852 resultados para RCE-PD (resonant-cavity-enhanced photodiode)


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We present models for the optical functions of 11 metals used as mirrors and contacts in optoelectronic and optical devices: noble metals (Ag, Au, Cu), aluminum, beryllium, and transition metals (Cr, Ni, Pd, Pt, Ti, W). We used two simple phenomenological models, the Lorentz-Drude (LD) and the Brendel-Bormann (BB), to interpret both the free-electron and the interband parts of the dielectric response of metals in a wide spectral range from 0.1 to 6 eV. Our results show that the BE model was needed to describe appropriately the interband absorption in noble metals, while for Al, Be, and the transition metals both models exhibit good agreement with the experimental data. A comparison with measurements on surface normal structures confirmed that the reflectance and the phase change on reflection from semiconductor-metal interfaces (including the case of metallic multilayers) can be accurately described by use of the proposed models for the optical functions of metallic films and the matrix method for multilayer calculations. (C) 1998 Optical Society of America.

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Multidimensional spatiotemporal parametric simultons (simultaneous solitary waves) are possible in a nonlinear chi((2)) medium with a Bragg grating structure, where large effective dispersion occurs near two resonant band gaps for the carrier and second-harmonic field, respectively. The enhanced dispersion allows much reduced interaction lengths, as compared to bulk medium parametric simultons. The nonlinear parametric band-gap medium permits higher-dimensional stationary waves to form. In addition, solitons can occur with lower input powers than conventional nonlinear Schrodinger equation gap solitons. In this paper, the equations for electromagnetic propagation in a grating structure with a parametric nonlinearity are derived from Maxwell's equation using a coupled mode Hamiltonian analysis in one, two, and three spatial dimensions. Simultaneous solitary wave solutions are proved to exist by reducing the equations to the coupled equations describing a nonlinear parametric waveguide, using the effective-mass approximation (EMA). Exact one-dimensional numerical solutions in agreement with the EMA solutions are also given. Direct numerical simulations show that the solutions have similar types of stability properties to the bulk case, providing the carrier waves are tuned to the two Bragg resonances, and the pulses have a width in frequency space less than the band gap. In summary, these equations describe a physically accessible localized nonlinear wave that is stable in up to 3 + 1 dimensions. Possible applications include photonic logic and switching devices. [S1063-651X(98)06109-1].

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We establish a connection between the simple harmonic oscillator and a two-level atom interacting with resonant, quantized cavity and strong driving fields, which suggests an experiment to measure the harmonic-oscillator's probability distribution function. To achieve this, we calculate the Autler-Townes spectrum by coupling the system to a third level. We find that there are two different regions of the atomic dynamics depending on the ratio of the: Rabi frequency Omega (c) of the cavity field to that of the Rabi frequency Omega of the driving field. For Omega (c)

