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.

Adaptive Routing of QoS-constrained Media Streams over Scalable Overlay Topologies

Current research on Internet-based distributed systems emphasizes the scalability of overlay topologies for efficient search and retrieval of data items, as well as routing amongst peers. However, most existing approaches fail to address the transport of data across these logical networks in accordance with quality of service (QoS) constraints. Consequently, this paper investigates the use of scalable overlay topologies for routing real-time media streams between publishers and potentially many thousands of subscribers. Specifically, we analyze the costs of using k-ary n-cubes for QoS-constrained routing. Given a number of nodes in a distributed system, we calculate the optimal k-ary n-cube structure for minimizing the average distance between any pair of nodes. Using this structure, we describe a greedy algorithm that selects paths between nodes in accordance with the real-time delays along physical links. We show this method improves the routing latencies by as much as 67%, compared to approaches that do not consider physical link costs. We are in the process of developing a method for adaptive node placement in the overlay topology, based upon the locations of publishers, subscribers, physical link costs and per-subscriber QoS constraints. One such method for repositioning nodes in logical space is discussed, to improve the likelihood of meeting service requirements on data routed between publishers and subscribers. Future work will evaluate the benefits of such techniques more thoroughly.

Informed Content Delivery Across Adaptive Overlay Networks

Overlay networks have emerged as a powerful and highly flexible method for delivering content. We study how to optimize throughput of large, multipoint transfers across richly connected overlay networks, focusing on the question of what to put in each transmitted packet. We first make the case for transmitting encoded content in this scenario, arguing for the digital fountain approach which enables end-hosts to efficiently restitute the original content of size n from a subset of any n symbols from a large universe of encoded symbols. Such an approach affords reliability and a substantial degree of application-level flexibility, as it seamlessly tolerates packet loss, connection migration, and parallel transfers. However, since the sets of symbols acquired by peers are likely to overlap substantially, care must be taken to enable them to collaborate effectively. We provide a collection of useful algorithmic tools for efficient estimation, summarization, and approximate reconciliation of sets of symbols between pairs of collaborating peers, all of which keep messaging complexity and computation to a minimum. Through simulations and experiments on a prototype implementation, we demonstrate the performance benefits of our informed content delivery mechanisms and how they complement existing overlay network architectures.

Adaptive Weighing Designs for Keyword Value Computation

Attributing a dollar value to a keyword is an essential part of running any profitable search engine advertising campaign. When an advertiser has complete control over the interaction with and monetization of each user arriving on a given keyword, the value of that term can be accurately tracked. However, in many instances, the advertiser may monetize arrivals indirectly through one or more third parties. In such cases, it is typical for the third party to provide only coarse-grained reporting: rather than report each monetization event, users are aggregated into larger channels and the third party reports aggregate information such as total daily revenue for each channel. Examples of third parties that use channels include Amazon and Google AdSense. In such scenarios, the number of channels is generally much smaller than the number of keywords whose value per click (VPC) we wish to learn. However, the advertiser has flexibility as to how to assign keywords to channels over time. We introduce the channelization problem: how do we adaptively assign keywords to channels over the course of multiple days to quickly obtain accurate VPC estimates of all keywords? We relate this problem to classical results in weighing design, devise new adaptive algorithms for this problem, and quantify the performance of these algorithms experimentally. Our results demonstrate that adaptive weighing designs that exploit statistics of term frequency, variability in VPCs across keywords, and flexible channel assignments over time provide the best estimators of keyword VPCs.

