Petri Net Siphon Analysis and Network Centrality Measures for Identifying Combination Therapies in Signaling Pathways

Aberrant behavior of biological signaling pathways has been implicated in diseases such as cancers. Therapies have been developed to target proteins in these networks in the hope of curing the illness or bringing about remission. However, identifying targets for drug inhibition that exhibit good therapeutic index has proven to be challenging since signaling pathways have a large number of components and many interconnections such as feedback, crosstalk, and divergence. Unfortunately, some characteristics of these pathways such as redundancy, feedback, and drug resistance reduce the efficacy of single drug target therapy and necessitate the employment of more than one drug to target multiple nodes in the system. However, choosing multiple targets with high therapeutic index poses more challenges since the combinatorial search space could be huge. To cope with the complexity of these systems, computational tools such as ordinary differential equations have been used to successfully model some of these pathways. Regrettably, for building these models, experimentally-measured initial concentrations of the components and rates of reactions are needed which are difficult to obtain, and in very large networks, they may not be available at the moment. Fortunately, there exist other modeling tools, though not as powerful as ordinary differential equations, which do not need the rates and initial conditions to model signaling pathways. Petri net and graph theory are among these tools. In this thesis, we introduce a methodology based on Petri net siphon analysis and graph network centrality measures for identifying prospective targets for single and multiple drug therapies. In this methodology, first, potential targets are identified in the Petri net model of a signaling pathway using siphon analysis. Then, the graph-theoretic centrality measures are employed to prioritize the candidate targets. Also, an algorithm is developed to check whether the candidate targets are able to disable the intended outputs in the graph model of the system or not. We implement structural and dynamical models of ErbB1-Ras-MAPK pathways and use them to assess and evaluate this methodology. The identified drug-targets, single and multiple, correspond to clinically relevant drugs. Overall, the results suggest that this methodology, using siphons and centrality measures, shows promise in identifying and ranking drugs. Since this methodology only uses the structural information of the signaling pathways and does not need initial conditions and dynamical rates, it can be utilized in larger networks.

Immersive Learning Research Network

Computer games have now been around for over three decades and the term serious games has been attributed to the use of computer games that are thought to have educational value. Game-based learning (GBL) has been applied in a number of different fields such as medicine, languages and software engineering. Furthermore, serious games can be a very effective as an instructional tool and can assist learning by providing an alternative way of presenting instructions and content on a supplementary level, and can promote student motivation and interest in subject matter resulting in enhanced learning effectiveness. REVLAW (Real and Virtual Reality Law) is a research project that the departments of Law and Computer Science of Westminster University have proposed as a new framework in which law students can explore a real case scenario using Virtual Reality (VR) technology to discover important pieces of evidence from a real-given scenario and make up their mind over the crime case if this is a murder or not. REVLAW integrates the immersion into VR as the perception of being physically present in a non-physical world. The paper presents the prototype framework and the mechanics used to make students focus on the crime case and make the best use of this immersive learning approach.

Distributed parallelization of greedy Mobile Network Optimization algorithms

The Mobile Network Optimization (MNO) technologies have advanced at a tremendous pace in recent years. And the Dynamic Network Optimization (DNO) concept emerged years ago, aimed to continuously optimize the network in response to variations in network traffic and conditions. Yet, DNO development is still at its infancy, mainly hindered by a significant bottleneck of the lengthy optimization runtime. This paper identifies parallelism in greedy MNO algorithms and presents an advanced distributed parallel solution. The solution is designed, implemented and applied to real-life projects whose results yield a significant, highly scalable and nearly linear speedup up to 6.9 and 14.5 on distributed 8-core and 16-core systems respectively. Meanwhile, optimization outputs exhibit self-consistency and high precision compared to their sequential counterpart. This is a milestone in realizing the DNO. Further, the techniques may be applied to similar greedy optimization algorithm based applications.

