A large number of biological information has been available from genome sequencing and bioinformatics. To further understand the qualities of the biological networks (such as metabolic network) in the complex biological system, representations of integrated function in silico have been widely investigated, and various modeling approaches have been designed, most of which are based on detailed kinetic information except flux balance analysis (FBA). FBA, just based on stoichimetrical information of reactions, is a suitable method for the study of metabolic pathways, and it analyzes the behaviors of the network from the viewpoint of the whole system. Herein, this modeling approach has been utilized to reconstruct the mitochondrial metabolic network to integrate and analyze its capability of producing energy. Besides, extreme pathways analysis (EPA) and shadow prices analysis have also been integrated to study the interior characters of the network. Our modeling results have indicated for the first time that the covalent regulative property of pyruvate dehydrogenase is restrained by the feedback of acetyl-CoA. Combined with the biological experiments, these simulations in silico could be pretty useful for the further understanding of functions and characters of the biological network as a complex system.

Voltage-sensitive dyes have become an important tool in visualizing electrical activity in cardiac tissue. However, there are no established methods for assessing the contribution of intramural electrical excitation to recorded optical signals. Here, we develop algorithms to calculate voltage-dependent optical signals from three-dimensional distributions of transmembrane voltage inside the myocardial wall (the forward problem). Optical diffusion theory is applied for different imaging modes including subsurface imaging or epi-illumination, transillumination and coaxial scanning. We use the solutions of the forward problem to assess these imaging methods with respect to their effectiveness in visualizing two types of 3D cardiac activity: electrical point sources and intramural scroll waves initiated at various depths. Simulations were performed both for fluorescent and absorptive voltage-sensitive dyes. In the case of point sources, we focus on the lateral optical resolution, as a function of the source depth. We find that, among the studied methods, fluorescent coaxial scanning yields the best optical resolution (<2.5 mm). In the case of scroll waves we investigate how well the filament, i.e. the organizing center, can be visualized as function of its depth. Our results show that using absorptive transillumination, filaments can be detected up to 3 mm below the recording surface. The presented results provide a powerful tool for the interpretation of experimental data and are the first step towards the development of inverse procedures.

Near-infrared spectro-imaging (NIRSI) is a quickly developing method for the in-vivo imaging of biological tissues. In particular, it is now extensively employed for imaging the human brain. In this non-invasive technique, the information about the brain is obtained from the analysis of spatial light bundles formed by the photons traveling from light sources to detectors placed on the surface of the head. Most significant problems in the functional brain NIRSI are the separation of the brain information from the physiological noise in non-cerebral tissues, and the localization of functional signals. In this paper we describe signal and image processing techniques we developed in order to measure two types of functional cerebral signals: the hemodynamic responses, and neuronal responses.

Brain-derived neurotrophic factor (BDNF), like other neurotrophins, has long-term effects on neuronal survival and differentiation; furthermore, BDNF has been reported to exert an acute potentiation of synaptic activity and are critically involved in long-term potentiation (LTP). We found that BDNF rapidly induced potentiation of synaptic activity and an increase in the intracellular Ca²⁺ concentration in cultured cortical neurons. Within minutes of BDNF application to cultured cortical neurons, spontaneous firing rate was dramatically increased as were the frequency and amplitude of excitatory spontaneous postsynaptic currents (EPSCs). Fura-2 recordings showed that BDNF acutely elicited an increase in intracellular calcium concentration ([Ca²⁺]_c). This effect was partially dependent on [Ca²⁺]_o; The BDNF-induced increase in [Ca²⁺]_c can not be completely blocked by Ca²⁺-free solution. It was completely blocked by K252a and partially blocked by Cd²⁺ and TTX. The results demonstrate that BDNF can enhances synaptic transmission and that this effect is accompanied by a rise in [Ca²⁺]_c that requires two route: the release of Ca²⁺ from intracellular calcium stores and influx of extracellular Ca²⁺ through voltage-dependent Ca²⁺ channels in cultured cortical neurons.

