Studying biological systems is a difficult but important task. Traditional methods include laboratory experimentation and computer simulations. However, often researchers need to explore important but potentially rare events that are not easily observed or simulated. We use UPPAAL-SMC, a formal verification tool to support a methodology that allows us to model biological systems, specify events and conditions that we want to analyze, and to explore system executions using controlled simulations. We also describe an efficient way to reproduce laboratory experimentsin silico. Unlike traditional simulations, we are able to guide the experiment to explore special events and conditions by expressing these conditions in temporal logic formulas. We have applied this methodology to create a more detailed model of Palytoxin-induced Na$^+$/K$^+$pump channels than was previously possible. Moreover, we have reproduced experimental protocols and their associated electrophysiological recordings, which has not been done in previous works. As a consequence, we have been able to propose a new diprotomeric model for the PTX-pump complex and study its behaviour. The use of our methodology has enabled us to reduce the effort and time to perform this research. It can be used to model and analyze other complex biological systems, potentially increasing the productivity of such studies.

Live streaming platforms employ advanced mechanisms to guarantee continuous and scalable video playback to large user bases. One such mechanism is CDN-P2P streaming, where servers are hosted on content distribution networks and client resources are used to help disseminate content in a peer-to-peer overlay. In CDN-P2P streaming, a peer that is about to miss the playback deadline of a content piece issues an emergency request to the CDN. Emergency requests allow the retrieval of nearly missed pieces and guarantee continuous playback. We show that emergency requests deliver a chunk close to its deadline and leave no time for dissemination through the peer-to-peer overlay, decreasing scalability. We present AERO, a mechanism that dynamically adjusts the rate at which CDN-hosted servers seed content pieces into the peer-to-peer overlay as a function of network conditions. Our evaluation of AERO under diverse conditions shows it reduces emergency requests, guarantees efficient peer-to-peer dissemination, and provides significant server upload bandwidth savings.

Video streaming now amounts to the majority of traffic in the Internet. Media streaming relies on large-scale content distribution networks (CDNs), that incur significant costs to build or use. P2P distribution of video content reduce reliance on CDNs and costs. Unfortunately, P2P distribution is fraught with QoE problems, specially during flash crowds or in scenarios where users have limited bandwidth to contribute to the overlay. In this paper, we propose a new P2P overlay construction mechanism to speed up peer joining during flash crowd events while preserving QoE for peers already in the overlay. We also show that our techniques work on resource-constrained overlays where a fraction of peers lack resources to contribute to the overlay, e.g., users on mobile devices and metered connections.

Concerns over the security and privacy of patient information are one of the biggest hindrances to sharing health information and the wide adoption of eHealth systems. At present, there are competing requirements between healthcare consumers' (i.e. patients) requirements and healthcare professionals' (HCP) requirements. While consumers want control over their information, healthcare professionals want access to as much information as required in order to make well-informed decisions and provide quality care. In order to balance these requirements, the use of an Information Accountability Framework devised for eHealth systems has been proposed. In this paper, we take a step closer to the adoption of the Information Accountability protocols and demonstrate their functionality through an implementation in FluxMED, a customisable EHR system.

Overtaking vehicles is a risky task and could cause serious accidents, especially on two-lane highways. There are various efforts in order to make this a safer task. An alternative to this is the use of communication between vehicles and advanced techniques to decide the safest time for overtaking. Thus, in this paper we propose a driver assistance service that uses real-time information transmitted among vehicles and formal methods to calculate the trajectories and to assign the optimal behavior to overtake. For this, we used Probabilistic Model Checking (PMC), which explores all the possibilities of the system indicating the correct configuration to the vehicles involved. In the evaluated study case, the results showed that it is possible to find a secure configuration in a scenario with three vehicles and a collision's probability of 98%.

This paper describes a formal probabilistic analysis of protocols and applications proposed in Vehicular Ad-Hoc Networks (VANET). Services using this technology have been studied and must be tested in a realistic way in order to work properly. Therefore, we have proposed a complete modeling structure which includes mobility, communication and signal propagation modules. We have used PRISM, a model checker for probabilistic systems, instead of traditional simulations. It determines exact probabilities and performance bounds,even if the model is non-deterministic. We present an analysis of a Vehicular Warning System involving three automobiles. The case study shows the influence of the initial positions, speed and timeout on communication, indicating that an interval of three seconds to broadcast packages is enough to guarantee 99% of reception's chance with a good message traffic. Furthermore, this work presents a practical example to future analysis of VANET.

