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Showing papers by "Fraunhofer Society published in 2017"


Proceedings ArticleDOI
13 Jun 2017
TL;DR: This work describes the ongoing collection of the “something-something” database of video prediction tasks whose solutions require a common sense understanding of the depicted situation, and describes the challenges in crowd-sourcing this data at scale.
Abstract: Neural networks trained on datasets such as ImageNet have led to major advances in visual object classification. One obstacle that prevents networks from reasoning more deeply about complex scenes and situations, and from integrating visual knowledge with natural language, like humans do, is their lack of common sense knowledge about the physical world. Videos, unlike still images, contain a wealth of detailed information about the physical world. However, most labelled video datasets represent high-level concepts rather than detailed physical aspects about actions and scenes. In this work, we describe our ongoing collection of the “something-something” database of video prediction tasks whose solutions require a common sense understanding of the depicted situation. The database currently contains more than 100,000 videos across 174 classes, which are defined as caption-templates. We also describe the challenges in crowd-sourcing this data at scale.

1,062 citations



Journal ArticleDOI
TL;DR: Benefiting from its scalable preparation and stability, the MoNi4 electrocatalyst is promising for practical water-alkali electrolysers and comparable to the results for platinum and superior to those for state-of-the-art platinum-free electrocatalysts.
Abstract: Various platinum-free electrocatalysts have been explored for hydrogen evolution reaction in acidic solutions. However, in economical water-alkali electrolysers, sluggish water dissociation kinetics (Volmer step) on platinum-free electrocatalysts results in poor hydrogen-production activities. Here we report a MoNi4 electrocatalyst supported by MoO2 cuboids on nickel foam (MoNi4/MoO2@Ni), which is constructed by controlling the outward diffusion of nickel atoms on annealing precursor NiMoO4 cuboids on nickel foam. Experimental and theoretical results confirm that a rapid Tafel-step-decided hydrogen evolution proceeds on MoNi4 electrocatalyst. As a result, the MoNi4 electrocatalyst exhibits zero onset overpotential, an overpotential of 15 mV at 10 mA cm-2 and a low Tafel slope of 30 mV per decade in 1 M potassium hydroxide electrolyte, which are comparable to the results for platinum and superior to those for state-of-the-art platinum-free electrocatalysts. Benefiting from its scalable preparation and stability, the MoNi4 electrocatalyst is promising for practical water-alkali electrolysers.

785 citations


Journal ArticleDOI
TL;DR: Green et al. as discussed by the authors presented consolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules, and guidelines for inclusion of results into these tables are outlined and new entries since June 2016 are reviewed.
Abstract: Consolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules are presented. Guidelines for inclusion of results into these tables are outlined and new entries since June 2016 are reviewed. URI: http://onlinelibrary.wiley.com/doi/10.1002/pip.2855/abstract [1] Authors: GREEN Martin A. EMERY Keith HISHIKAWA Y. WARTA W. DUNLOP Ewan LEVI Dean HO-BAILLIE Anita Publication Year: 2017 Science Areas: Energy and transport [2]

626 citations


Journal ArticleDOI
TL;DR: This review discusses various enhancement technologies such as the use of ultrasounds for in-process nanoparticles dispersion and of processing aspects to reach optimal properties for using nanocomposites in the selected applications.
Abstract: For the last decades, nanocomposites materials have been widely studied in the scientific literature as they provide substantial properties enhancements, even at low nanoparticles content. Their performance depends on a number of parameters but the nanoparticles dispersion and distribution state remains the key challenge in order to obtain the full nanocomposites’ potential in terms of, e.g., flame retardance, mechanical, barrier and thermal properties, etc., that would allow extending their use in the industry. While the amount of existing research and indeed review papers regarding the formulation of nanocomposites is already significant, after listing the most common applications, this review focuses more in-depth on the properties and materials of relevance in three target sectors: packaging, solar energy and automotive. In terms of advances in the processing of nanocomposites, this review discusses various enhancement technologies such as the use of ultrasounds for in-process nanoparticles dispersion. In the case of nanocoatings, it describes the different conventionally used processes as well as nanoparticles deposition by electro-hydrodynamic processing. All in all, this review gives the basics both in terms of composition and of processing aspects to reach optimal properties for using nanocomposites in the selected applications. As an outlook, up-to-date nanosafety issues are discussed.

