The Individualized Genetic Barrier Predicts Treatment Response in a Large Cohort of HIV-1 Infected Patients

The success of combination antiretroviral therapy is limited by the evolutionary escape dynamics of HIV-1. We used Isotonic Conjunctive Bayesian Networks (I-CBNs), a class of probabilistic graphical models, to describe this process. We employed partial order constraints among viral resistance mutations, which give rise to a limited set of mutational pathways, and we modeled phenotypic drug resistance as monotonically increasing along any escape pathway. Using this model, the individualized genetic barrier (IGB) to each drug is derived as the probability of the virus not acquiring additional mutations that confer resistance. Drug-specific IGBs were combined to obtain the IGB to an entire regimen, which quantifies the virus' genetic potential for developing drug resistance under combination therapy. The IGB was tested as a predictor of therapeutic outcome using between 2,185 and 2,631 treatment change episodes of subtype B infected patients from the Swiss HIV Cohort Study Database, a large observational cohort. Using logistic regression, significant univariate predictors included most of the 18 drugs and single-drug IGBs, the IGB to the entire regimen, the expert rules-based genotypic susceptibility score (GSS), several individual mutations, and the peak viral load before treatment change. In the multivariate analysis, the only genotype-derived variables that remained significantly associated with virological success were GSS and, with 10-fold stronger association, IGB to regimen. When predicting suppression of viral load below 400 cps/ml, IGB outperformed GSS and also improved GSS-containing predictors significantly, but the difference was not significant for suppression below 50 cps/ml. Thus, the IGB to regimen is a novel data-derived predictor of treatment outcome that has potential to improve the interpretation of genotypic drug resistance tests.

Adaptive Beaconless Opportunistic Routing for Multimedia Distribution

User experience on watching live videos must be satisfactory even under the inuence of different network conditions and topology changes, such as happening in Flying Ad-Hoc Networks (FANETs). Routing services for video dissemination over FANETs must be able to adapt routing decisions at runtime to meet Quality of Experience (QoE) requirements. In this paper, we introduce an adaptive beaconless opportunistic routing protocol for video dissemination over FANETs with QoE support, by taking into account multiple types of context information, such as link quality, residual energy, buffer state, as well as geographic information and node mobility in a 3D space. The proposed protocol takes into account Bayesian networks to define weight vectors and Analytic Hierarchy Process (AHP) to adjust the degree of importance for the context information based on instantaneous values. It also includes a position prediction to monitor the distance between two nodes in order to detect possible route failure.

Dynamic Transmission Modes to Support Opportunistic Information-Centric Networks

In this paper, we describe dynamic unicast to increase communication efficiency in opportunistic Information-centric networks. The approach is based on broadcast requests to quickly find content and dynamically creating unicast links to content sources without the need of neighbor discovery. The links are kept temporarily as long as they deliver content and are quickly removed otherwise. Evaluations in mobile networks show that this approach maintains ICN flexibility to support seamless mobile communication and achieves up to 56.6% shorter transmission times compared to broadcast in case of multiple concurrent requesters. Apart from that, dynamic unicast unburdens listener nodes from processing unwanted content resulting in lower processing overhead and power consumption at these nodes. The approach can be easily included into existing ICN architectures using only available data structures.

Dynamic Unicast: Information-Centric Multi-hop Routing for Mobile Ad-hoc Networks

