Combined Intra- and Inter-domain Traffic Engineering using Hot-Potato Aware Link Weights Optimization

A well-known approach to intradomain traffic engineering consists in finding the set of link weights that minimizes a network-wide objective function for a given intradomain traffic matrix. This approach is inadequate because it ignores a potential impact on interdomain routing. Indeed, the resulting set of link weights may trigger BGP to change the BGP next hop for some destination prefixes, to enforce hot-potato routing policies. In turn, this results in changes in the intradomain traffic matrix that have not been anticipated by the link weights optimizer, possibly leading to degraded network performance. We propose a BGP-aware link weights optimization method that takes these effects into account, and even turns them into an advantage. This method uses the interdomain traffic matrix and other available BGP data, to extend the intradomain topology with external virtual nodes and links, on which all the well-tuned heuristics of a classical link weights optimizer can be applied. A key innovative asset of our method is its ability to also optimize the traffic on the interdomain peering links. We show, using an operational network as a case study, that our approach does so efficiently at almost no extra computational cost.Comment: 12 pages, Short version to be published in ACM SIGMETRICS 2008, International Conference on Measurement and Modeling of Computer Systems, June 2-6, 2008, Annapolis, Maryland, US

Teaching and Learning by Analogy: Psychological Perspectives on the Parables of Jesus

Christian teachers are often encouraged to use Jesus’ teaching strategies as models for their own pedagogy. Jesus frequently utilized analogical comparisons, or parables, to help his learners understand elements of his Gospel message. Although teachers can use analogical models to facilitate comprehension, such models also can sow the seeds of confusion and misconception. Recent advances in cognitive psychology have provided new theoretical frameworks to help us understand how instructional analogies function in the teaching-learning process. The goal of this paper is to analyze Jesus’ analogical teaching from these psychological perspectives, with implications for all teachers who utilize instructional analogies. In addition to reviewing basic analogical learning processes, I explore a six-variable model to account systematically for potential analogical misconceptions

A common theme in interaction of bacterial immunoglobulin-binding proteins with immunoglobulins illustrated in the equine system

The M protein of Streptococcus equi subsp. equi known as fibrinogen-binding protein (FgBP) is a cell wall-associated protein with antiphagocytic activity that binds IgG. Recombinant versions of the seven equine IgG subclasses were used to investigate the subclass specificity of FgBP. FgBP bound predominantly to equine IgG4 and IgG7, with little or no binding to the other subclasses. Competitive binding experiments revealed that FgBP could inhibit the binding of staphylococcal protein A and streptococcal protein G to both IgG4 and IgG7, implicating the Fc interdomain region in binding to FgBP. To identify which of the two IgG Fc domains contributed to the interaction with FgBP, we tested two human IgG1/IgA1 domain swap mutants and found that both domains are required for full binding, with the CH3 domain playing a critical role. The binding site for FgBP was further localized using recombinant equine IgG7 antibodies with single or double point mutations to residues lying at the CH2-CH3 interface. We found that interaction of FgBP with equine IgG4 and IgG7 was able to disrupt C1q binding and antibody-mediated activation of the classical complement pathway, demonstrating an effective means by which S. equi may evade the immune response. The mode of interaction of FgBP with IgG fits a common theme for bacterial Ig-binding proteins. Remarkably, for those interactions studied in detail, it emerges that all the Ig-binding proteins target the CH2-CH3 domain interface, regardless of specificity for IgG or IgA, streptococcal or staphylococcal origin, or host species (equine or human)

On Compact Routing for the Internet

While there exist compact routing schemes designed for grids, trees, and Internet-like topologies that offer routing tables of sizes that scale logarithmically with the network size, we demonstrate in this paper that in view of recent results in compact routing research, such logarithmic scaling on Internet-like topologies is fundamentally impossible in the presence of topology dynamics or topology-independent (flat) addressing. We use analytic arguments to show that the number of routing control messages per topology change cannot scale better than linearly on Internet-like topologies. We also employ simulations to confirm that logarithmic routing table size scaling gets broken by topology-independent addressing, a cornerstone of popular locator-identifier split proposals aiming at improving routing scaling in the presence of network topology dynamics or host mobility. These pessimistic findings lead us to the conclusion that a fundamental re-examination of assumptions behind routing models and abstractions is needed in order to find a routing architecture that would be able to scale ``indefinitely.''Comment: This is a significantly revised, journal version of cs/050802

