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Annotation with widely used, well-structured ontologies, combined with the use of ontology-aware software tools, ensures data and analyses are Findable, Accessible, Interoperable and Reusable (FAIR). Standardized terms with synonyms support lexical search. Ontology structure supports biologically meaningful grouping of annotations (typically by location and type). However, there are significant barriers to the adoption and use of ontologies by researchers and resource developers. One barrier is complexity. Ontologies serving diverse communities are often more complex than needed for individual applications. It is common for atlases to attempt their own simplifications by manually constructing hierarchies of terms linked to ontologies, but these typically include relationship types that are not suitable for grouping annotations. Here, we present a suite of tools for validating user hierarchies against ontology structure, using them to generate graphical reports for discussion and ontology views tailored to the needs of the HuBMAP Human Reference Atlas, and the Human Developmental Cell Atlas. In both cases, validation is a source of corrections and content for both ontologies and user hierarchies.

Phenotypic data are critical for understanding biological mechanisms and consequences of genomic variation, and are pivotal for clinical use cases such as disease diagnostics and treatment development. For over a century, vast quantities of phenotype data have been collected in many different contexts covering a variety of organisms. The emerging field of phenomics focuses on integrating and interpreting these data to inform biological hypotheses. A major impediment in phenomics is the wide range of distinct and disconnected approaches to recording the observable characteristics of an organism. Phenotype data are collected and curated using free text, single terms or combinations of terms, using multiple vocabularies, terminologies, or ontologies. Integrating these heterogeneous and often siloed data enables the application of biological knowledge both within and across species. Existing integration efforts are typically limited to mappings between pairs of terminologies; a generic knowledge representation that captures the full range of cross-species phenomics data is much needed. We have developed the Unified Phenotype Ontology (uPheno) framework, a community effort to provide an integration layer over domain-specific phenotype ontologies, as a single, unified, logical representation. uPheno comprises (1) a system for consistent computational definition of phenotype terms using ontology design patterns, maintained as a community library; (2) a hierarchical vocabulary of species-neutral phenotype terms under which their species-specific counterparts are grouped; and (3) mapping tables between species-specific ontologies. This harmonized representation supports use cases such as cross-species integration of genotype-phenotype associations from different organisms and cross-species informed variant prioritization., Competing Interests: 7.Conflict of Interest None declared.

Background: Computational approaches to support rare disease diagnosis are challenging to build, requiring the integration of complex data types such as ontologies, gene-to-phenotype associations, and cross-species data into variant and gene prioritisation algorithms (VGPAs). However, the performance of VGPAs has been difficult to measure and is impacted by many factors, for example, ontology structure, annotation completeness or changes to the underlying algorithm. Assertions of the capabilities of VGPAs are often not reproducible, in part because there is no standardised, empirical framework and openly available patient data to assess the efficacy of VGPAs - ultimately hindering the development of effective prioritisation tools., Results: In this paper, we present our benchmarking tool, PhEval, which aims to provide a standardised and empirical framework to evaluate phenotype-driven VGPAs. The inclusion of standardised test corpora and test corpus generation tools in the PhEval suite of tools allows open benchmarking and comparison of methods on standardised data sets., Conclusions: PhEval and the standardised test corpora solve the issues of patient data availability and experimental tooling configuration when benchmarking and comparing rare disease VGPAs. By providing standardised data on patient cohorts from real-world case-reports and controlling the configuration of evaluated VGPAs, PhEval enables transparent, portable, comparable and reproducible benchmarking of VGPAs. As these tools are often a key component of many rare disease diagnostic pipelines, a thorough and standardised method of assessment is essential for improving patient diagnosis and care.

Rationale: Preoperative patient education through 'joint class' has potential to improve quality of care for total joint replacement (TJR). However, no formal guidance exists regarding curriculum content, potentially resulting in inter-institutional variation., Objective: We aimed to (a) synthesize curriculum components of 'joint classes' across high-volume institutions and (b) develop a preliminary theory of change model for development and evaluation guided by the existing curricula and related literature., Methods: We reviewed 'joint class' curricula from the websites of the 10 highest-volume TJR centres (by average annual 2017-2019 volume) that publicly disclosed this information. Two reviewers qualitatively compared available content and noted common categories, which were synthesized into key domains across institutions. We then reviewed the PubMed database for literature on pre-TJR patient education and education needs in the past 10 years. Drawing on our curriculum synthesis and related literature, we proposed a theory of change model: hypothesized mechanisms through which 'joint class' confers benefits to patients and health systems., Results: We identified 30 categories in our review of existing class content, which we synthesized into seven key domains: (I) Practical Elements, (II) Logistics, (III) Medical Information, (IV) Modifiable Risk Factors, (V) Expected Outcomes, (VI) Patient Role in Recovery and (VII) Enhanced Education. Variation across institutions was noted. Our preliminary model based on the curriculum synthesis and related literature on the impact of 'joint class' includes three levels: (1) Practical Elements ('joint class' accessibility and information quality), (2) Class Goals (increased health literacy, increased adherence, risk mitigation, realistic expectations, and reduced anxiety) and (3) Target Outcomes (improved clinical outcomes, positive patient experience and increased patient satisfaction)., Conclusion: Our synthesis identified core common topics included in pre-TJR education but also highlighted variation across institutions, supporting opportunities for standardization. Clinicians and researchers can use our preliminary model to systematically develop and evaluate 'joint classes,' with the goal of establishing a standard of care for TJR preoperative education., (© 2023 John Wiley & Sons Ltd.)

Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis and understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing open ontologies, semantic data models, and knowledge graphs for translational research. The Monarch App is an integrated platform combining data about genes, phenotypes, and diseases across species. Monarch's APIs enable access to carefully curated datasets and advanced analysis tools that support the understanding and diagnosis of disease for diverse applications such as variant prioritization, deep phenotyping, and patient profile-matching. We have migrated our system into a scalable, cloud-based infrastructure; simplified Monarch's data ingestion and knowledge graph integration systems; enhanced data mapping and integration standards; and developed a new user interface with novel search and graph navigation features. Furthermore, we advanced Monarch's analytic tools by developing a customized plugin for OpenAI's ChatGPT to increase the reliability of its responses about phenotypic data, allowing us to interrogate the knowledge in the Monarch graph using state-of-the-art Large Language Models. The resources of the Monarch Initiative can be found at monarchinitiative.org and its corresponding code repository at github.com/monarch-initiative/monarch-app., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Respiratory viruses' detection is vitally important in coping with pandemics such as COVID-19. Conventional methods typically require laboratory-based, high-cost equipment. An emerging alternative method is Near-Infrared (NIR) spectroscopy, especially a portable one of the type that has the benefits of low cost, portability, rapidity, ease of use, and mass deployability in both clinical and field settings. One obstacle to its effective application lies in its common limitations, which include relatively low specificity and general quality. Characteristically, the spectra curves show an interweaving feature for the virus-present and virus-absent samples. This then provokes the idea of using machine learning methods to overcome the difficulty. While a subsequent obstacle coincides with the fact that a direct deployment of the machine learning approaches leads to inadequate accuracy of the modelling results. This paper presents a data-driven study on the detection of two common respiratory viruses, the respiratory syncytial virus (RSV) and the Sendai virus (SEV), using a portable NIR spectrometer supported by a machine learning solution enhanced by an algorithm of variable selection via the Variable Importance in Projection (VIP) scores and its Quantile value, along with variable truncation processing, to overcome the obstacles to a certain extent. We conducted extensive experiments with the aid of the specifically developed algorithm of variable selection, using a total of four datasets, achieving classification accuracy of: (1) 0.88, 0.94, and 0.93 for RSV, SEV, and RSV + SEV, respectively, averaged over multiple runs, for the neural network modelling of taking in turn 3 sessions of data for training and the remaining one session of an 'unknown' dataset for testing. (2) the average accuracy of 0.94 (RSV), 0.97 (SEV), and 0.97 (RSV + SEV) for model validation and 0.90 (RSV), 0.93 (SEV), and 0.91 (RSV + SEV) for model testing, using two of the datasets for model training, one for model validation and the other for model testing. These results demonstrate the feasibility of using portable NIR spectroscopy coupled with machine learning to detect respiratory viruses with good accuracy, and the approach could be a viable solution for population screening.

Sepsis is the body's response to an infection. Existing diagnostic testing equipment is not available in primary care settings and requires long waiting times. Lateral flow devices (LFDs) could be employed in point-of-care (POC) settings for sepsis detection; however, they currently lack the required sensitivity. Herein, LFDs are constructed using 150-310 nm sized selenium nanoparticles (SeNPs) and are compared to commercial 40 nm gold nanoparticles (AuNPs) for the detection of the sepsis biomarker interleukin-6 (IL-6). Both 310 and 150 nm SeNPs reported a lower limit of detection (LOD) than 40 nm AuNPs (0.1 ng/mL compared to 1 ng/mL), although at the cost of test line visual intensity. This is to our knowledge the first use of larger SeNPs (>100 nm) in LFDs and the first comparison of the effect of the size of SeNPs on assay sensitivity in this context. The results herein demonstrate that large SeNPs are viable alternatives to existing commercial labels, with the potential for higher sensitivity than standard 40 nm AuNPs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Introduction: The AbC-19™ lateral flow immunoassay (LFIA) performance was evaluated on plasma samples from a SARS-CoV-2 vaccination cohort, WHO international standards for anti-SARS-CoV-2 IgG (human), individuals ≥2 weeks from infection of RT-PCR confirmed SARS-CoV-2 genetic variants, as well as microorganism serology., Methods: Pre-vaccination to three weeks post-booster samples were collected from a cohort of 111 patients (including clinically extremely vulnerable patients) from Northern Ireland. All patients received Oxford-AstraZeneca COVID-19 vaccination for the first and second dose, and Pfizer-BioNTech for the third (first booster). WHO international standards, 15 samples from 2 variants of concern (Delta and Omicron) and cross-reactivity with plasma samples from other microorganism infections were also assessed on AbC-19™., Results: All 80 (100%) participants sampled post-booster had high positive IgG responses, compared to 38/95 (40%) participants at 6 months post-first vaccination. WHO standard results correlated with information from corresponding biological data sheets, and antibodies to all genetic variants were detected by LFIA. No cross-reactivity was found with exception of one (of five) Dengue virus samples., Conclusion: These findings suggest BNT162b2 booster vaccination enhanced humoral immunity to SARS-CoV-2 from pre-booster levels, and that this antibody response was detectable by the LFIA. In combination with cross-reactivity, standards and genetic variant results would suggest LFIA may be a cost-effective measure to assess SARS-CoV-2 antibody status., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Professor Tara Moore acted as a consultant for Abingdon Health during the final period of sampling. At time of conception and commencement of this study, none of the authors received payment from Abingdon Health., (© 2022 The Authors. Published by Elsevier Inc.)