Working memory (WM) refers to the temporary maintenance of information that is no longer accessible in the environment, and the manipulation of this information for subsequent use. PET and functional MRI studies suggest that prefrontal cortex (PFC) is involved in WM. Here, we report a functional near-infrared spectroscopy (NIRS) study on the PFC activation caused by a WM task, a verbal n-back task. During performance of the task, concentration changes of oxy-Hb (HbO₂), deoxy-Hb (Hb), and total-Hb (HbT) in subjects’ prefrontal cortex were monitored by a 24-channel functional NIRS imager. The behavioral performances (accuracy and response time) were recorded simultaneously. Results revealed that as memory load increased, subjects showed poorer behavioral performance as well as monotonously increasing magnitudes of the activations in the left ventrolateral PFC (VLPFC) and bilateral dorsolateral PFC (DLPFC). In addition, the analysis of comparison between subjects showed that certain relations likely exist between the cerebral activation and the performance parameters for an individual subject: lower accuracy is accompanied by longer response time and further activation. Such means that the subject with difficulty in solving a problem will demonstrate more significant hemodynamic changes compared with the subject without difficulty in solving the same problem.

In this work, we use Monte Carlo simulation to obtain model OCT signals from a horizontally orientated blood layer at different stages of red blood cell (RBC) aggregation and sedimentation processes. The parameters for aggregating and sedimenting blood cells were chosen basing on the data available from literature and our earlier experimental studies. Two different models of simulated medium are considered: a suspension of washed RBC in physiological solution (where the aggregation does not take place) and RBC in blood plasma (which provides necessary conditions for aggregation). Good agreement of the simulation results with the available experimental data shows that the chosen optical parameters are reasonable. Dependencies of the numbers of photons contributing to the OCT signal on the number of experienced scattering events were analyzed for each simulated signal. It was shown, that maxima on these dependencies correspond to the peaks in the OCT signals related to the interfaces between the layers of blood plasma and blood cells. Their positions can be calculated from the optical thicknesses of the layers, and the absorption and scattering coefficients of the media.

The high resolution (~350 nm) transmission digital microscopy (TDM) with increased speed is promising tool for in vivo image flow cytometry to real time identification of flowing cells in microlymphatics of rat mesentery without any contrast agents. The main mesenteric microstructures (lymph-vessel diameter, valve geometry, cells, etc.) and their dynamics (wall motion, valve function, cell velocity, etc.) were monitored with TDM. Depending on structure size, different magnifications were used to images of relatively large the whole lymphangion (x4 - x10) as well as to image single cells (x40 - x100) in lymph and blood flow including estimation of their shape, size and aggregation types. Different potential applications of the TDM in vivo are discussed including visualization of circulating of cells in lymph flow, study the kinetics of leukocytes and rare erythrocytes, as well as image absorbing nonfluorescent mesentery structures with high sensitivity and resolution.

Laser speckle instrument for complex bioflow dynamics studies is described. The instrument is developed for investigation of lymph flow dynamics in transillumination geometry simultaneously with microscopic examination of rat lymfangions. The use of two independent channels of laser speckle registration allows both to measure flow velocity and to localize centerline flow along the probing beam direction.

The intensity of light backscattered when low-power laser radiation is incident on the skin is investigated under in vivo conditions. The exposure of blood to low-power laser light in the absorption range of haemoglobin leads an increased intensity of the backscattered light. The theoretical calculation using the existing optical model of erythrocyte aggregation has suggest that the fragmentation of erythrocyte aggregates is it most probable mechanism leading to the enhanced backscattering.

Confluent monolayers of Malme-3M (ATCC HTB-64) cells, which is a melanoma cell line, and Malme-3 (ATCC HTB-102) cells, which are normal skin fibroblast cells, were cultured and plated onto glass coverslips. The two lines were isolated from the same patient, providing a tumor and normal counterpart for comparative studies. The forward-scattered objective speckle patterns were observed using a HeNe lasers that emitted at 543 and 633 nm. First and second-order speckle statistics from the two cell types were compared and contrasted. Of particular interest were the mean and maximum speckle size for a given observation geometry, degree of polarization, contrast, and the intensity probability distribution function. The speckle patterns from dry, densely-packed single layer latex sphere samples of various sizes were also investigated for comparison. The results indicate that the far-forward speckle patterns from these confluent monolayers can be used to discriminate between the cell types and can be used to derive specific morphological parameters of the cells.

