A collagen network phase improves cell seeding of open-pore structure scaffolds under perfusion

Scaffolds with open-pore morphologies offer several advantages in cell-based tissue engineering, but their use is limited by a low cell seeding efficiency. We hypothesized that inclusion of a collagen network as filling material within the open-pore architecture of polycaprolactone-tricalcium phosphate (PCL-TCP) scaffolds increases human bone marrow stromal cells (hBMSC) seeding efficiency under perfusion and in vivo osteogenic capacity of the resulting constructs. PCL-TCP scaffolds, rapid prototyped with a honeycomb-like architecture, were filled with a collagen gel and subsequently lyophilized, with or without final crosslinking. Collagen-free scaffolds were used as controls. The seeding efficiency was assessed after overnight perfusion of expanded hBMSC directly through the scaffold pores using a bioreactor system. By seeding and culturing freshly harvested hBMSC under perfusion for 3 weeks, the osteogenic capacity of generated constructs was tested by ectopic implantation in nude mice. The presence of the collagen network, independently of the crosslinking process, significantly increased the cell seeding efficiency (2.5-fold), and reduced the loss of clonogenic cells in the supernatant. Although no implant generated frank bone tissue, possibly due to the mineral distribution within the scaffold polymer phase, the presence of a non crosslinked collagen phase led to in vivo formation of scattered structures of dense osteoids. Our findings verify that the inclusion of a collagen network within open morphology porous scaffolds improves cell retention under perfusion seeding. In the context of cell-based therapies, collagen-filled porous scaffolds are expected to yield superior cell utilization, and could be combined with perfusion-based bioreactor devices to streamline graft manufacture.

Digital signal processing

Signal Processing (SP) is a subject of central importance in engineering and the applied sciences. Signals are information-bearing functions, and SP deals with the analysis and processing of signals (by dedicated systems) to extract or modify information. Signal processing is necessary because signals normally contain information that is not readily usable or understandable, or which might be disturbed by unwanted sources such as noise. Although many signals are non-electrical, it is common to convert them into electrical signals for processing. Most natural signals (such as acoustic and biomedical signals) are continuous functions of time, with these signals being referred to as analog signals. Prior to the onset of digital computers, Analog Signal Processing (ASP) and analog systems were the only tool to deal with analog signals. Although ASP and analog systems are still widely used, Digital Signal Processing (DSP) and digital systems are attracting more attention, due in large part to the significant advantages of digital systems over the analog counterparts. These advantages include superiority in performance,s peed, reliability, efficiency of storage, size and cost. In addition, DSP can solve problems that cannot be solved using ASP, like the spectral analysis of multicomonent signals, adaptive filtering, and operations at very low frequencies. Following the recent developments in engineering which occurred in the 1980's and 1990's, DSP became one of the world's fastest growing industries. Since that time DSP has not only impacted on traditional areas of electrical engineering, but has had far reaching effects on other domains that deal with information such as economics, meteorology, seismology, bioengineering, oceanology, communications, astronomy, radar engineering, control engineering and various other applications. This book is based on the Lecture Notes of Associate Professor Zahir M. Hussain at RMIT University (Melbourne, 2001-2009), the research of Dr. Amin Z. Sadik (at QUT & RMIT, 2005-2008), and the Note of Professor Peter O'Shea at Queensland University of Technology. Part I of the book addresses the representation of analog and digital signals and systems in the time domain and in the frequency domain. The core topics covered are convolution, transforms (Fourier, Laplace, Z. Discrete-time Fourier, and Discrete Fourier), filters, and random signal analysis. There is also a treatment of some important applications of DSP, including signal detection in noise, radar range estimation, banking and financial applications, and audio effects production. Design and implementation of digital systems (such as integrators, differentiators, resonators and oscillators are also considered, along with the design of conventional digital filters. Part I is suitable for an elementary course in DSP. Part II (which is suitable for an advanced signal processing course), considers selected signal processing systems and techniques. Core topics covered are the Hilbert transformer, binary signal transmission, phase-locked loops, sigma-delta modulation, noise shaping, quantization, adaptive filters, and non-stationary signal analysis. Part III presents some selected advanced DSP topics. We hope that this book will contribute to the advancement of engineering education and that it will serve as a general reference book on digital signal processing.

