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Radio-frequency particle accelerators are engines of discovery, powering high-energy physics and photon science, but are also large and expensive due to their limited accelerating fields. Plasma-wakefield accelerators (PWFAs) provide orders-of-magnitude stronger fields in the charge-density wave behind a particle bunch travelling in a plasma, promising particle accelerators of greatly reduced size and cost. However, PWFAs can easily degrade the beam quality of the bunches they accelerate. Emittance, which determines how tightly beams can be focused, is a critical beam quality in for instance colliders and free-electron lasers, but is particularly prone to degradation. We demonstrate, for the first time, emittance preservation in a high-gradient and high-efficiency PWFA while simultaneously preserving charge and energy spread. This establishes that PWFAs can accelerate without degradation-an essential step toward energy boosters in photon science and multistage facilities for compact high-energy particle colliders.
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Planetary exploration relies considerably on mineral characterization to advance our understanding of the solar system, the planets and their evolution. Thus, we must understand past and present processes that can alter materials exposed on the surface, affecting space mission data. Here, we analyze the first dataset monitoring the evolution of a known mineral target in situ on the Martian surface, brought there as a SuperCam calibration target onboard the Perseverance rover. We used Raman spectroscopy to monitor the crystalline state of a synthetic apatite sample over the first 950 Martian days (sols) of the Mars2020 mission. We note significant variations in the Raman spectra acquired on this target, specifically a decrease in the relative contribution of the Raman signal to the total signal. These observations are consistent with the results of a UV-irradiation test performed in the laboratory under conditions mimicking ambient Martian conditions. We conclude that the observed evolution reflects an alteration of the material, specifically the creation of electronic defects, due to its exposure to the Martian environment and, in particular, UV irradiation. This ongoing process of alteration of the Martian surface needs to be taken into account for mineralogical space mission data analysis.
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We aimed to assess DPNCheck's reliability for repeated sural nerve conduction (NC) parameters. This post hoc analysis used data from the randomized controlled ACUDPN trial assessing NC of the N. Suralis every eight weeks over a 6-month period in 62 patients receiving acupuncture against diabetic peripheral neuropathy (DPN) symptoms. The reliability of DPNCheck for nerve conduction velocity and amplitude was assessed using intraclass correlation coefficients (ICC) and was calculated using data from single time points and repeated measures design. The results of the NC measurements were correlated with the Total Neuropathy Score clinical (TNSc). Overall, for both nerve velocity and amplitude, the reliability at each measurement time point can be described as moderate to good and the reliability using repeated measures design can be described as moderate. Nerve velocity and amplitude showed weak correlation with TNSc. DPNCheck's reliability results question its suitability for monitoring DPN's progression. Given the limitation of our analysis, a long-term, pre-specified, fully crossed study should be carried out among patients with DPN to fully determine the suitability of the device for DPN progression monitoring. This was the first analysis assessing the reliability of the DPNCheck for DPN progression monitoring using data from multiple collection time points.
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Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/terapia , Condução Nervosa/fisiologia , Sistemas Automatizados de Assistência Junto ao Leito , Reprodutibilidade dos Testes , Nervo Sural , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
In thin film deposition processes, the lower limit of the deposition temperature is determined by the used coating technology and the duration of the coating process and is usually higher than room temperature. Hence, the processing of thermally sensitive materials and the adjustability of thin film morphology are limited. In consequence, for factual low-temperature deposition processes, an active cooling of the substrate is required. The effect of low substrate temperature on thin film properties during ion beam sputtering was investigated. The S i O 2 and T a 2 O 5 films grown at 0°C show a trend of lower optical losses and higher laser induced damage threshold (LIDT) compared to 100°C.
