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1.
Magn Reson Med ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31840296

RESUMO

PURPOSE: To enhance the utility of motion detection with nuclear magnetic resonance (NMR) markers by removing the need for sequence-dependent calibration. METHODS: Two sets of NMR markers are used for simultaneous observation of magnetic field dynamics during imaging procedures. A set of stationary markers at known positions in the laboratory frame serves to determine the field evolution in that frame. Concurrent recording from a set of head-mounted markers then permits calculating their lab-frame positions and derived rigid-body motion parameters. The precision and accuracy of this approach are evaluated relative to current calibration-based solutions. Use for prospective motion correction is then demonstrated in high-resolution imaging of long scan duration. RESULTS: Motion detection with real-time field tracking overcomes the need for explicit calibration without compromising precision, which is assessed at 10 to 30 µm. Relative to full conventional calibration, it is found to offer superior robustness against thermal drift. Relative to more economical modes of calibration, it achieves substantially higher accuracy. Prospective motion correction based on real-time field tracking resulted in consistently high image quality even when head motion exceeded the image resolution by one order of magnitude. CONCLUSION: Real-time field tracking enables motion detection with NMR markers without calibration overhead and thus overcomes a key obstacle toward routine use. In addition, it renders this mode of motion tracking more robust against system imperfections.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31837270

RESUMO

Mechanical flexibility in single crystals of covalently bound materials is a fascinating and poorly understood phenomenon. We present here the first example of a plastically-flexible one dimensional (1D) coordination polymer. The compound [Zn(m-Cl)2(3,5-Cl2Py)2]n,  is flexible over two crystallographic faces. Remarkably, the single crystal remains intact when bent to 180o. Through the combination of microscopy, diffraction, and spectroscopic studies we probe the structural response of the crystal lattice to mechanical bending. Deformation of the covalent polymer chains does not appear to be responsible for the observed macroscopic bending. Instead, our results suggest that mechanical bending occurs by displacement of the coordination polymer chains. Based on experimental and theoretical evidence, we propose a new model for mechanical flexibility in 1D coordination polymers. Moreover, our calculations propose an origin for the different mechanical properties of this compound and a structurally similar elastic material. The results presented here offer novel insight into the mechanism of mechanical flexibility in coordination polymer crystals and the potential of tuning their physical properties by mechanical force.

3.
PLoS One ; 14(11): e0224873, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31765436

RESUMO

Proton radiotherapy using minibeams of sub-millimeter dimensions reduces side effects in comparison to conventional proton therapy due to spatial fractionation. Since the proton minibeams widen with depth, the homogeneous irradiation of a tumor can be ensured by adjusting the beam distances to tumor size and depth to maintain tumor control as in conventional proton therapy. The inherent advantages of protons in comparison to photons like a limited range that prevents a dosage of distal tissues are maintained by proton minibeams and can even be exploited for interlacing from different beam directions. A first animal study was conducted to systematically investigate and quantify the tissue-sparing effects of proton pencil minibeams as a function of beam size and dose distributions, using beam widths between σ = 95, 199, 306, 411, 561 and 883 µm (standard deviation) at a defined center-to-center beam distance (ctc) of 1.8 mm. The average dose of 60 Gy was distributed in 4x4 minibeams using 20 MeV protons (LET ~ 2.7 keV/µm). The induced radiation toxicities were measured by visible skin reactions and ear swelling for 90 days after irradiation. The largest applied beam size to ctc ratio (σ/ctc = 0.49) is similar to a homogeneous irradiation and leads to a significant 3-fold ear thickness increase compared to the control group. Erythema and desquamation was also increased significantly 3-4 weeks after irradiation. With decreasing beam sizes and thus decreasing σ/ctc, the maximum skin reactions are strongly reduced until no ear swelling or other visible skin reactions should occur for σ/ctc < 0.032 (extrapolated from data). These results demonstrate that proton pencil minibeam radiotherapy has better tissue-sparing for smaller σ/ctc, corresponding to larger peak-to-valley dose ratios PVDR, with the best effect for σ/ctc < 0.032. However, even quite large σ/ctc (e.g. σ/ctc = 0.23 or 0.31, i.e. PVDR = 10 or 2.7) show less acute side effects than a homogeneous dose distribution. This suggests that proton minibeam therapy spares healthy tissue not only in the skin but even for dose distributions appearing in deeper layers close to the tumor enhancing its benefits for clinical proton therapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31655869

