Form-finding and analysis of bending-active systems using dynamic relaxation

A common challenge for architects and engineers in the development of structurally efficient systems is the generation of good structural forms for a specific set of boundary conditions, a process known as form-finding. Dynamic relaxation is a wellestablished explicit numerical analysis method used for the form-finding and analysis of highly non-linear structures. With the incorporation of bending and clustered elements, the method can be extended for the analysis of complex curved and bending-active structural systems. Bending-active structures employ elastic deformation to generate complex curved shapes. With low computational cost, dynamic relaxation has large potential as a design and analysis technique of novel large span structural systems such as spline stressed membranes and small scale robotics, bio-mechanics and architectural applications made of novel materials such as electro- active polymers (EAP)

Charge Transport Properties of a Metal-free Phthalocyanine Discotic Liquid Crystal

Discotic liquid crystals can self-align to form one-dimensional semiconducting wires, many tens of microns long. In this letter, we describe the preparation of semiconducting films where the stacking direction of the disc-like molecules is perpendicular to the substrate surface. We present measurements of the charge carrier mobility, applying temperature-dependent time-of-flight transient photoconductivity, space-charge limited current measurements, and field-effect mobility measurements. We provide experimental verification of the highly anisotropic nature of semiconducting films of discotic liquid crystals, with charge carrier mobilities of up to 2.8x10$^{-3}$cm$^2$/Vs. These properties make discotics an interesting choice for applications such as organic photovoltaics.Comment: 5 pages, 5 figure

RNA-viromics reveals diverse communities of soil RNA viruses with the potential to affect grassland ecosystems across multiple trophic levels

The distribution and diversity of RNA viruses in soil ecosystems are largely unknown, despite their significant impact on public health, ecosystem functions, and food security. Here, we characterise soil RNA viral communities along an altitudinal productivity gradient of peat, managed grassland and coastal soils. We identified 3462 viral contigs in RNA viromes from purified virus-like-particles in five soil-types and assessed their spatial distribution, phylogenetic diversity and potential host ranges. Soil types exhibited minimal similarity in viral community composition, but with >10-fold more viral contigs shared between managed grassland soils when compared with peat or coastal soils. Phylogenetic analyses predicted soil RNA viral communities are formed from viruses of bacteria, plants, fungi, vertebrates and invertebrates, with only 12% of viral contigs belonging to the bacteria-infecting Leviviricetes class. 11% of viral contigs were found to be most closely related to members of the Ourmiavirus genus, suggesting that members of this clade of plant viruses may be far more widely distributed and diverse than previously thought. These results contrast with soil DNA viromes which are typically dominated by bacteriophages. RNA viral communities, therefore, have the potential to exert influence on inter-kingdom interactions across terrestrial biomes

Viromic Analysis of Wastewater Input to a River Catchment Reveals a Diverse Assemblage of RNA Viruses

Enteric viruses cause gastrointestinal illness and are commonly transmitted through the fecal-oral route. When wastewater is released into river systems, these viruses can contaminate the environment. Our results show that we can use viromics to find the range of potentially pathogenic viruses that are present in the environment and identify prevalent genotypes. The ultimate goal is to trace the fate of these pathogenic viruses from origin to the point where they are a threat to human health, informing reference-based detection methods and water quality management.Detection of viruses in the environment is heavily dependent on PCR-based approaches that require reference sequences for primer design. While this strategy can accurately detect known viruses, it will not find novel genotypes or emerging and invasive viral species. In this study, we investigated the use of viromics, i.e., high-throughput sequencing of the biosphere’s viral fraction, to detect human-/animal-pathogenic RNA viruses in the Conwy river catchment area in Wales, United Kingdom. Using a combination of filtering and nuclease treatment, we extracted the viral fraction from wastewater and estuarine river water and sediment, followed by high-throughput RNA sequencing (RNA-Seq) analysis on the Illumina HiSeq platform, for the discovery of RNA virus genomes. We found a higher richness of RNA viruses in wastewater samples than in river water and sediment, and we assembled a complete norovirus genotype GI.2 genome from wastewater effluent, which was not contemporaneously detected by conventional reverse transcription-quantitative PCR (qRT-PCR). The simultaneous presence of diverse rotavirus signatures in wastewater indicated the potential for zoonotic infections in the area and suggested runoff from pig farms as a possible origin of these viruses. Our results show that viromics can be an important tool in the discovery of pathogenic viruses in the environment and can be used to inform and optimize reference-based detection methods provided appropriate and rigorous controls are included

Tracing the fate of wastewater viruses reveals catchment-scale virome diversity and connectivity

The discharge of wastewater-derived viruses in aquatic environments impacts catchment-scale virome composition and is a potential hazard to human health. Here, we used viromic analysis of RNA and DNA virus-like particle preparations to track virus communities entering and leaving wastewater treatment plants and the connecting river catchment system and estuary. We found substantial viral diversity and geographically distinct virus communities associated with different wastewater treatment plants. River and estuarine water bodies harboured more diverse viral communities in downstream locations, influenced by tidal movement and proximity to wastewater treatment plants. Shellfish and beach sand were enriched in viral communities when compared with the surrounding water, acting as entrapment matrices for virus particles. We reconstructed >40,000 partial viral genomes into 10,149 species-level groups, dominated by dsDNA and (+)ssRNA bacteriophages (Caudovirales and Leviviridae). We identified 73 (partial) genomes comprising six families that could pose a risk to human health; Astroviridae, Caliciviridae (sapovirus), Picornaviridae (cocksackievirus), Reoviridae (rotavirus), Parvoviridae and Circoviridae. Based on the pattern of viral incidence, we observe that wastewater-derived viral genetic material is commonly deposited in the environment, but due to fragemented nature of these viral genomes, the risk to human health is low, and is more likely driven by community transmission, with wastewater-derived viruses subject to cycles of dilution, enrichment and virion degradation influenced by local geography, weather events and tidal effects. Our data illustrate the utility of viromic analyses for wastewater- and environment-based epidemiology, and we present a conceptual model for the circulation of viruses in a freshwater catchment

