• .

      Vasilogianni, Areti-Maria; orcid: 0000-0001-6665-6115; Achour, Brahim; orcid: 0000-0002-2595-5626; Scotcher, Daniel; orcid: 0000-0001-9144-3824; Peters, Sheila Annie; Al-Majdoub, Zubida M; orcid: 0000-0002-1497-3140; Barber, Jill; orcid: 0000-0002-5424-0291; Rostami-Hodjegan, Amin; orcid: 0000-0003-3917-844X; email: amin.rostami@manchester.ac.uk (2021-05-12)
      linked with physiologically based pharmacokinetic (PBPK) modelling is used to predict the fates of drugs in patients. Ideally, the IVIVE-PBPK models should incorporate "systems" information accounting for characteristics of the specific target population. There is a paucity of such scaling factors in cancer, particularly microsomal protein per gram of liver (MPPGL) and cytosolic protein per gram of liver (CPPGL). In this study, cancerous and histologically normal liver tissue from 16 patients with colorectal liver metastasis (CRLM) were fractionated to microsomes and cytosol. Protein content was measured in homogenates, microsomes and cytosol. The loss of microsomal protein during fractionation was accounted for using corrections based on NADPH cytochrome P450 reductase activity in different matrices. MPPGL was significantly lower in cancerous tissue (24.8 {plus minus} 9.8 mg/g) than histologically normal tissue (39.0 {plus minus} 13.8 mg/g). CPPGL in cancerous tissue was 42.1 {plus minus} 12.9 mg/g compared with 56.2 {plus minus} 16.9 mg/g in normal tissue. No correlations between demographics (sex, age and BMI) and MPPGL or CPPGL were apparent in the data. The generated scaling factors together with assumptions regarding the relative volumes of cancerous versus non-cancerous tissue were used to simulate plasma exposure of drugs with different extraction ratios. The PBPK simulations revealed a substantial difference in drug exposure (AUC), up to 3.3-fold, when using typical scaling factors (healthy population) instead of disease-related parameters in cancer population. These indicate the importance of using population-specific scalars in IVIVE-PBPK for different disease states. Accuracy in predicting the fate of drugs from in vitro data using IVIVE-PBPK depends on using correct scaling factors. The values for two of such scalars, namely microsomal and cytosolic protein per gram of liver, is not known in cancer patients. This study presents, for the first time, scaling factors from cancerous and matched histologically normal livers. PBPK simulations of various metabolically cleared drugs demonstrate the necessity of population-specific scaling for model-informed precision dosing in oncology. [Abstract copyright: Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics.]
    • .

      El-Khateeb, Eman; orcid: 0000-0002-8365-6528; email: eman.elkhateeb@manchester.ac.uk; Al-Majdoub, Zubida M; orcid: 0000-0002-1497-3140; Rostami-Hodjegan, Amin; orcid: 0000-0003-3917-844X; Barber, Jill; orcid: 0000-0002-5424-0291; Achour, Brahim; orcid: 0000-0002-2595-5626 (2021-05-27)
      Model-based assessment of the effects of liver disease on drug pharmacokinetics requires quantification of changes in enzymes and transporters responsible for drug metabolism and disposition. Different proteomic methods are currently used for protein quantification in tissues and systems, each with specific procedures and requirements. The outcome of quantitative proteomic assays from four different methods (one targeted and three label-free), applied to the same sample set, were compared in this study. Three pooled cirrhotic liver microsomal samples, corresponding to cirrhosis with non-alcoholic fatty liver disease, biliary disease or cancer, and a control microsomal pool, were analyzed using QconCAT-based targeted proteomics, the total protein approach (TPA), high three (Hi3) ion intensity approach, and intensity-based absolute quantification (iBAQ), to determine the absolute and relative abundance in disease compared with control. The relative abundance data provided a 'disease perturbation factor' (DPF) for each target protein. Absolute and relative abundances generated by standard-based label-free methods (iBAQ and Hi3) showed good agreement with targeted proteomics (limited bias and scatter) but TPA (standard-free method) over-estimated absolute abundances by approximately 2 fold. DPF was consistent between different proteomic methods but varied between enzymes and transporters, indicating discordance of effects of cirrhosis on various ADME proteins. DPF ranged from no change (e.g. for UGT1A6 in NAFLD group) to less than 0.3 (e.g. CES1 in cirrhosis of biliary origin). This study demonstrated that relative changes in enzymes and transporters (DPF) are independent of the quantitative proteomic methods used. Standard-based label-free methods such as high three ion intensity (Hi3) and intensity-based absolute quantification (iBAQ) methods, were less biased and more precise than the total protein approach (TPA), when compared with targeted data. The DPF reconciled differences across proteomic methods observed with absolute levels. Using this approach, differences were revealed in the expression of enzymes/transporters in cirrhosis associated with different etiologies. [Abstract copyright: Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics.]
    • A Bayesian Estimation of Child Labour in India

