Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling

Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculate

Design Space Exploration and Manipulation for Cyber Physical Systems

Abstract. Cyber-Physical Systems (CPS) [1] are engineered systems that require tight interaction between physical and computational components. Designing a CPS is highly challenging [2] because these systems are inherently complex, need significant effort to describe and evaluate a vast set of crossdisciplinary interactions, and require seamless meshing of physical elements with corresponding software artifacts. Moreover, a large set of architectural and composable alternatives must be systematically explored and evaluated in the context of a highly constrained design space. The constraints imposed on the selection of alternatives are derived from the system’s functional, performance, dimensional, physical, and economical objectives. Furthermore, the design process of these systems is highly iterative and requires continuous integration of design generation with design selection and manipulation supported by design analyses. Existing computer-aided design tools are not well-suited for this method of design. To facilitate the iterative design process for CPS-s, we have developed a design toolchain, OpenMETA [4] [9], built around a Domain-Specific Modeling Language (DSML) [3], called the Cyber-Physical Modeling Language (CyPhyML). In this paper, we present parts OpenMETA that address the requirements of Design Space Exploration and Manipulation (DSEM) for CPS-s

2004 IEEE International Conference on Systems, Man and Cybernetics Synthesis of Robust Task Schedules for Minimum Disruption Repair?

Abstract: An of-line scheduling algorithm considers resource. precedence, and synchroniiariori requiremenrs of a task graph, and generates a schedule guaranteeing its timing reqiiiremenrs. This schedule must, howe~~er, be executed in a dyamic arid rrnpredictoble operating envirotiment nhere resources may fail arid tasks may ereciite loriger than eryected. To accormnodate such execution iincerrairities, this paper addresses the synthesis of robirst task schedirles using a slack-based approach and proposes a solution using integer linear prograninling (ILP). An ILP mode/, whose solirrion nia.vimiies the teniporal j7e.ribility of rhe overall task schedule, is fornirrlated; Tiuo different ILP solvers are used to solve this model and their perforniarice compared. For laige task graphs. an efJicienr approximate method is presented arid its peiformartce evaluated