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We analyze refraction of electromagnetic wave packets on passing from an isotropic positive to an isotropic negative refractive index medium. We definitively show that in all cases the energy is always refracted negatively. For localized wave packets, the group refraction is also always negative., 5 pages, 3 figures

Purpose: To quantify the relative in vitro dose enhancement due to the presence of goldnanoparticles (GNPs) in a clinical 6 MV beam. It is expected that depths and delivery modes that produce larger proportions of low energy photons will have a larger effect on cell samples containing GNP. Methods: HeLa cells were combined with 50 nm GNPs at a concentration of 0 or 0.05 mg/ml. The cells were irradiated in clinical solid water at depths of 1.5, 5, 10, 15 and 20 cm (SAD setup). Conventional beams with square aperture sizes 5, 10 and 15 cm at isocenter, IMRT and flattening filter free (FFF) beams were used. DNA double strand breaks (DSBs) were evaluated by H2AX staining. Results: Statistically significant dose enhancement was observed for all depths and delivery modes. Dose enhancement ratios varied between 1.1 and 1.7. Relative to the shallowest depth, dose enhancement was observed to increase as a function of increasing depth for all deliveries. For the conventional (open field) delivery, dose enhancement was seen to increase as a function of field size. The IMRT delivery chosen for this study did not significantly increase the dose enhancement at each depth, but did in the aggregate. For FFF delivery, a substantial increase in gH2AX foci was found, relative to the conventional field delivery. Without GNP, no enhancement was observed as a function of depth, indicating that the enhancing effect with GNP is due to the change in energy spectrum under each delivery condition. Conclusions: The measured relative dose enhancement validates the theoretically predicted trends in dose enhancement as a function of depth and delivery mode for a clinical MV beam. The results of this study open new possibilities for the clinical development of goldnanoparticle aided radiation therapy.

We study the statistics of the experimental eigenfunctions of chaotic and disordered microwave billiards in terms of the moments of their spatial distributions, such as the Inverse Participation Ratio (IPR) and density-density auto-correlation. A path from chaos to disorder is described in terms of increasing IPR. In the chaotic, ballistic limit, the data correspond well with universal results from random matrix theory. Deviations from universal distributions are observed due to disorder induced localization, and for the weakly disordered case the data are well-described by including finite conductance and mean free path contributions in the framework of nonlinear sigma models of supersymetry., 5 pages + 2 JPG figures

Precision measurements of the microwave surface resistance $R_{s}$ of in situ $MgB_{2}$ films directly reveal an exponential behavior of $R_{s}$ at low temperature indicating a fully-gapped order parameter. The entire temperature dependence of $R_{s}$ is well described by a Mattis-Bardeen formalism but with a small gap ratio of $\Delta (0)/kT_{c}=0.72$, corresponding to $\Delta (0)=1.9meV$.

Introduction: Poly ADP Ribose Polymerase inhibitor therapy (PARPi) exploits a synthetic lethality strategy in cancers specifically endowed with inherent damage in DNA repair or transcription pathways. Olaparib and BMN-673 are potent PARP inhibitors that are currently indicated for oral PARPi in several clinical trials for a variety of cancers. Oral administration in general results in poor bioavailability and tumor accumulation. Here we report novel and well characterized nanoformulations customized for olaparib (NanoOlaparib) and BMN-673 (NanoBMN) , thus enabling a platform which provides a safe vehicle for intravenous delivery specifically targeted to the tumor, thereby increasing the bioavailability while reducing systemic toxicity. Our nanoplatform is also tailored for the combinatorial chemotherapy and radio-sensitization in several cancers including prostate, ovarian and breast cancer cell lines with and without the BRCA mutations. Methods: Two nanoparticle formulations NanoOlaparib and NanoBMN have been successfully formulated and tested in vitro on several cancer cell lines. The initial combination studies were performed with Cisplatin and PARPi nanoformulations defined by ∼163 nm diameter, zeta potential ∼ +10mV, and loaded with olaparib (2.3mM) or BMN-673 (200µM) and cisplatin (∼3.3mM). Dose response curves over a dynamic range of nanoPARPi therapy on several cell lines were generated using MTS assay and EC50's were determined using Prism. The synergism due to radiosensitization using 220 keV beam was studied for both therapies using isobolograms developed from clonogenic assays on prostate and breast cancer cells. The efficacy of combination PARPi and Pt therapy with nanoparticle platform was determined on ovarian cancer cell lines including PA-1, KURAMOCHI etc. The functionality of nanoPARPi/combination formulations on all the cancers, reflected by inhibition of PARylation, γ-H2AX and RAD-51 was determined by immunoflourescence assays. Results: Radiosensitization showed strong radiosensitization, achieving long-term cell kill of more than 90% with NanOlaparib and 4 Gy radiation in prostate cancer PC3, VCaP and LNCaP cell lines. VCaP which carries a TMPRSS2: ERG fusion was more responsive than PC3 for monotherapy using NanoOlaparib alone, and had better radiation sensitization compared to the other cell lines tested so far. In all studies NanoOlaparib showed better efficacy in combination with radiation than free Olaparib. Similar studies with nanoBMN are underway. Conclusions: Robust nanoparticle formulations NanoOlaparib and NanoOlaparibPt have been successfully demonstrated. We observed a significant enhancement in the efficacy with both nanoformulations. Strong radiosensitization was observed after several days. These results imply an important role for the nanoOlaparib and nanoBMN formulations as chemo and radio-sensitizers enabling several therapeutic approaches. Citation Format: Shifalika Tangutoori, Paige Baldwin, Houari Korideck, Robert Cormack, Mike G. Makrigiorgos, Srinivas Sridhar. Nanoformulations of PARP inhibtors for cancer therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2397. doi:10.1158/1538-7445.AM2014-2397

