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Towards detection of structurally-diverse glycated epitopes in native proteins : single-chain antibody directed to non-A1c epitope in human haemoglobin
Get PDFOver 500 million people worldwide are affected by diabetes mellitus, a chronic disease that leads to high blood glucose levels and causes severe side effects. The predominant biological marker for diagnosis of diabetes is glycated haemoglobin (GHb). In human blood the predominant reducing sugar, glucose, irreversibly conjugates onto accessible amine groups within Hb. Most methods for diagnosis and monitoring of diabetes selectively detect N-terminal glycation at Val-1 on the β-globin chain, but not glycation at other sites. Detection of other glycated epitopes of GHb has the potential to provide new information on the extent, duration and timing of elevated glucose, facilitating personalised diagnosis and intelligent diabetic control. In this work, a new anti-GHb Fab antibody (Fab-1) specific for haemoglobin A1c (HbA1c) with nanomolar affinity was discovered via epitope-directed immunisation and phage display. A single chain variable fragment (scFv) antibody derived from Fab-1 retained affinity and specificity for HbA1c, and affinity was enhanced tenfold upon addition of an enhanced green fluorescent protein tag. Both the scFv and Fab-1 recognised an epitope within HbA1c that was distinct from β-Val-1, and our data suggest that this epitope may include glycation at Lys-66 in the β-globin chain. To our knowledge, this is the first report of an scFv/Fab anti-glycated epitope antibody that recognises a non-A1c epitope in GHb, and confirms that fructosamine attached to different, discrete glycation sites within the same protein can be resolved from one another by immunoassay. [Abstract copyright: Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
Ca2+ signatures in symbiosis : another level of dynamism for this key messenger
Get PDFThis article comments on: Binci F, Offer E, Crosino A, Sciascia I, Kleine-Vehn J, Genre A, Giovannetti M, Navazio L. 2024. Spatially and temporally distinct Ca2+ changes in Lotus japonicus roots orient fungal-triggered signalling pathways towards symbiosis or immunity. Journal of Experimental Botany 75,605–619
Improved carrier phase recovery for high-capacity optical communication systems with high-order modulation formats
No full textA modified Viterbi-Viterbi (MVV) carrier phase recovery (CPR) algorithm is comprehensively studied based on the quadrature phase-shift-keying (QPSK) partition scheme. By improving the QPSK partition scheme for the 16-ary quadrature amplitude modulation (16QAM), MVV algorithm is developed for the optical fiber communication systems with the modulation formats of dual-polarization 64-QAM (DP-64QAM) and DP-256QAM. Numerical simulations have been carried out in a 9-channel Nyquist-spaced 32-Gbaud optical transmission system for different modulation formats and the performance of MVV CPR with respect to pilot-aided (PA) CPR has been examined. Results show that MVV CPR can significantly mitigate the laser phase noise in the system using high-order modulation formats. Compared to PA CPR, MVV CPR performs better with the increase of the transmission distance, where the impact of equalization enhanced phase noise has to be taken into account. Furthermore, MVV has been compared with other CPR approaches in terms of the performance and the computational complexity
Arts & cultural organisations in cultures of sustainability
Get PDFPaper and presentation delivered to the programme on Sustainability, Humak University of Applied Sciences, Helsinki, directed by Dr Marcin Proprawski: 12 October 2023. Lecture title: ‘Arts & Cultural Organisations in Cultures of Sustainability’ by Dr Jonathan Vickery, Reader in Cultural Policy Studies, Centre for Cultural and Media Policy Studie
Understanding of Lithium-ion battery degradation using multisine-based nonlinear characterization method
No full textThe nonlinearity of lithium-ion battery voltage response has been recently gained high attention in battery characterization and health diagnosis. The multisine-based nonlinear characterization method has the potential for development as an expedient on-board technique for analyzing nonlinear responses. Despite this, it remains challenging to analyze the effect of aging degradation on LIB nonlinearity. In this study, the odd random-phase multisine method is performed on fresh and aged three-electrode experimental cells. This allowed for the separation of impedance-related linear approximation and odd or even order nonlinearity toward the full-cell voltage into their respective electrodes. The results demonstrate that, as the LIB degrades, the increase of impedance-related linear approximation estimated by the multisine-based method agrees well with the results of conventional EIS. The variation of nonlinearities is demonstrated in relation to the effect of degradation modes. The multisine-based method presents the advantage of simultaneously capturing impedance-related and nonlinearity information. This makes it become a fast diagnostic method that can be implemented in a BMS to quantify the causes of battery degradation, thereby supporting battery utilization optimization and future battery designs
