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© 2019, The Author(s). Protein methyltransferases (PMTs) comprise a major class of epigenetic regulatory enzymes with therapeutic relevance. Here we present a collection of chemical probes and associated reagents and data to elucidate the function of human and murine PMTs in cellular studies. Our collection provides inhibitors and antagonists that together modulate most of the key regulatory methylation marks on histones H3 and H4, providing an important resource for modulating cellular epigenomes. We describe a comprehensive and comparative characterization of the probe collection with respect to their potency, selectivity, and mode of inhibition. We demonstrate the utility of this collection in CD4 + T cell differentiation assays revealing the potential of individual probes to alter multiple T cell subpopulations which may have implications for T cell-mediated processes such as inflammation and immuno-oncology. In particular, we demonstrate a role for DOT1L in limiting Th1 cell differentiation and maintaining lineage integrity. This chemical probe collection and associated data form a resource for the study of methylation-mediated signaling in epigenetics, inflammation and beyond.

Internet eXchange Points (IXPs) play an ever-growing role in Internet inter-connection. To facilitate the exchange of routes amongst their members, IXPs provide Route Server (RS) services to dispatch the routes according to each member's peering policies. Nowadays, to make use of RSes, these policies must be disclosed to the IXP. This poses fundamental questions regarding the privacy guarantees of route-computation on confidential business information. Indeed, as evidenced by interaction with IXP administrators and a survey of network operators, this state of affairs raises privacy concerns among network administrators and even deters some networks from subscribing to RS services. We design sixpack1, an RS service that leverages Secure Multi-Party Computation (SMPC) to keep peering policies confidential, while extending, the functionalities of today's RSes. As SMPC is notoriously heavy in terms of communication and computation, our design and implementation of sixpack aims at moving computation outside of the SMPC without compromising the privacy guarantees. We assess the effectiveness and scalability of our system by evaluating a prototype implementation using traces of data from one of the largest IXPs in the world. Our evaluation results indicate that sixpack can scale to support privacy-preserving route-computation, even at IXPs with many hundreds of member networks., QC 20180122

Fast reroute and other forms of immediate failover have long been used to recover from certain classes of failures without invoking the network control plane. While the set of such techniques is growing, the level of resiliency to failures that this approach can provide is not adequately understood. In this paper, we embarked upon a systematic algorithmic study of the resiliency of forwarding tables in a variety of models (i.e., deterministic/probabilistic routing, with packet-headerrewriting, with packet-duplication). Our results show that the resiliency of a routing scheme depends on the "connectivity" k of a network, i.e., the minimum number of link deletions that partition a network. We complement our theoretical result with extensive simulations. We show that resiliency to four simultaneous link failures, with limited path stretch, can be achieved without any packet modification/duplication or randomization. Furthermore, our routing schemes provide resiliency against k - 1 failures, with limited path stretch, by storing log(k) bits in the packet header, with limited packet duplication, or with randomized forwarding technique., QC 20180207

To efficiently exploit the network resources operators, do traffic engineering (TE), i.e., adapt the routing of traffic to the prevailing demands. TE in large IP networks typically relies on configuring static link weights and splitting traffic between the resulting shortest paths via the Equal-Cost-MultiPath (ECMP) mechanism. Yet, despite its vast popularity, crucial operational aspects of TE via ECMP are still little-understood from an algorithmic viewpoint. We embark upon a systematic algorithmic study of TE with ECMP. We consider the standard model of TE with ECMP and prove that, in general, even approximating the optimal link-weight configuration for ECMP within any constant ratio is an intractable feat, settling a long-standing open question. We establish, in contrast, that ECMP can provably achieve optimal traffic flow for the important category of Clos datacenter networks. We last consider a well-documented shortcoming of ECMP: suboptimal routing of large ("elephant") flows. We present algorithms for scheduling "elephant" flows on top of ECMP (as in, e.g., Hedera) with provable approximation guarantees. Our results complement and shed new light on past experimental and empirical studies of the performance of TE with ECMP., QC 20180207