      Kim, Jihye; email: jihye.kim@postgrad.manchester.ac.uk; Olsen, Wendy; Wiśniowski, Arkadiusz (Springer Netherlands, 2020-06-18)
      Abstract: Child labour in India involves the largest number of children in any single country in the world. In 2011, 11.8 million children between the ages of 5 and 17 were main workers (those working more than 6 mo) according to the Indian Census. Our estimate of child labour using a combined-data approach is slightly higher than that: 13.2 million (11.4–15.2 million) for ages 5 to 17. There are various opinions on how best to measure the prevalence of child labour. In this study, we use the International Labour Organization (ILO)‘s methodology to define hazardousness and combine it with the most recent United Nations Children’s Fund (UNICEF)‘s time thresholds for economic work and household chores. The specific aims of this study are to estimate the prevalence of child labour in the age group 5 to 17 and to suggest a combined-data approach using Bayesian inference to improve the accuracy of the child labour estimation. This study combines the National Sample Survey on Employment and Unemployment 2011/12 and the India Human Development Survey 2011/12 and compares the result with the reported figures for the incidence of child labour from the Indian Census. Our unique combined-data approach provides a way to improve accuracy, smooth the variations between ages and provide reliable estimates of the scale of child labour in India.
    • A breakthrough from 60 years ago: “General nature of the genetic code for proteins” (1961)

      Cobb, Matthew; orcid: 0000-0002-8258-4913; email: cobb@manchester.ac.uk (2021-06-07)
      Abstract: In 1961, Francis Crick and Sydney Brenner, together with two Cambridge colleagues, published an article in Nature that used simple genetic experiments to demonstrate that the genetic code was almost certainly based on groups of three nucleotides. Six decades later, this article continues to be an inspiration to scientists due to its elegant argumentation and its use of simple, powerful experimentation to reveal fundamental truths about the organisation of living matter. This essay explores how and why the research was carried out, showing how the aims of the experiment gradually changed over time, and highlighting how the intense intellectual interactions between Crick and Brenner contributed to this model of scientific endeavour.
    • A case of chain propagation: α-aminoalkyl radicals as initiators for aryl radical chemistry.

      Constantin, Timothée; orcid: 0000-0001-5376-1557; Juliá, Fabio; orcid: 0000-0001-8903-4482; Sheikh, Nadeem S; orcid: 0000-0002-0716-7562; Leonori, Daniele; orcid: 0000-0002-7692-4504 (2020-10-20)
      The generation of aryl radicals from the corresponding halides by redox chemistry is generally considered a difficult task due to their highly negative reduction potentials. Here we demonstrate that α-aminoalkyl radicals can be used as both initiators and chain-carriers for the radical coupling of aryl halides with pyrrole derivatives, a transformation often employed to evaluate new highly reducing photocatalysts. This mode of reactivity obviates for the use of strong reducing species and was also competent in the formation of sp C-P bonds. Mechanistic studies have delineated some of the key features operating that trigger aryl radical generation and also propagate the chain process. [Abstract copyright: This journal is © The Royal Society of Chemistry.]
    • A case of chain propagation: α-aminoalkyl radicals as initiators for aryl radical chemistry.

