Life Sciences: Recent submissions
Now showing items 21-40 of 2597
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Multi-isotopic study of the earliest medieval inhabitants of Santiago de Compostela (Galicia, Spain)Santiago de Compostela is, together with Rome and Jerusalem, one of the three main pilgrimage and religious centres for Catholicism. The belief that the remains of St James the Great, one of the twelve apostles of Jesus Christ, is buried there has stimulated, since their reported discovery in the 9th century AD, a significant flow of people from across the European continent and beyond. Little is known about the practical experiences of people living within the city during its rise to prominence, however. Here, for the first time, we combine multi-isotope analysis (δ13C, δ15N, δ18Oap, δ13Cap, and 87Sr/86Sr) and radiocarbon dating (14C) of human remains discovered at the crypt of the Cathedral of Santiago to directly study changes in diet and mobility during the first three centuries of Santiago’s emergence as an urban centre (9th-12th centuries AD). Together with assessment of the existing archaeological data, our radiocarbon chronology broadly confirms historical tradition regarding the first occupation of the site. Isotopic analyses reveal that the foundation of the religious site attracted migrants from the wider region of the northwest corner of the Iberian Peninsula, and possibly from further afield. Stable isotope analysis of collagen, together with information on tomb typology and location, indicates that the inhabitants of the city experienced increasing socioeconomic diversity as it became wealthier as the hub of a wide network of pilgrimage. Our research represents the potential of multidisciplinary analyses to reveal insights into the origins and impacts of the emergence of early pilgrimage centres on the diets and status of communities within Christian medieval Europe and beyond.
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Proteomic features of skeletal muscle adaptation to resistance exercise training as a function of ageResistance exercise training (RET) can counteract negative features of muscle ageing but older age associates with reduced adaptive capacity to RET. Altered muscle protein networks likely contribute to ageing RET adaptation; therefore, associated proteome-wide responses warrant exploration. We employed quantitative sarcoplasmic proteomics to compare age-related proteome and phosphoproteome responses to RET. Thigh muscle biopsies were collected from eight young (25 ± 1.1 years) and eight older (67.5 ± 2.6 years) adults before and after 20 weeks supervised RET. Muscle sarcoplasmic fractions were pooled for each condition and analysed using Isobaric Tags for Relative and Absolute Quantification (iTRAQ) labelling, tandem mass spectrometry and network-based hub protein identification. Older adults displayed impaired RET-induced adaptations in whole-body lean mass, body fat percentage and thigh lean mass (P > 0.05). iTRAQ identified 73 differentially expressed proteins with age and/or RET. Despite possible proteomic stochasticity, RET improved ageing profiles for mitochondrial function and glucose metabolism (top hub; PYK (pyruvate kinase)) but failed to correct altered ageing expression of cytoskeletal proteins (top hub; YWHAZ (14-3-3 protein zeta/delta)). These ageing RET proteomic profiles were generally unchanged or oppositely regulated post-RET in younger muscle. Similarly, RET corrected expression of 10 phosphoproteins altered in ageing, but these responses were again different vs. younger adults. Older muscle is characterised by RET-induced metabolic protein profiles that, whilst not present in younger muscle, improve untrained age-related proteomic deficits. Combined with impaired cytoskeletal adhesion responses, these results provide a proteomic framework for understanding and optimising ageing muscle RET adaptation.
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Interfacial cocrystallization using oily phase via liquid−liquid phase separationCocrystals consist of two molecules bonded together in a single crystal lattice giving rise to wide applications including improving solubility of poorly soluble pharmaceuticals. Cocrystallization reaction occurs in the oily phase of liquid–liquid phase separation (LLPS) after it is mixed with coformers. Indomethacin–saccharin cocrystal formation was monitored in situ, and the kinetics of crystallization were determined. The crystallization rates show that the process can be proposed to prevent unwanted oily phase formation during LLPS.