BAG3 Pro209 mutants associated with myopathy and neuropathy relocate chaperones of the CASA-complex to aggresomes

Three missense mutations targeting the same proline 209 (Pro209) codon in the co-chaperone Bcl2-associated athanogene 3 (BAG3) have been reported to cause distal myopathy, dilated cardiomyopathy or Charcot-Marie-Tooth type 2 neuropathy. Yet, it is unclear whether distinct molecular mechanisms underlie the variable clinical spectrum of the rare patients carrying these three heterozygous Pro209 mutations in BAG3. Here, we studied all three variants and compared them to the BAG3_Glu455Lys mutant, which causes dilated cardiomyopathy. We found that all BAG3_Pro209 mutants have acquired a toxic gain-of-function, which causes these variants to accumulate in the form of insoluble HDAC6- and vimentin-positive aggresomes. The aggresomes formed by mutant BAG3 led to a relocation of other chaperones such as HSPB8 and Hsp70, which, together with BAG3, promote the so-called chaperone-assisted selective autophagy (CASA). As a consequence of their increased aggregation-proneness, mutant BAG3 trapped ubiquitinylated client proteins at the aggresome, preventing their efficient clearance. Combined, these data show that all BAG3_Pro209 mutants, irrespective of their different clinical phenotypes, are characterized by a gain-of-function that contributes to the gradual loss of protein homeostasis

Automatic 3D aortic annulus sizing by computed tomography in the planning of transcatheter aortic valve implantation

Background: Accurate imaging assessment of aortic annulus (AoA) dimension is paramount to decide on the correct transcatheter heart valve (THV) size for patients undergoing transcatheter aortic valve implantation (TAVI). We evaluated the feasibility and accuracy of a novel automatic framework for multi detector row computed tomography (MDCT)-based TAVI planning. Methods: Among 122 consecutive patients undergoing TAVI and retrospectively reviewed for this study, 104 patients with preoperative MDCT of sufficient quality were enrolled and analyzed with the proposed software. Fully automatic (FA) and semi-automatic (SA) AoA measurements were compared to manual measurements, with both automated and manual-based interobserver variability (IOV) being assessed. Finally, the effect of these measures on hypothetically selected THV size was evaluated against the implanted size, as well as with respect to manually-derived sizes. Results: FA analysis was feasible in 92.3% of the cases, increasing to 100% if using the SA approach. Automatically-extracted measurements showed excellent agreement with manually-derived ones, with small biases and narrow limits of agreement, and comparable to the interobserver agreement. The SA approach presented a statistically lower IOV than manual analysis, showing the potential to reduce interobserver sizing disagreements. Moreover, the automated approaches displayed close agreement with the implanted sizes, similar to the ones obtained by the experts. Conclusion: The proposed automatic framework provides an accurate and robust tool for AoA measurements and THV sizing in patients undergoing TAVI.FCT - Fundação para a Ciência e a Tecnologia, Portugal, and the European Social Found, European Union, through the Programa Operacional Capital Humano (POCH) in the scope of the PhD grants SFRH/BD/93443/2013 (S. Queirós) and SFRH/BD/95438/2013 (P. Morais), and the project ‘PersonalizedNOS (01-0145-FEDER-000013)’ co-funded by Programa Operacional Regional do Norte (QREN), through Fundo Europeu de Desenvolvimento Regional (FEDER)info:eu-repo/semantics/publishedVersio

Consumption of antibiotics in the community, European Union/European Economic Area, 1997-2017: data collection, management and analysis

This article introduces a series of articles on antibiotic consumption in the community between 1997 and 2017, which provide an update of previous articles covering the periods 1997-2003 and 1997-2009.In this article, differences in participating countries, the ATC/DDD classification system, and data collection, validation and analysis between the current and previous series are described.In the previous series, 33 European countries provided valid data for further analysis, while the current series focused on 30 countries belonging to the EU or the European Economic Area (EEA). For both series, data were collected in accordance with the WHO ATC classification system. While the previous series reported data in accordance with the ATC/DDD index 2011, the current series employed the ATC/DDD index 2019. Both series focused on consumption of antibacterials for systemic use (ATC J01) and collected data expressed in DDD per 1000 inhabitants per day and packages per 1000 inhabitants per day. When studying consumption expressed in packages per 1000 inhabitants per day, countries reporting total care data, i.e. community and hospital sector combined, were included in the previous series but excluded in the current series. While the previous series used non-linear mixed models to evaluate time trends in antibiotic consumption, the current series allowed for inclusion of change-points with a data-driven location. In addition, both series assessed the composition and quality of antibiotic consumption in the EU/EEA.The updated analyses of two decades of ESAC-Net data provide the most comprehensive and detailed description of antibiotic consumption in the community in Europe