nt inside the spine were modeled as four binding reactions with different speeds, but the same affinity. Parameter definition: the activated area The activation of calcineurin and CaMKII by calmodulin displays distinct temporal characteristics. For the purpose of representing effective enzyme activity, we integrated the concentration of activated calcineurin and CaMKII over time, and calculated the area above the basal level of activity. This is defined as the “activated area”as shown in Modeling and simulation software The model was based on the description of biochemical processes using continuous variables, that were simulated with a deterministic method. Modeling and simulation were performed using the E-Cell system, version 3. E-Cell is a module based, object-oriented simulation environment suitable for the modeling, simulation and analysis of large scale cell biological models. E-Cell defines the simulation model as a set of objects connected to each other. A biochemical reaction can be built by connecting variable, process, and stepper objects, where a variable represents a molecular species, a parameter or a container, a Calcium Spikes Modulate Synaptic Plasticity process represents the kinetic law that results in changes in the values of one or several variables, and a stepper attaches a specific simulation algorithm to a set of processes. E-Cell supports various stepper functions, and can incorporate different algorithms and time scales into one model via its unique discrete integration metaalgorithm. A generic ODEStepper, based on combined Radau 5 and Dormand-Prince 57M algorithms, was used for the elementary reactions. E-Cell switches between these two algorithms depending on the stiffness of the system of equations at a given time point. Simulations were performed on the computing cluster of the European Bioinformatics Institute, which is composed of Intel-based nodes under GNU/Linux. The simulations were launched concurrently, with each simulation for a specific calcium firing frequency running on an individual core. the system considered the opening was 5 milliseconds, and calculated the new influx constant 
based on this new opening time. In 2004, it was discovered that the reason why some patients with adenocarcinomas of the lung responded in spectacular form to treatment with tyrosine kinase inhibitors of EGFR was specifically due to the existence of activating mutations of this gene. This discovery caused a wave of enthusiasm in the therapy of such an aggressive tumour. Study of the mutational state of EGFR became a matter of urgent necessity in patients with adenocarcinomas of the lung. The most commonly used methodology for this purpose has been, and will probably continue to be, direct sequencing of PCR products. The main drawbacks of this method are its low sensitivity and the significant risk of contamination involved in handling post-PCR products. Nevertheless, useful and ingenious alternatives have been developed but, despite their proven sensitivity, they have never become popular. Furthermore, recent advances in molecular techniques have enabled the development of more sensitive methods for detecting mutations with MLN1117 site real-time quantitative PCR, using specific probes or amplified refractory mutation system technology. Most recently, the development of EGFR mutant-specific antibodies for immunohistochemistry has presented a new method for consideration. Seven years after this major discovery, there is still no st
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