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Abstract Part I : Background : Isolated lung perfusion (ILP) was designed for the treatment of loco-regional malignancies of the lung. In contrast to intravenous (IV) drug application, ILP allows for a selective administration of cytostatic agents such as doxorubicin to the lung while sparing non-affected tissues. However, the clinical results with ILP were disappointing. Doxorubicinbased ILP on sarcoma rodent lungs suggested high overall doxorubicin concentrations within the perfused lung but a poor penetration of the cytostatic agent into tumors. The same holds true for liposomal-encapsulated macromolecular doxorubicin (LiporubicinTM) In specific conditions, low-dose photodynamic therapy (PDT) can enhance the distribution of macromolecules across the endothelial bamer in solid tumors. It was recently postulated that tumor neovessels were more responsive to PDT than the normal vasculature. We therefore hypothesized that Visudyne®-mediated PDT could selectively increase liposomal doxorubicin (LiporubicinTM) uptake in sarcoma tumors to rodent lungs during intravenous (IV) drug administration and isolated lung perfusion (ILP). Material and Methods : A sarcoma tumor was generated in the left lung of Fisher rats by subpleural injection of a sarcoma cell ,suspension via thoracotomy. Ten days later, LiporubicinTM is administered IV or by single pass antegrade ILP, with or without Visudyne® -mediated low-dose PDT pre-treatment of the sarcoma bearing lung. The drug concentration and distribution were assessed separately in tumors and lung tissues by high pressure liquid chromatography (HPLC) and fluorescence microscopy (FNI~, respectively. Results : PDT pretreatment before IV LiporubicinTM administration resulted in a significantly higher tumor drug uptake and tumor to lung drug ratio compared to IV drug injection alone without affecting the blood flow and drug distribution in the lung. PDT pre-treatment before LiporubicinTM-based ILP also resulted in a higher tumor drug uptake and a higher tumor to lung drug ratio compared to ILP alone, however, these differences were not significant due to a heterogeneous blood flow drug distribution during ILP which was further accentuated by PDT. Conclusions : Low-dose Visudyne®-mediated PDT pre-treatment has the potential to selectively enhance liposomal encapsulated doxorubicin uptake in tumors but not in normal lung tissue after IV drug application in a rat model of sarcoma tumors to the lung which opens new perspectives for the treatment of superficially spreading chemoresistant tumors of the chest cavity such as mesothelioma or malignant effusion. However, the impact of PDT on macromolecular drug uptake during ILP is limited since its therapeutic advantage is circumvented by ILP-induced heterogeneicity of blood flow and drug distribution Abstract Part II Background : Photodynamic therapy (PDT) with Visudyne® acts by direct cellular phototoxicity and/or by an indirect vascular-mediated effect. Here, we demonstrate that the vessel integrity interruption by PDT can promote the extravasation of a macromolecular agent in normal tissue. To obtain extravasation in normal tissue PDT conditions were one order of magnitude more intensive than the ones in tissue containing neovessels reported in the literature. Material and Methods : Fluorescein isothiocyanate dextran (FITC-D, 2000kDa), a macromolecular agent, was intravenously injected 10 minutes before (LKO group, n=14) or 2 hours (LK2 group, n=16) after Visudyne® mediated PDT in nude mice bearing a dorsal skin fold chamber. Control animals had no PDT (CTRL group, n=8). The extravasation of FITC-D from blood vessels in striated muscle tissue was observed in both groups in real-time for up to 2500 seconds after injection. We also monitored PDT-induced leukocyte rolling in-vivo and assessed, by histology, the corresponding inflammatory reaction score in the dorsal skin fold chambers. Results : In all animals, at the applied PDT conditions, FITC-D extravasation was significantly enhanced in the PDT treated areas as compared to the surrounding non-treated areas (p<0.0001). There was no FITC-D leakage in the control animals. Animals from the LKO group had significantly less FITC-D extravasation than those from the LK2 group (p = 0.0002). In the LKO group FITC-D leakage correlated significantly with the inflammation (p < 0.001). Conclusions: At the selected conditions, Visudyne-mediated PDT promotes vascular leakage and FITC-D extravasation into the interstitial space of normal tissue. The intensity of vascular leakage depends on the time interval between PDT and FITC-D injection. This concept could be used to locally modulate the delivery of macromolecules in vivo. Résumé : La perfusion cytostatique isolée du poumon permet une administration sélective des agents cytostatiques sans implication de la circulation systémique avec une forte accumulation au niveau du poumon mais une faible pénétration dans les tumeurs. La thérapie photodynamique (PDT) qui consiste en l'application d'un sensibilisateur activé par lumière laser non- thermique d'une longueur d'onde définie permet dans certaines conditions, une augmentation de la pénétration des agents cytostatiques macromoléculaires à travers la barrière endothéliale tumorale. Nous avons exploré cet avantage thérapeutique de la PDT dans un modèle expérimental afin d'augmenter d'une manière sélective la pénétration tumorale de la doxorubicin pegylée, liposomal- encapsulée macromoléculaire (Liporubicin). Une tumeur sarcomateuse a été générée au niveau du poumon de rongeur suivie d'administration de Liporubicin, soit par voie intraveineuse soit par perfusion isolée du poumon (ILP). Une partie des animaux ont reçus un prétraitement de la tumeur et du poumon sous jacent par PDT avec Visudyne comme photosensibilisateur. Les résultats ont démontrés que la PDT permet, sous certaines conditions, une augmentation sélective de Liporubicin dans les tumeurs mais pas dans le parenchyme pulmonaire sous jacent. Après administration intraveineuse de Liporubicin et prétraitement par PDT, l'accumulation dans les tumeurs était significative par rapport au poumon, et aux tumeurs sans PDT. Le même phénomène est observé après ILP du poumon. Cependant, les différences avec ou sans PDT n'étaient pas significatives lié à und distribution hétérogène de Liporubicin dans le poumon perfusé après ILP. Dans une deuxième partie de l'expérimentation, nous avons exploré la microscopie intra-vitale pour déterminer l'extravasion des substances macromoléculaires (FITS) à travers la barrière endothéliale avec ou sans Visudyne-PDT au niveau des chambres dorsales des souris nues. Les résultats montrent qu'après PDT, l'extravasion de FITS a été augmentée de manière significative par rapport au tissu non traité. L'intensité de l'extravasion de FITS dépendait également de l'intervalle entre PDT et injection de FITS. En conclusion, les expérimentations montrent que la PDT est capable, sous certaines conditions, d'augmenter de manière significative l'extravasion des macromolécules à travers la barrière endothéliale et leur accumulation dans des tumeurs mais pas dans le parenchyme pulmonaire. Ces résultats permettent une nouvelle perspective de traitement pour des tumeurs superficielles intrathoraciques chimio-résistent comme l'épanchement pleural malin ou le mésothéliome pleural.