BACKGROUND: Cytotoxicity assays have been used by researchers to screen for cytotoxicity in compound libraries. Researchers can either look for cytotoxic compounds or screen "hits" from initial high-throughput drug screens for unwanted cytotoxic effects before investing in their development as a pharmaceutical. These assays may be used as an alternative to animal experimentation and are becoming increasingly important in modern laboratories. However, the execution of these assays in large scale and different laboratories requires, among other things, the management of protocols, reagents, cell lines used as well as the data produced, which can be a challenge. The management of all this information is greatly improved by the utilization of computational tools to save time and guarantee quality. However, a tool that performs this task designed specifically for cytotoxicity assays is not yet available. RESULTS: In this work, we have used a workflow based LIMS -- the Flux system -- and the Together Workflow Editor as a framework to develop FluxCTTX, a tool for management of data from cytotoxicity assays performed at different laboratories. The main work is the development of a workflow, which represents all stages of the assay and has been developed and uploaded in Flux. This workflow models the activities of cytotoxicity assays performed as described in the OECD 129 Guidance Document. CONCLUSIONS: FluxCTTX presents a solution for the management of the data produced by cytotoxicity assays performed at Interlaboratory comparisons. Its adoption will contribute to guarantee the quality of activities in the process of cytotoxicity tests and enforce the use of Good Laboratory Practices (GLP). Furthermore, the workflow developed is complete and can be adapted to other contexts and different tests for management of other types of data.

BACKGROUND: There exists a large number of rare and complex diseases that are neglected due to the difficulty in diagnosis and treatment. Being rare, they normally do not justify the costs of developing an especialized Electronic Health Record (EHR) system to assist doctors and patients of these diseases. In this work we propose the use of Computer applications known as Laboratory Information Management Systems (LIMS) to address this issue. RESULTS: In this work we describe a fully customizable EHR system that uses a workflow based LIMS with an easy to adapt interface for data collection and retrieval. This system can easily be customized to manage different types of medical data. The customization for a new disease can be done in a few hours with the help of a specialist. CONCLUSION: We have used the proposed system to manage data from patients of three complex diseases: neuromyelitis optica, paracoccidioidomycosis and adrenoleukodistrofy. These diseases have very different symptoms, exams, diagnostics and treatments, but the FluxMED system is able to manage these data in a highly specialized manner without any modifications to its code.

Peer-to-Peer live streaming systems help content providers and distributors drastically reduce bandwidth costs by sharing costs among peers. Researchers have dedicated significant effort developing techniques to discourage or exclude uncooperative peers from peer-to-peer systems. However, users are often unable to cooperate, e.g., users using a mobile device with limited, costly bandwidth. We study the impact of uncooperative peers on video discontinuity and latency using PlanetLab. We find that simple mechanisms, like forwarding video data requests to cooperative peers instead of wasting effort sending requests to uncooperative peers, allows peer-to-peer live streaming to serve 50% of uncooperative peers without performance degradation. We argue that denying service to uncooperative peers may not be the best long-term approach; our findings suggest that peer-to-peer live streaming can support uncooperative peers.

Probabilistic model checking (PMC) is a technique used for the specification and analysis of complex systems. It can be applied directly to biological systems which present these characteristics, including cell transport systems. These systems are structures responsible for exchanging ions through the plasma membrane. Their correct behavior is essential for animal cells, since changes on those are responsible for diseases. In this work, PMC is used to model and analyze the effects of the palytoxin toxin (PTX) interactions with one of these systems. Our model suggests that ATP could inhibit PTX action. Therefore, individuals with ATP deficiencies, such as in brain disorders, may be more susceptible to the toxin. We have also used heat maps to enhance the kinetic model, which is used to describe the system reactions. The map reveals unexpected situations, such as a frequent reaction between unlikely pump states, and hot spots such as likely states and reactions. This type of analysis provides a better understanding on how transmembrane ionic transport systems behave and may lead to the discovery and development of new drugs to treat diseases associated to their incorrect behavior.

Peer-to-Peer live video streaming systems are becoming increasingly popular. Nevertheless, in spite of various studies of client behavior aspects and system optimizations, the current knowledge about the dynamic properties of the system, particularly how the P2P overlay network changes over time during a live transmission, is still superficial. In this paper, we provide a characterization of the dynamic properties of a popular P2P live streaming media application, namely Sop Cast. We use complex network metrics to analyze how the structure of the network evolves over time from the perspective of individual nodes (local view) and of the whole network (global view). We find that Sop Cast peers may be clustered into three profiles based on their centrality properties in the network. Moreover, in spite of peers changing their partners over time, they tend to remain with the same centrality profile. Also, the global network structure tends to remain roughly stable over time, except for a decaying clustering coefficient. Our findings can be used to generate more realistic synthetic P2P workloads and to drive future system designs and simulations.