Performance Evaluation of a Statistical and a Neural Network Model for Nonrigid Shape-Based Registration

Shape-based registration methods frequently encounters in the domains of computer vision, image processing and medical imaging. The registration problem is to find an optimal transformation/mapping between sets of rigid or nonrigid objects and to automatically solve for correspondences. In this paper we present a comparison of two different probabilistic methods, the entropy and the growing neural gas network (GNG), as general feature-based registration algorithms. Using entropy shape modelling is performed by connecting the point sets with the highest probability of curvature information, while with GNG the points sets are connected using nearest-neighbour relationships derived from competitive hebbian learning. In order to compare performances we use different levels of shape deformation starting with a simple shape 2D MRI brain ventricles and moving to more complicated shapes like hands. Results both quantitatively and qualitatively are given for both sets.

Detecting stealthy attacks: Efficient monitoring of suspicious activities on computer networks

Stealthy attackers move patiently through computer networks - taking days, weeks or months to accomplish their objectives in order to avoid detection. As networks scale up in size and speed, monitoring for such attack attempts is increasingly a challenge. This paper presents an efficient monitoring technique for stealthy attacks. It investigates the feasibility of proposed method under number of different test cases and examines how design of the network affects the detection. A methodological way for tracing anonymous stealthy activities to their approximate sources is also presented. The Bayesian fusion along with traffic sampling is employed as a data reduction method. The proposed method has the ability to monitor stealthy activities using 10-20% size sampling rates without degrading the quality of detection.

Cooperative Proxying: An Approach to Reduce Network Energy Waste

A network connected host is expected to generate/respond to applications and protocols specific messages. Billions of Euro of electricity is wasted to keep idle hosts powered up 24/7 just to maintain network presence. This short paper describes the design of our cooperative Network Connectivity Proxy (NCP) that can impersonate sleeping hosts and responds to packets on their behalf as they were connected and fully operational. Thus, NCP is in fact an efficient approach to reduce network energy waste.

A secure authentication and key management scheme for Wireless Sensors Network

In recent years, the adaptation of Wireless Sensor Networks (WSNs) to application areas requiring mobility increased the security threats against confidentiality, integrity and privacy of the information as well as against their connectivity. Since, key management plays an important role in securing both information and connectivity, a proper authentication and key management scheme is required in mobility enabled applications where the authentication of a node with the network is a critical issue. In this paper, we present an authentication and key management scheme supporting node mobility in a heterogeneous WSN that consists of several low capabilities sensor nodes and few high capabilities sensor nodes. We analyze our proposed solution by using MATLAB (analytically) and by simulation (OMNET++ simulator) to show that it has less memory requirement and has good network connectivity and resilience against attacks compared to some existing schemes. We also propose two levels of secure authentication methods for the mobile sensor nodes for secure authentication and key establishment.

Model-driven development of sensor network applications with optimization of non-functional constraints

Wireless sensor networks (WSNs) differ from conventional distributed systems in many aspects. The resource limitation of sensor nodes, the ad-hoc communication and topology of the network, coupled with an unpredictable deployment environment are difficult non-functional constraints that must be carefully taken into account when developing software systems for a WSN. Thus, more research needs to be done on designing, implementing and maintaining software for WSNs. This thesis aims to contribute to research being done in this area by presenting an approach to WSN application development that will improve the reusability, flexibility, and maintainability of the software. Firstly, we present a programming model and software architecture aimed at describing WSN applications, independently of the underlying operating system and hardware. The proposed architecture is described and realized using the Model-Driven Architecture (MDA) standard in order to achieve satisfactory levels of encapsulation and abstraction when programming sensor nodes. Besides, we study different non-functional constrains of WSN application and propose two approaches to optimize the application to satisfy these constrains. A real prototype framework was built to demonstrate the developed solutions in the thesis. The framework implemented the programming model and the multi-layered software architecture as components. A graphical interface, code generation components and supporting tools were also included to help developers design, implement, optimize, and test the WSN software. Finally, we evaluate and critically assess the proposed concepts. Two case studies are provided to support the evaluation. The first case study, a framework evaluation, is designed to assess the ease at which novice and intermediate users can develop correct and power efficient WSN applications, the portability level achieved by developing applications at a high-level of abstraction, and the estimated overhead due to usage of the framework in terms of the footprint and executable code size of the application. In the second case study, we discuss the design, implementation and optimization of a real-world application named TempSense, where a sensor network is used to monitor the temperature within an area.

