On-chip non-invasive and label-free cell discrimination by impedance spectroscopy

OBJECTIVES: Many flow-cytometric cell characterization methods require costly markers and colour reagents. We present here a novel device for cell discrimination based on impedance measurement of electrical cell properties in a microfluidic chip, without the need of extensive sample preparation steps and the requirement of labelling dyes. MATERIALS AND METHODS, RESULTS: We demonstrate that in-flow single cell measurements in our microchip allow for discrimination of various cell line types, such as undifferentiated mouse fibroblasts 3T3-L1 and adipocytes on the one hand, or human monocytes and in vitro differentiated dendritic cells and macrophages on the other hand. In addition, viability and apoptosis analyses were carried out successfully for Jurkat cell models. Studies on several species, including bacteria or fungi, demonstrate not only the capability to enumerate these cells, but also show that even other microbiological life cycle phases can be visualized. CONCLUSIONS: These results underline the potential of impedance spectroscopy flow cytometry as a valuable complement to other known cytometers and cell detection systems.

Multi-antenna non-line-of-sight identification techniques for target localization in mobile ad-hoc networks

Target localization has a wide range of military and civilian applications in wireless mobile networks. Examples include battle-field surveillance, emergency 911 (E911), traffc alert, habitat monitoring, resource allocation, routing, and disaster mitigation. Basic localization techniques include time-of-arrival (TOA), direction-of-arrival (DOA) and received-signal strength (RSS) estimation. Techniques that are proposed based on TOA and DOA are very sensitive to the availability of Line-of-sight (LOS) which is the direct path between the transmitter and the receiver. If LOS is not available, TOA and DOA estimation errors create a large localization error. In order to reduce NLOS localization error, NLOS identifcation, mitigation, and localization techniques have been proposed. This research investigates NLOS identifcation for multiple antennas radio systems. The techniques proposed in the literature mainly use one antenna element to enable NLOS identifcation. When a single antenna is utilized, limited features of the wireless channel can be exploited to identify NLOS situations. However, in DOA-based wireless localization systems, multiple antenna elements are available. In addition, multiple antenna technology has been adopted in many widely used wireless systems such as wireless LAN 802.11n and WiMAX 802.16e which are good candidates for localization based services. In this work, the potential of spatial channel information for high performance NLOS identifcation is investigated. Considering narrowband multiple antenna wireless systems, two xvNLOS identifcation techniques are proposed. Here, the implementation of spatial correlation of channel coeffcients across antenna elements as a metric for NLOS identifcation is proposed. In order to obtain the spatial correlation, a new multi-input multi-output (MIMO) channel model based on rough surface theory is proposed. This model can be used to compute the spatial correlation between the antenna pair separated by any distance. In addition, a new NLOS identifcation technique that exploits the statistics of phase difference across two antenna elements is proposed. This technique assumes the phases received across two antenna elements are uncorrelated. This assumption is validated based on the well-known circular and elliptic scattering models. Next, it is proved that the channel Rician K-factor is a function of the phase difference variance. Exploiting Rician K-factor, techniques to identify NLOS scenarios are proposed. Considering wideband multiple antenna wireless systems which use MIMO-orthogonal frequency division multiplexing (OFDM) signaling, space-time-frequency channel correlation is exploited to attain NLOS identifcation in time-varying, frequency-selective and spaceselective radio channels. Novel NLOS identi?cation measures based on space, time and frequency channel correlation are proposed and their performances are evaluated. These measures represent a better NLOS identifcation performance compared to those that only use space, time or frequency.