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Odds ratios for head and neck cancer increase with greater cigarette and alcohol use and lower body mass index (BMI; weight (kg)/height(2) (m(2))). Using data from the International Head and Neck Cancer Epidemiology Consortium, the authors conducted a formal analysis of BMI as a modifier of smoking- and alcohol-related effects. Analysis of never and current smokers included 6,333 cases, while analysis of never drinkers and consumers of < or =10 drinks/day included 8,452 cases. There were 8,000 or more controls, depending on the analysis. Odds ratios for all sites increased with lower BMI, greater smoking, and greater drinking. In polytomous regression, odds ratios for BMI (P = 0.65), smoking (P = 0.52), and drinking (P = 0.73) were homogeneous for oral cavity and pharyngeal cancers. Odds ratios for BMI and drinking were greater for oral cavity/pharyngeal cancer (P < 0.01), while smoking odds ratios were greater for laryngeal cancer (P < 0.01). Lower BMI enhanced smoking- and drinking-related odds ratios for oral cavity/pharyngeal cancer (P < 0.01), while BMI did not modify smoking and drinking odds ratios for laryngeal cancer. The increased odds ratios for all sites with low BMI may suggest related carcinogenic mechanisms; however, BMI modification of smoking and drinking odds ratios for cancer of the oral cavity/pharynx but not larynx cancer suggests additional factors specific to oral cavity/pharynx cancer.

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PURPOSE: To determine whether syngeneic retinal cells injected in the vitreous cavity of the rat are able to initiate a proliferative process and whether the ocular inflammation induced in rats by lipopolysaccharide (LPS) promotes this proliferative vitreoretinopathy (PVR). METHODS: Primary cultured differentiated retinal Müller glial (RMG) and retinal pigmented epithelial (RPE) cells isolated from 8 to 12 postnatal Lewis rats were injected into the vitreous cavity of 8- to 10-week-old Lewis rats (10(5) cells/eye in 2 microlieter sterile saline), with or without the systemic injection of 150 microgram LPS to cause endotoxin-induced uveitis (EIU). Control groups received an intravitreal injection of 2 microliter saline. At 5, 15, and 28 days after cell injections, PVR was clinically quantified, and immunohistochemistry for OX42, ED1, vimentin (VIM), glial fibrillary acidic protein (GFAP), and cytokeratin was performed. RESULTS: The injection of RMG cells, alone or in combination with RPE cells, induced the preretinal proliferation of a GFAP-positive tissue, that was enhanced by the systemic injection of LPS. Indeed, when EIU was induced at the time of RMG cell injection into the vitreous cavity, the proliferation led to retinal folds and localized tractional detachments. In contrast, PVR enhanced the infiltration of inflammatory cells in the anterior segment of the eye. CONCLUSIONS: In the rat, syngeneic retinal cells of glial origin induce PVR that is enhanced by the coinduction of EIU. In return, vitreoretinal glial proliferation enhanced the intensity and duration of EIU.