Artificial Neural Network and Neutron Aplication in a Volume Fraction Calculation in Annular and Stratified Multiphase System

Multiphase flows, type oil–water-gas are very common among different industrial activities, such as chemical industries and petroleum extraction, and its measurements show some difficulties to be taken. Precisely determining the volume fraction of each one of the elements that composes a multiphase flow is very important in chemical plants and petroleum industries. This work presents a methodology able to determine volume fraction on Annular and Stratified multiphase flow system with the use of neutrons and artificial intelligence, using the principles of transmission/scattering of fast neutrons from a 241Am-Be source and measurements of point flow that are influenced by variations of volume fractions. The proposed geometries used on the mathematical model was used to obtain a data set where the thicknesses referred of each material had been changed in order to obtain volume fraction of each phase providing 119 compositions that were used in the simulation with MCNP-X –computer code based on Monte Carlo Method that simulates the radiation transport. An artificial neural network (ANN) was trained with data obtained using the MCNP-X, and used to correlate such measurements with the respective real fractions. The ANN was able to correlate the data obtained on the simulation with MCNP-X with the volume fractions of the multiphase flows (oil-water-gas), both in the pattern of annular flow as stratified, resulting in a average relative error (%) for each production set of: annular (air= 3.85; water = 4.31; oil=1.08); stratified (air=3.10, water 2.01, oil = 1.45). The method demonstrated good efficiency in the determination of each material that composes the phases, thus demonstrating the feasibility of the technique.

Computer simulations of soft particles in flow

Understanding the dynamics of blood cells is a crucial element to discover biological mechanisms, to develop new efficient drugs, design sophisticated microfluidic devices, for diagnostics. In this work, we focus on the dynamics of red blood cells in microvascular flow. Microvascular blood flow resistance has a strong impact on cardiovascular function and tissue perfusion. The flow resistance in microcirculation is governed by flow behavior of blood through a complex network of vessels, where the distribution of red blood cells across vessel cross-sections may be significantly distorted at vessel bifurcations and junctions. We investigate the development of blood flow and its resistance starting from a dispersed configuration of red blood cells in simulations for different hematocrits, flow rates, vessel diameters, and aggregation interactions between red blood cells. Initially dispersed red blood cells migrate toward the vessel center leading to the formation of a cell-free layer near the wall and to a decrease of the flow resistance. The development of cell-free layer appears to be nearly universal when scaled with a characteristic shear rate of the flow, which allows an estimation of the length of a vessel required for full flow development, $l_c \approx 25D$, with vessel diameter $D$. Thus, the potential effect of red blood cell dispersion at vessel bifurcations and junctions on the flow resistance may be significant in vessels which are shorter or comparable to the length $l_c$. The presence of aggregation interactions between red blood cells lead in general to a reduction of blood flow resistance. The development of the cell-free layer thickness looks similar for both cases with and without aggregation interactions. Although, attractive interactions result in a larger cell-free layer plateau values. However, because the aggregation forces are short-ranged at high enough shear rates ($\bar{\dot{\gamma}} \gtrsim 50~\text{s}^{-1}$) aggregation of red blood cells does not bring a significant change to the blood flow properties. Also, we develop a simple theoretical model which is able to describe the converged cell-free-layer thickness with respect to flow rate assuming steady-state flow. The model is based on the balance between a lift force on red blood cells due to cell-wall hydrodynamic interactions and shear-induced effective pressure due to cell-cell interactions in flow. We expect that these results can also be used to better understand the flow behavior of other suspensions of deformable particles such as vesicles, capsules, and cells. Finally, we investigate segregation phenomena in blood as a two-component suspension under Poiseuille flow, consisting of red blood cells and target cells. The spatial distribution of particles in blood flow is very important. For example, in case of nanoparticle drug delivery, the particles need to come closer to microvessel walls, in order to adhere and bring the drug to a target position within the microvasculature. Here we consider that segregation can be described as a competition between shear-induced diffusion and the lift force that pushes every soft particle in a flow away from the wall. In order to investigate the segregation, on one hand, we have 2D DPD simulations of red blood cells and target cell of different sizes, on the other hand the Fokker-Planck equation for steady state. For the equation we measure force profile, particle distribution and diffusion constant across the channel. We compare simulation results with those from the Fokker-Planck equation and find a very good correspondence between the two approaches. Moreover, we investigate the diffusion behavior of target particles for different hematocrit values and shear rates. Our simulation results indicate that diffusion constant increases with increasing hematocrit and depends linearly on shear rate. The third part of the study describes development of a simulation model of complex vascular geometries. The development of the model is important to reproduce vascular systems of small pieces of tissues which might be gotten from MRI or microscope images. The simulation model of the complex vascular systems might be divided into three parts: modeling the geometry, developing in- and outflow boundary conditions, and simulation domain decomposition for an efficient computation. We have found that for the in- and outflow boundary conditions it is better to use the SDPD fluid than DPD one because of the density fluctuations along the channel of the latter. During the flow in a straight channel, it is difficult to control the density of the DPD fluid. However, the SDPD fluid has not that shortcoming even in more complex channels with many branches and in- and outflows because the force acting on particles is calculated also depending on the local density of the fluid.

