EXPERIMENTAL AND COMPUTATIONAL STUDIES OF ELECTROMAGNETIC CLOAKING AT MICROWAVES

An invisibility cloak is a device that can hide the target by enclosing it from the incident radiation. This intriguing device has attracted a lot of attention since it was first implemented at a microwave frequency in 2006. However, the problems of existing cloak designs prevent them from being widely applied in practice. In this dissertation, we try to remove or alleviate the three constraints for practical applications imposed by loosy cloaking media, high implementation complexity, and small size of hidden objects compared to the incident wavelength. To facilitate cloaking design and experimental characterization, several devices and relevant techniques for measuring the complex permittivity of dielectric materials at microwave frequencies are developed. In particular, a unique parallel plate waveguide chamber has been set up to automatically map the electromagnetic (EM) field distribution for wave propagation through the resonator arrays and cloaking structures. The total scattering cross section of the cloaking structures was derived based on the measured scattering field by using this apparatus. To overcome the adverse effects of lossy cloaking media, microwave cloaks composed of identical dielectric resonators made of low loss ceramic materials are designed and implemented. The effective permeability dispersion was provided by tailoring dielectric resonator filling fractions. The cloak performances had been verified by full-wave simulation of true multi-resonator structures and experimental measurements of the fabricated prototypes. With the aim to reduce the implementation complexity caused by metamaterials employment for cloaking, we proposed to design 2-D cylindrical cloaks and 3-D spherical cloaks by using multi-layer ordinary dielectric material (εr>1) coating. Genetic algorithm was employed to optimize the dielectric profiles of the cloaking shells to provide the minimum scattering cross sections of the cloaked targets. The designed cloaks can be easily scaled to various operating frequencies. The simulation results show that the multi-layer cylindrical cloak essentially outperforms the similarly sized metamaterials-based cloak designed by using the transformation optics-based reduced parameters. For the designed spherical cloak, the simulated scattering pattern shows that the total scattering cross section is greatly reduced. In addition, the scattering in specific directions could be significantly reduced. It is shown that the cloaking efficiency for larger targets could be improved by employing lossy materials in the shell. At last, we propose to hide a target inside a waveguide structure filled with only epsilon near zero materials, which are easy to implement in practice. The cloaking efficiency of this method, which was found to increase for large targets, has been confirmed both theoretically and by simulations.

Direction finding in the presence of a more realistic environment model

Direction-of-arrival (DOA) estimation is susceptible to errors introduced by the presence of real-ground and resonant size scatterers in the vicinity of the antenna array. To compensate for these errors pre-calibration and auto-calibration techniques are presented. The effects of real-ground constituent parameters on the mutual coupling (MC) of wire type antenna arrays for DOA estimation are investigated. This is accomplished by pre-calibration of the antenna array over the real-ground using the finite element method (FEM). The mutual impedance matrix is pre-estimated and used to remove the perturbations in the received terminal voltage. The unperturbed terminal voltage is incorporated in MUSIC algorithm to estimate DOAs. First, MC of quarter wave monopole antenna arrays is investigated. This work augments an existing MC compensation technique for ground-based antennas and proposes reduction in MC for antennas over finite ground as compared to the perfect ground. A factor of 4 decrease in both the real and imaginary parts of the MC is observed when considering a poor ground versus a perfectly conducting one for quarter wave monopoles in the receiving mode. A simulated result to show the compensation of errors direction of arrival (DOA) estimation with actual realization of the environment is also presented. Secondly, investigations for the effects on received MC of λ/2 dipole arrays placed near real-earth are carried out. As a rule of thumb, estimation of mutual coupling can be divided in two regions of antenna height that is very near ground 0

On-chip Non-reciprocal Optical Devices Based on Quantum Inspired Photonic Lattices

We propose integrated optical structures that can be used as isolators and polarization splitters based on engineered photonic lattices. Starting from optical waveguide arrays that mimic Fock space (quantum state with a well-defined particle number) representation of a non-interacting two-site Bose Hubbard Hamiltonian, we show that introducing magneto-optic nonreciprocity to these structures leads to a superior optical isolation performance. In the forward propagation direction, an input TM polarized beam experiences a perfect state transfer between the input and output waveguide channels while surface Bloch oscillations block the backward transmission between the same ports. Our analysis indicates a large isolation ratio of 75 dB after a propagation distance of 8mm inside seven coupled waveguides. Moreover, we demonstrate that, a judicious choice of the nonreciprocity in this same geometry can lead to perfect polarization splitting.