      Constantin, Timothée; orcid: 0000-0001-5376-1557; Juliá, Fabio; orcid: 0000-0001-8903-4482; Sheikh, Nadeem S; orcid: 0000-0002-0716-7562; Leonori, Daniele; orcid: 0000-0002-7692-4504 (2020-10-20)
      The generation of aryl radicals from the corresponding halides by redox chemistry is generally considered a difficult task due to their highly negative reduction potentials. Here we demonstrate that α-aminoalkyl radicals can be used as both initiators and chain-carriers for the radical coupling of aryl halides with pyrrole derivatives, a transformation often employed to evaluate new highly reducing photocatalysts. This mode of reactivity obviates for the use of strong reducing species and was also competent in the formation of sp<sup>2</sup> C-P bonds. Mechanistic studies have delineated some of the key features operating that trigger aryl radical generation and also propagate the chain process.
    • A Case Study of a Negotiated Tender within a Small-to-Medium Construction Contractor: Modelling Project Cost Variance

      Ellis, James; email: james_ellis1998@me.com; Edwards, David John; email: drdavidedwards@aol.com; Thwala, Wellington Didibhuku; email: didi-bhukut@uj.ac.za; Ejohwomu, Obuks; orcid: 0000-0001-7098-8999; email: obuks.ejohwomu@manchester.ac.uk; Ameyaw, Ernest Effah; email: ernest.ameyaw@northumbria.ac.uk; Shelbourn, Mark; email: mark.shelbourn@bcu.ac.uk (MDPI, 2021-06-18)
      This research explores the failure of competitively tendered projects in the UK construction industry to procure the most suited contractor(s) to conduct the works. Such work may have equal relevance for other developed nations globally. This research seeks to teach clients and their representatives that “lowest price” does not mean “best value”, by presenting a case study of a successfully negotiated tender undertaken by a small-to-medium enterprise (SME) contractor; SME studies are relatively scant in academic literature. By applying the “lessons learnt” principle, this study seeks to improve future practice through the development of a novel alternative procurement option (i.e., negotiation). A mixed philosophical stance combining interpretivism and pragmatism was used—interpretivism to critically review literature in order to form the basis of inductive research to discuss negotiation as a viable procurement route, and pragmatism to analyse perceptions of tendering and procurement. The methods used follow a three-stage waterfall process including: (1) literature review and pilot study; (2) quantitative analysis of case study data; and (3) qualitative data collection via a focus group. Our research underscores the need to advise clients and their representatives of the importance of understanding the scope of works allowed within a tender submission before discounting it based solely on price. In addition, we highlight the failings of competitive tendering, which results in increased costs and project duration once the works commence on site. These findings provide new contemporary insight into procurement and tendering in the construction industry, with emphasis on SME contractors, existing relationships, and open-book negotiation. This research illustrates the adverse effects of early cost estimates produced without first securing a true understanding of project buildability and programming. Our work concludes with a novel insight into an alternative procurement option that involves early SME contractor involvement in an open-book environment, without the need for a third-party cost control.
    • A catalysis-driven artificial molecular pump.

      Amano, Shuntaro; orcid: 0000-0001-6017-6823; Fielden, Stephen D P; orcid: 0000-0001-7883-8135; Leigh, David A; orcid: 0000-0002-1202-4507; email: david.leigh@manchester.ac.uk (2021-06-23)
      All biological pumps are autonomous catalysts; they maintain the out-of-equilibrium conditions of the cell by harnessing the energy released from their catalytic decomposition of a chemical fuel . A number of artificial molecular pumps have been reported to date , but they are all either fuelled by light or require repetitive sequential additions of reagents or varying of an electric potential during each cycle to operate . Here we describe an autonomous chemically fuelled information ratchet that in the presence of fuel continuously pumps crown ether macrocycles from bulk solution onto a molecular axle without the need for further intervention. The mechanism uses the position of a crown ether on an axle both to promote barrier attachment behind it upon threading and to suppress subsequent barrier removal until the ring has migrated to a catchment region. Tuning the dynamics of both processes enables the molecular machine to pump macrocycles continuously from their lowest energy state in bulk solution to a higher energy state on the axle. The ratchet action is experimentally demonstrated by the progressive pumping of up to three macrocycles onto the axle from bulk solution under conditions where barrier formation and removal occur continuously. The out-of-equilibrium [n]rotaxanes (characterized with n up to 4) are maintained for as long as unreacted fuel is present, after which the rings slowly de-thread. The use of catalysis to drive artificial molecular pumps opens up new opportunities, insights and research directions at the interface of catalysis and molecular machinery.
    • A Cross-Sectional Study Investigating the Relationship Between Alexithymia and Suicide, Violence, and Dual Harm in Male Prisoners

