SNA--a toolbox for the stoichiometric analysis of metabolic networks

BACKGROUND: Despite recent algorithmic and conceptual progress, the stoichiometric network analysis of large metabolic models remains a computationally challenging problem. RESULTS: SNA is a interactive, high performance toolbox for analysing the possible steady state behaviour of metabolic networks by computing the generating and elementary vectors of their flux and conversions cones. It also supports analysing the steady states by linear programming. The toolbox is implemented mainly in Mathematica and returns numerically exact results. It is available under an open source license from: http://bioinformatics.org/project/?group_id=546. CONCLUSION: Thanks to its performance and modular design, SNA is demonstrably useful in analysing genome scale metabolic networks. Further, the integration into Mathematica provides a very flexible environment for the subsequent analysis and interpretation of the results.

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.

Using Bayes' rule to define the value of evidence from syndromic surveillance

In this work we propose the adoption of a statistical framework used in the evaluation of forensic evidence as a tool for evaluating and presenting circumstantial "evidence" of a disease outbreak from syndromic surveillance. The basic idea is to exploit the predicted distributions of reported cases to calculate the ratio of the likelihood of observing n cases given an ongoing outbreak over the likelihood of observing n cases given no outbreak. The likelihood ratio defines the Value of Evidence (V). Using Bayes' rule, the prior odds for an ongoing outbreak are multiplied by V to obtain the posterior odds. This approach was applied to time series on the number of horses showing clinical respiratory symptoms or neurological symptoms. The separation between prior beliefs about the probability of an outbreak and the strength of evidence from syndromic surveillance offers a transparent reasoning process suitable for supporting decision makers. The value of evidence can be translated into a verbal statement, as often done in forensics or used for the production of risk maps. Furthermore, a Bayesian approach offers seamless integration of data from syndromic surveillance with results from predictive modeling and with information from other sources such as disease introduction risk assessments.

Dangers of ‘Facebook Login’ for Mobile Apps: Is There a Price Tag for Social Information?

Social networks offer horizontal integration for any mobile platform providing app users with a convenient single sign-on point. Nonetheless, there are growing privacy concerns regarding its use. These vulnerabilities trigger alarm among app developers who fight for their user base: While they are happy to act on users’ information collected via social networks, they are not always willing to sacrifice their adoption rate for this goal. So far, understanding of this trade-off has remained ambiguous. To fill this gap, we employ a discrete choice experiment to explore the role of Facebook Login and investigate the impact of accompanying requests for different information items / actions in the mobile app adoption process. We quantify users’ concerns regarding these items in monetary terms. Beyond hands-on insights for providers, our study contributes to the theoretical discourse on the value of privacy in the growing world of Social Media and mobile web.

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.

Feasibility of Information-Centric Networking Integration into LTE Mobile Networks

With the current growth of mobile devices usage, mobile net- works struggle to deliver content with an acceptable Quality of Experience. In this paper, we propose the integration of Information Centric Networking into 3GPP Long Term Evolution mobile networks, allowing its inherent caching feature to be explored in close proximity to the end users by deploying components inside the evolved Node B. Apart from the advantages brought by Information-Centric Networking’s content requesting paradigm, its inherent caching features enable lower latencies to access content and reduce traffic at the core network. Results show that the impact on the evolved Node B performance is low and ad- vantages coming from Information-Centric Networking are considerable. Thus, mobile network operators reduce operational costs and users end up with a higher perceived network quality even in peak utilization periods.

Increased phase synchronization during continuous face integration measured simultaneously with EEG and fMRI

Gamma zero-lag phase synchronization has been measured in the animal brain during visual binding. Human scalp EEG studies used a phase locking factor (trial-to-trial phase-shift consistency) or gamma amplitude to measure binding but did not analyze common-phase signals so far. This study introduces a method to identify networks oscillating with near zero-lag phase synchronization in human subjects.