RESUMO

Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich compact light source (MuCLS), one of these novel compact X-ray facilities, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay. For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3 Gy or 5 Gy and tumor growth delay was measured. Microbeams had a width of 50 µm and a center-to-center distance of 350 µm with peak doses of either 21 Gy or 35 Gy. A dose rate of up to 5 Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that MRT can be successfully performed in vivo at compact inverse Compton sources.

6.
PLoS One ; 14(9): e0221454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31483811

RESUMO

Side effects caused by radiation are a limiting factor to the amount of dose that can be applied to a tumor volume. A novel method to reduce side effects in radiotherapy is the use of spatial fractionation, in which a pattern of sub-millimeter beams (minibeams) is applied to spare healthy tissue. In order to determine the skin reactions in dependence of single beam sizes, which are relevant for spatially fractionated radiotherapy approaches, single pencil beams of submillimeter to 6 millimeter size were applied in BALB/c mice ears at a Small Animal Radiation Research Platform (SARRP) with a plateau dose of 60 Gy. Radiation toxicities in the ears were observed for 25 days after irradiation. Severe radiation responses were found for beams ≥ 3 mm diameter. The larger the beam diameter the stronger the observed reactions. No ear swelling and barely reddening or desquamation were found for the smallest beam sizes (0.5 and 1 mm). The findings were confirmed by histological sections. Submillimeter beams are preferred in minibeam therapy to obtain optimized tissue sparing. The gradual increase of radiation toxicity with beam size shows that also larger beams are capable of healthy tissue sparing in spatial fractionation.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31484112

RESUMO

In magnetic resonance imaging, the use of array detection and the number of detector elements have seen a steady increase over the past two decades. As a result, per-channel analog connection via long coaxial cable, as commonly used, poses an increasing challenge in terms of handling, safety, and coupling among cables. This situation is exacerbated when complementary recording of radiofrequency transmission or NMR-based magnetic field sensing further add to channel counts. A generic way of addressing this trend is the transition to digital signal transmission, enabled by digitization and first-level digital processing close to detector coils and sensors in the magnet bore. The foremost challenge that comes with this approach is to achieve high dynamic range, linearity, and phase stability despite interference by strong static, audiofrequency, and radiofrequency fields. The present work reports implementation of a 16-channel in-bore receiver, performing signal digitization and processing with subsequent optical transmission over fiber. Along with descriptions of the system design and construction, performance evaluation is reported. The resulting device is fully MRI compatible providing practically equal performance and signal quality compared to state-of-the-art RF digitizers operating outside the magnet. Its use is demonstrated by examples of head imaging and magnetic field recording.

8.
J Cell Sci ; 132(19)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31492757

RESUMO

Nucleoli have attracted interest for their role as cellular stress sensors and as potential targets for cancer treatment. The effect of DNA double-strand breaks (DSBs) in nucleoli on rRNA transcription and nucleolar organisation appears to depend on the agent used to introduce DSBs, DSB frequency and the presence (or not) of DSBs outside the nucleoli. To address the controversy, we targeted nucleoli with carbon ions at the ion microbeam SNAKE. Localized ion irradiation with 1-100 carbon ions per point (about 0.3-30 Gy per nucleus) did not lead to overall reduced ribonucleotide incorporation in the targeted nucleolus or other nucleoli of the same cell. However, both 5-ethynyluridine incorporation and Parp1 protein levels were locally decreased at the damaged nucleolar chromatin regions marked by γH2AX, suggesting localized inhibition of rRNA transcription. This locally restricted transcriptional inhibition was not accompanied by nucleolar segregation, a structural reorganisation observed after inhibition of rRNA transcription by treatment with actinomycin D or UV irradiation. The presented data indicate that even multiple complex DSBs do not lead to a pan-nucleolar response if they affect only a subnucleolar region.

