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1.
Nature ; 618(7964): 270-275, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37225995

RESUMO

The gravitational pressure in many astrophysical objects exceeds one gigabar (one billion atmospheres)1-3, creating extreme conditions where the distance between nuclei approaches the size of the K shell. This close proximity modifies these tightly bound states and, above a certain pressure, drives them into a delocalized state4. Both processes substantially affect the equation of state and radiation transport and, therefore, the structure and evolution of these objects. Still, our understanding of this transition is far from satisfactory and experimental data are sparse. Here we report on experiments that create and diagnose matter at pressures exceeding three gigabars at the National Ignition Facility5 where 184 laser beams imploded a beryllium shell. Bright X-ray flashes enable precision radiography and X-ray Thomson scattering that reveal both the macroscopic conditions and the microscopic states. The data show clear signs of quantum-degenerate electrons in states reaching 30 times compression, and a temperature of around two million kelvins. At the most extreme conditions, we observe strongly reduced elastic scattering, which mainly originates from K-shell electrons. We attribute this reduction to the onset of delocalization of the remaining K-shell electron. With this interpretation, the ion charge inferred from the scattering data agrees well with ab initio simulations, but it is significantly higher than widely used analytical models predict6.

3.
Sci Rep ; 11(1): 12883, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145307

RESUMO

We present structure and equation of state (EOS) measurements of biaxially orientated polyethylene terephthalate (PET, [Formula: see text], also called mylar) shock-compressed to ([Formula: see text]) GPa and ([Formula: see text]) K using in situ X-ray diffraction, Doppler velocimetry, and optical pyrometry. Comparing to density functional theory molecular dynamics (DFT-MD) simulations, we find a highly correlated liquid at conditions differing from predictions by some equations of state tables, which underlines the influence of complex chemical interactions in this regime. EOS calculations from ab initio DFT-MD simulations and shock Hugoniot measurements of density, pressure and temperature confirm the discrepancy to these tables and present an experimentally benchmarked correction to the description of PET as an exemplary material to represent the mixture of light elements at planetary interior conditions.

4.
PLoS One ; 16(4): e0249342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33793644

RESUMO

BACKGROUND: ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis and holds promise to sustain liver function and recovery of patients with acute-on-chronic liver failure (ACLF). Previously, ADVOS was tested as continuous treatment for intensive care patients with liver failure. Data related to the applicability and safety as discontinuous treatment outside of ICU is not available. AIM: Evaluation of ADVOS as discontinuous treatment for patients with ACLF outside intensive care unit and comparison with a matched historic cohort. METHODS AND RESULTS: In this retrospective study, 26 patients with ACLF and the indication for renal replacement therapy related to HRS-AKI were included. Majority of patients were male (65%) with alcoholic cirrhosis in 88% and infections as a trigger of ACLF in 96%. Liver function was severely compromised reflected by high median MELD and CLIF-C ACLF scores of 37 (IQR 32;40) and 56.5 (IQR 51;60), respectively. Patients were treated discontinuously with ADVOS over a median time of 12 days (IQR 8.25;17) and received 8 (IQR 4.25;9.75) treatment cycles on average. No treatment related adverse events were recorded, and safety laboratory parameters remained constant during the observation time. After 16 h cumulative dialysis therapy, ADVOS significantly reduced protein-bound bilirubin (14%), creatinine (11.8%) and blood urea nitrogen (BUN, 33%). Using a matched cohort with ACLF treated with hemodialysis, ADVOS achieved a stronger decrease in bilirubin (p = 0.01), while detoxification of water-soluble catabolites' including creatinine and BUN was comparable. The 28-days mortality in the ADVOS group was 56% (14/26) and was not inferior to predicted survival (predicted median 28-days mortality was 44%, IQR 30; 59). CONCLUSION: Discontinuous ADVOS treatment was safe and effective in patients with ACLF outside intensive care and outperformed hemodialysis in reducing protein-bound metabolites.


