The adsorption of biomolecules to multi-walled carbon nanotubes is influenced by both pulmonary surfactant lipids and surface chemistry

Background During production and processing of multi-walled carbon nanotubes (MWCNTs), they may be inhaled and may enter the pulmonary circulation. It is essential that interactions with involved body fluids like the pulmonary surfactant, the blood and others are investigated, particularly as these interactions could lead to coating of the tubes and may affect their chemical and physical characteristics. The aim of this study was to characterize the possible coatings of different functionalized MWCNTs in a cell free environment. Results To simulate the first contact in the lung, the tubes were coated with pulmonary surfactant and subsequently bound lipids were characterized. The further coating in the blood circulation was simulated by incubating the tubes in blood plasma. MWCNTs were amino (NH2)- and carboxyl (-COOH)-modified, in order to investigate the influence on the bound lipid and protein patterns. It was shown that surfactant lipids bind unspecifically to different functionalized MWCNTs, in contrast to the blood plasma proteins which showed characteristic binding patterns. Patterns of bound surfactant lipids were altered after a subsequent incubation in blood plasma. In addition, it was found that bound plasma protein patterns were altered when MWCNTs were previously coated with pulmonary surfactant. Conclusions A pulmonary surfactant coating and the functionalization of MWCNTs have both the potential to alter the MWCNTs blood plasma protein coating and to determine their properties and behaviour in biological systems.

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Pulmonary surfactant coating of multi-walled carbon nanotubes (MWCNTs) influences their oxidative and pro-inflammatory potential in vitro

Background Increasing concern has been expressed regarding the potential adverse health effects that may be associated with human exposure to inhaled multi-walled carbon nanotubes (MWCNTs). Thus it is imperative that an understanding as to the underlying mechanisms and the identification of the key factors involved in adverse effects are gained. In the alveoli, MWCNTs first interact with the pulmonary surfactant. At this interface, proteins and lipids of the pulmonary surfactant bind to MWCNTs, affecting their surface characteristics. Aim of the present study was to investigate if the pre-coating of MWCNTs with pulmonary surfactant has an influence on potential adverse effects, upon both (i) human monocyte derived macrophages (MDM) monocultures, and (ii) a sophisticated in vitro model of the human epithelial airway barrier. Both in vitro systems were exposed to MWCNTs either pre-coated with a porcine pulmonary surfactant (Curosurf) or not. The effect of MWCNTs surface charge was also investigated in terms of amino (−NH2) and carboxyl (−COOH) surface modifications. Results Pre-coating of MWCNTs with Curosurf affects their oxidative potential by increasing the reactive oxygen species levels and decreasing intracellular glutathione depletion in MDM as well as decreases the release of Tumour necrosis factor alpha (TNF-α). In addition, an induction of apoptosis was observed after exposure to Curosurf pre-coated MWCNTs. In triple cell-co cultures the release of Interleukin-8 (IL-8) was increased after exposure to Curosurf pre-coated MWCNTs. Effects of the MWCNTs functionalizations were minor in both MDM and triple cell co-cultures. Conclusions The present study clearly indicates that the pre-coating of MWCNTs with pulmonary surfactant more than the functionalization of the tubes is a key factor in determining their ability to cause oxidative stress, cytokine/chemokine release and apoptosis. Thus the coating of nano-objects with pulmonary surfactant should be considered for future lung in vitro risk assessment studies. Keywords: Multi-walled carbon nanotubes (MWCNTs); Pulmonary surfactant (Curosurf); Macrophages; Epithelial cells; Dendritic cells; Triple cell co-culture; Pro-inflammatory and oxidative reactions

Assessing The Role Of Multi-protein Complexes In Determining Phenotype

Understanding regulatory mechanisms in complex biological systems is an important challenge, in particular to understand disease mechanisms, and to discover new therapies and drugs. In this paper, we consider the important question of cellular regulation of phenotype. Using single gene deletion data, we address the problem of linking a phenotype to underlying functional roles in the organism and provide a sound computational and statistical paradigm that can be extended to address more complex experimental settings such as multiple deletions. We apply the proposed approaches to publicly available data sets to demonstrate strong evidence for the involvement of multi-protein complexes in the phenotypes studied.

