A combined modelling and experimental study of heat shock factor SUMOylation in response to heat shock.

One of the most important questions in cell biology is how cell fate is determined when exposed to extreme stresses such as heat shock. It has been long understood that organisms exposed to high temperature stresses typically protect themselves with a heat shock response (HSR), where accumulation of denatured or unfolded proteins triggers the synthesis of heat shock proteins (HSPs) through the heat shock transcription factor, e.g., heat shock factor 1 (HSF1). In this study, a dynamical model validated with experiments is presented to analyse the role of HSF1 SUMOylation in response to heat shock. Key features of this model are inclusion of heat shock response and SUMOylation of HSF1, and HSP synthesis at molecular level, describing the dynamical evolution of the key variables involved in the regulation of HSPs. The model has been employed to predict the SUMOylation levels of HSF1 with different external temperature stimuli. The results show that the SUMOylated HSF1 levels agree closely with the experimental findings. This demonstrates the validity of this nonlinear dynamic model for the important role of SUMOylation in response to heat shock.

A New Proxy Measurement Algorithm with Application to the Estimation of Vertical Ground Reaction Forces Using Wearable Sensors.

Measurement of the ground reaction forces (GRF) during walking is typically limited to laboratory settings, and only short observations using wearable pressure insoles have been reported so far. In this study, a new proxy measurement method is proposed to estimate the vertical component of the GRF (vGRF) from wearable accelerometer signals. The accelerations are used as the proxy variable. An orthogonal forward regression algorithm (OFR) is employed to identify the dynamic relationships between the proxy variables and the measured vGRF using pressure-sensing insoles. The obtained model, which represents the connection between the proxy variable and the vGRF, is then used to predict the latter. The results have been validated using pressure insoles data collected from nine healthy individuals under two outdoor walking tasks in non-laboratory settings. The results show that the vGRFs can be reconstructed with high accuracy (with an average prediction error of less than 5.0%) using only one wearable sensor mounted at the waist (L5, fifth lumbar vertebra). Proxy measures with different sensor positions are also discussed. Results show that the waist acceleration-based proxy measurement is more stable with less inter-task and inter-subject variability than the proxy measures based on forehead level accelerations. The proposed proxy measure provides a promising low-cost method for monitoring ground reaction forces in real-life settings and introduces a novel generic approach for replacing the direct determination of difficult to measure variables in many applications.

Automatic segmentation of lower limb muscles from MR images of post-menopausal women based on deep learning and data augmentation.

Individual muscle segmentation is the process of partitioning medical images into regions representing each muscle. It can be used to isolate spatially structured quantitative muscle characteristics, such as volume, geometry, and the level of fat infiltration. These features are pivotal to measuring the state of muscle functional health and in tracking the response of the body to musculoskeletal and neuromusculoskeletal disorders. The gold standard approach to perform muscle segmentation requires manual processing of large numbers of images and is associated with significant operator repeatability issues and high time requirements. Deep learning-based techniques have been recently suggested to be capable of automating the process, which would catalyse research into the effects of musculoskeletal disorders on the muscular system. In this study, three convolutional neural networks were explored in their capacity to automatically segment twenty-three lower limb muscles from the hips, thigh, and calves from magnetic resonance images. The three neural networks (UNet, Attention UNet, and a novel Spatial Channel UNet) were trained independently with augmented images to segment 6 subjects and were able to segment the muscles with an average Relative Volume Error (RVE) between -8.6% and 2.9%, average Dice Similarity Coefficient (DSC) between 0.70 and 0.84, and average Hausdorff Distance (HD) between 12.2 and 46.5 mm, with performance dependent on both the subject and the network used. The trained convolutional neural networks designed, and data used in this study are openly available for use, either through re-training for other medical images, or application to automatically segment new T1-weighted lower limb magnetic resonance images captured with similar acquisition parameters.

Automatic segmentation of skeletal muscles from MR images using modified U-Net and a novel data augmentation approach.

Rapid and accurate muscle segmentation is essential for the diagnosis and monitoring of many musculoskeletal diseases. As gold standard, manual annotation suffers from intensive labor and high inter-operator reproducibility errors. In this study, deep learning (DL) based automatic muscle segmentation from MR scans is investigated for post-menopausal women, who normally experience a decline in muscle volume. The performance of four Deep Learning (DL) models was evaluated: U-Net and UNet++ and two modified U-Net networks, which combined feature fusion and attention mechanisms (Feature-Fusion-UNet, FFU, and Attention-Feature-Fusion-UNet, AFFU). The models were tested for automatic segmentation of 16-lower limb muscles from MRI scans of two cohorts of post-menopausal women (11 subjects in PMW-1, 8 subjects in PMW-2; from two different studies so considered independent datasets) and 10 obese post-menopausal women (PMW-OB). Furthermore, a novel data augmentation approach is proposed to enlarge the training dataset. The results were assessed and compared by using the Dice similarity coefficient (DSC), relative volume error (RVE), and Hausdorff distance (HD). The best performance among all four DL models was achieved by AFFU (PMW-1: DSC 0.828 ± 0.079, 1-RVE 0.859 ± 0.122, HD 29.9 mm ± 26.5 mm; PMW-2: DSC 0.833 ± 0.065, 1-RVE 0.873 ± 0.105, HD 25.9 mm ± 27.9 mm; PMW-OB: DSC 0.862 ± 0.048, 1-RVE 0.919 ± 0.076, HD 34.8 mm ± 46.8 mm). Furthermore, the augmentation of data significantly improved the DSC scores of U-Net and AFFU for all 16 tested muscles (between 0.23% and 2.17% (DSC), 1.6%-1.93% (1-RVE), and 9.6%-19.8% (HD) improvement). These findings highlight the feasibility of utilizing DL models for automatic segmentation of muscles in post-menopausal women and indicate that the proposed augmentation method can enhance the performance of models trained on small datasets.