Laser-induced graphene (LIG) on paper substrates is a desirable material for single-use point-of-care sensing with its high-quality electrical properties, low fabrication cost, and ease of disposal. While a prior study has shown how the repeated lasing of substrates enables the synthesis of high-quality porous graphitic films, however, the process-property correlation of lasing process on the surface microstructure and electrochemical behavior, including charge-transfer kinetics, is missing. The current study presents a systematic in-depth study on LIG synthesis to elucidate the complex relationship between the surface microstructure and the resulting electroanalytical properties. The observed improvements were then applied to develop high-quality LIG-based electrochemical biosensors for uric acid detection. We show that the optimal paper LIG produced via a dual pass (defocused followed by focused lasing) produces high-quality graphene in terms of crystallinity, sp 2 content, and electrochemical surface area. The highest quality LIG electrodes achieved a high rate constant k 0 of 1.5 × 10 -2 cm s -1 and a significant reduction in charge-transfer resistance (818 Ω compared with 1320 Ω for a commercial glassy carbon electrode). By employing square wave anodic stripping voltammetry and chronoamperometry on a disposable two-electrode paper LIG-based device, the improved charge-transfer kinetics led to enhanced performance for sensing of uric acid with a sensitivity of 24.35 ± 1.55 μA μM -1 and a limit of detection of 41 nM. This study shows how high-quality, sensitive LIG electrodes can be integrated into electrochemical paper analytical devices.

Despite progress in the development of standards for describing and exchanging scientific information, the lack of easy-to-use standards for mapping between different representations of the same or similar objects in different databases poses a major impediment to data integration and interoperability. Mappings often lack the metadata needed to be correctly interpreted and applied. For example, are two terms equivalent or merely related? Are they narrow or broad matches? Or are they associated in some other way? Such relationships between the mapped terms are often not documented, which leads to incorrect assumptions and makes them hard to use in scenarios that require a high degree of precision (such as diagnostics or risk prediction). Furthermore, the lack of descriptions of how mappings were done makes it hard to combine and reconcile mappings, particularly curated and automated ones. We have developed the Simple Standard for Sharing Ontological Mappings (SSSOM) which addresses these problems by: (i) Introducing a machine-readable and extensible vocabulary to describe metadata that makes imprecision, inaccuracy and incompleteness in mappings explicit. (ii) Defining an easy-to-use simple table-based format that can be integrated into existing data science pipelines without the need to parse or query ontologies, and that integrates seamlessly with Linked Data principles. (iii) Implementing open and community-driven collaborative workflows that are designed to evolve the standard continuously to address changing requirements and mapping practices. (iv) Providing reference tools and software libraries for working with the standard. In this paper, we present the SSSOM standard, describe several use cases in detail and survey some of the existing work on standardizing the exchange of mappings, with the goal of making mappings Findable, Accessible, Interoperable and Reusable (FAIR). The SSSOM specification can be found at http://w3id.org/sssom/spec. Database URL: http://w3id.org/sssom/spec., (© The Author(s) 2022. Published by Oxford University Press.)

As an engineering endeavor, synthetic biology requires effective sharing of genetic design information that can be reused in the construction of new designs. While there are a number of large community repositories of design information, curation of this information has been limited. This in turn limits the ways in which design information can be put to use. The aim of this work was to improve this situation by creating a curated library of parts from the International Genetically Engineered Machines (iGEM) registry data set. To this end, an analysis of the Synthetic Biology Open Language (SBOL) version of the iGEM registry was carried out using four different approaches-simple statistics, SnapGene autoannotation, SYNBICT autoannotation, and expert analysis-the results of which are presented herein. Key challenges encountered include the use of free text, insufficient part provenance, part duplication, lack of part removal, and insufficient continuous curation. On the basis of these analyses, the focus has shifted from the creation of a curated iGEM part library to instead the extraction of a set of lessons, which are presented here. These lessons can be exploited to facilitate the creation and curation of other part libraries using a simpler and less labor intensive process.

Purpose: To evaluate the relationship between choriocapillaris (CC), flow deficits (FD), and structural optical coherence tomography (OCT) biomarkers, and the progression of intermediate age-related macular degeneration (iAMD) to complete retinal pigment epithelial and outer retinal atrophy (cRORA) or macular neovascularization (MNV)., Methods: Consecutive patients with iAMD were sequentially reviewed to define three equal sized groups: progressed to MNV, progressed to cRORA, or remained stable over 12 months of follow-up. Odds ratios for progression to cRORA and MNV were estimated by logistic regression for intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), subretinal drusenoid deposits (SDDs), high central drusen volume, fellow eye with late AMD, and peripheral and central CC FD., Results: Thirty iAMD eyes from 30 patients were enrolled into each group. The CC FD was greater in the peripheral sectors of the macula of eyes which progressed to cRORA compared to the other two groups (P < 0.0001). The central CC FD was also significantly impaired in eyes that progressed to cRORA or MNV compared to eyes that did not progress (P = 0.001 and P = 0.02, respectively). CC FD in the peripheral macula was significantly and independently associated with the development of cRORA, while CC FD in the center was significantly and independently associated with the development of MNV., Conclusions: While the CC is diffusely impaired throughout the macula in iAMD eyes that progress to cRORA, it is relatively spared in the more peripheral macula among eyes which progress to MNV. These differential findings may have implications for the pathophysiology of the different late-stage manifestations of AMD., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

VisBOL is a web-based visualization tool used to depict genetic circuit designs. This tool depicts simple DNA circuits adequately, but it has become increasingly outdated as new versions of SBOL Visual were released. This paper introduces VisBOL2, a heavily redesigned version of VisBOL that makes a number of improvements to the original VisBOL, including proper functional interaction rendering, dynamic viewing, a more maintainable code base, and modularity that facilitates compatibility with other software tools. This modularity is demonstrated by incorporating VisBOL2 into a sequence visualization plugin for SynBioHub.

