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.

Generalized binomial Tau-leap method for biochemical kinetics incorporating both delay and intrinsic noise

The delay stochastic simulation algorithm (DSSA) by Barrio et al. [Plos Comput. Biol.2, 117–E (2006)] was developed to simulate delayed processes in cell biology in the presence of intrinsic noise, that is, when there are small-to-moderate numbers of certain key molecules present in a chemical reaction system. These delayed processes can faithfully represent complex interactions and mechanisms that imply a number of spatiotemporal processes often not explicitly modeled such as transcription and translation, basic in the modeling of cell signaling pathways. However, for systems with widely varying reaction rate constants or large numbers of molecules, the simulation time steps of both the stochastic simulation algorithm (SSA) and the DSSA can become very small causing considerable computational overheads. In order to overcome the limit of small step sizes, various τ-leap strategies have been suggested for improving computational performance of the SSA. In this paper, we present a binomial τ- DSSA method that extends the τ-leap idea to the delay setting and avoids drawing insufficient numbers of reactions, a common shortcoming of existing binomial τ-leap methods that becomes evident when dealing with complex chemical interactions. The resulting inaccuracies are most evident in the delayed case, even when considering reaction products as potential reactants within the same time step in which they are produced. Moreover, we extend the framework to account for multicellular systems with different degrees of intercellular communication. We apply these ideas to two important genetic regulatory models, namely, the hes1 gene, implicated as a molecular clock, and a Her1/Her 7 model for coupled oscillating cells.

A plasmonic 'ac Wheatstone bridge' circuit for high-sensitivity phase measurement and single-molecule detection

In this paper, a plasmonic “ac Wheatstone bridge” circuit is proposed and theoretically modeled for the first time. The bridge circuit consists of three metallic nanoparticles, shaped as rectangular prisms, with two nanoparticles acting as parallel arms of a resonant circuit and the third bridging nanoparticle acting as an optical antenna providing an output signal. Polarized light excites localized surface plasmon resonances in the two arms of the circuit, which generate an optical signal dependent on the phase-sensitive excitations of surface plasmons in the antenna. The circuit is analyzed using a plasmonic coupling theory and numerical simulations. The analyses show that the plasmonic circuit is sensitive to phase shifts between the arms of the bridge and has the potential to detect the presence of single molecules.

Shape discrimination using invariants defined from higher-order spectra

An approach to pattern recognition using invariant parameters based on higher-order spectra is presented. In particular, bispectral invariants are used to classify one-dimensional shapes. The bispectrum, which is translation invariant, is integrated along straight lines passing through the origin in bifrequency space. The phase of the integrated bispectrum is shown to be scale- and amplification-invariant. A minimal set of these invariants is selected as the feature vector for pattern classification. Pattern recognition using higher-order spectral invariants is fast, suited for parallel implementation, and works for signals corrupted by Gaussian noise. The classification technique is shown to distinguish two similar but different bolts given their one-dimensional profiles

Improving visual noise insensitivity in small vocabulary audio visual speech recognition applications

Visual noise insensitivity is important to audio visual speech recognition (AVSR). Visual noise can take on a number of forms such as varying frame rate, occlusion, lighting or speaker variabilities. The use of a high dimensional secondary classifier on the word likelihood scores from both the audio and video modalities is investigated for the purposes of adaptive fusion. Preliminary results are presented demonstrating performance above the catastrophic fusion boundary for our confidence measure irrespective of the type of visual noise presented to it. Our experiments were restricted to small vocabulary applications.

Computational approaches for modelling intrinsic noise and delays in genetic regulatory networks

This chapter focuses on the interactions and roles between delays and intrinsic noise effects within cellular pathways and regulatory networks. We address these aspects by focusing on genetic regulatory networks that share a common network motif, namely the negative feedback loop, leading to oscillatory gene expression and protein levels. In this context, we discuss computational simulation algorithms for addressing the interplay of delays and noise within the signaling pathways based on biological data. We address implementational issues associated with efficiency and robustness. In a molecular biology setting we present two case studies of temporal models for the Hes1 gene (Monk, 2003; Hirata et al., 2002), known to act as a molecular clock, and the Her1/Her7 regulatory system controlling the periodic somite segmentation in vertebrate embryos (Giudicelli and Lewis, 2004; Horikawa et al., 2006).