An extended discrete element method for the estimation of contact pressure at the ankle joint during stance phase.

Abnormalities in the ankle contact pressure are related to the onset of osteoarthritis. In vivo measurements are not possible with currently available techniques, so computational methods such as the finite element analysis (FEA) are often used instead. The discrete element method (DEM), a computationally efficient alternative to time-consuming FEA, has also been used to predict the joint contact pressure. It describes the articular cartilage as a bed of independent springs, assuming a linearly elastic behaviour and absence of relative motion between the bones. In this study, we present the extended DEM (EDEM) which is able to track the motion of talus over time. The method was used, with input data from a subject-specific musculoskeletal model, to predict the contact pressure in the ankle joint during gait. Results from EDEM were also compared with outputs from conventional DEM. Predicted values of contact area were larger in EDEM than they were in DEM (4.67 and 4.18 cm2, respectively). Peak values of contact pressure, attained at the toe-off, were 7.3 MPa for EDEM and 6.92 MPa for DEM. Values predicted from EDEM fell well within the ranges reported in the literature. Overall, the motion of the talus had more effect on the extension and shape of the pressure distribution than it had on the magnitude of the pressure. The results indicated that EDEM is a valid methodology for the prediction of ankle contact pressure during daily activities.

The Detection of Freezing of Gait in Parkinson's Disease Using Asymmetric Basis Function TV-ARMA Time-Frequency Spectral Estimation Method.

Freezing of gait (FOG) is an episodic gait disturbance affecting locomotion in Parkinson's disease. As a biomarker to detect FOG, the Freeze index (FI), which is defined as the ratio of the areas under power spectra in 'freeze' band and in 'locomotion' band, can negatively be affected by poor time and frequency resolution of time-frequency spectrum estimate when short-time Fourier transform (STFT) or Wavelet transform (WT) is used. In this study, a novel high-resolution parametric time-frequency spectral estimation method is proposed to improve the accuracy of FI. A time-varying autoregressive moving average model (TV-ARMA) is first identified where the time-varying parameters are estimated using an asymmetric basis function expansion method. The TV-ARMA model is then transformed into frequency domain to estimate the time-frequency spectrum and calculate the FI. Results evaluated on the Daphnet Freezing of Gait Dataset show that the new method improves the time and frequency resolutions of the time-frequency spectrum and the associate FI has better performance in the detection of FOG than its counterparts based on STFT and WT methods do. Moreover, FOGs can be predicted in advance of its occurrence in most cases using the new method.

Real-Life Measurement of Tri-Axial Walking Ground Reaction Forces Using Optimal Network of Wearable Inertial Measurement Units.

Monitoring natural human gait in real-life environment is essential in many applications including the quantification of disease progression, and monitoring the effects of treatment and alteration of performance biomarkers in professional sports. Nevertheless, reliable and practical techniques and technologies necessary for continuous real-life monitoring of gait is still not available. This paper explores in detail the correlations between the acceleration of different body segments and walking ground reaction forces GRF(t) in three dimensions and proposes three sensory systems, with one, two, and three inertial measurement units (IMUs), to estimate GRF(t) in the vertical (V), medial-lateral (ML), and anterior-posterior (AP) directions. The nonlinear autoregressive moving average model with exogenous inputs (NARMAX) non-linear system identification method was utilized to identify the optimal location for IMUs on the body for each system. A simple linear model was then proposed to estimate GRF(t) based on the correlation of segmental accelerations with each other. It was found that, for the three-IMU system, the proposed model estimated GRF(t) with average peak-to-peak normalized root mean square error (NRMSE) of 7%, 16%, and 18% in V, AP, and ML directions, respectively. With a simple subject-specific training at the beginning, these errors were reduced to 7%, 13%, and 13% in V, AP, and ML directions, respectively. These results were found favorably comparable with the results of the benchmark NARMAX model, with subject-specific training, with 0% (V), 4% (AP), and 1% (ML) NRMSE difference.

Stable adaptive neurocontrol for nonlinear discrete-time systems.

This paper presents a novel approach in designing neural network based adaptive controllers for a class of nonlinear discrete-time systems. This type of controllers has its simplicity in parallelism to linear generalized minimum variance (GMV) controller design and efficiency to deal with complex nonlinear dynamics. A recurrent neural network is introduced as a bridge to compensation simplify controller design procedure and efficiently to deal with nonlinearity. The network weight adaptation law is derived from Lyapunov stability analysis and the connection between convergence of the network weight and the reconstruction error of the network is established. A theorem is presented for the conditions of the stability of the closed-loop systems. Two simulation examples are provided to demonstrate the efficiency of the approach.

Lattice dynamical wavelet neural networks implemented using particle swarm optimization for spatio-temporal system identification.

In this brief, by combining an efficient wavelet representation with a coupled map lattice model, a new family of adaptive wavelet neural networks, called lattice dynamical wavelet neural networks (LDWNNs), is introduced for spatio-temporal system identification. A new orthogonal projection pursuit (OPP) method, coupled with a particle swarm optimization (PSO) algorithm, is proposed for augmenting the proposed network. A novel two-stage hybrid training scheme is developed for constructing a parsimonious network model. In the first stage, by applying the OPP algorithm, significant wavelet neurons are adaptively and successively recruited into the network, where adjustable parameters of the associated wavelet neurons are optimized using a particle swarm optimizer. The resultant network model, obtained in the first stage, however, may be redundant. In the second stage, an orthogonal least squares algorithm is then applied to refine and improve the initially trained network by removing redundant wavelet neurons from the network. An example for a real spatio-temporal system identification problem is presented to demonstrate the performance of the proposed new modeling framework.