Oral intake and serum levels of ascorbic acid in continuous ambulatory peritoneal dialysis patients

Oral intake of ascorbic acid is essential for optimum health in human beings. Continuous ambulatory peritoneal dialysis (CAPD) patients have an increased need for ascorbic acid, because of increased loss through dialysate, reduced intake owing to nausea and loss of appetite, and increased oxidative stress. However, optimum intake is still controversial. We studied 50 clinically stable patients to determine the relationship between oral ascorbic acid intake and serum ascorbic acid (SAA) level. Total oral intake ranged from 28 mg daily to 412 mg daily. Only one patient had an oral intake of ascorbic acid below 60 mg per day. The SAA levels ranged from 1 mg/L to 36.17 mg/L. Although a strong correlation existed between intake and SAA (p < 0.001, R2 = 0.47), the variation in SAA at any given intake level was wide. Of the studied patients, 62% had an SAA < 8.7 mg/L, 40% had an SAA < 5.1 mg/L (below the level in a healthy population), and 12% had a level below 2 mg/L (scorbutic). None of the patients demonstrated clinical manifestations of scurvy. Our results show that, in CAPD patients, ascorbic acid deficiency can be reliably detected only with SAA measurements, and oral intake may influence SAA level. To maintain ascorbic acid in the normal range for healthy adults, daily oral intake needs to be increased above the U.S. recommended dietary allowance to 80-140 mg.

Social network and aesthetic reflexivity in the creative industries

This article reviews some key critical writing about the commodification or exploitation of networked social relations in the creative industries. Through a comparative case study of networks in fashion and new media industries in the city of Manchester, UK, the article draws attention to the social, cultural and aesthetic aspects of the networks among creative practitioners. It argues that within the increasing commercialisation in the creative industries there are networked spaces within which non-instrumental values are created. The building of social networks reflects on the issue of how creatives perceive their work in these industries both economically and socially/culturally.

The sample complexity of pattern classification with neural networks: the size of the weights is more important than the size of the network

Sample complexity results from computational learning theory, when applied to neural network learning for pattern classification problems, suggest that for good generalization performance the number of training examples should grow at least linearly with the number of adjustable parameters in the network. Results in this paper show that if a large neural network is used for a pattern classification problem and the learning algorithm finds a network with small weights that has small squared error on the training patterns, then the generalization performance depends on the size of the weights rather than the number of weights. For example, consider a two-layer feedforward network of sigmoid units, in which the sum of the magnitudes of the weights associated with each unit is bounded by A and the input dimension is n. We show that the misclassification probability is no more than a certain error estimate (that is related to squared error on the training set) plus A3 √((log n)/m) (ignoring log A and log m factors), where m is the number of training patterns. This may explain the generalization performance of neural networks, particularly when the number of training examples is considerably smaller than the number of weights. It also supports heuristics (such as weight decay and early stopping) that attempt to keep the weights small during training. The proof techniques appear to be useful for the analysis of other pattern classifiers: when the input domain is a totally bounded metric space, we use the same approach to give upper bounds on misclassification probability for classifiers with decision boundaries that are far from the training examples.

Neural network learning:theoretical foundations

This important work describes recent theoretical advances in the study of artificial neural networks. It explores probabilistic models of supervised learning problems, and addresses the key statistical and computational questions. Chapters survey research on pattern classification with binary-output networks, including a discussion of the relevance of the Vapnik Chervonenkis dimension, and of estimates of the dimension for several neural network models. In addition, Anthony and Bartlett develop a model of classification by real-output networks, and demonstrate the usefulness of classification with a "large margin." The authors explain the role of scale-sensitive versions of the Vapnik Chervonenkis dimension in large margin classification, and in real prediction. Key chapters also discuss the computational complexity of neural network learning, describing a variety of hardness results, and outlining two efficient, constructive learning algorithms. The book is self-contained and accessible to researchers and graduate students in computer science, engineering, and mathematics

Infinite-horizon policy-gradient estimation

Gradient-based approaches to direct policy search in reinforcement learning have received much recent attention as a means to solve problems of partial observability and to avoid some of the problems associated with policy degradation in value-function methods. In this paper we introduce GPOMDP, a simulation-based algorithm for generating a biased estimate of the gradient of the average reward in Partially Observable Markov Decision Processes (POMDPs) controlled by parameterized stochastic policies. A similar algorithm was proposed by Kimura, Yamamura, and Kobayashi (1995). The algorithm's chief advantages are that it requires storage of only twice the number of policy parameters, uses one free parameter β ∈ [0,1) (which has a natural interpretation in terms of bias-variance trade-off), and requires no knowledge of the underlying state. We prove convergence of GPOMDP, and show how the correct choice of the parameter β is related to the mixing time of the controlled POMDP. We briefly describe extensions of GPOMDP to controlled Markov chains, continuous state, observation and control spaces, multiple-agents, higher-order derivatives, and a version for training stochastic policies with internal states. In a companion paper (Baxter, Bartlett, & Weaver, 2001) we show how the gradient estimates generated by GPOMDP can be used in both a traditional stochastic gradient algorithm and a conjugate-gradient procedure to find local optima of the average reward. ©2001 AI Access Foundation and Morgan Kaufmann Publishers. All rights reserved.

