Dynamic Server Selection in the Internet

As distributed information services like the World Wide Web become increasingly popular on the Internet, problems of scale are clearly evident. A promising technique that addresses many of these problems is service (or document) replication. However, when a service is replicated, clients then need the additional ability to find a "good" provider of that service. In this paper we report on techniques for finding good service providers without a priori knowledge of server location or network topology. We consider the use of two principal metrics for measuring distance in the Internet: hops, and round-trip latency. We show that these two metrics yield very different results in practice. Surprisingly, we show data indicating that the number of hops between two hosts in the Internet is not strongly correlated to round-trip latency. Thus, the distance in hops between two hosts is not necessarily a good predictor of the expected latency of a document transfer. Instead of using known or measured distances in hops, we show that the extra cost at runtime incurred by dynamic latency measurement is well justified based on the resulting improved performance. In addition we show that selection based on dynamic latency measurement performs much better in practice that any static selection scheme. Finally, the difference between the distribution of hops and latencies is fundamental enough to suggest differences in algorithms for server replication. We show that conclusions drawn about service replication based on the distribution of hops need to be revised when the distribution of latencies is considered instead.

Dynamic Server Selection using Bandwidth Probing in Wide-Area Networks

Replication is a commonly proposed solution to problems of scale associated with distributed services. However, when a service is replicated, each client must be assigned a server. Prior work has generally assumed that assignment to be static. In contrast, we propose dynamic server selection, and show that it enables application-level congestion avoidance. To make dynamic server selection practical, we demonstrate the use of three tools. In addition to direct measurements of round-trip latency, we introduce and validate two new tools: bprobe, which estimates the maximum possible bandwidth along a given path; and cprobe, which estimates the current congestion along a path. Using these tools we demonstrate dynamic server selection and compare it to previous static approaches. We show that dynamic server selection consistently outperforms static policies by as much as 50%. Furthermore, we demonstrate the importance of each of our tools in performing dynamic server selection.

Load Profiling for Efficient Route Selection in Multi-Class Networks

High-speed networks, such as ATM networks, are expected to support diverse Quality of Service (QoS) constraints, including real-time QoS guarantees. Real-time QoS is required by many applications such as those that involve voice and video communication. To support such services, routing algorithms that allow applications to reserve the needed bandwidth over a Virtual Circuit (VC) have been proposed. Commonly, these bandwidth-reservation algorithms assign VCs to routes using the least-loaded concept, and thus result in balancing the load over the set of all candidate routes. In this paper, we show that for such reservation-based protocols|which allow for the exclusive use of a preset fraction of a resource's bandwidth for an extended period of time-load balancing is not desirable as it results in resource fragmentation, which adversely affects the likelihood of accepting new reservations. In particular, we show that load-balancing VC routing algorithms are not appropriate when the main objective of the routing protocol is to increase the probability of finding routes that satisfy incoming VC requests, as opposed to equalizing the bandwidth utilization along the various routes. We present an on-line VC routing scheme that is based on the concept of "load profiling", which allows a distribution of "available" bandwidth across a set of candidate routes to match the characteristics of incoming VC QoS requests. We show the effectiveness of our load-profiling approach when compared to traditional load-balancing and load-packing VC routing schemes.

Improving the Performance of Overlay Routing and P2P File Sharing using Selfish Neighbor Selection

A foundational issue underlying many overlay network applications ranging from routing to P2P file sharing is that of connectivity management, i.e., folding new arrivals into the existing mesh and re-wiring to cope with changing network conditions. Previous work has considered the problem from two perspectives: devising practical heuristics for specific applications designed to work well in real deployments, and providing abstractions for the underlying problem that are tractable to address via theoretical analyses, especially game-theoretic analysis. Our work unifies these two thrusts first by distilling insights gleaned from clean theoretical models, notably that under natural resource constraints, selfish players can select neighbors so as to efficiently reach near-equilibria that also provide high global performance. Using Egoist, a prototype overlay routing system we implemented on PlanetLab, we demonstrate that our neighbor selection primitives significantly outperform existing heuristics on a variety of performance metrics; that Egoist is competitive with an optimal, but unscalable full-mesh approach; and that it remains highly effective under significant churn. We also describe variants of Egoist's current design that would enable it to scale to overlays of much larger scale and allow it to cater effectively to applications, such as P2P file sharing in unstructured overlays, based on the use of primitives such as scoped-flooding rather than routing.

EGOIST: Overlay Routing Using Selfish Neighbor Selection

A foundational issue underlying many overlay network applications ranging from routing to P2P file sharing is that of connectivity management, i.e., folding new arrivals into an existing overlay, and re-wiring to cope with changing network conditions. Previous work has considered the problem from two perspectives: devising practical heuristics for specific applications designed to work well in real deployments, and providing abstractions for the underlying problem that are analytically tractable, especially via game-theoretic analysis. In this paper, we unify these two thrusts by using insights gleaned from novel, realistic theoretic models in the design of Egoist – a prototype overlay routing system that we implemented, deployed, and evaluated on PlanetLab. Using measurements on PlanetLab and trace-based simulations, we demonstrate that Egoist's neighbor selection primitives significantly outperform existing heuristics on a variety of performance metrics, including delay, available bandwidth, and node utilization. Moreover, we 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 overhead. Finally, we discuss some of the potential benefits Egoist may offer to applications.

