Stochastic modelling of T cell homeostasis for two competing clonotypes via the master equation

Stochastic models for competing clonotypes of T cells by multivariate, continuous-time, discrete state, Markov processes have been proposed in the literature by Stirk, Molina-París and van den Berg (2008). A stochastic modelling framework is important because of rare events associated with small populations of some critical cell types. Usually, computational methods for these problems employ a trajectory-based approach, based on Monte Carlo simulation. This is partly because the complementary, probability density function (PDF) approaches can be expensive but here we describe some efficient PDF approaches by directly solving the governing equations, known as the Master Equation. These computations are made very efficient through an approximation of the state space by the Finite State Projection and through the use of Krylov subspace methods when evolving the matrix exponential. These computational methods allow us to explore the evolution of the PDFs associated with these stochastic models, and bimodal distributions arise in some parameter regimes. Time-dependent propensities naturally arise in immunological processes due to, for example, age-dependent effects. Incorporating time-dependent propensities into the framework of the Master Equation significantly complicates the corresponding computational methods but here we describe an efficient approach via Magnus formulas. Although this contribution focuses on the example of competing clonotypes, the general principles are relevant to multivariate Markov processes and provide fundamental techniques for computational immunology.

Elements pour adapter les systemes de recherche d'information aux dyslexiques [Elements to adapt information retrieval systems to dyslexic users]

RÉSUMÉ. La prise en compte des troubles de la communication dans l’utilisation des systèmes de recherche d’information tels qu’on peut en trouver sur le Web est généralement réalisée par des interfaces utilisant des modalités n’impliquant pas la lecture et l’écriture. Peu d’applications existent pour aider l’utilisateur en difficulté dans la modalité textuelle. Nous proposons la prise en compte de la conscience phonologique pour assister l’utilisateur en difficulté d’écriture de requêtes (dysorthographie) ou de lecture de documents (dyslexie). En premier lieu un système de réécriture et d’interprétation des requêtes entrées au clavier par l’utilisateur est proposé : en s’appuyant sur les causes de la dysorthographie et sur les exemples à notre disposition, il est apparu qu’un système combinant une approche éditoriale (type correcteur orthographique) et une approche orale (système de transcription automatique) était plus approprié. En second lieu une méthode d’apprentissage automatique utilise des critères spécifiques , tels que la cohésion grapho-phonémique, pour estimer la lisibilité d’une phrase, puis d’un texte. ABSTRACT. Most applications intend to help disabled users in the information retrieval process by proposing non-textual modalities. This paper introduces specific parameters linked to phonological awareness in the textual modality. This will enhance the ability of systems to deal with orthographic issues and with the adaptation of results to the reader when for example the reader is dyslexic. We propose a phonology based sentence level rewriting system that combines spelling correction, speech synthesis and automatic speech recognition. This has been evaluated on a corpus of questions we get from dyslexic children. We propose a specific sentence readability measure that involves phonetic parameters such as grapho-phonemic cohesion. This has been learned on a corpus of reading time of sentences read by dyslexic children.

Stochastic chemical kinetics and the quasi-steady-state assumption : application to the stochastic simulation algorithm and chemical master equation

Recently the application of the quasi-steady-state approximation (QSSA) to the stochastic simulation algorithm (SSA) was suggested for the purpose of speeding up stochastic simulations of chemical systems that involve both relatively fast and slow chemical reactions [Rao and Arkin, J. Chem. Phys. 118, 4999 (2003)] and further work has led to the nested and slow-scale SSA. Improved numerical efficiency is obtained by respecting the vastly different time scales characterizing the system and then by advancing only the slow reactions exactly, based on a suitable approximation to the fast reactions. We considerably extend these works by applying the QSSA to numerical methods for the direct solution of the chemical master equation (CME) and, in particular, to the finite state projection algorithm [Munsky and Khammash, J. Chem. Phys. 124, 044104 (2006)], in conjunction with Krylov methods. In addition, we point out some important connections to the literature on the (deterministic) total QSSA (tQSSA) and place the stochastic analogue of the QSSA within the more general framework of aggregation of Markov processes. We demonstrate the new methods on four examples: Michaelis–Menten enzyme kinetics, double phosphorylation, the Goldbeter–Koshland switch, and the mitogen activated protein kinase cascade. Overall, we report dramatic improvements by applying the tQSSA to the CME solver.

