First use of silicon carbide detectors with graphene-enhanced contacts for medical dosimetry.

Silicon Carbide (SiC) is a radiation hard wide bandgap semiconductor, which makes it an interesting alternative for radiation detector fabrication, with potential applications such as High Energy Physics, synchrotron and radiotherapy instrumentation. In addition, by reducing the amount of metal over the active area of said detectors (typically used for electrical connectivity with the implant of the pn-junction) unwanted effects from secondary interactions which can affect the accuracy of the measurement can be diminished, essential to meet the medical standards of precision. In this article, the use of epitaxially-grown graphene is explored as an alternative to metallic contacts with these prototypes. To this end, the first prototypes of SiC diodes with epitaxial graphene contacts were produced at IMB-CNM for radiation detection,along with reference devices. In order to characterise the feasibility of the technology in the medical application, the dose rate linearity of the SiC device with graphene was measured in a radiotherapy Linac in the dose rate range of 1-6 Gy/min. The response of the device was compared to that observed on devices with similar geometries reported elsewhere. To fully characterise the devices, the same exercise was repeated in a laboratory X-ray tube. Under the later set-up, the prototype is compared against a device with a fully metallised active region.

First experimental measurements of 2D microdosimetry maps in proton therapy.

BACKGROUND: Empirical data in proton therapy indicate that relative biological effectiveness (RBE) is not constant, and it is directly related to the linear energy transfer (LET). The experimental assessment of LET with high resolution would be a powerful tool for minimizing the LET hot spots in intensity-modulated proton therapy, RBE- or LET-guided evaluation and optimization to achieve biologically optimized proton plans, verifying the theoretical predictions of variable proton RBE models, and so on. This could impact clinical outcomes by reducing toxicities in organs at risk. PURPOSE: The present work shows the first 2D LET maps obtained at a proton therapy facility using the double scattering delivery mode in clinical conditions by means of new silicon 3D-cylindrical microdetectors. METHODS: The device consists of a matrix of 121 independent silicon-based detectors that have 3D-cylindrical electrodes of 25-µm diameter and 20-µm depth, resulting each one of them in a well-defined micrometric radiation sensitive volume etched inside the silicon. They have been specifically designed for a hadron therapy, improving the performance of current silicon-based microdosimeters. Microdosimetry spectra were obtained at different positions of the Bragg curve by using a water-equivalent phantom along an 89-MeV pristine proton beam generated in the Y1 proton passive scattering beamline of the Orsay Proton Therapy Centre (Institut Curie, France). RESULTS: Microdosimetry 2D-maps showing the variation of the lineal energy with depth in the three dimensions were obtained in situ during irradiation at clinical fluence rates (∼108  s-1  cm-2 ) for the first time with a spatial resolution of 200 µm, the highest achieved in the transverse plane so far. The experimental results were cross-checked with Monte Carlo simulations and a good agreement between the spectra shapes was found. The experimental frequency-mean lineal energy values in silicon were 1.858 ± 0.019 keV µm-1 at the entrance, 2.61 ± 0.03 keV µm-1 at the proximal distance, 4.97 ± 0.05 keV µm-1 close to the Bragg peak, and 8.6 ± 0.1 keV µm-1 at the distal edge. They are in good agreement with the expected trends in the literature in clinical proton beams. CONCLUSIONS: We present the first 2D microdosimetry maps obtained in situ during irradiation at clinical fluence rates in proton therapy. Our results show that the arrays of 3D-cylindrical microdetectors are a reliable microdosimeter to evaluate LET maps not only in the longitudinal axis of the beam, but also in the transverse plane allowing for LET characterization in three dimensions. This work is a proof of principle showing the capacity of our system to deliver LET 2D maps. This kind of experimental data is needed to validate variable proton RBE models and to optimize LET-guided plans.

Colorimetric Detection of SARS-CoV-2 Using Plasmonic Biosensors and Smartphones.