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A qualitative analysis of stressors affecting 999 ambulance call handlers' mental health and well-beingPurpose The 999 ambulance call handler is critical in responding to emergency patient treatment; however, the call handlers are often a hidden component of the healthcare workforce and an under-researched group. The objective of this study is to understand stress triggers experienced by 999 ambulance call handlers that could lead to burnout and examine personal and organisational mechanisms and strategies which reduced the risk of burnout. Design/methodology/approach A single interview case study approach applying qualitative methods was undertaken. Participants were identified through a purposive sample of 999 ambulance call handlers with the Yorkshire Ambulance Service National Health Service Trust (UK). Participants were interviewed via telephone between July 2019 and September 2019. Findings In total, 18 staff participated in this study. Societal factors including public incivility and media representation and organisational factors, such as a demanding environment, lack of appreciation and career progression, training issues and protocols were key stressors. Organisational well-being services were helpful for some, but for others lacked accessibility and appropriateness. Positive public feedback and speaking with peers bolstered well-being. 999 ambulance call handlers suggested that sufficient breaks, co-design or feeding back on training and protocols and creating more informal opportunities to discuss ongoing everyday stressors as methods to reduce stress and burnout. Originality/value This paper explores a previously under researched area on stressors and potential burnout in 999 call handlers. This paper highlights the need for improved organisational support services and appropriate public and sector peer recognition of the role of ambulance 999 ambulance call handlers.
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The MK2 cascade mediates transient alteration in mGluR-LTD and spatial learning in a murine model of Alzheimer's diseaseA key aim of Alzheimer disease research is to develop efficient therapies to prevent and/or delay the irreversible progression of cognitive impairments. Early deficits in long-term potentiation (LTP) are associated with the accumulation of amyloid beta in rodent models of the disease; however, less is known about how mGluR-mediated long-term depression (mGluR-LTD) is affected. In this study, we have found that mGluR-LTD is enhanced in the APPswe /PS1dE9 mouse at 7 but returns to wild-type levels at 13 months of age. This transient over-activation of mGluR signalling is coupled with impaired LTP and shifts the dynamic range of synapses towards depression. These alterations in synaptic plasticity are associated with an inability to utilize cues in a spatial learning task. The transient dysregulation of plasticity can be prevented by genetic deletion of the MAP kinase-activated protein kinase 2 (MK2), a substrate of p38 MAPK, demonstrating that manipulating the mGluR-p38 MAPK-MK2 cascade at 7 months can prevent the shift in synapse dynamic range. Our work reveals the MK2 cascade as a potential pharmacological target to correct the over-activation of mGluR signalling.
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Genetic Prediction of Myopia in Different Ethnic AncestriesBackground: Myopia has been shown to have a complex mode of inheritance, being influenced by both genetic and environmental factors. Here, an introduction into myopia genetics is given, with the shortcomings of current genetic prediction for myopia discussed, including the proportionally limited research on genetic prediction in people of non-European ancestry. A previously developed genetic risk score derived from European participants was evaluated in participants of non-European ancestry. Methods: Participants from UK Biobank who self-reported their ethnicity as “Asian”, “Chinese”, or “Black” and who had refractive error and genetic data available were included in the analysis. Ancestral homogeneity was confirmed using principal component analysis, resulting in samples of 3500 Asian, 444 Chinese, and 3132 Black participants. A published refractive error GWAS meta-analysis of 711,984 participants of European ancestry was used to create a weighted genetic risk score model which was then applied to participants from each ethnic group. Accuracy of genetic prediction of refractive error was estimated as the proportion of variance explained (PVE). Receiver operating characteristic (ROC) curves were developed to estimate myopia prediction performance at three thresholds: any myopia (equal to or more than 0.75D), moderate myopia (between -3.00D and -4.99D) and high myopia (equal to or more than -5.00D). Odds ratios for myopia were calculated for the participants in the top 10th or 5th percentile of genetic risk score distribution, comparing them to the remainder of the population. Results: The PVE value for refractive error was 6.4%, 6.2%, and 1.5% for those with Asian, Chinese and Black ethnicity, respectively (compared to 11.2% in Europeans). Odds ratios for any myopia and moderate myopia development for those within the top 10th and 5th percentile of genetic risk were significant in all ethnic groups P<0.05). However, the genetic risk score was not able to reliably identify those at risk of high myopia, other than for participants of Chinese ethnicity (P<0.05). Conclusion: Prediction of refractive error in Asian, Chinese and Black participants was ~57%, 55% and 13% as accurate in comparison to prediction in European participants. Further research in diverse ethnic populations is needed to improve prediction accuracy.