Electron transport in molecular systems

The remarkable advances in nanoscience and nanotechnology over the last two decades allow one to manipulate individuals atoms, molecules and nanostructures, make it possible to build devices with only a few nanometers, and enhance the nano-bio fusion in tackling biological and medical problems. It complies with the ever-increasing need for device miniaturization, from magnetic storage devices, electronic building blocks for computers, to chemical and biological sensors. Despite the continuing efforts based on conventional methods, they are likely to reach the fundamental limit of miniaturization in the next decade, when feature lengths shrink below 100 nm. On the one hand, quantum mechanical efforts of the underlying material structure dominate device characteristics. On the other hand, one faces the technical difficulty in fabricating uniform devices. This has posed a great challenge for both the scientific and the technical communities. The proposal of using a single or a few organic molecules in electronic devices has not only opened an alternative way of miniaturization in electronics, but also brought up brand-new concepts and physical working mechanisms in electronic devices. This thesis work stands as one of the efforts in understanding and building of electronic functional units at the molecular and atomic levels. We have explored the possibility of having molecules working in a wide spectrum of electronic devices, ranging from molecular wires, spin valves/switches, diodes, transistors, and sensors. More specifically, we have observed significant magnetoresistive effect in a spin-valve structure where the non-magnetic spacer sandwiched between two magnetic conducting materials is replaced by a self-assembled monolayer of organic molecules or a single molecule (like a carbon fullerene). The diode behavior in donor(D)-bridge(B)-acceptor(A) type of single molecules is then discussed and a unimolecular transistor is designed. Lastly, we have proposed and primarily tested the idea of using functionalized electrodes for rapid nanopore DNA sequencing. In these studies, the fundamental roles of molecules and molecule-electrode interfaces on quantum electron transport have been investigated based on first-principles calculations of the electronic structure. Both the intrinsic properties of molecules themselves and the detailed interfacial features are found to play critical roles in electron transport at the molecular scale. The flexibility and tailorability of the properties of molecules have opened great opportunity in a purpose-driven design of electronic devices from the bottom up. The results that we gained from this work have helped in understanding the underlying physics, developing the fundamental mechanism and providing guidance for future experimental efforts.

Wind plant interaction with series-compensated power systems

Wind power based generation has been rapidly growing world-wide during the recent past. In order to transmit large amounts of wind power over long distances, system planners may often add series compensation to existing transmission lines owing to several benefits such as improved steady-state power transfer limit, improved transient stability, and efficient utilization of transmission infrastructure. Application of series capacitors has posed resonant interaction concerns such as through subsynchronous resonance (SSR) with conventional turbine-generators. Wind turbine-generators may also be susceptible to such resonant interactions. However, not much information is available in literature and even engineering standards are yet to address these issues. The motivation problem for this research is based on an actual system switching event that resulted in undamped oscillations in a 345-kV series-compensated, typical ring-bus power system configuration. Based on time-domain ATP (Alternative Transients Program) modeling, simulations and analysis of system event records, the occurrence of subsynchronous interactions within the existing 345-kV series-compensated power system has been investigated. Effects of various small-signal and large-signal power system disturbances with both identical and non-identical wind turbine parameters (such as with a statistical-spread) has been evaluated. Effect of parameter variations on subsynchronous oscillations has been quantified using 3D-DFT plots and the oscillations have been identified as due to electrical self-excitation effects, rather than torsional interaction. Further, the generator no-load reactance and the rotor-side converter inner-loop controller gains have been identified as bearing maximum sensitivity to either damping or exacerbating the self-excited oscillations. A higher-order spectral analysis method based on modified Prony estimation has been successfully applied to the field records identifying dominant 9.79 Hz subsynchronous oscillations. Recommendations have been made for exploring countermeasures.

EVALUATING INFRASTRUCTURE PERFORMANCE TO ASSIST FACILITY MANAGEMENT TOWARD SUSTAINABLE SYSTEMS

Civil infrastructure provides essential services for the development of both society and economy. It is very important to manage systems efficiently to ensure sound performance. However, there are challenges in information extraction from available data, which also necessitates the establishment of methodologies and frameworks to assist stakeholders in the decision making process. This research proposes methodologies to evaluate systems performance by maximizing the use of available information, in an effort to build and maintain sustainable systems. Under the guidance of problem formulation from a holistic view proposed by Mukherjee and Muga, this research specifically investigates problem solving methods that measure and analyze metrics to support decision making. Failures are inevitable in system management. A methodology is developed to describe arrival pattern of failures in order to assist engineers in failure rescues and budget prioritization especially when funding is limited. It reveals that blockage arrivals are not totally random. Smaller meaningful subsets show good random behavior. Additional overtime failure rate is analyzed by applying existing reliability models and non-parametric approaches. A scheme is further proposed to depict rates over the lifetime of a given facility system. Further analysis of sub-data sets is also performed with the discussion of context reduction. Infrastructure condition is another important indicator of systems performance. The challenges in predicting facility condition are the transition probability estimates and model sensitivity analysis. Methods are proposed to estimate transition probabilities by investigating long term behavior of the model and the relationship between transition rates and probabilities. To integrate heterogeneities, model sensitivity is performed for the application of non-homogeneous Markov chains model. Scenarios are investigated by assuming transition probabilities follow a Weibull regressed function and fall within an interval estimate. For each scenario, multiple cases are simulated using a Monte Carlo simulation. Results show that variations on the outputs are sensitive to the probability regression. While for the interval estimate, outputs have similar variations to the inputs. Life cycle cost analysis and life cycle assessment of a sewer system are performed comparing three different pipe types, which are reinforced concrete pipe (RCP) and non-reinforced concrete pipe (NRCP), and vitrified clay pipe (VCP). Life cycle cost analysis is performed for material extraction, construction and rehabilitation phases. In the rehabilitation phase, Markov chains model is applied in the support of rehabilitation strategy. In the life cycle assessment, the Economic Input-Output Life Cycle Assessment (EIO-LCA) tools are used in estimating environmental emissions for all three phases. Emissions are then compared quantitatively among alternatives to support decision making.

