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Mutations in BRCA genes are the leading cause of hereditary breast cancer. Current options to prevent cancer in these high-risk patients, such as anti-estrogen drugs and radical mastectomy, are limited by lack of efficacy, undesirable toxicities, or physical and emotional challenges. We have previously shown that PARP inhibitors can significantly delay tumor development in BRCA1-deficient mice. Here, we fabricated the PARP inhibitor talazoparib (TLZ) into spacer implants (InCeT-TLZ) for localized and sustained delivery. We hypothesized that this novel formulation will provide an effective chemopreventive strategy with minimal toxicity. TLZ was released gradually over 30 days as implants degraded. InCeT-TLZ significantly decreased proliferation and increased DNA damage in the mammary glands of BRCA1-deficient mice. Notably, the number of mice that developed hyperplasia in the mammary glands was significantly lower with InCeT-TLZ treatment compared to the control group. Meanwhile, InCeT-TLZ was also better tolerated than oral TLZ, without loss of body weight or anemia. This study provides proof of concept for a novel and safe chemopreventive strategy using localized delivery of a PARP inhibitor for high-risk individuals. Future studies will directly evaluate the effects of InCeT-TLZ for preventing tumor development.

Background: Despite medicinal advances, cancer is still a big problem requiring better diagnostic and treatment tools. Magnetic nanoparticle (MNP)-based nanosystems for multiple-purpose applications were developed for these unmet needs. Methods: This study fabricated novel trifunctional MNPs of Fe3O4@PLA-PEG for drug release, MRI and magnetic fluid hyperthermia. Result: The MNPs provided a significant loading of curcumin (∼11%) with controllable release ability, a high specific absorption rate of 82.2 W/g and significantly increased transverse relaxivity (r2 = 364.75 mM-1 s-1). The in vivo study confirmed that the MNPs enhanced MRI contrast in tumor observation and low-field magnetic fluid hyperthermia could effectively reduce the tumor size in mice bearing sarcoma 180. Conclusion: The nanocarrier has potential for drug release, cancer treatment monitoring and therapy. The authors are grateful for the financial support by AOARD under award FA2386-17-1-4042. The Spanish government is acknowledged for the “Nanotechnology in translational hyperthermia (HIPERNANO)” research network (RED2018102626-T) and for funding under the project number MAT2017-83631-C3. NTK Thanh thanks EPSRC (EP/M015157/1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

PURPOSE: To evaluate the feasibility of Quantitative Ultrashort-Time-to-Echo Contrast Enhanced (QUTE-CE) MRA using ferumoxytol as a contrast agent for abdominal angiography in the kidney. METHODS: Four subjects underwent ferumoxytol-enhanced MRA with the 3D UTE Spiral VIBE WIP sequence at 3T. Image quality metrics were quantified, specifically the blood Signal-to-Noise Ratio (SNR), blood-tissue Contrast-to-Noise Ratio (CNR) and Intraluminal Signal Heterogeneity (ISH) from both the aorta and inferior vena cava (IVC). Morphometric analysis of the vessels was performed using manual approach and semi-automatic approach using Vascular Modeling ToolKit (VMTK). Image quality and branching order were compared between QUTE-CE MRA and the Gadolinium (Gd) CEMRA reference image. RESULTS: QUTE-CE MRA provides a bright blood snapshot that delineates arteries and veins equally in the same scan. The maximum SNR and CNR values were 3,282 ± 1,218 and 1,295 ± 580, respectively – significantly higher than available literature values using other CEMRA techniques. QUTE-CE MRA had lower ISH and depicted higher vessel branching order (7th vs 3rd) within the kidney compared to a standard dynamic clinical Gd CEMRA scan. Morphometric analysis yielded quantitative results for the total kidney volume, total cyst volume and for diameters of the branching arterial network down to the 7(th) branch. Vessel curvature was significantly increased (p < 0.001) in the presence of a renal cyst compared to equivalent vessels in normal kidney regions. CONCLUSION: QUTE-CE MRA is feasible for kidney angiography, providing greater detail of kidney vasculature, enabling quantitative morphometric analysis of the abdominal and intrarenal vessels and yielding metrics relevant to vascular diseases while using a contrast agent ferumoxytol that is safe for CKD patients.

International audience; This roadmap outlines the potential roles of metallic nanoparticles (MNPs) in the field of radiation therapy. MNPs made up of a wide range of materials (from Titanium, Z = 22, to Bismuth, Z = 83) and a similarly wide spectrum of potential clinical applications, including diagnostic, therapeutic (radiation dose enhancers, hyperthermia inducers, drug delivery vehicles, vaccine adjuvants, photosensitizers, enhancers of immunotherapy) and theranostic (combining both diagnostic and therapeutic), are being fabricated and evaluated. This roadmap covers contributions from experts in these topics summarizing their view of the current status and challenges, as well as expected advancements in technology to address these challenges.