Introduction: We have developed a new approach for chemoradiation therapy (CRT), termed Biological In-Situ Image Guided Radiation Therapy BIS-IGRT, which involves the coating of spacers routinely used during prostate I-125-based brachytherapy with radiosensitizing drugs (e.g. docetaxel DTX and gold nanoparticles). This approach provides localized in-situ delivery of the sensitizer to the tumor and avoids the toxicity associated with current systemic delivery of radiosensitizers. BIS-IGRT adds radiosensitization capability to the standard brachytherapy procedure providing sustained delivery and drug concentration and with minimal additional inconvenience to the patient. Thereby BIS-IGRT improves the therapeutic ratio of radiation therapy without introducing additional patient interventions over current brachytherapy procedures. Methods: We have fabricated a nanoparticles based smart ‘INCeRT’ (Implantable Nanoplatform for Chemo-Radiation Therapy) implant for localized delivery of radiosensitizing nanoparticles/ drugs in prostate cancer in conjunction with brachytherapy. These implants are physically similar to the clinically used brachytherapy spacers but have the added capability of imaging and local drug delivery. We have fabricated INCeRT spacers with biocompatible and biodegradable polymer, PLGA impregnated with nanoparticles encapsulating imaging probe (Cyanine 7.5) and chemotherapeutic drug, docetaxel (DTX). Using a similar approach, we have also fabricated PLGA spacers impregnated with high Z (atomic number) gold nanoparticles (Hi-Z-CuRE: High Z-Customizable Radiotherapy Enhancement) for effectively boosting the radiation dose locally. The morphology, composition and nanoparticle's distribution inside the spacers was studied by SEM (scanning electron microscopy) and EDS (Energy-dispersive X-ray spectroscopy). Further, preliminary in vivo imaging experiments with subcutaneous prostate cancer tumored mice implanted with INCeRT spacers showed a size dependent diffusion of nanoparticles from the spacers in the tumor matrix. Also, from in vivo therapeutic studies with these spacers showed a sustained and slow release of the DTX from the spacers and showed a better response in suppressing the tumor as opposed to control mice with saline injections. Further experiments for studying the combined chemo-radiation therapy are underway. Conclusions: BIS-IGRT is a powerful approach to locally radio-sensitize the prostate to enable prostate cancer (PCa) cure with the use of lower radiation doses, thereby leading to less rectal toxicity. This new treatment approach would be of crucial benefit for patients with local relapse who require salvage radiotherapy but have reached their radiotherapy normal tissue dose limits. This work was supported partially by NSF-DGE-0965843, HHS/1U54CA151881 CORE1, 1R03 CA164645-01 and a seed grant from the BWH Biomedical Research Institute. Note: This abstract was not presented at the meeting. Citation Format: Rajiv Kumar, Jodi Belz, Stacey Markovic, Mark Niedre, Wilfred Ngwa, Houari Korideck, Robert Cormack, Paul Nguyen, Anthony D'Amico, Mike Makrigiorgos, Srinivas Sridhar. Smart brachytherapy spacers eluting nanoencapsulated radiosensitizers for chemo-radiation therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4917. doi:10.1158/1538-7445.AM2014-4917

Radiation Therapy Biomaterials for Response Assessment and Nodal Detection (Brand) W. Ngwa, Y. Altundal, H. Korideck, R. Kumar, S. Sridhar, R. Cormack, and M. Makrigiorgos; Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, University of Massachusetts Lowell, Lowell, MA, Northeastern University, Boston, MA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Purpose: Permanent prostate brachytherapy often uses inert bio-absorbable spacers to achieve the desired geometric distribution of sources within the prostate. Transforming these spacers into implantable nanoplatforms for chemo-radiation therapy (INCeRT) provides a means of providing sustained in-situ release of radiosensitizers in the prostate to enhance the therapeutic ratio of the procedure. Olaparib, a PARP inhibitor, suppresses DNA repair processes present during low dose rate continuous irradiation. This work investigates the radiosensitizing/DNA damage repair inhibition by NanoOlaparib eluting nanospheres. Methods: Human cell line PC3 (from ATCC), was maintained in F12-k medium supplemented with fetal bovine serum. Clonogenic assay kit (from Fischer Scientific) was used to fix and stain the cells to determine the long term effects of irradiation. Nanoparticle size and zeta potential of nanospheres were determined using a Zeta particle size analyzer. The incorporation of Olaparib in nanospheres was evaluated by HPLC. Irradiation was performed in a small animal irradiator operating at 220 KeV.The long term effects of radio-sensitization with olaparib and nanoolaparib was determined using the clonogenic assay at 2 Gy and 4 Gy doses. The cells were allowed to grow for around 10 doubling cycles, The colonies were fixed and stained using clonogenic assay kit. The excess stain was washed off using DI water and the images were taken using a digital camera. Results: Radiosensitization studies were carried out in prostate cancer cell line, PC3 radiation at 0, 2 and 4Gy doses. Strongest dose response was observed with nanoolaparib treated cells compared to untreated cells. Conclusion: A two stage drug release of drug eluting nanospheres from a biodegradable spacer has been suggested for sustained in-situ release of Olaparib to suppress DNA repair processes during prostate brachytherapy. The Olaparib eluting nanospheres had the same in-vitro radiosensitizing effect as free olaparib. DOD 1R21CA16977501, A. David Mazzone Awards Program 2012PD164

We report the observation of two dielectric transitions at 110 and 60 K in the microwave response of nonsuperconducting ${\mathrm{YBa}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{6.0}$ crystals. The transitions are characterized by a change in polarizability and presence of loss peaks, associated with overdamped dielectric modes. An explanation is presented in terms of changes in polarizability of the apical O atoms in the Ba--O layer, affected by lattice softening at 110 K, due to change in buckling of the Cu--O layer. The onset of another mode at 60 K strongly suggests an additional local lattice change at this temperature. Thus microwave dielectric measurements are sensitive indicators of lattice softening which may be relevant to superconductivity.

Purpose: Image‐guidedradiation treatments routinely utilize radio‐opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. We study the hypothesis that the therapeutic efficiency of IGRT can be enhanced through simultaneous in‐situ delivery of radiosensitizers, contained within nanoparticles and nanoporouspolymer matrices coatinggold fiducial markers or spacers implanted in the tumor (BIS‐IGRT, Biological In‐Situ Image‐Guided Radiation Therapy). Methods and Materials: Biocompatible polymers loaded with model molecules were coated as a thin film on gold fiducials. The nanoporous morphology of the polymercoatings allowed controlled release of molecules and nanoparticles. Two experimental approaches were studied: (i) a free drug release system, (Doxorubicin, a hydrophilic drug in Poly(methyl methacrylate (PMMA) coating) and (ii) Poly(D,L‐lactic‐co‐glycolic acid) (PLGA) nanoparticles loaded with Coumarin‐6, a fluorescent model for a hydrophobic drug, in a chitosan matrix applied as gold fiducial coating. Measurements of temporal release kinetics in buffer and spatial release profiles in agarose were carried out using fluorescence spectroscopy. Results: For gold fiducials coated with Doxorubicin in PMMA matrix an initial release of Dox within the first few hours was followed by a sustained release over the course of next 3 months. Release of Dox from within PMMA matrix is dependent on the concentration of Dox, ratio of PMMA/Dox, thickness of PMMA/Dox coating on gold surface. The release profile of coumarin‐6 loaded nanoparticles from chitosan film on gold fiducials showed that (63±10)% of NPs were released in twenty days, and after that, the release became slower and additional 37% of release was observed after additional twenty‐days. Spatial release profiles in an agarose phantom were also measured and compared with release kinetics models. Conclusions: The results show that dosage and rate of release of these radiosenstizers can be precisely tailored to achieve the desired release profile for BIS‐IGRT.