Recent developments in optical clearing of biological tissue have shown a great promise in enhancing the capabilities of non-invasive light-based diagnostic and imaging techniques due to the increased light penetration into tissue. This study investigates the synergistic effect of hyperosmotic agents of dimethyl sulfoxide (DMSO) and glycerol solutions on optical clearing of skin in vitro. Experimental results from near infrared spectroscopy, direct imaging assessment and mass loss measurement showed that the mixed solutions of DMSO and glycerol caused better clearing effects than that of any single solution alone. In addition, the different clearing effects were observed when skin tissue was treated by different volume-mixing of DMSO and glycerol solutions. The results presented revealed that the DMSO is responsible for the synergistic effect on optical clearing due to its carrier effect and strong penetration capability.

Non-invasive glucose measurement by near-infrared spectroscopy is mainly based on the absorption of glucose. However, for non-invasive blood glucose measurement, the diffuse reflectance spectra are influenced not only by the absorption coefficient, but also by the scattering coefficient, anisotropy factor, and refractive index, which are normally nonlinear with the glucose concentrations. Furthermore, the variations of spectra depend on the relative changing direction of the absorption coefficient and scattering coefficient. In this paper, using the simulated samples of human tissues with different glucose concentrations in different conditions, we discussed the rules of how the glucose concentrations affected the absorption coefficient and scattering coefficient, respectively. The relations between the diffuse reflectance spectra and the absorption coefficient, as well as and the scattering coefficient were also investigated. Thus, we confirmed which of the optical parameters and measurement conditions would affect the diffuse reflectance spectra significantly. Based on the above results, proper methods could be selected to measure blood glucose concentration non-invasively according to different conditions, then the information of glucose absorption would be extracted more effectively, and higher measurement precision would be expected.

We study the response of a spherical absorber immersed in aqueous media. We investigate temporal resonant absorption and present initial numerical calculations of the same topic. Initial results indicate that, because of the dynamical characteristic of the system, the response after a sequence of energy pulses depends nonlinearly on the time between pulses. Specifically, the response exhibits resonant type behavior around a critical time, the time it would take a sound wave to traverse the absorber.

A dual-CCD based optical fluorescence system has been developed to facilitate ratio imaging. The system consists of two custom cameras capable of operating at 490 frames per second, with 128 by 128 detector elements, and 12 bits digitization. Tissue-simulating gel phantoms containing 5-(and-6)-carboxy seminaphthofluoresceins-1 (SNAFL-1) fluorescent dye were constructed. Using an excitation light at a wavelength of 489±11 nm and appropriate filtering, the fluorescence intensities of the dye-containing gel phantoms at different emission wavelengths were measured by the system. The dual-detector system can simultaneously collect two different intensity peaks. Gel phantoms with dye concentrations ranging from 0.00001 mg/mL to 0.1 mg/mL were used. Our results indicate that the dual-CCD fluorescence system is capable of detecting fluorescence signals at very low dye concentration (as low as 0.0001 mg/mL). To simulating real clinical situations, dye-containing gel was placed under normal gel of different thickness. Our results showed that the system can capture significant fluorescence signals of dye-containing gel under normal gel of a thickness up to 0.73 cm. The intensity ratios between different emission peaks were also measured. The system is a useful research tool in some biomedical experiments.

The development of methods of quantitative registration of movement character is actually to research of biophysical effects, which are specific for different forms of biological movements, for example, eye movement of human. These methods are based on use of new experimental foundation including high-resolution video techniques and computer analysis of big data arrays.

Flows with complex geometries, converging flows in a symmetric die-entry and an asymmetric oblique die-entry are investigated by means of direction sensitive one specific velocity (OSV) imaging. Near infrared, 1.3 nm, low coherence source giving resolution of about 10 micron is used for two-dimensional velocity mapping of the flows. Structural optical coherence tomography (OCT) images of a Y-junction of human subcutaneous macro blood vessels, with diameter up to 1 mm, are acquired noninvasively and in vivo. Images are acquired with transcutaneous coherence probing depth up to 1.5 - 1.6 mm. Application of the optical clearing and direction sensitive OSV imaging to monitor the blood flow in the subcutaneous human blood vessels are discussed.