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Delayed Dark Adapted vision Recovery (DAR) is a biomarker for Age-related Macular Degeneration (AMD), however its measurement is burdensome for patients and examiners. We developed a portable, wireless, quick-setup system that employs a headset with a smartphone to deliver controlled photobleach and monocular pattern reversal stimuli, while using custom electroencephalography (EEG) electrodes and electronics in order to measure objective Dark Adapted Visual Evoked Potentials (DAVEP) at multiple locations of the visual field - all in one comfortable 20-minute session, without requiring subject reporting. DAVEP responses post photobleach (up to 15 minutes), were measured concurrently in both eyes of 13 patients with AMD and 8 others not diagnosed with AMD. New, unexpected features at high latencies were observed in the DAVEP responses to scotopic stimulus intensities. The amplitude recovery of the DAVEP response was significantly delayed in AMD patients compared with controls. We developed DAVEP1 scores, a simple metric for DAR, using it to successfully identify all 100% of AMD subjects and classify 90% of subject eyes correctly. Deficits in DAR in patients with AMD can be identified using this objective VEP based system and the DAVEP1 metric, a promising new objective biomarker for this disease that can be easily tested in a clinic.

Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1-deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1-deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1Co/Co;MMTV-Cre;p53+/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro. Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors.

Background and aims Endothelial surface glycocalyx shedding plays a role in endothelial dysfunction and increases vessel wall permeability, which can lead to inflammation and atherogenesis. We sought to elucidate whether a high fat diet (HFD) or disturbed blood flow conditions, both of which are atherogenic risk factors, would contribute more detrimentally to pre-atherosclerotic loss of endothelial glycocalyx integrity and vascular inflammation. Methods Six to seven week-old C57BL/6-background apolipoprotein-E-knockout (ApoE-KO) male mice were either fed a chow diet, fed a modified Western HFD, and/or subjected to a partial left carotid artery (LCA) ligation procedure to induce disturbed blood flow patterns in the LCA. Mice were sacrificed after 1 week of experimental conditions. Both LCA and right carotid artery (RCA) vessels were dissected and preserved to compare glycocalyx coverage and thickness as well as macrophage accumulation in carotid arterial walls amongst and between cohorts. Results Glycocalyx coverage of the endothelium was significantly reduced in the LCAs of HFD fed mice when compared to the control. More significant reduction in glycocalyx coverage occurred in the LCAs of mice exposed to disturbed flow by partial LCA ligation when compared to the control. No differences were found in glycocalyx coverage of RCAs from all cohorts. Regarding inflammation, no difference in macrophage accumulation in carotid arterial walls was observed when comparing the LCAs and RCAs of control and HFD fed mice. However, macrophage infiltration in vessel walls showed a 20-fold increase in the LCAs exposed to disturbed flow following ligation, when compared to control LCAs, while no such statistical difference was observed between the RCAs of the group. Conclusions In our mouse model, endothelial glycocalyx integrity was compromised more by disturbed blood flow patterns than by exposure of the carotid vessel to HFD conditions. The pathophysiological implications include endothelial dysfunction, which correlates to macrophage infiltration in vessel walls and promotes atherogenesis.

Paige Baldwin,1 Shifalika Tangutoori,1,2 Srinivas Sridhar1,2 1Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA; 2Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, USA Abstract: PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an accumulation of deleterious mutations leading to genetic instability as a result of a number of cell replications. Currently, olaparib is only available in an oral form and has poor bioavailability, consequently leading to poor accumulation in the tumor due to first-pass metabolism. Therefore, in the present study, an injectable nanoparticle formulation of olaparib was created that offers a delivery route in which the drug would be fully bioavailable in the vasculature, suggesting greater tumor accumulation. Our results illustrated that injectable nanoformulations of olaparib and BMN-673, a next generation PARPi, could be developed, and an efficacy test indicated that BMN-673 is a much more potent PARPi than olaparib. The success of these molecular inhibitors as a monotherapy in inhibiting colony formation suggests enhanced efficacy of these treatments in combination with other therapies, even in tumors which have developed resistance. Keywords: PARP-l, olaparib, BMN-673, DNA repair protein, tumor accumulation