Abstract Information-centric networking (ICN) offers new perspectives on mobile ad-hoc communication because routing is based on names but not on endpoint identifiers. Since every content object has a unique name and is signed, authentic content can be stored and cached by any node. If connectivity to a content source breaks, it is not necessarily required to build a new path to the same source but content can also be retrieved from a closer node that provides the same content copy. For example, in case of collisions, retransmissions do not need to be performed over the entire path but due to caching only over the link where the collision occurred. Furthermore, multiple requests can be aggregated to improve scalability of wireless multi-hop communication. In this work, we base our investigations on Content-Centric Networking (CCN), which is a popular {ICN} architecture. While related works in wireless {CCN} communication are based on broadcast communication exclusively, we show that this is not needed for efficient mobile ad-hoc communication. With Dynamic Unicast requesters can build unicast paths to content sources after they have been identified via broadcast. We have implemented Dynamic Unicast in CCNx, which provides a reference implementation of the {CCN} concepts, and performed extensive evaluations in diverse mobile scenarios using NS3-DCE, the direct code execution framework for the {NS3} network simulator. Our evaluations show that Dynamic Unicast can result in more efficient communication than broadcast communication, but still supports all {CCN} advantages such as caching, scalability and implicit content discovery.

Mechanisms of intrinsic beating variability in cardiac cell cultures and model pacemaker networks

Heart rate variability (HRV) exhibits fluctuations characterized by a power law behavior of its power spectrum. The interpretation of this nonlinear HRV behavior, resulting from interactions between extracardiac regulatory mechanisms, could be clinically useful. However, the involvement of intrinsic variations of pacemaker rate in HRV has scarcely been investigated. We examined beating variability in spontaneously active incubating cultures of neonatal rat ventricular myocytes using microelectrode arrays. In networks of mathematical model pacemaker cells, we evaluated the variability induced by the stochastic gating of transmembrane currents and of calcium release channels and by the dynamic turnover of ion channels. In the cultures, spontaneous activity originated from a mobile focus. Both the beat-to-beat movement of the focus and beat rate variability exhibited a power law behavior. In the model networks, stochastic fluctuations in transmembrane currents and stochastic gating of calcium release channels did not reproduce the spatiotemporal patterns observed in vitro. In contrast, long-term correlations produced by the turnover of ion channels induced variability patterns with a power law behavior similar to those observed experimentally. Therefore, phenomena leading to long-term correlated variations in pacemaker cellular function may, in conjunction with extracardiac regulatory mechanisms, contribute to the nonlinear characteristics of HRV.

Dynamic Languages and Applications. Report on the Workshop Dyla 07 at ECOOP 2007

Following last two years’ workshop on dynamic languages at the ECOOP conference, the Dyla 2007 workshop was a successful and popular event. As its name implies, the workshop’s focus was on dynamic languages and their applications. Topics and discussions at the workshop included macro expansion mechanisms, extension of the method lookup algorithm, language interpretation, reflexivity and languages for mobile ad hoc networks. The main goal of this workshop was to bring together different dynamic language communities and favouring cross communities interaction. Dyla 2007 was organised as a full day meeting, partly devoted to presentation of submitted position papers and partly devoted to tool demonstration. All accepted papers can be downloaded from the workshop’s web site. In this report, we provide an overview of the presentations and a summary of discussions.

A Smart TCP Acknowledgment Approach for Multihop Wireless Networks

Reliable data transfer is one of the most difficult tasks to be accomplished in multihop wireless networks. Traditional transport protocols like TCP face severe performance degradation over multihop networks given the noisy nature of wireless media as well as unstable connectivity conditions in place. The success of TCP in wired networks motivates its extension to wireless networks. A crucial challenge faced by TCP over these networks is how to operate smoothly with the 802.11 wireless MAC protocol which also implements a retransmission mechanism at link level in addition to short RTS/CTS control frames for avoiding collisions. These features render TCP acknowledgments (ACK) transmission quite costly. Data and ACK packets cause similar medium access overheads despite the much smaller size of the ACKs. In this paper, we further evaluate our dynamic adaptive strategy for reducing ACK-induced overhead and consequent collisions. Our approach resembles the sender side's congestion control. The receiver is self-adaptive by delaying more ACKs under nonconstrained channels and less otherwise. This improves not only throughput but also power consumption. Simulation evaluations exhibit significant improvement in several scenarios

Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study

BACKGROUND Empirical research has illustrated an association between study size and relative treatment effects, but conclusions have been inconsistent about the association of study size with the risk of bias items. Small studies give generally imprecisely estimated treatment effects, and study variance can serve as a surrogate for study size. METHODS We conducted a network meta-epidemiological study analyzing 32 networks including 613 randomized controlled trials, and used Bayesian network meta-analysis and meta-regression models to evaluate the impact of trial characteristics and study variance on the results of network meta-analysis. We examined changes in relative effects and between-studies variation in network meta-regression models as a function of the variance of the observed effect size and indicators for the adequacy of each risk of bias item. Adjustment was performed both within and across networks, allowing for between-networks variability. RESULTS Imprecise studies with large variances tended to exaggerate the effects of the active or new intervention in the majority of networks, with a ratio of odds ratios of 1.83 (95% CI: 1.09,3.32). Inappropriate or unclear conduct of random sequence generation and allocation concealment, as well as lack of blinding of patients and outcome assessors, did not materially impact on the summary results. Imprecise studies also appeared to be more prone to inadequate conduct. CONCLUSIONS Compared to more precise studies, studies with large variance may give substantially different answers that alter the results of network meta-analyses for dichotomous outcomes.

Virtual Infrastructures as a Service enabling Converged Optical Networks and Data Centres

Abstract Cloud computing service emerged as an essential component of the Enterprise {IT} infrastructure. Migration towards a full range and large-scale convergence of Cloud and network services has become the current trend for addressing requirements of the Cloud environment. Our approach takes the infrastructure as a service paradigm to build converged virtual infrastructures, which allow offering tailored performance and enable multi-tenancy over a common physical infrastructure. Thanks to virtualization, new exploitation activities of the physical infrastructures may arise for both transport network and Data Centres services. This approach makes network and Data Centres’ resources dedicated to Cloud Computing to converge on the same flexible and scalable level. The work presented here is based on the automation of the virtual infrastructure provisioning service. On top of the virtual infrastructures, a coordinated operation and control of the different resources is performed with the objective of automatically tailoring connectivity services to the Cloud service dynamics. Furthermore, in order to support elasticity of the Cloud services through the optical network, dynamic re-planning features have been provided to the virtual infrastructure service, which allows scaling up or down existing virtual infrastructures to optimize resource utilisation and dynamically adapt to users’ demands. Thus, the dynamic re-planning of the service becomes key component for the coordination of Cloud and optical network resource in an optimal way in terms of resource utilisation. The presented work is complemented with a use case of the virtual infrastructure service being adopted in a distributed Enterprise Information System, that scales up and down as a function of the application requests.

A Comparative Analysis of Beaconless Opportunistic Routing Protocols for Video Dissemination over Flying Ad-Hoc Networks

A reliable and robust routing service for Flying Ad-Hoc Networks (FANETs) must be able to adapt to topology changes, and also to recover the quality level of the delivered multiple video flows under dynamic network topologies. The user experience on watching live videos must also be satisfactory even in scenarios with network congestion, buffer overflow, and packet loss ratio, as experienced in many FANET multimedia applications. In this paper, we perform a comparative simulation study to assess the robustness, reliability, and quality level of videos transmitted via well-known beaconless opportunistic routing protocols. Simulation results shows that our developed protocol XLinGO achieves multimedia dissemination with Quality of Experience (QoE) support and robustness in a multi-hop, multi-flow, and mobile networks, as required in many multimedia FANET scenarios.

Context-Aware Adaptive Opportunistic Routing in Mobile Ad-hoc and Sensor Networks

