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Information technology (IT) is a vital part of every organization today. Not only the products and services are based on IT, but also IT is necessary for supporting the organization's processes. As the role of IT becomes more eminent, IT management frameworks become more demanding. IT management guarantees the optimal utilization of IT resources within an organization. Although each of the IT management frameworks focuses on a particular part of this wide scope, implementing frameworks individually, wastes budget, and time results in incompatible or redundant artifacts. The question we want to answer in this research is if a comprehensive IT management methodology could be implemented to provide all the effective results of different IT management frameworks, yet to avoid redundancies and costs of implementing each framework separately. In this study, the integration of the ITIL framework as the most well-known IT service management framework, the COBIT framework as one of the most widely used IT management frameworks, and IT enterprise architecture as a comprehensive solution for identifying, designing, and implementing a desirable IT structure, is analyzed. We present an intuitive methodology to integrate these frameworks by investigating the elements and components of each framework and identifying the interactions of these components. To validate the proposed model, it was implemented in a company active in the transportation industry and the results were qualitatively evaluated from experts’ points of view. We found that the proposed methodology could generate all of the expected artifacts with less time and budget and could prevent the production of redundant/inconsistent outputs. [ABSTRACT FROM AUTHOR]

Temozolomide (TMZ) is a chemotherapy agent used to treat Grade IV astrocytoma, also known as glioblastoma (GBM). TMZ treatment causes DNA damage that results in tumor cell apoptosis and increases the survival rate of GBM patients. However, chemoresistance as a result of TMZ‐induced autophagy significantly reduces this anticancer effects over time. Statins are competitive inhibitors of HMG‐CoA reductase, the rate‐limiting enzyme of the mevalonate (MEV) cascade. Statins are best known for their cholesterol (CH)‐lowering effect. Long‐term consumption of statins, prior to and in parallel with other cancer therapeutic approaches, has been reported to increase the survival rate of patients with various forms of cancers. In this study, we investigated the potentiation of TMZ‐induced apoptosis by simvastatin (Simva) in human GBM cell lines and patient GBM cells, using cell monolayers and three‐dimensional cell culture systems. The incubation of cells with a combination of Simva and TMZ resulted in a significant increase in apoptotic cells compared to cells treated with TMZ alone. Incubation of cells with CH or MEV cascade intermediates failed to compensate the decrease in cell viability induced by the combined Simva and TMZ treatment. Simva treatment inhibited the autophagy flux induced by TMZ by blocking autophago‐lysosome formation. Our results suggest that Simva sensitizes GBM cells to TMZ‐induced cell death in a MEV cascade‐independent manner and identifies the inhibition of autophagosome‐lysosome fusion as a promising therapeutic strategy in the treatment of GBM. [ABSTRACT FROM AUTHOR]

An integrated guidance and feedback control scheme for steering an underactuated vehicle through desired waypoints in three-dimensional space, is developed here. The underactuated vehicle is modeled as a rigid body with four control inputs. These control inputs actuate the three degrees of freedom of rotational motion and one degree of freedom of translational motion in a vehicle body-fixed coordinate frame. This actuation model is appropriate for a wide range of underactuated vehicles including spacecraft with internal attitude actuators, vertical take-off and landing (VTOL) aircraft, fixed-wing multirotor unmanned aerial vehicles (UAVs), maneuverable robotic vehicles, etc. The guidance problem is developed on the special Euclidean group of rigid body motions, SE(3), in the framework ofgeometric mechanics, which represents the vehicle dynamics globally on this configuration manifold. The integrated guidance and control algorithm selects the desired trajectory for the translational motion that passes through the given waypoints, and the desired trajectory for the attitude based on the desired thrust direction to achieve the translational motion trajectory. A feedback control law is then obtained to steer the underactuated vehicle towards the desired trajectories in translation and rotation. This integrated guidance and control scheme takes into account known bounds on control inputs and generates a trajectory that is continuous and at least twice differentiable, which can be implemented with continuous and bounded control inputs. The integrated guidance and feedback control scheme is applied to an underactuated quadcopter UAV to autonomously generate a trajectory through a series of given waypoints in SE(3) and track the desired trajectory in finite time. The overall stability analysis of the feedback system is addressed. Discrete time models for the dynamics and control schemes of the UAV are obtained in the form of Lie group variational integrators using the discrete Lagrange-d'Alembert principle. Almost global asymptotic stability of the feedback system over its state space is shown analytically and verified through numerical simulations. [ABSTRACT FROM AUTHOR]