The Scope of the IBGP Routing Anomaly Problem

Correctness problems in the iBGP routing, the de-facto standard to spread global routing information in Autonomous Systems, are a well-known issue. Configurations may route cost-suboptimal, inconsistent, or even behave non-convergent and -deterministic. However, even if a lot of studies have shown many exemplary problematic configurations, the exact scope of the problem is largely unknown: Up to now, it is not clear which problems may appear under which iBGP architectures. The exact scope of the iBGP correctness problem is of high theoretical and practical interest. Knowledge on the resistance of specific architecture schemes against certain anomaly classes and the reasons may help to improve other iBGP schemes. Knowledge on the specific problems of the different schemes helps to identify the right scheme for an AS and develop workarounds

Scalability of iBGP Path Diversity Concepts

Abstract. Improving the path diversity seems to be the next fundamental step in the iBGP evolution. Focusing the advantages an improvement of the path diversity implies, network protocol designers have disregarded the most critical drawback so far: The effect on the scalability of the iBGP routing, a fundamental requirement for production usage. This aspect is examined by the analyses discussed in our paper. In this paper, we provide the theoretical groundwork for scalability analyses of four highly relevant path diversity schemes. Based on this groundwork, we exemplarily predict the information load the schemes induce in a system of a large ISP. Generalizing the system-specific results, we give an outlook on the load that can be expected in comparable ASs. We found that for two schemes currently in the standardization process, scalability problems in large ASs as they are operated by ISPs seem likely

Scalability of iBGP Path Diversity Concepts

Part 9: Path DiversityInternational audienceImproving the path diversity seems to be the next fundamental step in the iBGP evolution. Focusing the advantages an improvement of the path diversity implies, network protocol designers have disregarded the most critical drawback so far: The effect on the scalability of the iBGP routing, a fundamental requirement for production usage. This aspect is examined by the analyses discussed in our paper.In this paper, we provide the theoretical groundwork for scalability analyses of four highly relevant path diversity schemes. Based on this groundwork, we exemplarily predict the information load the schemes induce in a system of a large ISP. Generalizing the system-specific results, we give an outlook on the load that can be expected in comparable ASs. We found that for two schemes currently in the standardization process, scalability problems in large ASs as they are operated by ISPs seem likely

Prediction of venetoclax activity in precursor B-ALL by functional assessment of apoptosis signaling

Deregulated cell death pathways contribute to leukemogenesis and treatment failure in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Intrinsic apoptosis signaling is regulated by different proapoptotic and antiapoptotic molecules: proapoptotic BCL-2 homology domain 3 (BH3) proteins activate prodeath molecules leading to cellular death, while antiapoptotic molecules including B-cell lymphoma 2 (BCL-2) prevent activation of prodeath proteins and counter-regulate apoptosis induction. Inhibition of these antiapoptotic regulators has become a promising strategy for anticancer treatment, but variable anticancer activities in different malignancies indicate the need for upfront identification of responsive patients. Here, we investigated the activity of the BCL-2 inhibitor venetoclax (VEN, ABT-199) in B-cell precursor acute lymphoblastic leukemia and found heterogeneous sensitivities in BCP-ALL cell lines and in a series of patient-derived primografts. To identify parameters of sensitivity and resistance, we evaluated genetic aberrations, gene-expression profiles, expression levels of apoptosis regulators, and functional apoptosis parameters analyzed by mitochondrial profiling using recombinant BH3-like peptides. Importantly, ex vivo VEN sensitivity was most accurately associated with functional BCL-2 dependence detected by BH3 profiling. Modeling clinical application of VEN in a preclinical trial in a set of individual ALL primografts, we identified that leukemia-free survival of VEN treated mice was precisely determined by functional BCL-2 dependence. Moreover, the predictive value of ex vivo measured functional BCL-2 dependence for preclinical in vivo VEN response was confirmed in an independent set of primograft ALL including T- and high risk-ALL. Thus, integrative analysis of the apoptosis signaling indicating mitochondrial addiction to BCL-2 accurately predicts antileukemia activity of VEN, robustly identifies VEN-responsive patients, and provides information for stratification and clinical guidance in future clinical applications of VEN in patients with ALL