CT saturation correction based on the estimated CT saturation time constant

A new method for CT saturation correction is presented that is based on an on-line estimation of the CT magnetizing inductance. The approach adopted is based on numerical solution of the differential equation, which describes the saturated current transformer. The correction procedure proposed has been tested with EMTP-ATP signals proving to be an effective tool for primary current reconstruction

Evidence for distinct coastal and offshore communities of bottlenose dolphins in the north east Atlantic.

Bottlenose dolphin stock structure in the northeast Atlantic remains poorly understood. However, fine scale photo-id data have shown that populations can comprise multiple overlapping social communities. These social communities form structural elements of bottlenose dolphin (Tursiops truncatus) [corrected] populations, reflecting specific ecological and behavioural adaptations to local habitats. We investigated the social structure of bottlenose dolphins in the waters of northwest Ireland and present evidence for distinct inshore and offshore social communities. Individuals of the inshore community had a coastal distribution restricted to waters within 3 km from shore. These animals exhibited a cohesive, fission-fusion social organisation, with repeated resightings within the research area, within a larger coastal home range. The offshore community comprised one or more distinct groups, found significantly further offshore (>4 km) than the inshore animals. In addition, dorsal fin scarring patterns differed significantly between inshore and offshore communities with individuals of the offshore community having more distinctly marked dorsal fins. Specifically, almost half of the individuals in the offshore community (48%) had characteristic stereotyped damage to the tip of the dorsal fin, rarely recorded in the inshore community (7%). We propose that this characteristic is likely due to interactions with pelagic fisheries. Social segregation and scarring differences found here indicate that the distinct communities are likely to be spatially and behaviourally segregated. Together with recent genetic evidence of distinct offshore and coastal population structures, this provides evidence for bottlenose dolphin inshore/offshore community differentiation in the northeast Atlantic. We recommend that social communities should be considered as fundamental units for the management and conservation of bottlenose dolphins and their habitat specialisations

Pharmacological Modulators of Sphingolipid Metabolism for the Treatment of Cystic Fibrosis Lung Inflammation

Cystic Fibrosis (CF) lung disease is characterised by progressive chronic infection and inflammation of the airways. This prolonged airway inflammatory response leads to irreversible lung damage and fibrosis which is believed to be driven by two distinct, coordinated events: a) a defective cystic fibrosis transmembrane regulator (CFTR) causes airway surface dehydration and increased mucus viscosity leading to chronic colonization with Pseudomonas aeruginosa (P.aeruginosa) (Boucher, 2007); b) mutated CFTR triggers the generation of pro-inflammatory and chemotactic cytokines orchestrated by bronchial epithelial cells, independently of infection (Rubin, 2007; Elizur et al., 2008). The chemokine IL-8, abundantly expressed at sites of chronic inflammation, seems to play a major role in driving the formation of neutrophil (PMN)-rich exudates into the lung of CF patients (Khan et al., 1995; Noah et al., 1997; DiMango et al., 1998; Puchelle et al., 2001; Joseph et al., 2005; Perez et al., 2007). Therefore, reduction of the exaggerated production of IL-8 is key therapeutic target in CF. Anti-inflammatory drugs are an attractive therapeutic tool in CF aimed to decrease the rate of decline in lung function. However, the inherent complexity of the inflammatory response combined with the obvious dependency on this response to contain infection and the side effect profiles of common anti-inflammatories, have made identifying the most suitable therapy a major priority. Consensus is growing on sphingolipids (SLs) as novel targets to cure pulmonary disorders including CF, since modulation of cellular ceramide reduces lung inflammation (Lahiri and Futerman, 2007; Uhlig and Gulbins, 2008). The results in the area of ceramide and CF pathophysiology are very interesting, although contradicting due to the animal models used and methods of ceramide detection (Wojewodka , 2011). The accumulation of ceramide has been identified as one of the key regulators of inflammation in CF airways in different CFTR-/- mouse models (Teichgraber, 2008). On the contrary, decreased ceramide levels have been shown in CFTR ko mice (Guibault, 2008). The possible explanation for this discrepancy seems to be the special diet required for CFTR ko mice, that severely affects the concentration of SLs. Other possible causes, such as genetic determinants, could influence individual levels of SLs (Hicks, 2009). In a different study, no significant difference has been found in basal ceramide levels in immortalised CF bronchial epithelial cells and lung homogenate from CFTR ko mice compared to wild type cells and mice (Yu, 2009). Very importantly, ceramide has been demonstrated to accumulate in the lower airways of CF patients and to be positively associated with neutrophilic inflammation (Brodlie, 2010), supporting the hypothesis that reduction of ceramide may be a therapeutic target for CF lung inflammation. Extending our previous study (Dechecchi, 2008), we have recently demonstrated that the iminosugar N-butyldeoxynojirimycin (miglustat), an inhibitor of the first step in glycosphingolipid (GSL) biosynthesis, reducing the P.aeruginosa induced immunoreactive ceramide expression, produces an anti-inflammatory effect in human bronchial epithelial cells in vitro and down-regulates the neutrophil chemotaxis in murine lungs in vivo (Dechecchi, 2011). These findings strengthen the notion that the metabolism of SLs can be manipulated as a therapeutic option for CF lung disease. With regard to new treatments for CF lung pathology, miglustat deserves great attention since it restores CFTR function in respiratory and pancreatic cells in vitro (Norez, 2006; Dechecchi, 2008) and in CF mice (Lubamba, 2009) and produces an anti-inflammatory effect in vitro and in vivo Dechecchi, 2011). Notably, miglustat is a FDA-approved and EMA−designated orally bioavailable orphan drug, used in Europe and USA for the treatment of Gaucher disease and other GSL storage diseases. In this chapter we review the pre-clinical evidence on the anti-inflammatory effect of miglustat in comparative effectiveness studies with the SL inhibitor amitriptyline and the glucocorticoid (GC) dexamethasone. Importance will be placed on the efficacy of each anti-inflammatory molecule to balance between the anti-inflammatory activity and possible impairment of the host defence