514 citations


Journal ArticleDOI
TL;DR: In this article, the efficiency of n-type silicon solar cells with a front side boron-doped emitter and a full-area tunnel oxide passivating electron contact was studied experimentally as a function of wafer thickness W and resistivity ρ b.

470 citations


Journal ArticleDOI
TL;DR: A rapid search in PubMed shows that using "flow cytometry immunology" as a search term yields more than 68 000 articles, the first of which is not about lymphocytes as mentioned in this paper.
Abstract: The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and sometimes esoteric instrument, the flow cytometer that is able to count hundreds of cells in a single second, and can provide repetitive results in a tireless manner. Given this, the possibility to analyse immune phenotypes in a variety of clinical conditions has changed the use of the flow cytometer, which was incidentally invented in the late 1960s to measure cellular DNA by using intercalating dyes, such as ethidium bromide. The epidemics of HIV/AIDS in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of the number of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring the therapy. As a consequence, the development of flow cytometers that had to be easy-to-use in all clinical laboratories helped to widely disseminate this technology. Nowadays, it is rare to find an immunological paper or read a conference abstract in which the authors did not use flow cytometry as the main tool to dissect the immune system and identify its fine and complex functions. Of note, recent developments have created the sophisticated technology of mass cytometry, which is able to simultaneously identify dozens of molecules at the single cell level and allows us to better understand the complexity and beauty of the immune system.

454 citations


Journal ArticleDOI
TL;DR: This review discusses in this review the principle mechanisms of Nrf2 regulation with a focus on inflammation and autophagy, extending the role of dysregulated NRF2 to chronic diseases and tumor development.
Abstract: Tight regulation of inflammation is very important to guarantee a balanced immune response without developing chronic inflammation. One of the major mediators of the resolution of inflammation is the transcription factor: the nuclear factor erythroid 2-like 2 (Nrf2). Stabilized following oxidative stress, Nrf2 induces the expression of antioxidants as well as cytoprotective genes, which provoke an anti-inflammatory expression profile, and is crucial for the initiation of healing. In view of this fundamental modulatory role, it is clear that both hyper- or hypoactivation of Nrf2 contribute to the onset of chronic diseases. Understanding the tight regulation of Nrf2 expression/activation and its interaction with signaling pathways, known to affect inflammatory processes, will facilitate development of therapeutic approaches to prevent Nrf2 dysregulation and ameliorate chronic inflammatory diseases. We discuss in this review the principle mechanisms of Nrf2 regulation with a focus on inflammation and autophagy, extending the role of dysregulated Nrf2 to chronic diseases and tumor development.

397 citations


Journal ArticleDOI
TL;DR: Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice, and highlighting future research priorities in the field.
Abstract: Breath tests cover the fraction of nitric oxide in expired gas (FENO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FENO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FENO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management. Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members. Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised. Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.

384 citations


Journal ArticleDOI
TL;DR: This work summarizes how hypoxia conditions mitochondria with consequences for ROS-production and the HIF-pathway is summarized.
Abstract: Hypoxia triggers several mechanisms to adapt cells to a low oxygen environment. Mitochondria are major consumers of oxygen and a potential source of reactive oxygen species (ROS). In response to hypoxia they exchange or modify distinct subunits of the respiratory chain and adjust their metabolism, especially lowering the citric acid cycle. Intermediates of the citric acid cycle participate in regulating hypoxia inducible factors (HIF), the key mediators of adaptation to hypoxia. Here we summarize how hypoxia conditions mitochondria with consequences for ROS-production and the HIF-pathway.

351 citations


Journal ArticleDOI
TL;DR: In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity.
Abstract: BackgroundTofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors. MethodsIn this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from b...

