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  • Cot MAP K is the sole MAP K that


    Cot (MAP3K8) is the sole MAP3K that activates the MEK1/2-Erk1/2 following the activation of the TLR/IL-1 receptor superfamily as well as some receptors of the TNF receptor family [8], [9], [10] and mediates the production of chemokines and cytokines in different cell systems [reviewed in [11]]. Thus, Cot has an unique role in innate an adaptive immunity that cannot be replaced by any other protein. The human COT gene was identified as an oncogene in a truncated/modified form [12], [13], and although DNA sequencing analysis have demonstrated that mutations in Cot are rarely observed in humans [14], [15], it has been reported to be overexpressed in different types of human tumours, such as gastric/colon adenocarcinomas or breast cancer [reviewed in [16]]. Besides, Cot is involved in the resistance to a selective B-RAF kinase inhibitor in melanoma cell lines [17]. All these data indicate that physiologically, Cot is involved in innate and adaptive immunity, but enhanced Cot activity leads to cell transformation.
    Material and methods
    Results and discussion
    Acknowledgments This work was supported by a grant from the Ministerio de Ciencia e Innovación (SAF 2008-00819) and Mutua Madrileña. We are very grateful to Dr. Casey Wright, Dr. Victor Clavo and Prof. Philip Cohen for providing us respectively CHO inhibitor chemistry expressing CD30L, rapamycin and a pharmacological Cot Inhibitor.
    Introduction The Electronics Robustness Project managed by Technology Research Institute (IRT) Saint-Exupery has two main objectives: For the next 3years, chosen technologies for study are GaN (gallium nitride) commercial technologies for power switching and a 28nm FDSOI (Fully Depleted Silicon On Insulator) digital technology.
    Characterization/modeling of reliability and life time expectancy The most used mathematical approach in forecasting reliability is based on the Arrhenius law. While in chemistry, transition state theory aimed to explain the kinetics of reaction for elementary chemical reactions. This theory postulates the existence of a kind of chemical equilibrium, the near-equilibrium between reactants and activated transition complex as illustrated by Fig. 1. This theory allows to use the Free Gibbs Energy to calculate the probability of transition for a chemical reaction characterized by its rate of reaction proportional to the energy height of the transition state between the initial state and the intermediate state named ΔG‡ or Ea. Similarly to this physical law, electronic reliability prediction presented in paper [1] will postulate that the initial state of the component is corresponding to healthy devices considered electrically “good” within its specification limits and the final state of the component corresponds to out of specification limit devices then considered as failed. This theory allows determining the time to failure (TTF) of a component based on the activation energy Ea expressed in eV and the temperature T expressed in Kelvin according Arrhenius law:where A is a frequency factor and k is the Boltzmann's constant. From this theory, an extensive mathematical model was constructed whereas the energy provided by external stresses γ·S acting on the components (e.g., electrical transient, overvoltage, natural radiations) decreases the activation energy necessary for a state change and therefore acts as a catalyst, accelerating the degradation process. As illustrated by Fig. 2, the new activation energy equals: Applying Eq. (2) to Eq. (1), time to failure becomes: This model is known in literature as Boltzmann–Arrhenius–Zhurkov (BAZ) model [2], [3]. Therefore, it becomes necessary to characterize Ea and γ·S for each functional and physical parameter (e.g., value of leakage current) representative of the initial state of the component. As these settings are multiple and the stresses are combined, the development of a plan of experience becomes essential. A theoretical identification of the parameters affecting the robustness of the component must be realized first. Experience plan will promote environmental stress and the operating conditions to be applied to reveal this influence: High Temperature Operating Life (HTOL), Low Temperature Operating Life (LTOL), thermal shock, Electrical Over Stress, short circuit, Avalanche Breakdown….