Reduced growth and proliferation dynamics of nasal epithelial stem/progenitor cells in nasal polyps in vitro

10.1038/srep04619Scientific Reports4

Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy

Mutations in the CNGB3 gene account for >50% of all known cases of achromatopsia. Although of early onset, its stationary character and the potential for rapid assessment of restoration of retinal function following therapy renders achromatopsia a very attractive candidate for gene therapy. Here we tested the efficacy of an rAAV2/8 vector containing a human cone arrestin promoter and a human CNGB3 cDNA in CNGB3 deficient mice. Following subretinal delivery of the vector, CNGB3 was detected in both M- and S-cones and resulted in increased levels of CNGA3, increased cone density and survival, improved cone outer segment structure and normal subcellular compartmentalization of cone opsins. Therapy also resulted in long-term improvement of retinal function, with restoration of cone ERG amplitudes of up to 90% of wild-type and a significant improvement in visual acuity. Remarkably, successful restoration of cone function was observed even when treatment was initiated at 6 months of age; however, restoration of normal visual acuity was only possible in younger animals (e.g. 2–4 weeks old). This study represents achievement of the most substantial restoration of visual function reported to date in an animal model of achromatopsia using a human gene construct, which has the potential to be utilized in clinical trials

Athens by Sound

Architecture is not only that which is built. Architecture is made up of different aspects, both material and immaterial. The atmosphere, the sounds, the smells, the possibility of interaction between human bodies: these all constitute characteristics of space, characteristics that are assuming an increasing importance within architectural research worldwide. Within this field of thought about “Architecture Beyond Building”, we focus on one particular non-material spatial phenomenon that lies ‘beyond the built’: sound. We have created, thus, an interactive sonic map of Athens, which presents, in an unexpected way, fragments of the atmosphere of the city. What would a non-visual map look like? What would it feel like if you wandered within a forest of headphones, playing sounds from different places in Athens? How would it feel if you found yourself in a ‘map’ that only appeared when you walked in it? What would it be like if the map only appeared when you invited one more person to be with you? The Greek pavilion addresses these questions through an atmospheric interactive ‘game’, presenting fragments of sounds and visual sequences of Athens. The visitor recreates the space around him through his own presence and movement. The map appears only where he walks, and/or when he invites one more person to sit next to him. The bodies of the visitors react with one another and with the space itself, creating a dynamic, changing field. This walk in the pavilion takes you “out there”, through invisible Athens. The pavilion brings forth the aspects of architecture that are ‘beyond the material’: the ‘beyond the built’, the almost unreachable, elusive aspects of space, such as sound, non-visual senses, atmosphere. It challenges, thus, the limits of architecture, the limits of what can be mapped and re-located and what cannot. An edited collection by A. Karandinou, C. Achtypi, S. Giamarelos, including texts by: Ιntothepill, Katie Lloyd Thomas, Martin Parker, Panayiotis Tournikiotis, Mark Wigley, Dorian Wiszniewski, Leslie Kavanaugh, Stephen Cairns, Jonathan Hill, Vassilis Ganiatsas, Anastasios Kotsiopoulos, Constance Classen, Stavros Stavrides, Ole Bouman, William Mitchell, Richard Coyne, Neil Spiller, Kas Oosterhuis, Nora Schueler, Zissis Kotionis, Stelarc, Andreas Angelidakis, Aristide Antonas, Slavoj Žižek, Nikolaos Laskaris, Argyris Rokas, Andreas Kourkoulas, John Peponis, Yorgos Ioannou, Yorgos Tzirtzilakis, Konstantinos Vita, Dionyssis Kapsalis, United Visual Artists, Platon Rivellis, and Dimitris Filippidis. Contributors to the Greek National Participation to the 11th International Architecture Exhibition La Biennale di Venezia "Out there. Architecture beyond building" (2008) Organised by: Hellenic Ministry of Culture [yppo.gr] General Directorate of Modern Culture Directorate of Visual Arts Department for the Promotion of Contemporary Art Curators: Anastasia Karandinou Christina Achtypi Stylianos Giamarelos Video works by Intothepill net [intothepill.net] Artists: Yiannis Grigoriadis Yiannis Isidorou Lina Theodorou Sound Recording / Sound Design Dimitris Miyakis [movement.gr] Vangelis Lympouridis Exhibition Graphics / Catalogue Design Company [company-london.com] Design and Implementation of interactive environment 2monochannels [2monochannels.com] Audiovisual and interactive systems design / acoustic design / construction supervision Iraklis Lampropoulos Giorgos Lampropoulos Software programming Vassilis Boukis Electronic subsystem design Michail Kritsotakis Electrical Design Giorgos Satolias Interconnection of interactive elements Vangelis Lympouridis [inter-axions.com] Dimitris Miyakis Light design L+DG lighting architects [lightingdg.com] Thomas Gravanis Christina Frangeti Construction Gavrilos Michalis [gavrilos.gr] Digital printing Polichromo [polichromo.com] Translations Rachel Howard Nikos Masourides Catalogue photographs Intothepill – Internet video platform Catalogue published by futura publications Marketing communication Chryssa Vrouzi Communication associate Katerina Stamidi Photographer Cathy Cunliffe [cathycunliffeΑΤgmail.com] For their financial and material support for the Greek participation at the 11th International Exhibition of Architecture, La Biennale di Venezia, we express our deepest thanks to the sponsors: Alexander S. Onassis Public Benefit Foundation [onassis.gr] Akzonobel [akzonobel.com] Carteco - Architectural Materials & Design [carteco.gr] L+DG Lighting Architects [lightingdg.com] Plaisio [plaisio.gr] Polichromo Advertising Applications [polichromo.com] iGuzzini illuminazione [iguzzini.com] Diathlasis Architectural Lighting [diathlasis.gr