Assuntos
Insuficiência Hepática Crônica Agudizada/terapia , Terapia de Substituição Renal , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/patologia , Bilirrubina/sangue , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Cuidados Críticos , Feminino , Humanos , Cirrose Hepática Alcoólica/complicações , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Diálise Renal , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
5.
Sci Total Environ ; 777: 146218, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-33689893

RESUMO

Environmental models aim to reproduce landscape processes with mathematical equations. Observations are used for validation. The performance and uncertainties are quantified either by single or multi-criteria model assessment. In a case-study, we combine both approaches. We use a coupled hydro-biogeochemistry landscape-scale model to simulate 14 target values on discharge, stream nitrate as well as soil moisture, soil temperature and trace gas emissions (N2O, CO2) from different land uses. We reveal typical mistakes that happen during both, single and multi-criteria model assessment. Such as overestimated uncertainty in multi-criteria and ignored wrong model processes in single-criterion calibration. These mistakes can mislead the development of water quality and in general all environmental models. Only the combination of both approaches reveals the five types of posterior probability distributions for model parameters. Each type allocates a specific type of error. We identify and locate mismatched parameter values, obsolete parameters, flawed model structures and wrong process representations. The presented method can guide model users and developers to the so far hidden errors in their models. We emphasize to include observations from physical, chemical, biological and ecological processes in the model assessment, rather than the typical discipline specific assessments.

6.
BMC Surg ; 21(1): 100, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622311

RESUMO

BACKGROUND: Epidermolysis bullosa is a group of rare inherited skin diseases characterized by blister formation following mechanical skin trauma. Epidermolysis bullosa is associated with increased skin cancer rates, predominantly squamous cell carcinomas, yet to our best knowledge, there is no reported case of dermatofibrosarcoma protuberans in a patient with Epidermolysis bullosa. CASE PRESENTATION: Here, we present a 26-year-old man with junctional epidermolysis bullosa, who developed a DFSP on the neck. Initial, the skin alteration was mistakenly not considered malignant, which resulted in inadequate safety margins. The complete resection required a local flap to close the defect, which is not unproblematic because of the chronic inflammation and impaired healing potential of the skin due to Epidermolysis bullosa. CONCLUSIONS: To our best knowledge, this is the first reported case of a skin-associated sarcoma in a patient with EB; however, further investigation is required to verify a correlation.


Assuntos
Dermatofibrossarcoma , Epidermólise Bolhosa Juncional , Neoplasias Cutâneas , Adulto , Dermatofibrossarcoma/diagnóstico , Dermatofibrossarcoma/cirurgia , Epidermólise Bolhosa Juncional/epidemiologia , Humanos , Masculino , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/cirurgia
7.
Phys Rev Lett ; 126(1): 015703, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33480771

RESUMO

We present results from the SPring-8 Angstrom Compact free electron LAser facility, where we used a high intensity (∼10^{20} W/cm^{2}) x-ray pump x-ray probe scheme to observe changes in the ionic structure of silicon induced by x-ray heating of the electrons. By avoiding Laue spots in the scattering signal from a single crystalline sample, we observe a rapid rise in diffuse scattering and a transition to a disordered, liquidlike state with a structure significantly different from liquid silicon. The disordering occurs within 100 fs of irradiation, a timescale that agrees well with first principles simulations, and is faster than that predicted by purely inertial behavior, suggesting that both the phase change and disordered state reached are dominated by Coulomb forces. This method is capable of observing liquid scattering without masking signal from the ambient solid, allowing the liquid structure to be measured throughout and beyond the phase change.

8.
Nat Commun ; 11(1): 2620, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457297

RESUMO

The gas and ice giants in our solar system can be seen as a natural laboratory for the physics of highly compressed matter at temperatures up to thousands of kelvins. In turn, our understanding of their structure and evolution depends critically on our ability to model such matter. One key aspect is the miscibility of the elements in their interiors. Here, we demonstrate the feasibility of X-ray Thomson scattering to quantify the degree of species separation in a 1:1 carbon-hydrogen mixture at a pressure of ~150 GPa and a temperature of ~5000 K. Our measurements provide absolute values of the structure factor that encodes the microscopic arrangement of the particles. From these data, we find a lower limit of [Formula: see text]% of the carbon atoms forming isolated carbon clusters. In principle, this procedure can be employed for investigating the miscibility behaviour of any binary mixture at the high-pressure environment of planetary interiors, in particular, for non-crystalline samples where it is difficult to obtain conclusive results from X-ray diffraction. Moreover, this method will enable unprecedented measurements of mixing/demixing kinetics in dense plasma environments, e.g., induced by chemistry or hydrodynamic instabilities.

