326 research outputs found
sj-docx-1-msj-10.1177_13524585221097560 – Supplemental material for Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study
No full textSupplemental material, sj-docx-1-msj-10.1177_13524585221097560 for Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study by Omar Al-Louzi, Sargis Manukyan, Maxime Donadieu, Martina Absinta, Vijay Letchuman, Brent Calabresi, Parth Desai, Erin S Beck, Snehashis Roy, Joan Ohayon, Dzung L Pham, Anish Thomas, Steven Jacobson, Irene Cortese, Pavan K Auluck, Govind Nair, Pascal Sati and Daniel S Reich in Multiple Sclerosis Journal</p
Context Dependent Neuroprotective Properties of Prion Protein (Prp)
No full textAlthough it has been known for more than twenty years that an aberrant conformation of the prion protein (PrP) is the causative agent in prion diseases, the role of PrP in normal biology is undetermined. Numerous studies have suggested a protective function for PrP, including protection from ischemic and excitotoxic lesions and several apoptotic insults. On the other hand, many observations have suggested the contrary, linking changes in PrP localization or domain structure—independent of infectious prion conformation—to severe neuronal damage. Surprisingly, a recent report suggests that PrP is a receptor for toxic oligomeric species of a-β, a pathogenic fragment of the amyloid precursor protein, and likely contributes to disease pathogenesis of Alzheimer’s disease. We sought to access the role of PrP in diverse neurological disorders. First, we confirmed that PrP confers protection against ischemic damage using an acute stroke model, a well characterized association. After ischemic insult, PrP knockouts had dramatically increased infarct volumes and decreased behavioral performance compared to controls. To examine the potential of PrP’s neuroprotective or neurotoxic properties in the context of other pathologies, we deleted PrP from several transgenic models of neurodegenerative disease. Deletion of PrP did not substantially alter the disease phenotypes of mouse models of Parkinson’s disease or tauopathy. Deletion of PrP in one of two Huntington’s disease models tested, R6/2, modestly slowed motor deterioration as measured on an accelerating rotarod but otherwise did not alter other major features of the disease. Finally, transgenic overexpression of PrP did not exacerbate the Huntington’s motor phenotype. These results suggest that PrP has a context-dependent neuroprotective function and does not broadly contribute to the disease models tested herein.Ellison Medical FoundationWhitaker Health Sciences Fund Fellowshi
Digital Media and Knowledge Production Within Social Movements: Insights From the Transition Movement in Italy
No full textsponsorship: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This article grounds in research activites carried out in the period 2016-2017 within the framework of the project "MAKERS- Movements as knowledge producers and learning spaces in the digital age" funded by the Scuola Normale Superiore. (Scuola Normale Superiore)status: Publishe
Esiste in Italia un diritto al figlio sano? (Riflessioni a margine della causa Costa et Pavan vs Italia)
No full textThe author, starting from the case Costa et Pavan vs Italy decided by the European Court of Human Rights, poses the question about the existence in Italy of the right to a healthy son. In the light of the data both legislative and jurisprudential, she concludes to deny the existence of such a right in italian law and casts doubt on the power of the Strasbourg Court to take basic policy decisions on "new rights", for which there are no specific constitutional requirements and there is a tragic conflict about them within society and societies
In Dowland’s Own Words: Poetry and Rhetoric in ‘Flow My Tears’ and ‘Lachrimae’ Pavan
No full textJohn Dowland (1563–1626) was among the finest lute players of his time and is widely recognized as the greatest English composer of lute music and lute song. Despite there being nearly 100 sources containing Dowland’s music, only 10 per cent of these can be directly connected to Dowland, and only his single-author songbooks can be considered authoritative texts. As a result, modern scholar-performers are required to look beyond the tablature to identify Dowland’s personal performance style, seeking justification for interpretive decisions in other historical sources. While treatises and organology dominate historical performance research, Dowland’s contrafacts—pieces existing as both songs and instrumental dances—offer equally valuable insights. This article focuses on the most famous example of this musical interrelationship: the instrumental solo ‘Lachrimae’ pavan and the corresponding lute song ‘Flow My Tears.’ The published lute song provides an important opportunity to directly examine an authoritative Dowland composition, with particular focus on his treatment of rhetorical devices, word stress, articulations, and punctuation. Although the links to the original instrumental pavan are not always immediately clear or easy to identify, once established, they provide robust opportunities to learn from the vocal version when interpreting the related solo piece
Linguistic Representations of Motion Do Not Depend on the Visual Motion System
