• A Decade of Mighty Lipophagy: What We Know and What Facts We Need to Know?

      Academic Editor: Tatone, Carla; email: carla.tatone@univaq.it; Khawar, Muhammad Babar; orcid: 0000-0002-1812-0591; email: babarkhawar@yahoo.com; Abbasi, Muddasir Hassan; orcid: 0000-0001-7856-7013; email: dr.muddasir@uo.edu.pk; Rafiq, Mussarat; orcid: 0000-0002-0300-5339; email: mussaratrafiq369@gmail.com; Naz, Naila; orcid: 0000-0002-8864-0250; email: naila.naz@manchester.ac.uk; Mehmood, Rabia; orcid: 0000-0002-9356-2787; email: rabia.wzd@gmail.com; Sheikh, Nadeem; orcid: 0000-0001-9503-9538; email: nadeem.zool@pu.edu.pk (Hindawi, 2021-11-05)
      Lipids are integral cellular components that act as substrates for energy provision, signaling molecules, and essential constituents of biological membranes along with a variety of other biological functions. Despite their significance, lipid accumulation may result in lipotoxicity, impair autophagy, and lysosomal function that may lead to certain diseases and metabolic syndromes like obesity and even cell death. Therefore, these lipids are continuously recycled and redistributed by the process of selective autophagy specifically termed as lipophagy. This selective form of autophagy employs lysosomes for the maintenance of cellular lipid homeostasis. In this review, we have reviewed the current literature about how lipid droplets (LDs) are recruited towards lysosomes, cross-talk between a variety of autophagy receptors present on LD surface and lysosomes, and lipid hydrolysis by lysosomal enzymes. In addition to it, we have tried to answer most of the possible questions related to lipophagy regulation at different levels. Moreover, in the last part of this review, we have discussed some of the pathological states due to the accumulation of these LDs and their possible treatments under the light of currently available findings.
    • A deep learning approach to building an intelligent video surveillance system

      Xu, Jie; orcid: 0000-0002-2287-9971; email: jie.xu-4@student.manchester.ac.uk (Springer US, 2020-10-07)
      Abstract: Recent advances in the field of object detection and face recognition have made it possible to develop practical video surveillance systems with embedded object detection and face recognition functionalities that are accurate and fast enough for commercial uses. In this paper, we compare some of the latest approaches to object detection and face recognition and provide reasons why they may or may not be amongst the best to be used in video surveillance applications in terms of both accuracy and speed. It is discovered that Faster R-CNN with Inception ResNet V2 is able to achieve some of the best accuracies while maintaining real-time rates. Single Shot Detector (SSD) with MobileNet, on the other hand, is incredibly fast and still accurate enough for most applications. As for face recognition, FaceNet with Multi-task Cascaded Convolutional Networks (MTCNN) achieves higher accuracy than advances such as DeepFace and DeepID2+ while being faster. An end-to-end video surveillance system is also proposed which could be used as a starting point for more complex systems. Various experiments have also been attempted on trained models with observations explained in detail. We finish by discussing video object detection and video salient object detection approaches which could potentially be used as future improvements to the proposed system.
    • 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 Delphi Study Investigating Clinicians’ Views on Access to, Delivery of, and Adaptations of MBCT in the UK Clinical Settings

      Williams, Kate; orcid: 0000-0001-8167-0951; email: kate.williams-4@manchester.ac.uk; Hartley, Samantha; Taylor, Peter (Springer US, 2021-07-30)
      Abstract: Objectives: Mindfulness-based cognitive therapy (MBCT) is a well-evidenced relapse-prevention intervention for depression with a growing evidence-base for use in other clinical populations. The UK initiatives have outlined plans for increasing access to MBCT in clinical settings, although evidence suggests that access remains limited. Given the increased popularity and access to MBCT, there may be deviations from the evidence-base and potential risks of harm. We aimed to understand what clinicians believe should be best clinical practice regarding access to, delivery of, and adaptations to MBCT. Methods: We employed a two-stage Delphi methodology. First, to develop statements around best practices, we consulted five mindfulness-based experts and reviewed the literature. Second, a total of 59 statements were taken forward into three survey rating rounds. Results: Twenty-nine clinicians completed round one, with 25 subsequently completing both rounds two and three. Forty-four statements reached consensus; 15 statements did not. Clinicians agreed with statements regarding sufficient preparation for accessing MBCT, adherence to the evidence-base and good practice guidelines, consideration of risks, sufficient access to training, support, and resources within services, and carefully considered adaptations. The consensus was not reached on statements which reflected a lack of evidence-base for specific clinical populations or the complex decision-making processes involved in delivering and making adaptations to MBCT. Conclusions: Our findings highlight the delicate balance of maintaining a client-centred and transparent approach whilst adhering to the evidence-base in clinical decisions around access to, delivery of, and adaptations in MBCT and have important wide-reaching implications.
    • A diagnostic evaluation of single screen testing for malaria in the returning traveler: A large retrospective cohort study

