A comparison of CMB- and HLA-based approaches to type I interoperability reference model problems for COTS-based distributed simulation

Commercial-off-the-shelf (COTS) simulation packages (CSPs) are software used by many simulation modellers to build and experiment with models of various systems in domains such as manufacturing, health, logistics and commerce. COTS distributed simulation deals with the interoperation of CSPs and their models. Such interoperability has been classified into six interoperability reference models. As part of an on-going standardisation effort, this paper introduces the COTS Simulation Package Emulator, a proposed benchmark that can be used to investigate Type I interoperability problems in COTS distributed simulation. To demonstrate its use, two approaches to this form of interoperability are discussed, an implementation of the CMB conservative algorithm, an example of a so-called “light” approach, and an implementation of the HLA TAR algorithm, an example of a so-called “heavy” approach. Results from experimentation over four federation topologies are presented and it is shown the HLA approach out performs the CMB approach in almost all cases. The paper concludes that the CSPE benchmark is a valid basis from which the most efficient approach to Type I interoperability problems for COTS distributed simulation can be discovered

Sweden: Political Developments and Data in 2019

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Interaction of the Retinoblastoma Protein with Orc1 and Its Recruitment to Human Origins of DNA Replication

Background: The retinoblastoma protein (Rb) is a crucial regulator of cell cycle progression by binding with E2F transcription factor and repressing the expression of a variety of genes required for the G1-S phase transition. Methodology/Principal Findings: Here we show that Rb and E2F1 directly participate in the control of initiation of DNA replication in human HeLa, U2OS and T98G cells by specifically binding to origins of DNA replication in a cell cycle regulated manner. We show that, both in vitro and inside the cells, the largest subunit of the origin recognition complex (Orc1) specifically binds hypo-phosphorylated Rb and that this interaction is competitive with the binding of Rb to E2F1. The displacement of Rb-bound Orc1 by E2F1 at origins of DNA replication marks the progression of the G1 phase of the cell cycle toward the G1-S border. Conclusions/Significance: The participation of Rb and E2F1 in the formation of the multiprotein complex that binds origins of DNA replication in mammalian cells appears to represent an effective mechanism to couple the expression of gene

The N-Terminal Domain of the Drosophila Retinoblastoma Protein Rbf1 Interacts with ORC and Associates with Chromatin in an E2F Independent Manner

The retinoblastoma (Rb) tumor suppressor protein can function as a DNA replication inhibitor as well as a transcription factor. Regulation of DNA replication may occur through interaction of Rb with the origin recognition complex (ORC).We characterized the interaction of Drosophila Rb, Rbf1, with ORC. Using expression of proteins in Drosophila S2 cells, we found that an N-terminal Rbf1 fragment (amino acids 1-345) is sufficient for Rbf1 association with ORC but does not bind to dE2F1. We also found that the C-terminal half of Rbf1 (amino acids 345-845) interacts with ORC. We observed that the amino-terminal domain of Rbf1 localizes to chromatin in vivo and associates with chromosomal regions implicated in replication initiation, including colocalization with Orc2 and acetylated histone H4.Our results suggest that Rbf1 can associate with ORC and chromatin through domains independent of the E2F binding site. We infer that Rbf1 may play a role in regulating replication directly through its association with ORC and/or chromatin factors other than E2F. Our data suggest an important role for retinoblastoma family proteins in cell proliferation and tumor suppression through interaction with the replication initiation machinery

On the Role of Mathematical Abstractions for Scientific Computing

A distinguished feature of scientific computing is the necessity to design software abstractions for approximations. The approximations are themselves abstractions of mathematical models, which also are abstractions. In this paper, the relation between different mathematical abstraction levels and scientific computing software is discussed, in particular with respect to the simulation of partial differential equations (PDEs). It is found that software based on continuous abstractions have more chances of being modular, than software based on discrete approximations of the continuous abstractions. Moreover, it is stated that coordinate-free abstractions are a solid foundation for the simulation of PDEs