Mobile ad-hoc networks (MANETs) and wireless sensor networks (WSNs) have been attracting increasing attention for decades due to their broad civilian and military applications. Basically, a MANET or WSN is a network of nodes connected by wireless communication links. Due to the limited transmission range of the radio, many pairs of nodes in MANETs or WSNs may not be able to communicate directly, hence they need other intermediate nodes to forward packets for them. Routing in such types of networks is an important issue and it poses great challenges due to the dynamic nature of MANETs or WSNs. On the one hand, the open-air nature of wireless environments brings many difficulties when an efficient routing solution is required. The wireless channel is unreliable due to fading and interferences, which makes it impossible to maintain a quality path from a source node to a destination node. Additionally, node mobility aggravates network dynamics, which causes frequent topology changes and brings significant overheads for maintaining and recalculating paths. Furthermore, mobile devices and sensors are usually constrained by battery capacity, computing and communication resources, which impose limitations on the functionalities of routing protocols. On the other hand, the wireless medium possesses inherent unique characteristics, which can be exploited to enhance transmission reliability and routing performance. Opportunistic routing (OR) is one promising technique that takes advantage of the spatial diversity and broadcast nature of the wireless medium to improve packet forwarding reliability in multihop wireless communication. OR combats the unreliable wireless links by involving multiple neighboring nodes (forwarding candidates) to choose packet forwarders. In opportunistic routing, a source node does not require an end-to-end path to transmit packets. The packet forwarding decision is made hop-by-hop in a fully distributed fashion. Motivated by the deficiencies of existing opportunistic routing protocols in dynamic environments such as mobile ad-hoc networks or wireless sensor networks, this thesis proposes a novel context-aware adaptive opportunistic routing scheme. Our proposal selects packet forwarders by simultaneously exploiting multiple types of cross-layer context information of nodes and environments. Our approach significantly outperforms other routing protocols that rely solely on a single metric. The adaptivity feature of our proposal enables network nodes to adjust their behaviors at run-time according to network conditions. To accommodate the strict energy constraints in WSNs, this thesis integrates adaptive duty-cycling mechanism to opportunistic routing for wireless sensor nodes. Our approach dynamically adjusts the sleeping intervals of sensor nodes according to the monitored traffic load and the estimated energy consumption rate. Through the integration of duty cycling of sensor nodes and opportunistic routing, our protocol is able to provide a satisfactory balance between good routing performance and energy efficiency for WSNs.

Cross-Layer Optimizations for Multimedia Distribution over Wireless Multimedia Sensor Networks and Flying Ad-Hoc Networks with Quality of Experience Support

The proliferation of multimedia content and the demand for new audio or video services have fostered the development of a new era based on multimedia information, which allowed the evolution of Wireless Multimedia Sensor Networks (WMSNs) and also Flying Ad-Hoc Networks (FANETs). In this way, live multimedia services require real-time video transmissions with a low frame loss rate, tolerable end-to-end delay, and jitter to support video dissemination with Quality of Experience (QoE) support. Hence, a key principle in a QoE-aware approach is the transmission of high priority frames (protect them) with a minimum packet loss ratio, as well as network overhead. Moreover, multimedia content must be transmitted from a given source to the destination via intermediate nodes with high reliability in a large scale scenario. The routing service must cope with dynamic topologies caused by node failure or mobility, as well as wireless channel changes, in order to continue to operate despite dynamic topologies during multimedia transmission. Finally, understanding user satisfaction on watching a video sequence is becoming a key requirement for delivery of multimedia content with QoE support. With this goal in mind, solutions involving multimedia transmissions must take into account the video characteristics to improve video quality delivery. The main research contributions of this thesis are driven by the research question how to provide multimedia distribution with high energy-efficiency, reliability, robustness, scalability, and QoE support over wireless ad hoc networks. The thesis addresses several problem domains with contributions on different layers of the communication stack. At the application layer, we introduce a QoE-aware packet redundancy mechanism to reduce the impact of the unreliable and lossy nature of wireless environment to disseminate live multimedia content. At the network layer, we introduce two routing protocols, namely video-aware Multi-hop and multi-path hierarchical routing protocol for Efficient VIdeo transmission for static WMSN scenarios (MEVI), and cross-layer link quality and geographical-aware beaconless OR protocol for multimedia FANET scenarios (XLinGO). Both protocols enable multimedia dissemination with energy-efficiency, reliability and QoE support. This is achieved by combining multiple cross-layer metrics for routing decision in order to establish reliable routes.