Expression of the Parkinson’s Disease-Associated Gene Alpha-Synuclein is Regulated by the Neuronal Cell Fate Determinant TRIM32

Alpha-synuclein is an abundant neuronal protein which has been associated with physiological processes like synaptic function, neurogenesis, and neuronal differentiation but also with pathological neurodegeneration. Indeed, alpha-synuclein (snca) is one of the major genes implicated in Parkinson’s disease (PD). However, little is known about the regulation of alpha-synuclein expression. Unveiling the mechanisms that control its regulation is of high importance, as it will enable to further investigate and comprehend the physiological role of alpha-synuclein as well as its potential contribution in the aetiology of PD. Previously, we have shown that the protein TRIM32 regulates fate specification of neural stem cells. Here, we investigated the impact of TRIM32 on snca expression regulation in vitro and in vivo in neural stem cells and neurons. We demonstrated that TRIM32 is positively influencing snca expression in a neuronal cell line, while the absence of TRIM32 is causing deregulated levels of snca transcripts. Finally, we provided evidence that TRIM32 binds to the promoter region of snca, suggesting a novel mechanism of its transcriptional regulation. On the one hand, the presented data link the PD-associated gene alpha-synuclein to the neuronal cell fate determinant TRIM32 and thereby support the concept that PD is a neurodevelopmental disorder. On the other hand, they imply that defects in olfactory bulb adult neurogenesis might contribute to early PD-associated non-motor symptoms like hyposmia.The J. C. S.’s lab is supported by the Boehringer Ingelheim Foundation and the fund “Innovative Medical Research” of the University of Münster Medical School, Schram-Stiftung (T287/21795/2011) by the Fonds National de la Recherche (FNR) Luxembourg (CORE, C13/BM/5791363), a University Luxembourg Internal Research Project (MidNSCs) and the EU Joint Programme - Neurodegenerative Disease Research (JPND) project (supported by the FNR). L.G.C. was supported by a fellowship from the FNR (AFR, Aides à la Formation-Recherche). M.C.M ’s lab is supported by Grant SAF2012-36143 from Spanish Ministerio de Ciencia e and LE310U14 from the Junta de Castilla y Leon. S.F.A holds a predoctoral contract (PIRTU) from Junta de Castilla y Leon

Joint Optimization of Intra- and Inter-Autonomous System Traffic Engineering

Traffic Engineering (TE) is used to optimize IP operational network performance. The existing literature generally considers intra- and inter-AS (Autonomous System) TE independently. However, the overall network performance may not be truly optimized when these aspects are considered separately. This is due to the interaction between intra- and inter-AS TE, where a solution of intra-AS TE may not be a good input to inter-AS TE and vice versa. To remedy this situation, we propose considering intra-AS aspects during inter-AS TE and vice versa. We propose a joint optimization of intra- and inter-AS TE to further improve the overall network performance by simultaneously finding the best egress points for the inter-AS traffic and the best routing scheme for the intra-AS traffic. Three strategies are presented to attack the problem, namely sequential, nested and integrated optimization. Our simulation study shows that, compared to sequential and nested optimization, integrated optimization can significantly improve the overall network performance by accommodating 30%-60% more traffic demands

Curling: Content-ubiquitous resolution and delivery infrastructure for next-generation services

CURLING, a Content-Ubiquitous Resolution and Delivery Infrastructure for Next Generation Services, aims to enable a future content-centric Internet that will overcome the current intrinsic constraints by efficiently diffusing media content of massive scale. It entails a holistic approach, supporting content manipulation capabilities that encompass the entire content life cycle, from content publication to content resolution and, finally, to content delivery. CURLING provides to both content providers and customers high flexibility in expressing their location preferences when publishing and requesting content, respectively, thanks to the proposed scoping and filtering functions. Content manipulation operations can be driven by a variety of factors, including business relationships between ISPs, local ISP policies, and specific content provider and customer preferences. Content resolution is also natively coupled with optimized content routing techniques that enable efficient unicast and multicast-based content delivery across the global Internet

Attitudes towards Cypriot Greek and Standard Modern Greek in London’s Greek Cypriot community

Aim To investigate whether the positive attitudes towards Standard Modern Greek and the mixture of positive and negative attitudes towards Cypriot Greek that have been documented in Cyprus are also present in London's Greek Cypriot community. Approach Unlike previous quantitative works, the study reported in this article was qualitative and aimed at capturing the ways in which attitudes and attitude-driven practices are experienced by members of London's diasporic community. Data and Analysis Data were collected by means of semi-structured, sociolinguistic interviews with 28 members of the community. All participants were second-generation heritage speakers, successive bilinguals in Cypriot Greek and English, and successive bidialectal speakers in Cypriot Greek and Standard Modern Greek. The data were analysed qualitatively (thematic analysis). Findings – Positive perceptions of Standard Modern Greek and mixed perceptions, both positive and negative, of Cypriot Greek are found in the context of London. – As in Cyprus, Standard Modern Greek is perceived as a prestigious, proper and 'correct' variety of Greek. Cypriot Greek, in contrast, is described as a villagey, heavy and even broken variety. – Greek complementary schools play a key role in engendering these attitudes. – Unlike in Cyprus, in the London community, the use of Cypriot Greek is also discouraged in informal settings such as the home. Originality Papapavlou & Pavlou contended that "there are no signs of negative attitudes towards Cypriot Greek [in London]" (2001, p. 104). This research shows this claim to be false. Significance/Implications Negative attitudes towards Cypriot Greek lead to a community-wide preference for the use of Standard Modern Greek in communication with other members of the Greek Cypriot community, which poses a great threat to the intergenerational transmission and maintenance of Cypriot Greek as a heritage language in London