Low-cost, instrument-free colorimetric tests were developed to detect SARS-CoV-2 using plasmonic biosensors with Au nanoparticles functionalized with polyclonal antibodies (f-AuNPs). Intense color changes were noted with the naked eye owing to plasmon coupling when f-AuNPs form clusters on the virus, with high sensitivity and a detection limit of 0.28 PFU mL-1 (PFU stands for plaque-forming units) in human saliva. Plasmon coupling was corroborated with computer simulations using the finite-difference time-domain (FDTD) method. The strategies based on preparing plasmonic biosensors with f-AuNPs are robust to permit SARS-CoV-2 detection via dynamic light scattering and UV-vis spectroscopy without interference from other viruses, such as influenza and dengue viruses. The diagnosis was made with a smartphone app after processing the images collected from the smartphone camera, measuring the concentration of SARS-CoV-2. Both image processing and machine learning algorithms were found to provide COVID-19 diagnosis with 100% accuracy for saliva samples. In subsidiary experiments, we observed that the biosensor could be used to detect the virus in river waters without pretreatment. With fast responses and requiring small sample amounts (only 20 µL), these colorimetric tests can be deployed in any location within the point-of-care diagnosis paradigm for epidemiological control.

Numerical modeling of air-vented parallel plate ionization chambers for ultra-high dose rate applications.

PURPOSE: Air-vented ionization chambers have been the secondary standard for radiation dosimetry since the origins of radiation metrology. However, the feasibility of their use in ultra-high dose rate pulsed beams has been a matter of discussion, as large losses are caused by ion recombinations and no suitable theoretical model is available for their correction. The theories developed by Boag and his contemporaries since the 1950s, which have provided the standard ion recombination correction factor in clinical dosimetry, do not provide an accurate description when used under the limit conditions of ultra-high dose rates (UHDRs). Moreover, the high-ion recombination effects of ionization chambers under extreme dose-rate applications are an obstacle to the development of adequate dosimetry standards. METHODS: In this article, the charge carrier transport equations within a parallel plate ionization chamber (PPIC) have been solved numerically with a double aim. First, this numerical model provides a more accurate tool that can be used to evaluate ion recombination correction for established PPICs in pulsed ultra-high dose rate regimes. Second, studying the chamber behavior in detail allow as to explore the limits of new chamber designs in order to improve their performance under UHDRs. The model presented here has been tested by measuring the instantaneous current of one unit of a Roos chamber (i.e., the time-resolved current during and after the irradiation pulse under UHDR conditions) and comparing these results with the absolute value of the simulated current. RESULTS: The experimental data show consistent agreement with the results obtained using the numerical model. The experimental instantaneous current reveals effects such as the variation of the free electron fraction with the dose per pulse that are supported by the numerical model but cannot be explained in the framework of Boag's theory. CONCLUSIONS: Numerical solutions of the charge carrier released and transport in ionization chambers are able to estimate the effects observed when PPICs are irradiated with ultra-high dose rate beams and to provide new insight into processes related to recombination losses at UHDRs. These models can be reliably extended to include regions where current analytical solutions are not valid. An agreement of better than 5 % between the experimental and simulated effective free electron fraction is found. We were able to reproduce the instantaneous current from a Roos chamber. The discrepancies observed between the experimental data and the numerical simulations can be attributed to the uncertainty about the transport parameters involved in the calculation.

Bulk Plasmon Polariton Modes in Hyperbolic Metamaterials for Giant Enhancement of the Transverse Magneto-Optical Kerr Effect.

We demonstrate a concept for the giant enhancement of the transverse magneto-optical Kerr effect (TMOKE) using bulk plasmon polariton (BPP) modes in non-magnetic multilayer hyperbolic metamaterials (HMMs). Since the BPP modes are excited through the attenuated total reflection (ATR) mechanism, using a Si-based prism-coupler, we considered a single dielectric magneto-optical (MO) spacer between the prism and the HMM. The working wavelength was estimated, using the effective medium approach for a semi-infinite dielectric-plasmonic multilayer, considering the region where the system exhibits type II HMM dispersion relations. Analytical results, by means of the scattering matrix method (SMM), were used to explain the physical principle behind our concept. Numerical results for giant TMOKE values (close to their maximum theoretical values, ±1) were obtained using the finite element method (FEM), applying the commercial software COMSOL Multiphysics. Our proposal comprises a simple and experimentally feasible structure that enables the study of MO phenomena in HMMs, which may find application in future nanostructured magnetoplasmonic metamaterials for active nanophotonic devices.

