Space-centred information management approach to improve CAD-based healthcare building design

This study focuses on developing a space-centred CAD tool to enable designers to effectively manage and implement the information of design guidance information and user requirements during design processes, especially for the stages of design briefing and conceptual design. It aims to structure and store design guidance and user requirements for healthcare building design into a relational database, and link them to relevant space entities in design plans. The tool is developed on the platform of Autodesk Architecture Desktop (ADT). It also enables users to store and retrieve pictures associated with textual information, because pictures have been always used by designers as an effective medium to represent and deliver design information and knowledge. This can give users directly visual and more understandable perceptions of the design guidance. The tool is fully embedded with Autodesk AutoCAD systems to ensure the application of this tool being fully merged with CAD-based design process. A set of design guidance about Alzheimer clinic built environments are adopted as a sample to demonstrate and validate the tool. Moreover, the scenario of expanding this application to more broad areas has also been foreseen

Host neutralizing responses and pathogenesis of hepatitis C virus infection.

International audienceThe recent development of novel model systems for the early steps of hepatitis C virus (HCV) infection has rapidly advanced our knowledge of antibody-mediated virus neutralization in patients with acute and chronic hepatitis C. This review summarizes our current understanding of host neutralizing responses during the course of HCV infection. It focuses on recent studies in HCV-infected patients investigating the role of antibody responses for viral clearance as well as the mechanisms of viral escape from virus neutralizing antibodies during progression into chronic infection. Moreover, the potential impact of virus neutralizing antibodies for the development of novel preventive and therapeutic antiviral strategies is discussed

Hepatitis C virus infection and related liver disease: the quest for the best animal model

Hepatitis C virus (HCV) is a major cause of cirrhosis and hepatocellular carcinoma (HCC) making the virus the most common cause of liver failure and transplantation. HCV is estimated to chronically affect 130 million individuals and to lead to more than 350,000 deaths per year worldwide. A vaccine is currently not available. The recently developed direct acting antivirals (DAAs) have markedly increased the efficacy of the standard of care but are not efficient enough to completely cure all chronically infected patients and their toxicity limits their use in patients with advanced liver disease, co-morbidity or transplant recipients. Because of the host restriction, which is limited to humans and non-human primates, in vivo study of HCV infection has been hampered since its discovery more than 20 years ago. The chimpanzee remains the most physiological model to study the innate and adaptive immune responses, but its use is ethically difficult and is now very restricted and regulated. The development of a small animal model that allows robust HCV infection has been achieved using chimeric liver immunodeficient mice, which are therefore not suitable for studying the adaptive immune responses. Nevertheless, these models allowed to go deeply in the comprehension of virus-host interactions and to assess different therapeutic approaches. The immunocompetent mouse models that were recently established by genetic humanization have shown an interesting improvement concerning the study of the immune responses but are still limited by the absence of the complete robust life cycle of the virus. In this review, we will focus on the relevant available animal models of HCV infection and their usefulness for deciphering the HCV life cycle and virus-induced liver disease, as well as for the development and evaluation of new therapeutics. We will also discuss the perspectives on future immunocompetent mouse models and the hurdles to their development

Deep levels in homoepitaxial boron-doped diamond films studied by capacitance transient spectroscopies

International audienceDeep level transient spectroscopies (DLTS) applied to Schottky junctions made on homoepitaxial boron-doped diamond films show the existence of two traps. A deep acceptor, negatively charged and strongly attractive for holes, 1.57 eV above the valence band edge displays the characteristic features of a complex defect due to interacting centers and impurities, also displaying some evolutions after thermal cycles, possibly due to hydrogen effusion or diffusion. It is tentatively ascribed to association of a boron atom, a vacancy and several hydrogen atoms. A deep donor, 1.13 eV above the valence band edge, able to compensate the boron acceptors, is attributed to a defect correlated with dislocations. It could be due to the positively charged carbon vacancy. These conclusions are drawn from the Fourier transform-DLTS results coupled with isothermal time domain algorithms allowing the discrimination of multiple emission rates with high resolution

Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs

High-resolution microbial community reconstruction by integrating short reads from multiple 16S rRNA regions

The emergence of massively parallel sequencing technology has revolutionized microbial profiling, allowing the unprecedented comparison of microbial diversity across time and space in a wide range of host-associated and environmental ecosystems. Although the high-throughput nature of such methods enables the detection of low-frequency bacteria, these advances come at the cost of sequencing read length, limiting the phylogenetic resolution possible by current methods. Here, we present a generic approach for integrating short reads from large genomic regions, thus enabling phylogenetic resolution far exceeding current methods. The approach is based on a mapping to a statistical model that is later solved as a constrained optimization problem. We demonstrate the utility of this method by analyzing human saliva and Drosophila samples, using Illumina single-end sequencing of a 750 bp amplicon of the 16S rRNA gene. Phylogenetic resolution is significantly extended while reducing the number of falsely detected bacteria, as compared with standard single-region Roche 454 Pyrosequencing. Our approach can be seamlessly applied to simultaneous sequencing of multiple genes providing a higher resolution view of the composition and activity of complex microbial communities