Hyperparameter on-line learning of stochastic resonance based threshold networks

Aiming at training the feed-forward threshold neural network consisting of nondifferentiable activation functions, the approach of noise injection forms a stochastic resonance based threshold network that can be optimized by various gradient-based optimizers. The introduction of injected noise extends the noise level into the parameter space of the designed threshold network, but leads to a highly non-convex optimization landscape of the loss function. Thus, the hyperparameter on-line learning procedure with respective to network weights and noise levels becomes of challenge. It is shown that the Adam optimizer, as an adaptive variant of stochastic gradient descent, manifests its superior learning ability in training the stochastic resonance based threshold network effectively. Experimental results demonstrate the significant improvement of performance of the designed threshold network trained by the Adam optimizer for function approximation and image classification.     

The Picone identity: A device to get optimal uniqueness results and global dynamics in Population Dynamics

This paper infers from a generalized Picone identity the uniqueness of the stable positive solution for a class of semilinear equations of superlinear indefinite type, as well as the uniqueness and global attractivity of the coexistence state in two generalized diffusive prototypes of the symbiotic and competing species models of Lotka–Volterra. The optimality of these uniqueness theorems reveals the tremendous strength of the Picone identity.     

Dynamics of Bacteriorhodopsin in the Dark-Adapted State from Solution Nuclear Magnetic Resonance Spectroscopy

To achieve efficient proton pumping in the light-driven proton pump bacteriorhodopsin (bR), the protein must be tightly coupled to the retinal to rapidly convert retinal isomerization into protein structural rearrangements. Methyl group dynamics of bR embedded in lipid nanodiscs were determined in the dark-adapted state, and were found to be mostly well ordered at the cytosolic side. Methyl groups in the M145A mutant of bR, which displays only 10 % residual proton pumping activity, are less well ordered, suggesting a link between side-chain dynamics on the cytosolic side of the bR cavity and proton pumping activity. In addition, slow conformational exchange, attributed to low frequency motions of aromatic rings, was indirectly observed for residues on the extracellular side of the bR cavity. This may be related to reorganization of the water network. These observations provide a detailed picture of previously undescribed equilibrium dynamics on different time scales for ground-state bR.     

Mass distribution and skewness for passive scalar transport in pipes with polygonal and smooth cross sections

We extend our previous results characterizing the loading properties of a diffusing passive scalar advected by a laminar shear flow in ducts and channels to more general cross‐sectional shapes, including regular polygons and smoothed corner ducts originating from deformations of ellipses. For the case of the triangle and localized, cross‐wise uniform initial distributions, short‐time skewness is calculated exactly to be positive, while long‐time asymptotics shows it to be negative. Monte Carlo simulations confirm these predictions, and document the timescale for sign change. The equilateral triangle appears to be the only regular polygon with this property—all others possess positive skewness at all times. Alternatively, closed‐form flow solutions can be constructed for smooth deformations of ellipses, and illustrate how both nonzero short‐time skewness and the possibility of multiple sign switching in time is unrelated to domain corners. Exact conditions relating the median and the skewness to the mean are developed which guarantee when the sign for the skewness implies front (more mass to the right of the mean) or back (more mass to the left of the mean) “loading” properties of the evolving tracer distribution along the pipe. Short‐ and long‐time asymptotics confirm this condition, and Monte Carlo simulations verify this at all times. The simulations are also used to examine the role of corners and boundaries on the distribution for short‐time evolution of point source , as opposed to cross‐wise uniform, initial data.     

Excited-State Dynamics of Non-Luminescent and Luminescent π-Radicals

Recently, the potential use of organic π-radicals and related spin systems has been expanded to modern technological applications. The unique excited-state dynamics of organic π-radicals can be useful to improve the stability of photochemically unstable organic compounds, make the polarization transfer applicable to information technology, and achieve effective up-conversion of interest for luminescence bioimaging, among others. Furthermore, highly luminescent stable π-radicals have been recently reported, which are especially interesting for application in organic light-emitting devices owing to their potential to provide an internal quantum efficiency of 100 %. Thus, the excited-state nature of stable π-radicals as well as the control of their excited-state spin dynamics are emerging topics both in terms of fundamental science and related technological applications. In this minireview, we focus on the excited-state dynamics of both photostable non(weakly)-luminescent and luminescent π-radicals, which are opposites of each other. In particular, we cover the following topics: 1) effective generation of high-spin photoexcited states and control of the excited-state dynamics by using non-luminescent π-radicals, 2) unique excited-state dynamics of luminescent π-radicals and radical excimers, and 3) applications utilizing excited-state dynamics of π-radicals.     

An improved LC–MS/MS method for determination of docetaxel and its application to population pharmacokinetic study in Chinese cancer patients

Because of its unpredictable side effects and efficacy, the anticancer drug docetaxel (DTX) requires improved characterisation of its pharmacokinetic profiles through population pharmacokinetic studies. A sensitive and rugged LC–MS/MS method for the detection of DTX in human plasma was developed and optimised using paclitaxel as an internal standard (IS). The plasma samples underwent rapid extraction using hybrid solid-phase extraction-protein precipitation. The analyte and IS were separated with an isocratic system on a Zorbax Eclipse Plus C₁₈ column using water containing 0.05% acetic acid along with 20 μM of sodium acetate and methanol (30/70, v/v) as the mobile phase. Quantification was performed using a triple quadrupole mass spectrometer through multiple reaction monitoring in positive mode, using the m/z 830.3 → 548.8 and m/z 876.3 → 307.7 transitions for DTX and paclitaxel, respectively. The range of the calibration curve was 1–500 ng/mL for DTX, and the linear correlation coefficient was >0.99. The accuracies ranged from −4.6 to 4.2%, and the precision was no higher than 7.0% for the analytes. No significant matrix effect was observed. Both DTX and the IS showed considerable recovery. This method was finally applied to the establishment of a population pharmacokinetic model to optimise the clinical use of DTX.     

Properties of bounded stochastic processes employed in biophysics

Abstract

Realistic stochastic modeling is increasingly requiring the use of bounded noises. In this work, properties and relationships of commonly employed bounded stochastic processes are investigated within a solid mathematical ground. Four families are object of investigation: the Sine-Wiener (SW), the Doering–Cai–Lin (DCL), the Tsallis–Stariolo–Borland (TSB), and the Kessler–Sørensen (KS) families. We address mathematical questions on existence and uniqueness of the processes defined through Stochastic Differential Equations, which often conceal non-obvious behavior, and we explore the behavior of the solutions near the boundaries of the state space. The expression of the time-dependent probability density of the Sine-Wiener noise is provided in closed form, and a close connection with the Doering–Cai–Lin noise is shown. Further relationships among the different families are explored, pathwise and in distribution. Finally, we illustrate an analogy between the Kessler–Sørensen family and Bessel processes, which allows to relate the respective local times at the boundaries.     

Computational Analysis Reveals a Critical Point Mutation in the N-Terminal Region of the Signaling Lymphocytic Activation Molecule Responsible for the Cross-Species Infection with Canine Distemper Virus

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the n-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown, partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables the formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable the determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.