Microdosimetry performance of the first multi-arrays of 3D-cylindrical microdetectors.

The present work reports on the microdosimetry measurements performed with the two first multi-arrays of microdosimeters with the highest radiation sensitive surface covered so far. The sensors are based on new silicon-based radiation detectors with a novel 3D cylindrical architecture. Each system consists of arrays of independent microdetectors covering 2 mm[Formula: see text]2 mm and 0.4 mm[Formula: see text]12 cm radiation sensitive areas, the sensor distributions are arranged in layouts of 11[Formula: see text]11 microdetectors and 3[Formula: see text]3 multi-arrays, respectively. We have performed proton irradiations at several energies to compare the microdosimetry performance of the two systems, which have different spatial resolution and detection surface. The unitcell of both arrays is a 3D cylindrical diode with a 25 [Formula: see text]m diameter and a 20 [Formula: see text]m depth that results in a welldefined and isolated radiation sensitive micro-volume etched inside a silicon wafer. Measurements were carried out at the Accélérateur Linéaire et Tandem à Orsay (ALTO) facility by irradiating the two detection systems with monoenergetic proton beams from 6 to 20 MeV at clinical-equivalent fluence rates. The microdosimetry quantities were obtained with a spatial resolution of 200 [Formula: see text]m and 600 [Formula: see text]m for the 11[Formula: see text]11 system and for the 3[Formula: see text]3 multi-array system, respectively. Experimental results were compared with Monte Carlo simulations and an overall good agreement was found. The good performance of both microdetector arrays demonstrates that this architecture and both configurations can be used clinically as microdosimeters for measuring the lineal energy distributions and, thus, for RBE optimization of hadron therapy treatments. Likewise, the results have shown that the devices can be also employed as a multipurpose device for beam monitoring in particle accelerators.

Small static radiosurgery field dosimetry with small volume ionization chambers.

PURPOSE: To evaluate the response of the four smallest active volume thimble type ionization chambers commercially available (IBA-dosimetry RAZOR Nano Chamber, Standard Imaging Exradin A16, IBA-dosimetry CC01 and PTW T31022) when measuring SRS cone collimated Flattening Filter Free (FFF) fields. METHODS: We employed Monte Carlo simulation for calculating correction factors as defined in IAEA TRS-483. Monte Carlo simulation beam model and ion chamber geometry definitions were supported by an extensive set of measurements. Type A and B uncertainty components were evaluated. RESULTS: Commissioning of Monte Carlo 6 MV and 10 MV FFF beam models yielded relative differences between measured and simulated dose distributions lower than 1.5%. Monte Carlo simulated output factors for 5 mm SRS field agree with experimental values within 1% local relative difference for all chambers. Smallest active volume ion chamber (IBA-dosimetry RAZOR Nano Chamber) exhibits smallest correction, being compatible with unity. Correction factor combined uncertainties range between 0.7% and 0.9%. Smallest uncertainties were recorded for smallest and largest active volume ion chambers, although the latter exhibited largest correction factor. Highest contribution to combined uncertainty was type B component associated with beam model initial electron spatial Full Width Half Maximum (FWHM) uncertainty. CONCLUSIONS: Among the investigated chambers, the IBA RAZOR Nano Chamber was found to be an excellent choice for narrow beam output factor measurement since it requires minimum correction (in line with IAEA TRS-483 recommendations). This is caused by its tiny size and tissue equivalence materials which produce minimum volume averaging and fluence perturbation.

Development of an ultra-thin parallel plate ionization chamber for dosimetry in FLASH radiotherapy.