Energy-Efficient Management Of Heterogeneous Wireless Sensor Networks

Various applications for the purposes of event detection, localization, and monitoring can benefit from the use of wireless sensor networks (WSNs). Wireless sensor networks are generally easy to deploy, with flexible topology and can support diversity of tasks thanks to the large variety of sensors that can be attached to the wireless sensor nodes. To guarantee the efficient operation of such a heterogeneous wireless sensor networks during its lifetime an appropriate management is necessary. Typically, there are three management tasks, namely monitoring, (re) configuration, and code updating. On the one hand, status information, such as battery state and node connectivity, of both the wireless sensor network and the sensor nodes has to be monitored. And on the other hand, sensor nodes have to be (re)configured, e.g., setting the sensing interval. Most importantly, new applications have to be deployed as well as bug fixes have to be applied during the network lifetime. All management tasks have to be performed in a reliable, time- and energy-efficient manner. The ability to disseminate data from one sender to multiple receivers in a reliable, time- and energy-efficient manner is critical for the execution of the management tasks, especially for code updating. Using multicast communication in wireless sensor networks is an efficient way to handle such traffic pattern. Due to the nature of code updates a multicast protocol has to support bulky traffic and endto-end reliability. Further, the limited resources of wireless sensor nodes demand an energy-efficient operation of the multicast protocol. Current data dissemination schemes do not fulfil all of the above requirements. In order to close the gap, we designed the Sensor Node Overlay Multicast (SNOMC) protocol such that to support a reliable, time-efficient and energy-efficient dissemination of data from one sender node to multiple receivers. In contrast to other multicast transport protocols, which do not support reliability mechanisms, SNOMC supports end-to-end reliability using a NACK-based reliability mechanism. The mechanism is simple and easy to implement and can significantly reduce the number of transmissions. It is complemented by a data acknowledgement after successful reception of all data fragments by the receiver nodes. In SNOMC three different caching strategies are integrated for an efficient handling of necessary retransmissions, namely, caching on each intermediate node, caching on branching nodes, or caching only on the sender node. Moreover, an option was included to pro-actively request missing fragments. SNOMC was evaluated both in the OMNeT++ simulator and in our in-house real-world testbed and compared to a number of common data dissemination protocols, such as Flooding, MPR, TinyCubus, PSFQ, and both UDP and TCP. The results showed that SNOMC outperforms the selected protocols in terms of transmission time, number of transmitted packets, and energy-consumption. Moreover, we showed that SNOMC performs well with different underlying MAC protocols, which support different levels of reliability and energy-efficiency. Thus, SNOMC can offer a robust, high-performing solution for the efficient distribution of code updates and management information in a wireless sensor network. To address the three management tasks, in this thesis we developed the Management Architecture for Wireless Sensor Networks (MARWIS). MARWIS is specifically designed for the management of heterogeneous wireless sensor networks. A distinguished feature of its design is the use of wireless mesh nodes as backbone, which enables diverse communication platforms and offloading functionality from the sensor nodes to the mesh nodes. This hierarchical architecture allows for efficient operation of the management tasks, due to the organisation of the sensor nodes into small sub-networks each managed by a mesh node. Furthermore, we developed a intuitive -based graphical user interface, which allows non-expert users to easily perform management tasks in the network. In contrast to other management frameworks, such as Mate, MANNA, TinyCubus, or code dissemination protocols, such as Impala, Trickle, and Deluge, MARWIS offers an integrated solution monitoring, configuration and code updating of sensor nodes. Integration of SNOMC into MARWIS further increases performance efficiency of the management tasks. To our knowledge, our approach is the first one, which offers a combination of a management architecture with an efficient overlay multicast transport protocol. This combination of SNOMC and MARWIS supports reliably, time- and energy-efficient operation of a heterogeneous wireless sensor network.

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.