9.
PLoS One ; 14(8): e0221502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31430337

RESUMO

INTRODUCTION: The major stress-inducible heat shock protein 70 (Hsp70) is induced after different stress stimuli. In tumors, elevated intracellular Hsp70 levels were associated on the one hand with radio- and chemotherapy resistance and on the other hand with a favorable outcome for patients. This study was undertaken to investigate cytosolic Hsp70 (cHsp70) as a potential biomarker for progression free (PFS) and overall survival (OS) in patients with primary glioblastomas (GBM). METHODS: The cHsp70 expression in tumor tissue of 60 patients diagnosed with primary GBM was analyzed by immunohistochemistry. The cHsp70 expression was correlated to the PFS and OS of the patients. RESULTS: A high cHsp70 expression was associated with a prolonged PFS (hazard ratio = 0.374, p = 0.001) and OS (hazard ratio = 0.416, p = 0.014) in GBM patients treated according to the standard Stupp protocol with surgery, radiotherapy and temozolomide. CONCLUSIONS: These data suggest that the intracellular Hsp70 expression might serve as a prognostic marker in patients with primary GBM.

10.
J Public Health Manag Pract ; 25(5): 464-471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31348161

RESUMO

OBJECTIVE: To develop a core set of capabilities and tasks for local health departments (LHDs) to engage in land use and transportation policy processes that promote active transportation. DESIGN: We conducted a 3-phase modified Delphi study from 2015 to 2017. SETTING: We recruited a multidisciplinary national expert panel for key informant interviews by telephone and completion of a 2-step online validation process. PARTICIPANTS: The panel consisted of 58 individuals with expertise in local transportation and policy processes, as well as experience in cross-sector collaboration with public health. Participants represented the disciplines of land use planning, transportation/public works, public health, municipal administration, and active transportation advocacy at the state and local levels. MAIN OUTCOME MEASURES: Key informant interviews elicited initial capabilities and tasks. An online survey solicited rankings of impact and feasibility for capabilities and ratings of importance for associated tasks. Feasibility rankings were used to categorize capabilities according to required resources. Results were presented via second online survey for final input. RESULTS: Ten capabilities were categorized according to required resources. Fewest resources were as follows: (1) collaborate with public officials; (2) serve on land use or transportation board; and (3) review plans, policies, and projects. Moderate resources were as follows: (4) outreach to the community; (5) educate policy makers; (6) participate in plan and policy development; and (7) participate in project development and design review. Most resources were as follows: (8) participate in data and assessment activities; (9) fund dedicated staffing; and (10) provide funding support. CONCLUSIONS: These actionable capabilities can guide planning efforts for LHDs of all resource levels.

11.
Radiat Environ Biophys ; 58(3): 433-438, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31201502

RESUMO

Supplementation with the antioxidant selenium is frequently performed in breast cancer patients to protect the normal tissue from radiation-induced side effects. However, concerns exist whether selenium also protects tumor cells from radiation-induced cell kill and thereby reduces the efficacy of radiotherapy. In this work, the effect of selenium administration on the radiosensitivity of breast cancer cells was evaluated in vitro. Physiological relevant selenium concentrations (70 and 140 µg/l) did not affect DNA double-strand breaks (γH2AX foci) after 4-Gy X-ray irradiation. Also apoptosis (caspase 3/7) after irradiation with 10 Gy was not influenced by selenium treatment in MDA-MB-231 and MCF7 cells. Most importantly, selenium supplementation did not impair the clonogenic survival of the breast cancer cell lines after irradiation (0, 2, 4, 6, 8 Gy). The data suggest that physiological relevant selenium concentrations administered in combination with radiation therapy do not deteriorate the efficacy of radiotherapy in breast cancer patients. However, randomized clinical trials comparing the effectiveness of radiotherapy and the associated side effects in patients with and without selenium supplementation are recommended.

