-[18F]-2-fluoroethyl-l-phenylalanine (2-[18F]FELP), was selected for further evaluation and in vitro comparison with [18F]FET. Subsequently, 2-[18F]FELP was assessed in vivo and compared with [18F]FET and [18F]FDG in a F98 glioblastoma rat model. 2-[18F]FELP showed improved in vitro characteristics over [18F]FET, especially when the affinity and specificity for system L is concerned. Based on our results, 2-[18F]FELP is a promising new PET tracer for brain tumor imaging

    Loss of DPP6 in neurodegenerative dementia : a genetic player in the dysfunction of neuronal excitability

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    Emerging evidence suggested a converging mechanism in neurodegenerative brain diseases (NBD) involving early neuronal network dysfunctions and alterations in the homeostasis of neuronal firing as culprits of neurodegeneration. In this study, we used paired-end short-read and direct long-read whole genome sequencing to investigate an unresolved autosomal dominant dementia family significantly linked to 7q36. We identified and validated a chromosomal inversion of ca. 4Mb, segregating on the disease haplotype and disrupting the coding sequence of dipeptidyl-peptidase 6 gene (DPP6). DPP6 resequencing identified significantly more rare variants-nonsense, frame-shift, and missense-in early-onset Alzheimer's disease (EOAD, p value = 0.03, OR = 2.21 95% CI 1.05-4.82) and frontotemporal dementia (FTD, p = 0.006, OR = 2.59, 95% CI 1.28-5.49) patient cohorts. DPP6 is a type II transmembrane protein with a highly structured extracellular domain and is mainly expressed in brain, where it binds to the potassium channel K(v)4.2 enhancing its expression, regulating its gating properties and controlling the dendritic excitability of hippocampal neurons. Using in vitro modeling, we showed that the missense variants found in patients destabilize DPP6 and reduce its membrane expression (p < 0.001 and p < 0.0001) leading to a loss of protein. Reduced DPP6 and/or K(v)4.2 expression was also detected in brain tissue of missense variant carriers. Loss of DPP6 is known to cause neuronal hyperexcitability and behavioral alterations in Dpp6-KO mice. Taken together, the results of our genomic, genetic, expression and modeling analyses, provided direct evidence supporting the involvement of DPP6 loss in dementia. We propose that loss of function variants have a higher penetrance and disease impact, whereas the missense variants have a variable risk contribution to disease that can vary from high to low penetrance. Our findings of DPP6, as novel gene in dementia, strengthen the involvement of neuronal hyperexcitability and alteration in the homeostasis of neuronal firing as a disease mechanism to further investigate

    Deep sequencing-based expression analysis shows major advances in robustness, resolution and inter-lab portability over five microarray platforms

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    The hippocampal expression profiles of wild-type mice and mice transgenic for δC-doublecortin-like kinase were compared with Solexa/Illumina deep sequencing technology and five different microarray platforms. With Illumina's digital gene expression assay, we obtained ∼2.4 million sequence tags per sample, their abundance spanning four orders of magnitude. Results were highly reproducible, even across laboratories. With a dedicated Bayesian model, we found differential expression of 3179 transcripts with an estimated false-discovery rate of 8.5%. This is a much higher figure than found for microarrays. The overlap in differentially expressed transcripts found with deep sequencing and microarrays was most significant for Affymetrix. The changes in expression observed by deep sequencing were larger than observed by microarrays or quantitative PCR. Relevant processes such as calmodulin-dependent protein kinase activity and vesicle transport along microtubules were found affected by deep sequencing but not by microarrays. While undetectable by microarrays, antisense transcription was found for 51% of all genes and alternative polyadenylation for 47%. We conclude that deep sequencing provides a major advance in robustness, comparability and richness of expression profiling data and is expected to boost collaborative, comparative and integrative genomics studies
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