A novel approach to nonlinear variable-order fractional viscoelasticity.

This paper addresses nonlinear viscoelastic behaviour of fractional systems with variable time-dependent fractional order. In this case, the main challenge is that the Boltzmann linear superposition principle, i.e. the theoretical basis on which linear viscoelastic fractional operators are formulated, does not apply in standard form because the fractional order is not constant with time. Moving from this consideration, the paper proposes a novel approach where the system response is derived by a consistent application of the Boltzmann principle to an equivalent system, built at every time instant based on the fractional order at that instant and the response at all the previous ones. The approach is readily implementable in numerical form, to calculate either stress or strain responses of any fractional system where fractional order may change with time. This article is part of the theme issue 'Advanced materials modelling via fractional calculus: challenges and perspectives'.

Design of a beam shaping assembly and preliminary modelling of a treatment room for accelerator-based BNCT at CNEA.

This work reports on the characterisation of a neutron beam shaping assembly (BSA) prototype and on the preliminary modelling of a treatment room for BNCT within the framework of a research programme for the development and construction of an accelerator-based BNCT irradiation facility in Buenos Aires, Argentina. The BSA prototype constructed has been characterised by means of MCNP simulations as well as a set of experimental measurements performed at the Tandar accelerator at the National Atomic Energy Commission of Argentina.

Treatment planning capability assessment of a beam shaping assembly for accelerator-based BNCT.

Within the frame of an ongoing project to develop a folded Tandem-Electrostatic-Quadrupole accelerator facility for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT) a theoretical study was performed to assess the treatment planning capability of different configurations of an optimized beam shaping assembly for such a facility. In particular this study aims at evaluating treatment plans for a clinical case of Glioblastoma.

Development of a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

We describe the present status of an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction. The machine currently being constructed is a folded TESQ with a high-voltage terminal at 0.6 MV. We report here on the progress achieved in a number of different areas.

Development of a tandem-electrostatic-quadrupole accelerator facility for BNCT.

In this work we describe the present status of an ongoing project to develop a tandem-electrostatic-quadrupole (TESQ) accelerator facility for accelerator-based (AB) BNCT at the Atomic Energy Commission of Argentina in Buenos Aires. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction slightly beyond its resonance at 2.25 MeV. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the (7)Li(p,n)(7)Be reaction, to perform BNCT treatment for deep-seated tumors in less than an hour. An electrostatic machine is the technologically simplest and cheapest solution for optimized AB-BNCT. The machine being designed and constructed is a folded TESQ with a high-voltage terminal at 1.2 MV intended to work in air. Such a machine is conceptually shown to be capable of transporting and accelerating a 30 mA proton beam to 2.4 MeV. The general geometric layout, its associated electrostatic fields, and the acceleration tube are simulated using a 3D finite element procedure. The design and construction of the ESQ modules is discussed and their electrostatic fields are investigated. Beam transport calculations through the accelerator are briefly mentioned. Likewise, work related to neutron production targets, strippers, beam shaping assembly and patient treatment room is briefly described.

Microdistributions of prospective BNCT-compound CuTCPH in tissue sections with a heavy ion microbeam.

Microdistributions of the prospective BNCT-compound CuTCPH, a carborane-containing tetraphenylporphyrin with one Cu atom in its molecular structure, have been obtained in tissue sections of different organs of tumor-bearing and normal Syrian hamsters injected with the boron compound by employing a heavy ion microbeam. High resolution X-ray spectroscopy following micro-PIXE (Particle Induced X-ray Emission with micrometer-sized beams) with a focused (16)O ion beam was used. Focusing was performed with a heavy-ion scanning high-precision magnetic quadrupole triplet microprobe. Squamous Cell Carcinomas were induced on the right Cheek Pouch of Syrian Hamsters (HCP), sampled, cryo-sectioned and freeze-dried. Two-dimensional maps of elemental concentration were obtained by scanning the beam over the samples. Very non-uniform Cu concentrations were found in all sections.

An optimized neutron-beam shaping assembly for accelerator-based BNCT.

Different materials and proton beam energies have been studied in order to search for an optimized neutron production target and beam shaping assembly for accelerator-based BNCT. The solution proposed in this work consists of successive stacks of Al, polytetrafluoroethylene, commercially known as Teflon, and LiF as moderator and neutron absorber, and Pb as reflector. This assembly is easy to build and its cost is relatively low. An exhaustive Monte Carlo simulation study has been performed evaluating the doses delivered to a Snyder model head phantom by a neutron production Li-metal target based on the (7)Li(p,n)(7)Be reaction for proton bombarding energies of 1.92, 2.0, 2.3 and 2.5 MeV. Three moderator thicknesses have been studied and the figures of merit show the advantage of irradiating with near-resonance-energy protons (2.3 MeV) because of the relatively high neutron yield at this energy, which at the same time keeps the fast neutron healthy tissue dose limited and leads to the lowest treatment times. A moderator of 34 cm length has shown the best performance among the studied cases.

Chromosome aberrations induced in human lymphocytes by heavy charged particles in track segment mode.

Human blood was irradiated with accelerated ions: 20 MeV 4He, 425 MeV 12C and 1480 MeV and 996 MeV 16O. For each ion, the blood was exposed to a range of doses as thin specimens in the track segment mode, so that irradiations took place at nearly constant LETs of 31.4, 61, 52 and 69 keV microm(-1), respectively. Lymphocytes were cultured to the first in vitro metaphase, analysed for chromosomal damage and the dicentric aberration frequencies fitted to the linear quadratic model of dose-response. For these high LET radiations, the linear (alpha) yield coefficient predominated and increased with LET, at least up to 60 keV microm(-1). Apart from the 996 MeV oxygen ions, the data indicated the presence of a quadratic (beta) coefficient, statistically consistent with values obtained with low LET radiations. However, the associated uncertainties on the measured beta values were large, illustrating the general problem that beta is more difficult to measure against a dominating and ever-increasing alpha term. The existence or otherwise of a beta component of the dose-response at these radiation qualities has important consequences for modelling mechanisms of aberration induction by radiation.

