A Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke.

AIM To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change. METHODS Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach. RESULTS Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes. CONCLUSION Chronic phase of sensorimotor cortical stroke has been characterized by a large scale co-varying structural network in the ipsilesional hemisphere associated specifically with sensorimotor hand skill. Its expression is related to GMV increase of md thalamus, one constituent of the network, and correlated with the cortico-striato-thalamic loop involved in control of motor execution and higher order sensorimotor cortices. A close relation between expression of this network with degree of recovery might indicate reduced compensatory resources in the impaired subgroup.

Mode of action of claudin peptidomimetics in the transient opening of cellular tight junction barriers

In epithelial/endothelial barriers, claudins form tight junctions, seal the paracellular cleft, and limit the uptake of solutes and drugs. The peptidomimetic C1C2 from the C-terminal half of claudin-1's first extracellular loop increases drug delivery through epithelial claudin-1 barriers. However, its molecular and structural mode of action remains unknown. In the present study, >100 μM C1C2 caused paracellular opening of various barriers with different claudin compositions, ranging from epithelial to endothelial cells, preferentially modulating claudin-1 and claudin-5. After 6 h incubation, C1C2 reversibly increased the permeability to molecules of different sizes; this was accompanied by redistribution of claudins and occludin from junctions to cytosol. Internalization of C1C2 in epithelial cells depended on claudin-1 expression and clathrin pathway, whereby most C1C2 was retained in recyclosomes >2 h. In freeze-fracture electron microscopy, C1C2 changed claudin-1 tight junction strands to a more parallel arrangement and claudin-5 strands from E-face to P-face association - drastic and novel effects. In conclusion, C1C2 is largely recycled in the presence of a claudin, which explains the delayed onset of barrier and junction loss, the high peptide concentration required and the long-lasting effect. Epithelial/endothelial barriers are specifically modulated via claudin-1/claudin-5, which can be targeted to improve drug delivery.

The Application of Digital Rights Management Systems in the Music Industry - An Empirical Investigation

Technology advances in hardware, software and IP-networks such as the Internet or peer-to-peer file sharing systems are threatening the music business. The result has been an increasing amount of illegal copies available on-line as well as off-line. With the emergence of digital rights management systems (DRMS), the music industry seems to have found the appropriate tool to simultaneously fight piracy and to monetize their assets. Although these systems are very powerful and include multiple technologies to prevent piracy, it is as of yet unknown to what extent such systems are currently being used by content providers. We provide empirical analyses, results, and conclusions related to digital rights management systems and the protection of digital content in the music industry. It shows that most content providers are protecting their digital content through a variety of technologies such as passwords or encryption. However, each protection technology has its own specific goal, and not all prevent piracy. The majority of the respondents are satisfied with their current protection but want to reinforce it for the future, due to fear of increasing piracy. Surprisingly, although encryption is seen as the core DRM technology, only few companies are currently using it. Finally, half of the respondents do not believe in the success of DRMS and their ability to reduce piracy.

Innovation and Development in the Age of Climate Change Adaptation: Open or Closed?

Change Adaptation: Open or Closed? Paper read at the Second African International Economic Law Network Conference, 7-8 March 2013, Wits School of Law, Johannesburg, South Africa. In a time of rapid convergence of technologies, goods, services, hardware, software, the traditional classifications that informed past treaties fail to remove legal uncertainty, or advance welfare and innovation. As a result, we turn our attention to the role and needs of the public domain at the interface of existing intellectual property rights and new modes of creation, production and distribution of goods and services. The concept of open culture would have it that knowledge should be spread freely and its growth should come from further developing existing works on the basis of sharing and collaboration without the shackles of intellectual property. Intellectual property clauses find their way into regional, multilateral, bilateral and free trade agreements more often than not, and can cause public discontent and incite unrest. Many of these intellectual property clauses raise the bar on protection beyond the clauses found in the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). In this paper we address the question of the protection and development of the public domain in service of open innovation in accord with Article 15 of the International Covenant on Economic, Social and Cultural Rights (ICESCR) in light of the Objectives (Article 7) and Principles (Article 8) set forth in TRIPS. Once areas of divergence and reinforcement between the intellectual property regime and human rights have been discussed, we will enter into options that allow for innovation and prosperity in the global south. We then conclude by discussing possible policy developments.