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Concordance of objectively-detected retinal nerve fiber bundle defects in en face OCT images with conventional structural and functional changes in glaucoma.To assess how objectively-detected defects of retinal nerve fibre bundle (RNFB) reflectance in en face OCT images relate to circumpapillary retinal nerve fibre layer thickness (cpRNFLT) and visual field defects. Cross-sectional study. 16 participants with early-glaucoma and 29 age-similar healthy controls, among which 22 had usable en face images to establish normative levels of RNFB reflectance. All participants underwent cpRNFLT scans, visual field examination and wide-field OCT. En face reflectivity was assessed objectively using the Summary of Multiple Anatomically-Adjusted Slabs (SMAS) method. En face defects were deemed concordant with cpRNFLT when they had at least one cpRNFLT point with p
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A Combined Rheological and Thermomechanical Analysis Approach for the Assessment of Pharmaceutical Polymer BlendsThe viscoelastic nature of polymeric formulations utilised in drug products imparts unique thermomechanical attributes during manufacturing and over the shelf life of the product. Nevertheless, it adds to the challenge of understanding the precise mechanistic behaviour of the product at the microscopic and macroscopic level during each step of the process. Current thermomechanical and rheological characterisation techniques are limited to assessing polymer performance to a single phase and are especially hindered when the polymers are undergoing thermomechanical transitions. Since pharmaceutical processing can occur at these transition conditions, this study successfully proposes a thermomechanical characterisation approach combining both mechanical and rheological data to construct a comprehensive profiling of polymeric materials spanning both glassy and rubbery phases. This approach has been used in this study to assess the mechanical and rheological behaviour of heterogenous polymer blends of hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) over a shearing rate range of 0.1–100 s−1 and a temperature range of 30–200 °C. The results indicate that HPC and HPMC do not appear to interact when mixing and that their mixture exhibits the mechanistic properties of the two individual polymers in accordance with their ratio in the mixture. The ability to characterise the behaviour of the polymers and their mixtures before, throughout, and after the glassy to rubbery phase transition by application of the combined techniques provides a unique insight towards a quality-by-design approach to this and other polymer-based solid dosage forms, designed with the potential to accelerate their formulation process through obviating the need for multiple formulation trials.
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The face of Stonehenge: 3D surface scanning, 3D printing and facial reconstruction of the Winterbourne Stoke craniumStonehenge is one of the world’s most iconic archaeological sites and yet we know relatively little about the people that created this important prehistoric monument. This chapter contributes to this narrative by reconstructing the face of a high-status male who was recovered during nineteenth-century excavation of a Neolithic Long Barrow. Situated in the barrow cemetery at Winterbourne Stoke, this site is important to the contextual setting and contemporary development of Stonehenge as a ceremonial and ritual centre. The chapter reports on the combination of digital bioarchaeology and visual heritage methods, together with forensic reconstruction, that transformed the physical remains of the individual into digital data that was manipulated for 3D printing; and subsequent anatomical and visual art interpretation to yield physical life-like characteristics. His facial features have been rebuilt on the 3D printed skull, muscle by muscle, to create a highly realistic face from the era. The aim of this project was to provide a tangible connection to the archaeology of the Stonehenge landscape and to the people that developed its ceremonial and ritual significance—narrowing the temporal distance through the emotional experience it means to gaze into the eyes of a Neolithic individual.
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Manual/digital interactions in 'Project code-named Humpty'‘Project code-named Humpty’ is a performative art piece involving the creation, fragmentation, and reconstruction of a 2.7 m high classically inspired sculpture. It was conceived to complement an archaeological science research project setting out to explore the use of digital scanning technologies in artefact reconstruction. The statue’s form was free sculpted in clay over a period of four years. It was cast in a self-supporting cementitious material specifically for the purpose of ceremonial fragmentation and subsequent reconstruction by archaeologists. In this chapter, we explore the project’s human/machine intentions, interactions, development processes and their wider implications leading to fragmentation. We explore how 3D terrestrial laser scanning with photogrammetry was used to chart the creation of the sculptural form and how scans informed finite element analysis, essential for safe casting and fragmentation. We show how structured light scanning was essential to create a digital backup of the mould and how drone imagery documented fragmentation tests and 360° imaging recorded studio and quarry activity.