Journal ArticleDOI
TL;DR: The effects of microplastic microfarms on the marine environment are well understood in terms of time scales for fragmentation and degradation, the evolution of particle morphology and properties, and hazards of the chemical mixture liberated by weathering as discussed by the authors.
Abstract: Plastic in the global oceans fulfills two of the three conditions for pollution to pose a planetary boundary threat because it is causing planetary-scale exposure that is not readily reversible. Plastic is a planetary boundary threat if it is having a currently unrecognized disruptive effect on a vital Earth system process. Discovering possible unknown effects is likely to be aided by achieving a fuller understanding of the environmental fate of plastic. Weathering of plastic generates microplastic, releases chemical additives, and likely also produces nanoplastic and chemical fragments cleaved from the polymer backbone. However, weathering of plastic in the marine environment is not well understood in terms of time scales for fragmentation and degradation, the evolution of particle morphology and properties, and hazards of the chemical mixture liberated by weathering. Biofilms that form and grow on plastic affect weathering, vertical transport, toxicity, and uptake of plastic by marine organisms and have...

Journal ArticleDOI
TL;DR: In this paper, the authors investigated heat pump systems in smart grids, focussing on fields of application and control approaches that have emerged in academic literature, based on a review of published literatu...
Abstract: This paper investigates heat pump systems in smart grids, focussing on fields of application and control approaches that have emerged in academic literature. Based on a review of published literatu ...

Journal ArticleDOI
TL;DR: In this article, the authors contribute to an improved understanding of the factors influencing the mechanical properties of laser powder bed and electron beam melted TiAl6V4, and determine tensile tests, fracture toughness tests, fatigue crack growth measurements for different r-ratios as well as high cycle fatigue properties were determined for different surface roughness and heat treatments.

Journal ArticleDOI
TL;DR: Optimized organoid culture methods are described that efficiently and reliably produce cortical and basal ganglia structures similar to those in the human fetal brain in vivo and are demonstrated for modeling the teratogenic effects of Zika virus on the developing brain and identifying more susceptibility receptors and therapeutic compounds that can mitigate its destructive actions.

Journal ArticleDOI
TL;DR: 10 recommendations to improve monitoring and to strengthen comprehensive prioritization, to foster consistent assessment and to support solution-oriented management of surface waters are given.

Journal ArticleDOI
TL;DR: The history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods.
Abstract: Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event relationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field.

Journal ArticleDOI
TL;DR: The IEA EBC Annex 67 (Energy in Buildings and Communities program) as discussed by the authors was started in 2015 to provide an overview and insight into how much Energy Flexibility different building may offer to the future energy systems in the sense of avoiding excess energy production, increase the stability of the energy networks, minimize congestion problems, enhance the efficiency and cost effectiveness of future energy networks.

Journal ArticleDOI
Diane Lefaudeux1, Bertrand De Meulder1, Matthew J. Loza2, Nancy Peffer2  +219 moreInstitutions (21)
TL;DR: Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters of asthmatic patients that associate with different pathobiological pathways.
Abstract: Background Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalized management approach can be provided. Objectives We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum. Methods Partition-around-medoids clustering was applied to a training set of 266 asthmatic participants from the European Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) adult cohort using 8 prespecified clinic-physiologic variables. This was repeated in a separate validation set of 152 asthmatic patients. The clusters were compared based on sputum proteomics and transcriptomics data. Results Four reproducible and stable clusters of asthmatic patients were identified. The training set cluster T1 consists of patients with well-controlled moderate-to-severe asthma, whereas cluster T2 is a group of patients with late-onset severe asthma with a history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chronic airflow obstruction but is composed of nonsmokers. Cluster T4 is predominantly composed of obese female patients with uncontrolled severe asthma with increased exacerbations but with normal lung function. The validation set exhibited similar clusters, demonstrating reproducibility of the classification. There were significant differences in sputum proteomics and transcriptomics between the clusters. The severe asthma clusters (T2, T3, and T4) had higher sputum eosinophilia than cluster T1, with no differences in sputum neutrophil counts and exhaled nitric oxide and serum IgE levels. Conclusion Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.

Journal ArticleDOI
TL;DR: This study systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression and confirmed the suitability of the models for drug transport studies.
Abstract: Summary In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm 2 and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies.

Journal ArticleDOI
TL;DR: In this article, the Intrinsic Heat Treatment (IHT) was exploited to induce the precipitation of NiAl nanoparticles in an Fe-19Ni-xAl (at%) model maraging steel, a system known for rapid clustering.