Effective drug delivery is severely restricted by the presence of complex pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, mature and hypopermeable tumor blood vessels limit the permeation and penetration of chemo or nanotherapeutics to cancer cells and substantially reduce the treatment efficacy. New, clinically-viable strategies are therefore sought to breach the neoplastic barriers that prevent optimal tumor-specific drug delivery. Here, we present an original idea to boost targeted drug delivery by selectively knocking down the tumor vascular barrier in a poorly permeable human pancreatic cancer model. For the first time, we demonstrate that clinical irradiation (10 Gy, 6 MV) can induce tumor vascular modulation when combined with tumor endothelial-targeting gold nanoparticles. Active disruption of tumor blood vessels by nanoparticle-combined radiotherapy led to increased vessel permeability and improved tumor uptake of two prototypical model nanodrugs: i) a short-circulating nanocarrier with MR-sensitive gadolinium (Gad-NC; 8 kDa; t1/2=1.5 h) and ii) a long-circulating nanocarrier with fluorescence-sensitive NIR dye (FL-NC; 30 kDa; t1/2=25 h). Functional changes in the altered tumor vessel dynamics, measured by relative changes in permeability (Ktrans), flux rate (Kep) and extracellular interstitial volume (Ve) were consistent with the concomitant increase in nanodrug delivery. This combination of radiation-induced antivascular and nanodrug-mediated anti-tumor treatment offers high therapeutic benefit for tumors with pathophysiology that restricts efficient drug delivery.

Surinder P Singh,1 Rishi Shanker,2 Srinivas Sridhar,3 Thomas J Webster3 1CSIR-National Physical Laboratory, New Delhi, India; 2School of Arts & Sciences, Ahmedabad University, Ahmedabad, India; 3College of Engineering, Northeastern University, Boston, USAIn the 21st century, nanomedicine is one of the fastest growing research areas in medicine and is expected to revolutionize health care by developing innovative diagnostic and therapeutic tools. In this context, an International Conference on Translational Nanomedicine (T-NANO 2014) was jointly organized by the CSIR-National Physical Laboratory, New Delhi, India; Northeastern University, Boston, USA; and the Institute of Life Sciences (ILS), Ahmedabad University, Ahmedabad, India, under the auspices of the IUSSTF-funded Indo-US Joint Centre on Nanomedicine for Head and Neck Cancer, Ahmedabad, from December 15–17, 2014. Center partners included Northeastern University; DFCI, Harvard Medical School, USA; CSIR-National Physical Laboratory; the CSIR-Indian Institute of Toxicology Research, Lucknow, India; the All India Institute of Medical Sciences, New Delhi, India; and the ILS. The central theme of the conference was to discuss the recent developments in nanotherapeutics, theranostics, nanomedicines, regenerative medicine, tissue engineering, diagnostics and imaging, toxicology, models for disease biology, and commercialization of all nanomedicines. The topics covered provided an understanding of how nanomaterials and nanotechnologies have played a pivotal role in advancing our understanding of biomedicine and in generating new tools toward the goal of improving human health.&nbsp

Cardiovascular diseases are facilitated by endothelial cell (EC) dysfunction and coincide with EC glycocalyx coat shedding. These diseases may be prevented by delivering medications to affected vascular regions using circulating nanoparticle (NP) drug carriers. The objective of the present study was to observe how the delivery of 10 nm polyethylene glycol-coated gold NPs (PEG-AuNP) to ECs is impacted by glycocalyx structure on the EC surface. Rat fat pad endothelial cells were chosen for their robust glycocalyx, verified by fluorescent immunolabeling of adsorbed albumin and integrated heparan sulfate (HS) chains. Confocal fluorescent imaging revealed a ~3 µm thick glycocalyx layer, covering 75% of the ECs and containing abundant HS. This healthy glycocalyx hindered the uptake of PEG-AuNP as expected because glycocalyx pores are typically 7 nm wide. Additional glycocalyx models tested included: a collapsed glycocalyx obtained by culturing cells in reduced protein media, a degraded glycocalyx obtained by applying heparinase III enzyme to specifically cleave HS, and a recovered glycocalyx obtained by supplementing exogenous HS into the media after enzyme degradation. The collapsed glycocalyx waŝ2 µm thick with unchanged EC coverage and sustained HS content. The degraded glycocalyx showed similar changes in EC thickness and coverage but its HS thickness was reduced to 0.7 µm and spanned only 10% of the original EC surface. Both dysfunctional models retained six- to sevenfold more PEG-AuNP compared to the healthy glycocalyx. The collapsed glycocalyx permitted NPs to cross the glycocalyx into intracellular spaces, whereas the degraded glycocalyx trapped the PEG-AuNP within the glycocalyx. The repaired glycocalyx model partially restored HS thickness to 1.2 µm and 44% coverage of the ECs, but it was able to reverse the NP uptake back to baseline levels. In summary, this study showed that the glycocalyx structure is critical for NP uptake by ECs and may serve as a passive pathway for delivering NPs to dysfunctional ECs., Video abstract