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The paradoxical coexistence of spontaneous tumor antigen-specific immune responses with progressive disease in cancer patients furthers the need to dissect the molecular pathways involved in tumor-induced T cell dysfunction. In patients with advanced melanoma, we have previously shown that the cancer-germline antigen NY-ESO-1 stimulates spontaneous NY-ESO-1-specific CD8(+) T cells that up-regulate PD-1 expression. We also observed that PD-1 regulates NY-ESO-1-specific CD8(+) T cell expansion upon chronic antigen stimulation. In the present study, we show that a fraction of PD-1(+) NY-ESO-1-specific CD8(+) T cells in patients with advanced melanoma up-regulates Tim-3 expression and that Tim-3(+)PD-1(+) NY-ESO-1-specific CD8(+) T cells are more dysfunctional than Tim-3(-)PD-1(+) and Tim-3(-)PD-1(-) NY-ESO-1-specific CD8(+) T cells, producing less IFN-γ, TNF, and IL-2. Tim-3-Tim-3L blockade enhanced cytokine production by NY-ESO-1-specific CD8(+) T cells upon short ex vivo stimulation with cognate peptide, thus enhancing their functional capacity. In addition, Tim-3-Tim-3L blockade enhanced cytokine production and proliferation of NY-ESO-1-specific CD8(+) T cells upon prolonged antigen stimulation and acted in synergy with PD-1-PD-L1 blockade. Collectively, our findings support the use of Tim-3-Tim-3L blockade together with PD-1-PD-L1 blockade to reverse tumor-induced T cell exhaustion/dysfunction in patients with advanced melanoma.

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We present analytical calculations of the turn-on-time probability distribution of intensity-modulated lasers under resonant weak optical feedback. Under resonant conditions, the external cavity round-trip time is taken to be equal to the modulation period. The probability distribution of the solitary laser results are modified to give reduced values of the mean turn-on-time and its variance. Numerical simulations have been carried out showing good agreement with the analytical results.

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Although melanoma vaccines stimulate tumor antigen-specific CD8(+) T cells, objective clinical responses are rarely observed. To investigate this discrepancy, we evaluated the character of vaccine-induced CD8(+) T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. The vaccines included incomplete Freund's adjuvant, CpG oligodeoxynucleotide (CpG), and the HLA-A2-restricted analog peptide NY-ESO-1 157-165V, either by itself or in combination with the pan-DR epitope NY-ESO-1 119-143. Both vaccines stimulated rapid tumor antigen-specific CD8(+) T-cell responses detected ex vivo, however, tumor antigen-specific CD8(+) T cells produced more IFN-γ and exhibited higher lytic function upon immunization with MHC class I and class II epitopes. Notably, the vast majority of vaccine-induced CD8(+) T cells upregulated PD-1 and a minority also upregulated Tim-3. Levels of PD-1 and Tim-3 expression by vaccine-induced CD8(+) T cells at the time of vaccine administration correlated inversely with their expansion in vivo. Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8(+) T cells in vitro. Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma.