      editor: Runyon, Michael S.; Reynard, Charles; orcid: 0000-0002-7534-2668; email: Charles.reynard@postgrad.manchester.ac.uk; Geary, Katie; Chiodini, Peter; Brereton, Michelle; Burthem, John; McDermott, John; van den Berg, Patricia; Body, Richard (2021-02-27)
      Abstract: Background: Screening for malaria in the returning traveler has often required repeat testing; however, audit data suggest that patients have not been reattending. We sought to ascertain if this was safe by examining the diagnostic efficacy of a single screen consisting of a rapid diagnostic test (RDT) and a thin film. Methods: We conducted a retrospective cohort study of patients with suspected malaria who attended in the past 5 years from two large teaching hospitals. We assessed the diagnostic accuracy of a single screen, reporting measures of sensitivity and specificity. To establish a reference standard, we cross‐linked data with the national malaria registry held at Public Health England and regional centers. Results: The cohort consisted of 1365 patients, of whom 33 opted out of the research and one did not have a complete initial screen. Of those 1331 screens there were 74 cases of Plasmodium falciparum (prevalence of 5.6%) and 104 of any malaria species (prevalence of 7.8%). Sensitivity for the detection of P. falciparum was 100.00% (95% confidence interval [CI] = 95.1 to 100), with a specificity of 99.4% (95% CI = 98.9 to 99.8). For the detection of any species of malaria the sensitivity was slightly lower due to the presence of one false negative; sensitivity was 99.0% (95% CI = 94.8 to 100) and specificity was 99.5% (95% CI = 98.9 to 99.8). Conclusions: A single thin film and RDT is likely to be sufficient as a first screen for falciparum malaria in the returning traveler with important caveats. For those sent home from emergency departments, appropriate safety netting must be provided. Further prospective study is required to investigate this approach.
    • 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 higher river sinuosity increased riparian soil structural stability on the downstream of a dammed river.

      Ran, Yiguo; email: ranyiguo@cigit.ac.cn; Liu, Yan; email: yan.liu-23@postgrad.manchester.ac.uk; Wu, Shengjun; email: wsj@cigit.ac.cn; Li, Wenjuan; email: liwenjuan@cigit.ac.cn; Zhu, Kai; email: zhukai@cigit.ac.cn; Ji, Yongyue; Mir, Yaseen; email: yaseenghp@mails.ucas.ac.cn; Ma, Maohua; email: mamaohua@cigit.ac.cn; Huang, Ping; email: huangping@cigit.ac.cn (2021-08-25)
      Hydropower dam constructions and operations have dramatically changed the original hydrological regime of natural rivers. Because of significantly slashed and suspended sediments blocked by damming, discharged "clear" water was found to play a strong undercutting effect on the riverbank and to exacerbate riparian soil erosion on the downstream near dams. Yet, it is still an unsettled issue whether the instability of riparian soil structure would be simply correlated negatively with the distance to a dam. In this study, soils along the downstream riparian zone of a huge dam on the River Yangtze, China, were sampled to examine the distance effect on the riparian soil structural stability. Water-stable aggregates were fractionated by the wet-sieving method. Mean weight diameter (MWD) and geometric mean diameter (GMD) were used to indicate riparian soil stability. Further, the fractal dimension (D) and soil erodibility parameter (K) were used to represent the likelihood of riparian erosion. Our results revealed that riparian soil structural stability demonstrated a high spatial heterogeneity along the River Yangtze, and was less affected by the spatial distance to the dam. Rather, the soil stability was primarily influenced by a river shape index (sinuosity) and local edaphic properties. The river sinuosity index demonstrated a positive relationship with soil structural stability. Additionally, soil organic matter was found as a major edaphic factor in stabilizing soil structure. The results indicated that river sinuosity plays a crucial role in stabilizing soil by accumulating soil organic matters. Our findings implied that the potential negative impact of damming effect on soil stability may be attenuated by maintaining a higher sinuosity of the river. Against the risk of riparian soil erosion along the dammed river, the configuration of river morphology shall be considered as one of the potential managements in offsetting the negative impacts of damming. [Abstract copyright: Copyright © 2021. Published by Elsevier B.V.]
    • 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 lesson from the wild: The natural state of eosinophils is Ly6G hi

