Single-Circulating Tumor Cell Whole Genome Amplification to Unravel Cancer Heterogeneity and Actionable Biomarkers

The field of single-cell analysis has advanced rapidly in the last decade and is providing new insights into the characterization of intercellular genetic heterogeneity and complexity, especially in human cancer. In this regard, analyzing single circulating tumor cells (CTCs) is becoming particularly attractive due to the easy access to CTCs from simple blood samples called “liquid biopsies”. Analysis of multiple single CTCs has the potential to allow the identification and characterization of cancer heterogeneity to guide best therapy and predict therapeutic response. However, single-CTC analysis is restricted by the low amounts of DNA in a single cell genome. Whole genome amplification (WGA) techniques have emerged as a key step, enabling single-cell downstream molecular analysis. Here, we provide an overview of recent advances in WGA and their applications in the genetic analysis of single CTCs, along with prospective views towards clinical applications. First, we focus on the technical challenges of isolating and recovering single CTCs and then explore different WGA methodologies and recent developments which have been utilized to amplify single cell genomes for further downstream analysis. Lastly, we list a portfolio of CTC studies which employ WGA and single-cell analysis for genetic heterogeneity and biomarker detection.     

Micromechanical digital-to-analog converter for out-of-plane motion

This paper describes a novel micromechanical digital-to-analog converter (MDAC) for out-of-plane motion using electrostatic parallel-plate actuators. The proposed mechanism converts an N-bit digital signal to a mechanical out-of-plane displacement that is proportional to the analog value represented by the N-bit binary word. The mechanism is analogous to that of an electrical binary-weighted-input digital-to-analog converter (DAC). It consists of a movable platform, an array of parallel-plate microactuators each operating in an ON/OFF mode and a set of connection springs that connect the actuators to the platform. The spring constants of the connection springs are weighted so that the stiffness of successive springs is related by a factor of 2. A 4-bit mechanism has been fabricated using the Poly-MUMPS process, achieving a total stroke of 675 nm (full-scale output) and step size (LSB) of 45 nm in a highly repeatable and stable manner. The linearity error (LE) of the device is within /spl plusmn/0.28 LSB, and the differential linearity error (DLE) is within /spl plusmn/0.25 LSB. This mechanism can be configured for many promising applications, particularly in optical devices and systems such as tunable external cavity diode laser, tunable VCSELs, adaptive micromirror array and tunable wavelength filter.     

Answering similarity queries in peer-to-peer networks

A variety of peer-to-peer (P2P) systems for sharing digital information are currently available and most of them perform searching by exact key matching. In this paper we focus on similarity searching and describe FuzzyPeer, a generic broadcast-based P2P system which supports a wide range of fuzzy queries. As a case study we present an image retrieval application implemented on top of FuzzyPeer. Users provide sample images whose sets of features are propagated through the peers. The answer consists of the top-k most similar images within the query horizon. In our system the participation of peers is ad hoc and dynamic, their functionality is symmetric and there is no centralized index.     

A novel optimization-based bandwidth-aware minimum power multicast routing algorithm in green wireless networks

Multicast routing in wireless networks that possess the wireless multicast advantage could significantly reduce the power and energy consumption. However, this kind of multicast routing that only addresses the transmission radius coverage might not be able to meet the bandwidth requirement of the users. As a result, additional transmissions are required to incur more energy consumption and carbon dioxide emissions that make existing algorithms not applicable to bandwidth constrained applications. In this paper, for the first time, we address the bandwidth aware minimum power multicast routing problem in wireless networks where the objective function is to minimize the total power consumption subject to the users?? bandwidth requirements. This problem is a challenging cross-layer design problem that requires seamless and sophisticated integrated design in the network layer (multicast routing) and physical layer (bandwidth-aware wireless transmission and power control). We first formulate this problem as a mixed integer linear programming problem and then propose a Lagrangian relaxation based algorithm to solve this problem. Numerical results demonstrate that the proposed approach is a sound green networking algorithm that outperforms the existing power efficient multicast routing approaches under all tested cases, especially in large bandwidth request, fine radius granularity, large group size and sparse network.     

The Growth of Thin Lubricating Films of Plant Oils

The extreme conditions of high pressure and shear imposed in a lubricated sliding contact could influence tribochemical reactions that could occur over long sliding distances and time scales, possibly leading to changes in both friction and film thickness. Experiments conducted with 12 plant oils reveal for the first time, that thin lubricating films of some plant oils can grow to thicknesses much greater than what is predicted from either elastohydrodyamic theory or their adsorbed molecular heights. Some films grew as much as 25 times in thickness (unrefined canola oil), while others remained roughly unchanged (flaxseed and olive oil), or grew slightly and then collapsed during the test (safflower oil). The absence of a loss in film thickness and the viscoelastic-like behavior of the film when speeds are reduced to zero, support the view that polymerization could be the main mechanism of film growth. However, the lack of correlation between the degree of unsaturation and the film growth rate suggests that other mechanisms could also be at work.     