12.
Sci Total Environ ; 678: 146-161, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31075581

RESUMO

During the next decade it will be necessary to develop novel combinations of management strategies to sustainably increase crop production and soil resilience. Improving agricultural productivity, while conserving and enhancing biotic and abiotic resources, is an essential requirement to increase global food production on a sustainable basis. The role of farmers in increasing agricultural productivity growth sustainably will be crucial. Farmers are at the center of any process of change involving natural resources and for this reason they need to be encouraged and guided, through appropriate incentives and governance practices, to conserve natural ecosystems and their biodiversity, and minimize the negative impact agriculture can have on the environment. Farmers and stakeholders need to revise traditional approaches not as productive as the modern approaches but more friendly with natural and environmental ecosystems values as well as emerging novel tools and approaches addressing precise farming, organic amendments, lowered water consumption, integrated pest control and beneficial plant-microbe interactions. While practical solutions are developing, science based recommendations for crop rotations, breeding and harvest/postharvest strategies leading to environmentally sound and pollinator friendly production and better life in rural areas have to be provided.


Assuntos
Agricultura/métodos , Conservação dos Recursos Naturais/métodos , Biodiversidade , Produção Agrícola , Produtos Agrícolas , Ecossistema , Europa (Continente) , Melhoramento Vegetal
13.
Cancers (Basel) ; 11(5)2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31130616

RESUMO

The use of different scoring systems for radiation-induced toxicity limits comparability between studies. We examined dose-dependent tissue alterations following hypofractionated X-ray irradiation and evaluated their use as scoring criteria. Four dose fractions (0, 5, 10, 20, 30 Gy/fraction) were applied daily to ear pinnae. Acute effects (ear thickness, erythema, desquamation) were monitored for 92 days after fraction 1. Late effects (chronic inflammation, fibrosis) and the presence of transforming growth factor beta 1 (TGFß1)-expressing cells were quantified on day 92. The maximum ear thickness displayed a significant positive correlation with fractional dose. Increased ear thickness and erythema occurred simultaneously, followed by desquamation from day 10 onwards. A significant dose-dependency was observed for the severity of erythema, but not for desquamation. After 4 × 20 and 4 × 30 Gy, inflammation was significantly increased on day 92, whereas fibrosis and the abundance of TGFß1-expressing cells were only marginally increased after 4 × 30 Gy. Ear thickness significantly correlated with the severity of inflammation and fibrosis on day 92, but not with the number of TGFß1-expressing cells. Fibrosis correlated significantly with inflammation and fractional dose. In conclusion, the parameter of ear thickness can be used as an objective, numerical and dose-dependent quantification criterion to characterize the severity of acute toxicity and allow for the prediction of late effects.