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Cytotoxic T cells that are present in tumors and capable of recognizing tumor epitopes are nevertheless generally impotent in eliciting tumor rejection. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8(+) T-cell dysfunction may reveal effective strategies for immune therapy. The inhibitory receptors PD-1 and Tim-3 are known to negatively regulate CD8(+) T-cell responses directed against the well-characterized tumor antigen NY-ESO-1. Here, we report that the upregulation of the inhibitory molecule BTLA also plays a critical role in restricting NY-ESO-1-specific CD8(+) T-cell expansion and function in melanoma. BTLA-expressing PD-1(+)Tim-3(-) CD8(+) T cells represented the largest subset of NY-ESO-1-specific CD8(+) T cells in patients with melanoma. These cells were partially dysfunctional, producing less IFN-γ than BTLA(-) T cells but more IFN-γ, TNF, and interleukin-2 than the highly dysfunctional subset expressing all three receptors. Expression of BTLA did not increase with higher T-cell dysfunction or upon cognate antigen stimulation, as it does with PD-1, suggesting that BTLA upregulation occurs independently of functional exhaustion driven by high antigen load. Added with PD-1 and Tim-3 blockades, BTLA blockade enhanced the expansion, proliferation, and cytokine production of NY-ESO-1-specific CD8(+) T cells. Collectively, our findings indicate that targeting BTLA along with the PD-1 and Tim-3 pathways is critical to reverse an important mechanism of immune escape in patients with advanced melanoma.

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Nanoantennae show potential for photosynthesis research for two reasons; first by spatially confining light for experiments which require high spatial resolution, and second by enhancing the photon emission of single light-harvesting complexes. For effective use of nanoantennae a detailed understanding of the interaction between the nanoantenna and the light-harvesting complex is required. Here we report how the excitation and emission of multiple purple bacterial LH2s (light-harvesting complex 2) are controlled by single gold nanorod antennae. LH2 complexes were chemically attached to such antennae, and the antenna length was systematically varied to tune the resonance with respect to the LH2 absorption and emission. There are three main findings. (i) The polarization of the LH2 emission is fully controlled by the resonant nanoantenna. (ii) The largest fluorescence enhancement, of 23 times, is reached for excitation with light at λ = 850 nm, polarized along the long antenna-axis of the resonant antenna. The excitation enhancement is found to be 6 times, while the emission efficiency is increased 3.6 times. (iii) The fluorescence lifetime of LH2 depends strongly on the antenna length, with shortest lifetimes of [similar]40 ps for the resonant antenna. The lifetime shortening arises from an 11 times resonant enhancement of the radiative rate, together with a 2–3 times increase of the non-radiative rate, compared to the off-resonant antenna. The observed length dependence of radiative and non-radiative rate enhancement is in good agreement with simulations. Overall this work gives a complete picture of how the excitation and emission of multi-pigment light-harvesting complexes are influenced by a dipole nanoantenna.

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In this study, cantilever-enhanced photoacoustic spectroscopy (CEPAS) was applied in different drug detection schemes. The study was divided into two different applications: trace detection of vaporized drugs and drug precursors in the gas-phase, and detection of cocaine abuse in hair. The main focus, however, was the study of hair samples. In the gas-phase, methyl benzoate, a hydrolysis product of cocaine hydrochloride, and benzyl methyl ketone (BMK), a precursor of amphetamine and methamphetamine were investigated. In the solid-phase, hair samples from cocaine overdose patients were measured and compared to a drug-free reference group. As hair consists mostly of long fibrous proteins generally called keratin, proteins from fingernails and saliva were also studied for comparison. Different measurement setups were applied in this study. Gas measurements were carried out using quantum cascade lasers (QLC) as a source in the photoacoustic detection. Also, an external cavity (EC) design was used for a broader tuning range. Detection limits of 3.4 particles per billion (ppb) for methyl benzoate and 26 ppb for BMK in 0.9 s were achieved with the EC-QCL PAS setup. The achieved detection limits are sufficient for realistic drug detection applications. The measurements from drug overdose patients were carried out using Fourier transform infrared (FTIR) PAS. The drug-containing hair samples and drug-free samples were both measured with the FTIR-PAS setup, and the measured spectra were analyzed statistically with principal component analysis (PCA). The two groups were separated by their spectra with PCA and proper spectral pre-processing. To improve the method, ECQCL measurements of the hair samples, and studies using photoacoustic microsampling techniques, were performed. High quality, high-resolution spectra with a broad tuning range were recorded from a single hair fiber. This broad tuning range of an EC-QCL has not previously been used in the photoacoustic spectroscopy of solids. However, no drug detection studies were performed with the EC-QCL solid-phase setup.

