Bacterial growth rate and host factors as determinants of intracellular bacterial distributions in systemic Salmonella enterica infections.

Bacteria of the species Salmonella enterica cause a range of life-threatening diseases in humans and animals worldwide. The within-host quantitative, spatial, and temporal dynamics of S. enterica interactions are key to understanding how immunity acts on these infections and how bacteria evade immune surveillance. In this study, we test hypotheses generated from mathematical models of in vivo dynamics of Salmonella infections with experimental observation of bacteria at the single-cell level in infected mouse organs to improve our understanding of the dynamic interactions between host and bacterial mechanisms that determine net growth rates of S. enterica within the host. We show that both bacterial and host factors determine the numerical distributions of bacteria within host cells and thus the level of dispersiveness of the infection.

Campylobacter jejuni colonization and transmission in broiler chickens: a modelling perspective.

Campylobacter jejuni is one of the most common causes of acute enteritis in the developed world. The consumption of contaminated poultry, where C. jejuni is believed to be a commensal organism, is a major risk factor. However, the dynamics of this colonization process in commercially reared chickens is still poorly understood. Quantification of these dynamics of infection at an individual level is vital to understand transmission within populations and formulate new control strategies. There are multiple potential routes of introduction of C. jejuni into a commercial flock. Introduction is followed by a rapid increase in environmental levels of C. jejuni and the level of colonization of individual broilers. Recent experimental and epidemiological evidence suggest that the celerity of this process could be masking a complex pattern of colonization and extinction of bacterial strains within individual hosts. Despite the rapidity of colonization, experimental transmission studies exhibit a highly variable and unexplained delay time in the initial stages of the process. We review past models of transmission of C. jejuni in broilers and consider simple modifications, motivated by the plausible biological mechanisms of clearance and latency, which could account for this delay. We show how simple mathematical models can be used to guide the focus of experimental studies by providing testable predictions based on our hypotheses. We conclude by suggesting that competition experiments could be used to further understand the dynamics and mechanisms underlying the colonization process. The population models for such competition processes have been extensively studied in other ecological and evolutionary contexts. However, C. jejuni can potentially adapt phenotypically through phase variation in gene expression, leading to unification of ecological and evolutionary time-scales. For a theoretician, the colonization dynamics of C. jejuni offer an experimental system to explore these 'phylodynamics', the synthesis of population dynamics and evolutionary biology.

Motor task variation induces structural learning.

When we have learned a motor skill, such as cycling or ice-skating, we can rapidly generalize to novel tasks, such as motorcycling or rollerblading [1-8]. Such facilitation of learning could arise through two distinct mechanisms by which the motor system might adjust its control parameters. First, fast learning could simply be a consequence of the proximity of the original and final settings of the control parameters. Second, by structural learning [9-14], the motor system could constrain the parameter adjustments to conform to the control parameters' covariance structure. Thus, facilitation of learning would rely on the novel task parameters' lying on the structure of a lower-dimensional subspace that can be explored more efficiently. To test between these two hypotheses, we exposed subjects to randomly varying visuomotor tasks of fixed structure. Although such randomly varying tasks are thought to prevent learning, we show that when subsequently presented with novel tasks, subjects exhibit three key features of structural learning: facilitated learning of tasks with the same structure, strong reduction in interference normally observed when switching between tasks that require opposite control strategies, and preferential exploration along the learned structure. These results suggest that skill generalization relies on task variation and structural learning.

Optimal H2 order-one reduction by solving eigenproblems for polynomial equations

A method is given for solving an optimal H2 approximation problem for SISO linear time-invariant stable systems. The method, based on constructive algebra, guarantees that the global optimum is found; it does not involve any gradient-based search, and hence avoids the usual problems of local minima. We examine mostly the case when the model order is reduced by one, and when the original system has distinct poles. This case exhibits special structure which allows us to provide a complete solution. The problem is converted into linear algebra by exhibiting a finite-dimensional basis for a certain space, and can then be solved by eigenvalue calculations, following the methods developed by Stetter and Moeller. The use of Buchberger's algorithm is avoided by writing the first-order optimality conditions in a special form, from which a Groebner basis is immediately available. Compared with our previous work the method presented here has much smaller time and memory requirements, and can therefore be applied to systems of significantly higher McMillan degree. In addition, some hypotheses which were required in the previous work have been removed. Some examples are included.

Short- and long-term changes in joint co-contraction associated with motor learning as revealed from surface EMG.