Adaptive Reliable Multicast

An increasing number of applications, such as distributed interactive simulation, live auctions, distributed games and collaborative systems, require the network to provide a reliable multicast service. This service enables one sender to reliably transmit data to multiple receivers. Reliability is traditionally achieved by having receivers send negative acknowledgments (NACKs) to request from the sender the retransmission of lost (or missing) data packets. However, this Automatic Repeat reQuest (ARQ) approach results in the well-known NACK implosion problem at the sender. Many reliable multicast protocols have been recently proposed to reduce NACK implosion. But, the message overhead due to NACK requests remains significant. Another approach, based on Forward Error Correction (FEC), requires the sender to encode additional redundant information so that a receiver can independently recover from losses. However, due to the lack of feedback from receivers, it is impossible for the sender to determine how much redundancy is needed. In this paper, we propose a new reliable multicast protocol, called ARM for Adaptive Reliable Multicast. Our protocol integrates ARQ and FEC techniques. The objectives of ARM are (1) reduce the message overhead due to NACK requests, (2) reduce the amount of data transmission, and (3) reduce the time it takes for all receivers to receive the data intact (without loss). During data transmission, the sender periodically informs the receivers of the number of packets that are yet to be transmitted. Based on this information, each receiver predicts whether this amount is enough to recover its losses. Only if it is not enough, that the receiver requests the sender to encode additional redundant packets. Using ns simulations, we show the superiority of our hybrid ARQ-FEC protocol over the well-known Scalable Reliable Multicast (SRM) protocol.

SomeCast: A Paradigm for Real-Time Adaptive Reliable Multicast

SomeCast is a novel paradigm for the reliable multicast of real-time data to a large set of receivers over the Internet. SomeCast is receiver-initiated and thus scalable in the number of receivers, the diverse characteristics of paths between senders and receivers (e.g. maximum bandwidth and round-trip-time), and the dynamic conditions of such paths (e.g. congestion-induced delays and losses). SomeCast enables receivers to dynamically adjust the rate at which they receive multicast information to enable the satisfaction of real-time QoS constraints (e.g. rate, deadlines, or jitter). This is done by enabling a receiver to join SOME number of concurrent multiCAST sessions, whereby each session delivers a portion of an encoding of the real-time data. By adjusting the number of such sessions dynamically, client-specific QoS constraints can be met independently. The SomeCast paradigm can be thought of as a generalization of the AnyCast (e.g. Dynamic Server Selection) and ManyCast (e.g. Digital Fountain) paradigms, which have been proposed in the literature to address issues of scalability of UniCast and MultiCast environments, respectively. In this paper we overview the SomeCast paradigm, describe an instance of a SomeCast protocol, and present simulation results that quantify the significant advantages gained from adopting such a protocol for the reliable multicast of data to a diverse set of receivers subject to real-time QoS constraints.

An Adaptive Policy Management Approach to BGP Convergence

The Border Gateway Protocol (BGP) is the current inter-domain routing protocol used to exchange reachability information between Autonomous Systems (ASes) in the Internet. BGP supports policy-based routing which allows each AS to independently adopt a set of local policies that specify which routes it accepts and advertises from/to other networks, as well as which route it prefers when more than one route becomes available. However, independently chosen local policies may cause global conflicts, which result in protocol divergence. In this paper, we propose a new algorithm, called Adaptive Policy Management Scheme (APMS), to resolve policy conflicts in a distributed manner. Akin to distributed feedback control systems, each AS independently classifies the state of the network as either conflict-free or potentially-conflicting by observing its local history only (namely, route flaps). Based on the degree of measured conflicts (policy conflict-avoidance vs. -control mode), each AS dynamically adjusts its own path preferences—increasing its preference for observably stable paths over flapping paths. APMS also includes a mechanism to distinguish route flaps due to topology changes, so as not to confuse them with those due to policy conflicts. A correctness and convergence analysis of APMS based on the substability property of chosen paths is presented. Implementation in the SSF network simulator is performed, and simulation results for different performance metrics are presented. The metrics capture the dynamic performance (in terms of instantaneous throughput, delay, routing load, etc.) of APMS and other competing solutions, thus exposing the often neglected aspects of performance.