Quantum modeling of bioconjugated nanomaterials

In recent years, the bio-conjugated nanostructured materials have emerged as a new class of materials for the bio-sensing and medical diagnostics applications. In spite of their multi-directional applications, interfacing nanomaterials with bio-molecules has been a challenge due to somewhat limited knowledge about the underlying physics and chemistry behind these interactions and also for the complexity of biomolecules. The main objective of this dissertation is to provide such a detailed knowledge on bioconjugated nanomaterials toward their applications in designing the next generation of sensing devices. Specifically, we investigate the changes in the electronic properties of a boron nitride nanotube (BNNT) due to the adsorption of different bio-molecules, ranging from neutral (DNA/RNA nucleobases) to polar (amino acid molecules). BNNT is a typical member of III-V compounds semiconductors with morphology similar to that of carbon nanotubes (CNTs) but with its own distinct properties. More specifically, the natural affinity of BNNTs toward living cells with no apparent toxicity instigates the applications of BNNTs in drug delivery and cell therapy. Our results predict that the adsorption of DNA/RNA nucleobases on BNNTs amounts to different degrees of modulation in the band gap of BNNTs, which can be exploited for distinguishing these nucleobases from each other. Interestingly, for the polar amino acid molecules, the nature of interaction appeared to vary ranging from Coulombic, van der Waals and covalent depending on the polarity of the individual molecules, each with a different binding strength and amount of charge transfer involved in the interaction. The strong binding of amino acid molecules on the BNNTs explains the observed protein wrapping onto BNNTs without any linkers, unlike carbon nanotubes (CNTs). Additionally, the widely varying binding energies corresponding to different amino acid molecules toward BNNTs indicate to the suitability of BNNTs for the biosensing applications, as compared to the metallic CNTs. The calculated I-V characteristics in these bioconjugated nanotubes predict notable changes in the conductivity of BNNTs due to the physisorption of DNA/RNA nucleobases. This is not the case with metallic CNTs whose transport properties remained unaltered in their conjugated systems with the nucleobases. Collectively, the bioconjugated BNNTs are found to be an excellent system for the next generation sensing devices.

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.

Spray characterization under flash boiling conditions of a DI multi-hole injector at high injection pressures in a combustion vessel

Spray characterization under flash boiling conditions was investigated utilizing a symmetric multi-hole injector applicable to the gasoline direct injection (GDI) engine. Tests were performed in a constant volume combustion vessel using a high-speed schlieren and Mie scattering imaging systems. Four fuels including n-heptane, 100% ethanol, pure ethanol blended with 15% iso-octane by volume, and test grade E85 were considered in the study. Experimental conditions included various ambient pressure, fuel temperature, and fuel injection pressure. Visualization of the vaporizing spray development was acquired by utilizing schlieren and laser-based Mie scattering techniques. Time evolved spray tip penetration, spray angle, and the ratio of the vapor to liquid region were analyzed by utilizing digital image processing techniques in MATLAB. This research outlines spray characteristics at flash boiling and non-flash boiling conditions. At flash boiling conditions it was observed that individual plumes merge together, leading to significant contraction in spray angle as compared to non-flash boiling conditions. The results indicate that at flash boiling conditions, spray formation and expansion of vapor region is dependent on momentum exchange offered by the ambient gas. A relation between momentum exchange and liquid spray angle formed was also observed.