No full textEmbodied semantics proposes that constructing the meaning of motion verb phrases relies on representations of motion in sensory cortex. However, the data reported by earlier studies as evidence for this claim are also explained by a symbolic-semantics view proposing interactions between dissociable systems. In the experiments reported here, participants were visually adapted to real and implied leftward or rightward motion, which produced a motion aftereffect opposite to the direction of the adapting stimulus. Participants then decided whether a directionally ambiguous or a leftward- or rightward-directional verb phrase implied leftward or rightward motion. Because the visual system is engaged in the motion aftereffect, embodied semantics predicts that responses in the motion-aftereffect direction (opposite to the direction of the adapting stimulus) are facilitated, whereas symbolic semantics predicts response facilitation in the direction of the adapting stimulus (opposite to the direction of the motion aftereffect). We found response facilitation in the direction of real- and implied-motion adapting stimuli in ambiguous and directional verb phrases. These results suggest that visual and linguistic representations of motion can be dissociated. © The Author(s) 2012
Modelling Parkinson\u27s disease in Drosophila: The protective role of molecular chaperones
No full textParkinson\u27s disease (PD) is a neurodegenerative disorder characterized by resting tremor and postural rigidity. The progressive loss of dopaminergic neurons in the substantia nigra pars compacta is the key pathologic feature underlying these symptoms. Mutations in the synaptic protein α-synuclein are linked to autosomal-dominant PD. Moreover, α-synuclein is also a major component of Lewy bodies (LBs) found in idiopathic PD. We modelled PD in Drosophila by directing the expression of asynuclein to dopaminergic neurons. Expression of α-synuclein resulted in both the age-dependent degeneration of 50% of the dopaminergic neurons in the dorsomedial clusters of the fly brain and the formation of LB-like aggregates. As a genetic organism, Drosophila is an ideal system in which to study modifiers of α-synuclein toxicity with potential therapeutic relevance. We therefore tested whether the molecular chaperone Hsp70 could protect against α-synuclein toxicity. Transgenic expression of Hsp70 fully protected against the toxicity of α-synuclein to dopaminergic neurons. Furthermore, compromising endogenous chaperone activity accelerated α-synuclein-mediated neurodegeneration. Hsp70 and other chaperones also found to localize to LBs in postmortem PD brain tissue and to LB-like aggregates in the brains of transgenic α-synuclein flies. Thus it appears that chaperone activity may be altered in PD patients and contributes to the toxicity of α-synuclein. We next examined whether pharmacological enhancement of chaperone activity might also protect against α-synuclein toxicity. Geldanamycin (GA) is an antibiotic that inhibits the activity of Hsp90 which negatively regulates heat shock factor (HSF), the transcriptional activator of Hsp70 and other chaperones. Treatment of adult flies with GA fully suppressed the toxicity of α-synuclein. Using a temperature-sensitive null allele of HSF, we found that GA-mediated neuroprotection was fully dependent upon HSF activity; genetic elimination of HSF activity abrogated the drug\u27s cytoprotective activity. Finally, we determined that other pathways modified by Hsp90 were not responsible for neuroprotection by GA. Through these studies, we have shown that enhancement of chaperone activity, both genetically and pharmacologically, is a potent mitigator of α-synuclein toxicity in Drosophila. We propose that targeted enhancement of chaperone pathways should be further investigated as a cytoprotective treatment for PD and related neurodegenerative disorders
Spatially evolving cascades in wall turbulence with and without interface
No full textDirect numerical simulations of channel flow and temporal boundary layer at a Reynolds number Reτ=1500 are used to assess the scale-by-scale mechanisms of wall turbulence. From the peak of turbulence production embedded at the small scales of the near-wall region, spatially ascending reverse cascades are generated that move through self-similar eddies growing in size with the wall distance. These fluxes are followed by spatially ascending forward cascades through detached eddies thus reaching sufficiently small scales where eventually scale energy is dissipated. This phenomenology is shared by both boundary layer and channel flow and is recognized as a robust physical feature characterizing wall turbulence in general. Specific features related to the flow configuration are indeed identified in the outer region. In particular, the central region of channels is characterized by a generalized Richardson energy cascade where large scales are in equilibrium with small scales at different wall distances through a combined forward cascade and spatial flux. On the contrary, the interface region of boundary layers is characterized by an almost two-dimensional physics where spatially ascending reverse cascades sustain long and wide interface structures with a forward cascade that survives only in the wall-normal scales. The overall scenario consists in a variety of scale motions that while protruding from the turbulent core towards the external region, squeeze at the interface thus sustaining vertical shear in a thin layer. The observed multidimensional physics sheds light on the complex interactions between outer entrainment and near-wall self-sustaining mechanisms with possible repercussions for theories.Energy Technolog
Modeling NAND Flash memories for circuit simulations
No full textIn this paper, we will present the basic structure and the parameter extraction procedure for a compact model of a NAND Flash memory string working in Spice-like circuit simulators. To the author knowledge, this is the first Spice-like model of a NAND Flash memory string. This model is modular and simple to be implemented. It will allow accurately reproducing both DC and transient behavior of NAND Flash memories without increasing computational effort, thus becoming an indispensable tool for designers to optimize circuits especially in multi-level applications
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