Spindle burst like spike discharge oscillations in organotypic cultures of neonatal rat cortex

Early network oscillations and spindle bursts are typical patterns of spontaneous rhythmic activity in cortical networks of neonatal rodents in vivo and in vitro. The latter can also be triggered in vivo by stimulation of afferent inputs. The mechanisms underlying such oscillations undergo profound developmental changes in the first postnatal weeks. Their possible role in cortical development is postulated but not known in detail. We have studied spontaneous and evoked patterns of activity in organotypic cultures of slices from neonatal rat cortex grown on multielectrode arrays (MEAs) for extracellular single- and multi-unit recording. Episodes of spontaneous spike discharge oscillations at 7 - 25 Hz lasting for 0.6 - 3 seconds appeared in about half of these cultures spontaneously and could be triggered by electrical stimulation of few distinct electrodes. These oscillations usually covered only restricted areas of the slices. Besides oscillations, single population bursts that spread in a wavelike manner over the whole slice also appeared spontaneously and were triggered by electrical stimulation. In most but not all cultures, population bursts preceded the oscillations. Both population bursts and spike discharge oscillations required intact glutamatergic synaptic transmission since they were suppressed by the AMPA/kainate glutamate receptor antagonist CNQX. The NMDA antagonist d-APV suppressed the oscillations but not the population bursts, suggesting an involvement of NMDA receptors in the oscillations. These findings show that spindle burst like cortical rhythms are reproduced in organotypic cultures of neonatal cortex. The culture model thus allows investigating the role of such rhythms in cortical circuit formation. Supported by SNF grant No. 3100A0-107641/1.

HIGH PERFORMANCE, LOW COST SUBSPACE DECOMPOSITION AND POLYNOMIAL ROOTING FOR REAL TIME DIRECTION OF ARRIVAL ESTIMATION: ANALYSIS AND IMPLEMENTATION

This thesis develops high performance real-time signal processing modules for direction of arrival (DOA) estimation for localization systems. It proposes highly parallel algorithms for performing subspace decomposition and polynomial rooting, which are otherwise traditionally implemented using sequential algorithms. The proposed algorithms address the emerging need for real-time localization for a wide range of applications. As the antenna array size increases, the complexity of signal processing algorithms increases, making it increasingly difficult to satisfy the real-time constraints. This thesis addresses real-time implementation by proposing parallel algorithms, that maintain considerable improvement over traditional algorithms, especially for systems with larger number of antenna array elements. Singular value decomposition (SVD) and polynomial rooting are two computationally complex steps and act as the bottleneck to achieving real-time performance. The proposed algorithms are suitable for implementation on field programmable gated arrays (FPGAs), single instruction multiple data (SIMD) hardware or application specific integrated chips (ASICs), which offer large number of processing elements that can be exploited for parallel processing. The designs proposed in this thesis are modular, easily expandable and easy to implement. Firstly, this thesis proposes a fast converging SVD algorithm. The proposed method reduces the number of iterations it takes to converge to correct singular values, thus achieving closer to real-time performance. A general algorithm and a modular system design are provided making it easy for designers to replicate and extend the design to larger matrix sizes. Moreover, the method is highly parallel, which can be exploited in various hardware platforms mentioned earlier. A fixed point implementation of proposed SVD algorithm is presented. The FPGA design is pipelined to the maximum extent to increase the maximum achievable frequency of operation. The system was developed with the objective of achieving high throughput. Various modern cores available in FPGAs were used to maximize the performance and details of these modules are presented in detail. Finally, a parallel polynomial rooting technique based on Newton’s method applicable exclusively to root-MUSIC polynomials is proposed. Unique characteristics of root-MUSIC polynomial’s complex dynamics were exploited to derive this polynomial rooting method. The technique exhibits parallelism and converges to the desired root within fixed number of iterations, making this suitable for polynomial rooting of large degree polynomials. We believe this is the first time that complex dynamics of root-MUSIC polynomial were analyzed to propose an algorithm. In all, the thesis addresses two major bottlenecks in a direction of arrival estimation system, by providing simple, high throughput, parallel algorithms.