Dynamic response of the somatic frog nerve under electrical pulsed excitation and processes of inactivation under local laser influence (λ=900 nm) was investigated ex vivo. The dependence of propagation speed of action potential from external laser power was discovered. The propagation speed of action potential was growing up in axons bunch of frog’s somatic nerve with increasing of laser power. More than 90% of axons were inactivated when the power of probing radiation was equal to 10W, and the propagation speed increased up to 50%. Strong fluctuation of propagation speed compound action potential and its amplitude was discovered in ensemble of neurons near threshold. Complex dynamic of compound action potential was discovered. Excitation threshold was growing up with increasing the power of laser radiation and only several neurons from ensemble were activated.

In the paper, the analytical method of constructing special generating functions for eigenfunctions and eigenvalues of the Perron-Frobenius operator corresponding to piece-wise symmetric one-dimensional chaotic maps is justified. Some properties of eigenfunctions are illustrated. An extension of the results for maps related with piece-wise ones by invertible nonlinear transformations is showed. The results for chaotic one-dimensional maps modeling biological and physiological rythmes (neuron activity or heart beats) and having invariant distributions in the form of various types of exponential law (standard distribution and its generalizations) are presented.

Intrinsic optical signals imaging (IOSI) is a novel technique for functional neuroimaging in vivo, especially in the study of cortical spreading depression (CSD). At 550 nm wavelength, the optical images during CSD showed significant vasodilatation of some small arteries in the surface of cortex of rats. In order to quantify the arteries’ diameter change, two kinds of threshold segmentation methods are applied, one is Isodata algorithm thresholding, the other is Otsu’s thresholding. Firstly, we set up a simple model to prove that segmentation of the vessel in a rectangle region could be equally transferred to describe the diameter change. The two methods could automatically select right thresholds for segmentation, so they were suitable for acquiring the dynamic vasodilatation in a series of optical images by computer. Comparing with the traditional method, the new methods were more robust and with high performance. By the methods, we found the vasodilatation could be distinguished as two processes during one CSD episode, a small vasodilatation before the great one that had been commonly reported before. The hemodynamic character during CSD deserves further study. And the methods can be easily applied to the other optical imaging experiments when the vascular dynamic is concerned.

Fluorescence recovery after photobleaching (FRAP) has become a popular technique to investigate the behavior of protein in living cells. There are various mathematical models for the processing of FRAP data. Among them, Compartmental modeling enables researchers to extract information such as the association and dissociation constants, distribution of a protein between mobile and immobilized pools, and the effective diffusion transfer coefficient of the molecule under study. This model is a simple system of linear ordinary differential equations, and its solution used to fit the FRAP data is a simple two exponential function. Therefore, Gustavo Carrero and some other scientists suggest the use of this model. However we find that the length of FRAP data affects the stabilization of data processing. We believe that it is the two-exponential fitting function that causes the instabilization. This paper attempts the study of fitting FRAP data using three exponential sum function and gets better and more stable fitting. As researchers begin to focus on the relative influence of protein domains within individual protein, this approach will allow a quantitative assessment of the relative effect of different molecular interactions on the steady-state distribution of protein in vivo.

In order to treat the effect of subthreshold dynamics on noisy neuron behavior we focus on parameters region of FitzHugh-Nagumo model close to the so called canard-explosion. Such parameter region corresponds to transition from excitable regime to continuous spiking. We observe the number of noise-induced effects, such as (i) noise-induced stabilization of firing frequency; (ii) noise-induced suppression of spiking; (iii) noise-induced chaos. We show that for small ensemble of resonator-type neurons activated by noise there is the global maxima of firing frequency at some optimal noise intensity. The underlying mechanisms of such behavior are closely related to noise-activated subthreshold dynamics.

Mathematical models construction of motor proteins dynamics at a transport of intracellular organelles is considered with taking into account the rheological properties of organelle membrane and cytoplasm. The possibility of extension of the existing idealized models of hard motors and a transported particle on the this general case is discussed.