Exponentiated gradient algorithms for conditional random fields and max-margin Markov Networks

Log-linear and maximum-margin models are two commonly-used methods in supervised machine learning, and are frequently used in structured prediction problems. Efficient learning of parameters in these models is therefore an important problem, and becomes a key factor when learning from very large data sets. This paper describes exponentiated gradient (EG) algorithms for training such models, where EG updates are applied to the convex dual of either the log-linear or max-margin objective function; the dual in both the log-linear and max-margin cases corresponds to minimizing a convex function with simplex constraints. We study both batch and online variants of the algorithm, and provide rates of convergence for both cases. In the max-margin case, O(1/ε) EG updates are required to reach a given accuracy ε in the dual; in contrast, for log-linear models only O(log(1/ε)) updates are required. For both the max-margin and log-linear cases, our bounds suggest that the online EG algorithm requires a factor of n less computation to reach a desired accuracy than the batch EG algorithm, where n is the number of training examples. Our experiments confirm that the online algorithms are much faster than the batch algorithms in practice. We describe how the EG updates factor in a convenient way for structured prediction problems, allowing the algorithms to be efficiently applied to problems such as sequence learning or natural language parsing. We perform extensive evaluation of the algorithms, comparing them to L-BFGS and stochastic gradient descent for log-linear models, and to SVM-Struct for max-margin models. The algorithms are applied to a multi-class problem as well as to a more complex large-scale parsing task. In all these settings, the EG algorithms presented here outperform the other methods.

Overcoming the complexity of diagnostic problems due to sensor network architecture

In fault detection and diagnostics, limitations coming from the sensor network architecture are one of the main challenges in evaluating a system’s health status. Usually the design of the sensor network architecture is not solely based on diagnostic purposes, other factors like controls, financial constraints, and practical limitations are also involved. As a result, it quite common to have one sensor (or one set of sensors) monitoring the behaviour of two or more components. This can significantly extend the complexity of diagnostic problems. In this paper a systematic approach is presented to deal with such complexities. It is shown how the problem can be formulated as a Bayesian network based diagnostic mechanism with latent variables. The developed approach is also applied to the problem of fault diagnosis in HVAC systems, an application area with considerable modeling and measurement constraints.

Group maintenance scheduling : a case study for a pipeline network

This paper presents a group maintenance scheduling case study for a water distributed network. This water pipeline network presents the challenge of maintaining aging pipelines with the associated increases in annual maintenance costs. The case study focuses on developing an effective maintenance plan for the water utility. Current replacement planning is difficult as it needs to balance the replacement needs under limited budgets. A Maintenance Grouping Optimization (MGO) model based on a modified genetic algorithm was utilized to develop an optimum group maintenance schedule over a 20-year cycle. The adjacent geographical distribution of pipelines was used as a grouping criterion to control the searching space of the MGO model through a Judgment Matrix. Based on the optimum group maintenance schedule, the total cost was effectively reduced compared with the schedules without grouping maintenance jobs. This optimum result can be used as a guidance to optimize the current maintenance plan for the water utility.

Stochastic models for regulatory networks of the genetic toggle switch

Bistability arises within a wide range of biological systems from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.

Numerical methods for second-order stochastic differential equations

We seek numerical methods for second‐order stochastic differential equations that reproduce the stationary density accurately for all values of damping. A complete analysis is possible for scalar linear second‐order equations (damped harmonic oscillators with additive noise), where the statistics are Gaussian and can be calculated exactly in the continuous‐time and discrete‐time cases. A matrix equation is given for the stationary variances and correlation for methods using one Gaussian random variable per timestep. The only Runge–Kutta method with a nonsingular tableau matrix that gives the exact steady state density for all values of damping is the implicit midpoint rule. Numerical experiments, comparing the implicit midpoint rule with Heun and leapfrog methods on nonlinear equations with additive or multiplicative noise, produce behavior similar to the linear case.