9.
Landsc Ecol ; 35(2): 483-499, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32165789

RESUMO

CONTEXT: The contribution of forest understory to the temperate forest carbon sink is not well known, increasing the uncertainty in C cycling feedbacks on global climate as estimated by Earth System Models. OBJECTIVES: We aimed at quantifying the effect of woody and non-woody understory vegetation on net ecosystem production (NEP) for a forested area of 158 km2 in the European Alps. METHODS: We simulated C dynamics for the period 2000-2014, characterized by above-average temperatures, windstorms and a subsequent bark beetle outbreak for the area, using the regional ecosystem model LandscapeDNDC. RESULTS: In the entire study area, woody and non-woody understory vegetation caused between 16 and 37% higher regional NEP as compared to a bare soil scenario over the 15-year period. The mean annual contribution of the understory to NEP was in the same order of magnitude as the average annual European (EU-25) forest C sink. After wind and bark beetle disturbances, the understory effect was more pronounced, leading to an increase in NEP between 35 and 67% compared to simulations not taking into account these components. CONCLUSIONS: Our findings strongly support the importance of processes related to the understory in the context of the climate change mitigation potential of temperate forest ecosystems. The expected increases in stand replacing disturbances due to climate change call for a better representation of understory vegetation dynamics and its effect on the ecosystem C balance in regional assessments and Earth System Models.

10.
J Cell Physiol ; 234(12): 21903-21914, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31026063

RESUMO

The aim of this study was to get new insights into molecular processes involved in tumor propagation of immortalized oral keratinocytes induced by the keystone pathogen Porphyromonas gingivalis. Cell culture experiments with immortalized OKF6 cells were performed to analyze cellular effects caused by bacterial stimulation focusing on altered gene expression, signaling pathways, proliferation rate, cell viability, migration and invasion behavior, and on the development of antiapoptotic pathways. Gene and protein expression were analyzed using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, western blot, and protein arrays. Trypan blue staining was used to analyze proliferation and viability, transwell assays for cellular migration, Matrigel assays for invasion, and anoikis-assays for evaluating anoikis resistance. Stimulation of OKF6 cells with Porphyromonas gingivalis led to an alteration in the molecular repertoire of proteins which are involved in cell proliferation, epithelial-mesenchymal transition, stem cell formation, migration, invasion, and anoikis resistance. Higher proliferation rates were detected in conjunction with an activation of PI3K/Akt signaling and the mTOR-pathway. Additionally, inhibition of glycogen-synthase-kinase3-ß led to stabilization of ß-catenin and Snail, which resulted in a switch from predominant E-cadherin to N-cadherin expression and increased expression of the stem cell markers Oct3/4, Sox2, and Nanog. Enhanced biosynthesis and enzyme activity of matrix metalloproteinase-9 was accompanied by elevated invasion behavior. Finally, anoikis resistance was detected in stimulated keratinocytes by decreased apoptosis of nonadherent cells and elevated expression of epidermal growth factor receptor and c-Met. Hence, Porphyromonas gingivalis is able to induce a more aggressive tumor-like phenotype in immortalized oral keratinocytes, thus contributing to enhanced tumor features.


Assuntos
Células Epiteliais/metabolismo , Queratinócitos/metabolismo , Neoplasias/patologia , Porphyromonas gingivalis/metabolismo , Movimento Celular/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Regulação da Expressão Gênica/fisiologia , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo
11.
Sci Rep ; 9(1): 4196, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30862904

RESUMO

We investigated the high-pressure behavior of polyethylene (CH2) by probing dynamically-compressed samples with X-ray diffraction. At pressures up to 200 GPa, comparable to those present inside icy giant planets (Uranus, Neptune), shock-compressed polyethylene retains a polymer crystal structure, from which we infer the presence of significant covalent bonding. The A2/m structure which we observe has previously been seen at significantly lower pressures, and the equation of state measured agrees with our findings. This result appears to contrast with recent data from shock-compressed polystyrene (CH) at higher temperatures, which demonstrated demixing and recrystallization into a diamond lattice, implying the breaking of the original chemical bonds. As such chemical processes have significant implications for the structure and energy transfer within ice giants, our results highlight the need for a deeper understanding of the chemistry of high pressure hydrocarbons, and the importance of better constraining planetary temperature profiles.

12.
Rev Sci Instrum ; 89(10): 10G111, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30399716

RESUMO

We have developed and fielded a new x-ray pinhole-imaging snout that exploits time-resolved penumbral imaging of low-emission hot spots in capsule implosion experiments at the National Ignition Facility. We report results for a series of indirectly driven Be capsule implosions that aim at measuring x-ray Thomson scattering (XRTS) spectra at extreme density conditions near stagnation. In these implosions, x-ray emission at stagnation is reduced by 100-1000× compared to standard inertial confinement fusion (ICF) implosions to mitigate undesired continuum background in the XRTS spectra. Our snout design not only enables measurements of peak x-ray emission times, t o , where standard ICF diagnostics would not record any signal, but also allows for inference of hot spot shapes. Measurement of t o is crucial to account for shot-to-shot variations in implosion velocity and therefore to benchmark the achieved plasma conditions between shots and against radiation hydrodynamic simulations. Additionally, we used differential filtering to infer a hot spot temperature of 520 ± 80 eV, which is in good agreement with predictions from radiation hydrodynamic simulations. We find that, despite fluctuations of the x-ray flash intensity of up to 5×, the emission time history is similar from shot to shot and slightly asymmetric with respect to peak x-ray emission.