      Hemming, Laura; Shaw, Jennifer; Haddock, Gillian; Carter, Lesley-Anne; Pratt, Daniel; email: daniel.pratt@manchester.ac.uk (Frontiers Media S.A., 2021-04-29)
      Background: Suicide and violence are common within male prisoners. One suggested risk factor for both behaviors is alexithymia. Alexithymia describes a deficit in identifying and describing feelings and is also related to externally oriented thinking. This study aimed to explore the relationship between alexithymia, suicide, violence and dual harm in male prisoners. Methods: Eighty male prisoners were recruited from three prisons. Participants were asked to complete a battery of questionnaires including measures of alexithymia (TAS-20), suicide ideation (ASIQ), suicide behavior, violence ideation (SIV), violence behavior, depression (BDI-II), hopelessness (BHS), impulsivity (DII) and anger (NAS-PI). Regression analyses and ANOVAS were conducted to assess the association between alexithymia (and its subcomponents) with six outcomes; suicide ideation, suicide behavior, violence ideation, violence behavior, dual harm ideation and dual harm behavior. Results: Alexithymia was a univariate predictor of suicide ideation, though was not a significant predictor when considered in a multivariate model. Alexithymia was a significant multivariate predictor of suicide behavior. Alexithymia was not a significant multivariate predictor of violence ideation or behavior. There were no significant differences in alexithymia or subscales between those with suicide ideation/behavior alone, violence ideation/behavior alone and those with dual harm ideation/behavior. Conclusion: In male prisoners, alexithymia appears an important univariate predictor of suicide and violence, though the current study suggests no significant contribution above other well-known correlates of suicide and violence.
    • A deep-learning model for urban traffic flow prediction with traffic events mined from twitter

      Essien, Aniekan; orcid: 0000-0001-9501-0647; email: a.e.essien@swansea.ac.uk; email: aniekan.essien@manchester.ac.uk; Petrounias, Ilias; Sampaio, Pedro; Sampaio, Sandra (Springer US, 2020-03-14)
      Abstract: Short-term traffic parameter forecasting is critical to modern urban traffic management and control systems. Predictive accuracy in data-driven traffic models is reduced when exposed to non-recurring or non-routine traffic events, such as accidents, road closures, and extreme weather conditions. The analytical mining of data from social networks – specifically twitter – can improve urban traffic parameter prediction by complementing traffic data with data representing events capable of disrupting regular traffic patterns reported in social media posts. This paper proposes a deep learning urban traffic prediction model that combines information extracted from tweet messages with traffic and weather information. The predictive model adopts a deep Bi-directional Long Short-Term Memory (LSTM) stacked autoencoder (SAE) architecture for multi-step traffic flow prediction trained using tweets, traffic and weather datasets. The model is evaluated on an urban road network in Greater Manchester, United Kingdom. The findings from extensive empirical analysis using real-world data demonstrate the effectiveness of the approach in improving prediction accuracy when compared to other classical/statistical and machine learning (ML) state-of-the-art models. The improvement in predictive accuracy can lead to reduced frustration for road users, cost savings for businesses, and less harm to the environment.
    • A Double-Level Model Checking Approach for an Agent-Based Autonomous Vehicle and Road Junction Regulations

      Alves, Gleifer Vaz; orcid: 0000-0002-5937-8193; email: gleifer@utfpr.edu.br; Dennis, Louise; orcid: 0000-0003-1426-1896; email: louise.dennis@manchester.ac.uk; Fisher, Michael; orcid: 0000-0002-0875-3862; email: michael.fisher@manchester.ac.uk (MDPI, 2021-06-25)
      Usually, the design of an Autonomous Vehicle (AV) does not take into account traffic rules and so the adoption of these rules can bring some challenges, e.g., how to come up with a Digital Highway Code which captures the proper behaviour of an AV against the traffic rules and at the same time minimises changes to the existing Highway Code? Here, we formally model and implement three Road Junction rules (from the UK Highway Code). We use timed automata to model the system and the MCAPL (Model Checking Agent Programming Language) framework to implement an agent and its environment. We also assess the behaviour of our agent according to the Road Junction rules using a double-level Model Checking technique, i.e., UPPAAL at the design level and AJPF (Agent Java PathFinder) at the development level. We have formally verified 30 properties (18 with UPPAAL and 12 with AJPF), where these properties describe the agent’s behaviour against the three Road Junction rules using a simulated traffic scenario, including artefacts like traffic signs and road users. In addition, our approach aims to extract the best from the double-level verification, i.e., using time constraints in UPPAAL timed automata to determine thresholds for the AVs actions and tracing the agent’s behaviour by using MCAPL, in a way that one can tell when and how a given Road Junction rule was selected by the agent. This work provides a proof-of-concept for the formal verification of AV behaviour with respect to traffic rules.
    • A dynamic, spatially periodic, micro‐pattern of HES5 underlies neurogenesis in the mouse spinal cord