BACKGROUND: Conventional air ionization chambers (ICs) exhibit ion recombination correction factors that deviate substantially from unity when irradiated with dose per pulse magnitudes higher than those used in conventional radiotherapy. This fact makes these devices unsuitable for the dosimetric characterization of beams in ultra-high dose per pulse as used for FLASH radiotherapy. PURPOSE: We present the design, development, and characterization of an ultra-thin parallel plate IC that can be used in ultra-high dose rate (UHDR) deliveries with minimal recombination. METHODS: The charge collection efficiency (CCE) of parallel plate ICs was modeled through a numerical solution of the coupled differential equations governing the transport of charged carriers produced by ionizing radiation. It was used to find out the optimal parameters for the purpose of designing an IC capable of exhibiting a linear response with dose (deviation less than 1%) up to 10 Gy per pulse at 4 µ $\umu$ s pulse duration. As a proof of concept, two vented parallel plate IC prototypes have been built and tested in different ultra-high pulse dose rate electron beams. RESULTS: It has been found that by reducing the distance between electrodes to a value of 0.25 mm it is possible to extend the dose rate operating range of parallel plate ICs to ultra-high dose per pulse range, at standard voltage of clinical grade electrometers, well into several Gy per pulse. The two IC prototypes exhibit behavior as predicted by the numerical simulation. One of the so-called ultra-thin parallel plate ionization chamber (UTIC) prototypes was able to measure up to 10 Gy per pulse, 4 µ $\umu$ s pulse duration, operated at 300 V with no significant deviation from linearity within the uncertainties (ElectronFlash Linac, SIT). The other prototype was tested up to 5.4 Gy per pulse, 2.5 µ $\umu$ s pulse duration, operated at 250 V with CCE higher than 98.6% (Metrological Electron Accelerator Facility, MELAF at Physikalisch-Technische Bundesanstalt, PTB). CONCLUSIONS: This work demonstrates the ability to extend the dose rate operating range of ICs to ultra-high dose per pulse range by reducing the spacing between electrodes. The results show that UTICs are suitable for measurement in UHDR electron beams.

Silicon 3D Microdetectors for Microdosimetry in Hadron Therapy.

The present overview describes the evolution of new microdosimeters developed in the National Microelectronics Center in Spain (IMB-CNM, CSIC), ranging from the first ultra-thin 3D diodes (U3DTHINs) to the advanced 3D cylindrical microdetectors, which have been developed over the last 10 years. In this work, we summarize the design, main manufacture processes, and electrical characterization of these devices. These sensors were specifically customized for use in particle therapy and overcame some of the technological challenges in this domain, namely the low noise capability, well-defined sensitive volume, high spatial resolution, and pile-up robustness. Likewise, both architectures reduce the loss of charge carriers due to trapping effects, the charge collection time, and the voltage required for full depletion compared to planar silicon detectors. In particular, a 3D‒cylindrical architecture with electrodes inserted into the silicon bulk and with a very well‒delimited sensitive volume (SV) mimicked a cell array with shapes and sizes similar to those of mammalian cells for the first time. Experimental tests of the carbon beamlines at the Grand Accélérateur National d'Lourds (GANIL, France) and Centro Nazionale Adroterapia Oncologica (CNAO, Italy) showed the feasibility of the U3DTHINs in hadron therapy beams and the good performance of the 3D‒cylindrical microdetectors for assessing linear energy distributions of clinical beams, with clinical fluence rates of 5 × 107 s-1cm-2 without saturation. The dose-averaged lineal energies showed a generally good agreement with Monte Carlo simulations. The results indicated that these devices can be used to characterize the microdosimetric properties in hadron therapy, even though the charge collection efficiency (CCE) and electronic noise may pose limitations on their performance, which is studied and discussed herein. In the last 3D‒cylindrical microdetector generation, we considerably improved the CCE due to the microfabrication enhancements, which have led to shallower and steeper dopant profiles. We also summarize the successive microdosimetric characterizations performed with both devices in proton and carbon beamlines.

The European Joint Research Project UHDpulse - Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates.

UHDpulse - Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates is a recently started European Joint Research Project with the aim to develop and improve dosimetry standards for FLASH radiotherapy, very high energy electron (VHEE) radiotherapy and laser-driven medical accelerators. This paper gives a short overview about the current state of developments of radiotherapy with FLASH electrons and protons, very high energy electrons as well as laser-driven particles and the related challenges in dosimetry due to the ultra-high dose rate during the short radiation pulses. We summarize the objectives and plans of the UHDpulse project and present the 16 participating partners.