13.
Phys Rev Lett ; 121(2): 025001, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30085737

RESUMO

We have developed an experimental platform for the National Ignition Facility that uses spherically converging shock waves for absolute equation-of-state (EOS) measurements along the principal Hugoniot. In this Letter, we present one indirect-drive implosion experiment with a polystyrene sample that employs radiographic compression measurements over a range of shock pressures reaching up to 60 Mbar (6 TPa). This significantly exceeds previously published results obtained on the Nova laser [R. Cauble et al., Phys. Rev. Lett. 80, 1248 (1998)PRLTAO0031-900710.1103/PhysRevLett.80.1248] at a strongly improved precision, allowing us to discriminate between different EOS models. We find excellent agreement with Kohn-Sham density-functional-theory-based molecular dynamics simulations.

14.
Phys Rev Lett ; 121(24): 245501, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30608736

RESUMO

We present results for the ionic structure in hydrocarbons (polystyrene, polyethylene) that were shock compressed to pressures of up to 190 GPa, inducing rapid melting of the samples. The structure of the resulting liquid is then probed using in situ diffraction by an x-ray free electron laser beam, demonstrating the capability to obtain reliable diffraction data in a single shot, even for low-Z samples without long range order. The data agree well with ab initio simulations, validating the ability of such approaches to model mixed samples in states where complex interparticle bonds remain, and showing that simpler models are not necessarily valid. While the results clearly exclude the possibility of complete carbon-hydrogen demixing at the conditions probed, they also, in contrast to previous predictions, indicate that diffraction is not always a sufficient diagnostic for this phenomenon.

15.
Mol Oral Microbiol ; 33(2): 133-142, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28992390

RESUMO

The present in vitro study examines molecular processes that are relevant during bone homeostasis after Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis infection with a focus on the differentiation level of osteoblasts. Regenerative processes are often hindered by the recurrence of bacterial infections, which can ultimately provoke a severe destruction of bone tissue. To obtain more detailed insights into such a complex scenario, we have used undifferentiated MG63 osteoblast-like cells as an experimental paradigm to examine the impact of two oral pathogens, A. actinomycetemcomitans and P. gingivalis, on proliferation, cytotoxicity and osteogenic differentiation. Cell culture experiments were performed to analyze cellular behavior. The level of genes interfering with bone tissue integrity (matrix metalloproteinases and their tissue inhibitors) and osteogenic markers (alkaline phosphatase, Runx2, human ß-defensin-2) was compared in undifferentiated versus differentiated MG63 cells using real-time polymerase chain reaction. Functional activity of matrix metalloproteinases was quantified by zymography. Western blot analysis was used to verify the phosphorylation state of mitogen-activated protein kinases p38 and extracellular-signal-regulated kinases 1/2. When co-cultured with undifferentiated MG63 cells, oral pathogens provoked distinct cellular effects. Only A. actinomycetemcomitans reduced cell proliferation, increased cell death, and induced osteogenic differentiation. A comparison of matrix metalloproteinase network stability in the presence of oral pathogens revealed a partial sensitivity towards P. gingivalis but not A. actinomycetemcomitans. So, beside the proof of concept that MG63 cells co-cultured with oral pathogens can serve as an in vitro model for mimicking destructive and regenerative events after bacterial infections, our data indicate that double infections might counterbalance otherwise positive effects.


Assuntos
Aggregatibacter actinomycetemcomitans/patogenicidade , Diferenciação Celular , Osteoblastos/metabolismo , Osteoblastos/microbiologia , Porphyromonas gingivalis/patogenicidade , Fosfatase Alcalina/metabolismo , Técnicas de Cultura de Células , Morte Celular , Proliferação de Células , Técnicas de Cocultura , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Osteogênese/genética , Osteogênese/fisiologia , Inibidores Teciduais de Metaloproteinases/genética , Inibidores Teciduais de Metaloproteinases/metabolismo , Células Tumorais Cultivadas , beta-Defensinas/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Nat Commun ; 8: 15693, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28569766