This paper presents the results of a study on developing an effective technique to increase the performance characteristics of antenna arrays for sub-THz integrated circuit applications. This is essential to compensate the limited power available from sub-THz sources. Although conventional array structures can provide a solution to enhance the radiation-gain performance however in the case of small-sized array structures the radiation properties can be adversely affected by mutual coupling that exists between the radiating elements. It is demonstrated here the effectiveness of using SIW technology to suppress surface wave propagations and near field mutual coupling effects. Prototype of 2 × 3 antenna arrays were designed and constructed on a polyimide dielectric substrate with thickness of 125 μm for operation across 0.19-0.20 THz. The dimensions of the array were 20 × 13.5 × 0.125 mm 3 . Metallization of the antenna was coated with 500 nm layer of Graphene. With the proposed technique the isolation between the radiating elements was improved on average by 22.5 dB compared to a reference array antenna with no SIW isolation. The performance of the array was enhanced by transforming the patch to exhibit metamaterial characteristics. This was achieved by embedding the patch antennas in the array with sub-wavelength slots. Compared to the reference array the metamaterial inspired structure exhibits improvement in isolation, radiation gain and efficiency on average by 28 dB, 6.3 dBi, and 34%, respectively. These results show the viability of proposed approach in developing antenna arrays for application in sub-THz integrated circuits.

Purpose: To evaluate the association between choriocapillaris (CC) flow deficits and structural optical coherence tomography biomarkers and the progression of intermediate age-related macular degeneration (iAMD) to complete retinal pigment epithelial and outer retinal atrophy., Methods: Retrospective analysis of consecutive patients with iAMD with a minimum follow-up of 12 months. Odds ratios of intraretinal hyperreflective foci, hyporeflective drusen cores, subretinal drusenoid deposits, the presence of drusen volume ≥0.03 mm3 within a central 3-mm circle, fellow eye with late stage of AMD, and CC flow deficits at baseline and months of follow-up were estimated from logistic regression., Results: A total of 112 eyes with iAMD were included. Eyes that progressed were significantly more likely to show intraretinal hyperreflective foci, hyporeflective drusen cores, and drusen volume ≥0.03 mm3. The CC flow deficit was also significantly greater in eyes that developed complete retinal pigment epithelial and outer retinal atrophy. Intraretinal hyperreflective foci, hyporeflective drusen cores, drusen volume ≥0.03 mm3, and higher CC flow deficits were significantly and independently associated with the development of complete retinal pigment epithelial and outer retinal atrophy., Conclusion: The CC flow deficit was significantly greater in iAMD eyes that progressed to complete retinal pigment epithelial and outer retinal atrophy and remained an independent risk factor when structural optical coherence tomography biomarkers were considered. CC flow deficits may be useful for enhancing risk stratification and prognostication of patients with iAMD.

Miniaturized total analysis systems, for the rapid detection of disease biomarkers, with features including high biomarker sensitivity, selectivity, biocompatibility, and disposability, all at low cost are of profound importance in the healthcare sector. Within this frame of reference, we developed a lab-on-a-carbohydrate-microneedle biodevice by integrating localized surface plasmon resonance (LSPR) paper-based substrates with biocompatible microneedles of high aspect ratio (>60:1 length:width). These microneedles are completely fabricated with carbohydrate (maltose) and further coated with poly lactic- co -glycolic acid (PLGA), which together serves the purpose of fluid channels. The porous nature of PLGA, in addition to drawing blood by capillary action, filters out the whole blood, allowing only the blood plasma to reach the biorecognition layer of the developed biodevice. While the use of maltose provides biocompatibility to the microneedle, the axial compression and transverse load analysis revealed desired mechanical strength of the microneedle, with mechanical failure occurring at 11N and 9 N respectively for the compressive and transverse load. For a proof-of-principle demonstration, the developed biodevice is validated for its operational features by direct detection of cystatin C in finger-prick blood and up to a concentration of 0.01 μg/mL in buffered conditions using the LSPR technique. Furthermore, by changing the biorecognition layer, the use of the developed needle can be extended to other disease biomarkers, and therefore the innovation presented in this work represents a hallmark in the state of the art of lab-on-a-chip biodevices.

Synthetic biology aims to develop novel biological systems and increase their reproducibility using engineering principles such as standardization and modularization. It is important that these systems can be represented and shared in a standard way to ensure they can be easily understood, reproduced, and utilized by other researchers. The Synthetic Biology Open Language (SBOL) is a data standard for sharing biological designs and information about their implementation and characterization. Previously, this standard has only been used to represent designs in systems where the same design is implemented in every cell; however, there is also much interest in multicellular systems, in which designs involve a mixture of different types of cells with differing genotype and phenotype. Here, we show how the SBOL standard can be used to represent multicellular systems, and, hence, how researchers can better share designs with the community and reliably document intended system functionality.