An Adaptive Management Approach to Resolving Policy Conflicts

The Border Gateway Protocol (BGP) is the current inter-domain routing protocol used to exchange reachability information between Autonomous Systems (ASes) in the Internet. BGP supports policy-based routing which allows each AS to independently define a set of local policies on which routes it accepts and advertises from/to other networks, as well as on which route it prefers when more than one route becomes available. However, independently chosen local policies may cause global conflicts, which result in protocol divergence. In this paper, we propose a new algorithm, called Adaptive Policy Management Scheme(APMS), to resolve policy conflicts in a distributed manner. Akin to distributed feedback control systems, each AS independently classifies the state of the network as either conflict-free or potentially conflicting by observing its local history only (namely, route flaps). Based on the degree of measured conflicts, each AS dynamically adjusts its own path preferences---increasing its preference for observably stable paths over flapping paths. APMS also includes a mechanism to distinguish route flaps due to topology changes, so as not to confuse them with those due to policy conflicts. A correctness and convergence analysis of APMS based on the sub-stability property of chosen paths is presented. Implementation in the SSF network simulator is performed, and simulation results for different performance metrics are presented. The metrics capture the dynamic performance (in terms of instantaneous throughput, delay, etc.) of APMS and other competing solutions, thus exposing the often neglected aspects of performance.

Adaptive Neural Models of Queuing and Timing in Fluent Action

Temporal structure in skilled, fluent action exists at several nested levels. At the largest scale considered here, short sequences of actions that are planned collectively in prefrontal cortex appear to be queued for performance by a cyclic competitive process that operates in concert with a parallel analog representation that implicitly specifies the relative priority of elements of the sequence. At an intermediate scale, single acts, like reaching to grasp, depend on coordinated scaling of the rates at which many muscles shorten or lengthen in parallel. To ensure success of acts such as catching an approaching ball, such parallel rate scaling, which appears to be one function of the basal ganglia, must be coupled to perceptual variables, such as time-to-contact. At a fine scale, within each act, desired rate scaling can be realized only if precisely timed muscle activations first accelerate and then decelerate the limbs, to ensure that muscle length changes do not under- or over-shoot the amounts needed for the precise acts. Each context of action may require a much different timed muscle activation pattern than similar contexts. Because context differences that require different treatment cannot be known in advance, a formidable adaptive engine-the cerebellum-is needed to amplify differences within, and continuosly search, a vast parallel signal flow, in order to discover contextual "leading indicators" of when to generate distinctive parallel patterns of analog signals. From some parts of the cerebellum, such signals controls muscles. But a recent model shows how the lateral cerebellum, such signals control muscles. But a recent model shows how the lateral cerebellum may serve the competitive queuing system (in frontal cortex) as a repository of quickly accessed long-term sequence memories. Thus different parts of the cerebellum may use the same adaptive engine system design to serve the lowest and the highest of the three levels of temporal structure treated. If so, no one-to-one mapping exists between levels of temporal structure and major parts of the brain. Finally, recent data cast doubt on network-delay models of cerebellar adaptive timing.

Adaptive Resonance Theory

SyNAPSE program of the Defense Advanced Projects Research Agency (Hewlett-Packard Company, subcontract under DARPA prime contract HR0011-09-3-0001, and HRL Laboratories LLC, subcontract #801881-BS under DARPA prime contract HR0011-09-C-0001); CELEST, an NSF Science of Learning Center (SBE-0354378)

Cerebellar Learning in an Opponent Motor Controller for Adaptive Load Compensation and Synergy Formation

This paper shows how a minimal neural network model of the cerebellum may be embedded within a sensory-neuro-muscular control system that mimics known anatomy and physiology. With this embedding, cerebellar learning promotes load compensation while also allowing both coactivation and reciprocal inhibition of sets of antagonist muscles. In particular, we show how synaptic long term depression guided by feedback from muscle stretch receptors can lead to trans-cerebellar gain changes that are load-compensating. It is argued that the same processes help to adaptively discover multi-joint synergies. Simulations of rapid single joint rotations under load illustrates design feasibility and stability.