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A rapid approach to the digital documentation of Bradford's rich industrial heritageThe industrial heritage for the City of Bradford Metropolitan District is of international significance, with the city formerly being the centre of the world’s worsted trade during the nineteenth century. The intensification of textile production during the industrial revolution resulted in exponential growth of all aspects of the city, the legacy seen in the townscape heritage of the city today. The structures from this period have played a key role in defining the city’s identity. Since the decline of the textile industry the fabric of many of these buildings from the city’s golden age are under threat and at high risk of loss due to weathering, vandalism and fire. Given the varied nature and condition of these structures, a rapid approach has been applied that complements initiatives in train with Bradford Council to regenerate the ‘Top of Town’; that are reflective of Historic England’s ‘Engines of Prosperity’ report into the regeneration of Industrial Heritage; and with the Management of Saltaire World Heritage site. This chapter focuses on the digital documentation of a conservation area which is highly vulnerable, producing a dataset to aid conservation, management, interpretation and promotion of Bradford’s rich heritage.
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Digital refit analysis of anthropogenically fragmented equine bone from the Schoningen 13 II-4 Deposits, GermanyExcavation of the Schöningen lignite mine in Germany produced the earliest examples of hunting spears to date, and a large assemblage of anthropogenically fragmented faunal remains deposited in anaerobic lacustrine silt sediments during the Middle Pleistocene. The exceptional preservation of the assemblage makes the site of prime importance to our understanding of the behavioural, social and economic patterns of hominins in the Lower Palaeolithic of the Middle Pleistocene in Europe. This chapter describes the digital refitting analysis, part of the AHRC-funded Fragmented Heritage project, undertaken to address the logistical challenge posed by manually comparing individual bone fragments within the assemblage to identify refitting sequences. This logistical refit challenge uses the Schöningen assemblage to investigate the effectiveness of a digital refit approach to the analysis of large faunal assemblages. We describe the process from digitisation of the bone fragments by macro structured light scanning, digital segmentation of refitting surfaces, and digital comparison of the refitting and non-refitting surfaces to produce statistical matches. We discuss how taphonomic data can be visualised from the analysis and can be used to inform interpretation of the taphonomic histories of these faunal remains and the human behaviours associated with the formation of this unique assemblage.
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Getting the measure of brochs: using survey records old and new to investigate Shetland's Iron Age archaeologyBrochs are monumental Iron Age (c.400–200 BC) drystone towers or roundhouses. They are only found in Scotland, particularly the Atlantic north and west. Whilst the structural layout of brochs has long been debated, few measured surveys have been conducted. Three significant broch sites form the tentative World Heritage site of “Mousa, Old Scatness and Jarlshof: the Zenith of Iron Age Shetland” (UNESCO in Mousa, Old Scatness and Jarlshof: the zenith of Iron Age Shetland, UNESCO (2019) Mousa, Old Scatness and Jarlshof: the zenith of Iron Age Shetland. http://whc.unesco.org/en/tentativelists/5677. Accessed 9 Aug 2019). All three sites have undergone new surveys as part of a collaborative doctoral partnership research project. This chapter presents a diachronic perspective using digital documentation techniques to detect stone displacement and weathering at the site of Old Scatness using historic imagery, including photographs from the Old Scatness excavations (1995–2006) and regular condition monitoring undertaken by Shetland Amenity Trust to undertake retrospective digital structure-from-motion (SfM) photogrammetry. Whilst point clouds and 3D meshes were successfully generated from low-resolution digital images, analogue film transparencies without metadata could not produce accurate geospatial data without manually trying to extant reference data. It was possible to detect displacements in stonework over time by comparing two meshes together and measuring the distances between vertex point pairs. The reliability and accuracy of these results were dependent on how well pairs of meshes could be aligned.
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Visualising animal hard tissuesThis chapter summarises AHRC/EPSRC Science and Heritage Programme-funded research to develop a digital resource to disseminate knowledge of the identification of osseous and keratinous animal hard tissues. The choice of materials in the manufacture of individual artefacts or classes of objects can make a major contribution to understanding their cultural significance and questions of provenance or authenticity. This resource builds on understanding gained through a Fellowship to O’Connor in developing, evaluating and validating identification criteria for these materials in raw, worked and decayed states. The resource concentrates on the non-destructive visual methods of particular relevance to the examination of artworks, historic and archaeological artefacts. The chapter highlights the potential of various visualisation methods and digital technologies to capture and combine 2D images and 3D models and guide the viewer through the multi-scalar visual cues of each material to a reliable identification. By accessing a range of collections, the project has produced a comprehensive and accessible resource, disseminating these findings more widely than could be achieved by a physical reference collection. This resource supports the identification of cultural heritage objects for conservation scientists and heritage professionals and informs the fight against the illegal hunting and trafficking of rare and endangered species.