Optimal game theoretic distributed control methodologies in small scale power systems

This dissertation presents the competitive control methodologies for small-scale power system (SSPS). A SSPS is a collection of sources and loads that shares a common network which can be isolated during terrestrial disturbances. Micro-grids, naval ship electric power systems (NSEPS), aircraft power systems and telecommunication system power systems are typical examples of SSPS. The analysis and development of control systems for small-scale power systems (SSPS) lacks a defined slack bus. In addition, a change of a load or source will influence the real time system parameters of the system. Therefore, the control system should provide the required flexibility, to ensure operation as a single aggregated system. In most of the cases of a SSPS the sources and loads must be equipped with power electronic interfaces which can be modeled as a dynamic controllable quantity. The mathematical formulation of the micro-grid is carried out with the help of game theory, optimal control and fundamental theory of electrical power systems. Then the micro-grid can be viewed as a dynamical multi-objective optimization problem with nonlinear objectives and variables. Basically detailed analysis was done with optimal solutions with regards to start up transient modeling, bus selection modeling and level of communication within the micro-grids. In each approach a detail mathematical model is formed to observe the system response. The differential game theoretic approach was also used for modeling and optimization of startup transients. The startup transient controller was implemented with open loop, PI and feedback control methodologies. Then the hardware implementation was carried out to validate the theoretical results. The proposed game theoretic controller shows higher performances over traditional the PI controller during startup. In addition, the optimal transient surface is necessary while implementing the feedback controller for startup transient. Further, the experimental results are in agreement with the theoretical simulation. The bus selection and team communication was modeled with discrete and continuous game theory models. Although players have multiple choices, this controller is capable of choosing the optimum bus. Next the team communication structures are able to optimize the players’ Nash equilibrium point. All mathematical models are based on the local information of the load or source. As a result, these models are the keys to developing accurate distributed controllers.

High precision range estimation techniques for multi-path wireless environments

Range estimation is the core of many positioning systems such as radar, and Wireless Local Positioning Systems (WLPS). The estimation of range is achieved by estimating Time-of-Arrival (TOA). TOA represents the signal propagation delay between a transmitter and a receiver. Thus, error in TOA estimation causes degradation in range estimation performance. In wireless environments, noise, multipath, and limited bandwidth reduce TOA estimation performance. TOA estimation algorithms that are designed for wireless environments aim to improve the TOA estimation performance by mitigating the effect of closely spaced paths in practical (positive) signal-to-noise ratio (SNR) regions. Limited bandwidth avoids the discrimination of closely spaced paths. This reduces TOA estimation performance. TOA estimation methods are evaluated as a function of SNR, bandwidth, and the number of reflections in multipath wireless environments, as well as their complexity. In this research, a TOA estimation technique based on Blind signal Separation (BSS) is proposed. This frequency domain method estimates TOA in wireless multipath environments for a given signal bandwidth. The structure of the proposed technique is presented and its complexity and performance are theoretically evaluated. It is depicted that the proposed method is not sensitive to SNR, number of reflections, and bandwidth. In general, as bandwidth increases, TOA estimation performance improves. However, spectrum is the most valuable resource in wireless systems and usually a large portion of spectrum to support high performance TOA estimation is not available. In addition, the radio frequency (RF) components of wideband systems suffer from high cost and complexity. Thus, a novel, multiband positioning structure is proposed. The proposed technique uses the available (non-contiguous) bands to support high performance TOA estimation. This system incorporates the capabilities of cognitive radio (CR) systems to sense the available spectrum (also called white spaces) and to incorporate white spaces for high-performance localization. First, contiguous bands that are divided into several non-equal, narrow sub-bands that possess the same SNR are concatenated to attain an accuracy corresponding to the equivalent full band. Two radio architectures are proposed and investigated: the signal is transmitted over available spectrum either simultaneously (parallel concatenation) or sequentially (serial concatenation). Low complexity radio designs that handle the concatenation process sequentially and in parallel are introduced. Different TOA estimation algorithms that are applicable to multiband scenarios are studied and their performance is theoretically evaluated and compared to simulations. Next, the results are extended to non-contiguous, non-equal sub-bands with the same SNR. These are more realistic assumptions in practical systems. The performance and complexity of the proposed technique is investigated as well. This study’s results show that selecting bandwidth, center frequency, and SNR levels for each sub-band can adapt positioning accuracy.