An Information-Centric Communication Infrastructure for Real-Time State Estimation of Active Distribution Networks

© 2010-2012 IEEE.The evolution toward emerging active distribution networks (ADNs) can be realized via a real-time state estimation (RTSE) application facilitated by the use of phasor measurement units (PMUs). A critical challenge in deploying PMU-based RTSE applications at large scale is the lack of a scalable and flexible communication infrastructure for the timely (i.e., sub-second) delivery of the high volume of synchronized and continuous synchrophasor measurements. We address this challenge by introducing a communication platform called C-DAX based on the information-centric networking (ICN) concept. With a topic-based publish-subscribe engine that decouples data producers and consumers in time and space, C-DAX enables efficient synchrophasor measurement delivery, as well as flexible and scalable (re)configuration of PMU data communication for seamless full observability of power conditions in complex and dynamic scenarios. Based on the derived set of requirements for supporting PMU-based RTSE in ADNs, we design the ICN-based C-DAX communication platform, together with a joint optimized physical network resource provisioning strategy, in order to enable the agile PMU data communications in near real-time. In this paper, C-DAX is validated via a field trial implementation deployed over a sample feeder in a real-distribution network; it is also evaluated through simulation-based experiments using a large set of real medium voltage grid topologies currently operating live in The Netherlands. This is the first work that applies emerging communication paradigms, such as ICN, to smart grids while maintaining the required hard real-time data delivery as demonstrated through field trials at national scale. As such, it aims to become a blueprint for the application of ICN-based general purpose communication platforms to ADNs

Acute exposure to diesel affects inflammation and vascular function.

BACKGROUND: Diesel exhaust fumes represent one of the most common toxic pollutants. The prolonged effects of acute exposure to this pollutant on inflammatory status and vascular properties are unknown. METHODS: During a 2-h session, 40 healthy subjects were exposed to diesel exhaust fumes and/or filtered air. Endothelial function was assessed with flow mediated dilation, arterial stiffness with pulse wave velocity and reflected waves with augmentation index. C-reactive protein, fibrinogen, protein C levels and protein S activity were also measured. Standard deviation of normal to normal R-R intervals (SDNN) was used to assess heart rate variability. Measurements were assessed before exposure and 2 and 24 h after diesel exposure. RESULTS: Compared with filtered air, exposure to diesel exhaust fumes decreased flow mediated dilation and increased pulse wave velocity and augmentation index up to 24 h after the exposure (p < 0.001 for all). Similarly, compared with filtered air, diesel exhaust exposure impaired SDNN during the 24-h study period (p = 0.007). C-reactive protein and fibrinogen levels were significantly increased after diesel exhaust exposure while protein C levels and protein S activity decreased (p < 0.01 for all). Exposure to diesel exhaust fumes resulted in higher C-reactive protein concentration in smokers compared with non-smokers (p < 0.001). CONCLUSION: Short-term exposure to diesel exhaust fumes has a prolonged adverse impact on endothelial function and vascular wall properties, along with impaired heart rate variability, abnormal fibrinolytic activity and increased markers of inflammation. These findings give insights into the mechanisms underlining the increased cardiovascular risk of subjects regularly exposed to diesel exhaust fumes

Visual Dependency and Dizziness after Vestibular Neuritis

Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36–80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques

A Project Portfolio Management Approach to Tacklingthe Exploration/Exploitation Trade-off

Organizational ambidexterity (OA) is an essen-tial capability for surviving in dynamic business environ-ments that advocates the simultaneous engagement inexploration and exploitation. Over the last decades,knowledge on OA has substantially matured, coveringinsights into antecedents, outcomes, and moderators of OA.However, there is little prescriptive knowledge that offersguidance on how to put OA into practice and to tackle thetrade-off between exploration and exploitation. To addressthis gap, the authors adopt the design science researchparadigm and propose an economic decision model asartifact. The decision model assists organizations inselecting and scheduling exploration and exploitation pro-jects to become ambidextrous in an economically reason-able manner. As for justificatory knowledge, the decisionmodel draws from prescriptive knowledge on projectportfolio management and value-based management, andfrom descriptive knowledge related to OA to structure thefield of action. To evaluate the decision model, its designspecification is discussed against theory-backed designobjectives and with industry experts. The paper alsoinstantiates the decision model as a software prototype andapplies the prototype to a case based on real-world data