Lessons learned from additional research analyses of unsolved clinical exome cases

BACKGROUND: Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. METHODS: We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent-offspring trios. Analyses performed on a research basis employed both WES from additional family members and complementary bioinformatics approaches and protocols. RESULTS: Analysis of all possible modes of Mendelian inheritance, focusing on both single nucleotide variants (SNV) and copy number variant (CNV) alleles, yielded a likely contributory variant in 36% (27/74) of cases. If one includes candidate genes with variants identified within a single family, a potential contributory variant was identified in a total of ~51% (38/74) of cases enrolled in this pilot study. The molecular diagnosis was achieved in 30/63 trios (47.6%). Besides this, the analysis workflow yielded evidence for pathogenic variants in disease-associated genes in 4/6 singleton cases (66.6%), 1/1 multiplex family involving three affected siblings, and 3/4 (75%) quartet families. Both the analytical pipeline and the collaborative efforts between the diagnostic and research laboratories provided insights that allowed recent disease gene discoveries (PURA, TANGO2, EMC1, GNB5, ATAD3A, and MIPEP) and increased the number of novel genes, defined in this study as genes identified in more than one family (DHX30 and EBF3). CONCLUSION: An efficient genomics pipeline in which clinical sequencing in a diagnostic laboratory is followed by the detailed reanalysis of unsolved cases in a research environment, supplemented with WES data from additional family members, and subject to adjuvant bioinformatics analyses including relaxed variant filtering parameters in informatics pipelines, can enhance the molecular diagnostic yield and provide mechanistic insights into Mendelian disorders. Implementing these approaches requires collaborative clinical molecular diagnostic and research efforts

Widespread impact of horizontal gene transfer on plant colonization of land

In complex multicellular eukaryotes such as animals and plants, horizontal gene transfer is commonly considered rare with very limited evolutionary significance. Here we show that horizontal gene transfer is a dynamic process occurring frequently in the early evolution of land plants. Our genome analyses of the moss Physcomitrella patens identified 57 families of nuclear genes that were acquired from prokaryotes, fungi or viruses. Many of these gene families were transferred to the ancestors of green or land plants. Available experimental evidence shows that these anciently acquired genes are involved in some essential or plant-specific activities such as xylem formation, plant defence, nitrogen recycling as well as the biosynthesis of starch, polyamines, hormones and glutathione. These findings suggest that horizontal gene transfer had a critical role in the transition of plants from aquatic to terrestrial environments. On the basis of these findings, we propose a model of horizontal gene transfer mechanism in nonvascular and seedless vascular plants

Predation Risk Shapes Social Networks in Fission-Fusion Populations

Predation risk is often associated with group formation in prey, but recent advances in methods for analysing the social structure of animal societies make it possible to quantify the effects of risk on the complex dynamics of spatial and temporal organisation. In this paper we use social network analysis to investigate the impact of variation in predation risk on the social structure of guppy shoals and the frequency and duration of shoal splitting (fission) and merging (fusion) events. Our analyses revealed that variation in the level of predation risk was associated with divergent social dynamics, with fish in high-risk populations displaying a greater number of associations with overall greater strength and connectedness than those from low-risk sites. Temporal patterns of organisation also differed according to predation risk, with fission events more likely to occur over two short time periods (5 minutes and 20 minutes) in low-predation fish and over longer time scales (>1.5 hours) in high-predation fish. Our findings suggest that predation risk influences the fine-scale social structure of prey populations and that the temporal aspects of organisation play a key role in defining social systems