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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.

Despite the long-standing belief that seawater viscosity is driven by temperature and salinity, biologically increased seawater viscosity has repeatedly been reported in relation to phytoplankton exudates in shallow, productive coastal waters. Here, seawater viscosity was investigated in relation to microbial and phytoplanktonic communities off the coast of East Antarctica along latitudinal transects located between 30°E and 80°E in sub-surface waters and at the deep chlorophyll maximum (DCM). The physical component of seawater viscosity observed along each transects ranged from 1.80 to 1.95 cP, while the actual seawater viscosity ranged from 1.85 to 3.69 cP. This resulted in biologically increased seawater viscosity reaching up to 84.9% in sub-surface waters and 77.6% at the DCM. Significant positive correlations were found between elevated seawater viscosity and (i) bacterial abundance in sub-surface waters and (ii) chlorophyll a concentration and the abundance of flow cytometrically-defined auto- and heterotrophic protists at the DCM. Among the 12 groups and 108 species of protists identified under light microscopy, dinoflagellates and more specifically Alexandrium tamarense and Prorocentrum sp. were the main contributors to the patterns observed for elevated seawater viscosity. Our observations, which generalised the link previously identified between seawater viscosity and phytoplankton composition and standing stock to the Southern Ocean, are the first demonstration of increases in seawater viscosity linked to marine bacterial communities, and suggest that the microbially-increased viscosity might quantitatively be at least as important as the one related to phytoplankton secretion. © 2009 Elsevier Ltd.

Wet atmospheric deposition of dissolved N, P and Si species is studied in well-mixed coastal ecosystem to evaluate its potential to stimulate photosynthetic activities in nutrient-depleted conditions. Our results show that, during spring, seawater is greatly depleted in major nutrients: Dissolved Inorganic Nitrogen (DIN), Dissolved Inorganic Phosphorus (DIP) and Silicic acid (Si), in parallel with an increase of phytoplanktonic biomass. In spring (March-May) and summer (June-September), wet atmospheric deposition is the predominant source (> 60%, relative to riverine contribution) for nitrates and ammonium inputs to this N-limited coastal ecosystem. During winter (October-February), riverine inputs of DIN predominate (> 80%) and are annually the most important source of DIP (> 90%). This situation allows us to calculate the possibility for a significant contribution to primary production in May 2003, from atmospheric deposition (total input for DIN approximate to 300 kg km(-2) month(-1)). Based on usual Redfield ratios and assuming that all of the atmospheric-derived N (AD-N) in rainwater is bioavailable for phytoplankton growth, we can estimate new production due to AD-N of 950 mg C m(-2) month(-1), during this period of depletion in the water column. During the same episode (May 2003), photosynthetic activity rate. considered as gross primary production, was estimated to approximately 30300 mg C m(-2) month(-1). Calculation indicates that new photosynthetic activity due to wet atmospheric inputs of nitrogen could be up to 3%. (c) 2006 Elsevier Ltd. All rights reserved.

Screening and prevention of colorectal cancer must be a public health priority. It is the most frequent malignancy in Europe, the second leading cause of cancer death, including Belgium where more than 6.000 new cases occur per year. Various screening modalities, from non invasive to invasive are available and currently in use and they are all cost-effective in comparison with no screening. The decision as to which screening test to use should be made by the patient and clinician. Consensus documents prepared by the Belgian scientific community appear in this issue of Acta Gastroenterologica Belgica, summarizing the scientific evidence in favour as well as the limitations of fecal occult blood tests, flexible sigmoidoscopy, videocolonoscopy and virtual colonoscopy.

SCOPUS: cp.j, info:eu-repo/semantics/published

SCOPUS: cp.j, info:eu-repo/semantics/published

BACKGROUND: The association between unexplained falls and cardiovascular causes is increasingly recognized. Neurally mediated cardiovascular disorders and hypotensive syndromes are found in almost 20 percent of the patients with unexplained falls. However, the approach to these patients remains unclear. Gait assessment might be an interesting approach to these patients as clinical observations suggests that those with cardiovascular or hypotensive causes may not manifest obvious gait alterations. Our primary objective is to analyze the association between gait disorders and a non-cardiovascular cause of falls in patients with unexplained falls. A second objective is to test the sensitivity and specificity of a gait assessment approach for detecting non-cardiovascular causes when compared with intrinsic-extrinsic classification. METHODS: Cross-sectional study performed in a falls clinic at a university hospital in 41 ambulatory elderly participants with unexplained falls. Neurally mediated cardiovascular conditions, neurological diseases, gait and balance problems were assessed. Gait disorder was defined as a gait velocity < 0.8 m/s or Tinetti Gait Score < 9. An attributable etiology of the fall was determined in each participant. Comparisons between the gait assessment approach and the attributable etiology regarding a neurally mediated cardiovascular cause were performed. Fisher exact test was used to test the association hypothesis. Sensitivity and specificity of gait assessment approach and intrinsic-extrinsic classification to detect a non-cardiovascular mediated fall was calculated with 95% confidence intervals (CI95%). RESULTS: A cardiovascular etiology (orthostatic and postprandial hypotension, vasovagal syndrome and carotid sinus hypersensitivity) was identified in 14% of participants (6/41). Of 35 patients with a gait disorder, 34 had a non-cardiovascular etiology of fall; whereas in 5 out of 6 patients without a gait disorder, a cardiovascular diagnosis wa

OBJECTIVES: The purpose of this retrospective study was to report a series of 9 new cases of fulminant hepatic failure due to metastatic liver disease and to identify signs to support a theory of hypoxia. METHODS: In these 9 cases and in 38 previously published cases of fulminant or subfulminant liver failure, we looked for clinical (shock, sepsis, and cutaneous signs of circulatory failure), laboratory (marked increase in serum aminotransferases levels) and histological (cell necrosis) parameters compatible with liver hypoxia. RESULTS: Cutaneous signs of circulatory failure or shock were observed in 3 of the 9 cases in this study, and were not due to cardiogenic or septic shock. A marked increase in serum aminotransferases levels, 10 times above the upper limit of normal, was observed in 8 of the 9 cases in the present study and in 23 of 37 cases of the literature. Liver cell necrosis was observed in 6 of the 7 autopsied patients in this series and in 20 of 34 cases in the literature. Generally, liver cell necrosis was more severe than tumor cell necrosis and was related to the degree of sinusoidal involvement by tumoral cells. In one case, hepatic blood flow was decreased despite a high level of cardiac blood flow suggesting impairment of circulation in the liver. CONCLUSIONS: These 9 cases and a review of the literature support the hypothesis of hypoxic liver cell necrosis leading to acute liver failure in cases of metastatic liver disease. However, liver hypoxia cannot explain all the reported cases and was never due to circulatory failure from cardiac or septic causes, but to the sinusoidal involvement by tumor cells.

Patients with gastroparesia or intestinal pseudo-obstruction frequently have a motility disorder of the antro-pyloric region that makes the passage of tubes through the pylorus impossible or a very long procedure. We describe a rapid endoscopic method, inspired by the one used for nasobiliary drainage, that simplifies this procedure. In our manometric studies, we observed that spontaneous positioning needed a mean of 57 min (SD 34) in nondyspeptic subjects and a mean of 147 min (SD 68) in non-organic highly dyspeptic patients. Our method allowed us to shorten to a mean of 22 min (SD 5) the time needed to position the manometric tube and to start the recording of gastro-intestinal contractions in highly dyspeptic patients.