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1.
Phys Med Biol ; 64(21): 215008, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31569085

RESUMO

In the framework of RBE modelling for hadron therapy, the BIANCA biophysical model was extended to O-ions and was used to construct a radiobiological database describing the survival of V79 cells as a function of ion type (1 ⩽ Z ⩽ 8) and energy. This database allowed performing RBE predictions in very good agreement with experimental data. A method was then developed to construct analogous databases for different cell lines, starting from the V79 database as a reference. Following interface to the FLUKA Monte Carlo radiation transport code, BIANCA was then applied for the first time to predict cell survival in a typical patient treatment scenario, consisting of two opposing fields of range-equivalent protons or C-ions. The model predictions were found to be in good agreement with CHO cell survival data obtained at the Heidelberg ion-beam therapy (HIT) centre, as well as predictions performed by the local effect model (version LEM IV). This work shows that BIANCA can be used to predict cell survival and RBE not only for V79 and AG01522 cells, as shown previously, but also, in principle, for any cell line of interest. Furthermore, following interface to a transport code like FLUKA, BIANCA can provide predictions of 3D biological dose distributions for hadron therapy treatments, thus laying the foundations for future applications in clinics.


Assuntos
Benchmarking , Partículas Elementares/uso terapêutico , Radioterapia com Íons Pesados/métodos , Método de Monte Carlo , Planejamento da Radioterapia Assistida por Computador/métodos , Animais , Células CHO , Sobrevivência Celular , Cricetinae , Cricetulus , Humanos , Eficiência Biológica Relativa
2.
Nature ; 573(7774): 385-389, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31485075

RESUMO

Phase transitions are driven by collective fluctuations of a system's constituents that emerge at a critical point1. This mechanism has been extensively explored for classical and quantum systems in equilibrium, whose critical behaviour is described by the general theory of phase transitions. Recently, however, fundamentally distinct phase transitions have been discovered for out-of-equilibrium quantum systems, which can exhibit critical behaviour that defies this description and is not well understood1. A paradigmatic example is the many-body localization (MBL) transition, which marks the breakdown of thermalization in an isolated quantum many-body system as its disorder increases beyond a critical value2-11. Characterizing quantum critical behaviour in an MBL system requires probing its entanglement over space and time4,5,7, which has proved experimentally challenging owing to stringent requirements on quantum state preparation and system isolation. Here we observe quantum critical behaviour at the MBL transition in a disordered Bose-Hubbard system and characterize its entanglement via its multi-point quantum correlations. We observe the emergence of strong correlations, accompanied by the onset of anomalous diffusive transport throughout the system, and verify their critical nature by measuring their dependence on the system size. The correlations extend to high orders in the quantum critical regime and appear to form via a sparse network of many-body resonances that spans the entire system12,13. Our results connect the macroscopic phenomenology of the transition to the system's microscopic structure of quantum correlations, and they provide an essential step towards understanding criticality and universality in non-equilibrium systems1,7,13.


Assuntos
Modelos Teóricos , Teoria Quântica , Partículas Elementares , Termodinâmica
3.
J Comp Neurol ; 526(17): 2845-2855, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30198564

RESUMO

High-energy charged particles are considered particularly hazardous components of the space radiation environment. Such particles include fully ionized energetic nuclei of helium, silicon, and oxygen, among others. Exposure to charged particles causes reactive oxygen species production, which has been shown to result in neuronal dysfunction and myelin degeneration. Here we demonstrate that mice exposed to high-energy charged particles exhibited alterations in dendritic spine density in the hippocampus, with a significant decrease of thin spines in mice exposed to helium, oxygen, and silicon, compared to sham-irradiated controls. Electron microscopy confirmed these findings and revealed a significant decrease in overall synapse density and in nonperforated synapse density, with helium and silicon exhibiting more detrimental effects than oxygen. Degeneration of myelin was also evident in exposed mice with significant changes in the percentage of myelinated axons and g-ratios. Our data demonstrate that exposure to all types of high-energy charged particles have a detrimental effect, with helium and silicon having more synaptotoxic effects than oxygen. These results have important implications for the integrity of the central nervous system and the cognitive health of astronauts after prolonged periods of space exploration.