Wireless broadband communications: some research activities inSingapore

Almost a decade ago, Singapore started crafting and implementing its IT2000 master plan to transform the city-state into an information-technology-based intelligent island. Since 1997, the main infrastructure of a high-speed ATM-based backbone network, called SingaporeONE, has been in place along with a host of commercial and governmental application service sites providing a plethora of online services. Because of its small size and extensive wired infrastructure, broadband access to homes and offices is currently provided via ADSL and cable modems. There is, however, interest in the use of wireless broadband communication technologies to access SingaporeONE, motivated primarily by its lower cost and faster deployment. In this article we describe some of our R&D activities motivated by the above interest to provide wireless broadband access to SingaporeONE. Specifically, we describe our study of LMDS, and the design and development of a wireless ATM LAN     

A Soft Resistive Acoustic Sensor Based on Suspended Standing Nanowire Membranes with Point Crack Design

An artificial basilar membrane (ABM) is an acoustic transducer that mimics the mechanical frequency selectivity of the real basilar membrane, which has the potential to revolutionize current cochlear implant technology. While such ABMs can be potentially realized using piezoelectric, triboelectric, and capacitive transduction methods, it remains notoriously difficult to achieve resistive ABM due to the poor frequency discrimination of resistive‐type materials. Here, a point crack technology on noncracking vertically aligned gold nanowire (V‐AuNW) films is reported, which allows for designing soft acoustic sensors with electric signals in good agreement with vibrometer output—a capability not achieved with corresponding bulk cracking system. The strategy can lead to soft microphones for music recognition comparable to the conventional microphone. Moreover, a soft resistive ABM is demonstrated by integrating eight nanowire‐based sensor strips on a soft trapezoid frame. The wearable ABM exhibits high‐frequency selectivity in the range of 319–1951 Hz and high sensitivity of 0.48–4.26 Pa^?1. The simple yet efficient fabrication in conjunction with programmable crack design indicates the promise of the methodology for a wide range of applications in future wearable voice recognition devices, cochlea implants, and human–machine interfaces.     

Adaptive viewpoints for co-browsing on heterogeneous devices

Co-browsing is an activity in which a group of users navigate their way through of a set of Web pages together for a shared purpose. Effective co-browsing among users with different device capabilities requires a shared understanding of those Web pages. This paper demonstrates the concept of shared viewpoints (SVPs), and personal viewpoints (PVPs), for co-browsing, before detailing a framework for implementing these concepts. Finally, the effectiveness of the framework is presented through a perceptual experiment.     

Scheduling sensor activity for information coverage of discrete targets in sensor networks

In this paper, we study the problem of scheduling sensor activity to cover a set of targets with known locations such that all targets can be monitored all the time and the network can operate as long as possible. A solution to this scheduling problem is to partition all sensors into some sensor covers such that each cover can monitor all targets and the covers are activated sequentially. In this paper, we propose to provide information coverage instead of the conventional sensing disk coverage for target. The notion of information coverage is based on estimation theory to exploit the collaborative nature of geographically distributed sensors. Due to the use of information coverage, a target that is not within the sensing disk of any single sensor can still be considered to be monitored (information covered) by the cooperation of more than one sensor. This change of the problem settings complicates the solutions compared to that by using a disk coverage model. We first define the target information coverage (TIC) problem and prove its NP‐completeness. We then propose a heuristic to approximately solve our problem. Simulation results show that our heuristic is better than an existing algorithm and is close to the upper bound when only the sensing disk coverage model is used. Furthermore, simulation results also show that the network lifetime can be significantly improved by using the notion of information coverage compared with that by using the conventional definition of sensing disk coverage. Copyright © 2008 John Wiley & Sons, Ltd.     

Bright Aggregation‐Induced Emission Dots for Dynamic Tracking and Grading of Patient‐Derived Xenografts in Zebrafish

Cancer prognosis will benefit from a scoring system that could grade malignant traits of patient‐derived cells by assessing their growth and metastasis in a living system. Specific tracking of patient‐derived cells requires labeling by contrast agents with good signal‐to‐noise ratio and no specific stain of host tissues. Towards this aim, aggregation‐induced emission (AIE) dots are developed for in vivo cancer tracking with emphasis on reproducible optimized formulation and specific fluorescent labeling of cells that enable enhanced spatial temporal resolution in vivo. The importance of energy‐dependent AIE dots uptake for patient‐derived cell labeling is emphasized to reveal their specific uptake by viable cancer cells. Using optically transparent zebrafish embryo, the ability is demonstrated to follow the engraftment of transplanted AIE dot labeled cells in zebrafish brains over one week. Cells detected outside the brain after 7 d are quantified as metastatic cells. Results from seven clinical samples demonstrate the utility of this methodology to differentiate low engraftment level of benign neoplasms from higher engraftment level and metastasis detected in malignant ovarian cancer specimens. Achieving clinically validated results supports the use of AIE dot labeled patient derived cells in zebrafish xenografts for future cancer prognosis.