Time-reversal ultrawideband breast imaging: pulse design criteria considering multiple tumors with unknown tissue properties

Pulse design is investigated for time-reversal (TR) imaging as applied to ultrawideband (UWB) breast cancer detection. Earlier it has been shown that a suitably-designed UWB pulse may help to improve imaging performance for a single-tumor breast phantom with predetermined lesion properties. The current work considers the following more general and practical situations: presence of multiple malignancies with unknown tumor size and dielectric properties. Four pulse selection criteria are proposed with each focusing on one of the following aspects: eliminating signal clutter generated by tissue inhomogeneities, canceling mutual interference among tumors, improving image resolution, and suppressing artifacts created by sidelobe of the target response. By applying the proposed criteria, the shape parameters of UWB waveforms with desirable characteristics are identified through search of all the possible pulses. Simulation example using a numerical breast phantom, comprised of two tumors and structured clutter distribution, demonstrates the effectiveness of the proposed approach. Specifically, a tradeoff between the image resolution and signal-to-clutter contrast (SCC) is observed in terms of selection of the excitation waveforms.

The conserved Helix C region in the superfamily of interferon-a/interleukin-10-related cytokines corresponds to a high-affinity binding site for the HSP70 chaperone DnaK.

HSP70 chaperones mediate protein folding by ATP-dependent interaction with short linear peptide segments that are exposed on unfolded proteins. The mode of action of the Escherichia coli homolog DnaK is representative of all HSP70 chaperones, including the endoplasmic reticulum variant BiP/GRP78. DnaK has been shown to be effective in assisting refolding of a wide variety of prokaryotic and eukaryotic proteins, including the -helical homodimeric secretory cytokine interferon- (IFN-). We screened solid-phase peptide libraries from human and mouse IFN- to identify DnaK-binding sites. Conserved DnaK-binding sites were identified in the N-terminal half of helix B and in the C-terminal half of helix C, both of which are located at the IFN- dimer interface. Soluble peptides derived from helices B and C bound DnaK with high affinity in competition assays. No DnaK-binding sites were found in the loops connecting the -helices. The helix C DnaK-binding site appears to be conserved in most members of the superfamily of interleukin (IL)-10-related cytokines that comprises, apart from IL-10 and IFN-, a series of recently discovered small secretory proteins, including IL-19, IL-20, IL-22/IL-TIF, IL-24/MDA-7 (melanoma differentiation-associated gene), IL-26/AK155, and a number of viral IL-10 homologs. These cytokines belong to a relatively small group of homodimeric proteins with highly interdigitated interfaces that exhibit the strongly hydrophobic character of the interior core of a single-chain folded domain. We propose that binding of DnaK to helix C in the superfamily of IL-10-related cytokines may constitute the hallmark of a novel conserved regulatory mechanism in which HSP70-like chaperones assist in the formation of a hydrophobic dimeric "folding" interface.

Ice-binding proteins adsorb to their ligand via anchored clathrate waters

The main success of my thesis has been to establish the mechanism by which antifreeze proteins (AFPs) bind irreversibly to ice crystals, and hence prevent their growth. AFPs organize ice-like water on their ice-binding site, which then merges and freezes with the quasi-liquid layer of ice. This was revealed from studying the exceptionally large (ca. 1.5-MDa) Ca 2+-dependent AFP from the Antarctic bacterium Marinomonas primoryensis (MpAFP). The 34-kDa antifreeze- active region of MpAFP was predicted to fold as a novel Ca 2+-binding β-helix. Site-directed mutagenesis confirmed the model and demonstrated that its ice-binding site (IBS) consisted of solvent-exposed Thr and Asx parallel arrays on the Ca 2+-binding turns. The X-ray crystal structure of the antifreeze region was solved to a resolution of 1.7 Å. Two of the four molecules within the unit cell of the crystal had portions of their IBSs freely exposed to solvent. Identical clathrate-like cages of water molecules were present on each IBS. These waters were organized by the hydrophobic effect and anchored to the protein via hydrogen bonds. They matched the spacing of water molecules in an ice lattice, demonstrating that anchored clathrate waters bind AFPs to ice. This mechanism was extended to other AFPs including the globular type III AFP from fishes. Site-directed mutagenesis and a modified ice-etching technique demonstrated this protein uses a compound ice-binding site, comprised of two flat and relatively hydrophobic surfaces, to bind at least two planes of ice. Reinvestigation of several crystal structures of type III AFP identified anchored clathrate waters on the solvent-exposed portion of its compound IBS that matched the spacing of waters on the primary prism plane of ice. Ice nucleation proteins (INPs), which can raise the temperature at which ice forms in solution to just slightly below 0oC, have the opposite effect to AFPs. A novel dimeric β-helical model was proposed for the INP produced by the bacterium Pseudomonas borealis. Molecular dynamics simulations showed that INPs are also capable of ordering water molecules into an ice- like lattice. However, their multimerization brings together sufficient ordered waters to form an ice nucleus and initiate freezing.

