Long‐Term Electrical and Mechanical Function Monitoring of a Human‐on‐a‐Chip System

The goal of human‐on‐a‐chip systems is to capture multiorgan complexity and predict the human response to compounds within physiologically relevant platforms. The generation and characterization of such systems is currently a focal point of research given the long‐standing inadequacies of conventional techniques for predicting human outcome. Functional systems can measure and quantify key cellular mechanisms that correlate with the physiological status of a tissue, and can be used to evaluate therapeutic challenges utilizing many of the same endpoints used in animal experiments or clinical trials. Culturing multiple organ compartments in a platform creates a more physiologic environment (organ–organ communication). Here is reported a human 4‐organ system composed of heart, liver, skeletal muscle, and nervous system modules that maintains cellular viability and function over 28 days in serum‐free conditions using a pumpless system. The integration of noninvasive electrical evaluation of neurons and cardiac cells and mechanical determination of cardiac and skeletal muscle contraction allows the monitoring of cellular function, especially for chronic toxicity studies in vitro. The 28‐day period is the minimum timeframe for animal studies to evaluate repeat dose toxicity. This technology can be a relevant alternative to animal testing by monitoring multiorgan function upon long‐term chemical exposure.     

Identifying a Threshold Impurity Level for Organic Solar Cells: Enhanced First‐Order Recombination Via Well‐Defined PC84BM Traps in Organic Bulk Heterojunction Solar Cells

Small amounts of impurity, even one part in one thousand, in polymer bulk heterojunction solar cells can alter the electronic properties of the device, including reducing the open circuit voltage, the short circuit current and the fill factor. Steady state studies show a dramatic increase in the trap‐assisted recombination rate when [6,6]‐phenyl C₈₄ butyric acid methyl ester (PC₈₄BM) is introduced as a trap site in polymer bulk heterojunction solar cells made of a blend of the copolymer poly[N‐9″‐hepta‐decanyl‐2,7‐carbazole‐alt‐5,5‐(4′,7′‐di‐2‐thienyl‐2′,1′,3′‐benzothiadiazole) (PCDTBT) and the fullerene derivative [6,6]‐phenyl C₆₁ butyric acid methyl ester (PC₆₀BM). The trap density dependent recombination studied here can be described as a combination of bimolecular and Shockley–Read–Hall recombination; the latter is dramatically enhanced by the addition of the PC₈₄BM traps. This study reveals the importance of impurities in limiting the efficiency of organic solar cell devices and gives insight into the mechanism of the trap‐induced recombination loss.     

Scalability and performance of an agent‐based network management middleware

Rapid growth of computer network sizes and uses necessitate analysis of network application middleware in terms of its scalability as well as performance. In this paper we analyze a distributed network management middleware based on agents that can be dispatched to locations where they can execute close to the managed nodes. The described middleware operates between the network protocol layer and the application layer and uses standard TCP protocol and SNMP probes to interface the network. By aggregating requests from many users into a single agent, our system allows multiple managers to probe problem areas with minimal management traffic overhead. We discuss and quantify the benefits of the described middleware by implementing real‐time network managers using our system. The main result of this paper is a comparison of scalability and efficiency of our agent‐based management middleware and traditional SNMP‐based data collection. To this end, we measured traffic in both real and simulated networks. In the latter case, we designed, used and described here a method of separating simulated application flow into separate subflows to simplify design of simulations. Copyright © 2004 John Wiley & Sons, Ltd.     

Analysis of external latch-up protection test structure design using numerical simulation

With each new CMOS technology the latch-up sensitivity and effects of prevention strategies change. Products built in these technologies must adhere to stringent guidelines for latch-up ‘Hardness’, and for this reason characterisation of new technologies is needed through the use of test structures. This paper shows a numerical simulation approach which can determine the relative effectiveness of guard-rings in ESD protection device test structures. In this work, time taken to characterise latch-up protection test structures and to chose a protection strategy is greatly reduced by using numerical simulations to design the test structures. The results presented are for variations to the guard-rings for two technologies. Included in these are the typical simulation times and resources required. The technique outlined has the joint advantages of providing accurately representative simulations of the technology and test structure layout in a practical time frame.     

NORMAL MODES OF FLUID-STRUCTURE INTERACTION IN INTERNAL FLOWS

As an important cornerstone, the methodology of normal modal analysis plays a quite important role in dynamic analyses of linear vibrating systems, and makes much easy to access an understanding of frequency-domain characteristics of the systems. However, most reported work on fluid-structure interaction (FSI) in liquid-filled pipes has been directly carried out in the time domain. When needed, information in the frequency domain has been deduced by the discrete Fourier transforms. In this paper, an analysis is undertaken directly to get modal information of FSI in internal flows and has the advantage of enabling dispersive and dissipative terms to be included in a fully coupled manner. The development used herein highlights common features of the analysis in the frequency domain. The method is validated by comparison with an exact analytical solution, with the results obtained by the discrete Fourier transform from an analysis using the method of characteristics and by comparison with measured data fr     

Analysis of the Electromagnetic Signals of the Human Brain: Milestones, Obstacles, and Goals