Cautious Weight Tuning for Link State Routing Protocols

Link state routing protocols are widely used for intradomain routing in the Internet. These protocols are simple to administer and automatically update paths between sources and destinations when the topology changes. However, finding link weights that optimize network performance for a given traffic scenario is computationally hard. The situation is even more complex when the traffic is uncertain or time-varying. We present an efficient heuristic for finding link settings that give uniformly good performance also under large changes in the traffic. The heuristic combines efficient search techniques with a novel objective function. The objective function combines network performance with a cost of deviating from desirable features of robust link weight settings. Furthermore, we discuss why link weight optimization is insensitive to errors in estimated traffic data from link load measurements. We assess performance of our method using traffic data from an operational IP backbone

Steric regulation of tandem calponin homology domain actin-binding affinity.

Tandem calponin homology (CH1-CH2) domains are common actin-binding domains in proteins that interact with and organize the actin cytoskeleton. Despite regions of high sequence similarity, CH1-CH2 domains can have remarkably different actin-binding properties, with disease-associated point mutants known to increase as well as decrease affinity for F-actin. To investigate features that affect CH1-CH2 affinity for F-actin in cells and in vitro, we perturbed the utrophin actin-binding domain by making point mutations at the CH1-CH2 interface, replacing the linker domain, and adding a polyethylene glycol (PEG) polymer to CH2. Consistent with a previous model describing CH2 as a steric negative regulator of actin binding, we find that utrophin CH1-CH2 affinity is both increased and decreased by modifications that change the effective "openness" of CH1 and CH2 in solution. We also identified interface mutations that caused a large increase in affinity without changing solution "openness," suggesting additional influences on affinity. Interestingly, we also observe nonuniform subcellular localization of utrophin CH1-CH2 that depends on the N-terminal flanking region but not on bulk affinity. These observations provide new insights into how small sequence changes, such as those found in diseases, can affect CH1-CH2 binding properties

Architecture for Mobile Heterogeneous Multi Domain Networks

Multi domain networks can be used in several scenarios including military, enterprize networks, emergency networks and many other cases. In such networks, each domain might be under its own administration. Therefore, the cooperation among domains is conditioned by individual domain policies regarding sharing information, such as network topology, connectivity, mobility, security, various service availability and so on. We propose a new architecture for Heterogeneous Multi Domain (HMD) networks, in which one the operations are subject to specific domain policies. We propose a hierarchical architecture, with an infrastructure of gateways at highest-control level that enables policy based interconnection, mobility and other services among domains. Gateways are responsible for translation among different communication protocols, including routing, signalling, and security. Besides the architecture, we discuss in more details the mobility and adaptive capacity of services in HMD. We discuss the HMD scalability and other advantages compared to existing architectural and mobility solutions. Furthermore, we analyze the dynamic availability at the control level of the hierarchy

Using cellular fitness to map the structure and function of a major facilitator superfamily effluxer.

The major facilitator superfamily (MFS) effluxers are prominent mediators of antimicrobial resistance. The biochemical characterization of MFS proteins is hindered by their complex membrane environment that makes in vitro biochemical analysis challenging. Since the physicochemical properties of proteins drive the fitness of an organism, we posed the question of whether we could reverse that relationship and derive meaningful biochemical parameters for a single protein simply from fitness changes it confers under varying strengths of selection. Here, we present a physiological model that uses cellular fitness as a proxy to predict the biochemical properties of the MFS tetracycline efflux pump, TetB, and a family of single amino acid variants. We determined two lumped biochemical parameters roughly describing Km and Vmax for TetB and variants. Including in vivo protein levels into our model allowed for more specified prediction of pump parameters relating to substrate binding affinity and pumping efficiency for TetB and variants. We further demonstrated the general utility of our model by solely using fitness to assay a library of tet(B) variants and estimate their biochemical properties