Ring-opening polymerisation of silver-diphosphine [M2L3] coordination cages to give [M2L3](infinity) coordination polymers

[M2L3] coordination cages and linear [M2L3]infinity polymers of the rigid, bridging diphosphines bis(diphenylphosphino)acetylene (dppa) and trans-1,2-bis(diphenylphosphino)ethylene (dppet) with silver(I) salts have been investigated in the solution and solid states. Unlike flexible diphosphines, 1:1 dppa/AgX mixtures do not selectively form discrete [Ag2(diphos)2(X)2] macrocycles; instead dynamic mixtures of one-, two- and three-coordinate complexes are formed. However, 3:2 dppa/AgX ratios (X = SbF6. BF4, O3SCF3 or NO3) do lead selectively to new [M2L3] triply bridged cage complexes [Ag2(dppa)3(X)2] 1a-d (X = SbF6 a, BF4 b, O3SCF3 c, NO3 d), which do not exhibit Ag-P bond dissociation at room temperature on the NMR time scale (121 MHz). Complexes la-d were characterised by X-ray crystallography and were found to have small internal cavities, helical conformations and multiple intramolecular aromatic interactions. The nucleophilicity of the anion subtly influences the cage shape: Increasing nucleophilicity from SbF6 (1a) through BF4 (1b) and O3SCF3 (1c) to NO3 (1d) increases the pyramidal distortion at the AgP3 centres, stretching the cage framework (with Ag...Ag distances increasing from 5.48 in 1a to 6.21 A in 1d) and giving thinner internal cavities. Crystal packing strongly affected the size of the helical twist angle, and no correlation between this parameter and the Ag-Ag distance was observed. When crystalline 1c was stored in its supernatant for 16 weeks, conversion occured to the isostoichiometric [M2L3]infinity coordination polymer [Ag(dppa)2Ag(dppa)(O3SCF3)2]infinity (1c'). X-ray crystallography revealed a structure with ten-membered Ag2(dppa)2 rings linked into infinite one-dimensional chains by a third dppa unit. The clear structural relationship between this polymer and the precursor cage 1c suggests a novel example of ring-opening polymerisation. With dppet, evidence for discrete [M2L3] cages was also found in solution, although 31P NMR spectroscopy suggested some Ag-P bond dissociation. On crystallisation, only the corresponding ring-opened polymeric structures [M2L3]infinity could be obtained. This may be because the greater steric bulk of dppet versus dppa destabilises the cage and favours the ring-opening polymerisation.

EMI Suppression in an Aircraft Cooling Vent

Digital avionics systems are increasingly under threat from external electromagnetic interference (EMI). The same avionics systems require a thermal cooling mechanism and one method of providing this is to mount an air vent on the body of the aircraft. For the first time, a nacelle-mounted air vent that may expose the flight critical full authority digital engine controller (FADEC) to high intensity radiated fields (HIRF) is examined. The reflection/transmission characteristics of the vent are reported and the current shielding method employed is shown to provide a low shielding level (5 dB at 18 GHz). A new design has been proposed, providing over 100 dB of attenuation at 18 GHz. To the authors' knowledge this is the first time this shielding method has been applied to aircraft air vents.

Full-Wave Analysis of Layered Aperture Arrays

The new rigorous numerical-analytical technique based upon Galerkin method with the entire domain basis functions has been developed and applied to the study of the periodic aperture arrays containing multiple dissimilar apertures of complex shapes in stratified medium. The rapid uniform convergence of the solutions has enabled a comprehensive parametric study of complex array arrangements. The developed theory has revealed new effects of the aperture shape and layout on the array performance. The physical mechanisms underlying the TM wave resonances and Luebbers' anomaly have been explained for the first time.

Channelled Waves in Anisotropic Mesh Metamaterials

Channelled waves in 2-D periodic anisotropic L-C mesh metamaterials have been investigated. Circuit simulation and the newly developed analytical model of a unit cell have demonstrated full qualitative agreement for both lossless and lossy cases. Isofrequencies for a lattice unit cell and the circuit simulations of finite meshes have shown that propagating waves are channelled from a point source as pencil beams which can travel only along specific trajectories. The beam direction varies with frequency, and at the resonance frequency, the phase and group velocities of the travelling wave are orthogonal. The effect of losses was explored, and it was shown that losses cause qualitative changes of the channelled wave type. It was proven that the channelled waves do not follow the laws of geometrical optics (Snell's law, specular reflection, etc.) at the interfaces of L-C meshes but are governed by the conditions of phase synchronism and impedance matching. Only in the special case of dual L-C and C-L meshes with the interface parallel to the axis of rectangular grid excited at the resonance frequency (X=1) do the channels follow the trajectories of optical rays. A planar mesh test cell has been designed and used for retrieving the unit cell L-C parameters from the S-parameter measurements.