MODELING AND PROTOCOL DESIGN FOR EMERGING WIRELESS SYSTEMS

Mobile Mesh Network based In-Transit Visibility (MMN-ITV) system facilitates global real-time tracking capability for the logistics system. In-transit containers form a multi-hop mesh network to forward the tracking information to the nearby sinks, which further deliver the information to the remote control center via satellite. The fundamental challenge to the MMN-ITV system is the energy constraint of the battery-operated containers. Coupled with the unique mobility pattern, cross-MMN behavior, and the large-spanned area, it is necessary to investigate the energy-efficient communication of the MMN-ITV system thoroughly. First of all, this dissertation models the energy-efficient routing under the unique pattern of the cross-MMN behavior. A new modeling approach, pseudo-dynamic modeling approach, is proposed to measure the energy-efficiency of the routing methods in the presence of the cross-MMN behavior. With this approach, it could be identified that the shortest-path routing and the load-balanced routing is energy-efficient in mobile networks and static networks respectively. For the MMN-ITV system with both mobile and static MMNs, an energy-efficient routing method, energy-threshold routing, is proposed to achieve the best tradeoff between them. Secondly, due to the cross-MMN behavior, neighbor discovery is executed frequently to help the new containers join the MMN, hence, consumes similar amount of energy as that of the data communication. By exploiting the unique pattern of the cross-MMN behavior, this dissertation proposes energy-efficient neighbor discovery wakeup schedules to save up to 60% of the energy for neighbor discovery. Vehicular Ad Hoc Networks (VANETs)-based inter-vehicle communications is by now growingly believed to enhance traffic safety and transportation management with low cost. The end-to-end delay is critical for the time-sensitive safety applications in VANETs, and can be a decisive performance metric for VANETs. This dissertation presents a complete analytical model to evaluate the end-to-end delay against the transmission range and the packet arrival rate. This model illustrates a significant end-to-end delay increase from non-saturated networks to saturated networks. It hence suggests that the distributed power control and admission control protocols for VANETs should aim at improving the real-time capacity (the maximum packet generation rate without causing saturation), instead of the delay itself. Based on the above model, it could be determined that adopting uniform transmission range for every vehicle may hinder the delay performance improvement, since it does not allow the coexistence of the short path length and the low interference. Clusters are proposed to configure non-uniform transmission range for the vehicles. Analysis and simulation confirm that such configuration can enhance the real-time capacity. In addition, it provides an improved trade off between the end-to-end delay and the network capacity. A distributed clustering protocol with minimum message overhead is proposed, which achieves low convergence time.

Virosomes can enter cells by non-phagocytic mechanisms

Phagocytosis of fine particles (1 mum) by macrophages is a ligand-receptor-mediated, actin-based process, whereas the entering of smaller particles (systems for drugs, vectors, and plasmids in cancer therapy or for vaccines. We investigated their interactions with airway cells, in particular penetration into monocyte-derived macrophages. The microscopic analysis of phagocytic cells incubated with virosomes and polystyrene particles showed that virosomes and particles penetrated cells even in the presence of cytochalasin D, a drug inhibiting actin-based phagocytosis. The charge of the virosomes and particles did not influence their penetration. Also, different inhibitors of endocytotic pathways did not prevent the particles and virosomes from penetrating into the cells. Additionally, to study the ability of virosomes to overcome the epithelial airway barrier, a triple cell co-culture model composed of epithelial cells, monocyte-derived macrophages and dendritic cells of the respiratory tract was used. We found virosomes and polystyrene particles in both populations of antigen-presenting cells, monocyte-derived macrophages, and dendritic cells, in the latter even if they were not directly exposed. In conclusion, virosomes are readily taken up by monocyte-derived macrophages, both by conventional phagocytosis and by actin-independent mechanisms. Further, they can penetrate the airway barrier and reach resident dendritic cells. Therefore, virosomes are promising vaccine candidates.

