Long‐term potentiation (LTP) of excitatory synapses is a leading model to explain the concept of information storage in the brain. Multiple mechanisms contribute to LTP, but central amongst them is an increased sensitivity of the postsynaptic membrane to neurotransmitter release. This sensitivity is predominantly determined by the abundance and localization of AMPA‐type glutamate receptors (AMPARs). A combination of AMPAR structural data, super‐resolution imaging of excitatory synapses, and an abundance of electrophysiological studies are providing an ever‐clearer picture of how AMPARs are (...) recruited and organized at synaptic junctions. Here, we review the latest insights into this process, and discuss how both cytoplasmic and extracellular receptor elements cooperate to tune the AMPAR response at the hippocampal CA1 synapse. (shrink)

Background: Although convolutional neural networks (CNNs) achieve high diagnostic accuracy for detecting Alzheimer’s disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not yet applied in clinical routine. One important reason for this is a lack of model comprehensibility. Recently developed visualization methods for deriving CNN relevance maps may help to fill this gap as they allow the visualization of key input image features that drive the decision of the model. We investigated whether models with higher accuracy (...) also rely more on discriminative brain regions predefined by prior knowledge. Methods: We trained a CNN for the detection of AD in N = 663 T1-weighted MRI scans of patients with dementia and amnestic mild cognitive impairment (MCI) and verified the accuracy of the models via cross-validation and in three independent samples including in total N = 1655 cases. We evaluated the association of relevance scores and hippocampus volume to validate the clinical utility of this approach. To improve model comprehensibility, we implemented an interactive visualization of 3D CNN relevance maps, thereby allowing intuitive model inspection. Results: Across the three independent datasets, group separation showed high accuracy for AD dementia versus controls (AUC ≥ 0.91) and moderate accuracy for amnestic MCI versus controls (AUC ≈ 0.74). Relevance maps indicated that hippocampal atrophy was considered the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearson’s r ≈ −0.86, p < 0.001). Conclusion: The relevance maps highlighted atrophy in regions that we had hypothesized a priori. This strengthens the comprehensibility of the CNN models, which were trained in a purely data-driven manner based on the scans and diagnosis labels. The high hippocampus relevance scores as well as the high performance achieved in independent samples support the validity of the CNN models in the detection of AD-related MRI abnormalities. The presented data-driven and hypothesis-free CNN modeling approach might provide a useful tool to automatically derive discriminative features for complex diagnostic tasks where clear clinical criteria are still missing, for instance for the differential diagnosis between various types of dementia. (shrink)

Regular musical activity as a complex multimodal lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer’s disease. This cross-sectional study investigated the association and interplay between musical instrument playing during life, multi-domain cognitive abilities and brain morphology in older adults from the DZNE-Longitudinal Cognitive Impairment and Dementia Study study. Participants reporting having played a musical instrument across three life periods were compared to controls without a history of musical instrument playing, well-matched for reserve proxies of education, (...) intelligence, socioeconomic status and physical activity. Participants with musical activity outperformed controls in global cognition, working memory, executive functions, language, and visuospatial abilities, with no effects seen for learning and memory. The musically active group had greater gray matter volume in the somatosensory area, but did not differ from controls in higher-order frontal, temporal, or hippocampal volumes. However, the association between gray matter volume in distributed frontal-to-temporal regions and cognitive abilities was enhanced in participants with musical activity compared to controls. We show that playing a musical instrument during life relates to better late-life cognitive abilities and greater brain capacities in OA. Musical activity may serve as a multimodal enrichment strategy that could help preserve cognitive and brain health in late life. Longitudinal and interventional studies are needed to support this notion. (shrink)

Open peer commentary on the article “Religion: A Radical-Constructivist Perspective” by Andreas Quale. Upshot: Quale offers a way of categorizing religious discourse based on radical constructivism. This commentary raises questions about the inter-relation of cognitive and non-cognitive knowledge, the role of testimony in learning about religion, and whether knowledge and belief have different roles in cognitive and non-cognitive knowledge, and suggests that Quale’s analysis opens a tolerant perspective on religious discourse.

Geschichte der neueren Philosophie ist ein unveränderter, hochwertiger Nachdruck der Originalausgabe aus dem Jahr 1895. Hansebooks ist Herausgeber von Literatur zu unterschiedlichen Themengebieten wie Forschung und Wissenschaft, Reisen und Expeditionen, Kochen und Ernährung, Medizin und weiteren Genres. Der Schwerpunkt des Verlages liegt auf dem Erhalt historischer Literatur. Viele Werke historischer Schriftsteller und Wissenschaftler sind heute nur noch als Antiquitäten erhältlich. Hansebooks verlegt diese Bücher neu und trägt damit zum Erhalt selten gewordener Literatur und historischem Wissen auch für die Zukunft bei.

Based on an ethnographic fieldwork the article analyses the experiences of 8-10 year old children in three different institutions. It is shown how the children create and maintain different social landscapes in each setting. This means that children's experiences are related to the position they have in the landscape. The notion social identity is used to discuss and explain these findings. With this notion identity is explained as an interplay between internal and external factors: between group-identification and categorisation. Children's different (...) identities in different settings are not created by children themselves, but must bee seen in relation to the categorisation used by the adults to classify children. The professional categorisations of children are a central part of the social space in relation to which children act, talk, and play. (shrink)

ḥeleḳ 1. Hadrakhah le-shalom bayit : sefer hadrakhah meforaṭ be-ʻinyene shidukhim ṿe-shelom bayit be-niśuʼin ʻa. p. maʼamre Ḥazal -- ḥeleḳ 2. Hadrakhah le-ṭaharat ha-bayit : ʻiḳre ha-halakhot ha-ḥiyuniyot : ʻa. p. pisḳe maran ha-Shu. ʻa. ṿeha-Rema uve-tsiruf hakhraʻot aḥarone zemanenu.

Articles; chiefly on Islamic ethics and conveying non Muslims for Islam.

This paper focuses on the preliminary evaluation of expressions of moral sentiment under conditions of cultural pluralism. The advance of science and technology puts ever new power over nature in human hands, and if this new power is to more fully serve human ends, then it must become the means or material of human virtue. This prospect poses the question of the relationship between power and virtue, and equally, the question of how scientific advances may be understood to enter into (...) a pluralism of moral doctrines and deliberations. Taking a page from the philosophy of science, the present approach examines the relationship between scientific advances and moral evaluations of developing practices as mediated by contemporary accounts of the virtues of hypotheses. If we conceive of expressions of moral sentiment as hypotheses for the amendment or expansion of existing moral doctrines in the light of new possibilities for action, then this suggests that expressions of moral sentiment may be evaluated, in a preliminary way, by reference to standard lists of the virtues of hypotheses: refutability, conservatism, modesty or simplicity, precision, elegance, and generality. Expressions of moral sentiment are subject to preliminary evaluation, on cognitive grounds, by reference to their prospective integration and/or modification of on-going moral traditions. (shrink)