In cancer therapy, effective delivery of the therapeutic plays a critical role in determining the success of the treatment planning system. In last decade, there is a major thrust in developing novel nanoparticles based delivery systems to improve the therapeutic benefits in cancer. An efficient delivery system should be able to target the diseased site with minimal systemic toxicity and a slow sustained release of the drug. Here, we have fabricated a nanoparticles based smart ‘INCeRT’ (Implantable Nanoplatform for Chemo-Radiation Therapy) implant for localized delivery of radiosensitizing nanoparticles/ drugs in prostate cancer in conjunction with brachytherapy. These implants are physically similar to the clinically used brachytherapy spacers but have the added capability of imaging and local drug delivery. We have fabricated INCeRT spacers with biocompatible and biodegradable polymer, PLGA (poly-(lactide-co-glycolide)) impregnated with nanoparticles encapsulating imaging probe (Cyanine 7.5) and chemotherapeutic drug, docetaxel (DTX). Using a similar approach, we have also fabricated PLGA spacers impregnated with high Z (atomic number) gold nanoparticles (Hi-Z-CuRE: High Z-Customizable Radiotherapy Enhancement) for effectively boosting the radiation dose locally. The morphology, composition and nanoparticle's distribution inside the spacers was studied by SEM (scanning electron microscopy) and EDS (Energy-dispersive X-ray spectroscopy). Further, preliminary in vivo imaging experiments with subcutaneous prostate cancer tumored mice implanted with INCeRT spacers showed a size dependent diffusion of nanoparticles from the spacers in the tumor matrix. Also, from in vivo therapeutic studies with these spacers showed a sustained and slow release of the DTX from the spacers and showed a better response in suppressing the tumor as opposed control mice with saline injections. Further experiments for studying the combined chemo-radiation therapy are underway. This new treatment approach would be of crucial benefit for patients with local relapse who require salvage radiotherapy but have reached their radiotherapy normal tissue dose limits. This work was supported partially by NSF-DGE-0965843, HHS/1U54CA151881 CORE1, 1R03 CA164645-01 and a seed grant from the BWH Biomedical Research Institute. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A82. Citation Format: Rajiv Kumar, Jodi E. Belz, Stacey Markovic, Houari Korideck, Wilfred F. Ngwa, Mark Niedre, Ross I. Berbeco, Robert Cormack, Mike G. Makrigiorgos, Srinivas Sridhar. Localized tumor delivery of radiosensitizers and chemotherapeutics using ‘INCeRT’ implants. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A82.

Introduction: PARP (Poly ADP Ribose Polymerase) plays a crucial role in the DNA repair pathways in a cell. In cancer cells that often exhibit DNA repair, PARP can be deemed as the "Achilles Heel." Several PARP inhibitors (PARPi) are currently in clinical trials. Olaparib is the first inhibitor which is clinically proven to be the most potent and successful to date. Olaparib is an orally administered drug, which binds competitively to the NAD+ binding site of PARP, thus attenuating the DNA repair mechanisms mediated by PARP. Here we report a novel and well characterized "Nano-Olaparib," thus enabling a platform which can provide a safe vehicle for intravenous delivery specifically targeted to the tumor, thereby increasing the bioavailability. Our nanopaltform can also be tailored for the combinatorial drug delivery for both chemo and radiosensitization in prostate cancer. Methods: A nanoparticle formulation Nano-Olaparib of the PARP inhibitor olaparib has been successfully formulated and tested in vitro. Initial studies showed that lipid based nanoparticles were better than polymer based nanoparticles to achieve the high loading efficiency needed. Cell viability of PC3 and VCaP after various treatments was determined by MTS assay. The effect of radiosensitization using 220 keV beam was studied for 2 Gy and 4 Gy radiation doses on all the treatment groups using MTS (2 days) and clonogenic assays (9 days). Results: Our Nano-Olaparib formulation is defined by nanoparticles of 120 nm (mean diameter), ∼ +15mV (zeta potential), polydispersity index ∼0.05 and loaded with at clinically relevant concentrations of olaparib (400μM to 2.3mM). As determined by MTS assay immediately after irradiation, we observed that there is a ∼10% cell death with irradiation alone compared to the untreated cells. The effect of irradiation is observed to be the greatest with nanoolaparib treated cells (∼50 % cell death) compared with Olaparib (∼20% cell death). The long term effects of radiosensitization were also determined using the clonogenic assay. We observed a decrease in cell viability after radiation alone, at 2 Gy and 4 Gy. As expected, Olaparib showed a decrease in the cell viability, indicating a lasting effect of Olaparib on the cells, irrespective of radiation treatment. Nano-Olaparib (formulation ST-18-2) treated groups displayed higher susceptibility to radiosensitization at 2 Gy and 4 Gy, when compared with olaparib, where the maximum effect was observed at 4 Gy. Conclusions: A robust nanoparticle formulation of the PARP inhibitor, Olaparib, has been successfully demonstrated. Both chemo sensitization and radio sensitization were studied in PC3, VCaP cell lines. Combinatorial administration of Nano (Olaparib+Cisplatin) showed greater cell death than Cisplatin alone or Cisplatin+Olaparib. The effect of radiosensitization with olaprib and Nano-Olaparib, was studied using 2 Gy and 4Gy radiation doses. We observed a significant enhancement in the cell killing ability (both immediate and delayed) with Nano-Olaparib when compared to olaparib alone. These results imply a very role for the Nano-Olaparib formulation as a chemo and radiosensitizer. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A81. Citation Format: Shifalika Tangutoori, Houari Korideck, Mike Makrigiorgos, Robert Cormack, Srinivas Sridhar. A novel nano-formulation for systemic administration of PARPi-olaparib (Nano-Olaparib) for radiosensitization, chemosensitization, and combinatorial therapy in prostate cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A81.