14.
BMC Public Health ; 19(1): 335, 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30902073

RESUMO

BACKGROUND: Active play and physical activity are important for preventing childhood obesity, building healthy bones and muscles, reducing anxiety and stress, and increasing self-esteem. Unfortunately, safe and accessible play places are often lacking in under-resourced communities. Play Streets (temporary closure of streets) are an understudied intervention that provide safe places for children, adolescents, and their families to actively play. This systematic review examines how Play Streets impact opportunities for children and adolescents to engage in safe active play and physical activity, and for communities and neighborhoods. Methods for evaluating Play Streets were also examined. METHODS: A systematic literature review was conducted in Academic Search Complete, CINHAL, PsycINFO, PubMED, Web of Science, and Google Scholar. Peer-reviewed intervention studies published worldwide were included if they were published in English, through December 2017 and documented free-to-access Play Streets or other temporary spaces that incorporated a designated area for children and/or adolescents to engage in active play. Systematic data extraction documented sample, implementation, and measurement characteristics and outcomes. RESULTS: Of 180 reviewed abstracts, 6 studies met inclusion criteria. Studies were conducted in five different countries (n = 2 in U.S.), using mostly cross-sectional study designs (n = 4). Physical activity outcomes were measured in half of the studies; one used observational and self-report measures, and two used device-based and self-report measures. In general, Play Streets provided safe places for child play, increased sense of community, and when measured, data suggest increased physical activity overall and during Play Streets. CONCLUSIONS: Play Streets can create safe places for children to actively play, with promise of increasing physical activity and strengthening community. Given the popularity of Play Streets and the potential impact for active play, physical activity, and community level benefits, more rigorous evaluations and systematic reporting of Play Streets' evaluations are needed.


Assuntos
Exercício , Jogos e Brinquedos , Características de Residência , Adolescente , Criança , Estudos Transversais , Humanos , Segurança
15.
Sci Rep ; 9(1): 3060, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816134

RESUMO

Metal nanoparticles form potent nanoreactors, driven by the optical generation of energetic electrons and nanoscale heat. The relative influence of these two factors on nanoscale chemistry is strongly debated. This article discusses the temperature dependence of the dimerization of 4-nitrothiophenol (4-NTP) into 4,4'-dimercaptoazobenzene (DMAB) adsorbed on gold nanoflowers by Surface-Enhanced Raman Scattering (SERS). Raman thermometry shows a significant optical heating of the particles. The ratio of the Stokes and the anti-Stokes Raman signal moreover demonstrates that the molecular temperature during the reaction rises beyond the average crystal lattice temperature of the plasmonic particles. The product bands have an even higher temperature than reactant bands, which suggests that the reaction proceeds preferentially at thermal hot spots. In addition, kinetic measurements of the reaction during external heating of the reaction environment yield a considerable rise of the reaction rate with temperature. Despite this significant heating effects, a comparison of SERS spectra recorded after heating the sample by an external heater to spectra recorded after prolonged illumination shows that the reaction is strictly photo-driven. While in both cases the temperature increase is comparable, the dimerization occurs only in the presence of light. Intensity dependent measurements at fixed temperatures confirm this finding.

16.
Chem Sci ; 10(3): 936-942, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30774888

RESUMO

We present a versatile and simple method using electrochemistry for the exclusive functionalization of the edge of a graphene monolayer with metal nanoparticles or polymeric amino groups. The attachment of metal nanoparticles allows us to exploit surface-enhanced Raman scattering to characterize the chemistry of both the pristine and the functionalized graphene edge. For the pristine patterned graphene edge, we observe the typical edge-related modes, while for the functionalized graphene edge we identify the chemical structure of the functional layer by vibrational fingerprinting. The ability to obtain single selectively functionalized graphene edges routinely on an insulating substrate opens an avenue for exploring the effect of edge chemistry on graphene properties systematically.

17.
Am J Health Promot ; 33(2): 191-198, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29860864

RESUMO

PURPOSE: The purpose of this study was to examine the association between the presence of supportive community planning documents in US municipalities with design standards and requirements supportive of active living. DESIGN: Cross-sectional study using data from the 2014 National Survey of Community-Based Policy and Environmental Supports for Healthy Eating and Active Living. SETTING: Nationally representative sample of US municipalities. PARTICIPANTS: Respondents are 2005 local officials. MEASURES: Assessed: (1) The presence of design standards and feature requirements and (2) the association between planning documents and design standards and feature requirements supportive of active living in policies for development. ANALYSIS: Using logistic regression, significant trends were identified in the presence of design standards and feature requirements by plan and number of supportive objectives present. RESULTS: Prevalence of design standards ranged from 19% (developer dedicated right-of-way for bicycle infrastructure development) to 50% (traffic-calming features in areas with high pedestrian and bicycle volume). Features required in policies for development ranged from 14% (short/medium pedestrian-scale block sizes) to 44% (minimum sidewalk widths of 5 feet) of municipalities. As the number of objectives in municipal plans increased, there was a significant and positive trend ( P < .05) in the prevalence of each design standard and requirement. CONCLUSIONS: Municipal planning documents containing objectives supportive of physical activity are associated with design standards and feature requirements supportive of activity-friendly communities.