Fast Reroute (FRR) and other forms of immediate failover have long been used to recover from certain classes of failures without invoking the network control plane. While the set of such techniques is growing, the level of resiliency to failures that this approach can provide is not adequately understood. We embark upon a systematic algorithmic study of the resiliency of immediate failover in a variety of models (with/without packet marking/duplication, etc.). We leverage our findings to devise new schemes for immediate failover and show, both theoretically and experimentally, that these outperform existing approaches., QC 20180207

To optimize the flow of traffic in IP networks, operators do traffic engineering (TE), i.e., tune routing-protocol parameters in response to traffic demands. TE in IP networks typically involves configuring static link weights and splitting traffic between the resulting shortest-paths via the Equal- Cost-MultiPath (ECMP) mechanism. Unfortunately, ECMP is a notoriously cumbersome and indirect means for optimizing traffic flow, often leading to poor network performance. Also, obtaining accurate knowledge of traffic demands as the input to TE is elusive, and traffic conditions can be highly variable, further complicating TE.We leverage recently proposed schemes for increasing ECMP's expressiveness via carefully disseminated bogus information ("lies") to design COYOTE, a readily deployable TE scheme for robust and efficient network utilization. COYOTE leverages new algorithmic ideas to configure (static) traffic splitting ratios that are optimized with respect to all (even adversarially chosen) traffic scenarios within the operator's "uncertainty bounds". Our experimental analyses show that COYOTE significantly outperforms today's prevalent TE schemes in a manner that is robust to traffic uncertainty and variation. We discuss experiments with a prototype implementation of COYOTE., QC 20180206

The growing relevance of Internet eXchange Points (IXPs), where an increasing number of networks exchange routing information, poses fundamental questions regarding the privacy guarantees of confidential business information. To facilitate the exchange of routes among their members, IXPs provide Route Server (RS) services to dispatch the routes according to each member's export policies. Nowadays, to make use of RSes, these policies must be disclosed to the IXP. This state of affairs raises privacy concerns among network administrators and even deters some networks from subscribing to RS services. We design SIXPACK (which stands for "Securing Internet eXchange Points Against Curious onlooKers"), a RS service that leverages Secure Multi-Party Computation (SMPC) techniques to keep export policies confidential, while maintaining the same functionalities as today's RSes. We assess the effectiveness and scalability of our system by evaluating our prototype implementation and using traces of data from one of the largest IXPs in the world., QC 20180207

We study the Static-Routing-Resiliency problem, motivated by routing on the Internet: Given a graph G = (V, E), a unique destination vertex d, and an integer constant c > 0, does there exist a static and destination-based routing scheme such that the correct delivery of packets from any source s to the destination d is guaranteed so long as (1) no more than c edges fail and (2) there exists a physical path from s to d? We embark upon a study of this problem by relating the edge-connectivity of a graph, i.e., the minimum number of edges whose deletion partitions G, to its resiliency. Following the success of randomized routing algorithms in dealing with a variety of problems (e.g., Valiant load balancing in the network design problem), we embark upon a study of randomized routing algorithms for the Static-Routing-Resiliency problem. For any k-connected graph, we show a surprisingly simple randomized algorithm that has expected number of hops O(|V|k) if at most k-1 edges fail, which reduces to O(|V|) if only a fraction t of the links fail (where t < 1 is a constant). Furthermore, our algorithm is deterministic if the routing does not encounter any failed link., QC 20180207

Fast reroute and other forms of immediate failover have long been used to recover from certain classes of failures without invoking the network control plane. While the set of such techniques is growing, the level of resiliency to failures that this approach can provide is not adequately understood. In this paper, we embarked upon a systematic algorithmic study of the resiliency of forwarding tables in a variety of models (i.e., deterministic/probabilistic routing, with packet-header-rewriting, with packet-duplication). Our results show that the resiliency of a routing scheme depends on the “connectivity” k of a network, i.e., the minimum number of link deletions that partition a network. We complement our theoretical result with extensive simulations. We show that resiliency to four simultaneous link failures, with limited path stretch, can be achieved without any packet modification/duplication or randomization. Furthermore, our routing schemes provide resiliency against k-1 failures, with limited path stretch, by storing log(k) bits in the packet header, with limited packet duplication, or with randomized forwarding technique.