We show that the autocorrelation of quantum spectra of an open chaotic system is well described by the classical Ruelle-Pollicott resonances of the associated chaotic strange repeller. This correspondence is demonstrated utilizing microwave experiments on 2-D n-disk billiard geometries, by determination of the wave-vector autocorrelation C(\kappa) from the experimental quantum spectra S_{21}(k). The correspondence is also established via "numerical experiments" that simulate S_{21}(k) and C(\kappa) using periodic orbit calculations of the quantum and classical resonances. Semiclassical arguments that relate quantum and classical correlation functions in terms of fluctuations of the density of states and correlations of particle density are also examined and support the experimental results. The results establish a correspondence between quantum spectral correlations and classical decay modes in an open systems., Comment: 10 pages, 5 eps figures, "Quantum chaos Y2K" Nobel symposium, to appear in Physica Scripta

N-disk microwave billiards, which are representative of open quantum systems, are studied experimentally. The transmission spectrum yields the quantum resonances which are consistent with semiclassical calculations. The spectral autocorrelation of the quantum spectrum is shown to be determined by the classical Ruelle-Pollicot resonances, arising from the complex eigenvalues of the Perron-Frobenius operator. This work establishes a fundamental connection between quantum and classical correlations in open systems., Comment: 6 pages, 2 eps figures included, submitted to PRL

Non-universal correlations due to localization are observed in statistical properties of experimental eigenfunctions of quantum chaotic and disordered microwave cavities. Varying energy {E} and mean free path {l} enable us to experimentally tune from localized to delocalized states. Large level-to-level Inverse Participation Ratio (IPR I_{2}) fluctuations are observed for the disordered billiards, whose distribution is strongly asymmetric about . The density auto-correlations of eigenfunctions are shown to decay exponentially and the decay lengths are experimentally determined. All the results are quantitatively consistent with calculations based upon nonlinear sigma-models., Comment: 4 pages, LaTex, 5 .jpg figures. This paper with 5 embedded postscript figures available (PS,PDF) at http://sagar.physics.neu.edu/preprints/

The successful fabrication is reported of a five-pole interdigital stripline filter made of the 93 K superconductor Y1Ba2Cu3O(y) coated on a silver substrate, with a center frequency of 8.5 GHz and an extremely high rejection ratio of 80 dB. The lowest insertion loss measured was 0.1 dB at 12 K, with a return loss better than 16 dB, representing significant improvements over a similar Cu filter, and comparable to low Tc filters. The insertion loss appears to be limited by extrinsic factors such as tuning mismatch and joint losses, and not by the superconducting material losses.

We describe a wave-mechanical implementation of classically chaotic n-disk scattering based on thin 2-D microwave cavities. Two, three, and four-disk scattering are investigated in detail. The experiments, which are able to probe the stationary Green's function of the system, yield both frequencies and widths of the low-lying quantum resonances. The observed spectra are found to be in good agreement with calculations based on semiclassical periodic orbit theory. Wave-vector autocorrelation functions are analyzed for various scattering geometries, the small wave-vector behavior allowing one to extract the escape rate from the quantum repeller. Quantitative agreement is found with the value predicted from classical scattering theory. For intermediate energies, non-universal oscillations are detected in the autocorrelation function, reflecting the presence of periodic orbits., 13 pages, 8 eps figures included

The quantum resonances of classically chaotic n-disk geometries were studied experimentally utilizing thin 2-D microwave geometries. The experiments yield the frequencies and widths of low-lying resonances, which are compared with semiclassical calculations. The longtime or small energy behavior of the wave-vector auto-correlation gives information about the quantum decay rate, which is in good agreement with that obtained from classical scattering theory. The intermediate energy behavior shows non-universal oscillations determined by periodic orbits., Comment: 5 pages, 3 eps figs included

A sensitive tunnel diode oscillator (TDO) technique operating at 4MHz is used to probe the dynamic response of La1−xSrxMnO3 single crystals for x = 0.125, 0.175, 0.28 and 0.33 doping. Systematics of the measured change in reactance (δX) as a function of temperature (30K < T < 320K) and DC magnetic field (0 < H < 6kOe) reveal distinct temperature and field scales associated with the dynamic response of spin. It is notable that these features are far more striking than the corresponding features in static measurements. The results are discussed in the context of structural changes leading to polaron ordering.

Dynamic susceptibility measurements at microwave frequencies (2 – 10GHz) are a sensitive probe of charge dynamcis in La5/3Sr1/3NiO4. Below the charge ordering temperature of 240K, a dielectric loss peak due to a relaxation mode with a large dielectric susceptibility is observed, and is associated with charge stripe formation. The dielectric response for Hω∥b (Eω ⊥ b) is well represented by ε(T) = εo/(1 – iωτ(T)), with εo, ∼ 50, and τ(T) = 2 × 10−9(sec) exp(−T/37K). Parallel conductivity σ(T) contributions dominate at higher temperatures and for Hω∥c (Eω ⊥ c). The dielectric loss peak observed indicates that the charge relaxation rates lie in the GHz frequency ranges.

The non-linear dependence on applied $ac$ field ($b_{\omega}$) or current ($% i_{\omega}$) of the microwave (ac) impedance $R_{\omega}+iX_{\omega}$ of both short and long Josephson junctions is calculated under a variety of excitation conditions. The dependence on the junction width is studied, for both field symmetric (current anti-symmetric) and field anti-symmetric (current symmetric) excitation configurations.The resistance shows step-like features every time a fluxon (soliton) enters the junction, with a corresponding phase slip seen in the reactance. For finite widths the interference of fluxons leads to some interesting effects which are described. Many of these calculated results are observed in microwave impedance measurements on intrinsic and fabricated Josephson junctions in the high temperature superconductors, and new effects are suggested. When a $% dc$ field ($b_{dc}$) or current ($i_{dc}$) is applied, interesting phase locking effects are observed in the ac impedance $Z_{\omega}$. In particular an almost periodic dependence on the dc bias is seen similar to that observed in microwave experiments at very low dc field bias. These results are generic to all systems with a $\cos (\phi)$ potential in the overdamped limit and subjected to an ac drive., Comment: 7 pages, 11 figures

We report novel non-linear phenomena in the $ab$-plane microwave impedance of $YBaCu_{2}O_{7-\delta }$ single crystals. The $R_s$ vs. $H_{rf}$ data are well described by the non-linear RSJ model : $\dot{\phi}+\sin \phi =i_{rf}\cos \omega t$. The entire crystal behaves like a single Josephson junction. The extraordinary coherence of the data suggests an intrinsic mechanism., Comment: 2 pages,1 figure, Submitted to Proc. of M^2SHTSC-V (Beijing), also available at http://sagar.physics.neu.edu/preprints

The radio frequency (RF) response of La1-xSrxMnO3 single crystals reveal a variety of features associated with the structural, electronic and magnetic properties of the system. The resonance technique operating at ∼ 4 MHz employed in this study is sensitive to small changes in both the magnetic susceptibility and resistivity of the samples. Very sharp changes in frequency are observed at the ferromagnetic (FM) and structural phase transitions in both the metallic (x = 0.175) and insulating (0.125) crystals studied.In addition to the known transitions identified as FM and orthorhombic distortions, our experiments show rich structures which are not observed in conventional DC magnetization and transport experiments. Our results demonstrate that RF experiments are ideally suited to investigate the complex phase diagram in the manganites.The colossal frequency change that we observe at the FM transition in the La1-xSrxMnO3 crystals is indicative of the enormous potential for using these materials in high frequency switching applications.