Chiral Plasmonics and Their Potential for Point-of-Care Biosensing Applications.

There has been growing interest in using strong field enhancement and light localization in plasmonic nanostructures to control the polarization properties of light. Various experimental techniques are now used to fabricate twisted metallic nanoparticles and metasurfaces, where strongly enhanced chiral near-fields are used to intensify circular dichroism (CD) signals. In this review, state-of-the-art strategies to develop such chiral plasmonic nanoparticles and metasurfaces are summarized, with emphasis on the most recent trends for the design and development of functionalizable surfaces. The major objective is to perform enantiomer selection which is relevant in pharmaceutical applications and for biosensing. Enhanced sensing capabilities are key for the design and manufacture of lab-on-a-chip devices, commonly named point-of-care biosensing devices, which are promising for next-generation healthcare systems.

Designing Silver Nanoparticles for Detecting Levodopa (3,4-Dihydroxyphenylalanine, L-Dopa) Using Surface-Enhanced Raman Scattering (SERS).

Detection of the drug Levodopa (3,4-dihydroxyphenylalanine, L-Dopa) is essential for the medical treatment of several neural disorders, including Parkinson's disease. In this paper, we employed surface-enhanced Raman scattering (SERS) with three shapes of silver nanoparticles (nanostars, AgNS; nanospheres, AgNP; and nanoplates, AgNPL) to detect L-Dopa in the nanoparticle dispersions. The sensitivity of the L-Dopa SERS signal depended on both nanoparticle shape and L-Dopa concentration. The adsorption mechanisms of L-Dopa on the nanoparticles inferred from a detailed analysis of the Raman spectra allowed us to determine the chemical groups involved. For instance, at concentrations below/equivalent to the limit found in human plasma (between 10-7-10-8 mol/L), L-Dopa adsorbs on AgNP through its ring, while at 10-5-10-6 mol/L adsorption is driven by the amino group. At even higher concentrations, above 10-4 mol/L, L-Dopa polymerization predominates. Therefore, our results show that adsorption depends on both the type of Ag nanoparticles (shape and chemical groups surrounding the Ag surface) and the L-Dopa concentration. The overall strategy based on SERS is a step forward to the design of nanostructures to detect analytes of clinical interest with high specificity and at varied concentration ranges.

All-Dielectric Chiral Metasurfaces Based on Crossed-Bowtie Nanoantennas.

Circular dichroism spectroscopy is a technique used to discriminate molecular chirality, which is essential in fields like biology, chemistry, or pharmacology where different chiral agents often show different biological activities. Nevertheless, due to the inherently weak molecular-chiroptical activity, this technique is limited to high concentrations or large analyte volumes. Finding novel ways to enhance the circular dichroism would boost the performance of these techniques. So far, the enhancement of light-matter interaction mediated by plasmons is the most common way to develop chiral plasmonic structures with extraordinarily strong chiroptical responses. However, absorptive losses of metals at optical frequencies has hindered its practical use in many scenarios. In this work, we propose an all-dielectric low-loss chiral metasurface with unit cells built by high-refractive-index crossed-bowtie nanoantennas. These unit cells, built of silicon, strongly increase the chiroptical effect through the simultaneous interaction of their electric and magnetic modes, which in contrast to other recent proposals shows at the same time a high concentration of the electric field in its gap that leads to the presence of hotspots. The proposed structure exhibits a circular dichroism spectra up to 3-fold higher than that of previous proposals that use complex plasmonic or hybrid nanostructures, making it a clear alternative to develop low-loss metasurfaces with potential applications in chiral target sensing/biosensing. For completeness, single triangular shaped and symmetric (achiral) bowtie nanostructures were also studied as possible candidates for a detection up to the single-molecule level due the lack of a circular dichroism background of the nanostructures themselves.

An EGS Monte Carlo model for Varian TrueBEAM treatment units: Commissioning and experimental validation of source parameters.

