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Challenges of analysing stochastic gene expression in bacteria using single-cell time-lapse experiments
No full textStochastic gene expression causes phenotypic heterogeneity in a population of genetically identical bacterial cells. Such non-genetic heterogeneity can have important consequences for the population fitness, and therefore cells implement regulation strategies to either suppress or exploit such heterogeneity to adapt to their circumstances. By employing time-lapse microscopy of single cells, the fluctuation dynamics of gene expression may be analysed, and their regulatory mechanisms thus deciphered. However, a careful consideration of the experimental design and data-analysis is needed to produce useful data for deriving meaningful insights from them. In the present paper, the individual steps and challenges involved in a time-lapse experiment are discussed, and a rigorous framework for designing, performing, and extracting single-cell gene expression dynamics data from such experiments is outlined
A simple and robust Abaqus implementation of the phase field fracture method
No full textThe phase field fracture method is attracting significant interest. Phase field approaches have enabled predicting - on arbitrary geometries and dimensions - complex fracture phenomena such as crack branching, coalescence, deflection and nucleation. In this work, we present a simple and robust implementation of the phase field fracture method in the commercial finite element package Abaqus. The implementation exploits the analogy between the phase field evolution law and the heat transfer equation, enabling the use of Abaqus' in-built features and circumventing the need for defining user elements. The framework is general, and is shown to accommodate different solution schemes (staggered and monolithic), as well as various constitutive choices for preventing damage under compression. The robustness and applicability of the numerical framework presented is demonstrated by addressing several 2D and 3D boundary value problems of particular interest. Focus is on the solution of paradigmatic case studies that are known to be particularly demanding from a convergence perspective. The results reveal that our phase field fracture implementation can be readily combined with other advanced computational features, such as contact, and deliver robust and precise solutions. The code developed can be downloaded from www.empaneda.com/codes
Estimating commuting matrix and error mitigation – A complementary use of aggregate travel survey, location-based big data and discrete choice models
No full textThe prevalence of location-based big data has opened a new research frontier for estimating origin–destination commuting matrices for cities where granular flow data are not yet available from official sources. However, investigations into estimation errors and potential correction methods have been rare in the literature. To address the research gap, this paper first compares the performance of two estimated commuting matrices for Shanghai, derived by two distinct matrix estimation methods, namely a big-data approach using mobile phone signalling data and a discrete choice model for simulating the residential location of commuters. The empirical results indicate an outstanding analytical complementarity of the two approaches. A novel method is then proposed for mitigating the errors associated with the big-data approach. The proposed method features a selective blending of the big-data based flow estimation and the model-based estimation. By comparing the blended flow estimation with benchmark travel statistics, we find that the proposed method would significantly reduce the estimation errors and hence improve the robustness of the estimated matrix. It is expected that the proposed method will set a new standard for correcting potential errors in big-data based flow estimation
Digital twin-driven decision making and planning for energy consumption
No full textThe Internet of Things (IoT) is revolutionising how energy is delivered from energy producers and used throughout residential households. Optimising the residential energy consumption is a crucial step toward having greener and sustainable energy production. Such optimisation requires a household-centric energy management system as opposed to a one-rule-fits all approach. In this paper, we propose a data-driven multi-layer digital twin of the energy system that aims to mirror households’ actual energy consumption in the form of a household digital twin (HDT). When linked to the energy production digital twin (EDT), HDT empowers the household-centric energy optimisation model to achieve the desired efficiency in energy use. The model intends to improve the efficiency of energy production by flattening the daily energy demand levels. This is done by collaboratively reorganising the energy consumption patterns of residential homes to avoid peak demands whilst accommodating the resident needs and reducing their energy costs. Indeed, our system incorporates the first HDT model to gauge the impact of various modifications on the household energy bill and, subsequently, on energy production. The proposed energy system is applied to a real-world IoT dataset that spans over two years and covers seventeen households. Our conducted experiments show that the model effectively flattened the collective energy demand by 20.9% on synthetic data and 20.4% on a real dataset. At the same time, the average energy cost per household was reduced by 10.7% for the synthetic data and 17.7% for the real dataset
The impact of the coronavirus disease 2019 pandemic on gastroenterologists in Southeast Asia: A mixed-methods study.