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The design of structurally diverse enzymes is constrained by long-range interactions that are necessary for accurate folding. We introduce an atomistic and machine learning strategy for the combinatorial assembly and design of enzymes (CADENZ) to design fragments that combine with one another to generate diverse, low-energy structures with stable catalytic constellations. We applied CADENZ to endoxylanases and used activity-based protein profiling to recover thousands of structurally diverse enzymes. Functional designs exhibit high active-site preorganization and more stable and compact packing outside the active site. Implementing these lessons into CADENZ led to a 10-fold improved hit rate and more than 10,000 recovered enzymes. This design-test-learn loop can be applied, in principle, to any modular protein family, yielding huge diversity and general lessons on protein design principles.
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Técnicas de Química Combinatória , Endo-1,4-beta-Xilanases , Engenharia de Proteínas , Catálise , Domínio Catalítico , Engenharia de Proteínas/métodos , Endo-1,4-beta-Xilanases/químicaRESUMO
Before the Perseverance rover landing, the acoustic environment of Mars was unknown. Models predicted that: (1) atmospheric turbulence changes at centimetre scales or smaller at the point where molecular viscosity converts kinetic energy into heat1, (2) the speed of sound varies at the surface with frequency2,3 and (3) high-frequency waves are strongly attenuated with distance in CO2 (refs. 2-4). However, theoretical models were uncertain because of a lack of experimental data at low pressure and the difficulty to characterize turbulence or attenuation in a closed environment. Here, using Perseverance microphone recordings, we present the first characterization of the acoustic environment on Mars and pressure fluctuations in the audible range and beyond, from 20 Hz to 50 kHz. We find that atmospheric sounds extend measurements of pressure variations down to 1,000 times smaller scales than ever observed before, showing a dissipative regime extending over five orders of magnitude in energy. Using point sources of sound (Ingenuity rotorcraft, laser-induced sparks), we highlight two distinct values for the speed of sound that are about 10 m s-1 apart below and above 240 Hz, a unique characteristic of low-pressure CO2-dominated atmosphere. We also provide the acoustic attenuation with distance above 2 kHz, allowing us to explain the large contribution of the CO2 vibrational relaxation in the audible range. These results establish a ground truth for the modelling of acoustic processes, which is critical for studies in atmospheres such as those of Mars and Venus.
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The interaction of intense particle bunches with plasma can give rise to plasma wakes1,2 capable of sustaining gigavolt-per-metre electric fields3,4, which are orders of magnitude higher than provided by state-of-the-art radio-frequency technology5. Plasma wakefields can, therefore, strongly accelerate charged particles and offer the opportunity to reach higher particle energies with smaller and hence more widely available accelerator facilities. However, the luminosity and brilliance demands of high-energy physics and photon science require particle bunches to be accelerated at repetition rates of thousands or even millions per second, which are orders of magnitude higher than demonstrated with plasma-wakefield technology6,7. Here we investigate the upper limit on repetition rates of beam-driven plasma accelerators by measuring the time it takes for the plasma to recover to its initial state after perturbation by a wakefield. The many-nanosecond-level recovery time measured establishes the in-principle attainability of megahertz rates of acceleration in plasmas. The experimental signatures of the perturbation are well described by simulations of a temporally evolving parabolic ion channel, transferring energy from the collapsing wake to the surrounding media. This result establishes that plasma-wakefield modules could be developed as feasible high-repetition-rate energy boosters at current and future particle-physics and photon-science facilities.
