Publications by authors named "Sinclair I"

In fiber-reinforced polymer composites, the fiber-matrix interface controls stress transfer mechanisms, thereby affecting mechanical performance. Interfacial properties are often extracted via single-fiber composite tests. In these tests, the load is transferred from the polymer to the fiber through interfacial shear stresses, necessitating the evaluation of interfacial shear properties.

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Background: The University of Southampton, in collaboration with the University Hospital Southampton (UHS) NHS Foundation Trust and industrial partners, has been at the forefront of developing three-dimensional (3D) imaging workflows using X-ray microfocus computed tomography (μCT) -based technology. This article presents the outcomes of these endeavours and highlights the distinctive characteristics of a μCT facility tailored explicitly for 3D X-ray Histology, with a primary focus on applications in biomedical research and preclinical and clinical studies.

Methods: The UHS houses a unique 3D X-ray Histology (XRH) facility, offering a range of services to national and international clients.

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Background: Displacement due to natural disaster exposure is a major source of distress, and disproportionately affects people in low- and middle-income countries (LMICs). Public mental health resources following natural disasters and displacement are often limited in LMICs. In 2017, the population of one island in Vanuatu, a lower-middle income country, was displaced due to volcanic activity.

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Fragment based drug discovery is a critical part of the lead generation toolbox and relies heavily on a readily available, high quality fragment library. Over years of use, the AstraZeneca fragment set had become partially depleted and instances of compound deterioration had been found. It was recognised that a redevelopment was required.

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Article Synopsis
  • * Redox cycling compounds (RCCs) generate harmful reactive oxygen species that can affect protein functionality and complicate screening results.
  • * The study introduces Acoustic Mist Ionisation Mass Spectrometry (AMI-MS) as a faster, more compatible method for detecting TCEP oxidation in high-throughput settings compared to traditional NMR techniques.
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Large compound libraries utilised for HTS often include metal contaminated compounds which can interfere with assay signal or target biology, and therefore appear as hits. Pursuit of these compounds can divert considerable time and resource away from more propitious hits, yet there is currently no established method of detecting metal impurities in a rapid and effective manner. Here we describe the development and application of a high-throughput method to identify metal contaminants using acoustic mist ionisation mass spectrometry (AMI-MS).

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Article Synopsis
  • Vegetation, particularly roots from species like willow and gorse, increases soil shearing resistance by absorbing water and reinforcing the soil structure.
  • Traditional models for predicting how rooted soils behave often rely on hard-to-measure parameters, resulting in inconsistent predictions due to the complex interactions between soil and roots.
  • Researchers used advanced imaging techniques to measure soil behavior and found that root characteristics significantly affect shear resistance, leading to an improved model that accurately predicted the increased resistance in root-reinforced soils.
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Advanced manufacturing technologies, led by additive manufacturing, have undergone significant growth in recent years. These technologies enable engineers to design parts with reduced weight while maintaining structural and functional integrity. In particular, metal additive manufacturing parts are increasingly used in application areas such as aerospace, where a failure of a mission-critical part can have dire safety consequences.

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We performed tensile tests on two carbon fibre/epoxy composites with continuous scanning using synchrotron computed tomography (CT). Both composites were cross-ply laminates, and two specimens were tested for each composite. The voxel size was sufficiently small to recognize individual fibres and fibre breaks.

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Background: Although numerous studies have assessed physical activity during pregnancy and relationships with infant outcomes, such as birthweight, few have evaluated sedentary behavior. Our objective was to evaluate sedentary behavior across pregnancy and relationships with infant birthweight in a sociodemographically diverse sample.

Methods: We measured device-assessed sedentary behavior and physical activity over three days at 16-18, 24-26, and 32-34 weeks gestation and infant birthweight from medical records among 71 participants.

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It is clear from the analysis of the distribution of approved drug targets that enzymes continue to be a major target class for the pharmaceutical industry. The application of high-throughput screens designed to monitor the activity of these enzyme targets, and the ability of test compounds to modulate this activity, is still the predominant hit finding approach in the industry. The widespread use of enzyme activity-based screens has led to the development of several useful guidelines for the development and validation of robust and reliable assays.

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Cellular metabolites and phospholipids contain a vast amount of information about the current state of a cell, and are a useful resource for understanding the effects of drug candidates in vitro. Typical human cell-based assays in early drug discovery rely on simple readouts such as cell viability, or focus on single end-points revealed by an antibody or other label-based technologies. We introduce a generic 384-well plate-based workflow for data-rich cellular assays using facile sample preparation and direct analysis by acoustic mist ionization mass spectrometry (AMI-MS).

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Introduction: Past research shows that stress during pregnancy predicts adverse birth outcomes. These patterns might differ based on immigration status. Our objective was to analyze differences in relationships between perceived stress during pregnancy and birth outcomes by immigration status.

