Neurologic Wilson's disease

Despite a long history, Wilson's disease, an autosomal recessive disease caused by mutations in the ATP7B gene, remains a commonly misdiagnosed import disease. Mutations in ATP7B result in abnormal copper metabolism and subsequent toxic accumulation of copper. Clinical manifestations of neurologic Wilson's disease include variable combinations of dysarthria, dystonia, tremor, and choreoathetosis. Among neurodegenerative diseases, it is unusual in that misdiagnosis and delay in treatment are clinically relevant because treatments can prevent and cure Wilson's disease, if they are given appropriately. If left untreated, Wilson's disease progresses to hepatic failure or severe neurologic disability and death, while those adequately treated have normal life spans. This review focuses on the neurologic features of Wilson's disease, its diagnosis, and treatment options.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78731/1/j.1749-6632.2009.05109.x.pd

Universal Slip Dynamics in Metallic Glasses and Granular Matter – Linking Frictional Weakening with Inertial Effects

Slowly strained solids deform via intermittent slips that exhibit a material-independent critical size distribution. Here, by comparing two disparate systems - granular materials and bulk metallic glasses - we show evidence that not only the statistics of slips but also their dynamics are remarkably similar, i.e. independent of the microscopic details of the material. By resolving and comparing the full time evolution of avalanches in bulk metallic glasses and granular materials, we uncover a regime of universal deformation dynamics. We experimentally verify the predicted universal scaling functions for the dynamics of individual avalanches in both systems, and show that both the slip statistics and dynamics are independent of the scale and details of the material structure and interactions, thus settling a long-standing debate as to whether or not the claim of universality includes only the slip statistics or also the slip dynamics. The results imply that the frictional weakening in granular materials and the interplay of damping, weakening and inertial effects in bulk metallic glasses have strikingly similar effects on the slip dynamics. These results are important for transferring experimental results across scales and material structures in a single theory of deformation dynamics

An Experimental Evaluation of Position Estimation Methods for Person Localization in Wireless Sensor Networks

In this paper, the localization of persons by means of a Wireless Sensor Network (WSN) is considered. Persons carry on-body sensor nodes and move within a WSN. The location of each person is calculated on this node and communicated through the network to a central data sink for visualization. Applications of such a system could be found in mass casualty events, firefighter scenarios, hospitals or retirement homes for example. For the location estimation on the sensor node, three derivatives of the Kalman Filter and a closed-form solution (CFS) are applied, compared, and evaluated in a real-world scenario. A prototype 65-node ZigBee WSN is implemented and data are collected in in- and outdoor environments with differently positioned on-body nodes. The described estimators are then evaluated off-line on the experimentally collected data. The goal of this paper is to present a comprehensive real-world evaluation of methods for person localization in a WSN based on received signal strength (RSS) range measurements. It is concluded that person localization in in- and outdoor environments is possible under the considered conditions with the considered filters. The compared methods allow for suffciently accurate localization results and are robust against inaccurate range measurements

In vivo editing of the pan-endothelium by immunity evading simian adenoviral vector

Biological applications deriving from the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 site-specific nuclease system continue to impact and accelerate gene therapy strategies. Safe and effective in vivo co-delivery of the CRISPR/Cas9 system to target somatic cells is essential in the clinical therapeutic context. Both non-viral and viral vector systems have been applied for this delivery matter. Despite elegant proof-of-principle studies, available vector technologies still face challenges that restrict the application of CRISPR/Cas9-facilitated gene therapy. Of note, the mandated co-delivery of the gene-editing components must be accomplished in the potential presence of pre-formed anti-vector immunity. Additionally, methods must be sought to limit the potential of off-target editing. To this end, we have exploited the molecular promiscuities of adenovirus (Ad) to address the key requirements of CRISPR/Cas9-facilitated gene therapy. In this regard, we have endeavored capsid engineering of a simian (chimpanzee) adenovirus isolate 36 (SAd36) to achieve targeted modifications of vector tropism. The SAd36 vector with the myeloid cell-binding peptide (MBP) incorporated in the capsid has allowed selective in vivo modifications of the vascular endothelium. Importantly, vascular endothelium can serve as an effective non-hepatic cellular source of deficient serum factors relevant to several inherited genetic disorders. In addition to allowing for re-directed tropism, capsid engineering of nonhuman primate Ads provide the means to circumvent pre-formed vector immunity. Herein we have generated a SAd36. MBP vector that can serve as a single intravenously administered agent allowing effective and selective in vivo editing for endothelial target cells of the mouse spleen, brain and kidney. DATA AVAILABILITY: The data that support the findings of this study are available from the corresponding author upon reasonable request

Event-related alpha suppression in response to facial motion

This article has been made available through the Brunel Open Access Publishing Fund.While biological motion refers to both face and body movements, little is known about the visual perception of facial motion. We therefore examined alpha wave suppression as a reduction in power is thought to reflect visual activity, in addition to attentional reorienting and memory processes. Nineteen neurologically healthy adults were tested on their ability to discriminate between successive facial motion captures. These animations exhibited both rigid and non-rigid facial motion, as well as speech expressions. The structural and surface appearance of these facial animations did not differ, thus participants decisions were based solely on differences in facial movements. Upright, orientation-inverted and luminance-inverted facial stimuli were compared. At occipital and parieto-occipital regions, upright facial motion evoked a transient increase in alpha which was then followed by a significant reduction. This finding is discussed in terms of neural efficiency, gating mechanisms and neural synchronization. Moreover, there was no difference in the amount of alpha suppression evoked by each facial stimulus at occipital regions, suggesting early visual processing remains unaffected by manipulation paradigms. However, upright facial motion evoked greater suppression at parieto-occipital sites, and did so in the shortest latency. Increased activity within this region may reflect higher attentional reorienting to natural facial motion but also involvement of areas associated with the visual control of body effectors. © 2014 Girges et al