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PURPOSE: To evaluate the protein expression characteristics of genes employed in a recently introduced prognostic gene expression assay for patients with cutaneous melanoma (CM). METHODS: We studied 37 patients with CM and 10 with benign (melanocytic) nevi (BN). Immunohistochemistry of primary tumor tissue was performed for eight proteins: COL6A6, DCD, GBP4, KLHL41, KRT9, PIP, SCGB1D2, SCGB2A2. RESULTS: The protein expression of most markers investigated was relatively low (e.g., DCD, KRT9, SCGB1D2) and predominantly cytoplasmatic in melanocytes and keratinocytes. COL6A6, GBP4, and KLHL41 expression was significantly enhanced in CM when compared to BN. DCD protein expression was significantly correlated with COL6A6, GBP4, and KLHL41. GBP4 was positively correlated with KLHL41 and inversely correlated with SCGB2B2. The latter was also inversely correlated with serum S100B levels at time of initial diagnosis. The presence of SCGB1D2 expression was significantly associated with ulceration of the primary tumor. KRT9 protein expression was significantly more likely found in acral lentiginous melanoma. The presence of DCD expression was less likely associated with superficial spreading melanoma subtype but significantly associated with non-progressive disease. The absence of SCGB2A2 expression was significantly more often observed in patients who did not progress to stage III or IV. CONCLUSIONS: The expression levels observed were relatively low but differed in part with those found in BN. Even though we detected some significant correlations between the protein expression levels and clinical parameters (e.g., CM subtype, course of disease), there was no major concordance with the protective or risk-associated functions of the corresponding genes included in a recently introduced prognostic gene expression assay.
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Melanoma , Nevo Pigmentado , Neoplasias Cutâneas , Humanos , Melanoma/metabolismo , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/metabolismo , Nevo Pigmentado/patologia , Prognóstico , Secretoglobinas , Neoplasias Cutâneas/patologia , Melanoma Maligno CutâneoRESUMO
Engineering non-linear hybrid light-matter states in tailored lattices is a central research strategy for the simulation of complex Hamiltonians. Excitons in atomically thin crystals are an ideal active medium for such purposes, since they couple strongly with light and bear the potential to harness giant non-linearities and interactions while presenting a simple sample-processing and room temperature operability. We demonstrate lattice polaritons, based on an open, high-quality optical cavity, with an imprinted photonic lattice strongly coupled to excitons in a WS2 monolayer. We experimentally observe the emergence of the canonical band-structure of particles in a one-dimensional lattice at room temperature, and demonstrate frequency reconfigurability over a spectral window exceeding 85 meV, as well as the systematic variation of the nearest-neighbour coupling, reflected by a tunability in the bandwidth of the p-band polaritons by 7 meV. The technology presented in this work is a critical demonstration towards reconfigurable photonic emulators operated with non-linear photonic fluids, offering a simple experimental implementation and working at ambient conditions.
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BACKGROUND: Acupuncture is used to treat patients with diabetic peripheral neuropathy; however, the evidence is unclear. We present the design and methodology of the ACUDPN (ACUpuncture in Diabetic Peripheral Neuropathy) trial, which investigates the effectiveness of acupuncture for the treatment of diabetic peripheral neuropathy (DPN) symptoms. The aim of this study is to investigate whether acupuncture is effective for the treatment of DPN symptoms. METHODS: This study is a two-armed, randomized, controlled, parallel group, open-label, confirmatory, multicenter trial (8-week intervention period plus 16 weeks of follow-up). Physicians in outpatient units in Germany who specialize in acupuncture treatment will treat 110 diabetes type II patients with clinical symptoms of peripheral neuropathy in the feet and legs with signs of neuropathy according to nerve conduction testing. The patients will be randomized in a 1:1 ratio to one of the following two groups: (a) semi-standardized acupuncture plus routine care or (b) routine care alone. Acupuncture will consist of 12 treatments per patient over 8 weeks. The primary outcome will be the overall DPN-related complaints in the extremities after 8 weeks as measured by the Visual Analog Scale (VAS). Further outcome measures will include DPN-related pain, the Neuropathic Pain Symptom Inventory (NPSI), Diabetic Peripheral Neuropathic Pain Impact (DPNPI) scores, and nerve conduction parameters of the sural nerve at weeks 8, 16, and 24. DISCUSSION: The results of this trial will be available in 2021 and will help clarify whether acupuncture can be considered effective for the treatment of DPN with regard to the subdimensions of the neuropathic clinical picture. TRIAL REGISTRATION: ClinicalTrials.gov NCT03755960 . Registered on 11 August 2018.