DVHs were generated and compared. Monte Carlo calculations were performed to simulate ISA and to verify plan robustness. Results: On average the total number of seeds compared to the standard plan is 32% and 70% less for hemi and ultra focal plans respectively, whereas the average needles were 38% and 58% less for hemi and ultra focal respectively. Target volume coverage was adequately achieved for all plans with V100 above 97.8%. D90 was increased by 19% and 69% for hemi and ultra focal plans respectively. Meanwhile, D10 of urethral dose was reduced by 7% and 55% for hemi and ultra focal plans respectively. D2cc of rectum was reduced by 28% and 60% for hemi and ultra focal respectively. Plan robustness shows that a random shift in seed position of 4 mm would result in V100 and D90 dropping by 7.2% and 14%, respectively, for standard plans, with a corresponding reduction of 7.3% and 20% for hemi plans and 5% and 32% for ultra focal plans. Despite the fact that seed density is higher for the hemi and ultra focal approaches, ISA has similar effect on DHV parameters. For example, V100 and D90 are reduced by less than 1% and 3%, respectively, for all types of plans. Conclusions: Treatment planning for hemi and ultra focal options is feasible. Dose constraints are easily met with a notable reduction to organs at risk such as the bladder, urethra and rectum. Treating smaller targets, such as for ultra focal, makes seed positioning more critical. This should be taken into consideration during treatment planning. ISA has the same effect on DVH calculations for standard, hemi and ultra focal plans. Author Disclosure: B. Al-Qaisieh: G. Consultant; GE Oncura Ltd. J. Mason: None. A. Henry: None. P. Bownes: None. L. Dickinson: None. A. Hashim: None. M. Emberton: None. S. Langley: None.

Detection of ultrasmall masses and identification of biological molecules have been made possible as a result of advances in nanotechnology. Development of biosensing tools has significantly contributed to high-throughput diagnosis and analytical sensing exploiting high affinity of biomolecules. MicroCantilever (MC)-based detection has emerged as a promising biosensing tool for offering label-free and cost-effective sensing capabilities. One of the main criteria determining the success of each biosensor is the capability of the sensing platform to operate in aqueous media. Although being characterized with high sensitivity and simplicity, MCs do not provide an effective tool for measurement of marker proteins in liquid media due to large hydrodynamic damping and losses in the surrounding liquid. In this study, we describe two approaches to high sensitivity biomolecular detection using piezoelectric microcantilevers. (i) Immobilized Mass Detection in Air using electro-mechanical resonance: a unique self-se...

During the last 2 decades no new clinical MRI agents have been approved for clinical use. While Gadolinium based agents have been very popular, Gd cannot be used in emerging multi-functional nano platforms that have the potential to be retained in the body leading to severe toxicity. Superparamagnetic iron-oxide nanoparticles (SPIONs) are most attractive as offering a significant alternative that is far less toxic than Gd based agents. They can be incorporated into nanoplatforms combining other therapeutic agents to achieve image guided drug delivery. Conventionally, SPIONs are imaged via T2 and T2* weighted techniques which manifest signal voids for SPION-containing media. This proves to be disadvantageous in most circumstances because of the difficulty in discriminating signal loss from tissue associated partial voluming, perivascular effects, susceptibility artifacts and motion or flow artifacts. The unique combination of SPIONs with ultra-short TE (UTE) imaging has the specific advantages of rendering positive contrast with high SNR and high CNR, since non-SPION containing regions are dramatically dark due to native tissue's comparatively higher T1. With UTE, it may be possible to take advantage of SPION's inherent biocompatibility allowing for incorporation into drug loaded nanoplatforms leading to bright contrast and the possibility of in vivo quantification. Here, we report on a systematic study of positive contrast MR imaging using magnetic nanoplatforms incorporating SPIONs of varying particle size and functionalization. In the first step, nanoparticles of various sizes from 4 nm to 20 nm were synthesized by the thermal decomposition method in organic solvents and then coated with phospholipids containing PEG. The use of PEGylated phospholipid enables water solubility, imparts better dispersity and long circulation in blood stream. This results in a core-shell like morphology with iron oxide nanoparticle forming the core and phospholipid PEG forming the shell. The nanoparticles were characterized for their size and morphology using dynamic light scattering (DLS) and transmission electron microscopy (TEM). UTE was optimized on a Bruker 7T Biospec at the Center for Translational Neuroimaging (CTNI) at Northeastern University. High-contrast images were obtained by modification of various imaging parameters such as TE, TR, flip angle, pulse length, polar under-sampling, bandwidth and FOV/Geometry. The results are compared in vivo with Feraheme and show good promise for this approach to MR nanoparticle imaging. We acknowledge partial support from NSF DGE 0965843, HHS/5U54CA151881-02, and the Electronics Materials Research Institute at Northeastern University. Citation Format: Codi Gharagouzloo, Manasa Jillela, Rajiv Kumar, Dattatri Nagesha, Srinivas Sridhar. Positive contrast imaging of magnetic nanoplatforms for image-guided drug delivery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2673. doi:10.1158/1538-7445.AM2013-2673

Systemic chemotherapy is often used with radiation therapy in the management of prostate, cervix and lung cancer patients, but leads to severe systemic toxicities. We have introduced a new modality of loco-regional chemoradiation therapy termed in-situ image guided radiation therapy (BIS-IGRT) that offers the potential to deliver planned, localized and sustained delivery of chemotherapy agent, without systemic toxicities, as part of routine minimally invasive image guided radiation therapy procedures. Such image guided chemoradiation therapy requires characterization of the drug distribution produced by implantable drug eluters. This work presents imaging based means to measure temporal and spatial properties of diffusion distributions around spacers coated with dye-loaded nanoparticles. The distribution of 250nm silica nanoparticles (NP) conjugated to Cyanine 7.5 dye was evaluated with a custom built high-speed near-infrared small animal imaging platform providing 0.1 millimeter spatial resolution with >1Hz image acquisition rate. A brachytherapy spacer loaded with the Cy7.5/silica NP was injected subcutaneously on the left hind flank of a mouse and one was inserted into a xenograft tumor on the opposite flank as part of an approved animal research protocol. The mouse was imaged more than 36 days. The in vivo imaging experiments show that the area of high signal increases with time suggesting that NP accumulate in the vicinity of a spacer without diffusing to the rest of the body. The spatial and temporal characteristics of NP accumulation indicate that a BIS-IGRT approach may provide an effective means to improve the therapeutic ratio of brachytherapy. Conclusion: In-vivo measurements demonstrate that NP remain resident in the vicinity of the implanted eluting spacers with accumulation over times appropriate to improve brachytherapy's therapeutic ratio. Future work will optimize the NP and substrate properties of an implantable spacer to attain the optimal chemotherapy distributions for simultaneous placement during image guided brachytherapy implants. We acknowledge partial support from NSF DGE 0965843 and HHS/5U54CA151881-02. Citation Format: Rajiv Kumar, Jodi Belz, Stacey Markovic, Tej Jadhav, Paul Nguyen, Mark Niedre, Anthony DAmico, Mike Makrigiorgos, Robert Cormack, Srinivas Sridhar. Sustained release of drug eluting nanoparticles from implantable devices for loco-regional chemoradiation therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1594. doi:10.1158/1538-7445.AM2013-1594