STOCHASTIC CHARGE TRANSPORT IN MULTI-ISLAND SINGLE-ELECTRON TUNNELING DEVICES

The physics of the operation of singe-electron tunneling devices (SEDs) and singe-electron tunneling transistors (SETs), especially of those with multiple nanometer-sized islands, has remained poorly understood in spite of some intensive experimental and theoretical research. This computational study examines the current-voltage (IV) characteristics of multi-island single-electron devices using a newly developed multi-island transport simulator (MITS) that is based on semi-classical tunneling theory and kinetic Monte Carlo simulation. The dependence of device characteristics on physical device parameters is explored, and the physical mechanisms that lead to the Coulomb blockade (CB) and Coulomb staircase (CS) characteristics are proposed. Simulations using MITS demonstrate that the overall IV characteristics in a device with a random distribution of islands are a result of a complex interplay among those factors that affect the tunneling rates that are fixed a priori (e.g. island sizes, island separations, temperature, gate bias, etc.), and the evolving charge state of the system, which changes as the source-drain bias (VSD) is changed. With increasing VSD, a multi-island device has to overcome multiple discrete energy barriers (up-steps) before it reaches the threshold voltage (Vth). Beyond Vth, current flow is rate-limited by slow junctions, which leads to the CS structures in the IV characteristic. Each step in the CS is characterized by a unique distribution of island charges with an associated distribution of tunneling probabilities. MITS simulation studies done on one-dimensional (1D) disordered chains show that longer chains are better suited for switching applications as Vth increases with increasing chain length. They are also able to retain CS structures at higher temperatures better than shorter chains. In sufficiently disordered 2D systems, we demonstrate that there may exist a dominant conducting path (DCP) for conduction, which makes the 2D device behave as a quasi-1D device. The existence of a DCP is sensitive to the device structure, but is robust with respect to changes in temperature, gate bias, and VSD. A side gate in 1D and 2D systems can effectively control Vth. We argue that devices with smaller island sizes and narrower junctions may be better suited for practical applications, especially at room temperature.

The Influence of Enterprise Systems on Business and Information Technology

Business strategy is important to all organizations. Nearly all Fortune 500 firms are implementing Enterprise Resource Planning (ERP) systems to improve the execution of their business strategy and to improve integration with its information technology (IT) strategy. Successful implementation of these multi-million dollar software systems are requiring new emphasis on change management and on Business and IT strategic alignment. This paper examines business and IT strategic alignment and seeks to explore whether an ERP implementation can drive business process reengineering and business and IT strategic alignment. An overview of business strategy and strategic alignment are followed by an analysis of ERP. The “As-Is/To-Be” process model is then presented and explained as a simple, but vital tool for improving business strategy, strategic alignment, and ERP implementation success.

Control concept for autonomous changeable material flow systems

Today’s material flow systems for mass customization or dynamic productions are usually realized with manual transportation systems. However new concepts in the domain of material flow and device control like function-oriented modularization and intelligent multi-agent-systems offer the possibility to employ changeable and automated material flow systems in dynamic production structures. These systems need the ability to react on unplanned and unexpected events autonomously.

A Cooperative and Adaptive Variable Neighborhood Search for the Multi Depot Vehicle Routing Problem with Time Windows

In this paper we propose two cooperation schemes to compose new parallel variants of the Variable Neighborhood Search (VNS). On the one hand, a coarse-grained cooperation scheme is introduced which is well suited for being enhanced with a solution warehouse to store and manage the so far best found solutions and a self-adapting mechanism for the most important search parameters. This makes an a priori parameter tuning obsolete. On the other hand, a fine-grained scheme was designed to reproduce the successful properties of the sequential VNS. In combination with the use of parallel exploration threads all of the best solutions and 11 out of 20 new best solutions for the Multi Depot Vehicle Routing Problem with Time Windows were found.