Measuring the functioning of the human brain is one of the most formidable scientific/engineering endeavors ever undertaken. It is difficult to extract information about any particular processing function from brain electromagnetic signals (BEMS) since, at any instant, only a small fraction of the brain's hundreds of simultaneously active major systems might be performing processing related to the function being studied. With recent developments, a new era of research is dawning based on an interdisciplinary approach in which advanced signal processing methods are focused on increasingly more specific neuroanatomical, neurophysiological, and neuropsychological research questions and clinical applications. This brief review highlights the major accomplishments of the last several decades in human BEMS analysis and discusses obstacles to progress. Five main topics are addressed: 1) the historical problem of developing a computerized expert clinical electroencephalogram (EEG) system; 2) advances in signal processing methods, including primary analysis, feature extraction, and statistical hypothesis testing and pattern classification; 3) integrated computing systems for BEMS analysis; 4) biophysical, basic science, practical and conceptual obstacles to progress; and 5) the long-term goal of developing a device for measuring the functional integrity of major neural systems, and the related topic of neurocybernetics. Cutting-edge issues discussed include measurement and modeling of nonstationary event-related signals, characterization of spatial processes, single-trial signal detection, location of the sources of scalp-recorded field distributions, and studies of the functional significance of BEMS.     

Performance bounds for VDE-SAT R-Mode

There has been growing interest within the satellite navigation community in the possibility of delivering positioning and timing services from existing or emerging constellations of Low-Earth Orbit communication satellites. At the same time, the international maritime community has been investigating the potential use of communication signals transmitted from shore-based stations for positioning—a concept commonly referred to as ‘ranging mode’, or R-Mode. The driving force for these developments is the desire to reduce the reliance on traditional Global Navigation Satellite Systems (GNSS). One of the technologies being considered for use in R-Mode is the evolution of the Automatic Identification System (AIS) known as the Very High Frequency Data Exchange System (VDES). VDES has a terrestrial and a satellite component. The feasibility of using terrestrial VDES transmissions for ranging was studied in a previous publication by the authors. This paper builds on the previous study and extends its results to the satellite component of VDES. Statistical bounds on the ranging error are derived for all downlink waveforms currently being considered for use in satellite VDES and for several custom-designed transmission formats. The analysis supports the feasibility of using both the existing and custom waveforms in ranging applications and points to related trade-offs that will need to be considered in the design of satellite VDES R-Mode systems.     

Design of linear equalizers optimized for the structural similarity index.

We propose an algorithm for designing linear equalizers that maximize the structural similarity (SSIM) index between the reference and restored signals. The SSIM index has enjoyed considerable application in the evaluation of image processing algorithms. Algorithms, however, have not been designed yet to explicitly optimize for this measure. The design of such an algorithm is nontrivial due to the nonconvex nature of the distortion measure. In this paper, we reformulate the nonconvex problem as a quasi-convex optimization problem, which admits a tractable solution. We compute the optimal solution in near closed form, with complexity of the resulting algorithm comparable to complexity of the linear minimum mean squared error (MMSE) solution, independent of the number of filter taps. To demonstrate the usefulness of the proposed algorithm, it is applied to restore images that have been blurred and corrupted with additive white gaussian noise. As a special case, we consider blur-free image denoising. In each case, its performance is compared to a locally adaptive linear MSE-optimal filter. We show that the images denoised and restored using the SSIM-optimal filter have higher SSIM index, and superior perceptual quality than those restored using the MSE-optimal adaptive linear filter. Through these results, we demonstrate that a) designing image processing algorithms, and, in particular, denoising and restoration-type algorithms, can yield significant gains over existing (in particular, linear MMSE-based) algorithms by optimizing them for perceptual distortion measures, and b) these gains may be obtained without significant increase in the computational complexity of the algorithm.     

An infobutton for Web 2.0 clinical discussions: the knowledge linkage framework

This paper aims to develop an infobutton to automatically retrieve published papers corresponding to a topic-specific online clinical discussion. The knowledge linkages infobutton is designed to supplement online clinical conversations with pertinent medical literature from Pubmed. The project involves three distinct steps: 1) Clinical messages around a specific problem are grouped together into a thread. 2) These threads are processed using Metamap to link the conversations to keywords from the MeSH lexicon. 3) These keywords are used in a novel search strategy to retrieve a set of papers from Pubmed, which are then returned to the user. A pilot study using the messages from 2007 and 2008, was conducted to compare the knowledge linkage search strategy to a vector space model and extended Boolean model. The knowledge linkage model proved to be significantly better in terms of precision ( p = 0.013 and 0.003, respectively) and recall ( p = 0.351 and 0.013). Pertinent papers were returned to over 55% of the threads. This approach has demonstrated how clinicians can supplement their peer communications with evidence based research. Future work should focus on how to improve the threading and keyword-mapping strategies.     

Electrode activation sequencing employing conductivity changes in irreversible electroporation tissue ablation

Irreversible electroporation (IRE) uses high-voltage pulses applied to tissue, which cause dielectric breakdown of cell membranes resulting in cell death. IRE is a promising technique for ablation of nonresectable tumors because it can be configured to spare critical structures such as blood vessels. A consequence of pulse application is an increase in tissue electrical conductivity due to current pathways being opened in cell membranes. We propose a novel IRE method introducing electrode switching and pulse sequencing in which tissue conductivity is first increased using preparatory pulses in order to form high-conductivity zones, which then helps provide higher electric field intensity within the targeted tissue as subsequent pulses are applied, and hence, enhances the efficiency and selectivity of the IRE treatment. We demonstrate the potential of this method using computational models on simple geometries.