342 research outputs found

    Characteristic Basis Function Method for Solving Electromagnetic Scattering Problems over Rough Terrain Profiles

    Get PDF
    Cataloged from PDF version of article.A computationally efficient algorithm, which combines the characteristic basis function method (CBFM), the physical optics (PO) approach (when applicable) with the forward backward method (FBM), is applied for the investigation of electromagnetic scattering from—and propagation over—large-scale rough terrain problems. The algorithm utilizes high-level basis functions defined on macro-domains (blocks), called the characteristic basis functions (CBFs) that are constructed by aggregating low-level basis functions (i.e., conventional sub-domain basis functions). The FBM as well as the PO approach (when applicable) are used to construct the aforementioned CBFs. The conventional CBFM is slightly modified to handle large-terrain problems, and is further embellished by accelerating it, as well as reducing its storage requirements, via the use of an extrapolation procedure. Numerical results for the total fields, as well as for the path loss are presented and compared with either measured or previously published reference solutions to assess the efficiency and accuracy of the algorithm

    Prognosis of operable squamous cell carcinoma of the esophagus. Relationship with clinicopathologic features and DNA ploidy

    Get PDF
    Background: Reports on the influence of various prognostic factors in carcinoma of the esophagus are conflicting. The prognostic value of a set of clinicopathologic factors and DNA ploidy were examined in 74 patients with surgically resected squamous cell carcinoma of the lower and middle third of the esophagus. Methods: All patients had surgery performed in a single thoracic surgical unit at the Tata Memorial Hospital between January, 1984 and December, 1987. The clinicopathologic factors studied were (1) gross residual disease at operation; (2) morphology of the tumor; (3) depth of microscopic invasion; (4) lymph node involvement; (5) histologic grade; (6) vascular and lymphatic embolism; and (7) sex. DNA ploidy and S-phase fraction (SpF) were determined by flow cytometry on archival tissues extracted from paraffin blocks. Ploidy status could be determined successfully in all 74 tumors, whereas SpF could be assessed only in 25. Results: Of the various prognostic factors examined with the Cox stepwise regression model, residual disease (P = 0.000), depth of invasion (P = 0.047), and lymph node status (P = 0.077) were found to be correlated with overall survival. Conclusions: DNA ploidy was not related to prognosis. The overall survival of this group of patients at 36 months was 28%, and median survival was 18 months

    Brightness of a phase-conjugating mirror behind a random medium

    Get PDF
    A random-matrix theory is presented for the reflection of light by a disordered medium backed by a phase-conjugating mirror. Two regimes are distinguished, depending on the relative magnitude of the inverse dwell time of a photon in the disordered medium and the frequency shift acquired at the mirror. The qualitatively different dependence of the reflectance on the degree of disorder in the two regimes suggests a distinctive experimental test for cancellation of phase shifts in a random medium.Comment: 4 pages LaTeX. 2 Postscript figures include

    Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus

    Get PDF
    Introduction: Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (hNIS) cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153. Methods: GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET) utilizing carrier-free (124)I radiotracer. Results: GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of hNIS expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P < 0.001). In vivo, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P < 0.001). Finally, intratumoral injection of GLV-1h153 facilitated imaging of virus replication in tumors via (124)I-PET. Conclusion: Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy

    Reflection of light from a disordered medium backed by a phase-conjugating mirror

    Get PDF
    This is a theoretical study of the interplay of optical phase-conjugation and multiple scattering. We calculate the intensity of light reflected by a phase-conjugating mirror when it is placed behind a disordered medium. We compare the results of a fully phase-coherent theory with those from the theory of radiative transfer. Both methods are equivalent if the dwell time \tau_{dwell} of a photon in the disordered medium is much larger than the inverse of the frequency shift 2\Delta\omega acquired at the phase-conjugating mirror. When \tau_{dwell} \Delta\omega < 1, in contrast, phase coherence drastically affects the reflected intensity. In particular, a minimum in the dependence of the reflectance on the disorder strength disappears when \Delta\omega is reduced below 1/\tau_{dwell}. The analogies and differences with Andreev reflection of electrons at the interface between a normal metal and a superconductor are discussed.Comment: 27 pages RevTeX with 11 figures included with psfi

    Restoring tumour selectivity of the bioreductive prodrug pr-104 by developing an analogue resistant to aerobic metabolism by human aldo-keto reductase 1c3

    Get PDF
    PR-104 is a phosphate ester pre-prodrug that is converted in vivo to its cognate alcohol, PR-104A, a latent alkylator which forms potent cytotoxins upon bioreduction. Hypoxia selectivity results from one-electron nitro reduction of PR-104A, in which cytochrome P450 oxidoreductase (POR) plays an important role. However, PR-104A also undergoes ‘off-target’ two-electron reduction by human aldo-keto reductase 1C3 (AKR1C3), resulting in activation in oxygenated tissues. AKR1C3 expression in human myeloid progenitor cells probably accounts for the dose-limiting myelotoxicity of PR-104 documented in clinical trials, resulting in human PR-104A plasma exposure levels 3.4- to 9.6-fold lower than can be achieved in murine models. Structure-based design to eliminate AKR1C3 activation thus represents a strategy for restoring the therapeutic window of this class of agent in humans. Here, we identified SN29176, a PR-104A analogue resistant to human AKR1C3 activation. SN29176 retains hypoxia selectivity in vitro with aerobic/hypoxic IC(50) ratios of 9 to 145, remains a substrate for POR and triggers γH2AX induction and cell cycle arrest in a comparable manner to PR-104A. SN35141, the soluble phosphate pre-prodrug of SN29176, exhibited superior hypoxic tumour log cell kill (>4.0) to PR-104 (2.5–3.7) in vivo at doses predicted to be achievable in humans. Orthologues of human AKR1C3 from mouse, rat and dog were incapable of reducing PR-104A, thus identifying an underlying cause for the discrepancy in PR-104 tolerance in pre-clinical models versus humans. In contrast, the macaque AKR1C3 gene orthologue was able to metabolise PR-104A, indicating that this species may be suitable for evaluating the toxicokinetics of PR-104 analogues for clinical development. We confirmed that SN29176 was not a substrate for AKR1C3 orthologues across all four pre-clinical species, demonstrating that this prodrug analogue class is suitable for further development. Based on these findings, a prodrug candidate was subsequently identified for clinical trials
    corecore