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Curious Travellers: Using web-scraped and crowd-sourced imagery in support of heritage under threatDesigned as a pragmatic approach that anticipates change to cultural heritage, this chapter discusses responses that encompass records for tangible cultural heritage (monuments, sites and landscapes) and the narratives that see the impact upon them. The Curious Travellers project provides a mechanism for digitally documenting heritage sites that have been destroyed or are under immediate threat from unsympathetic development, neglect, natural disasters, conflict and cultural vandalism. The project created and tested data-mining and crowd-sourced workflows that enable the accurate digital documentation and 3D visualisation of buildings, archaeological sites, monuments and heritage at risk. When combined with donated content, image data are used to recreate 3D models of endangered and lost monuments and heritage sites using a combination of open-source and proprietary methods. These models are queried against contextual information, helping to place and interrogate structures with relevant site and landscape data for the surrounding environment. Geospatial records such as aerial imagery and 3D mobile mapping laser scan data serve as a framework for adding new content and testing accuracy. In preserving time-event records, image metadata offers important information on visitor habits and conservation pressures, which can be used to inform measures for site management.
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Zirconium-based MOFs and their biodegradable polymer composites for controlled and sustainable delivery of herbicidesAdsorption and controlled release of agrochemicals has been studied widely using different nanomaterials and a variety of formulations. However, the potential for application of high surface-area metal-organic frameworks (MOFs) for the controlled release of agrochemicals has not been thoroughly explored. Herein, we report controlled and sustainable release of a widely used herbicide (2-methyl-4-chlorophenoxyacetic acid, MCPA) via incorporation in a range of zirconium-based MOFs and their biodegradable polymer composites. Three Zr-based MOFs, viz., UiO-66, UiO-66-NH2, and UiO-67 were loaded with MCPA either postsynthetically or in situ during synthesis of the MOFs. The MCPA-loaded MOFs were then incorporated into a biodegradable polycaprolactone (PCL) composite membrane. All three MOFs and their PCL composites were thoroughly characterized using FT-IR, TGA, SEM, PXRD, BET, and mass spectrometry. Release of MCPA from each of these MOFs and their PCL composites was then studied in both distilled water and in ethanol for up to 72 h using HPLC. The best performance for MCPA release was observed for the postsynthetically loaded MOFs, with PS-MCPA@UiO-66-NH2 showing the highest MCPA concentrations in ethanol and water of 0.056 and 0.037 mg/mL, respectively. Enhanced release of MCPA was observed in distilled water when the MOFs were incorporated in PCL. The concentrations of herbicides in the release studies provide us with a range of inhibitory concentrations that can be utilized depending on the crop, making this class of composite materials a promising new route for future agricultural applications.
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Generation and Use of Functional Hydrogels That Can Rapidly Sample Infected SurfacesThis paper outlined our method for developing polymer-linked contact lens type materials for rapid detection and differentiation of Gram-positive, Gram-negative bacteria and fungi in infected corneas. It can be applied to both model synthetic or ex-vivo corneal models and has been successfully trialed in an initial efficacy tested animal study. First a hydrogel substrate for the swab material is selected, we have demonstrated selective swabs using a glycerol monomethacrylate hydrogel. Alternatively any commercial material with carboxylic acid functional groups is suitable but risks nonspecific adhesion. This is then functionalised via use of N-hydroxysuccinimide reaction with amine groups on the specified highly branched polymer ligand (either individually gram negative, gram positive or fungal binding polymers or a combination of all three can be employed for desired sensing application). The hydrogel is then cut into swabs suitable for sampling, used, and then the presence of gram positive, game negative and fungi are disclosed by the sequential addition of dyes (fluorescent vancomycin, fluorescein isothiocyanate and calcofluor white). In summary this method presents: Method to produce glycerol monomethacrylate hydrogels to minimize nonspecific binding Methods of attaching pathogen binding highly branched polymers to produce selective hydrogel swabs Method for disclosing bound pathogens to this swab using sequential dye addition