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Terapia por Acupuntura , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Terapia por Acupuntura/efeitos adversos , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/terapia , Alemanha , Humanos , Estudos Multicêntricos como Assunto , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Energy-efficient plasma-wakefield acceleration of particle bunches with low energy spread is a promising path to realizing compact free-electron lasers and particle colliders. High efficiency and low energy spread can be achieved simultaneously by strong beam loading of plasma wakefields when accelerating bunches with carefully tailored current profiles [M. Tzoufras et al., Phys. Rev. Lett. 101, 145002 (2008)PRLTAO0031-900710.1103/PhysRevLett.101.145002]. We experimentally demonstrate such optimal beam loading in a nonlinear electron-driven plasma accelerator. Bunches with an initial energy of 1 GeV were accelerated by 45 MeV with an energy-transfer efficiency of (42±4)% at a gradient of 1.3 GV/m while preserving per-mille energy spreads with full charge coupling, demonstrating wakefield flattening at the few-percent level.
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BACKGROUND AND OBJECTIVE: Toric intraocular lenses (IOL) provide a reliable and predictable option for permanent correction of corneal astigmatism. In order to determine the lens strength necessary for achieving the desired correction, the operator can either use the calculation mode implemented in the biometry device or the calculation service offered by the lens manufacturer; however, in many cases a classical lens calculation from biometric data is not carried out but only a simplified estimation, which translates the corneal astigmatism into the torus of the toric IOL. This translational ratio, which is mostly used as an average standard value, can however show a substantial range of variation, so that in a worst case scenario an undercorrection of the refractive cylinder of up to 12.5â¯% or an overcorrection of up to 17â¯% can result. The purpose of this study was to elaborate the biometric effect sizes which determine the relationship between the corneal astigmatism to be corrected and the torus necessary for a full correction of an IOL. METHODS: A total of 16,744 datasets were extracted from the IOLCon web platform and initially the axial position of the IOL implant was derived independent of a formula, based on the preoperative biometric values and the postoperative spherical equivalent. Subsequently, based on a ray propagation strategy for spherocylindrical vergences, the corresponding refractive value of a full correcting toric IOL was calculated. The translational relationship as a ratio between lens toricity and corneal astigmatism was analyzed for potential biometric effect sizes with a Monte Carlo simulation. RESULTS: The Monte Carlo simulation showed that the ratio of lens toricity to corneal astigmatism cannot be assumed as being constant. The analyzed data revealed an average translational ratio of 1.3938⯱ 0.0595 (median 1.3921) with a range from 1.2131 to 1.5974. The axial position of the IOL was found to have the greatest influence, whereby the more posterior the lens position the higher the ratio. Due to the correlation of axial eye length and axial lens position, the eye length can be assumed to be an indirect effect size. The corneal equivalent refractive strength and the corneal astigmatism have no noteworthy effect on the translational ratio. CONCLUSION: Many calculation tools on the market simplify toric IOL power calculation by assuming a constant ratio of lens toricity to corneal astigmatism; however, the present simulation study showed that such a simplification can lead to clearly incorrect results. Accordingly, an individual calculation of IOL toricity based on biometric parameters (e.g. based on vergence propagation matrices or full aperture ray tracing) is recommended.
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Astigmatismo , Lentes Intraoculares , Facoemulsificação , Astigmatismo/diagnóstico , Astigmatismo/cirurgia , Biometria , Humanos , Implante de Lente Intraocular , Método de Monte Carlo , Óptica e Fotônica , Refração OcularRESUMO
Plasma-wakefield accelerators driven by intense particle beams promise to significantly reduce the size of future high-energy facilities. Such applications require particle beams with a well-controlled energy spectrum, which necessitates detailed tailoring of the plasma wakefield. Precise measurements of the effective wakefield structure are therefore essential for optimising the acceleration process. Here we propose and demonstrate such a measurement technique that enables femtosecond-level (15 fs) sampling of longitudinal electric fields of order gigavolts-per-meter (0.8 GV m-1). This method-based on energy collimation of the incoming bunch-made it possible to investigate the effect of beam and plasma parameters on the beam-loaded longitudinally integrated plasma wakefield, showing good agreement with particle-in-cell simulations. These results open the door to high-quality operation of future plasma accelerators through precise control of the acceleration process.