Proceedings ArticleDOI
22 May 2017
TL;DR: In this article, the authors quantified the proliferation of security-related code snippets from Stack Overflow in Android applications available on Google Play and observed insecure code snippets being copied into Android applications millions of users install from Google Play every day.
Abstract: Online programming discussion platforms such as Stack Overflow serve as a rich source of information for software developers. Available information include vibrant discussions and oftentimes ready-to-use code snippets. Previous research identified Stack Overflow as one of the most important information sources developers rely on. Anecdotes report that software developers copy and paste code snippets from those information sources for convenience reasons. Such behavior results in a constant flow of community-provided code snippets into production software. To date, the impact of this behaviour on code security is unknown. We answer this highly important question by quantifying the proliferation of security-related code snippets from Stack Overflow in Android applications available on Google Play. Access to the rich source of information available on Stack Overflow including ready-to-use code snippets provides huge benefits for software developers. However, when it comes to code security there are some caveats to bear in mind: Due to the complex nature of code security, it is very difficult to provide ready-to-use and secure solutions for every problem. Hence, integrating a security-related code snippet from Stack Overflow into production software requires caution and expertise. Unsurprisingly, we observed insecure code snippets being copied into Android applications millions of users install from Google Play every day. To quantitatively evaluate the extent of this observation, we scanned Stack Overflow for code snippets and evaluated their security score using a stochastic gradient descent classifier. In order to identify code reuse in Android applications, we applied state-of-the-art static analysis. Our results are alarming: 15.4% of the 1.3 million Android applications we analyzed, contained security-related code snippets from Stack Overflow. Out of these 97.9% contain at least one insecure code snippet.

Journal ArticleDOI
TL;DR: In this paper, a broader conceptualization of policy mixes for sustainability transitions has emerged which is adopted in this special issue, which includes fifteen papers with different analytical perspectives drawing on a range of social science disciplines, such as environmental economics, innovation studies and policy sciences.
Abstract: Energy transitions face multiple barriers, lock-in, path dependencies and resistance to change which require strategic policy efforts to be overcome. In this regard, it has been increasingly recognised that a multiplicity of instruments – or instrument mixes – are needed to foster low-carbon transitions. In addition, over the past few years a broader conceptualization of policy mixes for sustainability transitions has emerged which we adopt in this special issue. Such a broader perspective not only examines the interaction of instruments, but also captures corresponding policy strategies with their long-term targets and pays greater attention to the associated policy processes. It also encompasses the analysis of overarching policy mix characteristics such as consistency, coherence or credibility, as well as policy design considerations. Furthermore, it embraces the analysis of actors and institutions involved in developing and implementing such policy mixes. To explicitly consider these further aspects of policy mixes, this special issue includes fifteen papers with different analytical perspectives drawing on a range of social science disciplines, such as environmental economics, innovation studies and policy sciences. It is our hope that the conceptual and empirical advances presented here will stimulate diverse future research and inform policy advice on policy mixes for energy transitions.

Journal ArticleDOI
TL;DR: In this article, a business model based on the sharing economy principle has been developed and analyzed, where the energy storage operator offers its storage system to different kinds of customers, each customer uses the ESS for their single use case.

DOI
17 Dec 2017
TL;DR: The sigsep musdb18 data set consists of a total of 150 full-track songs of different styles and includes both the stereo mixtures and the original sources, divided between a training subset and a test subset.
Abstract: The sigsep musdb18 data set consists of a total of 150 full-track songs of different styles and includes both the stereo mixtures and the original sources, divided between a training subset and a test subset. Its purpose is to serve as a reference database for the design and the evaluation of source separation algorithms. The objective of such signal processing methods is to estimate one or more sources from a set of mixtures, e.g. for karaoke applications. It has been used as the official dataset in the professionally-produced music recordings task for SiSEC 2018, which is the international campaign for the evaluation of source separation algorithms.

Journal ArticleDOI
TL;DR: How hypoxia and cell death adds the cross‐talk between cancer cells and macrophages is discussed.

