105 research outputs found

    Interaction of REPS2 with NF-kappaB in Prostate Cancer Cells

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    Like normal prostate cells, prostate cancer cells are dependent on androgens for growth and survival, and prostate cancer can be treated by androgen ablation therapy. However, after a period of time some of the prostate cancer cells no longer respond to androgen ablation and survive the therapy. This transition of androgen-dependent prostate cancer (ADPC) to androgen-independent prostate cancer (AIPC) is critical, since no effective therapy is available for the androgen-independent stage of the disease. The molecular mechanisms that underlie the transition are largely unknown. REPS2, the protein that is studied in this PhD thesis project, might be involved in a molecular mechanism that contributes to AIPC development, since REPS2 mRNA is downregulated in AIPC compared to ADPC. With specific antibodies it was shown that the REPS2 protein level in AIPC is decreased compared to ADPC. Transient overexpression of REPS2 in prostate cancer cell lines induced apoptosis within 48 h, which indicates that REPS2 may play a role in the life-death balance of the cell. To elucidate cellular functions of REPS2, proteins were identified that bind REPS2. A large fragment of the NF-κB subunit p65 (RELA) was found to bind REPS2. This protein p65 is inactive in ADPC but active in AIPC, and might cause cell survival through inhibition of apoptotic cell death. Two other protein sequences that were found to bind REPS2 represent parts of TRAF4 and STAT6. Interestingly, these two proteins, like p65, are implicated in control of some aspects of the NF-κB pathway. Taken together, the results point to a putative inhibitory effect of REPS2 on NF-kB signalling and prostate cancer cell survival

    Highly confined electromagnetic fields in arrays of strongly coupled Ag nanoparticles

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    Linear arrays of very small Ag nanoparticles (diameter ~10 nm, spacing 0–4 nm) were fabricated in sodalime glass using an ion irradiation technique. Optical extinction spectroscopy of the arrays reveals a large polarization-dependent splitting of the collective plasmon extinction band. Depending on the preparation condition, a redshift of the longitudinal resonance as large as 1.5 eV is observed. Simulations of the three-dimensional electromagnetic field evolution are used to determine the resonance energy of idealized nanoparticle arrays with different interparticle spacings and array lengths. Using these data, the experimentally observed redshift is attributed to collective plasmon coupling in touching particles and/or in long arrays of strongly coupled particles. The simulations also indicate that for closely coupled nanoparticles (1–2 nm spacing) the electromagnetic field is concentrated in nanoscale regions (10 dB radius: 3 nm) between the particles, with a 5000-fold local field intensity enhancement. In arrays of 1-nm-spaced particles the dipolar particle interaction extends to over 10 particles, while for larger spacing the interaction length decreases. Spatial images of the local field distribution in 12-particle arrays of touching particles reveal a particlelike coupled mode with a resonance at 1.8 eV and a wirelike mode at 0.4 eV

    Nine years of plan of the day for cervical cancer:Plan library remains effective compared to fully online-adaptive techniques

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    Background and purpose: Since 2011, our center has been using a library-based Plan-of-the-Day (PotD) strategy for external beam radiotherapy of cervical cancer patients to reduce normal tissue dose while maintaining adequate target coverage. With the advent of fully online-adaptive techniques such as daily online-adaptive replanning, further dose reduction may be possible. However, it is unknown how this reduction relates to plan library approaches, and how the most recent PotD strategies relate to no adaptation. In this study we compare the performance of our current PotD strategy with non-adaptive and fully online-adaptive techniques in terms of target volume size and normal tissue sparing. Materials and methods: Treatment data of 376 patients treated with the PotD protocol between June 2011 and April 2020 were included. The size of the Planning Target Volumes (PTVs) was reconstructed for different strategies: full online adaptation, no adaptation, and the latest clinical version of the PotD protocol. Normal tissue sparing was estimated by the difference in margin volume to construct the PTV and the volume overlap of the PTV with bladder and rectum. Results: The current version of our PotD approach reduced the PTV margin volume by a median of 250 cm3 compared to no adaptation. Bladder-PTV overlap decreased from a median of 142 to 71 cm3, and from 39 to 16 cm3 for rectum-PTV. Fully online-adaptive approaches could further decrease the PTV volume by 144 cm3 using a 5 mm margin for residual errors. In this scenario, bladder-PTV overlap was reduced to 35 cm3 and rectum-PTV overlap to 11 cm3. Conclusion: The current version of the PotD protocol is an effective technique to improve normal tissue sparing compared to no adaptation. Further sparing can be achieved using fully online-adaptive techniques, but at the cost of a more complex workflow and with a potentially limited impact. PotD-type protocols can therefore be considered as a suitable alternative to fully online-adaptive approaches.</p

    Mega-electron-volt ion beam induced anisotropic plasmon resonance of silver nanocrystals in glass

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    30 MeV Si ion beam irradiation of silica glass containing Ag nanocrystals causes alignment of Ag nanocrystals in arrays along the ion tracks. Optical transmission measurements show a large splitting of the surface plasmon resonance bands for polarizations longitudinal and transversal to the arrays. The splitting is in qualitative agreement with a model for near-field electromagnetic plasmon coupling within the arrays. Resonance shifts as large as 1.5 eV are observed, well into the near-infrared.

    Optical response of metal nanoparticle chains

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    We study the optical responses of metal nanoparticle chains. Multiple scattering calculations are used to study the extinction cross sections of silver nanosphere chains of finite length embedded in a glass matrix. The transmission and reflection coefficients of periodic 2D arrays of silver nanospheres are also calculated to understand the interaction between nanoparticle chains. The results are in agreement with recent experiments. The splitting of plasmon-resonance modes for different polarizations of the incident light are explored. Results on the effect of disorder are also presented.Comment: 9 pages, 10 figure

    Gradient Optics of subwavelength nanofilms

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    Propagation and tunneling of light through subwavelength photonic barriers, formed by dielectric layers with continuous spatial variations of dielectric susceptibility across the film are considered. Effects of giant heterogeneity-induced non-local dispersion, both normal and anomalous, are examined by means of a series of exact analytical solutions of Maxwell equations for gradient media. Generalized Fresnel formulae, visualizing a profound influence of gradient and curvature of dielectric susceptibility profiles on reflectance/transmittance of periodical photonic heterostructures are presented. Depending on the cutoff frequency of the barrier, governed by technologically managed spatial profile of its refractive index, propagation or tunneling of light through these barriers are examined. Nonattenuative transfer of EM energy by evanescent waves, tunneling through dielectric gradient barriers, characterized by real values of refractive index, decreasing in the depth of medium, is shown. Scaling of the obtained results for different spectral ranges of visible, IR and THz waves is illustrated. Potential of gradient optical structures for design of miniaturized filters, polarizers and frequency-selective interfaces of subwavelength thickness is considered
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