Do Integration Policies Affect Immigrants' Voluntary Engagement? An Exploration at Switzerland's Subnational Level

This paper investigates whether integration policies influence immigrants' propensity to volunteer, the latter being an important element of immigrants' integration into the host society. By distinguishing different categories of integration policies at Switzerland's subnational level and applying a Bayesian multilevel approach, our results suggest varying policy effects: while policies fostering socio-structural rights enhance immigrants' propensity to volunteer, we observe a negative curvilinear relationship between cultural rights and obligations and immigrants' volunteerism implying that a combination of cultural entitlements and obligations is most conducive to immigrants' civic engagement.

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.

The structural substrate of brain function: analysis of brain structural networks based on diffusion-weighted imaging

The brain is a complex neural network with a hierarchical organization and the mapping of its elements and connections is an important step towards the understanding of its function. Recent developments in diffusion-weighted imaging have provided the opportunity to reconstruct the whole-brain structural network in-vivo at a large scale level and to study the brain structural substrate in a framework that is close to the current understanding of brain function. However, methods to construct the connectome are still under development and they should be carefully evaluated. To this end, the first two studies included in my thesis aimed at improving the analytical tools specific to the methodology of brain structural networks. The first of these papers assessed the repeatability of the most common global and local network metrics used in literature to characterize the connectome, while in the second paper the validity of further metrics based on the concept of communicability was evaluated. Communicability is a broader measure of connectivity which accounts also for parallel and indirect connections. These additional paths may be important for reorganizational mechanisms in the presence of lesions as well as to enhance integration in the network. These studies showed good to excellent repeatability of global network metrics when the same methodological pipeline was applied, but more variability was detected when considering local network metrics or when using different thresholding strategies. In addition, communicability metrics have been found to add some insight into the integration properties of the network by detecting subsets of nodes that were highly interconnected or vulnerable to lesions. The other two studies used methods based on diffusion-weighted imaging to obtain knowledge concerning the relationship between functional and structural connectivity and about the etiology of schizophrenia. The third study integrated functional oscillations measured using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) as well as diffusion-weighted imaging data. The multimodal approach that was applied revealed a positive relationship between individual fluctuations of the EEG alpha-frequency and diffusion properties of specific connections of two resting-state networks. Finally, in the fourth study diffusion-weighted imaging was used to probe for a relationship between the underlying white matter tissue structure and season of birth in schizophrenia patients. The results are in line with the neurodevelopmental hypothesis of early pathological mechanisms as the origin of schizophrenia. The different analytical approaches selected in these studies also provide arguments for discussion of the current limitations in the analysis of brain structural networks. To sum up, the first studies presented in this thesis illustrated the potential of brain structural network analysis to provide useful information on features of brain functional segregation and integration using reliable network metrics. In the other two studies alternative approaches were presented. The common discussion of the four studies enabled us to highlight the benefits and possibilities for the analysis of the connectome as well as some current limitations.

Structural and Institutional Determinants of Influence Reputation: A Comparison of Collaborative and Adversarial Policy Networks in Decision Making and Implementation

The central assumption in the literature on collaborative networks and policy networks is that political outcomes are affected by a variety of state and nonstate actors. Some of these actors are more powerful than others and can therefore have a considerable effect on decision making. In this article, we seek to provide a structural and institutional explanation for these power differentials in policy networks and support the explanation with empirical evidence. We use a dyadic measure of influence reputation as a proxy for power, and posit that influence reputation over the political outcome is related to vertical integration into the political system by means of formal decision-making authority, and to horizontal integration by means of being well embedded into the policy network. Hence, we argue that actors are perceived as influential because of two complementary factors: (a) their institutional roles and (b) their structural positions in the policy network. Based on temporal and cross-sectional exponential random graph models, we compare five cases about climate, telecommunications, flood prevention, and toxic chemicals politics in Switzerland and Germany. The five networks cover national and local networks at different stages of the policy cycle. The results confirm that institutional and structural drivers seem to have a crucial impact on how an actor is perceived in decision making and implementation and, therefore, their ability to significantly shape outputs and service delivery.