Mathematical modeling of tumor therapy with oncolytic viruses: Effects of parametric heterogeneity on cell dynamics

One of the mechanisms that ensure cancer robustness is tumor heterogeneity, and its effects on tumor cells dynamics have to be taken into account when studying cancer progression. There is no unifying theoretical framework in mathematical modeling of carcinogenesis that would account for parametric heterogeneity. Here we formulate a modeling approach that naturally takes stock of inherent cancer cell heterogeneity and illustrate it with a model of interaction between a tumor and an oncolytic virus. We show that several phenomena that are absent in homogeneous models, such as cancer recurrence, tumor dormancy, an others, appear in heterogeneous setting. We also demonstrate that, within the applied modeling framework, to overcome the adverse effect of tumor cell heterogeneity on cancer progression, a heterogeneous population of an oncolytic virus must be used. Heterogeneity in parameters of the model, such as tumor cell susceptibility to virus infection and virus replication rate, can lead to complex, time-dependent behaviors of the tumor. Thus, irregular, quasi-chaotic behavior of the tumor-virus system can be caused not only by random perturbations but also by the heterogeneity of the tumor and the virus. The modeling approach described here reveals the importance of tumor cell and virus heterogeneity for the outcome of cancer therapy. It should be straightforward to apply these techniques to mathematical modeling of other types of anticancer therapy.Comment: 45 pages, 6 figures; submitted to Biology Direc

Uncertainty Quantification of the Responses of Transient Electromagnetic Disturbance Coupling to Transmission Lines Based on Stochastic Models

L'abstract è presente nell'allegato / the abstract is in the attachmen

Glaucoma detection of retinal images based on boundary segmentation

The rapid growth of technology makes it possible to implement in immediate diagnosis for patients using image processing. By using morphological processing and adaptive thresholding method for segmentation of optic disc and optic cup, various sizes of retinal fundus images captured through fundus camera from online databases can be processed. This paper explains the use of color channel separation method for pre-processing to remove noise for better optic disc and optic cup segmentation. Noise removal will improve image quality and in return help to increase segmentation standard. Then, morphological processing and adaptive thresholding method is used to extract out optic disc and optic cup from fundus image. The proposed method is tested on two publicly available online databases: RIM-ONE and DRIONS-DB. On RIM-ONE database, the average PSNR value acquired is 0.01891 and MSE is 65.62625. Meanwhile, for DRIONS-DB database, the best PSNR is 64.0928 and the MSE is 0.02647. In conclusion, the proposed method can successfully filter out any unwanted noise in the image and are able to help clearer optic disc and optic cup segmentation to be performed

Simplicity of Completion Time Distributions for Common Complex Biochemical Processes

Biochemical processes typically involve huge numbers of individual reversible steps, each with its own dynamical rate constants. For example, kinetic proofreading processes rely upon numerous sequential reactions in order to guarantee the precise construction of specific macromolecules. In this work, we study the transient properties of such systems and fully characterize their first passage (completion) time distributions. In particular, we provide explicit expressions for the mean and the variance of the completion time for a kinetic proofreading process and computational analyses for more complicated biochemical systems. We find that, for a wide range of parameters, as the system size grows, the completion time behavior simplifies: it becomes either deterministic or exponentially distributed, with a very narrow transition between the two regimes. In both regimes, the dynamical complexity of the full system is trivial compared to its apparent structural complexity. Similar simplicity is likely to arise in the dynamics of many complex multi-step biochemical processes. In particular, these findings suggest not only that one may not be able to understand individual elementary reactions from macroscopic observations, but also that such understanding may be unnecessary

High-Performance Computing for the Electromagnetic Modeling and Simulation of Interconnects

The electromagnetic modeling of packages and interconnects plays a very important role in the design of high-speed digital circuits, and is most efficiently performed by using computer-aided design algorithms. In recent years, packaging has become a critical area in the design of high-speed communication systems and fast computers, and the importance of the software support for their development has increased accordingly. Throughout this project, our efforts have focused on the development of modeling and simulation techniques and algorithms that permit the fast computation of the electrical parameters of interconnects and the efficient simulation of their electrical performance

Time domain analysis of switching transient fields in high voltage substations

Switching operations of circuit breakers and disconnect switches generate transient currents propagating along the substation busbars. At the moment of switching, the busbars temporarily acts as antennae radiating transient electromagnetic fields within the substations. The radiated fields may interfere and disrupt normal operations of electronic equipment used within the substation for measurement, control and communication purposes. Hence there is the need to fully characterise the substation electromagnetic environment as early as the design stage of substation planning and operation to ensure safe operations of the electronic equipment. This paper deals with the computation of transient electromagnetic fields due to switching within a high voltage air-insulated substation (AIS) using the finite difference time domain (FDTD) metho

Temporal Precision of Spike Trains in Extrastriate Cortex of the Behaving Macaque Monkey

How reliably do action potentials in cortical neurons encode information about a visual stimulus? Most physiological studies do not weigh the occurrences of particular action potentials as significant but treat them only as reflections of average neuronal excitation. We report that single neurons recorded in a previous study by Newsome et al. (1989; see also Britten et al. 1992) from cortical area MT in the behaving monkey respond to dynamic and unpredictable motion stimuli with a markedly reproducible temporal modulation that is precise to a few milliseconds. This temporal modulation is stimulus dependent, being present for highly dynamic random motion but absent when the stimulus translates rigidly