In the field of motor control, two hypotheses have been controversial: whether the brain acquires internal models that generate accurate motor commands, or whether the brain avoids this by using the viscoelasticity of musculoskeletal system. Recent observations on relatively low stiffness during trained movements support the existence of internal models. However, no study has revealed the decrease in viscoelasticity associated with learning that would imply improvement of internal models as well as synergy between the two hypothetical mechanisms. Previously observed decreases in electromyogram (EMG) might have other explanations, such as trajectory modifications that reduce joint torques. To circumvent such complications, we required strict trajectory control and examined only successful trials having identical trajectory and torque profiles. Subjects were asked to perform a hand movement in unison with a target moving along a specified and unusual trajectory, with shoulder and elbow in the horizontal plane at the shoulder level. To evaluate joint viscoelasticity during the learning of this movement, we proposed an index of muscle co-contraction around the joint (IMCJ). The IMCJ was defined as the summation of the absolute values of antagonistic muscle torques around the joint and computed from the linear relation between surface EMG and joint torque. The IMCJ during isometric contraction, as well as during movements, was confirmed to correlate well with joint stiffness estimated using the conventional method, i.e., applying mechanical perturbations. Accordingly, the IMCJ during the learning of the movement was computed for each joint of each trial using estimated EMG-torque relationship. At the same time, the performance error for each trial was specified as the root mean square of the distance between the target and hand at each time step over the entire trajectory. The time-series data of IMCJ and performance error were decomposed into long-term components that showed decreases in IMCJ in accordance with learning with little change in the trajectory and short-term interactions between the IMCJ and performance error. A cross-correlation analysis and impulse responses both suggested that higher IMCJs follow poor performances, and lower IMCJs follow good performances within a few successive trials. Our results support the hypothesis that viscoelasticity contributes more when internal models are inaccurate, while internal models contribute more after the completion of learning. It is demonstrated that the CNS regulates viscoelasticity on a short- and long-term basis depending on performance error and finally acquires smooth and accurate movements while maintaining stability during the entire learning process.

Combining information sources for confidence estimation with CRF models

Obtaining accurate confidence measures for automatic speech recognition (ASR) transcriptions is an important task which stands to benefit from the use of multiple information sources. This paper investigates the application of conditional random field (CRF) models as a principled technique for combining multiple features from such sources. A novel method for combining suitably defined features is presented, allowing for confidence annotation using lattice-based features of hypotheses other than the lattice 1-best. The resulting framework is applied to different stages of a state-of-the-art large vocabulary speech recognition pipeline, and consistent improvements are shown over a sophisticated baseline system. Copyright © 2011 ISCA.

Use of contexts in language model interpolation and adaptation

Language models (LMs) are often constructed by building multiple individual component models that are combined using context independent interpolation weights. By tuning these weights, using either perplexity or discriminative approaches, it is possible to adapt LMs to a particular task. This paper investigates the use of context dependent weighting in both interpolation and test-time adaptation of language models. Depending on the previous word contexts, a discrete history weighting function is used to adjust the contribution from each component model. As this dramatically increases the number of parameters to estimate, robust weight estimation schemes are required. Several approaches are described in this paper. The first approach is based on MAP estimation where interpolation weights of lower order contexts are used as smoothing priors. The second approach uses training data to ensure robust estimation of LM interpolation weights. This can also serve as a smoothing prior for MAP adaptation. A normalized perplexity metric is proposed to handle the bias of the standard perplexity criterion to corpus size. A range of schemes to combine weight information obtained from training data and test data hypotheses are also proposed to improve robustness during context dependent LM adaptation. In addition, a minimum Bayes' risk (MBR) based discriminative training scheme is also proposed. An efficient weighted finite state transducer (WFST) decoding algorithm for context dependent interpolation is also presented. The proposed technique was evaluated using a state-of-the-art Mandarin Chinese broadcast speech transcription task. Character error rate (CER) reductions up to 7.3 relative were obtained as well as consistent perplexity improvements. © 2012 Elsevier Ltd. All rights reserved.

N-best error simulation for training spoken dialogue systems

A recent trend in spoken dialogue research is the use of reinforcement learning to train dialogue systems in a simulated environment. Past researchers have shown that the types of errors that are simulated can have a significant effect on simulated dialogue performance. Since modern systems typically receive an N-best list of possible user utterances, it is important to be able to simulate a full N-best list of hypotheses. This paper presents a new method for simulating such errors based on logistic regression, as well as a new method for simulating the structure of N-best lists of semantics and their probabilities, based on the Dirichlet distribution. Off-line evaluations show that the new Dirichlet model results in a much closer match to the receiver operating characteristics (ROC) of the live data. Experiments also show that the logistic model gives confusions that are closer to the type of confusions observed in live situations. The hope is that these new error models will be able to improve the resulting performance of trained dialogue systems. © 2012 IEEE.

Discriminative spoken language understanding using word confusion networks

Current commercial dialogue systems typically use hand-crafted grammars for Spoken Language Understanding (SLU) operating on the top one or two hypotheses output by the speech recogniser. These systems are expensive to develop and they suffer from significant degradation in performance when faced with recognition errors. This paper presents a robust method for SLU based on features extracted from the full posterior distribution of recognition hypotheses encoded in the form of word confusion networks. Following [1], the system uses SVM classifiers operating on n-gram features, trained on unaligned input/output pairs. Performance is evaluated on both an off-line corpus and on-line in a live user trial. It is shown that a statistical discriminative approach to SLU operating on the full posterior ASR output distribution can substantially improve performance both in terms of accuracy and overall dialogue reward. Furthermore, additional gains can be obtained by incorporating features from the previous system output. © 2012 IEEE.

A confidence-based approach for improving keyword hypothesis scores

The task in keyword spotting (KWS) is to hypothesise times at which any of a set of key terms occurs in audio. An important aspect of such systems are the scores assigned to these hypotheses, the accuracy of which have a significant impact on performance. Estimating these scores may be formulated as a confidence estimation problem, where a measure of confidence is assigned to each key term hypothesis. In this work, a set of discriminative features is defined, and combined using a conditional random field (CRF) model for improved confidence estimation. An extension to this model to directly address the problem of score normalisation across key terms is also introduced. The implicit score normalisation which results from applying this approach to separate systems in a hybrid configuration yields further benefits. Results are presented which show notable improvements in KWS performance using the techniques presented in this work. © 2013 IEEE.