This paper studies the deterministic and stochastic dynamics of a biological burster model. Special emphasis is paid to the transition zones between the main spiking patterns. In these zones, noise can induce or suppress spike generation. We explain this in terms of bifurcation phenomena in the underlying deterministic model. We also show how coupled bursters can interact to provide in-phase and out-of-phase synchronous regimes with varying noise intensity.

Currently, tissue optical clearing technique has shown a great potential in enhancing the capabilities of non-invasive light-based diagnostic and imaging techniques due to the increased light penetration into tissue. In order to facilitate the clinical availability of tissue optical clearing technique by the use of hyperosmotic agents, this study introduces oleic acid, a mono-unsaturated fatty acid which is generally believed to be safe, as enhancer and investigates the synergistic effect of oleic acid and propylene glycol (PG) on optical clearing of skin tissue in vitro. Experimental results from near infrared spectroscopy, mass loss measurement and transdermal skin resistance (TSR) assessment showed that, compared with dimethyl sulfoxide (DMSO) as enhancer, oleic acid obtained the similar clearing effect. However, due to its potential toxicity, DMSO has been controversial in clinical application. Therefore, in terms of optical application and clinic safety, the results presented revealed that oleic acid could be an optimum choice as enhancer for optical clearing of skin tissue.

Non-invasive glucose monitoring with optical methods has obtained increasing interest, in that the methods have shown great benefit for diabetes. Nevertheless, low sensitivity and signal to noise ratio (ratio of effective photons) are two major difficulties in non-invasively NIR spectral monitoring of blood glucose concentration. Designing the optical probe properly is one of the effective ways to improve measuring sensitivity and ratio of effective photons. In this paper, definition about ratio of effective photons in measurement of glucose is introduced. And then effect of glucose on optical properties of human skin is analyzed, based on this, two kind of sensitivities for diffuse reflectance, namely sensitivity to absorption and that to scattering, is derived. To investigate the ratio of effective photons and sensitivities, Monte Carlo simulations have been performed on a three-layered media with optical parameters similar to those of human skin. The results have shown that (1) high ratio of effective photons, even as high as 60%, can be obtained by choosing proper the separation between source and detector; (2) sensitivity of diffuse reflectance to absorption and scattering has different dependence on source-detector separation, which enables one can have different options by making use of different effect from glucose level changing. In the end, some suggestions have been put forward to improve precision of measurement of blood glucose.

Effects of laser at the wavelength of 650 nm on the isolated vessels of white rat mesentery have been analyzed. Influence of laser irradiation on the statement of blood microcirculation in mucous membrane of human oral cavity has been investigated. Temporal changes of hemodynamics have been studied by methods of laser photoplethysmography, Doppler diagnostics and laser speckle imaging technique. Influence of coherent light (at the wavelength 630 nm) on the intensity of microcirculation in the capillary net of mucous membrane has been demonstrated directly during the short-time session of laser therapy.

A non-invasive and continuous blood glucose monitoring would be of great advantage for diabetic patients. Many techniques have been proposed for the purpose. But so far, none of these methods has been proven to be reliable and precise enough for in vivo monitoring. In non-invasive glucose measurement using near-infrared (NIR) spectroscopy, the difficulty is that the spectral variations due to the glucose concentration are extremely small compared with other sources of variations. Therefore extracting the variation signal of glucose in complicated background is challenging. We investigated the relationship between sample complexity and prediction accuracy, which was the fundamental research of non-invasive sensing and a kind of method to determine whether the OGTT or non-invasive sensing can achieve the required accuracy of clinic. A series of in vitro experiments had been conducted with different complex samples and same measurement system to analyze the relation between the sample complexity and the prediction accuracy, and some conclusions had been drawn. In general, the increase of sample complexity doesn’t lead to the distinct increase of prediction error.

The main idea of our work is studying of human brain activity for intense NIR-radiation, cold stress or visual stimulation. For the first part of solution we need to find the power density, which needed for brain response observation. For this, we created Monte-Carlo simulation software and make a comparing with out experimental data.