MULTISCALE EXAMINATION AND MODELING OF ELECTRON TRANSPORT IN NANOSCALE MATERIALS AND DEVICES

For half a century the integrated circuits (ICs) that make up the heart of electronic devices have been steadily improving by shrinking at an exponential rate. However, as the current crop of ICs get smaller and the insulating layers involved become thinner, electrons leak through due to quantum mechanical tunneling. This is one of several issues which will bring an end to this incredible streak of exponential improvement of this type of transistor device, after which future improvements will have to come from employing fundamentally different transistor architecture rather than fine tuning and miniaturizing the metal-oxide-semiconductor field effect transistors (MOSFETs) in use today. Several new transistor designs, some designed and built here at Michigan Tech, involve electrons tunneling their way through arrays of nanoparticles. We use a multi-scale approach to model these devices and study their behavior. For investigating the tunneling characteristics of the individual junctions, we use a first-principles approach to model conduction between sub-nanometer gold particles. To estimate the change in energy due to the movement of individual electrons, we use the finite element method to calculate electrostatic capacitances. The kinetic Monte Carlo method allows us to use our knowledge of these details to simulate the dynamics of an entire device— sometimes consisting of hundreds of individual particles—and watch as a device ‘turns on’ and starts conducting an electric current. Scanning tunneling microscopy (STM) and the closely related scanning tunneling spectroscopy (STS) are a family of powerful experimental techniques that allow for the probing and imaging of surfaces and molecules at atomic resolution. However, interpretation of the results often requires comparison with theoretical and computational models. We have developed a new method for calculating STM topographs and STS spectra. This method combines an established method for approximating the geometric variation of the electronic density of states, with a modern method for calculating spin-dependent tunneling currents, offering a unique balance between accuracy and accessibility.

A MEMS Light Modulator Based on Diffractive Nanohole Gratings

We present the design, fabrication, and testing of a microelectromechanical systems (MEMS) light modulator based on pixels patterned with periodic nanohole arrays. Flexure-suspended silicon pixels are patterned with a two dimensional array of 150 nm diameter nanoholes using nanoimprint lithography. A top glass plate assembled above the pixel array is used to provide a counter electrode for electrostatic actuation. The nanohole pattern is designed so that normally-incident light is coupled into an in-plane grating resonance, resulting in an optical stop-band at a desired wavelength. When the pixel is switched into contact with the top plate, the pixel becomes highly reflective. A 3:1 contrast ratio at the resonant wavelength is demonstrated for gratings patterned on bulk Si substrates. The switching time is 0.08 ms and the switching voltage is less than 15V.

Fabrication of a Large, Ordered, Three-Dimensional Nanocup Array

Metallic nanocups provide a unique method for redirecting scattered light by creating magnetic plasmon responses at optical frequencies. Despite considerable development of nanocup fabrication processes, simultaneously achieving accurate control over the placement, orientation, and geometry of nanocups has remained a significant challenge. Here we present a technique for fabricating large, periodically ordered arrays of uniformly oriented three-dimensional gold nanocups for manipulating light at subwavelength scales. Nanoimprint lithography, soft lithography, and shadow evaporation were used to fabricate nanocups onto the tips of polydimethylsiloxane nanopillars with precise control over the shapes and optical properties of asymmetric nanocups.

Pollinator responses to variation in floral display and flower size in dioecious Sagittaria latifolia (Alismataceae)

In animal-pollinated plants with unisexual flowers, sexual dimorphism in floral traits may be the consequence of pollinator-mediated selection. Experimental investigations of the effects of variation in flower size and floral display on pollinator visitation can provide insights into the evolution of floral dimorphism in dioecious plants. Here, we investigated pollinator responses to experimental arrays of dioecious Sagittaria latifolia in which we manipulated floral display and flower size. We also examined whether there were changes in pollinator visitation with increasing dimorphism in flower size. In S. latifolia, males have larger flowers and smaller floral displays than females. Visitation by pollinators, mainly flies and bees, was more frequent for male than for female inflorescences and increased with increasing flower size, regardless of sex. The number of insect visits per flower decreased with increasing floral display in males but remained constant in females. Greater sexual dimorphism in flower size increased visits to male inflorescences but had no influence on the number of visits to female inflorescences. These results suggest that larger flower sizes would be advantageous to both females and males, and no evidence was found that females suffer from increased flower-size dimorphism. Small daily floral displays may benefit males by allowing extended flowering periods and greater opportunities for effective pollen dispersal.