Potentials and limitations of coordinated spatial and non-spatial information

Information management and geoinformation systems (GIS) have become indispensable in a large majority of protected areas all over the world. These tools are used for management purposes as well as for research and in recent years have become even more important for visitor information, education and communication. This study is divided into two parts: the first part provides a general overview of GIS and information management in a selected number of national park organizations. The second part lists and evaluates the needs of evolving large protected areas in Switzerland. The results show a wide use of GIS and information management tools in well established protected areas. The more isolated use of singular GIS tools has increasingly been replaced by an integrated geoinformation management. However, interview partners pointed out that human resources for GIS in most parks are limited. The interviews also highlight uneven access to national geodata. The view of integrated geoinformation management is not yet fully developed in the park projects in Switzerland. Short-term needs, such as software and data availability, motivate a large number of responses collected within an exhaustive questionnaire. Nevertheless, the need for coordinated action has been identified and should be followed up. The park organizations in North America show how an effective coordination and cooperation might be organized.

Comparative Analysis of Evolving Software Systems Using the Gini Coefficient

Software metrics offer us the promise of distilling useful information from vast amounts of software in order to track development progress, to gain insights into the nature of the software, and to identify potential problems. Unfortunately, however, many software metrics exhibit highly skewed, non-Gaussian distributions. As a consequence, usual ways of interpreting these metrics --- for example, in terms of "average" values --- can be highly misleading. Many metrics, it turns out, are distributed like wealth --- with high concentrations of values in selected locations. We propose to analyze software metrics using the Gini coefficient, a higher-order statistic widely used in economics to study the distribution of wealth. Our approach allows us not only to observe changes in software systems efficiently, but also to assess project risks and monitor the development process itself. We apply the Gini coefficient to numerous metrics over a range of software projects, and we show that many metrics not only display remarkably high Gini values, but that these values are remarkably consistent as a project evolves over time.

Selection and hydroponic growth of bread wheat cultivars for bioregenerative life support systems

As part of the ESA-funded MELiSSA program, the suitability, the growth and the development of four bread wheat cultivars were investigated in hydroponic culture with the aim to incorporate such a cultivation system in an Environmental Control and Life Support System (ECLSS). Wheat plants can fulfill three major functions in space: (a) fixation of CO2 and production of O2, (b) production of grains for human nutrition and (c) production of cleaned water after condensation of the water vapor released from the plants by transpiration. Four spring wheat cultivars (Aletsch, Fiorina, Greina and CH Rubli) were grown hydroponically and compared with respect to growth and grain maturation properties. The height of the plants, the culture duration from germination to harvest, the quantity of water used, the number of fertile and non-fertile tillers as well as the quantity and quality of the grains harvested were considered. Mature grains could be harvested after around 160 days depending on the varieties. It became evident that the nutrient supply is crucial in this context and strongly affects leaf senescence and grain maturation. After a first experiment, the culture conditions were improved for the second experiment (stepwise decrease of EC after flowering, pH adjusted twice a week, less plants per m2) leading to a more favorable harvest (higher grain yield and harvest index). Considerably less green tillers without mature grains were present at harvest time in experiment 2 than in experiment 1. The harvest index for dry matter (including roots) ranged from 0.13 to 0.35 in experiment 1 and from 0.23 to 0.41 in experiment 2 with modified culture conditions. The thousand-grain weight for the four varieties ranged from 30.4 to 36.7 g in experiment 1 and from 33.2 to 39.1 g in experiment 2, while market samples were in the range of 39.4–46.9 g. Calcium levels in grains of the hydroponically grown wheat were similar to those from field-grown wheat, while potassium, magnesium, phosphorus, iron, zinc, copper, manganese and nickel levels tended to be higher in the grains of experimental plants. It remains a challenge for future experiments to further adapt the nutrient supply in order to improve senescence of vegetative plant parts, harvest index and the composition of bread wheat grains.