Spatial Demultiplexing in the sub-millimeter wave band using multlayer free-standing frequency selective surfaces

In this paper, we show that a multilayer freestanding slot array can be designed to give an insertion loss which is significantly lower than the value obtainable from a conventional dielectric backed printed frequency selective surface (FSS). This increase in filter efficiency is highlighted by comparing the performance of two structures designed to provide frequency selective beamsplitting in the quasioptical feed train of a submillimeter wave space borne radiometer. A two layer substrateless FSS providing more than 20 dB of isolation between the bands 316.5â??325.5 GHz and 349.5â??358.5 GHz, gives an insertion loss of 0.6 dB when the filter is orientated at 45 incidence in the TM plane, whereas the loss exhibited by a conventional printed FSS is in excess of 2 dB. A similar frequency response can be obtained in the TE plane, but here a triple screen structure is required and the conductor loss is shown to be comparable to the absorption loss of a dielectric backed FSS. Experimental devices have been fabricated using a precision micromachining technique. Transmission measurements performed in the range 250â??360 GHz are in good agreement with the simulated spectral performance of the individual periodic screens and the two multilayer freestanding FSS structures.

Micromachined 300GHz high Q resonant slot frequency selective surface filter

The design of a low loss quasi-optical beam splitter which is required to provide efficient diplexing of the bands 316.5-325.5 GHz and 349.5-358.5 GHz is presented. To minimise the filter insertion loss, the chosen architecture is a three-layer freestanding array of dipole slot elements. Floquet modal analysis and finite element method computer models are used to establish the geometry of the periodic structure and to predict its spectral response. Two different micromachining approaches have been employed to fabricate close packed arrays of 460 mm long elements in the screens that form the basic building block of the 30mm diameter multilayer frequency selective surface. Comparisons between simulated and measured transmission coefficients for the individual dichroic surfaces are used to determine the accuracy of the computer models and to confirm the suitability of the fabrication methods.

Quadrifilar Loop Antenna

A new quadrifilar antenna has been developed for generating circularly polarized backfire radiation. The antenna consists of two orthogonal rectangular conducting loops, each incorporating capacitive coupling and fed using either a single or two coaxial cables. Though the geometry is much simpler than a conventional quadrifilar helix antenna, the radiation pattern performance is very similar. Measured and simulated patterns are compared for two antennas with different feed arrangements. It is shown that the resonant structure can produce a cardioid pattern with a directivity of 4.5 dB (120 3-dB beamwidth) and a front-to-back ratio of more than 20 dB at the center operating frequency. A 10% impedance bandwidth (VSWR

Characterization and Modeling of the Indoor Radio Channel at 868 MHz for a Mobile Bodyworn Wireless Personal Area Network

This letter reports the statistical characterization and modeling of the indoor radio channel for a mobile wireless personal area network operating at 868 MHz. Line of sight (LOS) and non-LOS conditions were considered for three environments: anechoic chamber, open office area and hallway. Overall, the Nakagami-m cdf best described fading for bodyworn operation in 60% of all measured channels in anechoic chamber and open office area environments. The Nakagami distribution was also found to provide a good description of Rician distributed channels which predominated in the hallway. Multipath played an important role in channel statistics with the mean recorded m value being reduced from 7.8 in the anechoic chamber to 1.3 in both the open office area and hallway.

Structure-activity studies on position 14 of human alpha-calcitonin gene-related peptide

A structure-activity study was performed to examine the role of position 14 of human alpha-calcitonin gene-related peptide (h-alpha-CGRP) in activating the CGRP receptor. Interestingly, position 14 of h-alpha-CGRP contains a glycyl residue and is part of an alpha-helix spanning residues 8-18. Analogues [Ala(14)]-h-alpha-CGRP, [Aib(14)]-h-alpha-CGRP, [Asp(14)]-h-alpha-CGRP, [Asn(14)]-h-alpha-CGRP, and [Pro(14)]-h-alpha-CGRP were synthesized by solid phase peptide methodology and purified by RP-HPLC. Secondary structure was measured by circular dichroism spectroscopy. Agonist activities were determined as the analogues' ability to stimulate amylase secretion from guinea pig pancreatic acini and to relax precontracted porcine coronary arteries. Analogues [Ala(1)4]-h-alpha-CGRP, [Aib(14)]-h-alpha-CGRP, [Asp(14)]-h-alpha-CGRP, and [Asn(14)]-h-alpha-CGRP, all containing residues with a high helical propensity in position 14, were potent full agonists compared to h-alpha-CGRP in both tissues. Interestingly, replacement of Gly(14) of h-alpha-CGRP with these residues did not substantially increase the helical content of these analogues. [Pro(14)]-h-alpha-CGRP, predictably, has significantly lower helical content and is a 20-fold less potent agonist on coronary artery, known to contain CGRP-1 receptor subtypes, and an antagonist on pancreatic acini, known to contain CGRP-2 receptor subtypes. In conclusion, the residue in position 14 plays a structural role in stabilizing the alpha-helix spanning residues 8-18. The alpha-helix is crucial for maintaining highly potent agonist effects of h-alpha-CGRP at CGRP receptors. The wide variety of functional groups that can be tolerated in position 14 with no substantial modification of agonist effects suggests the residue in this position is not in contact with the CGRP receptor. [Pro(14)]-h-alpha-CGRP may be a useful pharmacological tool to distinguish between CGRP-1 and CGRP-2 receptor subtypes.