The Synthetic Biology Open Language (SBOL) is a community-developed data standard that allows knowledge about biological designs to be captured using a machine-tractable, ontology-backed representation that is built using Semantic Web technologies. While early versions of SBOL focused only on the description of DNA-based components and their sub-components, SBOL can now be used to represent knowledge across multiple scales and throughout the entire synthetic biology workflow, from the specification of a single molecule or DNA fragment through to multicellular systems containing multiple interacting genetic circuits. The third major iteration of the SBOL standard, SBOL3, is an effort to streamline and simplify the underlying data model with a focus on real-world applications, based on experience from the deployment of SBOL in a variety of scientific and industrial settings. Here, we introduce the SBOL3 specification both in comparison to previous versions of SBOL and through practical examples of its use., (Copyright © 2020 McLaughlin, Beal, Mısırlı, Grünberg, Bartley, Scott-Brown, Vaidyanathan, Fontanarrosa, Oberortner, Wipat, Gorochowski and Myers.)

Synthetic biology builds upon genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. When designing a synthetic system, synthetic biologists need to exchange information about multiple types of molecules, the intended behavior of the system, and actual experimental measurements. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, following an open community process involving both wet bench scientists and dry scientific modelers and software developers, across academia, industry, and other institutions. This document describes SBOL 3.0.0, which condenses and simplifies previous versions of SBOL based on experiences in deployment across a variety of scientific and industrial settings. In particular, SBOL 3.0.0, (1) separates sequence features from part/sub-part relationships, (2) renames Component Definition/Component to Component/Sub-Component, (3) merges Component and Module classes, (4) ensures consistency between data model and ontology terms, (5) extends the means to define and reference Sub-Components, (6) refines requirements on object URIs, (7) enables graph-based serialization, (8) moves Systems Biology Ontology (SBO) for Component types, (9) makes all sequence associations explicit, (10) makes interfaces explicit, (11) generalizes Sequence Constraints into a general structural Constraint class, and (12) expands the set of allowed constraints.

The Synthetic Biology Open Language (SBOL) is an emerging synthetic biology data exchange standard, designed primarily for unambiguous and efficient machine-to-machine communication. However, manual editing of SBOL is generally difficult for nontrivial designs. Here, we describe ShortBOL, a lightweight SBOL scripting language that bridges the gap between manual editing, visual design tools, and direct programming. ShortBOL is a shorthand textual language developed to enable users to create SBOL designs quickly and easily, without requiring strong programming skills or visual design tools.

Biological engineers often find it useful to communicate using diagrams. These diagrams can include information both about the structure of the nucleic acid sequences they are engineering and about the functional relationships between features of these sequences and/or other molecular species. A number of conventions and practices have begun to emerge within synthetic biology for creating such diagrams, and the Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard to organize, systematize, and extend such conventions in order to produce a coherent visual language. Here, we describe SBOL Visual version 2, which expands previous diagram standards to include new functional interactions, categories of molecular species, support for families of glyph variants, and the ability to indicate modular structure and mappings between elements of a system. SBOL Visual 2 also clarifies a number of requirements and best practices, significantly expands the collection of glyphs available to describe genetic features, and can be readily applied using a wide variety of software tools, both general and bespoke.

Standard representation of data is key for the reproducibility of designs in synthetic biology. The Synthetic Biology Open Language (SBOL) has already emerged as a data standard to represent information about genetic circuits, and it is based on capturing data using graphs. The language provides the syntax using a free text document that is accessible to humans only. This paper describes SBOL-OWL, an ontology for a machine understandable definition of SBOL. This ontology acts as a semantic layer for genetic circuit designs. As a result, computational tools can understand the meaning of design entities in addition to parsing structured SBOL data. SBOL-OWL not only describes how genetic circuits can be constructed computationally, it also facilitates the use of several existing Semantic Web tools for synthetic biology. This paper demonstrates some of these features, for example, to validate designs and check for inconsistencies. Through the use of SBOL-OWL, queries can be simplified and become more intuitive. Moreover, existing reasoners can be used to infer information about genetic circuit designs that cannot be directly retrieved using existing querying mechanisms. This ontological representation of the SBOL standard provides a new perspective to the verification, representation, and querying of information about genetic circuits and is important to incorporate complex design information via the integration of biological ontologies.

Computational models are essential to engineer predictable biological systems and to scale up this process for complex systems. Computational modeling often requires expert knowledge and data to build models. Clearly, manual creation of models is not scalable for large designs. Despite several automated model construction approaches, computational methodologies to bridge knowledge in design repositories and the process of creating computational models have still not been established. This paper describes a workflow for automatic generation of computational models of genetic circuits from data stored in design repositories using existing standards. This workflow leverages the software tool SBOLDesigner to build structural models that are then enriched by the Virtual Parts Repository API using Systems Biology Open Language (SBOL) data fetched from the SynBioHub design repository. The iBioSim software tool is then utilized to convert this SBOL description into a computational model encoded using the Systems Biology Markup Language (SBML). Finally, this SBML model can be simulated using a variety of methods. This workflow provides synthetic biologists with easy to use tools to create predictable biological systems, hiding away the complexity of building computational models. This approach can further be incorporated into other computational workflows for design automation.

This paper describes the development and characterisation of a novel, electrical impedance spectroscopy-based (EIS) immunosensor array for point-of-care applications. EIS is a highly sensitive, label-free, real time technique suitable for single use, point-of-care cardiac marker detection devices. However, the underlying source of the observed change in EIS immunoassay response has not been well characterised or understood. A full understanding of the relationship between target binding and impedance response would significantly advance biosensor design and most probably increase detection limit sensitivity. The development of micro-/nano- structured electrodes for multi-frequency EIS procedure propose substantial benefits over classical macro-structured systems.Countless manipulations of electrode features and inter-electrode spacing will enhance the electrode surface area, increase the charge-transfer resistance and reduce the double-layer capacitance. These in turn give rise to improved signal-to-noise ratios, therefore affording greater sensitivity, lower detection limits and faster detection times.The sensor sensitivity range was within that required for human myoglobin determination, following acute myocardial infarction (heart attack). Real-time MyAb-MyAg interaction monitoring, permitted the determination of the binding events in less than one minute.