Dynamic Workload Parallelization and System Calibration on Single-Chip Cloud Computer

Many-core systems are emerging from the need of more computational power and power efficiency. However there are many issues which still revolve around the many-core systems. These systems need specialized software before they can be fully utilized and the hardware itself may differ from the conventional computational systems. To gain efficiency from many-core system, programs need to be parallelized. In many-core systems the cores are small and less powerful than cores used in traditional computing, so running a conventional program is not an efficient option. Also in Network-on-Chip based processors the network might get congested and the cores might work at different speeds. In this thesis is, a dynamic load balancing method is proposed and tested on Intel 48-core Single-Chip Cloud Computer by parallelizing a fault simulator. The maximum speedup is difficult to obtain due to severe bottlenecks in the system. In order to exploit all the available parallelism of the Single-Chip Cloud Computer, a runtime approach capable of dynamically balancing the load during the fault simulation process is used. The proposed dynamic fault simulation approach on the Single-Chip Cloud Computer shows up to 45X speedup compared to a serial fault simulation approach. Many-core systems can draw enormous amounts of power, and if this power is not controlled properly, the system might get damaged. One way to manage power is to set power budget for the system. But if this power is drawn by just few cores of the many, these few cores get extremely hot and might get damaged. Due to increase in power density multiple thermal sensors are deployed on the chip area to provide realtime temperature feedback for thermal management techniques. Thermal sensor accuracy is extremely prone to intra-die process variation and aging phenomena. These factors lead to a situation where thermal sensor values drift from the nominal values. This necessitates efficient calibration techniques to be applied before the sensor values are used. In addition, in modern many-core systems cores have support for dynamic voltage and frequency scaling. Thermal sensors located on cores are sensitive to the core's current voltage level, meaning that dedicated calibration is needed for each voltage level. In this thesis a general-purpose software-based auto-calibration approach is also proposed for thermal sensors to calibrate thermal sensors on different range of voltages.

Introduction to Security Onion

Security Onion is a Network Security Manager (NSM) platform that provides multiple Intrusion Detection Systems (IDS) including Host IDS (HIDS) and Network IDS (NIDS). Many types of data can be acquired using Security Onion for analysis. This includes data related to: Host, Network, Session, Asset, Alert and Protocols. Security Onion can be implemented as a standalone deployment with server and sensor included or with a master server and multiple sensors allowing for the system to be scaled as required. Many interfaces and tools are available for management of the system and analysis of data such as Sguil, Snorby, Squert and Enterprise Log Search and Archive (ELSA). These interfaces can be used for analysis of alerts and captured events and then can be further exported for analysis in Network Forensic Analysis Tools (NFAT) such as NetworkMiner, CapME or Xplico. The Security Onion platform also provides various methods of management such as Secure SHell (SSH) for management of server and sensors and Web client remote access. All of this with the ability to replay and analyse example malicious traffic makes the Security Onion a suitable low cost alternative for Network Security Management. In this paper, we have a feature and functionality review for the Security Onion in terms of: types of data, configuration, interface, tools and system management.