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The large oscillator strength of excitons in transition metal dichalcogenide layers facilitates the formation of exciton-polariton resonances for monolayers and van-der-Waals heterostructures embedded in optical microcavities. Here, we show, that locally changing the number of layers in a WSe2/hBN/WSe2 van-der-Waals heterostructure embedded in a monolithic, high-quality-factor cavity gives rise to a local variation of the coupling strength. This effect yields a polaritonic stair case potential, which we demonstrate at room temperature. Our result paves the way towards engineering local polaritonic potentials at length scales down to atomically sharp interfaces, based on purely modifying its real part contribution via the coherent light-matter coupling strength g.
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The ability to create atomically perfect, epitaxial heterostructures of correlated complex perovskite oxides using state-of-art thin film deposition techniques has generated new physical phenomena at engineered interfaces. Here we report on the impact of growth kinetics on the magnetic structure and exchange coupling at the interface in heterostructures combining layers of antiferromagnetic La1/3Sr2/3FeO3 (LSFO) and ferromagnetic La2/3Sr1/3MnO3 (LSMO) on (0 0 1)-oriented SrTiO3 (STO) substrates. Two growth orders are investigated, (a) LSMO/LSFO/STO(0 0 1) and (b) LSFO/LSMO/STO(0 0 1), where the LSFO layer is grown by molecular beam epitaxy and the LSMO layer by high oxygen pressure sputtering. The interface has been investigated using electron microscopy and polarized neutron reflectometry. Interdiffusion over seven monolayers is observed in LSMO/LSFO (a) with an almost 50% reduction in magnetization at the interface and showing no exchange coupling. However, the exchange bias effect ([Formula: see text] mT at 10 K) could be realized when the interface is atomically sharp, as in LSFO/LSMO (b). Our study therefore reveals that, even for well ordered and lattice-matched structures, the kinetics involved in the growth processes drastically influences the interface quality with a strong correlation to the magnetic properties.
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Wastewater may contain a diverse group of unregulated pollutants known as emerging pollutants, such as pharmaceuticals and personal care products (PPCPs). Triclosan (TCS) is a personal care product widely used as an antiseptic or preservative in cosmetics, hand wash, toothpaste and deodorant soaps. Advanced oxidation processes (AOPs) have been used as effective and alternative treatments for complex wastewater. However, an important criterion for the assessment of AOPs and their operation conditions could be the potential formation of new toxic secondary products, such as polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), especially when emerging pollutants are present in the media. If these are omitted from environmental management studies, the real environmental impacts of a WWTPs (wastewater treatment plants) may be underestimated. Consequently, the current study aims to evaluate the environmental impacts derived from electrooxidation (EOX), one of the most effective oxidation technologies, of emerging pollutants using Life Cycle Assessment. The analyses were performed for the treatment of effluents containing TCS, firstly without considering the formation of PCDD/Fs and, thereafter, considering the effects of these compounds. Total toxicity, calculated through different methods and corresponding impact factors, were evaluated for each stage of the process when different electrolytes are used, including PCDD/Fs formation. Finally, a sensitivity analysis was carried out to study i) the effect of the TCS initial concentration on the environmental impacts associated to ecotoxicity for the different life cycle methods and ii) the influence of changing the organic pollutant on PCDD/Fs formation employing 2-chlorophenol (2-CP). As a result, LCIA methods demonstrate that they are not fully adapted to the computation of PCDD/Fs in the water compartment, since only 2,3,7,8-tetraclorodibenzo-p-dioxina (2,3,7,8-TCDD) is present as a substance in the impact categories assessed, ignoring the remaining list of PCDD/Fs.