The Synthetic Biology Open Language (SBOL) is a data standard for the representation of engineered biological systems. SBOL is implemented in the form of software libraries which can be used to add SBOL support to both new and existing software tools. While existing libraries allow for software to be developed that runs on a server or is installed locally, they lack the capability to create SBOL software that runs directly in a Web browser. Here, we address this issue by presenting sboljs, a JavaScript software library for SBOL that is capable of being used both on the server and in the Web browser.

In recent years, metal oxide-based, inexpensive, stable electrodes are being explored as a potent source of high performance, sustainable supercapacitors. Here, the employment of industrial waste red mud as a pseudocapacitive electrode material is reported. Mechanical milling is used to produce uniform red mud nanoparticles, which are rich in hematite (Fe 2 O 3 ), and lower amounts of other metal oxides. A comprehensive supercapacitive study of the electrode is presented as a function of ball-milling time up to 15 h. Ten-hour ball-milled samples exhibit the highest pseudocapacitive behavior with a specific capacitance value of ≈317 F g -1 , at a scan rate of 10 mV s -1 in 6 m aqueous potassium hydroxide electrolyte solution. The modified electrode shows an extraordinary retention of ≈97% after 5000 cycles. A detailed quantitative electrochemical analysis is carried out to understand the charge storage mechanism at the electrode-electrolyte interface. The formation of uniform nanoparticles and increased electrode stability are correlated with the high performance. This work presents two significant benefits for the environment; in energy storage, it shows the production of a stable and efficient supercapacitor electrode, and in waste management with new applications for the treatment of red mud., Competing Interests: The authors declare no conflict of interest., (© 2018 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The synthetic biology open language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.2.0 of SBOL that builds upon version 2.1.0 published in last year's JIB special issue. In particular, SBOL 2.2.0 includes improved description and validation rules for genetic design provenance, an extension to support combinatorial genetic designs, a new class to add non-SBOL data as attachments, a new class for genetic design implementations, and a description of a methodology to describe the entire design-build-test-learn cycle within the SBOL data model.

The SynBioHub repository ( https://synbiohub.org ) is an open-source software project that facilitates the sharing of information about engineered biological systems. SynBioHub provides computational access for software and data integration, and a graphical user interface that enables users to search for and share designs in a Web browser. By connecting to relevant repositories (e.g., the iGEM repository, JBEI ICE, and other instances of SynBioHub), the software allows users to browse, upload, and download data in various standard formats, regardless of their location or representation. SynBioHub also provides a central reference point for other resources to link to, delivering design information in a standardized format using the Synthetic Biology Open Language (SBOL). The adoption and use of SynBioHub, a community-driven effort, has the potential to overcome the reproducibility challenge across laboratories by helping to address the current lack of information about published designs.

As the Synthetic Biology Open Language (SBOL) data and visual standards gain acceptance for describing genetic designs in a detailed and reproducible way, there is an increasing need for an intuitive sequence editor tool that biologists can use that supports these standards. This paper describes SBOLDesigner 2, a genetic design automation (GDA) tool that natively supports both the SBOL data model (Version 2) and SBOL Visual (Version 1). This software is enabled to fetch and store parts and designs from SBOL repositories, such as SynBioHub. It can also import and export data about parts and designs in FASTA, GenBank, and SBOL 1 data format. Finally, it possesses a simple and intuitive user interface. This paper describes the design process using SBOLDesigner 2, highlighting new features over the earlier prototype versions. SBOLDesigner 2 is released freely and open source under the Apache 2.0 license.

As protein engineering becomes more sophisticated, practitioners increasingly need to share diagrams for communicating protein designs. To this end, we present a draft visual language, Protein Language, that describes the high-level architecture of an engineered protein with easy-to-draw glyphs, intended to be compatible with other biological diagram languages such as SBOL Visual and SBGN. Protein Language consists of glyphs for representing important features (e.g., globular domains, recognition and localization sequences, sites of covalent modification, cleavage and catalysis), rules for composing these glyphs to represent complex architectures, and rules constraining the scaling and styling of diagrams. To support Protein Language we have implemented an extensible web-based software diagram tool, Protein Designer, that uses Protein Language in a "drag and drop" interface for visualization and computer-aided-design of engineered proteins, as well as conversion of annotated protein sequences to Protein Language diagrams and figure export. Protein Designer can be accessed at http://biocad.ncl.ac.uk/protein-designer/ .

A synthetic biology workflow is composed of data repositories that provide information about genetic parts, sequence-level design tools to compose these parts into circuits, visualization tools to depict these designs, genetic design tools to select parts to create systems, and modeling and simulation tools to evaluate alternative design choices. Data standards enable the ready exchange of information within such a workflow, allowing repositories and tools to be connected from a diversity of sources. The present paper describes one such workflow that utilizes, among others, the Synthetic Biology Open Language (SBOL) to describe genetic designs, the Systems Biology Markup Language to model these designs, and SBOL Visual to visualize these designs. We describe how a standard-enabled workflow can be used to produce types of design information, including multiple repositories and software tools exchanging information using a variety of data standards. Recently, the ACS Synthetic Biology journal has recommended the use of SBOL in their publications., (© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.)