Fast Reroute (FRR) and other forms of immediate failover have long been used to recover from certain classes of failures without invoking the network control plane. While the set of such techniques is growing, the level of resiliency to failures that this approach can provide is not adequately understood. We embark upon a systematic algorithmic study of the resiliency of immediate failover in a variety of models (with/without packet marking/duplication, etc.). We leverage our findings to devise new schemes for immediate failover and show, both theoretically and experimentally, that these outperform existing approaches. © 2016 IEEE.

The growing relevance of Internet eXchange Points (IXPs), where an increasing number of networks exchange routing in-formation, poses fundamental questions regarding the privacy guarantees of confidential business information. To facilitate the exchange of routes among their members, IXPs provide Route Server (RS) services to dispatch the routes according to each member's export policies. Nowadays, to make use of RSes, these policies must be disclosed to the IXP. This state of affairs raises privacy concerns among network admin-istrators and even deters some networks from subscribing to RS services. We design sixpack (which stands for "Secur-ing Internet eXchange Points Against Curious onlooKers"), a RS service that leverages Secure Multi-Party Computa-tion (SMPC) techniques to keep export policies confidential, while maintaining the same functionalities as today's RSes. We assess the effectiveness and scalability of our system by evaluating our prototype implementation and using traces of data from one of the largest IXPs in the world. © 2016 Copyright held by the owner/author(s).

To efficiently exploit network resources operators do traffic engineering (TE), i.e., adapt the routing of traffic to the prevailing demands. TE in large IP networks typically relies on configuring static link weights and splitting traffic between the resulting shortest-paths via the Equal-Cost-MultiPath (ECMP) mechanism. Yet, despite its vast popularity, crucial operational aspects of TE via ECMP are still little-understood from an algorithmic viewpoint. We embark upon a systematic algorithmic study of TE with ECMP. We consider the standard model of TE with ECMP and prove that, in general, even approximating the optimal link-weight configuration for ECMP within any constant ratio is an intractable feat, settling a long-standing open question. We establish, in contrast, that ECMP can provably achieve optimal traffic flow for the important category of Clos datacenter networks. We last consider a well-documented shortcoming of ECMP: suboptimal routing of large ("elephant") flows. We present algorithms for scheduling "elephant" flows on top of ECMP (as in, e.g., Hedera [1]) with provable approximation guarantees. Our results complement and shed new light on past experimental and empirical studies of the performance of TE with ECMP., QC 20180207

To efficiently exploit network resources operators do traffic engineering (TE), i.e., adapt the routing of traffic to the prevailing demands. TE in large IP networks typically relies on configuring static link weights and splitting traffic between the resulting shortest-paths via the Equal-Cost-MultiPath (ECMP) mechanism. Yet, despite its vast popularity, crucial operational aspects of TE via ECMP are still little-understood from an algorithmic viewpoint. We embark upon a systematic algorithmic study of TE with ECMP. We consider the standard model of TE with ECMP and prove that, in general, even approximating the optimal link-weight configuration for ECMP within any constant ratio is an intractable feat, settling a long-standing open question. We establish, in contrast, that ECMP can provably achieve optimal traffic flow for the important category of Clos datacenter networks. We last consider a well-documented shortcoming of ECMP: suboptimal routing of large ('elephant') flows. We present algorithms for scheduling 'elephant' flows on top of ECMP (as in, e.g., Hedera [1]) with provable approximation guarantees. Our results complement and shed new light on past experimental and empirical studies of the performance of TE with ECMP. © 2014 IEEE.