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Vegetation on railway or highway slopes can improve slope stability through the generation of soil pore water suctions by plant transpiration and mechanical soil reinforcement by the roots. To incorporate the enhanced shearing resistance and stiffness of root-reinforced soils in stability calculations, it is necessary to understand and quantify its effectiveness. This requires integrated and sophisticated experimental and multi-scale modelling approaches to develop an understanding of the processes at different length scales, from individual root-soil interaction through to full soil-profile or slope scale.

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Background: Past research shows that psychosocial stress and distress predict sedentary behavior and physical activity, but few studies focus on pregnant women. Our objective was to analyze relationships between psychosocial stress and distress with sedentary behavior and physical activity among pregnant women in Canada.

Methods: We analyzed objectively-measured sedentary behavior and physical activity at 16-18, 24-26, and 32-24 weeks pregnancy in a sociodemographically diverse cohort of 70 women in Montreal, Canada.

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This scoping review identifies the best practices of community-based participatory research with Pacific Islanders in the United States and United States Affiliated Pacific Islands. Eighty-four articles from January 2000 to December 2017 were included in the review. Best practices included the importance of engaging Pacific Islander community leaders as research staff, community co-investigators, and community advisory board members.

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Objective: Psychosocial health predicts physical health outcomes in both clinical samples and the general population. One mechanism is through relationships with health behaviors. Results might differ based on sociodemographic characteristics such as education, income, ethnicity, and immigrant status.

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Historically, micro-computed tomography (μCT) has been considered unsuitable for histologic analysis of unstained formalin-fixed, paraffin-embedded soft tissue biopsy specimens because of a lack of image contrast between the tissue and the paraffin. However, we recently demonstrated that μCT can successfully resolve microstructural detail in routinely prepared tissue specimens. Herein, we illustrate how μCT imaging of standard formalin-fixed, paraffin-embedded biopsy specimens can be seamlessly integrated into conventional histology workflows, enabling nondestructive three-dimensional (3D) X-ray histology, the use and benefits of which we showcase for the exemplar of human lung biopsy specimens.

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The expansion of label free mass spectrometry into early drug discovery was always predicted to provide improvements in data quality and depth with the potential to reduce costs but has previously been limited by throughput. There are several techniques that vary by sample introduction technology or ionization technique that try to address the challenges in this area. In this review, the authors describe the deployment of such a device, combining acoustic mist ionization and time-of-flight mass spectrometry.

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Mass spectrometry (MS) has many advantages as a quantitative detection technology for applications within drug discovery. However, current methods of liquid sample introduction to a detector are slow and limit the use of mass spectrometry for kinetic and high-throughput applications. We present the development of an acoustic mist ionization (AMI) interface capable of contactless nanoliter-scale "infusion" of up to three individual samples per second into the mass detector.

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Introduction: Past research has shown relationships between stress during pregnancy, and related psychosocial health measures such as anxiety and depressive symptoms, with infant, child, and adult outcomes. However, most research is from high-income countries. We conducted a scoping review to identify research studies on prenatal stress and outcomes of the pregnancy or offspring in low- and middle-income countries (LMICs), and to synthesize the stress measures and outcomes assessed, the findings observed, and directions for future research.

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Background: The concept that small conducting airways less than 2 mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the scientific literature, and the last generation of small conducting airways, terminal bronchioles, are known to be destroyed in patients with very severe COPD. We aimed to determine whether destruction of the terminal and transitional bronchioles (the first generation of respiratory airways) occurs before, or in parallel with, emphysematous tissue destruction.

Methods: In this cross-sectional analysis, we applied a novel multiresolution CT imaging protocol to tissue samples obtained using a systematic uniform sampling method to obtain representative unbiased samples of the whole lung or lobe of smokers with normal lung function (controls) and patients with mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1), moderate COPD (GOLD 2), or very severe COPD (GOLD 4).

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Unlabelled: We hypothesized that plant exudates could either gel or disperse soil depending on their chemical characteristics. Barley (Hordeum vulgare L. cv.

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This study applied time lapse (four-dimensional) synchrotron X-ray computed tomography to observe micro-scale interactions between plant roots and soil. Functionally contrasting maize root tips were repeatedly imaged during ingress into soil columns of varying water content and compaction. This yielded sequences of three-dimensional densiometric data, representing time-resolved geometric soil and root configurations at the micronmetre scale.

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In this paper, we provide direct evidence of the importance of root hairs on pore structure development at the root-soil interface during the early stage of crop establishment. This was achieved by use of high-resolution (c. 5 μm) synchrotron radiation computed tomography (SRCT) to visualise both the structure of root hairs and the soil pore structure in plant-soil microcosms.

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