Identification of pathogen and host-response markers correlated with periodontal disease

BACKGROUND: Periodontitis is the major cause of tooth loss in adults and is linked to systemic illnesses, such as cardiovascular disease and stroke. The development of rapid point-of-care (POC) chairside diagnostics has the potential for the early detection of periodontal infection and progression to identify incipient disease and reduce health care costs. However, validation of effective diagnostics requires the identification and verification of biomarkers correlated with disease progression. This clinical study sought to determine the ability of putative host- and microbially derived biomarkers to identify periodontal disease status from whole saliva and plaque biofilm. METHODS: One hundred human subjects were equally recruited into a healthy/gingivitis group or a periodontitis population. Whole saliva was collected from all subjects and analyzed using antibody arrays to measure the levels of multiple proinflammatory cytokines and bone resorptive/turnover markers. RESULTS: Salivary biomarker data were correlated to comprehensive clinical, radiographic, and microbial plaque biofilm levels measured by quantitative polymerase chain reaction (qPCR) for the generation of models for periodontal disease identification. Significantly elevated levels of matrix metalloproteinase (MMP)-8 and -9 were found in subjects with advanced periodontitis with Random Forest importance scores of 7.1 and 5.1, respectively. The generation of receiver operating characteristic curves demonstrated that permutations of salivary biomarkers and pathogen biofilm values augmented the prediction of disease category. Multiple combinations of salivary biomarkers (especially MMP-8 and -9 and osteoprotegerin) combined with red-complex anaerobic periodontal pathogens (such as Porphyromonas gingivalis or Treponema denticola) provided highly accurate predictions of periodontal disease category. Elevated salivary MMP-8 and T. denticola biofilm levels displayed robust combinatorial characteristics in predicting periodontal disease severity (area under the curve = 0.88; odds ratio = 24.6; 95% confidence interval: 5.2 to 116.5). CONCLUSIONS: Using qPCR and sensitive immunoassays, we identified host- and bacterially derived biomarkers correlated with periodontal disease. This approach offers significant potential for the discovery of biomarker signatures useful in the development of rapid POC chairside diagnostics for oral and systemic diseases. Studies are ongoing to apply this approach to the longitudinal predictions of disease activity.

The NF-{kappa}B negative regulator TNFAIP3 (A20) is inactivated by somatic mutations and genomic deletions in marginal zone lymphomas

Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappaB, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal MZL (EMZL), nodal MZL (NMZL), and splenic MZL (SMZL). Inactivating mutations encoding truncated A20 proteins were identified in 6 (19%) of 32 MZLs, including 2 (18%) of 11 EMZLs, 3 (33%) of 9 NMZLs, and 1 (8%) of 12 SMZLs. Two additional unmutated nonsplenic MZLs also showed monoallelic or biallelic A20 deletions by fluorescent in situ hybridization (FISH) and/or SNP-arrays. Thus, A20 inactivation by either somatic mutation and/or deletion represents a common genetic aberration across all MZL subtypes, which may contribute to lymphomagenesis by inducing constitutive NF-kappaB activation.