The non-linear microwave surface impedance of patterned YBCO thin films, was measured using a suspended line resonator in the presence of a perpendicular DC magnetic field of magnitude comparable to that of the microwave field. Signature of the virgin state was found to be absent even for relatively low microwave power levels. The microwave loss was initially found to decrease for small applied DC field before increasing again. Also, non-linearities inherent in the sample were found to be substantially suppressed at low powers at these applied fields. These two features together can lead to significant improvement in device performance., 4 pages, LaTeX type, Uses IEEE style files, 600 dpi PostScript file with color figures available at http://sagar.physics.neu.edu/preprints.html Submitted to IEEE Transactions on Applied Superconductivity

Measurements of the rf penetration depth \lambda(T,H,\theta ) are used to study the superconducting order parameter, vortex dynamics in the mixed state and delineate critical fields in the borocarbide superconductor YNi_2B_2C. The lower critical field has an anomalous T dependence, H_{c1}(T)=1.12[1-(T/T_c)] kOe, which is however consistent with independent superfluid density measurements at microwave frequencies. The vortex response is dominated by viscous flux flow, indicative of extremely weak pinning, and is parametrized by a field scale H_{c2,eff}. The angular dependence of the vortex contribution \lambda(\theta) is in good agreement with the Coffey-Clem model. Structure is seen in the depairing transition in the vicinity of the upper critical field, with the existence of well-defined critical fields H_{c2a}, H_{c2b} and H_{c2c}, with the vortex field scale H_{c2,eff} closest to H_{c2b}. Overall the measurements indicate that YNi_2B_2C has a rich and unusual field dependence of its transport parameters., Comment: 6 LaTeX pages with 6 EPS figures, uses RevTeX, multicol and epsf. One figure bitmapped. Better PS file available at http://sagar.physics.neu.edu/preprints.html Submitted to Physica C

The overall goal of this project is to develop means to locally radio-sensitize the prostate to enable prostate cancer (PCa) cure with the use of lower radiation doses, thereby leading to less rectal toxicity. This new approach for chemoradiation therapy (CRT), termed Biological In-Situ Image Guided Radiation Therapy BIS-IGRT, involves the coating of spacers routinely used during prostate I-125-based brachytherapy with radiosensitizing drugs (e.g. docetaxel DTX for PCa). This approach provides localized in-situ delivery of the sensitizer to the tumor and avoids the toxicity associated with current systemic delivery of radiosensitizers. BIS-IGRT adds radiosensitization capability to the standard brachytherapy procedure and with minimal additional inconvenience to the patient. Current CRT with adjuvant systemic chemotherapy does not provide the sustained delivery and drug concentration needed for efficient radiosensitization. Thereby BIS-IGRT improves the therapeutic ratio of radiation therapy without introducing additional patient interventions over current brachytherapy procedures. We have established the following: 1. We have shown through modeling that drug distributions can be achieved that can lead to increased efficiency of image-guided brachytherapy (drug-coated spacers) or image guided external beam therapy (drug-coated fiducials). 2. Doxorubicine-coated fiducials (Dox/PLGA-PEG/CHIT) show release characteristics over 40 days in aqueous media, which is tailored to the time scales required for BIS-IGRT. The cytotoxicity of Dox/ PLGA-PEG NP is comparable to that of free Dox, so that there is no reduction of activity upon encapsulation in the NP. 3. Localized bolus injection of dye-loaded PLGA-PEG nanoparticles (NPs) distributes within 24 hours throughout the tumor, indicating that the sustained release from coated brachytherapy spacers has the potential to achieve the desired biological dose-painting of the tumor. BIS-IGRT could proffer radiation oncologists and medical physicists with a new treatment option for substantially enhancing therapeutic ratio and boosting cure rate for the hundreds of thousands of Americans diagnosed with prostate cancer each year. This new treatment approach would be of crucial benefit for patients with local relapse who require salvage radiotherapy but have reached their radiotherapy normal tissue dose limits. BIS-IGRT can still be accompanied by IV administration of chemotherapeutics, particularly for micro-metastasis, so that existing therapeutic approaches are not compromised. In addition BIS-IGRT could potentially become a mainstream treatment for patients newly diagnosed with prostate or other cancers, where radiation therapy is a common treatment modality. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1473. doi:1538-7445.AM2012-1473

Nanoparticle formulations of gold have shown a tremendous potential in various biomedical applications. The use of high atomic number (Z) materials presents an attractive approach in enhancing the therapeutic efficacy of the radiation therapy. The high Z number for gold (Z=79) makes them an ideal candidate for radiosensitization enhancement. The ability of the anisotropic gold nanorods to sustain the resonating surface plasmon with minimal damping results in highly efficient two-photon induced photoluminescence imaging. Here we present the synthesis and in vitro characterization of PEGylated gold nanorods as efficient radiosensitizing agents which can be imaged using inherent two-photon photoluminescence without a conjugated fluorophore. We have synthesized gold nanorods with an aspect ratio of 2.5 and functionalized the surface with different ratios of methoxy and amine PEG for modulating the charge and imparting the functional groups. The cellular uptake behavior in prostate cancer cell line PC3 was studied and the results indicated a robust uptake of the amine functionalized nanorods. The quantitative estimation of the nanorods uptake was performed with BCA assay as amount of nanorods present in per microgram of protein. Two photon photoluminescence imaging also confirmed a robust cellular uptake of the amine functionalized nanorods. The radiation damage enhancement of the gold nanorods was confirmed using PC3 cells. The cells treated with gold nanorods were irradiated with kilovoltage X-rays. A γH2AX assay was used for quantitation of the DNA damage with and without nanorods as controls. The results indicated an increased highly efficient DNA damage in cells treated with gold nanorods. The outcome of this research will enable further application of targeted nanorods in advanced animal models as efficient radiation dose enhancement agents wherein two-photon photoluminescence imaging will provide a real time assessment of the therapeutic response and disease progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1472. doi:1538-7445.AM2012-1472

The signatures of classical chaos and the role of periodic orbits in the wave-mechanical eigenvalue spectra of two-dimensional billiards are studied experimentally in microwave cavities. The survival probability for all the chaotic cavity data shows a "correlation hole," in agreement with theory, that is absent for the integrable cavity. The spectral rigidity Δ 3 (L), which is a measure of long-range correlation, is shown to be particularly sensitive to the presence of marginally stable periodic orbits. Agreement with random-matrix theory is achieved only after excluding such orbits, which we do by constructing a special geometry, the Sinai stadium. Pseudointegrable geometries are also studied, and are found to display intermediate behavior.