A real-time video quality estimator for emerging wireless multimedia systems

Wireless Mesh Networks (WMNs) are increasingly deployed to enable thousands of users to share, create, and access live video streaming with different characteristics and content, such as video surveillance and football matches. In this context, there is a need for new mechanisms for assessing the quality level of videos because operators are seeking to control their delivery process and optimize their network resources, while increasing the user’s satisfaction. However, the development of in-service and non-intrusive Quality of Experience assessment schemes for real-time Internet videos with different complexity and motion levels, Group of Picture lengths, and characteristics, remains a significant challenge. To address this issue, this article proposes a non-intrusive parametric real-time video quality estimator, called MultiQoE that correlates wireless networks’ impairments, videos’ characteristics, and users’ perception into a predicted Mean Opinion Score. An instance of MultiQoE was implemented in WMNs and performance evaluation results demonstrate the efficiency and accuracy of MultiQoE in predicting the user’s perception of live video streaming services when compared to subjective, objective, and well-known parametric solutions.

RNA-dependent genome processing during nuclear differentiation: the model systems of stichotrichous ciliates

We introduce ciliated protozoa, and more specifically the stichotrichous ciliates Oxytricha and Stylonychia, as biological model systems for the analysis of programmed DNA-reorganization processes during nuclear differentiation. These include DNA excision, DNA elimination, reordering of gene segments and specific gene amplification. We show that small nuclear RNAs specify DNA sequences to be excised or retained, but also discuss the need for a RNA template molecule derived from the parental nucleus for these processes. This RNA template guides reordering of gene segments to become functional genes and determines gene copy number in the differentiated nucleus. Since the template is derived from the parental macronucleus, gene reordering and DNA amplification are inherited in a non-Mendelian epigenetic manner.

Ultracold Quantum Gases and Lattice Systems: Quantum Simulation of Lattice Gauge Theories

Abelian and non-Abelian gauge theories are of central importance in many areas of physics. In condensed matter physics, AbelianU(1) lattice gauge theories arise in the description of certain quantum spin liquids. In quantum information theory, Kitaev’s toric code is a Z(2) lattice gauge theory. In particle physics, Quantum Chromodynamics (QCD), the non-Abelian SU(3) gauge theory of the strong interactions between quarks and gluons, is nonperturbatively regularized on a lattice. Quantum link models extend the concept of lattice gauge theories beyond the Wilson formulation, and are well suited for both digital and analog quantum simulation using ultracold atomic gases in optical lattices. Since quantum simulators do not suffer from the notorious sign problem, they open the door to studies of the real-time evolution of strongly coupled quantum systems, which are impossible with classical simulation methods. A plethora of interesting lattice gauge theories suggests itself for quantum simulation, which should allow us to address very challenging problems, ranging from confinement and deconfinement, or chiral symmetry breaking and its restoration at finite baryon density, to color superconductivity and the real-time evolution of heavy-ion collisions, first in simpler model gauge theories and ultimately in QCD.

Targeting the Blood-brain Barrier with a Non-canonical Iron-mimicry Mechanism

Treatment of central nervous system (CNS) diseases is limited by the blood-brain barrier (BBB), a selective vascular interface restricting passage of most molecules from blood into brain. Specific transport systems have evolved allowing circulating polar molecules to cross the BBB and gain access to the brain parenchyma. However, to date, few ligands exploiting such systems have proven clinically viable in the setting of CNS diseases. We reasoned that combinatorial phage-display screenings in vivo would yield peptides capable of crossing the BBB and allow for the development of ligand-directed targeting strategies of the brain. Here we show the identification of a peptide mediating systemic targeting to the normal brain and to an orthotopic human glioma model. We demonstrate that this peptide functionally mimics iron through an allosteric mechanism and that a non-canonical association of (i) transferrin, (ii) the iron-mimic ligand motif, and (iii) transferrin receptor mediates binding and transport of particles across the BBB. We also show that in orthotopic human glioma xenografts, a combination of transferrin receptor over-expression plus extended vascular permeability and ligand retention result in remarkable brain tumor targeting. Moreover, such tumor targeting attributes enables Herpes simplex virus thymidine kinase-mediated gene therapy of intracranial tumors for molecular genetic imaging and suicide gene delivery with ganciclovir. Finally, we expand our data by analyzing a large panel of primary CNS tumors through comprehensive tissue microarrays. Together, our approach and results provide a translational avenue for the detection and treatment of brain tumors.