Electroencephalogram (EEG) analysis has been widely used in the diagnosis of stroke diseases for its low cost and noninvasive characteristics. In order to classify the EEG signals of stroke patients ...with cerebral infarction and cerebral hemorrhage, this paper proposes a novel EEG stroke signal classification method. This method has two highlights. The first is that a multi-feature fusion method is given by combining wavelet packet energy, fuzzy entropy and hierarchical theory. The second highlight is that a suitable classification model based on ensemble classifier is constructed for perfectly classification stroke signals. Entropy is an accessible way to measure information and uncertainty of time series. Many entropy-based methods have been developed these years. By comparing with the performances of permutation entropy, sample entropy, approximate entropy in measuring the characteristic of stroke patient’s EEG signals, it can be found that fuzzy entropy has best performance in characterization stroke EEG signal. By combining hierarchical theory, wavelet packet energy and fuzzy entropy, a multi-feature fusion method is proposed. The method first calculates wavelet packet energy of EEG stroke signal, then extracts hierarchical fuzzy entropy feature by combining hierarchical theory and fuzzy entropy. The experimental results show that, compared with the fuzzy entropy feature, the classification accuracy based on the fusion feature of wavelet packet energy and hierarchical fuzzy entropy is much higher than benchmark methods. It means that the proposed multi-feature fusion method based on stroke EEG signal is an efficient measure in classifying ischemic and hemorrhagic stroke. Support vector machine (SVM), decision tree and random forest are further used as the stroke signal classification models for classifying ischemic stroke and hemorrhagic stroke. Experimental results show that, based on the proposed multi-feature fusion method, the ensemble method of random forest can get the best classification performance in accuracy among three models.
Hallux valgus (HV), the bunion of the first metatarsophalangeal joint (MTPJ), bothers many adults. No consensus has been reached about the causes of HV, be it a hereditary, or acquired, or ...multifactorial disease. Nor has agreement been reached using MTPJ angle to assess HV based on X-ray because in most cases the assessment of MTPJ is not reliable as it depends on the posture during scanning. In this study, we assume that HV is predominately acquired and that shoe wearing
per se
is an important player in HV pathogenesis. To verify our hypothesis, a CT-based finite element (FE) model of the first MTPJ of fossil remains of bear-footed
Homo naledi
was created and compared to that of five contemporary shoe-wearing wrestlers (10 models from two scans at an interval of about 18 months) because
Homo naledi
's first MTPJ is an ideal model for non-shoe wearing with parallel sesamoid grooves. We developed the first MTPJ structure transformation method and created MTPJ joint capsule model for both
Homo naledi
and wrestlers. Constraint on the medial side of the first MTPJ capsule was set to simulate shoe-wearing conditions compared to the lack of medial constraint for barefooted conditions. Analysis of eight FE models of different angles for the first MTPJ of
Homo naledi
was performed by the first MTPJ transformation method and results showed that stress concentrated on the medial capsule of the first MTPJ in simulated shoe-wearing conditions, even at MTPJ angle of 0°. Increase in the first MTPJ angle further increased stress concentration on the medial side, and stress-growth relationship might reveal the causes of HV. We further developed a method to position the first MTPJ in wrestlers and created CT-based models at two time points. It was evident that the first MTPJ angle increased in all but one athlete, with a maximal increase of 4.03 degrees. This verifies our hypothesis that HV might be developed by wearing shoes. Further longitudinal studies with larger sample sizes are needed to additionally validate our results and determine the magnitude of the effects of shoe wearing on development and progression of HV.
Ensuring consistent glycosylation‐associated quality of therapeutic monoclonal antibodies (mAbs) has become a priority in pharmaceutical bioprocessing given that the distribution and composition of ...the carbohydrates (glycans) bound to these molecules determines their therapeutic efficacy and immunogenicity. However, the interaction between bioprocess conditions, cellular metabolism and the intracellular process of glycosylation remains to be fully understood. To gain further insight into these interactions, we present a novel integrated modelling platform that links dynamic variations in mAb glycosylation with cellular secretory capacity. Two alternative mechanistic representations of how mAb specific productivity (qp) influences glycosylation are compared. In the first, mAb glycosylation is modulated by the linear velocity with which secretory cargo traverses the Golgi apparatus. In the second, glycosylation is influenced by variations in Golgi volume. Within our modelling framework, both mechanisms accurately reproduce experimentally‐observed dynamic changes in mAb glycosylation. In addition, an optimisation‐based strategy has been developed to estimate the concentration of glycosylation enzymes required to minimise mAb glycoform variability. Our results suggest that the availability of glycosylation machinery relative to cellular secretory capacity may play a crucial role in mAb glycosylation. In the future, the modelling framework presented here may aid in selecting and engineering cell lines that ensure consistent mAb glycosylatio.