Journal ArticleDOI
14 Nov 2017-Mbio
TL;DR: The data corroborate ZIKV-associated congenital disease and an association of low SES and ZikV infection and suggest that population immunity caused cessation of the outbreak.
Abstract: During 2015 to 2016, Brazil reported more Zika virus (ZIKV) cases than any other country, yet population exposure remains unknown. Serological studies of ZIKV are hampered by cross-reactive immune responses against heterologous viruses. We conducted serosurveys for ZIKV, dengue virus (DENV), and Chikungunya virus (CHIKV) in 633 individuals prospectively sampled during 2015 to 2016, including microcephaly and non-microcephaly pregnancies, HIV-infected patients, tuberculosis patients, and university staff in Salvador in northeastern Brazil using enzyme-linked immunosorbent assays (ELISAs) and plaque reduction neutralization tests. Sera sampled retrospectively during 2013 to 2015 from 277 HIV-infected patients were used to assess the spread of ZIKV over time. Individuals were georeferenced, and sociodemographic indicators were compared between ZIKV-positive and -negative areas and areas with and without microcephaly cases. Epidemiological key parameters were modeled in a Bayesian framework. ZIKV seroprevalence increased rapidly during 2015 to 2016, reaching 63.3% by 2016 (95% confidence interval [CI], 59.4 to 66.8%), comparable to the seroprevalence of DENV (75.7%; CI, 69.4 to 81.1%) and higher than that of CHIKV (7.4%; CI, 5.6 to 9.8%). Of 19 microcephaly pregnancies, 94.7% showed ZIKV IgG antibodies, compared to 69.3% of 257 non-microcephaly pregnancies (P = 0.017). Analyses of sociodemographic data revealed a higher ZIKV burden in low socioeconomic status (SES) areas. High seroprevalence, combined with case data dynamics allowed estimates of the basic reproduction number R0 of 2.1 (CI, 1.8 to 2.5) at the onset of the outbreak and an effective reproductive number Reff of <1 in subsequent years. Our data corroborate ZIKV-associated congenital disease and an association of low SES and ZIKV infection and suggest that population immunity caused cessation of the outbreak. Similar studies from other areas will be required to determine the fate of the American ZIKV outbreak.IMPORTANCE The ongoing American Zika virus (ZIKV) outbreak involves millions of cases and has a major impact on maternal and child health. Knowledge of infection rates is crucial to project future epidemic patterns and determine the absolute risk of microcephaly upon maternal ZIKV infection during pregnancy. For unknown reasons, the vast majority of ZIKV-associated microcephaly cases are concentrated in northeastern Brazil. We analyzed different subpopulations from Salvador, a Brazilian metropolis representing one of the most affected areas during the American ZIKV outbreak. We demonstrate rapid spread of ZIKV in Salvador, Brazil, and infection rates exceeding 60%. We provide evidence for the link between ZIKV and microcephaly, report that ZIKV predominantly affects geographic areas with low socioeconomic status, and show that population immunity likely caused cessation of the outbreak. Our results enable stakeholders to identify target populations for vaccination and for trials on vaccine efficacy and allow refocusing of research efforts and intervention strategies.

Journal ArticleDOI
TL;DR: An inference scheme using the currently available inflammatory biomarkers sputum eosinophilia and fractional exhaled nitric oxide levels, along with oral corticosteroid use, is described that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity.
Abstract: Rationale and objectives: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes. Methods: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement. Results: 9 GSVA signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper type 2 (Th-2) cytokines and lack of corticosteroid response (Group 1 and Group 3). Group 1 had the highest submucosal eosinophils, high exhaled nitric oxide (FeNO) levels, exacerbation rates and oral corticosteroid (OCS) use whilst Group 3 patients showed the highest levels of sputum eosinophils and had a high BMI. In contrast, Group 2 and Group 4 patients had an 86% and 64% probability of having non-eosinophilic inflammation. Using machine-learning tools, we describe an inference scheme using the currently-available inflammatory biomarkers sputum eosinophilia and exhaled nitric oxide levels along with OCS use that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity. Conclusion: This analysis demonstrates the usefulness of a transcriptomic-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target Th2-mediated inflammation and/or corticosteroid insensitivity.

Journal ArticleDOI
TL;DR: A new architecture design approach for modularised design of CPPS is presented and new capabilities in designing with modular construction kits, simulating functional behaviour and validating with virtual, functional prototype are introduced.

Journal ArticleDOI
TL;DR: In this paper, a nanostructured silicon/carbon anode derived from low-cost HSiCl 3 is tailored by the rational choice of the electrolyte component, to obtain an anode material outperforming current complex silicon structures.