In this work we have created and commissioned a Monte Carlo model of 6FFF Varian TrueBeam linear accelerator using BEAMnrc. For this purpose we have experimentally measured the focal spot size and shape of three Varian TrueBeam treatment units in 6FFF modality with a slit collimator and several depth dose and lateral beam profiles in a water phantom. The Monte Carlo model of a 6FFF TrueBeam machine was implemented with a primary electron source commissioned as a 2D Gaussian with Full Width Half Maximum selected by comparison of simulated and measured narrow beam profiles. The energy of the primary electron beam was optimized through a simultaneous fit to the measured beam depth dose profiles. Special attention was paid to evaluation of uncertainties of the selected Monte Carlo source parameters. These uncertainties were calculated by analysing the sensitivity of the commissioning process to changes in both primary beam size and energy. Both experimental and Monte Carlo commissioned focus size values were compared and found to be in excellent agreement. The commissioned Monte Carlo model reproduces within 1% accuracy the dose distributions of radiation field size from 3 cm × 3 cm to 15 cm × 15 cm.

A kinetic model of diode detector response to pulsed radiation beams.

Diodes dosimeters present a complex response to pulsed beams, with diode sensitivity varying with dose-per-pulse, monitor unit rate (time between pulses) or number of integrated pulses. Such a response is caused by the complex kinetics of the interplay among charge carriers, recombination-generation centers, which capture excess minority charge carriers and facilitate recombination with a majority charge carrier, and traps with energy levels close to the conduction/valence band, which can trap and release charge carriers. This behavior has been well characterized experimentally, and modeled with phenomenological models. In this work we present a kinetic multi-compartment model of the response of diode detectors, which includes the interplay among charge carriers, recombination-generation centers, and traps. The model can qualitatively fit experimental data extracted from the literature on diode response versus dose-per-pulse, monitor unit rate (time between pulses), or number of integrated pulses. In this regard, our work provides further insight on the response of diode detectors, and a theoretical framework for the development of simple phenomenological models.

Surface Plasmon Resonances in Silver Nanostars.

The recent development of silver nanostars (Ag-NSs) is promising for improved surface-enhanced sensing and spectroscopy, which may be further exploited if the mechanisms behind the excitation of localized surface plasmon resonances (LSPRs) are identified. Here, we show that LSPRs in Ag-NSs can be obtained with finite-difference time-domain (FDTD) calculations by considering the nanostars as combination of crossed nanorods (Ag-NRs). In particular, we demonstrate that an apparent tail at large wavelengths ( λ ≳ 700 nm) observed in the extinction spectra of Ag-NSs is due to a strong dipolar plasmon resonance, with no need to invoke heterogeneity (different number of arms) effects as is normally done in the literature. Our description also indicates a way to tune the strongest LSPR at desired wavelengths, which is useful for sensing applications.

Development and clinical characterization of a novel 2041 liquid-filled ionization chambers array for high-resolution verification of radiotherapy treatments.

PURPOSE: The aim of this study was to present a novel 2041 liquid-filled ionization chamber array for high-resolution verification of radiotherapy treatments. MATERIALS AND METHODS: The prototype has 2041 ionization chambers of 2.5 × 2.5 mm2 area filled with isooctane. The detection elements are arranged in a central square grid of 43 × 43, totally covering an area of 107.5 × 107.5 mm2 . The central inline and cross-line are extended to 227 mm and the diagonals to 321 mm to be able to perform profile measurements of large fields. We have studied stability, pixel response uniformity, dose rate dependence, depth and field size dependence and anisotropy. We present results for output factors, tongue-and-groove, garden fence, small field profiles, irregular fields, and verification of dose planes of patient treatments. RESULTS: Comparison with other detectors used for small field dosimetry (SFD, CC13, microDiamond) has shown good agreement. Output factors measured with the device for square fields ranging from 10 × 10 to 100 × 100 mm2 showed relative differences within 1%. The response of the detector shows a strong dependence on the angle of incident radiation that needs to be corrected for. On the other hand, inter-pixel relative response variations in the 0.95-1.08 range have been found and corrected for. The application of the device for the verification of dose planes of several treatments has shown gamma passing rates above 97% for tolerances of 2% and 2 mm. The verification of other clinical fields, like small fields and irregular fields used in the commissioning of the TPS, also showed large passing rates. The verification of garden fence and tongue-and-groove fields was affected by volume-averaging effects. CONCLUSIONS: The results show that the liquid filled ionization chamber prototype here presented is appropriate for the verification of radiotherapy treatments with high spatial resolution. Recombination effects do not affect very much the verification of relative dose distributions. However, verification of absolute dose distributions may require normalization to a radiation field which is representative of the dose rate of the treatment delivered.