Spectrogram-driven convolutional neural network for real-time non-invasive hyperglycaemia detection in paediatric Type-1 diabetes via wearable sensors
No full textReal-time detection of glycaemic events is crucial in the effective management of type 1 diabetes, particularly in paediatric patients. Recent advances in wearable sensors and machine learning have allowed for the inference of glycaemic events based on non-invasive physiological signals such as electrocardiogram (ECG). However, existing approaches have limitations due to the limited number of ECG features analysed and their applicability to real-life conditions. To overcome these limitations, we propose a spectrogram-driven deep learning methodology for real-time glycaemic event detection. We calculated beat-level spectrograms using Short Time Fourier Transform (STFT) on ECG beats extracted from continuous signals using our deep learning ECG segmentation tool. Subject-specific multi-layer 2D convolutional neural networks were trained on the spectrograms. We evaluated our methodology on an original dataset comprising continuous ECG and interstitial glucose data collected from children with type-1 diabetes over several days in real-life conditions. Our approach achieved an average personalised hyperglycaemia detection accuracy of 96.9%
Modelling and predicting online vaccination views using bow-tie decomposition
No full textSocial media has become increasingly important in shaping public vaccination views, especially since the COVID-19 outbreak. This paper uses bow-tie structure to analyse a temporal dataset of directed online social networks that represent the information exchange among anti-vaccination, pro-vaccination, and neutral Facebook pages. Bow-tie structure decomposes a network into seven components, with two components “SCC” and “OUT” emphasised in this paper: SCC is the largest strongly connected component, acting as an “information magnifier”, and OUT contains all nodes with a directed path from a node in SCC, acting as an “information creator”. We consistently observe statistically significant bow-tie structures with different dominant components for each vaccination group over time. In particular, the anti-vaccination group has a large OUT, and the pro-vaccination group has a large SCC. We further investigate changes in opinions over time, as measured by fan count variations, using agent-based simulations and machine learning models. Across both methods, accounting for bow-tie decomposition better reflects information flow differences among vaccination groups and improves our opinion dynamics prediction results. The modelling frameworks we consider can be applied to any multi-stance temporal network and could form a basis for exploring opinion dynamics using bow-tie structure in a wide range of applications
Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes
Get PDFBackground
Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network.
Methods
We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were overlayed with patient contacts to imply potential transmission events.
Results
Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations.
Conclusions
Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks
The Festival of India : development and diplomacy at the end of the cold war
No full textThis element is the first in-depth study of the Festival of India (1985-1986) in the United States, one of the biggest events ever mounted to promote goodwill between two countries. Comprising more than seven hundred programs of music, dance, drama, film shows, art exhibitions, and workshops sponsored by over two hundred cultural institutions across over a hundred cities, the festival constituted a prismatic event that refracted the complex forces at play on the global stage during the 1980s. The element delineates how this multi-sited spectacle of unprecedented size and near unfathomable political, economic, and cultural influence impacted theatre and performance studies. Simultaneously, it traces how two complex historical shifts were communicated to the global public at the end of the Cold War: India’s desire to transition from planned Nehruvian socialism to laissez faire capitalism and the efflorescence of the model of ‘cultural development’ that centred the arts in development