      Biga, Veronica; orcid: 0000-0001-9592-385X; Hawley, Joshua; orcid: 0000-0003-2122-7530; Soto, Ximena; orcid: 0000-0003-2680-1837; Johns, Emma; orcid: 0000-0002-6383-055X; Han, Daniel; orcid: 0000-0002-9088-1651; Bennett, Hayley; Adamson, Antony D; orcid: 0000-0002-5408-0013; Kursawe, Jochen; orcid: 0000-0002-0314-9623; Glendinning, Paul; Manning, Cerys S; orcid: 0000-0001-8656-5878; email: cerys.manning@manchester.ac.uk; et al. (2021-05-25)
      Abstract: Ultradian oscillations of HES Transcription Factors (TFs) at the single‐cell level enable cell state transitions. However, the tissue‐level organisation of HES5 dynamics in neurogenesis is unknown. Here, we analyse the expression of HES5 ex vivo in the developing mouse ventral spinal cord and identify microclusters of 4–6 cells with positively correlated HES5 level and ultradian dynamics. These microclusters are spatially periodic along the dorsoventral axis and temporally dynamic, alternating between high and low expression with a supra‐ultradian persistence time. We show that Notch signalling is required for temporal dynamics but not the spatial periodicity of HES5. Few Neurogenin 2 cells are observed per cluster, irrespective of high or low state, suggesting that the microcluster organisation of HES5 enables the stable selection of differentiating cells. Computational modelling predicts that different cell coupling strengths underlie the HES5 spatial patterns and rate of differentiation, which is consistent with comparison between the motoneuron and interneuron progenitor domains. Our work shows a previously unrecognised spatiotemporal organisation of neurogenesis, emergent at the tissue level from the synthesis of single‐cell dynamics.
    • A Eulerian–Lagrangian Coupled Method for the Simulation of Submerged Granular Column Collapse

      Wang, Chun; email: chunwang@sjtu.edu.cn; Ye, Guanlin; email: ygl@sjtu.edu.cn; Meng, Xiannan; email: xiannan.meng@manchester.ac.uk; Wang, Yongqi; orcid: 0000-0003-1292-0384; email: wang@fdy.tu-darmstadt.de; Peng, Chong; email: pengchong07@gmail.com (MDPI, 2021-06-03)
      A two-fluid Eulerian–Lagrangian coupled model is developed to investigate the complex interactions between solid particles and the ambient water during the process of submerged granular column collapse. In this model, the water phase is considered to be a Newtonian fluid, whereas the granular column is modeled as an elastic–perfectly plastic material. The water flow field is calculated by the mesh-based Eulerian Finite Volume Method (FVM), with the free surface captured by the Volume-of-Fluid (VOF) technique. The large deformation of the granular material is simulated by the mesh-free, particle-based Lagrangian Smoothed Particle Hydrodynamics method (SPH). Information transfer between Eulerian nodes and Lagrangian particles is performed by the aid of the SPH interpolation function. Both dry and submerged granular column collapses are simulated with the proposed model. Experiments of the submerged cases are also conducted for comparison. Effects of dilatancy (compaction) of initially dense (loose) packing granular columns on the mixture dynamics are investigated to reveal the mechanisms of different flow regimes. Pore water pressure field and granular velocity field are in good agreement between our numerical results and experimental observations, which demonstrates the capability of the proposed Eulerian–Lagrangian coupled method in dealing with complex submerged water–granular mixture flows.
    • A focus group study of older Chinese people with CVD patients in the North West of the UK.

