Analytical Study of Robustness of a Negative Feedback Oscillator by Multiparameter Sensitivity

BACKGROUND:One of the distinctive features of biological oscillators such as circadian clocks and cell cycles is robustness which is the ability to resume reliable operation in the face of different types of perturbations. In the previous study, we proposed multiparameter sensitivity (MPS) as an intelligible measure for robustness to fluctuations in kinetic parameters. Analytical solutions directly connect the mechanisms and kinetic parameters to dynamic properties such as period, amplitude and their associated MPSs. Although negative feedback loops are known as common structures to biological oscillators, the analytical solutions have not been presented for a general model of negative feedback oscillators.RESULTS:We present the analytical expressions for the period, amplitude and their associated MPSs for a general model of negative feedback oscillators. The analytical solutions are validated by comparing them with numerical solutions. The analytical solutions explicitly show how the dynamic properties depend on the kinetic parameters. The ratio of a threshold to the amplitude has a strong impact on the period MPS. As the ratio approaches to one, the MPS increases, indicating that the period becomes more sensitive to changes in kinetic parameters. We present the first mathematical proof that the distributed time-delay mechanism contributes to making the oscillation period robust to parameter fluctuations. The MPS decreases with an increase in the feedback loop length (i.e., the number of molecular species constituting the feedback loop).CONCLUSIONS:Since a general model of negative feedback oscillators was employed, the results shown in this paper are expected to be true for many of biological oscillators. This study strongly supports that the hypothesis that phosphorylations of clock proteins contribute to the robustness of circadian rhythms. The analytical solutions give synthetic biologists some clues to design gene oscillators with robust and desired period

Estimation of mutual information via quantum kernel method

Recently, the importance of analysing data and collecting valuable insight efficiently has been increasing in various fields. Estimating mutual information (MI) plays a critical role to investigate the relationship among multiple random variables with a nonlinear correlation. Particularly, the task to determine whether they are independent or not is called the independence test, whose core subroutine is estimating MI from given data. It is a fundamental tool in statistics and data analysis that can be applied in a wide range of application such as hypothesis testing, causal discovery and more. In this paper, we propose a method for estimating mutual information using the quantum kernel. We investigate the performance under various problem settings, such as different sample size or the shape of the probability distribution. As a result, the quantum kernel method showed higher performance than the classical one under the situation that the number of samples is small, the variance is large or the variables posses highly non-linear relationships. We discuss this behavior in terms of the central limit theorem and the structure of the corresponding quantum reproducing kernel Hilbert space.Comment: 20 pages, 10 figure

Kinematic characteristics of barefoot sprinting in habitually shod children

Background. Anecdotally, a wide variety of benefits of barefoot running have been advocated by numerous individuals. The influence of the alterations in the properties of the shoe on the running movement has been demonstrated in adults at submaximal jogging speeds. However, the biomechanical differences between shod and barefoot running in children at sprinting speeds and the potential developmental implications of these differences are still less examined. The purpose was to determine the potential differences in habitually shod children's sprint kinematics between shod and barefoot conditions. Methods. Ninety-four children (51 boys and 43 girls; 6-12 years-old; height, 135.0 ± 0.12 m; body mass, 29.0 ± 6.9 kg) performed 30 m maximal sprints from standing position for each of two conditions (shod and barefoot). To analyze sprint kinematics within sagittal plane sprint kinematics, a high-speed camera (300 fps) was set perpendicular to the runway. In addition, sagittal foot landing and take-offimages were recorded for multiple angles by using five high-speed cameras (300 fps). Spatiotemporal variables, the kinematics of the right leg (support leg) and the left leg (recovery leg), and foot strike patterns: rear-foot strike (RFS), mid-foot strike (MFS), and forefoot strike (FFS) were investigated. The paired t -test was used to test difference between shod and barefoot condition. Results. Barefoot sprinting in habitually shod children was mainly characterized by significantly lower sprint speed, higher step frequency, shorter step length and stance time. In shod running, 82% of children showed RFS, whereas it decreased to 29% in barefoot condition. The touch down state and the subsequent joint movements of both support and recovery legs during stance phase were significantly altered when running in condition with barefoot. Discussion. The acute effects of barefoot sprinting was demonstrated by significantly slower sprinting speeds that appear to reflect changes in a variety of spatiotemporal parameters as well as lower limb kinematics. It is currently unknown whether such differences would be observed in children who typically run in bare feet and what developmental benefits and risks may emerge from increasing the proportion of barefoot running and sprinting in children. Future research should therefore investigate potential benefits that barefoot sprinting may have on the development of key physical fitness such as nerve conduction velocity, muscular speed, power, and sprinting technique and on ways to minimize the risk of any acute or chronic injuries associated with this activity. © 2018 Mizushima et al