One aim of synthetic biologists is to create novel and predictable biological systems from simpler modular parts. This approach is currently hampered by a lack of well-defined and characterized parts and devices. However, there is a wealth of existing biological information, which can be used to identify and characterize biological parts, and their design constraints in the literature and numerous biological databases. However, this information is spread among these databases in many different formats. New computational approaches are required to make this information available in an integrated format that is more amenable to data mining. A tried and tested approach to this problem is to map disparate data sources into a single data set, with common syntax and semantics, to produce a data warehouse or knowledge base. Ontologies have been used extensively in the life sciences, providing this common syntax and semantics as a model for a given biological domain, in a fashion that is amenable to computational analysis and reasoning. Here, we present an ontology for applications in synthetic biology design, SyBiOnt, which facilitates the modeling of information about biological parts and their relationships. SyBiOnt was used to create the SyBiOntKB knowledge base, incorporating and building upon existing life sciences ontologies and standards. The reasoning capabilities of ontologies were then applied to automate the mining of biological parts from this knowledge base. We propose that this approach will be useful to speed up synthetic biology design and ultimately help facilitate the automation of the biological engineering life cycle.

VisBOL is a Web-based application that allows the rendering of genetic circuit designs, enabling synthetic biologists to visually convey designs in SBOL visual format. VisBOL designs can be exported to formats including PNG and SVG images to be embedded in Web pages, presentations and publications. The VisBOL tool enables the automated generation of visualizations from designs specified using the Synthetic Biology Open Language (SBOL) version 2.0, as well as a range of well-known bioinformatics formats including GenBank and Pigeoncad notation. VisBOL is provided both as a user accessible Web site and as an open-source (BSD) JavaScript library that can be used to embed diagrams within other content and software.

Recently, synthetic biologists have developed the Synthetic Biology Open Language (SBOL), a data exchange standard for descriptions of genetic parts, devices, modules, and systems. The goals of this standard are to allow scientists to exchange designs of biological parts and systems, to facilitate the storage of genetic designs in repositories, and to facilitate the description of genetic designs in publications. In order to achieve these goals, the development of an infrastructure to store, retrieve, and exchange SBOL data is necessary. To address this problem, we have developed the SBOL Stack, a Resource Description Framework (RDF) database specifically designed for the storage, integration, and publication of SBOL data. This database allows users to define a library of synthetic parts and designs as a service, to share SBOL data with collaborators, and to store designs of biological systems locally. The database also allows external data sources to be integrated by mapping them to the SBOL data model. The SBOL Stack includes two Web interfaces: the SBOL Stack API and SynBioHub. While the former is designed for developers, the latter allows users to upload new SBOL biological designs, download SBOL documents, search by keyword, and visualize SBOL data. Since the SBOL Stack is based on semantic Web technology, the inherent distributed querying functionality of RDF databases can be used to allow different SBOL stack databases to be queried simultaneously, and therefore, data can be shared between different institutes, centers, or other users.

Synthetic Biology Open Language (SBOL) Visual is a graphical standard for genetic engineering. It consists of symbols representing DNA subsequences, including regulatory elements and DNA assembly features. These symbols can be used to draw illustrations for communication and instruction, and as image assets for computer-aided design. SBOL Visual is a community standard, freely available for personal, academic, and commercial use (Creative Commons CC0 license). We provide prototypical symbol images that have been used in scientific publications and software tools. We encourage users to use and modify them freely, and to join the SBOL Visual community: http://www.sbolstandard.org/visual.

We report an investigation into the magnetic and electronic properties of partially hydrogenated vertically aligned few layers graphene (FLG) synthesized by microwave plasma enhanced chemical vapor deposition. The FLG samples are hydrogenated at different substrate temperatures to alter the degree of hydrogenation and their depth profile. The unique morphology of the structure gives rise to a unique geometry in which graphane/graphone is supported by graphene layers in the bulk, which is very different from other widely studied structures such as one-dimensional nanoribbons. Synchrotron based x-ray absorption fine structure spectroscopy measurements have been used to investigate the electronic structure and the underlying hydrogenation mechanism responsible for the magnetic properties. While ferromagnetic interactions seem to be predominant, the presence of antiferromagnetic interaction was also observed. Free spins available via the conversion of sp(2) to sp(3) hybridized structures, and the possibility of unpaired electrons from defects induced upon hydrogenation are thought to be likely mechanisms for the observed ferromagnetic orders.

The aim of this study is to assess in vitro cytotoxic effects of titania nanostructures and carbon nanotubes (CNTs) by exposing A549 lung epithelial cell line to these materials. Titania nanotubes (TiNTs) were grown by hydrothermal treatment of TiO(2) nanoparticles, followed by annealing them at 400°C. The titania nanostructures obtained on annealing (mixture of nanotubes and nanorods) were hollow and open ended, containing 3-5 layers of titania sheets, with an internal diameter ∼3-5 nm and external diameter ∼8-10 nm, and a specific surface area of 265 m(2)/g. As-supplied single walled (SWCNTs) and microwave plasma enhanced chemical vapour deposition (MPCVD) grown multi walled carbon nanotubes (MWCNTs) were used in this study. The lengths and diameters of the SWCNTs were 5-10nm and 0.5-3 nm respectively. The lengths and diameters of the MWCNTs were 25-30 μm and 10-30 nm respectively. The cell viability was evaluated using the MTT (3-(4,-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium) assay. No significant cytotoxic effects of titania nanostructures were observed over a period of a week of testing time, while the presence of CNTs in some cases demonstrated significant cytotoxic effects. Finally, possible reason of cytotoxicity is discussed in the light of microstructures of materials., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Polymethylmethacrylate (PMMA) microfluidic devices have been fabricated using a hot embossing technique to incorporate micro-pillar features on the bottom wall of the device which when combined with either a plasma treatment or the coating of a diamond-like carbon (DLC) film presents a range of surface modification profiles. Experimental results presented in detail the surface modifications in the form of distinct changes in the static water contact angle across a range from 44.3 to 81.2 when compared to pristine PMMA surfaces. Additionally, capillary flow of water (dyed to aid visualization) through the microfluidic devices was recorded and analyzed to provide comparison data between filling time of a microfluidic chamber and surface modification characteristics, including the effects of surface energy and surface roughness on the microfluidic flow. We have experimentally demonstrated that fluid flow and thus filling time for the microfluidic device was significantly faster for the device with surface modifications that resulted in a lower static contact angle, and also that the incorporation of micro-pillars into a fluidic device increases the filling time when compared to comparative devices.