Peer-to-peer live streaming media systems are becoming more popular each day. As in file sharing P2P system, they are susceptible to content pollution attack. In this kind of attack, a peer alters the media content decreasing the perceived quality of the streaming. In this paper we evaluate the impact of pollution attack in P2P live streaming and we present two reputation system to avoid content polluted dissemination and isolate malicious peers. Our results show that a few number of polluters is capable to compromise all the application and the 2 proposed reputation systems can quickly identify and isolate polluters and also be resistant to peers collusion.

Recently, a number of scalable stream sharing protocols have been proposed with the promise of great reductions in the server and network bandwidth required for delivering popular media content. Although the scalability of these protocols has been evaluated mostly for sequential user accesses, a high degree of interactivity has been observed in the accesses to several real media servers. Moreover, some studies have indicated that user interactivity can severely penalize the scalability of stream sharing protocols.This paper investigates alternative mechanisms for scalable streaming to interactive users. We first identify a set of workload aspects that are determinant to the scalability of classes of streaming protocols. Using real workloads and a new interactive media workload generator, we build a rich set of realistic synthetic workloads. We evaluate Bandwidth Skimming and Patching, two state-of-the-art streaming protocols, covering, with our workloads, a larger region of the design space than previous work. Finally, we propose and evaluate five optimizations to Bandwidth Skimming, the most scalable of the two protocols. Our best optimization reduces the average server bandwidth required for interactive workloads in up to 54%, for unlimited client buffers, and 29%, if buffers are constrained to 25% of media size.

Video on Demand (VoD) services are very appealing these days. In this work, we discuss four distinct alternatives for the architecture of a VoD server and compare their performances under different conditions. We later used the best configuration found in our analysis to evaluate, using simulations, the performance of a distributed VoD service in an ATM network covering an area the size of a large city neighborhood. We also introduced optimizations to the system, such as anticipated delivery and retrieval of video blocks from neighbor clients. Our results indicate that a server-driven operation mode (i.e., based on cycles) is not the most appropriate choice for a variety of workloads, even when the layout is striped (a result that challenges the conventional wisdom in the field). Also, our optimization strategies increased significantly the number of clients served in the system, which in our study case represented a savings of approximately 33% in the hardware required for the deployment of the service.

Multimedia systems such as video-on-demand (VOD) servers are time critical systems. These systems have strict response times, which implies that a delayed response can have serious consequence. For instance, in the case of a VOD server, an immediate consequence of a delayed response time can be user dissatisfaction, what can ultimately lead to the end of a business based on this system. Therefore, analysis and verification of timing properties of multimedia systems is an important problem. To verify if time critical systems satisfy their time bounds, we discuss the use of formal methods tools, in the verification and analysis of multimedia systems. We have used Verus (a formal verification tool) to model and analyze the ALMADEM-VOD server, a component of a true video-on-demand system. The modeling of this server in Verus has provided great insight into its design and its dynamic behavior. Using the quantitative estimates provided by Verus, we have determined performance bounds to the server. These bounds have pointed out that the performance curve of the actual server was almost at the predicted upper bound (worst case) level. These curves have uncovered design inefficiencies. After optimizing the server, its performance has improved over 40%, showing how useful formal verification can be used successfully during the design of multimedia systems.

Symbolic model checking is a successful technique for checking properties of large finite-state systems. This method has been used to verify a number of real-world hardware designs; however it is not able to determine timing or performance properties directly. Since these properties are extremely important in the design of high-performance systems and in time-critical applications, we have extended model checking techniques to produce timing information. Our results allow a more detailed analysis of a model than is possible with tools that simply determine whether a property is satisfied or not. We present algorithms that determine the exact bounds on the time interval between two specified events and the number of occurrences of another event in such an interval. To demonstrate how our method works, we have modelled the PCI local bus and analyzed its temporal behavior. The results demonstrate the usefulness of our technique in analyzing complex modem designs.

Presents a general method for computing quantitative information about finite-state real-time systems. We have developed algorithms that compute exact bounds on the delay between two specified events and on the number of occurrences of an event in a given interval. This technique allows us to determine performance measures such as schedulability, response time, and system load. Our algorithms produce more detailed information than traditional methods. This information leads to a better understanding of system behavior, in addition to determining its correctness. The algorithms presented in this paper are efficiently implemented using binary decision diagrams and have been incorporated into the SMV symbolic model verifier. Using this method, we have verified a model of an aircraft control system with 10/sup 15/ states. The results obtained demonstrate that our method can be successfully applied in the verification of real-time system designs.>