      Speed, Shaun; Sun, Zeyuan; Liu, Zhenmi (2021-06-03)
      Cardiovascular disease (CVD) is the leading cause of death for Chinese migrants around the world. Chinese CVD patients rely heavily on their native Chinese language, cultural values and beliefs, which adds challenges for the healthcare providers to offer primary healthcare services with standard protocol. The inappropriate treatment could lead to life loss, mistrust in doctor-patient relationship and heavy burden for healthcare funding. 28 participants were included for focus group study with the grounded theory methodology. There is considerable misunderstanding among the Chinese community about the role of primary care doctors in the treatment of cardiovascular disease resulting in the variable use of primary care services. Chinese CVD patients or identified risk factors for CVD arguably need closer management, culturally sensitive advice, support and robust follow-up compared to the general population. Doctors and nurses should enhance their practice and give them confidence in their interaction with Chinese patients on the basis of how they think and behave in relation to help seeking.
    • : a generic computer program for Monte Carlo modelling of crystal growth.

      Hill, Adam R; orcid: 0000-0002-1877-2231; Cubillas, Pablo; Gebbie-Rayet, James T; Trueman, Mollie; de Bruyn, Nathan; Harthi, Zulaikha Al; orcid: 0000-0002-1962-7490; Pooley, Rachel J S; Attfield, Martin P; orcid: 0000-0001-6508-1751; Blatov, Vladislav A; orcid: 0000-0002-4048-7218; Proserpio, Davide M; orcid: 0000-0001-6597-9406; et al. (2020-11-18)
      A Monte Carlo crystal growth simulation tool, , is described which is able to simultaneously model both the crystal habit and nanoscopic surface topography of any crystal structure under conditions of variable supersaturation or at equilibrium. This tool has been developed in order to permit the rapid simulation of crystal surface maps generated by scanning probe microscopies in combination with overall crystal habit. As the simulation is based upon a coarse graining at the nanoscopic level features such as crystal rounding at low supersaturation or undersaturation conditions are also faithfully reproduced. permits the incorporation of screw dislocations with arbitrary Burgers vectors and also the investigation of internal point defects in crystals. The effect of growth modifiers can be addressed by selective poisoning of specific growth sites. The tool is designed for those interested in understanding and controlling the outcome of crystal growth through a deeper comprehension of the key controlling experimental parameters. [Abstract copyright: This journal is © The Royal Society of Chemistry.]
    • A Global Survey of Current Zoo Housing and Husbandry Practices for Fossa: A Preliminary Review

      Harley, Jessica J.; orcid: 0000-0002-9355-9641; email: 1914124@chester.ac.uk; O’Hara, Lisa; email: education@taytopark.ie; Rose, Paul E.; orcid: 0000-0002-5375-8267; email: p.rose@exeter.ac.uk (MDPI, 2021-07-20)
      The fossa is a specialized Malagasy carnivore housed in ex situ facilities since the late 19th century. Moderate breeding success has occurred since the 1970s, and welfare issues (notably stereotypic pacing behaviour) are commonly documented. To understand challenges relating to fossa housing and husbandry (H) across global facilities and to identify areas of good practice that dovetail with available husbandry standards, a survey was distributed to ZIMS-registered zoos in 2017. Results showed that outdoor housing area and volume varied greatly across facilities, the majority of fossa expressed unnatural behaviours, with pacing behaviour the most frequently observed. All fossa received enrichment, and most had public access restricted to one or two sides of the enclosure. The majority of fossa were locked in/out as part of their daily management and forty-one percent of the fossa surveyed as breeding individuals bred at the zoo. Dense cover within an enclosure, restricted public viewing areas, a variable feeding schedule and limited view of another species from the fossa exhibit appear to reduce the risk of unnatural behavior being performed. The achievement of best practice fossa husbandry may be a challenge due to its specialized ecology, the limited wild information guiding captive care, and the range of housing dimensions and exhibit features provided by zoos that makes identification of standardized practices difficult. We recommended that holders evaluate how and when enrichment is provided and assess what they are providing for environmental complexity as well as consider how the public views their fossa.
    • A leftward bias for the arrangement of consumer items that differ in attractiveness

      Rodway, Paul; orcid: 0000-0002-7667-6782; Schepman, Astrid; orcid: 0000-0002-7407-362X (Informa UK Limited, 2020-06-24)
    • A massively multi-scale approach to characterizing tissue architecture by synchrotron micro-CT applied to the human placenta