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La sclérose en plaques (SEP) est une maladie inflammatoire démyélinisante et neurodégénérative du système nerveux central (SNC). Les cellules T activées qui expriment le PD-1 sont inhibées via l’interaction avec l’un des ligands: PD-L1 ou PD-L2. Des études effectuées chez le modèle murin de la SEP, l’encéphalomyélite auto-immune expérimentale (EAE), ont démontré que l’interaction du PD-1 avec ses ligands contribue à atténuer la maladie. Toutefois, le rôle du PD-1 et de ses ligands dans la pathogenèse de la SEP chez l’humain et dans le modèle murin n’a pas été complètement élucidé. Nous avons déterminé que plusieurs cellules du SNC humain peuvent exprimer les ligands du PD-1. Les astrocytes, les microglies, les oligodendrocytes et les neurones expriment faiblement le PD-L1 dans des conditions basales mais augmentent de façon significative cette expression en réponse à des cytokines inflammatoires. Le blocage de l’expression du PD-L1 par les astrocytes à l’aide de siRNA spécifiques mène à l’augmentation significative des réponses des cellules T CD8+ (prolifération, cytokines, enzymes lytiques). Nos résultats établissent ainsi que les cellules gliales humaines peuvent exprimer des niveaux suffisants de PD-L1 en milieu inflammatoire pour inhiber les réponses des cellules T CD8+. Notre analyse de tissus cérébraux post-mortem par immunohistochimie démontre que dans les lésions de la SEP les niveaux de PD-L1 sont significativement plus élevés que dans les tissus de témoins; les astrocytes et les microglies/macrophages expriment le PD-L1. Cependant, plus de la moitié des lymphocytes T CD8+ ayant infiltré des lésions de SEP n’expriment pas le récepteur PD-1. Au cours du développement de l’EAE, les cellules du SNC augmentent leur niveau de PD-L1. Le PD-1 est fortement exprimé par les cellules T dès le début des symptômes, mais son intensité diminue au cours de la maladie, rendant les cellules T insensibles au signal inhibiteur envoyé par le PD-L1. Nous avons observé que les cellules endothéliales humaines formant la barrière hémato-encéphalique (BHE) expriment de façon constitutive le PD-L2 mais pas le PD-L1 et que l’expression des deux ligands augmente dans des conditions inflammatoires. Les ligands PD-L1 et PD-L2 exprimés par les cellules endothéliales ont la capacité de freiner l’activation des cellules T CD8+ et CD4+, ainsi que leur migration à travers la BHE. L’endothélium du cerveau des tissus normaux et des lésions SEP n’exprime pas des taux détectables de PD-L1. En revanche, tous les vaisseaux sanguins des tissus de cerveaux normaux sont positifs pour le PD-L2, alors que seulement la moitié de ceux-ci expriment le PD-L2 dans des lésions SEP. Nos travaux démontrent que l’entrée des cellules T activées est contrôlée dans des conditions physiologiques grâce à la présence du PD-L2 sur la BHE. Cependant, l’expression plus faible du PD-L2 sur une partie des vaisseaux sanguins dans les lésions SEP nuit au contrôle de la migration des cellules immunes. De plus, une fois dans le SNC, les cellules T CD8+ étant dépourvues du PD-1 ne peuvent recevoir le signal inhibiteur fourni par le PD-L1 fortement exprimé par les cellules du SNC, leur permettant ainsi de rester activées.

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A novel technique fitr the bat dividth enhancement of conventional rectangular microstrip antenna is proposed in this paper. When a high permittivity dielectric resonator of suitable resonant frequency was loaded over the patch. the % bandwidth of the antenna was increased by more than five tunes without much affecting its gain and radiation performance. A much more improved bandwidth was obtained when the dielectric resonator was placed on the feedline. Experimental study shows a 2:1 VSWR bandwidth of more than 10% and excellent cross polarization performance with increased pass band and radiation coverage abnost the same as that of rectangular microstrip antenna