Genes involved in complex adaptive processes tend to have highly conserved upstream regions in mammalian genomes

BACKGROUND:Recent advances in genome sequencing suggest a remarkable conservation in gene content of mammalian organisms. The similarity in gene repertoire present in different organisms has increased interest in studying regulatory mechanisms of gene expression aimed at elucidating the differences in phenotypes. In particular, a proximal promoter region contains a large number of regulatory elements that control the expression of its downstream gene. Although many studies have focused on identification of these elements, a broader picture on the complexity of transcriptional regulation of different biological processes has not been addressed in mammals. The regulatory complexity may strongly correlate with gene function, as different evolutionary forces must act on the regulatory systems under different biological conditions. We investigate this hypothesis by comparing the conservation of promoters upstream of genes classified in different functional categories.RESULTS:By conducting a rank correlation analysis between functional annotation and upstream sequence alignment scores obtained by human-mouse and human-dog comparison, we found a significantly greater conservation of the upstream sequence of genes involved in development, cell communication, neural functions and signaling processes than those involved in more basic processes shared with unicellular organisms such as metabolism and ribosomal function. This observation persists after controlling for G+C content. Considering conservation as a functional signature, we hypothesize a higher density of cis-regulatory elements upstream of genes participating in complex and adaptive processes.CONCLUSION:We identified a class of functions that are associated with either high or low promoter conservation in mammals. We detected a significant tendency that points to complex and adaptive processes were associated with higher promoter conservation, despite the fact that they have emerged relatively recently during evolution. We described and contrasted several hypotheses that provide a deeper insight into how transcriptional complexity might have been emerged during evolution.

Real-Time Databases: Issues and Applications (RTDB'96 Workshop Report)

This report summarizes the technical presentations and discussions that took place during RTDB'96: the First International Workshop on Real-Time Databases, which was held on March 7 and 8, 1996 in Newport Beach, California. The main goals of this project were to (1) review recent advances in real-time database systems research, (2) to promote interaction among real-time database researchers and practitioners, and (3) to evaluate the maturity and directions of real-time database technology.

Overlay Network Creation and Maintenance with Selfish Users

Overlay networks have been used for adding and enhancing functionality to the end-users without requiring modifications in the Internet core mechanisms. Overlay networks have been used for a variety of popular applications including routing, file sharing, content distribution, and server deployment. Previous work has focused on devising practical neighbor selection heuristics under the assumption that users conform to a specific wiring protocol. This is not a valid assumption in highly decentralized systems like overlay networks. Overlay users may act selfishly and deviate from the default wiring protocols by utilizing knowledge they have about the network when selecting neighbors to improve the performance they receive from the overlay. This thesis goes against the conventional thinking that overlay users conform to a specific protocol. The contributions of this thesis are threefold. It provides a systematic evaluation of the design space of selfish neighbor selection strategies in real overlays, evaluates the performance of overlay networks that consist of users that select their neighbors selfishly, and examines the implications of selfish neighbor and server selection to overlay protocol design and service provisioning respectively. This thesis develops a game-theoretic framework that provides a unified approach to modeling Selfish Neighbor Selection (SNS) wiring procedures on behalf of selfish users. The model is general, and takes into consideration costs reflecting network latency and user preference profiles, the inherent directionality in overlay maintenance protocols, and connectivity constraints imposed on the system designer. Within this framework the notion of user’s "best response" wiring strategy is formalized as a k-median problem on asymmetric distance and is used to obtain overlay structures in which no node can re-wire to improve the performance it receives from the overlay. Evaluation results presented in this thesis indicate that selfish users can reap substantial performance benefits when connecting to overlay networks composed of non-selfish users. In addition, in overlays that are dominated by selfish users, the resulting stable wirings are optimized to such great extent that even non-selfish newcomers can extract near-optimal performance through naïve wiring strategies. To capitalize on the performance advantages of optimal neighbor selection strategies and the emergent global wirings that result, this thesis presents EGOIST: an SNS-inspired overlay network creation and maintenance routing system. Through an extensive measurement study on the deployed prototype, results presented in this thesis show that EGOIST’s neighbor selection primitives outperform existing heuristics on a variety of performance metrics, including delay, available bandwidth, and node utilization. Moreover, these results demonstrate that EGOIST is competitive with an optimal but unscalable full-mesh approach, remains highly effective under significant churn, is robust to cheating, and incurs minimal overheads. This thesis also studies selfish neighbor selection strategies for swarming applications. The main focus is on n-way broadcast applications where each of n overlay user wants to push its own distinct file to all other destinations as well as download their respective data files. Results presented in this thesis demonstrate that the performance of our swarming protocol for n-way broadcast on top of overlays of selfish users is far superior than the performance on top of existing overlays. In the context of service provisioning, this thesis examines the use of distributed approaches that enable a provider to determine the number and location of servers for optimal delivery of content or services to its selfish end-users. To leverage recent advances in virtualization technologies, this thesis develops and evaluates a distributed protocol to migrate servers based on end-users demand and only on local topological knowledge. Results under a range of network topologies and workloads suggest that the performance of the distributed deployment is comparable to that of the optimal but unscalable centralized deployment.

Forewarding in Mobile Opportunistic Networks

Recent advances in processor speeds, mobile communications and battery life have enabled computers to evolve from completely wired to completely mobile. In the most extreme case, all nodes are mobile and communication takes place at available opportunities – using both traditional communication infrastructure as well as the mobility of intermediate nodes. These are mobile opportunistic networks. Data communication in such networks is a difficult problem, because of the dynamic underlying topology, the scarcity of network resources and the lack of global information. Establishing end-to-end routes in such networks is usually not feasible. Instead a store-and-carry forwarding paradigm is better suited for such networks. This dissertation describes and analyzes algorithms for forwarding of messages in such networks. In order to design effective forwarding algorithms for mobile opportunistic networks, we start by first building an understanding of the set of all paths between nodes, which represent the available opportunities for any forwarding algorithm. Relying on real measurements, we enumerate paths between nodes and uncover what we refer to as the path explosion effect. The term path explosion refers to the fact that the number of paths between a randomly selected pair of nodes increases exponentially with time. We draw from the theory of epidemics to model and explain the path explosion effect. This is the first contribution of the thesis, and is a key observation that underlies subsequent results. Our second contribution is the study of forwarding algorithms. For this, we rely on trace driven simulations of different algorithms that span a range of design dimensions. We compare the performance (success rate and average delay) of these algorithms. We make the surprising observation that most algorithms we consider have roughly similar performance. We explain this result in light of the path explosion phenomenon. While the performance of most algorithms we studied was roughly the same, these algorithms differed in terms of cost. This prompted us to focus on designing algorithms with the explicit intent of reducing costs. For this, we cast the problem of forwarding as an optimal stopping problem. Our third main contribution is the design of strategies based on optimal stopping principles which we refer to as Delegation schemes. Our analysis shows that using a delegation scheme reduces cost over naive forwarding by a factor of O(√N), where N is the number of nodes in the network. We further validate this result on real traces, where the cost reduction observed is even greater. Our results so far include a key assumption, which is unbounded buffers on nodes. Next, we relax this assumption, so that the problem shifts to one of prioritization of messages for transmission and dropping. Our fourth contribution is the study of message prioritization schemes, combined with forwarding. Our main result is that one achieves higher performance by assigning higher priorities to young messages in the network. We again interpret this result in light of the path explosion effect.