Assuntos
Partículas Elementares , Bainha de Mielina/efeitos da radiação , Sinapses/efeitos da radiação , Animais , Axônios/efeitos da radiação , Axônios/ultraestrutura , Espinhas Dendríticas/efeitos da radiação , Comportamento Exploratório/efeitos da radiação , Hélio , Hipocampo/citologia , Hipocampo/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Bainha de Mielina/ultraestrutura , Oxigênio , Silício , Sinapses/ultraestrutura
4.
Nature ; 558(7710): 375-376, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29925972
5.
Nature ; 557(7704): 171-172, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29740137
6.
Radiother Oncol ; 128(1): 76-82, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29625810

RESUMO

The European Network for Light Ion Hadron Therapy (ENLIGHT) was established in 2002 following various European particle therapy network initiatives during the 1980s and 1990s (e.g. EORTC task group, EULIMA/PIMMS accelerator design). ENLIGHT started its work on major topics related to hadron therapy (HT), such as patient selection, clinical trials, technology, radiobiology, imaging and health economics. It was initiated through CERN and ESTRO and dealt with various disciplines such as (medical) physics and engineering, radiation biology and radiation oncology. ENLIGHT was funded until 2005 through the EC FP5 programme. A regular annual meeting structure was started in 2002 and continues until today bringing together the various disciplines and projects and institutions in the field of HT at different European places for regular exchange of information on best practices and research and development. Starting in 2006 ENLIGHT coordination was continued through CERN in collaboration with ESTRO and other partners involved in HT. Major projects within the EC FP7 programme (2008-2014) were launched for R&D and transnational access (ULICE, ENVISION) and education and training networks (Marie Curie ITNs: PARTNER, ENTERVISION). These projects were instrumental for the strengthening of the field of hadron therapy. With the start of 4 European carbon ion and proton centres and the upcoming numerous European proton therapy centres, the future scope of ENLIGHT will focus on strengthening current and developing European particle therapy research, multidisciplinary education and training and general R&D in technology and biology with annual meetings and a continuously strong CERN support. Collaboration with the European Particle Therapy Network (EPTN) and other similar networks will be pursued.


Assuntos
Partículas Elementares/uso terapêutico , Neoplasias/radioterapia , Europa (Continente) , Radioterapia com Íons Pesados , Humanos , Terapia com Prótons , Radiobiologia
7.
Int J Mol Sci ; 19(2)2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29414878

RESUMO

Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor, which has been widely utilized throughout the cancer research field. SAHA-induced radiosensitization in normal human fibroblasts AG1522 and lung carcinoma cells A549 were evaluated with a combination of γ-rays, proton, and carbon ion exposure. Growth delay was observed in both cell lines during SAHA treatment; 2 µM SAHA treatment decreased clonogenicity and induced cell cycle block in G1 phase but 0.2 µM SAHA treatment did not show either of them. Low LET (Linear Energy Transfer) irradiated A549 cells showed radiosensitization effects on cell killing in cycling and G1 phase with 0.2 or 2 µM SAHA pretreatment. In contrast, minimal sensitization was observed in normal human cells after low and high LET radiation exposure. The potentially lethal damage repair was not affected by SAHA treatment. SAHA treatment reduced the rate of γ-H2AX foci disappearance and suppressed RAD51 and RPA (Replication Protein A) focus formation. Suppression of DNA double strand break repair by SAHA did not result in the differences of SAHA-induced radiosensitization between human cancer cells and normal cells. In conclusion, our results suggest SAHA treatment will sensitize cancer cells to low and high LET radiation with minimum effects to normal cells.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Neoplasias/radioterapia , Radiossensibilizantes/farmacologia , Células A549 , Biomarcadores Tumorais/análise , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Partículas Elementares/uso terapêutico , Fibroblastos/efeitos dos fármacos , Raios gama/uso terapêutico , Inibidores de Histona Desacetilases/efeitos adversos , Humanos , Ácidos Hidroxâmicos/efeitos adversos , Fótons/uso terapêutico , Radiossensibilizantes/efeitos adversos , Vorinostat
8.
Sci Rep ; 8(1): 2790, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29434249

RESUMO

We investigate theoretically thermal and electrical conductances for the system consisting of a quantum dot (QD) connected both to a pair of Majorana fermions residing at the edges of a Kitaev wire and two metallic leads. We demonstrate that both quantities reveal pronounced resonances, whose positions can be controlled by tuning of an asymmetry of the couplings of the QD and a pair of MFs. Similar behavior is revealed for the thermopower, Wiedemann-Franz law and dimensionless thermoelectric figure of merit. The considered geometry can thus be used as a tuner of heat and charge transport assisted by MFs.