No full textBACKGROUND AND AIM: The coronavirus disease 2019 pandemic has impacted gastroenterology practices worldwide; however, its protracted effects within Southeast Asia were unknown. The primary aim of the study was to determine the impact of the pandemic on clinical demands including burnout among gastroenterologists within the region. The secondary aim was to identify risk factors for burnout and determine regional stressors. METHODS: This was a mixed-methods study. Gastroenterologists were surveyed electronically between September 1 and December 7, 2020, via gastroenterology and endoscopy societies of Brunei, Indonesia, Malaysia, Philippines, Singapore, and Thailand. Quantitative and qualitative data were collected. The 22-item Maslach Burnout Inventory-Human Services Survey (MBI-HSS) was used to detect burnout. Quantitative data were non-parametric; non-parametric methods were used for statistical comparisons. Logistic regression was used to determine risk factors for burnout. Content analysis method was used to analyze qualitative data. Ethical approval was obtained. RESULTS: A total of 73.0% reported that they were still significantly affected by the pandemic. Of these, 40.5% reported increased workload and 59.5% decreased workload. Statistically significant differences in weekly working hours, endoscopy, and inpatient volumes were present. No differences were observed in outpatient volumes, likely because of telemedicine. Burnout was common; however, 50.1% of gastroenterologists were unaware of or did not have access to mental health support. This, as well as depression, being a trainee, and public sector work, increased burnout risk significantly. CONCLUSION: The effects of the pandemic are multifaceted, and burnout is common among Southeast Asian gastroenterologists. Safeguards for mental health are suboptimal, and improvements are urgently needed
Using two-dimensional distributions to inform the mixing state of soot and salt particles produced in gas flares
No full textGas flaring is a common practice in the oil and gas industry, where droplets of flowback water with varying levels of dissolved salts (mainly composed of sodium and chloride) often become entrained in the flared gas. In this study, we examine the mixing state of the aerosol produced by a laboratory flare with and without entrained droplets of sodium chloride solutions. The resultant aerosol is cross-examined using several different methods, including: transmission electron microscopy (TEM), tandem measurements using a CPMA and a differential mobility analyzer (DMA), tandem measurements using a centrifugal particle mass analyzer (CPMA) and a single particle soot photometer (SP2), and Raman spectroscopy. A focus is placed on two-dimensional distributions of properties and the kind of morphological information contained therein. The TEM and CPMA-SP2 measurements both show that the majority of soot particles were internally mixed with salt, while TEM and CPMA-DMA measurements indicate that there are also a large number of isolated salt particles
Protein Conjugation by Electrophilic Alkynylation Using 5-(Alkynyl)dibenzothiophenium Triflates
No full text5-(Alkynyl)dibenzothiophenium triflates are introduced as new reagents to prepare different protein conjugates through site-selective cysteine alkynylation. The protocol developed allows a highly efficient label of free cysteine-containing proteins with relevant biological roles, such as ubiquitin, the C2A domain of Synaptotagmin-I, or HER2 targeting nanobodies. An electrophilic bis-alkynylating reagent was also designed. The second alkynylating handle thus introduced in the desired protein enables access to protein-thiol, protein-peptide, and protein-protein conjugates, and even diubiquitin dimers can be prepared through this approach. The low excess of reagent needed, mild reaction conditions used, short reaction times, and stability of the S-C(alkyne) bonds at physiological conditions make this approach an interesting addition to the toolbox of classical, site-selective cysteine-conjugation methods
Skin-compatible amorphous oxide thin-film-transistors with a stress-released elastic architecture
No full textA highly reliable reverse-trapezoid-structured polydimethylsiloxane (PDMS) is demon-strated to achieve mechanically enhanced amorphous indium-gallium-zinc oxide (a-IGZO) thin-film-transistors (TFTs) for skin-compatible electronics. Finite element analysis (FEA) simulation reveals that the stress within a-IGZO TFTs can be efficiently reduced compared to conventional substrates. Based on the results, a conventional photolithography process was employed to implement the reverse-trapezoid homogeneous structures using a negative photoresist (NPR). Simply accessible photolithography using NPR enabled high-resolution patterning and thus large-area scalable device architectures could be obtained. The a-IGZO TFTs on the reverse-trapezoid-structured PDMS exhibited a maximum saturation mobility of 6.06 cm2 V−1 s−1 under a drain bias voltage of 10 V with minimal strain stress. As a result, the proposed a-IGZO TFTs, including stress-released architecture, exhibited highly enhanced mechanical properties, showing saturation mobility variation within 12% under a strain of 15%, whereas conventional planar a-IGZO TFTs on PDMS showed mobility variation over 10% even under a 1% strain and failed to operate beyond a 2% strain
Rainwater Harvesting and Community Water Security in south-west Uganda