We report an experimental observation of slow-light in the GHz microwave regime utilizing the mechanism of the degeneracy of forward and backward waves in a planar waveguide consisting of a dielectric core cladded by single-negative metamaterial. The metamaterial cladding consists of periodic arrays of metallic split-ring resonators, exhibiting an effective negative permeability. Group delay dispersions obtained from pulsed measurements are in complete agreement with theoretical predictions.

We have developed magnetic nano-liposomes (MNL), incorporating superparamagnetic iron oxide nanoparticles (SPION), that are versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. MNL are prepared with a formuation of DPPC:DOTAP:CHOL and DOPE-PEG5000. Incorporation of SPIONs results in MNL with mean diameter of 150-250 nm. MNL are easily taken up by B16-F10 melanoma, HUMVEC-D and breast cancer cell lines. They preferentially target the tumor vasculature as shown in a dorsal skin fold chamber using fluorescently labeled MNL. MNL display superparamagnetic response that is essential for magnetic targeting, MR contrast enhancement and magnetic heating. MNL was administrated to SCID mouse with metastatic (B16-F10) melanoma grown in the right flank. Pre-injection and post-injection MR images were used to assess response to magnetic targeting effects. Biodistribution studies were conducted by 111In labeled MNL and amount of radioactivity recovered was used to confirm the effect of targeting for intratumoral administrations. We have shown that tumor signal intensities in T2 weighted images decreased an average of 20±5% and T2* values decreased and average of 14±7ms in the absence of magnetic targeting. This compares to an average signal decrease of 57±12% and a decrease in T2* relaxation times of 27±8ms with the aid of external magnet showing up to 2-fold greater accumulation by magnetic targeting. 111In radio-labeled MNL have been shown to enable multi-modal imaging in vivo using MRI and SPeCT/CT. The images show that an MNL bolus injected intra-tumorally was retained in the tumor 24 hours after injection. Application of a magnetic field enables redistribution of the MNL in the tumor. These MNL are also responsive to ac magnetic fields applied using a Copper coil at 360 kHz and 170A driving current. Both hyperthermia (upto 45C) and thermo-ablative temperatures upto 90C were achieved in 10 – 30 minutes ex vivo in buffer. The results indicate high efficiency for magnetic heating using MNL (Specific Absorption Rate ∼ 104 W/kg) and demonstrate the capability to couple ac magnetic fields to MNL to achieve any set of temperatures needed for hyperthermia and thermal ablation. To date there are no truly theranostic platforms that have been approved for clinical use that combine targeting, thermal heating and MRI imaging capabilities. Existing FDA approved magnetic nanoparticle formulations like ferridex and ferumoxytol, are optimized for MR imaging, and have not been shown to be usable for thermal therapy.The MNL platform is a novel nanoplatform combining multi-modal imaging capabilities, with magnetic targeting and thermal therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 380. doi:10.1158/1538-7445.AM2011-380

Image-guided radiation treatments routinely utilize implantable devices, such as radio-opaque fiducials or brachytherapy spacers, for improved spatial accuracy. We study the hypothesis that the therapeutic efficiency of IGRT can be further enhanced by biological in-situ dose painting (BIS-IGRT) using local delivery of radiosensitizers embedded within nanoparticles and nanoporous polymer matrices coating gold fiducial markers. Biocompatible polymers loaded with model molecules were coated as a thin film on gold fiducials. The nanoporous morphology of the polymer coatings allowed the controlled release of the molecules and nanoparticles. Two experimental approaches were studied: (i) a free drug release system Doxorubicin, a hydrophilic drug in Poly(methyl methacrylate (PMMA) coating and (ii) Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with Coumarin-6, a model for a fluorescent hydrophobic drug, in a chitosan matrix applied as fiducial coating. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. For flat gold films and gold fiducials coated with Doxorubicin in PMMA matrix, an initial release of Dox within the first few hours was followed by a sustained release over the course of next 3 months. Release of Dox from within PMMA matrix is dependent on the concentration of Dox, ratio of PMMA/Dox, thickness of PMMA/Dox coating on gold surface. The release profile of coumarin-6 loaded nanoparticles from chitosan film on gold fiducials showed a continuous release of NPs from the coating during forty days. (63±10)% of NPs were released in twenty days. After that, the release became slower and additional 37% of release was observed after twenty-days. Spatial release profiles in an agarose phantom were also measured and compared with release kinetics models. Results show that dosage and rate of release of these radiosensitizers can be precisely tailored to achieve the desired release profile for BIS-IGRT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2674. doi:10.1158/1538-7445.AM2011-2674

Purpose: Localized radiosensitization may improve the therapeutic ratio of 125I prostate brachytherapy. Spacers used in permanent implants may be manufactured from a drug‐releasing polymer. Loading the polymer with radio‐sensitizer would allow spacers to deliver protracted release of radio‐sensitizer localized to the prostate. Such devices will have a limited drug‐loading capacity, and the drug release schedule that optimizes outcome, under such a constraint, is not known. This work seeks optimal drug release schedules for 125I prostate brachytherapy and demonstrates the manufacture of such spacers. Method and Materials: Mathematical models of cell kill based using quadratic (LQ) models were used to compare biologic effectiveness of a number of drug release schedules where sensitization is present for a limited time (T). A range of radiosensitizations (S) was simulated by incorporating time dependent α and β values in the LQ model and calculating cell survival fractions. To avoid model dependence, a range of baseline α/β values were considered. A limited drug capacity was simulated by comparing schedules with equal products of sensitization and time (ST). To evaluate the ability to create drug‐releasing spacers, a gold fiducial marker was coated with a polymer loaded with fluorescent molecules. Results: Comparing cell kill for schedules with equivalent ST shows that the cell kill is increased more by delivering a substantial sensitization over a shorter time than by sensitizing less for a longer time. Extended duration of radio‐sensitization requires a time scale of weeks to achieve increased cell kill given sensitization levels reported for taxol. Polymercoated fiducials show 2‐week drug release is technically feasible. Conclusion: Using brachytherapy spacers to produce localized radio‐sensitization over the time scale relevant to prostate brachytherapy is feasible. Both traditional sensitizers and repair inhibitors may be employed to improve the therapeutic ratio of prostate brachytherapy.