Assuntos
Condutividade Elétrica , Teoria Quântica , Simulação por Computador , Partículas Elementares , Temperatura Alta , Modelos Teóricos , Pontos Quânticos , Vibração
9.
Radiat Prot Dosimetry ; 180(1-4): 138-141, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29036726

RESUMO

Cosmic radiation consists of primary high-energy galactic and solar particles. When passing through spacecraft walls and astronauts' bodies, the spectrum becomes even more complex due to generating of secondary particles through fragmentation and nuclear interactions. Total radiation exposure is contributed by both these components. With an advantage, space research uses track etched detectors from the group of passive detectors visualizing the tracks of particles, in this case by etching. The detectors can discriminate between various components of cosmic radiation. A method is introduced for the separation of the different types of particles according to their range using track etched detectors. The method is demonstrated using detectors placed in Russian segment of the International Space Station in 2009. It is shown that the primary high-energy heavy ions with long range contribute up to 56% of the absorbed dose and up to 50% to the dose equivalent.


Assuntos
Radiação Cósmica , Partículas Elementares , Modelos Teóricos , Exposição Ocupacional/análise , Monitoramento de Radiação/instrumentação , Monitoramento de Radiação/métodos , Astronave , Astronautas , Humanos , Doses de Radiação
10.
Astrobiology ; 18(2): 190-206, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29160728

RESUMO

Previous work has suggested that the chirality of the amino acids could be established in the magnetic field of a nascent neutron star from a core-collapse supernova or massive collapsar. The magnetic field would orient the 14N nuclei, and the alignment of its nuclear spin with respect to those of the electron antineutrinos emitted from the collapsing star would determine the probability of destruction of the 14N nuclei by interactions with the antineutrinos. Subsequent work estimated the bulk polarization of the 14N nuclei in large rotating meteoroids in such an environment. The present work adds a crucial piece of this model by describing the details by which the selective 14N nuclear destruction would produce molecular chiral selectivity. The effects of the neutrino-induced interactions on the 14N nuclei bound in amino acids polarized in strong magnetic fields are studied. It is shown that electric fields in the reference frame of the nuclei modify the magnetic field at the nucleus, creating nuclear magnetizations that are asymmetric in chirality. The antineutrino cross sections depend on this magnetization, creating a selective destructive effect. The environmental conditions and sites in which such a selection mechanism could occur are discussed. Selective destruction of D-enantiomers results in enantiomeric excesses which may be sufficient to drive subsequent autocatalysis necessary to produce the few-percent enantiomeric excesses found in meteorites and subsequent homochirality. Molecular quantum chemical calculations were performed for alanine, and the chirality-dependent effects studied were included. A preference for left-handed molecules was found, and enantiomeric excesses as high as 0.02% were estimated for molecules in the electromagnetic conditions expected from a core-collapse supernova. Key Words: Amino acids-Supernovae-Antineutrinos-Enantiomeric excess-Chirality. Astrobiology 18, 190-206.


Assuntos
Aminoácidos/química , Eletricidade , Evolução Química , Meio Ambiente Extraterreno/química , Campos Magnéticos , Partículas Elementares , Meteoroides , Modelos Químicos , Nitrogênio/química , Estereoisomerismo
11.
Int J Radiat Biol ; 93(12): 1299-1305, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28978247

RESUMO

PURPOSE: Characterization of soft tissue, water and air in terms of effective atomic number (Zeff) with respect to the interactions of hadrons, leptons and isotopes of hydrogen. METHOD: Mass collision stopping powers (MCSPs) were calculated first using Bethe formula. Then, these values were used to estimate Zeff using linear-logarithmic interpolation. A scale equation was also used to calculate MCSP. RESULTS: Variation in Zeff, over the 0.5-50 MeV energy range considered, is minimum for muon and pion (π meson) interactions (relative difference [RD] ≤ 7%), while maximum variation has been noticed in Zefffor heavy charged particles, i.e. alpha particle (RD ≤ 26%). The highest values of Zeff were obtained for muon particle, the lightest particle while the minimum values of Zeff were obtained for alpha particle interaction. Except for very low kinetic energies, water equivalence of soft tissue is very satisfactory (RD ≤ 3%). The Zeff of water relative to air was found to be almost constant at high energies. The present results should be valid for especially high energies where the Bethe formula can be applied. This applies to relatively higher energies (>2 MeV) for heavier particles such as alpha particles and applies to relatively lower energies (>0.5 MeV) for lighter particles such as protons. CONCLUSIONS: In view of the importance of water equivalence in particle therapy, new data on Zeff in soft tissue, water and air for fundamental particle interaction should be important. Results revealed that soft tissue could be considered as water equivalent for interaction of various fundamental particles.


