Link Capacity Assignment in Dynamic Hierarchical Networks

The dynamic hierarchy, which is a generalization of the centralized, tree structured network, is introduced in this paper. First, a queueing network model of the dynamic hierarchy is formulated. Following the derivation of a network performance measure, probabilistic and heuristic assignment strategies are created. These strategies are compared through the use of analysis of variance procedures and preferred strategies are selected. It is found that a relatively simple heuristic strategy produces capacity assignments whose quality is comparable to that of the preferred probabilistic strategy

Link Models for Networks with Dynamic Topologies

Dynamic hierarchical networks represent an architectural strategy for employing adaptive behavior in applications sensitive to highly variable external demands or uncertain internal conditions. The characteristics of such architectures are described, and the significance of adaptive capability is discussed. The necessity for assessing the tradeoffs between performance improvements (reduced and bounded message transmission time, increased throughput) and the added costs (reconfiguration delays, redundant links, etc.) leads to the use of complex queueing models. The assumptions underlying the general model are stated, and a class of applicable models (queues in random environments or RE-queues) is introduced. Matrix-geometric methods are reviewed in terms of their suitability for addressing several variations of a subclass of RE-queue models. Matrix-geometric techniques are considered to offer the greatest promise for obtaining usable results for assessing the cost/benefit tradeoffs

Model Analysis in a Model Development Environment

The Model Analyzer is a utility that renders automated and semi-automated support of the model development process. A prototype of this tool, demonstrating the capability for diagnostic analysis of non-executable model representations, is described from both a user and designer perspective. Key concepts affecting design decisions are discussed in the context of an underlying theory of model representation an analysis. The importance of world-view-independent model representation is stressed as a precursor to the early employment of model diagnosis and analysis. An example serves to illustrate the capability of the current prototype and the importance of the design concepts and the UNIX, utilities yacc and lex in the Analyzer development

Modeling Networks with Dynamic Topologies

Dynamic hierarchical networks represent an architectural strategy for employing adaptive behavior in applications sensitive to highly variable external demands or uncertain internal conditions. The characteristics of such architectures are described, and the significance of adaptive capability is discussed. The necessity for assessing cost/benefit tradeoffs leads to the use of queueing network models. The general model, a network of M/M/1 queues in a random environment, is introduced and then is simplified so that the links may be treated as isolated M/M/1 queues in a random environment. This treatment yields a formula for approximate mean network delay by combining matrix-geometric results (mean queue length and mean delay) for the individual links. A discrete event simulation model is defined as a basis for cross-validation of the analytic model. Conditions under which the analytic model is considered valid are identified through comparison of the two models

Locally invasive, castrate-resistant prostate cancer in a Pten/Trp53 double knockout mouse model of prostate cancer monitored with non-invasive bioluminescent imaging.

Here we have improved an existing mouse model of prostate cancer based on prostate-specific deletion of Pten and Trp53 by incorporating a Cre-activatable luciferase reporter. By coupling the deletion of those genes to the activation of a luciferase reporter, we were able to monitor tumor burden non-invasively over time. We show that, consistent with previous reports, deletion of both Pten and Trp53 on a C57BL/6 background accelerates tumor growth and results in both the loss of androgen receptor expression and castrate resistant tumors as compared with loss of Pten alone. Loss of Trp53 results in the development of sarcomatoid histology and the expression of markers of epithelial-to-mesenchymal transition Zeb1 and vimentin, with kinetics and penetrance dependent on whether one or both alleles of Trp53 were deleted. Homozygous deletion of Trp53 and Pten resulted in uniformly lethal disease by 25 weeks. While we were able to detect locally invasive disease in the peritoneal cavity in aggressive tumors from the double knockout mice, we were unable to detect lymphatic or hematogenous metastatic disease in lymph nodes or at distant sites