Giant Second-Harmonic Generation in Cantor-like Metamaterial Photonic Superlattices.

We present a nonlinear transfer matrix method for studying the second-harmonic generation (SHG) in nonperiodic metamaterial photonic superlattices. A large enhancement of up to 5 orders of magnitude in SHG efficiency was observed for superlattices made with a Cantor-like quasiperiodic assembly of a nonlinear material and a metamaterial. The enhancement was found to depend much more on the electric field amplitude along the structure because of self-similarity effects than on the amount of nonlinear material, which opens the way to design superlattices for tailored applications in broad-band tunable lasers.

Relevance of miR-21 in regulation of tumor suppressor gene PTEN in human cervical cancer cells.

BACKGROUND: Expression of the microRNA miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA or oncomir. Due to the critical functions of its target proteins in various signaling pathways, miR-21 is an attractive target for genetic and pharmacological modulation in various cancers. Cervical cancer is the second most common cause of death from cancer in women worldwide and persistent HPV infection is the main etiologic agent. This malignancy merits special attention for the development of new treatment strategies. In the present study we analyze the role of miR-21 in cervical cancer cells. METHODS: To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression in a cervical intraepithelial neoplasia-derived cell lines using siRNAs. The effect of miR-21 on gene expression was assessed in cervical cancer cells transfected with the siRNA expression plasmid pSIMIR21. We identified the tumor suppressor gene PTEN as a target of miR-21 and determined the mechanism of its regulation throughout reporter construct plasmids. Using this model, we analyzed the expression of miR-21 and PTEN as well as functional effects such as autophagy and apoptosis induction. RESULTS: In SiHa cells, there was an inverse correlation between miR-21 expression and PTEN mRNA level as well as PTEN protein expression in cervical cancer cells. Transfection with the pSIMIR21 plasmid increased luciferase reporter activity in construct plasmids containing the PTEN-3'-UTR microRNA response elements MRE21-1 and MRE21-2. The role of miR-21 in cell proliferation was also analyzed in SiHa and HeLa cells transfected with the pSIMIR21 plasmid, and tumor cells exhibited markedly reduced cell proliferation along with autophagy and apoptosis induction. CONCLUSIONS: We conclude that miR-21 post-transcriptionally down-regulates the expression of PTEN to promote cell proliferation and cervical cancer cell survival. Therefore, it may be a potential therapeutic target in gene therapy for cervical cancer.

Dose rate dependence of the PTW 60019 microDiamond detector in high dose-per-pulse pulsed beams.

Recombination effects can affect the detectors used for the dosimetry of radiotherapy fields. They are important when using ionization chambers, especially in liquid-filled ionization chambers, and should be corrected for. The introduction of flattening-filter-free accelerators increases the typical dose-per-pulse used in radiotherapy beams, which leads to more important recombination effects. Diamond detectors provide a good solution for the dosimetry and quality assurance of small radiotherapy fields, due to their low energy dependence and small volume. The group of Università di Roma Tor Vergata has developed a synthetic diamond detector, which is commercialized by PTW as microDiamond detector type 60019. In this work we present an experimental characterization of the collection efficiency of the microDiamond detector, focusing on high dose-per-pulse FFF beams. The collection efficiency decreases with dose-per-pulse, down to 0.978 at 2.2 mGy/pulse, following a Fowler-Attix-like curve. On the other hand, we have found no significant dependence of the collection efficiency on the pulse repetition frequency (or pulse period).