Glycosylation, which impacts the safety and therapeutic efficacy of monoclonal antibodies (mAbs), may vary as a function of cell‐specific productivity (qp). In this work, mathematical models of two distinct mechanistic representations linking mAb glycosylation with qp quantitatively reproduce the shift from processed to immature mAb glycoform secretion during CHO cell culture. If expression of glycosyltransferases remains unchanged throughout culture, their availability with respect to increased qp − due to either reduced Golgi residence time or dilution – may cause immature mAb glycoform secretion.
Fed-batch culture is the most commonly used upstream process in industry today for recombinant monoclonal antibody production using Chinese hamster ovary (CHO) cells. Developing and optimizing this ...process in the lab is crucial for establishing process knowledge, which enables rapid and predictable tech-transfer to manufacturing scale. In this chapter, we describe stepwise how to carry out fed-batch CHO cell culture for lab-scale antibody production.
Chinese hamster ovary (CHO) cells have become the primary expression system for the production of complex recombinant proteins due to their long-term success in industrial scale production and ...generating appropriate protein N-glycans similar to that of humans. Control and optimization of protein N-glycosylation is crucial, as the structure of N-glycans can largely influence both biological and physicochemical properties of recombinant proteins. Protein N-glycosylation in CHO cell culture can be controlled and tuned by engineering medium, feed, culture process, as well as genetic elements of the cell. In this chapter, we will focus on how to carry out experiments for N-glycosylation modulation through medium and feed optimization. The workflow and typical methods involved in the experiment process will be presented.
The detailed kinetics study of erythrocyte deformability is useful for the early diagnosis of blood diseases and for monitoring the blood rheology. Present solutions for a three-dimensional (3D) ...reconstruction of erythrocytes has a limited potential. This study aimed to use erythrocyte transmission electron images (ETIs) to evaluate the morphological relationship between adjacent ETIs and generate erythrocytes 3D model. First, ultrathin serial sections of skeletal muscle tissue were obtained using an ultramicrotome. Further, the set of ETIs in a capillary were captured by transmission electron microscopy. The images were aligned by translations and rotations using custom software to optimize the morphological relationship between adjacent ETIs. These coordinate transformations exploit the unique principal axis of inertia of each image to define the body coordinate system and hence provide the means to accurately reconnect the adjacent ETIs. The sum of the distances between the corresponding points on the boundary of adjacent ETIs was minimized and, further, was optimized by using physiological relationship between the adjacent ETIs. The analysis allowed to define precise virtual relationship between the adjacent erythrocytes. Finally, extracted erythrocytes’ cross-section images allowed to generate 3D model of the erythrocytes.
Cross-sectional imaging is considered the gold standard in diagnosing a range of diseases. However, despite its widespread use in clinical practice and research, no widely accepted method is ...available to reliably match cross-sectional planes in several consecutive scans. This deficiency can impede comparison between cross-sectional images and ultimately lead to misdiagnosis. Here, we propose and demonstrate a method for finding the same imaging plane in images obtained during separate scanning sessions. Our method is based on the reconstruction of a “virtual organ” from which arbitrary cross-sectional images can be extracted, independent of the axis orientation in the original scan or cut; the key is to establish unique body coordinates of the organ from its principal axes of inertia. To verify our method a series of tests were performed, and the same cross-sectional plane was successfully extracted. This new approach offers clinicians access, after just a single scanning session, to the morphology and structure of a lesion through cross-sectional images reconstructed along arbitrary axes. It also aids comparable detection of morphological and structural changes in the same imaging plane from scans of the same patient taken at different times—thus potentially reducing the misdiagnosis rate when cross-sectional images are interpreted.
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