Development of an accurate kinetic model for the central carbon metabolism of Escherichia coli

Additional file 2. Comparison of our kinetic model with other existing models

CADLIVE Optimizer: Web-based Parameter Estimation for Dynamic Models

Computer simulation has been an important technique to capture the dynamics of biochemical networks. In most networks, however, few kinetic parameters have been measured in vivo because of experimental complexity. We develop a kinetic parameter estimation system, named the CADLIVE Optimizer, which comprises genetic algorithms-based solvers with a graphical user interface. This optimizer is integrated into the CADLIVE Dynamic Simulator to attain efficient simulation for dynamic models

Newly Synthesized Compound, PABA-Ursodeoxycholic Acid, for Evaluation of Intestinal Bacteria

From the standpoint of utilizing a distinctive feature of para-aminobenzoic acid (PABA) and intestinal bile acid metabolism, a conjugate of ursodeoxycholic acid with PABA (PABA-UDCA) was newly synthesized for studying whether it can be a good material or not to evaluate enteric bacteria. In incubation experiment, this compound was reasonably deconjugated by cholylglycine hydrolase resulting in the release of PABA. In animal experiment, urinary excretions of PABA were determined during six hours following oral administration of 10 mg PABA-UDCA. Control rats (n=7) excreted 140.1 ± 59.5 μ,g (mean ± SD) of PABA. By contrast, the rats (n=9) with intestinal antisepsis by antibiotic administration excreted less (18.3 ± 16. 7 μg; P < 0.001) whereas those with intestinal bacterial overgrowth by making enteric blind loop excreted more (451.1 ± 223.6 μg; P < 0.01). These observations indicate that this new compound is likely to offer a simple and rapid method for evaluation of the intestinal microorganisms

Adenomyoepithelial adenosis associated with breast cancer: a case report and review of the literature

Adenomyoepithelial adenosis of the breast is an extremely rare type of adenosis. We herein present the case of a 35-year-old woman, who presented with a small painless hard lump and elastic soft induration of 5 cm in diameter in her left breast. Clinical examination and diagnostic workup were suggestive of a breast carcinoma, and a modified radical mastectomy and sentinel node biopsy were performed. Histopathological examination revealed adenomyoepithelial adenosis along with fibrocystic change and small invasive ductal carcinoma, slightly away from the adenosis. The presented case was thought to be initial-stage adenomyoepithelial adenosis and independently developing breast cancer. From a review of five reported cases of adenomyoepithelial adenosis, complete resection of the tumor and coexisting malignant disease may be recommended, owing to the tendency to develop breast cancer or malignant adenomyoepithelioma, or recurrence. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-50) contains supplementary material, which is available to authorized users

CADLIVE optimizer: web-based parameter estimation for dynamic models

Computer simulation has been an important technique to capture the dynamics of biochemical networks. In most networks, however, few kinetic parameters have been measured in vivo because of experimental complexity. We develop a kinetic parameter estimation system, named the CADLIVE Optimizer, which comprises genetic algorithms-based solvers with a graphical user interface. This optimizer is integrated into the CADLIVE Dynamic Simulator to attain efficient simulation for dynamic models