Assuntos
Ar , Hidrogênio/química , Água/química , Partículas Elementares , Isótopos
12.
Science ; 357(6356): 1098-1099, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28912232
13.
Life Sci Space Res (Amst) ; 14: 64-73, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28887946

RESUMO

For the first time, the American (NASA) and Russian (ROSCOSMOS) space radiation transport codes, HZETRN and SHIELD respectively, are directly compared to each other. Calculations are presented for Galactic Cosmic Ray (GCR) minimum Hydrogen, Oxygen and Iron projectiles incident on a uniform Aluminum cylinder of varying thickness. Comparisons are made for the flux spectra of neutrons, light ions (Z≤ 2), heavy ions (Z> 2) and pions emitted from the back of the Aluminum cylinder. In order to provide more benchmark comparisons, some calculations with the GEANT and FLUKA transport codes are also shown.


Assuntos
Radiação Cósmica , Partículas Elementares , Marte , Modelos Teóricos , Monitoramento de Radiação/métodos , Proteção Radiológica/métodos , Humanos , Doses de Radiação
14.
Radiother Oncol ; 124(2): 185-189, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28764925

RESUMO

BACKGROUND: We performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe. MATERIAL AND METHODS: The modified pFQ consisted of 235 questions distributed in 11 sections accessible on line on an EORTC server. Fifteen centers from 8 countries completed the pFQ between May 2015 and December 2015. RESULTS: The average number of patients treated per year and per particle center was 221 (range, 40-557). The majority (66.7%) of centers had pencil beam or raster scanning capability. Four (27%) centers were dedicated to eye treatment only. An increase in the patients-health professional FTE ratio was observed for eye tumor only centers when compared to other centers. All centers treated routinely chordomas/chondrosarcomas, brain tumors and sarcomas but rarely breast cancer. The majority of centers treated pediatric cases with particles. Only a minority of the queried institutions treated non-static targets. CONCLUSIONS: As the number of particle centers coming online will increase, the experience with this treatment modality will rise in Europe. Children can currently be treated in these facilities in a majority of cases. The majority of these centers provide state of the art particle beam therapy.


Assuntos
Radioterapia com Íons Pesados/métodos , Terapia com Prótons/métodos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Carbono/química , Carbono/uso terapêutico , Criança , Condrossarcoma/radioterapia , Cordoma/radioterapia , Partículas Elementares/uso terapêutico , Europa (Continente) , Neoplasias Oculares/radioterapia , Radioterapia com Íons Pesados/instrumentação , Radioterapia com Íons Pesados/estatística & dados numéricos , Humanos , Terapia com Prótons/instrumentação , Terapia com Prótons/estatística & dados numéricos , Inquéritos e Questionários
15.
Nature ; 546(7657): 185-186, 2017 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-28593976
16.
Nature ; 544(7648): 38-39, 2017 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-28382992
17.
Nat Rev Clin Oncol ; 14(8): 483-495, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28290489

RESUMO

Radiotherapy with high-energy charged particles has become an attractive therapeutic option for patients with several tumour types because this approach better spares healthy tissue from radiation than conventional photon therapy. The cost associated with the delivery of charged particles, however, is higher than that of even the most elaborate photon-delivery technologies. Reliable evidence of the relative cost-effectiveness of both modalities can only come from the results of randomized clinical trials. Thus, the hurdles that currently limit direct comparisons of these two approaches in clinical trials, especially those related to insurance coverage, should be removed. Herein, we review several randomized trials of charged-particle therapies that are ongoing, with results that will enable selective delivery to patients who are most likely to benefit from them. We also discuss aspects related to radiobiology, including the immune response and hypoxia, which will need to be taken into consideration in future randomized trials to fully exploit the potential of charged particles.