No full textLess than 40% of Uganda’s population has access to safe drinking water. Municipal water systems rarely reach the poorest, most remote communities, and where they do reach populations, quality and quantity are often inadequate due to poor system operation and maintenance. Decentralised water services, such as RWH can provide essential water where centralised supply is inadequate or does not reach. The Intergovernmental Panel on Climate Change (IPCC) encourages the use of rainwater harvesting (RWH) to improve community water access in sub-Saharan Africa (SSA). Nonetheless, uptake of RWH across SSA is below targets that have been set by the United Nations. If these targets are to be met, further research is needed to understand the drivers and barriers of RWH adoption for water insecure populations in Uganda. Water security has become a widely accepted term that communicates the broader social, political and environmental benefits of water-related services. Rather than focusing solely on the materiality of water access in itself, water security frameworks have been used to assess the less tangible outcomes of decentralised water access. For this thesis, a new water security framework was designed based on the perspectives of water practitioners and stakeholders involved in the delivery of water services in south-west Uganda. The framework provided structure to identify and assess the sociotechnical outcomes of RWH access. The framework includes ten sociotechnical water security goals and is based on a new definition of water security developed for this research: ‘water services that contribute to community water security provide sufficient water of acceptable quality for good health, which is affordable and available year-round. They sustain livelihoods and can be equitably accessed across all user-groups. These water services should minimise the risk of local conflict and boost community cohesion and climate resilience. The management of these services should be supported by local and national institutions so they can be reliably sustained over the long-term’. Building on previous research, the water security goals go above and beyond solely describing the fundamental physical characteristics of water provision, instead, they reference socioeconomic, environmental and technical outcomes. The structure of the framework encourages researchers to collect a range of qualitative and quantitative data. Using a ‘two-case’ case study strategy, the framework was applied to the assessment of ten RWH installations in a rural (Kabale) and an urban (Mbarara) community in south-West Uganda to identify the drivers, barriers and outcomes of RWH use in the region. Comparisons between the urban and rural community uncovered how localised socioeconomic, infrastructural and governance structures influence the delivery and uptake of RWH in Uganda. For the assessment, a mixed-methods approach was adopted which included water balance modelling, sanitary surveys, site inspections, key informant interviews, focus groups and physiochemical and bacteriological water quality tests. The significant drivers of RWH use in the rural community were proximity of water in comparison to alternative water sources, the potential for improved livelihoods, protection against climate unpredictability and support from a local NGO. RWH provided good quality water that met WHO standards at 80% of sites. There was enough water to support household and micro-enterprise activities. High capital cost was found to be a significant barrier to the adoption of the technology. The drivers for adoption among the urban community were poor municipal water quality, service interruptions and high costs associated with existing water services. This was compounded by poor sense of value for money and mistrust of the municipal service. In the urban community RWH provided good water quality for 70% of the sites assessed. A lack of awareness and financing mechanisms were highlighted as significant barriers to RWH use. In neither community could RWH provide year-round availability of water and so is most appropriate as a supplementary water source in this region of Uganda. The identification of the drivers, barriers and outcomes of RWH use in these two communities allows policymakers and water practitioners to better understand which incentives, programmes and mechanisms can support the uptake and sustained use of RWH in Uganda. The water security framework provides structure to assess the sociotechnical outcomes of decentralised water access, emphasising the importance of the human-water relationship to global development
Work structuring and product design for customized repetitive projects
No full textBallard’s concept of work structuring for production planning in construction can be applied to improve production flow in construction projects formed by repetitive units with extensive customization. Customization can increase the value of repetitive units (apartments in a building, houses in an allotment, or stores in a shopping mall) forming a project, by meeting clients’ specific requirements. However, in traditional construction production systems, it commonly causes delays, stoppages, rework, increased amounts of work in progress, and excessive movement of crews and materials. The problem has been thoroughly documented and various production systems have been designed to address the trade-off between flow and value. We identify five such systems, which were originally developed following exploratory design science principles. In this work, we analyse and compare them using nine metrics to assess their performance in terms of flow and value, and to explore the role of work structuring in customized projects. The systems with the most effective flow are the Fit-Out Company and the Ecosystem Platform systems. The analysis led to the theoretical proposition of a hybrid production system called Product/Process Modularization, which may be applied and tested in the future