Threat analysis of IoT networks using artificial neural network intrusion detection system

The Internet of things (IoT) is still in its infancy and has attracted much interest in many industrial sectors including medical fields, logistics tracking, smart cities and automobiles. However, as a paradigm, it is susceptible to a range of significant intrusion threats. This paper presents a threat analysis of the IoT and uses an Artificial Neural Network (ANN) to combat these threats. A multi-level perceptron, a type of supervised ANN, is trained using internet packet traces, then is assessed on its ability to thwart Distributed Denial of Service (DDoS/DoS) attacks. This paper focuses on the classification of normal and threat patterns on an IoT Network. The ANN procedure is validated against a simulated IoT network. The experimental results demonstrate 99.4% accuracy and can successfully detect various DDoS/DoS attacks.

New Directions in Commercial Secrecy and Encryption Protocols

Secure transmission of bulk data is of interest to many content providers. A commercially-viable distribution of content requires technology to prevent unauthorised access. Encryption tools are powerful, but have a performance cost. Without encryption, intercepted data may be illicitly duplicated and re-sold, or its commercial value diminished because its secrecy is lost. Two technical solutions make it possible to perform bulk transmissions while retaining security without too high a performance overhead. These are: 1. a) hierarchical encryption - the stronger the encryption, the harder it is to break but also the more computationally expensive it is. A hierarchical approach to key exchange means that simple and relatively weak encryption and keys are used to encrypt small chunks of data, for example 10 seconds of video. Each chunk has its own key. New keys for this bottom-level encryption are exchanged using a slightly stronger encryption, for example a whole-video key could govern the exchange of the 10-second chunk keys. At a higher level again, there could be daily or weekly keys, securing the exchange of whole-video keys, and at a yet higher level, a subscriber key could govern the exchange of weekly keys. At higher levels, the encryption becomes stronger but is used less frequently, so that the overall computational cost is minimal. The main observation is that the value of each encrypted item determines the strength of the key used to secure it. 2. b) non-symbolic fragmentation with signal diversity - communications are usually assumed to be sent over a single communications medium, and the data to have been encrypted and/or partitioned in whole-symbol packets. Network and path diversity break up a file or data stream into fragments which are then sent over many different channels, either in the same network or different networks. For example, a message could be transmitted partly over the phone network and partly via satellite. While TCP/IP does a similar thing in sending different packets over different paths, this is done for load-balancing purposes and is invisible to the end application. Network and path diversity deliberately introduce the same principle as a secure communications mechanism - an eavesdropper would need to intercept not just one transmission path but all paths used. Non-symbolic fragmentation of data is also introduced to further confuse any intercepted stream of data. This involves breaking up data into bit strings which are subsequently disordered prior to transmission. Even if all transmissions were intercepted, the cryptanalyst still needs to determine fragment boundaries and correctly order them. These two solutions depart from the usual idea of data encryption. Hierarchical encryption is an extension of the combined encryption of systems such as PGP but with the distinction that the strength of encryption at each level is determined by the "value" of the data being transmitted. Non- symbolic fragmentation suppresses or destroys bit patterns in the transmitted data in what is essentially a bit-level transposition cipher but with unpredictable irregularly-sized fragments. Both technologies have applications outside the commercial and can be used in conjunction with other forms of encryption, being functionally orthogonal.

A new distributed MIKEY mode to secure e-health applications.

Securing e-health applications in the context of Internet of Things (IoT) is challenging. Indeed, resources scarcity in such environment hinders the implementation of existing standard based protocols. Among these protocols, MIKEY (Multimedia Internet KEYing) aims at establishing security credentials between two communicating entities. However, the existing MIKEY modes fail to meet IoT specificities. In particular, the pre-shared key mode is energy efficient, but suffers from severe scalability issues. On the other hand, asymmetric modes such as the public key mode are scalable, but are highly resource consuming. To address this issue, we combine two previously proposed approaches to introduce a new hybrid MIKEY mode. Indeed, relying on a cooperative approach, a set of third parties is used to discharge the constrained nodes from heavy computational operations. Doing so, the pre-shared mode is used in the constrained part of the network, while the public key mode is used in the unconstrained part of the network. Preliminary results show that our proposed mode is energy preserving whereas its security properties are kept safe.