Extracted Memory from Temporal Patterns Using Adaptive Resonance and Recurrent Network

We can recognize objects through receiving continuously huge temporal information including redundancy and noise, and can memorize them. This paper proposes a neural network model which extracts pre-recognized patterns from temporally sequential patterns which include redundancy, and memorizes the patterns temporarily. This model consists of an adaptive resonance system and a recurrent time-delay network. The extraction is executed by the matching mechanism of the adaptive resonance system, and the temporal information is processed and stored by the recurrent network. Simple simulations are examined to exemplify the property of extraction.

Fusion ARTMAP: An Adaptive Fuzzy Network for Multi-Channel Classification

Fusion ARTMAP is a self-organizing neural network architecture for multi-channel, or multi-sensor, data fusion. Fusion ARTMAP generalizes the fuzzy ARTMAP architecture in order to adaptively classify multi-channel data. The network has a symmetric organization such that each channel can be dynamically configured to serve as either a data input or a teaching input to the system. An ART module forms a compressed recognition code within each channel. These codes, in turn, beco1ne inputs to a single ART system that organizes the global recognition code. When a predictive error occurs, a process called parallel match tracking simultaneously raises vigilances in multiple ART modules until reset is triggered in one of thmn. Parallel match tracking hereby resets only that portion of the recognition code with the poorest match, or minimum predictive confidence. This internally controlled selective reset process is a type of credit assignment that creates a parsimoniously connected learned network.

Adaptive Neural Networks for Control of Movement Trajectories Invariant under Speed and Force Rescaling

This article describes two neural network modules that form part of an emerging theory of how adaptive control of goal-directed sensory-motor skills is achieved by humans and other animals. The Vector-Integration-To-Endpoint (VITE) model suggests how synchronous multi-joint trajectories are generated and performed at variable speeds. The Factorization-of-LEngth-and-TEnsion (FLETE) model suggests how outflow movement commands from a VITE model may be performed at variable force levels without a loss of positional accuracy. The invariance of positional control under speed and force rescaling sheds new light upon a familiar strategy of motor skill development: Skill learning begins with performance at low speed and low limb compliance and proceeds to higher speeds and compliances. The VITE model helps to explain many neural and behavioral data about trajectory formation, including data about neural coding within the posterior parietal cortex, motor cortex, and globus pallidus, and behavioral properties such as Woodworth's Law, Fitts Law, peak acceleration as a function of movement amplitude and duration, isotonic arm movement properties before and after arm-deafferentation, central error correction properties of isometric contractions, motor priming without overt action, velocity amplification during target switching, velocity profile invariance across different movement distances, changes in velocity profile asymmetry across different movement durations, staggered onset times for controlling linear trajectories with synchronous offset times, changes in the ratio of maximum to average velocity during discrete versus serial movements, and shared properties of arm and speech articulator movements. The FLETE model provides new insights into how spina-muscular circuits process variable forces without a loss of positional control. These results explicate the size principle of motor neuron recruitment, descending co-contractive compliance signals, Renshaw cells, Ia interneurons, fast automatic reactive control by ascending feedback from muscle spindles, slow adaptive predictive control via cerebellar learning using muscle spindle error signals to train adaptive movement gains, fractured somatotopy in the opponent organization of cerebellar learning, adaptive compensation for variable moment-arms, and force feedback from Golgi tendon organs. More generally, the models provide a computational rationale for the use of nonspecific control signals in volitional control, or "acts of will", and of efference copies and opponent processing in both reactive and adaptive motor control tasks.

Fuzzy ART: An Adaptive Resonance Algorithm for Rapid, Stable Classification of Analog Patterns

The Fuzzy ART system introduced herein incorporates computations from fuzzy set theory into ART 1. For example, the intersection (n) operator used in ART 1 learning is replaced by the MIN operator (A) of fuzzy set theory. Fuzzy ART reduces to ART 1 in response to binary input vectors, but can also learn stable categories in response to analog input vectors. In particular, the MIN operator reduces to the intersection operator in the binary case. Learning is stable because all adaptive weights can only decrease in time. A preprocessing step, called complement coding, uses on-cell and off-cell responses to prevent category proliferation. Complement coding normalizes input vectors while preserving the amplitudes of individual feature activations.