Assuntos
Planejamento de Cidades/organização & administração , Participação da Comunidade/métodos , Planejamento Ambiental , Exercício , Promoção da Saúde/organização & administração , Estudos Transversais , Humanos , Políticas , Características de Residência , Fatores Socioeconômicos , Transportes , Estados Unidos
18.
Br J Radiol ; 92(1095): 20180466, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30359081

RESUMO

Extraordinary normal tissue response to highly spatially fractionated X-ray beams has been explored for over 25 years. More recently, alternative radiation sources have been developed and utilized with the aim to evoke comparable effects. These include protons, which lend themselves well for this endeavour due to their physical depth dose characteristics as well as corresponding variable biological effectiveness. This paper addresses the motivation for using protons to generate spatially fractionated beams and reviews the technological implementations and experimental results to date. This includes simulation and feasibility studies, collimation and beam characteristics, dosimetry and biological considerations as well as the results of in vivo and in vitro studies. Experimental results are emerging indicating an extraordinary normal tissue sparing effect analogous to what has been observed for synchrotron generated X-ray microbeams. The potential for translational research and feasibility of spatially modulated proton beams in clinical settings is discussed.


Assuntos
Fracionamento da Dose de Radiação , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Animais , Humanos , Radiometria/métodos
19.
Cancers (Basel) ; 10(11)2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30463322

RESUMO

Gliomas are primary brain tumors that present the majority of malignant adult brain tumors. Gliomas are subdivided into low- and high-grade tumors. Despite extensive research in recent years, the prognosis of malignant glioma patients remains poor. This is caused by naturally highly infiltrative capacities as well as high levels of radio- and chemoresistance. Additionally, it was shown that low linear energy transfer (LET) irradiation enhances migration and invasion of several glioma entities which might counteract today's treatment concepts. However, this finding is discussed controversially. In the era of personalized medicine, this controversial data might be attributed to the patient-specific heterogeneity that ultimately could be used for treatment. Thus, current developments in glioma therapy should be seen in the context of intrinsic and radiation-enhanced migration and invasion. Due to the natural heterogeneity of glioma cells and different radiation responses, a personalized radiation treatment concept is suggested and alternative radiation concepts are discussed.

20.
Sci Rep ; 8(1): 16063, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30375461

RESUMO

DNA double strand breaks (DSB) play a pivotal role for cellular damage, which is a hazard encountered in toxicology and radiation protection, but also exploited e.g. in eradicating tumors in radiation therapy. It is still debated whether and in how far clustering of such DNA lesions leads to an enhanced severity of induced damage. Here we investigate - using focused spots of ionizing radiation as damaging agent - the spatial extension of DNA lesion patterns causing cell inactivation. We find that clustering of DNA damage on both the nm and µm scale leads to enhanced inactivation compared to more homogeneous lesion distributions. A biophysical model interprets these observations in terms of enhanced DSB production and DSB interaction, respectively. We decompose the overall effects quantitatively into contributions from these lesion formation processes, concluding that both processes coexist and need to be considered for determining the resulting damage on the cellular level.


Assuntos
Fenômenos Biofísicos , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Dano ao DNA/efeitos da radiação , Reparo do DNA/efeitos da radiação , Humanos , Transferência Linear de Energia , Radiação Ionizante
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