Implications of Selfish Neighbor Selection in Overlay Networks

In a typical overlay network for routing or content sharing, each node must select a fixed number of immediate overlay neighbors for routing traffic or content queries. A selfish node entering such a network would select neighbors so as to minimize the weighted sum of expected access costs to all its destinations. Previous work on selfish neighbor selection has built intuition with simple models where edges are undirected, access costs are modeled by hop-counts, and nodes have potentially unbounded degrees. However, in practice, important constraints not captured by these models lead to richer games with substantively and fundamentally different outcomes. Our work models neighbor selection as a game involving directed links, constraints on the number of allowed neighbors, and costs reflecting both network latency and node preference. We express a node's "best response" wiring strategy as a k-median problem on asymmetric distance, and use this formulation to obtain pure Nash equilibria. We experimentally examine the properties of such stable wirings on synthetic topologies, as well as on real topologies and maps constructed from PlanetLab and AS-level Internet measurements. Our results indicate that selfish nodes can reap substantial performance benefits when connecting to overlay networks composed of non-selfish nodes. On the other hand, in overlays that are dominated by selfish nodes, the resulting stable wirings are optimized to such great extent that even non-selfish newcomers can extract near-optimal performance through naive wiring strategies.

A Neural Model of Visually Guided Steering, Obstacle Avoidance, and Route Selection

A neural model is developed to explain how humans can approach a goal object on foot while steering around obstacles to avoid collisions in a cluttered environment. The model uses optic flow from a 3D virtual reality environment to determine the position of objects based on motion discotinuities, and computes heading direction, or the direction of self-motion, from global optic flow. The cortical representation of heading interacts with the representations of a goal and obstacles such that the goal acts as an attractor of heading, while obstacles act as repellers. In addition the model maintains fixation on the goal object by generating smooth pursuit eye movements. Eye rotations can distort the optic flow field, complicating heading perception, and the model uses extraretinal signals to correct for this distortion and accurately represent heading. The model explains how motion processing mechanisms in cortical areas MT, MST, and VIP can be used to guide steering. The model quantitatively simulates human psychophysical data about visually-guided steering, obstacle avoidance, and route selection.

Target Selection by Frontal Cortex During Coordinated Saccadic and Smooth Pursuit Eye Movement

Oculomotor tracking of moving objects is an important component of visually based cognition and planning. Such tracking is achieved by a combination of saccades and smooth pursuit eye movements. In particular, the saccadic and smooth pursuit systems interact to often choose the same target, and to maximize its visibility through time. How do multiple brain regions interact, including frontal cortical areas, to decide the choice of a target among several competing moving stimuli? How is target selection information that is created by a bias (e.g., electrical stimulation) transferred from one movement system to another? These saccade-pursuit interactions are clarified by a new computational neural model, which describes interactions among motion processing areas MT, MST, FPA, DLPN; saccade specification, selection, and planning areas LIP, FEF, SNr, SC; the saccadic generator in the brain stem; and the cerebellum. Model simulations explain a broad range of neuroanatomical and neurophysiological data. These results are in contrast with the simplest parallel model with no interactions between saccades and pursuit than common-target selection and recruitment of shared motoneurons. Actual tracking episodes in primates reveal multiple systematic deviations from predictions of the simplest parallel model, which are explained by the current model.

A Neural Model of Visually Guided Steering, Obstacle Avoidance, and Route Selection

A neural model is developed to explain how humans can approach a goal object on foot while steering around obstacles to avoid collisions in a cluttered environment. The model uses optic flow from a 3D virtual reality environment to determine the position of objects based on motion discontinuities, and computes heading direction, or the direction of self-motion, from global optic flow. The cortical representation of heading interacts with the representations of a goal and obstacles such that the goal acts as an attractor of heading, while obstacles act as repellers. In addition the model maintains fixation on the goal object by generating smooth pursuit eye movements. Eye rotations can distort the optic flow field, complicating heading perception, and the model uses extraretinal signals to correct for this distortion and accurately represent heading. The model explains how motion processing mechanisms in cortical areas MT, MST, and posterior parietal cortex can be used to guide steering. The model quantitatively simulates human psychophysical data about visually-guided steering, obstacle avoidance, and route selection.