      Mair, Iris; orcid: 0000-0002-7326-3114; email: iris.mair@manchester.ac.uk; Wolfenden, Andrew; Lowe, Ann E.; Bennett, Alex; orcid: 0000-0003-4869-9132; Muir, Andrew; orcid: 0000-0002-1461-8712; Smith, Hannah; orcid: 0000-0001-8911-9048; Fenn, Jonathan; orcid: 0000-0002-9255-6975; Bradley, Janette E.; orcid: 0000-0003-3973-7977; email: jan.bradley1@nottingham.ac.uk; Else, Kathryn J.; orcid: 0000-0001-6660-055X; email: Kathryn.else@manchester.ac.uk (2021-09-15)
      Abstract: With a long history of promoting pathological inflammation, eosinophils are now emerging as important regulatory cells. Yet, findings from controlled laboratory experiments so far lack translation to animals, including humans, in their natural environment. In order to appreciate the breadth of eosinophil phenotype under non‐laboratory, uncontrolled conditions, we exploit a free‐living population of the model organism Mus musculus domesticus. Eosinophils were present at significantly higher proportions in the spleen and bone marrow of wild mice compared with laboratory mice. Strikingly, the majority of eosinophils of wild mice exhibited a unique Ly6Ghi phenotype seldom described in laboratory literature. Ly6G expression correlated with activation status in spleen and bone marrow, but not peritoneal exudate cells, and is therefore likely not an activation marker per se. Intermediate Ly6G expression was transiently induced in a small proportion of eosinophils from C57BL/6 laboratory mice during acute infection with the whipworm Trichuris muris, but not during low‐dose chronic infection, which better represents parasite exposure in the wild. We conclude that the natural state of the eosinophil is not adequately reflected in the standard laboratory mouse, which compromises our attempts to dissect their functional relevance. Our findings emphasize the importance of studying the immune system in its natural context – alongside more mechanistic laboratory experiments – in order to capture the entirety of immune phenotypes and functions.
    • A Lucas–Lehmer approach to generalised Lebesgue–Ramanujan–Nagell equations

      Patel, Vandita; orcid: 0000-0003-0252-963X; email: vandita.patel@manchester.ac.uk (Springer US, 2021-06-10)
      Abstract: We describe a computationally efficient approach to resolving equations of the form C1x2+C2=yn in coprime integers, for fixed values of C1, C2 subject to further conditions. We make use of a factorisation argument and the Primitive Divisor Theorem due to Bilu, Hanrot and Voutier.
    • 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 mathematical model which examines age-related stochastic fluctuations in DNA maintenance methylation.

      Zagkos, Loukas; email: l.zagkos@imperial.ac.uk; Roberts, Jason; Auley, Mark Mc (2021-11-11)
      Due to its complexity and its ubiquitous nature the ageing process remains an enduring biological puzzle. Many molecular mechanisms and biochemical process have become synonymous with ageing. However, recent findings have pinpointed epigenetics as having a key role in ageing and healthspan. In particular age related changes to DNA methylation offer the possibility of monitoring the trajectory of biological ageing and could even be used to predict the onset of diseases such as cancer, Alzheimer's disease and cardiovascular disease. At the molecular level emerging evidence strongly suggests the regulatory processes which govern DNA methylation are subject to intracellular stochasticity. It is challenging to fully understand the impact of stochasticity on DNA methylation levels at the molecular level experimentally. An ideal solution is to use mathematical models to capture the essence of the stochasticity and its outcomes. In this paper we present a novel stochastic model which accounts for specific methylation levels within a gene promoter. Uncertainty of the eventual site-specific methylation levels for different values of methylation age, depending on the initial methylation levels were analysed. Our model predicts the observed bistable levels in CpG islands. In addition, simulations with various levels of noise indicate that uncertainty predominantly spreads through the hypermethylated region of stability, especially for large values of input noise. A key outcome of the model is that CpG islands with high to intermediate methylation levels tend to be more susceptible to dramatic DNA methylation changes due to increasing methylation age. [Abstract copyright: Copyright © 2021 Elsevier Inc. All rights reserved.]
    • 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.
    • 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.