Analyzing real-time video microscopy : the dynamics and geometry of vesicles and tubules in endocytosis

With the advent of live cell imaging microscopy, new types of mathematical analyses and measurements are possible. Many of the real-time movies of cellular processes are visually very compelling, but elementary analysis of changes over time of quantities such as surface area and volume often show that there is more to the data than meets the eye. This unit outlines a geometric modeling methodology and applies it to tubulation of vesicles during endocytosis. Using these principles, it has been possible to build better qualitative and quantitative understandings of the systems observed, as well as to make predictions about quantities such as ligand or solute concentration, vesicle pH, and membrane trafficked. The purpose is to outline a methodology for analyzing real-time movies that has led to a greater appreciation of the changes that are occurring during the time frame of the real-time video microscopy and how additional quantitative measurements allow for further hypotheses to be generated and tested.

Optical waveguide and cavity effects on whispering-gallery mode resonances in a ZnO nanonail

Spatially resolved cathodoluminescence (CL) study of a ZnO nanonail, having thin shank, tapered neck, and hexagonal head sections, is reported. Monochromatic imaging and line scan profiling indicate that the wave guiding and leaking from growth imperfections in addition to the oxygen deficiency variation determine the spatial contrast of CL emissions. Occurrence of resonance peaks at identical wavelengths regardless of CL-excitation spots is inconsistent with the whispering-gallery mode (WGM) resonances of a two-dimensional cavity in the finite difference time domain simulation. However, three dimensioanl cavity simulation produced WGM peaks that are consistent with the experimental spectra, including transverse-electric resonances that are comparable to transverse-magnetic ones.

Characteristics of modal sound radiation of finite cylindrical shells

Characteristics of modal sound radiation of finite cylindrical shells are studied using finite element and boundary element methods in this paper. In the low frequency range, modal radiation efficiencies of finite cylindrical shells are found to asymptotically approach those of the corresponding infinite cylindrical shell when structural trace wavelengths of the cylindrical shells are greater than the acoustic wavelength. Modal radiation efficiencies for each group of modes having the same circumferential modal index decrease as the axial modal index increases. They converge to each other when the axial trace wavelength is much greater than the circumferential trace wavelength. The mechanism leading to lower radiation efficiency of modes with higher circumferential modal index of short cylinders is explained. Similar to those of flat plate panels, change in slope or waviness is observed in modal radiation efficiency curves of modes with higher order axial modal index at medium frequencies. This is attributed to the interference of sound radiated by neighbouring vibrating cells when the distance between nodal lines of a vibrating mode is in the same order or smaller than the acoustic wavelength. Effects of the internal sound field on modal radiation efficiencies of a finite open-end cylinder are discussed.

A continuous time model for election timing

We consider a continuous time model for election timing in a Majoritarian Parliamentary System where the government maintains a constitutional right to call an early election. Our model is based on the two-party-preferred data that measure the popularity of the government and the opposition over time. We describe the poll process by a Stochastic Differential Equation (SDE) and use a martingale approach to derive a Partial Differential Equation (PDE) for the government’s expected remaining life in office. A comparison is made between a three-year and a four-year maximum term and we also provide the exercise boundary for calling an election. Impacts on changes in parameters in the SDE, the probability of winning the election and maximum terms on the call exercise boundaries are discussed and analysed. An application of our model to the Australian Federal Election for House of Representatives is also given.