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Águas Residuárias/química , Dibenzofuranos , Dibenzofuranos Policlorados , Monitoramento Ambiental , Dibenzodioxinas Policloradas , TriclosanRESUMO
BACKGROUND: Sodium lauryl sulfate (SLS) is the best-studied detergent in irritant contact dermatitis. In atopic dermatitis, the two major pathophysiological abnormalities concern skin barrier function and regulation of cutaneous immune responses. The probability of atopic skin diathesis can be assessed by comprehensive analysis of patient history, as well as clinical and laboratory findings, resulting in the Erlangen Atopy Score (EAS). OBJECTIVES: To investigate the impacts of (i) atopic skin diathesis according to the EAS and (ii) the physician-assessed diagnoses 'atopic dermatitis', 'allergic rhinitis' and 'allergic asthma' on SLS skin reactions. METHODS: This is a retrospective analysis of data from 2030 consecutive patients patch tested with SLS (0·25% aqueous) from two tertiary referral centres in Germany, from 2008 to 2014. RESULTS: Patients with a high probability of atopic skin diathesis showed no significant increase in positive SLS reactions compared with patients without atopic skin diathesis (14·2% vs. 16·8%). The grading of positive SLS skin reactions (1-4) revealed no differences in patients with or without atopic skin diathesis. Furthermore, diagnoses of atopic dermatitis, allergic rhinitis or allergic asthma had no impact on positive SLS skin reactions in multivariate logistic regression analysis. CONCLUSIONS: We found no association of increased skin irritability to SLS with atopic skin diathesis, atopic dermatitis, allergic rhinitis or allergic asthma in a large patient cohort. It therefore seems that the test of skin irritability with SLS, which is currently common practice in many centres, does not allow prediction of susceptibility to irritant eczematous inflammation in atopic vs. nonatopic individuals. What's already known about this topic? Irritant contact dermatitis and atopic skin diathesis share impaired skin barrier function as a pathophysiological pattern. Sodium lauryl sulfate (SLS) is tested at 0·25% aqueous as an irritant control in patch testing, and hence the results might be affected by atopic skin diathesis. What does this study add? Challenging a long-standing paradigm, we found no association of increased reactivity to SLS patch tests in individuals with atopic skin diathesis, atopic dermatitis, allergic rhinitis or allergic asthma in a large patient cohort. Thus, irritant control testing with SLS, which is useful in interpreting doubtful allergen patch test results, does not depend on individual atopy status.
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Irritantes , Suscetibilidade a Doenças , Alemanha , Humanos , Irritantes/efeitos adversos , Testes do Emplastro , Estudos Retrospectivos , Dodecilsulfato de Sódio/efeitos adversosRESUMO
An international round-robin experiment has been conducted to test procedures and methods for the measurement of angle-resolved light scattering. ASTM E2387-05 has been used as the main guide, while the experience gained should also contribute to the new ISO standard of angle-resolved scattering currently under development (ISO/WD 19986:2016). Seven laboratories from Europe and the United States measured the angle-resolved scattering from Al/SiO2-coated substrates, transparent substrates, volume diffusors, quasi-volume diffusors, white calibration standards, and grating samples at laser wavelengths in the UV, VIS, and NIR spectra. Results were sent to Fraunhofer IOF, which coordinated the experiments and analyzed the data, while ESA-ESTEC, as the project donor, defined conditions and parameters. Depending mainly on the sample type, overall good to reasonable agreements were observed, with largest deviations at scattering angles very close to the specular beam. Volume diffusor characterization unexpectedly turned out to be challenging. Not all participants provided measurement uncertainty ranges according to the Guide to the Expression of Uncertainty in Measurement; often, a single general scatterometer-related measurement uncertainty value was stated. Although relative instrument measurement uncertainties close to 1% are sometimes claimed, the comparison results did not support these claims for specular scattering samples as mirrors, substrates, or gratings.