Enhanced antitumorigenic effects in glioblastoma on double targeting of pleiotrophin and its receptor ALK

In adults, glioblastomas are the most lethal and most frequent malignant brain tumors, and the poor prognosis despite aggressive treatment indicates the need to establish novel targets for molecular intervention. The secreted growth factor pleiotrophin (PTN, HB-GAM, HBNF, OSF-1) shows mitogenic, chemotactic, and transforming activity. Whereas PTN expression is tightly regulated during embryogenesis and is very limited in normal adult tissues, a marked PTN up-regulation is seen in tumors including glioblastomas. Likewise, the PTN receptor anaplastic lymphoma kinase (ALK) has been shown previously to be upregulated and functionally relevant in glioblastoma. In this study, we explore the antitumorigenic effects of the simultaneous ribozyme-mediated knockdown of both receptor and ligand. Various glioblastoma cell lines are analyzed for PTN and ALK expression. Beyond the individual efficacies of several specific ribozymes against PTN or ALK, respectively, antiproliferative and proapoptotic effects of a single gene targeting approach are strongly enhanced on double knockdown of both genes in vitro. More importantly, this results in the abolishment of tumor growth in an in vivo subcutaneous tumor xenograft model. Finally, the analysis of various downstream signaling pathways by antibody arrays reveals a distinct pattern of changes in the activation of signal transduction molecules on PTN/ALK double knockdown. Beyond the already known ones, it identifies additional pathways relevant for PTN/ALK signaling. We conclude that double targeting of PTN and ALK leads to enhanced antitumorigenic effects over single knockdown approaches, which offers novel therapeutic options owing to increased efficacy also after prolonged knockdown.

Cellular and network mechanisms of rhythm generation in spinal cord circuits

The generation of rhythmic electrical activity is a prominent feature of spinal cord circuits that is used for locomotion and also for circuit refinement during development. The mechanisms involved in rhythm generation in spinal cord networks are not fully understood. It is for example not known whether spinal cord rhythms are driven by pacemaker neurons and if yes, which neurons are involved in this function. We studied the mechanisms involved in rhythm generation in slice cultures from fetal rats that were grown on multielectrode arrays (MEAs). We combined multisite extracellular recordings from the MEA electrodes with intracellular patch clamp recordings from single neurons. We found that spatially restricted oscillations of activity appeared in most of the cultures spontaneously. Such activity was based on intrinsic activity in a percentage of the neurons that could activate the spinal networks through recurrent excitation. The local oscillator networks critically involved NMDA, AMPA and GABA / glycine receptors at subsequent phases of the oscillation cycle. Intrinsic spiking in individual neurons (in the absence of functional synaptic coupling) was based on persistent sodium currents. Intrinsic firing as well as persistent sodium currents were increased by 5-HT through 5-HT2 receptors. Comparing neuronal activity to muscle activity in co-cultures of spinal cord slices with muscle fibers we found that a percentage of the intrinsically spiking neurons were motoneurons. These motoneurons were electrically coupled among each other and they could drive the spinal networks through cholinergic recurrent excitation. These findings open the possibility that during development rhythmic activity in motoneurons is not only involved in circuit refinement downstream at the neuromuscular endplates but also upstream at the level of spinal cord circuits.

Loss of astrocyte polarity marks blood-brain barrier impairment during experimental autoimmune encephalomyelitis

In multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE), dysfunction of the blood-brain barrier (BBB) leads to edema formation within the central nervous system. The molecular mechanisms of edema formation in EAE/MS are poorly understood. We hypothesized that edema formation is due to imbalanced water transport across the BBB caused by a disturbed crosstalk between BBB endothelium and astrocytes. Here, we demonstrate at the light microscopic and ultrastructural level, the loss of polarized localization of the water channel protein aquaporin-4 (AQP4) in astrocytic endfeet surrounding microvessels during EAE. AQP4 was found to be redistributed over the entire astrocytic cell surface and lost its arrangement in orthogonal arrays of intramembranous particles as seen in the freeze-fracture replica. In addition, immunostaining for the astrocytic extracellular matrix receptor beta-dystroglycan disappeared from astroglial membranes in the vicinity of inflammatory cuffs, whereas immunostaining for the dystroglycan ligands agrin and laminin in the perivascular basement membrane remained unchanged. Our data suggest that during EAE, loss of beta-dystroglycan-mediated astrocyte foot process anchoring to the basement membrane leads to loss of polarized AQP4 localization in astrocytic endfeet, and thus to edema formation in EAE.

Novel autoantigens immunogenic in COPD patients

Background Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients. Methods An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC) for each clone and the separation COPD sera versus control sera. Results By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity. Conclusion The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.