Identity management : strengthening one-time password authentication through usability

Usability in HCI (Human-Computer Interaction) is normally understood as the simplicity and clarity with which the interaction with a computer program or a web site is designed. Identity management systems need to provide adequate usability and should have a simple and intuitive interface. The system should not only be designed to satisfy service provider requirements but it has to consider user requirements, otherwise it will lead to inconvenience and poor usability for users when managing their identities. With poor usability and a poor user interface with regard to security, it is highly likely that the system will have poor security. The rapid growth in the number of online services leads to an increasing number of different digital identities each user needs to manage. As a result, many people feel overloaded with credentials, which in turn negatively impacts their ability to manage them securely. Passwords are perhaps the most common type of credential used today. To avoid the tedious task of remembering difficult passwords, users often behave less securely by using low entropy and weak passwords. Weak passwords and bad password habits represent security threats to online services. Some solutions have been developed to eliminate the need for users to create and manage passwords. A typical solution is based on generating one-time passwords, i.e. passwords for single session or transaction usage. Unfortunately, most of these solutions do not satisfy scalability and/or usability requirements, or they are simply insecure. In this thesis, the security and usability aspects of contemporary methods for authentication based on one-time passwords (OTP) are examined and analyzed. In addition, more scalable solutions that provide a good user experience while at the same time preserving strong security are proposed.

Arterial travel time estimation : revisiting the classical procedure

Travel time is an important network performance measure and it quantifies congestion in a manner easily understood by all transport users. In urban networks, travel time estimation is challenging due to number of reasons such as, fluctuations in traffic flow due to traffic signals, significant flow to/from mid link sinks/sources, etc. The classical analytical procedure utilizes cumulative plots at upstream and downstream locations for estimating travel time between the two locations. In this paper, we discuss about the issues and challenges with classical analytical procedure such as its vulnerability to non conservation of flow between the two locations. The complexity with respect to exit movement specific travel time is discussed. Recently, we have developed a methodology utilising classical procedure to estimate average travel time and its statistic on urban links (Bhaskar, Chung et al. 2010). Where, detector, signal and probe vehicle data is fused. In this paper we extend the methodology for route travel time estimation and test its performance using simulation. The originality is defining cumulative plots for each exit turning movement utilising historical database which is self updated after each estimation. The performance is also compared with a method solely based on probe (Probe-only). The performance of the proposed methodology has been found insensitive to different route flow, with average accuracy of more than 94% given a probe per estimation interval which is more than 5% increment in accuracy with respect to Probe-only method.

Use of precision time protocol to synchronize sampled value process buses

Transmission smart grids will use a digital platform for the automation of high voltage substations. The IEC 61850 series of standards, released in parts over the last ten years, provide a specification for substation communications networks and systems. These standards, along with IEEE Std 1588-2008 Precision Time Protocol version 2 (PTPv2) for precision timing, are recommended by the both IEC Smart Grid Strategy Group and the NIST Framework and Roadmap for Smart Grid Interoperability Standards for substation automation. IEC 61850, PTPv2 and Ethernet are three complementary protocol families that together define the future of sampled value digital process connections for smart substation automation. A time synchronisation system is required for a sampled value process bus, however the details are not defined in IEC 61850-9-2. PTPv2 provides the greatest accuracy of network based time transfer systems, with timing errors of less than 100 ns achievable. The suitability of PTPv2 to synchronise sampling in a digital process bus is evaluated, with preliminary results indicating that steady state performance of low cost clocks is an acceptable ±300 ns, but that corrections issued by grandmaster clocks can introduce significant transients. Extremely stable grandmaster oscillators are required to ensure any corrections are sufficiently small that time synchronising performance is not degraded.