      Tun, W. M.; orcid: 0000-0003-0991-8785; Poologasundarampillai, G.; orcid: 0000-0002-8498-323X; Bischof, H.; Nye, G.; King, O. N. F.; orcid: 0000-0002-6152-7207; Basham, M.; orcid: 0000-0002-8438-1415; Tokudome, Y.; Lewis, R. M.; orcid: 0000-0003-4044-9104; Johnstone, E. D.; Brownbill, P.; orcid: 0000-0002-8328-7072; email: paul.brownbill@manchester.ac.uk; et al. (The Royal Society, 2021-06-02)
      Multi-scale structural assessment of biological soft tissue is challenging but essential to gain insight into structure–function relationships of tissue/organ. Using the human placenta as an example, this study brings together sophisticated sample preparation protocols, advanced imaging and robust, validated machine-learning segmentation techniques to provide the first massively multi-scale and multi-domain information that enables detailed morphological and functional analyses of both maternal and fetal placental domains. Finally, we quantify the scale-dependent error in morphological metrics of heterogeneous placental tissue, estimating the minimal tissue scale needed in extracting meaningful biological data. The developed protocol is beneficial for high-throughput investigation of structure–function relationships in both normal and diseased placentas, allowing us to optimize therapeutic approaches for pathological pregnancies. In addition, the methodology presented is applicable in the characterization of tissue architecture and physiological behaviours of other complex organs with similarity to the placenta, where an exchange barrier possesses circulating vascular and avascular fluid spaces.
    • A massively multi-scale approach to characterizing tissue architecture by synchrotron micro-CT applied to the human placenta

      Tun, W. M.; orcid: 0000-0003-0991-8785; Poologasundarampillai, G.; orcid: 0000-0002-8498-323X; Bischof, H.; Nye, G.; King, O. N. F.; orcid: 0000-0002-6152-7207; Basham, M.; orcid: 0000-0002-8438-1415; Tokudome, Y.; Lewis, R. M.; orcid: 0000-0003-4044-9104; Johnstone, E. D.; Brownbill, P.; orcid: 0000-0002-8328-7072; et al. (The Royal Society, 2021-06-02)
      Multi-scale structural assessment of biological soft tissue is challenging but essential to gain insight into structure–function relationships of tissue/organ. Using the human placenta as an example, this study brings together sophisticated sample preparation protocols, advanced imaging and robust, validated machine-learning segmentation techniques to provide the first massively multi-scale and multi-domain information that enables detailed morphological and functional analyses of both maternal and fetal placental domains. Finally, we quantify the scale-dependent error in morphological metrics of heterogeneous placental tissue, estimating the minimal tissue scale needed in extracting meaningful biological data. The developed protocol is beneficial for high-throughput investigation of structure–function relationships in both normal and diseased placentas, allowing us to optimize therapeutic approaches for pathological pregnancies. In addition, the methodology presented is applicable in the characterization of tissue architecture and physiological behaviours of other complex organs with similarity to the placenta, where an exchange barrier possesses circulating vascular and avascular fluid spaces.
    • A method for the measurement of mass and number of graphene oxide sheets in suspension based on non-spherical approximations

      Crica, Livia Elena; orcid: 0000-0002-9665-0862; Dennison, Thomas James; Guerini, Elise Andrea; Kostarelos, Kostas; orcid: 0000-0002-2224-6672; email: kostas.kostarelos@manchester.ac.uk (IOP Publishing, 2021-06-02)
      Abstract: Currently, particle analysis of 2D materials in suspension is commonly restricted to microscopic techniques in the dry state, and thus does not permit an accurate investigation of colloidal suspensions. Colloids in bulk can be assessed by light scattering and diffraction to investigate features such as their hydrodynamic size, charge and concentration. However, the main drawback of such techniques lies in the application of analytical and computational methods based on models assuming particle sphericity which are not representative for 2D materials. Resonance mass measurement (RMM) is a technique which can enable the analysis of 2D materials in suspension without the assumptions of spherical models. Here, we report the application of RMM to measure particle mass and concentration for three types of graphene oxide (GO) aqueous dispersions. Using micro- and nano-suspended resonating sensors, we were able to decipher gravimetric differences between GO and graphitic materials. Our results support the urge for proper definitions and standardisations of graphene based materials, and offer a new method of characterisation for 2D material colloids in liquid suspension.