Immunomodulatory effects exerted by Lactobacillus salivarius strains on innate immune cells

Despite increased application of commensal bacteria for attempting to improve the symptoms of a variety of inflammatory conditions, including inflammatory bowel diseases, diarrhoea and irritable bowel syndrome, therapeutic approaches that involve live bacteria are hampered by a limited understanding of bacterium-host interactions. Lactobacilli are natural inhabitants of the mammalian gastrointestinal tract and many lactobacilli are regarded as probiotics meaning that they exert a beneficial influence on the health status of their consumers. Modulation of immune responses is a plausible mechanism underlying these beneficial effects. The aim of this thesis was to investigate the effect of 33 Lactobacillus salivarius strains on the production of inflammatory cytokines from a variety of human and mouse immune cells. Induction of immune responses in vitro was shown to be bacterial- and mouse strain-dependent, cell type-dependent, blood donor-dependent and bacterial cell number-dependent. Collectively, these data suggest the importance of a case-by-case selection of candidate strains for their potential therapeutic application. Toll-like receptors (TLRs) recognize microbe-associated molecular patterns (MAMPs) and play a critical role in shaping microbial-specific innate and adaptive immune responses. Following ligand engagement, TLRs trigger a complex network of signalling that culminate in the production of inflammatory mediators. The investigation of the molecular mechanisms underlying the Lb. salivarius-host interaction resulted in the identification of a novel role for TLR2 in negatively regulating TLR4 signalling originated from subcellular compartments within macrophages. Notably, sustained activation of JAK/STAT cascade and M1-signature genes in TLR2-/- macrophages was ablated by selective TLR4 and JAK inhibitors and by absence of TLR4 in TLR2/4-/- cells. In addition, other negative regulators of TLR signalling triggered by Lb. salivarius strains were found to be the adapter molecules TIRAP and TRIF. Understanding negative regulation of TLR signalling may pave the way for the development of novel therapeutics to limit inflammation in multiple diseases.

The inverse limit of GIT quotients of Grassmannians by the maximal torus

There are finitely many GIT quotients of

Test-pattern selection for screening small-delay defects in very-deep submicrometer integrated circuits

Timing-related defects are major contributors to test escapes and in-field reliability problems for very-deep submicrometer integrated circuits. Small delay variations induced by crosstalk, process variations, power-supply noise, as well as resistive opens and shorts can potentially cause timing failures in a design, thereby leading to quality and reliability concerns. We present a test-grading technique that uses the method of output deviations for screening small-delay defects (SDDs). A new gate-delay defect probability measure is defined to model delay variations for nanometer technologies. The proposed technique intelligently selects the best set of patterns for SDD detection from an n-detect pattern set generated using timing-unaware automatic test-pattern generation (ATPG). It offers significantly lower computational complexity and excites a larger number of long paths compared to a current generation commercial timing-aware ATPG tool. Our results also show that, for the same pattern count, the selected patterns provide more effective coverage ramp-up than timing-aware ATPG and a recent pattern-selection method for random SDDs potentially caused by resistive shorts, resistive opens, and process variations. © 2010 IEEE.

Analysis of an asymptotic preserving scheme for linear kinetic equations in the diffusion limit

We present a mathematical analysis of the asymptotic preserving scheme proposed in [M. Lemou and L. Mieussens, SIAM J. Sci. Comput., 31 (2008), pp. 334-368] for linear transport equations in kinetic and diffusive regimes. We prove that the scheme is uniformly stable and accurate with respect to the mean free path of the particles. This property is satisfied under an explicitly given CFL condition. This condition tends to a parabolic CFL condition for small mean free paths and is close to a convection CFL condition for large mean free paths. Our analysis is based on very simple energy estimates. © 2010 Society for Industrial and Applied Mathematics.

Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice.

Excessive iron absorption is one of the main features of β-thalassemia and can lead to severe morbidity and mortality. Serial analyses of β-thalassemic mice indicate that while hemoglobin levels decrease over time, the concentration of iron in the liver, spleen, and kidneys markedly increases. Iron overload is associated with low levels of hepcidin, a peptide that regulates iron metabolism by triggering degradation of ferroportin, an iron-transport protein localized on absorptive enterocytes as well as hepatocytes and macrophages. Patients with β-thalassemia also have low hepcidin levels. These observations led us to hypothesize that more iron is absorbed in β-thalassemia than is required for erythropoiesis and that increasing the concentration of hepcidin in the body of such patients might be therapeutic, limiting iron overload. Here we demonstrate that a moderate increase in expression of hepcidin in β-thalassemic mice limits iron overload, decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. These data led us to suggest that therapeutics that could increase hepcidin levels or act as hepcidin agonists might help treat the abnormal iron absorption in individuals with β-thalassemia and related disorders.

Bayesian variable selection in structured high-dimensional covariate spaces with applications in genomics

We consider the problem of variable selection in regression modeling in high-dimensional spaces where there is known structure among the covariates. This is an unconventional variable selection problem for two reasons: (1) The dimension of the covariate space is comparable, and often much larger, than the number of subjects in the study, and (2) the covariate space is highly structured, and in some cases it is desirable to incorporate this structural information in to the model building process. We approach this problem through the Bayesian variable selection framework, where we assume that the covariates lie on an undirected graph and formulate an Ising prior on the model space for incorporating structural information. Certain computational and statistical problems arise that are unique to such high-dimensional, structured settings, the most interesting being the phenomenon of phase transitions. We propose theoretical and computational schemes to mitigate these problems. We illustrate our methods on two different graph structures: the linear chain and the regular graph of degree k. Finally, we use our methods to study a specific application in genomics: the modeling of transcription factor binding sites in DNA sequences. © 2010 American Statistical Association.