For the past decade engineered nanoplatforms have seen a momentous progress in developing a multimodal theranostic formulation which can be simultaneously used for imaging and therapy. In this report we describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. CdSe quantum dots (QDs) and anti-cancer drug, doxorubicin (Dox), were co-encapsulated into the hydrophobic core of the micelles. The micelles are characterized using optical spectroscopy for characteristic absorbance and fluorescence features of QDs and Dox. TEM and DLS studies yielded a size of

The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.

Atomically thin quaternary alloy of boron, nitrogen, carbon and oxygen, 2D-BNCO with tunable composition., In recent times, atomically thin alloys of boron, nitrogen, and carbon have generated significant excitement as a composition-tunable two-dimensional (2D) material that demonstrates rich physics as well as application potentials. The possibility of tunably incorporating oxygen, a group VI element, into the honeycomb sp2-type 2D-BNC lattice is an intriguing idea from both fundamental and applied perspectives. We present the first report on an atomically thin quaternary alloy of boron, nitrogen, carbon, and oxygen (2D-BNCO). Our experiments suggest, and density functional theory (DFT) calculations corroborate, stable configurations of a honeycomb 2D-BNCO lattice. We observe micrometer-scale 2D-BNCO domains within a graphene-rich 2D-BNC matrix, and are able to control the area coverage and relative composition of these domains by varying the oxygen content in the growth setup. Macroscopic samples comprising 2D-BNCO domains in a graphene-rich 2D-BNC matrix show graphene-like gate-modulated electronic transport with mobility exceeding 500 cm2 V−1 s−1, and Arrhenius-like activated temperature dependence. Spin-polarized DFT calculations for nanoscale 2D-BNCO patches predict magnetic ground states originating from the B atoms closest to the O atoms and sizable (0.6 eV < Eg < 0.8 eV) band gaps in their density of states. These results suggest that 2D-BNCO with novel electronic and magnetic properties have great potential for nanoelectronics and spintronic applications in an atomically thin platform.

Anne L van de Ven,1,2 Mary H Shann,3 Srinivas Sridhar1,2 1Nanomedicine Science and Technology Center, 2Department of Physics, Northeastern University, Boston, MA, USA; 3School of Education, Boston University, Boston, MA, USAAbstract: The Nanomedicine program at Northeastern University provides a unique interdisciplinary graduate education that combines experiential research, didactic learning, networking, and outreach. Students are taught how to apply nanoscience and nanotechnology to problems in medicine, translate basic research to the development of marketable products, negotiate ethical and social issues related to nanomedicine, and develop a strong sense of community involvement within a global perspective. Since 2006, the program has recruited 50 doctoral students from ten traditional science, technology, and engineering disciplines to participate in the 2-year specialization program. Each trainee received mentoring from two or more individuals, including faculty members outside the student’s home department and faculty members at other academic institutions, and/or clinicians. Both students and faculty members reported a significant increase in interdisciplinary scholarly activities, including publications, presentations, and funded research proposals, as a direct result of the program. Nearly 90% of students graduating with a specialization in nanomedicine have continued on to careers in the health care sector. Currently, 43% of graduates are performing research or developing products that directly involve nanomedicine. This article identifies some key elements of the Nanomedicine program, describes how they were implemented, and reports on the metrics of success.Keywords: nanomedicine, IGERT, nanotechnology, nanoscience, education, graduate training

Improvements in osteoconduction of implant biomaterials require focusing on the bone-implant interface, which is a complex multifactorial system. Surface topography of implants plays a crucial role at this interface. Nanostructured surfaces have been shown to promote serum protein adsorption and osteoblast adhesion when compared to micro-structured surfaces for bone-implant materials. We studied the influence of the serum proteins fibronectin and vitronectin on the attachment and proliferation of osteoblasts onto nanostructured titania surfaces. Human fetal osteoblastic cells hFOB 1.19 were used as model osteoblasts and were grown on nanoporous TiO2 templates, using Ti6AI4V and commercially pure Ti substrates as controls. Results show a significant increase in cell proliferation'on nanoporous TiO2 over flat substrates. Initial cell attachment data exhibited a significant effect by either fibronectin or vitronectin on cell adhesion at the surface of any of the tested materials. In addition, the extent of cell adhesion was significantly different between the nanoporous TiO2 and both Ti6AI4V and commercially pure Ti substrates, with the first showing the highest surface coverage. There was no significant difference on osteoblast attachment or proliferation between the presence of fibronectin or vitronectin using any of the material substrates. Taken together, these results suggest that the increase in osteoblast attachment and proliferation shown on the nanoporous TiO2 is due to an increase in the adsorption of fibronectin and vitronectin because of the higher surface area and to an enhanced protein unfolding, which allows access to osteoblast binding motifs within these proteins.