Low energy proton irradiation effects on alveolar macrophages from young and aged rats.

A prospective study was undertaken to assess the radiotoxicity of accelerated particles in pulmonary alveolar macrophages (AM). We evaluated the effects of a single dose (10-75 Gy) of an external low-energy (20 MeV) proton beam on cultured AM oxidative metabolism and phagocytic function. Macrophages are the first line of defense against invading pathogens and are known to generate superoxide anion (O2), nitric oxide (NO), and mediators of antimicrobial and antitumoral defense mechanisms. We obtained AM by bronchoalveolar lavage from young (1-2 month old) and aged (9-12 month old) male Wistar rats. Cell viability, phagocytosis, O2 and NO production in control and proton-irradiated cultured AM were evaluated The effect of proton irradiation on cell viability was dose-dependent The higher doses induced a dramatic decrease in viability in the aged population. Phagocytosis increased 1.3-1.4 fold inboth populations irrespective of the dose delivered. Generation of O2 was always higher in the aged population for all the doses assayed and showed no significant variation from the control values. In the young population a clear increase was observed with doses of 25 and 50 Gy. NO production in AM from young animals rose in a dose-dependent manner. Conversely, proton irradiation did not affect NO production in macrophages from aged animals. The results of this study demonstrate that AM isolated from young and aged rats are functionally different and show a distinct behavior when exposed to proton irradiation. These findings suggest that age may condition response and must be taken into account when accelerated particle-radiotherapy protocols are considered as a valid therapeutic option for the treatment of cancer. To the best of our knowledge, this is the first report comparing sham-irradiated and proton-irradiated young and aged AM.

Metabolic alterations without metal accumulation in the ovary of adult Bufo arenarum females, observed after long-term exposure to Zn(2+), followed by toxicity to embryos.

Long-term exposure of aquatic organisms to metals, even those considered micronutrients, may affect their metabolism and produce sublethal effects. We evaluated the effects of long-term exposure of adult amphibian (Bufo arenarum) females to 4 microg/L of Zn(2+) (ZnSO(4) x H(2)O) in Ringer solution on the concentration of Zn and Fe, the activity of the key enzyme of the pentose phosphate pathway glucose 6-phosphate dehydrogenase, and glutathione content, both in the liver and ovary of these animals. We also performed early embryonic development studies by in vitro insemination from control and treated females. Zn exposure rendered lower Zn concentrations in the ovaries than did exposure of animals to Ringer solution without metal addition (97 +/- 50 versus 149 +/- 46 Zn microg/wet tissue g). Zn and Fe concentration correlation was positive and linear in the ovary, but was negative and nonlinear in the liver of the studied females. The activity of the enzyme glucose 6-phosphate dehydrogenase decreased (0.0599 +/- 0.0109 versus 0.0776 +/- 0.0263 micromol of NADPH/min x mg of proteins) and the endogenous glutathione content increased (0.027 +/- 0.005 versus 0.018 +/- 0.007 mg/10 mg of proteins) in the ovary but remained unaltered in the liver as a consequence of Zn treatment. Our results suggest the existence of different mechanisms of regulation of Zn and Fe concentrations in the ovary and in the liver of adult B. arenarum females. Binding of Zn to low-molecular-weight proteins, as metallothioneins, may occur in the liver, thus protecting this organ from toxic effects. In the ovary high-molecular-weight proteins, like glucose-6-phosphate dehydrogenase, should be able to bind Zn, leading to oxidative stress responsible for the observed increase in endogenous glutathione content. Inhibition of the pentose phosphate pathway in the ovary by Zn can be responsible for the reproductive failure that we detected through embryos survival studies during early life stages: 81.3 +/- 6.3% of embryos from control females survived versus 63.1 +/- 13.8% of embryos from Zn-treated females at the branchial circulation stage of development.

In-phantom dosimetry for the 13C(d,n)14N reaction as a source for accelerator-based BNCT.

The use of the 13C(d,n) 14N reaction at Ed=1.5 MeV for accelerator-based boron neutron capture therapy (AB-BNCT) is investigated. Among the deuteron-induced reactions at low incident energy, the 3C(d,n)14N reaction turns out to be one of the best for AB-BNCT because of beneficial materials properties inherent to carbon and its relatively large neutron production cross section. The deuteron beam was produced by a tandem accelerator at MIT's Laboratory for Accelerator Beam Applications (LABA) and the neutron beam shaping assembly included a heavy water moderator and a lead reflector. The resulting neutron spectrum was dosimetrically evaluated at different depths inside a water-filled brain phantom using the dual ionization chamber technique for fast neutrons and photons and bare and cadmium-covered gold foils for the thermal neutron flux. The RBE doses in tumor and healthy tissue were calculated from experimental data assuming a tumor 10B concentration of 40 ppm and a healthy tissue 10B concentration of 11.4 ppm (corresponding to a reported ratio of 3.5:1). All results were simulated using the code MCNP, a general Monte Carlo radiation transport code capable of simulating electron, photon, and neutron transport. Experimental and simulated results are presented at 1, 2, 3, 4, 6, 8, and 10 cm depths along the brain phantom centerline. An advantage depth of 5.6 cm was obtained for a treatment time of 56 min assuming a 4 mA deuteron current and a maximum healthy tissue dose of 12.5 RBE Gy.