Purpose: The development of non‐invasive imaging techniques for the assessment of cancer treatment is rapidly becoming highly important. Magnetic Cationic Liposomes (MCL) that carry a cargo of anti‐cancer drugs and magnetic nanoparticles that will selectively target primary and metastatic cancertumorsdeliver drugs to them and visualize their effects through magnetic resonance imaging(MRI)single photon emission computed tomography(SPECT) and fluorescence spectroscopy. The aim of the present study is to evaluate MCL as a versatile theranostic nanoplatform for enhanced drug deliveryimaging and monitoring of cancer treatment. Materials and Method: Poly‐ethyleneglycol (PEG) coated cationic liposomes are loaded with superparamagnetic iron oxide nanoparticles (SPIONS) and tagged with the radioisotope Indium‐111. MCL was administered to SCID mouse with metastatic (B16‐F10) melanoma grown in the right flank. Pre‐injection and post‐injection MR and SPECT/CT images were used to assess response to magnetic targeting effects and tumor and organ distribution. Results:Tumor signal intensities in T2 weighted images decreased an average of 20±5% and T2* values decreased and average of 14±7ms in the absence of magnetic targeting. This compares to an average signal decrease of 57±12% and a decrease in T2* relaxation times of 27±8ms with the aid of external magnet showing up to 2‐fold greater accumulation by magnetic targeting. SPECT/CT images showed the localization and distribution of MCL in the tumor.Conclusion: MR SPECT/CT and biodistribution analyses clearly show the efficacy of MCL as MRI contrast agents prove the use of magnetic guidance and demonstrate the potential of MCL as agents for imaging guidance and therapeutic delivery.

We show that a nonresonant planar waveguide consisting of conventional dielectric cladded with single-negative materials supports degenerate propagating modes for which the group velocity and total energy flow can be zero if the media are lossless. Absorptive losses will destroy the zero-group velocity condition for real frequency/complex wave vector modes. We show that by incorporating gain G into the core dielectric, there exists a critical gain value Gc at which we can recover the condition of zero group velocity, so that light pulses can be stopped and stored. This structure is simpler to achieve than double-negative metamaterials, has small footprint, and can be incorporated into ultracompact on-chip optoelectronics.

Super-resolution imaging beyond Abbe’s diffraction limit can be achieved by utilizing an optical medium or “metamaterial” that can either amplify or transport the decaying near-field evanescent waves that carry subwavelength features of objects. Earlier approaches at optical frequencies mostly utilized the amplification of evanescent waves in thin metallic films or metal-dielectric multilayers, but were restricted to very small thicknesses (⪡λ, wavelength) and accordingly short object-image distances, due to losses in the material. Here, we present an experimental demonstration of super-resolution imaging by a low-loss three-dimensional metamaterial nanolens consisting of aligned gold nanowires embedded in a porous alumina matrix. This composite medium possesses strongly anisotropic optical properties with negative permittivity in the nanowire axis direction, which enables the transport of both far-field and near-field components with low-loss over significant distances (>6λ), and over a broad spectral range. We demonstrate the imaging of large objects, having subwavelength features, with a resolution of at least λ/4 at near-infrared wavelengths. The results are in good agreement with a theoretical model of wave propagation in anisotropic media.

We study chaotic quantum billiards using both microwave cavities and numerical simulations. For the same geometry, viz., a Sinai billiard, agreement to remarkable precision is found for both the eigenvalue magnitudes and the spatial detail of the eigenfunctions. The association of the eigenfunctions with classical periodic orbits is demonstrated, and scarred states are identified. Desymmetrizing the Sinai billiard by slightly moving the central disk is shown to lead to strong localization of the eigenfunction

The radiofrequency penetration depth \ensuremath{\lambda}(H,T) of the organic superconductor (BEDT-TTF${)}_{2}$Cu(NCS${)}_{2}$ was studied in the mixed state at moderate fields. The data can be scaled into a single functional form \ensuremath{\Delta}\ensuremath{\lambda}(H,T)=\ensuremath{\Delta}${\ensuremath{\lambda}}^{\mathrm{*}}$(T)f(H/${\mathit{H}}^{\mathrm{*}}$(T)), where ${\mathit{H}}^{\mathrm{*}}$(T)\ifmmode\times\else\texttimes\fi{}(1-t${)}^{3/2}$/t can be identified with a ``depinning'' or ``irreversibility'' line. We show that the scaling features are contained in a theory of vortex motion in a periodic pootential under the influence of thermal fluctuations, which describes the functional form quantitatively. The data for \ensuremath{\Delta}\ensuremath{\lambda}(H=0, T) are governed by the same (vortex) length scale as the finite-field data, suggesting that the zero-field state is not a conventional Meissner state obeying a London relation.

We demonstrate experimentally negative refraction by a photonic crystal prism and imaging of a point source by a photonic crystal slab at 1.5 microm wavelength. The photonic crystal structures were nanofabricated in a InGaAsP/InP heterostructure platform, and optical characterization was performed using a near-field scanning optical microscope. By designing a suitable lens surface termination, an image spot size of 0.12lambda2 was achieved, demonstrating superlens imaging with subwavelength resolution well below Abbe's diffraction limit (0.5lambda2).

Fe3O4 were synthesized nanoparticles by thermal decomposition method with oleic acid as the surfactant, and to make them suitable for aqueous environments, dopamine ligand exchange was carried out on the particles. The nanoparticle size and phase was quantified by transmission electron microscopy (TEM) and x-ray diffraction (XRD), respectively. Superconducting quantum interference device magnetometry confirmed superparamagnetic behavior in both nanoparticles. A surprising and significant increase in the remanence MR, saturation magnetization MS, and blocking temperature TB of the particles was found after dopamine functionalization, even though TEM and XRD studies revealed no change in the particles’ size and/or structure. The results are consistent with an increase in the magnetic size of the nanoparticle core induced by the dopamine ligand exchange process. These effects are tentatively attributed to surface bonding effects that alter the canted magnetic state of the Fe3O4 nanoparticles.

The wave functions of Sinai-billiard-shaped microwave cavities are experimentally studied. Some of the general features observed are parity breaking in the lowest eigenstates, ``bouncing-ball'' states, and states with quasirectangular or quasicircular symmetry. The above features are associated with nonisolated periodic orbits. Some states are observed which can be associated with isolated periodic orbits, leading to scars. This work represents the first direct experimental observation of scarred eigenfunctions. At high frequencies the eigenfunctions are very complex, and are yet to be classified in a general scheme.

We demonstrate three-dimensional directed assembly of single-wall carbon nanotubes (SWNT) into porous alumina nanotemplates on silicon substrates by means of electrophoresis and dielectrophoresis at ambient temperatures. Assembled SWNT provided an interconnection between the surface and base of the nanotemplate. I-V measurements clearly show that the connection between silicon and SWNT is established inside the templates. This technique is particularly useful for large scale, rapid, 3D assembly of SWNT over centimeter square areas under mild conditions for nanoscale electronics applications.