The surface morphology of bucky papers (BPs) made from single-walled carbon nanotubes (CNTs) is modified by plasma treatment resulting in the formation of vertical microstructures on the surface. The shapes of these structures are either pillarlike or conelike depending on whether the gas used during plasma treatment is Ar or CH(4) . A complex interplay between different factors, such as the electric field within the plasma sheath, polarization of the CNT, intertubular cohesive forces, and ion bombardment, result in the formation of these structures. The roles played by these factors are quantitatively and qualitatively analyzed. The final material is flexible, substrate-free, composite-free, made only of CNTs, and has discrete vertically aligned structures on its surface. It shows enhanced field emission and electrochemical charge-storage capabilities. The field enhancement factor is increased by 6.8 times, and the turn-on field drops by 3.5 times from an initial value of 0.35 to 0.1 V μm(-1) as a result of the treatment. The increase in Brunauer-Emmett-Teller surface area results in about a fourfold improvement in the specific capacitance of the BP electrodes. Capacitance values before and after the treatments are 75 and 290 F g(-1) , respectively. It is predicted that this controlled surface modification technique could be put to good use in several applications based on macroscopic CNT films., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We explored the hot embossing method for transferring vertically aligned carbon nanotubes (CNTs) into microfluidic channels, fabricated on poly-methyl-methacrylate (PMMA). Patterned and unpatterned CNTs were synthesized by microwave plasma-enhanced chemical vapour deposition on silicon to work as a stamp. For hot embossing, 115 degrees C and 1 kN force for 2 min were found to be the most suitable parameters for the complete transfer of aligned CNTs on the PMMA microchannel. Raman and SEM studies were used to analyse the microstructure of CNTs before and after hot embossing. The PMMA microparticles with dimensions (approx. 10 microm in diameter) similar to red blood cells were successfully filtered using laminar flow through these microfluidic channels. Finally, a microfluidic-based point-of-care device for blood filtration and detection of bio-molecules is drawn schematically.

An evaluation of a newly CE approved bedside monitoring device used in a general hospital ward is presented. This evaluation has shown that it is feasible to use the system within this environment to provide medical staff with supplementary information on patient health, at more frequent intervals than traditional monitoring methods. The physiological data recorded by the body worn device is wirelessly transmitted to a patient management system for storage and display. Good correlation between heart rate values recorded by hospital staff and those recorded by the automated Vitalsens VS100 system was observed. The system has highlighted clinical information that routine observations alone did not readily identify. This can provide clinicians with a better view of the overall health status of the patient. Such medical issues include those witnessed in this study, namely paroxysmal AF, ectopic beats, increasing heart rates recorded prior to a hypoglycaemic event, general high and low heart rate trends and various instances where clinically relevant ECG data has been captured.

Microwave plasma enhanced chemical vapour deposition (MPECVD) was used for the production of carbon nanotubes. Vertically aligned multi-walled carbon nanotubes (MWCNTs) were grown on silicon substrates coated with cobalt thin films of thickness ranging from 0.5 nm to 3 nm. Prior to the nanotube growth the catalyst were treated with N2 plasma for 5-10 minutes that break the films into small nanoparticles which favour the growth of nanotubes. The CNTs were grown at a substrate temperature of 700 degrees C for 5, 10 and 15 minutes. The height of the CNT films ranging from 10 microm-30 microm indicating that the initial growth rate of the CNTs are very high at a rate of approximately 100 nm/sec. Electrical resistivity of the above samples was evaluated from I-V measurements. The activation energy (E(a)) was also calculated from the temperature dependent studies and it was found that the E(a) lies in the range of 15-35 meV. Raman spectroscopy was used to identify the quality of the nanotubes.

We report the growth of vertically oriented carbon micro-cones without using any foreign catalyst on silicon (100) substrate by microwave plasma assisted chemical vapour deposition method. The average height and bottom diameter of the carbon micro-cones are approximately 20 microm and approximately 1.4 microm, respectively. The diameters of the carbon micro-cones decrease gradually from bottom to tip, terminating in a nanotube structure. Mechanical damage of micro-cones resulted in the breaking and partial removal of the carbon micro-cones to show the structures possessed a nanotube core. Outside the micro-cone, the nanotubes showed a flattened ribbon structure. Electron microscopy and micro-Raman spectroscopy shows the nanotubes are multi walled and highly graphitic, with low structural disorder. The advanced vacuum electron emission devices could be fabricated with the carbon micro-cones grown directly on silicon substrate without using any catalyst.