RESUMO

The energy deposition of ions in dense plasmas is a key process in inertial confinement fusion that determines the α-particle heating expected to trigger a burn wave in the hydrogen pellet and resulting in high thermonuclear gain. However, measurements of ion stopping in plasmas are scarce and mostly restricted to high ion velocities where theory agrees with the data. Here, we report experimental data at low projectile velocities near the Bragg peak, where the stopping force reaches its maximum. This parameter range features the largest theoretical uncertainties and conclusive data are missing until today. The precision of our measurements, combined with a reliable knowledge of the plasma parameters, allows to disprove several standard models for the stopping power for beam velocities typically encountered in inertial fusion. On the other hand, our data support theories that include a detailed treatment of strong ion-electron collisions.

18.
HIV Med ; 18(8): 564-572, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28247589

RESUMO

OBJECTIVES: The number of HIV-infected individuals from developed countries travelling to tropical and subtropical areas has increased as a result of the clinical and survival benefits of combination antiretroviral therapy. The aim of our study was to describe the traveler population in the SHCS and to determine the frequency of viral rebound in virologically suppressed individuals after a travel episode to the tropics compared to non-travelers. METHODS: Swiss HIV Cohort Study participants with at least one follow-up visit between 1 January 1989 and 28 February 2015 were eligible for inclusion in the study. The primary outcome was the occurrence of viral rebound (viral load > 200 HIV-1 RNA copies/mL) after a travel episode compared with a nontravel episode in previously suppressed individuals (≤ 200 copies/mL). All virologically suppressed patients contributed multiple travel or nontravel episodes to the analysis. Logistic regression was performed including factors associated with viral rebound. RESULTS: We included 16 635 patients in the study, of whom 6084 (36.5%) had ever travelled to the tropics. Travel frequency increased over time, with travellers showing better HIV parameters than nontravellers [less advanced Centers for Disease Control and Prevention (CDC) stage and higher CD4 count nadir]. Viral rebound was seen in 477 (3.9%) of 12 265 travel episodes and in 5121 (4.5%) of 114 884 nontravel episodes [unadjusted odds ratio (OR) 0.87; 95% confidence interval (CI) 0.78-0.97]. Among these 477 post-travel viral rebounds, 115 had a resistance test performed and 51 (44%) of these showed new resistance mutations. Compared with European and North American patients, the odds for viral rebound were significantly lower in Southeast Asian (OR 0.67; 95% CI 0.51-0.88) and higher in sub-Saharan African (SSA) patients (OR 1.41; 95% CI 1.22-1.62). Travel further increased the odds of viral rebound in SSA patients (OR 2.00; 95% CI 1.53-2.61). CONCLUSIONS: Region of origin is the main risk factor for viral rebound rather than travel per se. Pre-travel adherence counselling should focus on patients of SSA origin.


Assuntos
Etnicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Viagem , Carga Viral , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Adesão à Medicação/psicologia , Estudos Prospectivos , RNA Viral/sangue , Suíça
19.
Phys Rev E ; 96(4-1): 043210, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29347630

RESUMO

For ion energy loss measurements in plasmas with near solid densities, an indirect laser heating scheme for carbon foils has been developed at GSI Helmholtzzentrum für Schwerionenforschung GmbH (Darmstadt, Germany). To achieve an electron density of 10^{22}cm^{3} and an electron temperature of 10-30eV, two carbon foils with an areal density of 100µg/cm^{2} heated in a double-hohlraum configuration have been chosen. In this paper we present the results of temperature measurements of both primary and secondary hohlraums for two different hohlraum designs. They were heated by the PHELIX laser with a wavelength of 527nm and an energy of 150J in 1.5ns. For this purpose the temperature has been investigated by an x-ray streak camera with a transmission grating as the dispersive element.

20.
Rev Sci Instrum ; 87(11): 11E515, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27910303

RESUMO

We are developing x-ray Thomson scattering for applications in implosion experiments at the National Ignition Facility. In particular we have designed and fielded MACS, a high-efficiency, gated x-ray spectrometer at 7.5-10 keV [T. Döppner et al., Rev. Sci. Instrum. 85, 11D617 (2014)]. Here we report on two new Bragg crystals based on Highly Oriented Pyrolytic Graphite (HOPG), a flat crystal and a dual-section cylindrically curved crystal. We have performed in situ calibration measurements using a brass foil target, and we used the flat HOPG crystal to measure Mo K-shell emission at 18 keV in 2nd order diffraction. Such high photon energy line emission will be required to penetrate and probe ultra-high-density plasmas or plasmas of mid-Z elements.

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