Fixing the city one photo at a time : mobile logging of maintenance requests

We have designed a mobile application that takes advantage of the built-in features of smart phones such as camera and GPS that allow users to take geo-tagged photos while on the move. Urban residents can take pictures of broken street furniture and public property requiring repair, attach a brief description, and submit the information as a maintenance request to the local government organisation of their city. This paper discusses the design approach that led to the application, highlights a built-in mechanism to elicit user feedback, and evaluates the progress to date with user feedback and log statistics. It concludes with an outlook highlighting user requested features and our own design aspirations for moving from a reporting tool to a civic engagement tool.

An infinite-horizon robust filter for uncertain hidden Markov Models with conditional relative entropy constraints

We consider a robust filtering problem for uncertain discrete-time, homogeneous, first-order, finite-state hidden Markov models (HMMs). The class of uncertain HMMs considered is described by a conditional relative entropy constraint on measures perturbed from a nominal regular conditional probability distribution given the previous posterior state distribution and the latest measurement. Under this class of perturbations, a robust infinite horizon filtering problem is first formulated as a constrained optimization problem before being transformed via variational results into an unconstrained optimization problem; the latter can be elegantly solved using a risk-sensitive information-state based filtering.

Which older women could benefit from interventions to decrease sitting time and increase physical activity?

In addition to the well-known health risks associated with lack of physical activity (PA), evidence is emerging about the health risks of sedentary behaviour (sitting). Research about patterns and correlates of sitting and PA in older women is scarce. METHODS: Self-report data from 6,116 women aged 76-81 years were collected as part of the Australian Longitudinal Study on Woman’s Health. Linear regression models were computed to examine whether demographic, social and health factors were associated with sitting and PA. RESULTS: Women who did no PA sat more than women who did any PA (p<0.001). Seven correlates were associated with sitting and PA (p<0.05). Five of these were associated with more sitting and less PA: three health-related (BMI, chronic conditions, anxiety/depression) and two social correlates (caring duties, volunteering). One demographic (being from another English-speaking country) and one social correlate (more social interaction) were associated with more sitting and more PA. Four correlates, two demographic (living in a city; post-high school education), one social (being single), and one health-related correlate (dizziness/loss of balance) were associated with more sitting only. Two other health-related correlates (stiff/painful joints; feet problems) were associated with less PA only. CONCLUSION: Sedentary behaviour and PA are distinct behaviours in older Australian women. Information about the correlates of both behaviours can be used to identify population groups who might benefit from interventions to reduce sedentary behaviour and/or increase PA.

A conditional retransmission enabled transport protocol for real-time networked control systems

Real-time networked control systems (NCSs) over data networks are being increasingly implemented on a massive scale in industrial applications. Along with this trend, wireless network technologies have been promoted for modern wireless NCSs (WNCSs). However, popular wireless network standards such as IEEE 802.11/15/16 are not designed for real-time communications. Key issues in real-time applications include limited transmission reliability and poor transmission delay performance. Considering the unique features of real-time control systems, this paper develops a conditional retransmission enabled transport protocol (CRETP) to improve the delay performance of the transmission control protocol (TCP) and also the reliability performance of the user datagram protocol (UDP) and its variants. Key features of the CRETP include a connectionless mechanism with acknowledgement (ACK), conditional retransmission and detection of ineffective data packets on the receiver side.

Modelling and performance evaluation of the IEEE 802.11 DCF for real-time control

Popular wireless networks, such as IEEE 802.11/15/16, are not designed for real-time applications. Thus, supporting real-time quality of service (QoS) in wireless real-time control is challenging. This paper adopts the widely used IEEE 802.11, with the focus on its distributed coordination function (DCF), for soft-real-time control systems. The concept of the critical real-time traffic condition is introduced to characterize the marginal satisfaction of real-time requirements. Then, mathematical models are developed to describe the dynamics of DCF based real-time control networks with periodic traffic, a unique feature of control systems. Performance indices such as throughput and packet delay are evaluated using the developed models, particularly under the critical real-time traffic condition. Finally, the proposed modelling is applied to traffic rate control for cross-layer networked control system design.