Nietzsche Kaufmann, Walter A; Nehamas, Alexander
10/2013, Volume:
3
eBook
This classic is the benchmark against which all modern books about Nietzsche are measured. When Walter Kaufmann wrote it in the immediate aftermath of World War II, most scholars outside Germany ...viewed Nietzsche as part madman, part proto-Nazi, and almost wholly unphilosophical. Kaufmann rehabilitated Nietzsche nearly single-handedly, presenting his works as one of the great achievements of Western philosophy.
Responding to the powerful myths and countermyths that had sprung up around Nietzsche, Kaufmann offered a patient, evenhanded account of his life and works, and of the uses and abuses to which subsequent generations had put his ideas. Without ignoring or downplaying the ugliness of many of Nietzsche's proclamations, he set them in the context of his work as a whole and of the counterexamples yielded by a responsible reading of his books. More positively, he presented Nietzsche's ideas about power as one of the great accomplishments of modern philosophy, arguing that his conception of the "will to power" was not a crude apology for ruthless self-assertion but must be linked to Nietzsche's equally profound ideas about sublimation. He also presented Nietzsche as a pioneer of modern psychology and argued that a key to understanding his overall philosophy is to see it as a reaction against Christianity.
Many scholars in the past half century have taken issue with some of Kaufmann's interpretations, but the book ranks as one of the most influential accounts ever written of any major Western thinker. Featuring a new foreword by Alexander Nehamas, this Princeton Classics edition of Nietzsche introduces a new generation of readers to one the most influential accounts ever written of any major Western thinker.
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•The presented procedure records the full crack behaviour in large-scale experiments.•DIC results of the specimen’s surface provide highly accurate crack measurements.•Complex crack ...patters are automatically extracted using 2D image processing methods.•Several sensitivity analyses help in understanding the measurement uncertainty.•Crack measurements are represented with automated data visualisations tools.
The acquisition and evaluation of the crack behaviour in experiments on quasi-brittle materials, such as concrete, mortar, or masonry is essential for understanding their structural behaviour. This publication presents a fully automated procedure to detect cracks and measure crack kinematics in laboratory experiments instrumented with digital image correlation (DIC). Crack lines are extracted using well-established image processing methods showing excellent agreement with the physical crack pattern. In contrast to most existing crack detectors that rely on pixel intensities of true images, the presented crack detection is based on the DIC principal tensile strain field what allows the extraction of much finer cracks and more reliable crack locations. The crack widths and slips are measured using the DIC displacement field accounting for local rotations of the specimen. Additionally, automated visualisations of the crack kinematic measurements including data smoothing are presented. Several sensitivity analyses evaluating the performance and the uncertainty of the crack detector and the crack kinematic measurements have been conducted. These analyses show that the obtained results depend on the DIC configuration and that the procedure is limited in the case of very closely spaced cracks. With appropriate DIC parameters, the procedure allows detecting crack locations with high precision and measuring crack kinematics very accurately even in large-scale experiments with complex crack patterns.
Fifty years after the first publication on Rett syndrome, Banerjee et al. review the molecular, cellular and circuit neurobiology of the disorder. They summarize recent advances in therapeutic ...interventions explored in preclinical models, as well as lessons learnt from past clinical trials and how these might inform future therapeutic approaches.
Abstract
With the recent 50th anniversary of the first publication on Rett syndrome, and the almost 20 years since the first report on the link between Rett syndrome and MECP2 mutations, it is important to reflect on the tremendous advances in our understanding and their implications for the diagnosis and treatment of this neurodevelopmental disorder. Rett syndrome features an interesting challenge for biologists and clinicians, as the disorder lies at the intersection of molecular mechanisms of epigenetic regulation and neurophysiological alterations in synapses and circuits that together contribute to severe pathophysiological endophenotypes. Genetic, clinical, and neurobiological evidences support the notion that Rett syndrome is primarily a synaptic disorder, and a disease model for both intellectual disability and autism spectrum disorder. This review examines major developments in both recent neurobiological and preclinical findings of Rett syndrome, and to what extent they are beginning to impact our understanding and management of the disorder. It also discusses potential applications of knowledge on synaptic plasticity abnormalities in Rett syndrome to its diagnosis and treatment.
Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. We investigated relationships ...between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1,099 typically developing individuals between 3 and 20 years of age. Income was logarithmically associated with brain surface area. Among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data imply that income relates most strongly to brain structure among the most disadvantaged children.
Structural MRI allows unparalleled in vivo study of the anatomy of the developing human brain. For more than two decades 1, MRI research has revealed many new aspects of this multifaceted maturation ...process, significantly augmenting scientific knowledge gathered from postmortem studies. Postnatal brain development is notably protracted and involves considerable changes in cerebral cortical 2–4, subcortical 5, and cerebellar 6, 7 structures, as well as significant architectural changes in white matter fiber tracts 8–11 (see 12). Although much work has described isolated features of neuroanatomical development, it remains a critical challenge to characterize the multidimensional nature of brain anatomy, capturing different phases of development among individuals. Capitalizing on key advances in multisite, multimodal MRI, and using cross-validated nonlinear modeling, we demonstrate that developmental brain phase can be assessed with much greater precision than has been possible using other biological measures, accounting for more than 92% of the variance in age. Further, our composite metric of morphology, diffusivity, and signal intensity shows that the average difference in phase among children of the same age is only about 1 year, revealing for the first time a latent phenotype in the human brain for which maturation timing is tightly controlled.
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► Multimodal neuroanatomical measures predict child age with greater than 92% accuracy ► Morphology, diffusivity, and signal intensity capture brain maturity equally well ► Reveals a phenotype that varies by only about a year for most same-aged individuals ► Suggests timing of brain maturation is more tightly controlled than previously known
The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as ...the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1-3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abpl and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abpl mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization.
Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such “simple synapses” indicate that they contain a small complement ...of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Cav2.1 channels form several clusters per active zone with about nine channels per cluster. The mean value and range of intersynaptic variation are similar for Cav2.1 cluster numbers and for functional estimates of docking-site numbers obtained from the maximum numbers of released vesicles per action potential. Both numbers grow in relation with synaptic size and decrease by a similar extent with age between 2 wk and 4 wk postnatal. Thus, the mean docking-site numbers were 3.15 at 2 wk (range: 1–10) and 2.03 at 4 wk (range: 1–4), whereas the mean numbers of Cav2.1 clusters were 2.84 at 2 wk (range: 1–8) and 2.37 at 4 wk (range: 1–5). These changes were accompanied by decreases of miniature current amplitude (from 93 pA to 56 pA), active-zone surface area (from 0.0427 μm² to 0.0234 μm²), and initial success rate (from 0.609 to 0.353), indicating a tightening of synaptic transmission with development. Altogether, these results suggest a close correspondence between the number of functionally defined vesicular docking sites and that of clusters of voltage-gated calcium channels.
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