The advent of nanotechnology has bolstered a variety of nanoparticle-based platforms for different biomedical applications. A better understanding for engineering novel nanoparticles for applications in cancer staging and therapy requires careful assessment of the nanoparticle’s physico-chemical properties. Herein we report a facile synthesis method for PEGylated PLGA nanoparticles encapsulating anti-cancer drug doxorubicin for cancer imaging and therapy. The simple nanoprecipitation method reported here resulted in very robust PEGylated PLGA nanoparticles with close to 95 % drug encapsulation efficiency. The nanoparticles showed a size of ~110 nm as characterized by TEM and DLS. The nanoparticles were further characterized by optical UV–Visible and fluorescence spectroscopy. The encapsulated doxorubicin showed a sustained release (>80 %) from the nanoparticles matrix over a period of 8 days. The drug delivery efficiency of the nanoparticles was confirmed in vitro confocal imaging with PC3 and HeLa cell lines. In vitro quantitative estimation of drug accumulation in PC3 cell line showed a 22 times higher concentration of drug in case of nanoparticle-based formulation in comparison to free drug and this was further reflected in the in vitro cytotoxicity assays. Overall the synthesis method reported here provides a simple and robust PLGA-based platform for efficient drug delivery and imaging of cancer cells in vitro and in vivo.

Exact solutions are obtained for all the modes of wave propagation along an anisotropic cylindrical waveguide. Closed-form expressions for the energy flow on the waveguide are also derived. For extremely anisotropic waveguide where the transverse permittivity is negative while the longitudinal permittivity is positive, only transverse magnetic (TM) and hybrid modes will propagate on the waveguide. At any given frequency the waveguide supports an infinite number of eigenmodes. Among the TM modes, at most only one mode is forward wave. The rest of them are backward waves which can have very large effective index. At a critical radius, the waveguide supports degenerate forward- and backward-wave modes with zero group velocity. These waveguides can be used as phase shifters and filters, and as optical buffers to slow down and trap light., 11 pages, 15 figures, RevTex4

We show that with an appropriate surface modification, a slab of photonic crystal can be made to allow wave transmission within the band gap. Furthermore, negative refraction and all-angle-negative-refraction (AANR) can be achieved by this surface modification in frequency windows that were not realized before in two-dimensional photonic crystals [C. Luo et al, Phys. Rev. B 65, 201104 (2002)]. This approach to AANR leads to new applications in flat lens imaging. Previous flat lens using photonic crystals requires object-image distance u+v less than or equal to the lens thickness d, u+v d. Our approach can be used to design flat lens with u+v=sd with s>>1, thus being able to image large and/or far away objects. Our results are confirmed by FDTD simulations., 5 pages, 9 eps figs in RevTex format

We establish a duality between the quantum wave vector spectrum and the eigenmodes of the classical Liouvillian dynamics for integrable billiards. Signatures of the classical eigenmodes appear as peaks in the correlation function of the quantum wave vector spectrum. A semiclassical derivation and numerical calculations are presented in support of the results. These classical eigenmodes can be observed in physical experiments through the auto-correlation of the transmission coefficient of waves in quantum billiards. Exact classical trace formulas of the resolvent are derived for the rectangle, equilateral triangle, and circle billiards. We also establish a correspondence between the classical periodic orbit length spectrum and the quantum spectrum for integrable polygonal billiards., 12 pages, 4 figures

Remarkably slow propagation of microwaves in two different classes of left-handed materials (LHM's) is reported from microwave-pulse and continuous-wave transmission measurements. Microwave dispersion in a composite LHM made of split-ring resonators and wire strips reveals group velocity ${v}_{g}\ensuremath{\sim}c∕50$, where $c$ is the free-space light velocity. Photonic crystals (PhC's) made of dielectric ${\mathrm{Al}}_{2}{\mathrm{O}}_{3}$ rods reveal ${v}_{g}\ensuremath{\sim}c∕10$. Group delay dispersion of both the composite LHM and PhC's determined from the experiment is in complete agreement with that obtained from theory. The slow group velocities are quantitatively described by the strong dispersion observed in these materials.

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

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

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

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

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