Assuntos
Partículas Elementares/uso terapêutico , Neoplasias/radioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Radioterapia (Especialidade)/tendências
18.
Appl Radiat Isot ; 126: 130-133, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28314507

RESUMO

The Black Hills State University Underground Campus (BHUC) houses a low background counting facility on the 4850' level of the Sanford Underground Research Facility. There are currently four ultra-low background, high-purity germanium detectors installed in the BHUC and it is anticipated four more detectors will be installed within a year. In total, the BHUC will be able to accommodate up to twelve detectors with space inside a class 1000 cleanroom, an automated liquid nitrogen fill system, on-site personnel assistance and other required utilities.


Assuntos
Radiação de Fundo , Universidades , Fenômenos Astronômicos , Partículas Elementares , Ambiente Controlado , Arquitetura de Instituições de Saúde , Fenômenos Geológicos , Laboratórios , Mineração , Radiometria/instrumentação , Radiometria/métodos , South Dakota
19.
Phys Med Biol ; 62(4): 1248-1268, 2017 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-27995904

RESUMO

Particle therapy is increasingly attractive for the treatment of tumors and the number of facilities offering it is rising worldwide. Due to the well-known enhanced effectiveness of ions, it is of utmost importance to plan treatments with great care to ensure tumor killing and healthy tissues sparing. Hence, the accurate quantification of the relative biological effectiveness (RBE) of ions, used in the calculation of the biological dose, is critical. Nevertheless, the RBE is a complex function of many parameters and its determination requires modeling. The approaches currently used have allowed particle therapy to thrive, but still show some shortcomings. We present herein a short description of a new theoretical framework, NanOx, to calculate cell survival in the context of particle therapy. It gathers principles from existing approaches, while addressing some of their weaknesses. NanOx is a multiscale model that takes the stochastic nature of radiation at nanometric and micrometric scales fully into account, integrating also the chemical aspects of radiation-matter interaction. The latter are included in the model by means of a chemical specific energy, determined from the production of reactive chemical species induced by irradiation. Such a production represents the accumulation of oxidative stress and sublethal damage in the cell, potentially generating non-local lethal events in NanOx. The complementary local lethal events occur in a very localized region and can, alone, lead to cell death. Both these classes of events contribute to cell death. The comparison between experimental data and model predictions for the V79 cell line show a good agreement. In particular, the dependence of the typical shoulders of cell survival curves on linear energy transfer are well described, but also the effectiveness of different ions, including the overkill effect. These results required the adjustment of a number of parameters compatible with the application of the model in a clinical scenario thereby showing the potential of NanOx. Said parameters are discussed in detail in this paper.


Assuntos
Sobrevivência Celular/efeitos da radiação , Partículas Elementares/uso terapêutico , Fibroblastos/efeitos da radiação , Pulmão/efeitos da radiação , Modelos Teóricos , Animais , Células Cultivadas , Cricetinae , Cricetulus , Fibroblastos/citologia , Transferência Linear de Energia , Pulmão/citologia , Eficiência Biológica Relativa
20.
Radiother Oncol ; 121(3): 453-458, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27988058

RESUMO

BACKGROUND AND PURPOSE: Aside from the enhancement of physical dose deposited by antiprotons annihilating in tissue-like material compared to protons of the same range a further increase of biological effective dose has been demonstrated. This enhancement can be expressed in an increase of the relative biological effectiveness (RBE) of antiprotons near the end of range. We have performed the first-ever direct measurement of the RBE of antiprotons both at rest and in flight. MATERIALS AND METHODS: Experimental data were generated on the RBE of an antiproton beam entering a tissue-like target consisting of V79 cells embedded in gelatin with an energy providing a range of approximately 10cm. RESULTS: The RBE in the entrance channel (the "plateau") is only slightly above the value for a comparable proton beam, and remains low until the proximal edge of the spread-out Bragg peak (SOBP). A steep increase of RBE is seen starting from the onset of the SOBP. CONCLUSIONS: This paper reports the final results of the experiment AD-4/ACE at CERN on the first-ever direct measurement of RBE of antiprotons and constitutes the first step toward developing treatment plans.


Assuntos
Partículas Elementares/uso terapêutico , Radioterapia de Alta Energia/métodos , Humanos , Método de Monte Carlo , Neoplasias/radioterapia , Terapia com Prótons , Radiometria/métodos , Dosagem Radioterapêutica , Eficiência Biológica Relativa
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