Graphene-based materials are highly interesting in virtue of their excellent chemical, physical and mechanical properties that make them extremely useful as privileged materials in different industrial applications. Sonochemical methods allow the production of low-defect graphene materials, which are preferred for certain uses. Graphene nanosheets (GNS) have been prepared by exfoliation of a commercial micrographite (MG) using an ultrasound probe. Both materials were characterized by common techniques such as X-ray diffraction (XRD), Transmission Electronic Microscopy (TEM), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). All of them revealed the formation of exfoliated graphene nanosheets with similar surface characteristics to the pristine graphite but with a decreased crystallite size and number of layers. An exhaustive study of the particle size distribution was carried out by different analytical techniques such as dynamic light scattering (DLS), nanoparticle tracking analysis (NTA) and asymmetric flow field flow fractionation (AF4). The results provided by these techniques have been compared. NTA and AF4 gave higher resolution than DLS. AF4 has shown to be a precise analytical technique for the separation of GNS of different sizes. Particle size analysis is a key element because many properties of nanomaterials are size dependent . This paIt is well known that graphene has excellent properties that provide a multitude of technological applications in different fields. It is formed by a pattern of hexagonal rings of carbon atoms constituting a huge flat molecule . Some ofo-dichlorobenzene (ODBC) [Many methods for obtaining graphene have been reported. Graphene layers can be obtained by liquid-phase exfoliation of commercial graphite in different organic solvents using the ultrasonic technique. This method requires special experimental conditions at which very high pressures and temperatures are reached in very short periods of time . The cole (ODBC) ,12. By me (ODBC) . By carre (ODBC) . On the e (ODBC) . For inse (ODBC) . For thie (ODBC) .o-Dichlorobenzene is an organic solvent that has excellent properties to be used as liquid phase for the process of graphite exfoliation. It is commonly applied as a reaction medium in fullerene chemistry and it is well known that it forms very stable dispersions due to its very efficient interactions with graphene via π-π stacking [stacking . On the stacking . Graphene-based materials have been characterized by a variety of different techniques, such as X-ray diffraction, transmission electron microscopy and Raman spectroscopy, among others ,20. Alth6 to 109 particles/mL, aggregation and fluorescence [NTA is a relatively novel technique for the study of particle size distribution. Like DLS, NTA uses light scattering and the Brownian motion of liquid suspensions of particles to obtain the size distribution in a sample. This technique allows real-time visualization and recording of nanoparticles during the measurement by combining a charge-coupled device with laser light scattering microscopy . In thisrescence . The conrescence . Based orescence .2 nanoparticles [AF4 is one of the most promising techniques for the characterization of nanoparticles due to the high precision and wide separation range it provides, as well as the great variety of nanomaterials that can be analysed. Currently, this technique is in continuous progress and shows high versatility, because it has been used to characterize many types of nanomaterials such as nanodrugs, silica nanoparticles, nanocellulose and nanoplastics, among others ,29,30,31articles  and in carticles , renderiHerein, we report the synthesis of unfunctionalized, non-oxidized and isolated graphene nanosheets (GNS) applying the ultrasound-assisted method by liquid-phase exfoliation of a micrographite. The nanosheets obtained have been characterized using different techniques, particularly related to the study of particle size. Thus, besides XRD, TEM and Raman spectroscopy, three techniques, specifically oriented to the determination of particle size, i.e., DLS, NTA and AF4, were investigated. The proper choice of the parent micrographite has been essential because it has provided GNS particles measurable by all these techniques. A comparative study of the results obtained with the different characterization techniques is reported. Microcrystalline graphite powder (98%) was purchased from Nanostructured & Amorphous Materials Inc. . 1,2-dichlorobenzene , dichloromethane  and lanthanum hexaboride  were obtained from Sigma Aldrich .o-dichlorobenzene (ODCB) for 30 min. Subsequently, the resulting dispersion was subjected to treatment with a pulsed ultrasound probe for 2 h using an Ultrasonic Homogenizer 4710 Series from Cole Parmer Instrument Co.  . The power supplied by the equipment was 9.96 W, according to a calorimetric calibration method [g (4000 rpm) for 30 min to remove the non-exfoliated micrographite. The remaining suspension was again centrifuged at 12,096× g  to isolate the graphene nanosheets. They were washed three times with dichloromethane by successive redispersions and centrifugations to remove the ODCB. A Sorvall Super T-21 Tabletop Superspeed Centrifuge  was used to carry out all centrifugation processes. Dichloromethane was evaporated from the resulting graphene nanosheets dispersion at room temperature for 12 h and, finally, the powdered exfoliated GNS were dried under vacuum at 80 °C overnight.250 mg of microcrystalline graphite powder (MG) were stirred in 50 mL of n method   with a monochromatic CuKα radiation source. The scanning conditions for structural analysis were an angular range of 15°–80° (2θ), a 0.040° step size and 1.05 s per step. Additional measurements of X-ray diffraction were carried out using a Bruker D8 Advance. The scanning condition for this analysis were an angular range of 5°–40° (2θ), a 0.002° step size and 9 s per step.Transmission electron microscopy (TEM) images were recorded on a Jeol JEM-1400 transmission electron microscope  operated at an accelerating voltage of 120 kV. The instrument has a high-contrast objective-lens polepiece, enabling high-contrast TEM image observation at all magnifications and good image quality, as well as easy handling. In addition, it has an advanced vacuum system. The digital-camera configuration includes a CCD camera that enables focusing and image verification on the operation screen. The measurement CCD camera (MC), orthogonal to the alignment camera, has a resolution of 1344 × 1024 pixel (12 bits/pixel). The measurements have been made in a magnification range between 8000× and 150,000× with an instrument resolution of 0.38 nm between points.−1). Spectra were obtained by excitation with green laser light (532 nm) from 150 to 3500 cm−1. A total of 32 scans per spectrum were acquired to improve the signal-to-noise ratio.Raman spectra were acquired with a Renishaw Raman instrument  equipped with a Leica microscope furnished with various lenses, monochromators and filters in addition to a CCD camera. A silicon standard sample was used as reference for calibration (520 cmX-ray photoelectron spectroscopy (XPS) was performed through a SPECS mod. PHOIBOS 150 MCD spectrometer  using non-monochromatic Mg Kα radiation and a multichannel detector. All spectra were fitted to Gauss–Lorentz curves to better identify the different chemical environment of the elements in each material. The binding energy values were calibrated with the adventitious carbon C 1s signal (284.8 eV).Particle sizes were measured in a Zetasizer ZSP  at 25 °C based on laser Doppler velocimetry and dynamic light scattering (DLS) techniques. Previously, the suspension was homogenized using an ultrasonication probe for a period of 5 min. h) of the GNS particles, the hydrodynamic diameter (Dh) was calculated by using the Stokes–Einstein Equation (1):B is the Boltzmann constant, T the temperature in K degrees, t the translational diffusion coefficient.The refraction index values were set at 1.33 and 2.38 for the dispersant (deionized water) and the material (carbon), respectively. The analysis was carried out by triplicate and medium and standard deviation were calculated. To obtain the hydrodynamic radius , equipped with a sample chamber and a 488 nm laser.B is the Boltzmann constant and h in a medium of defined viscosity and temperature. All measurements were performed at room temperature.For the NTA measurements, 1 mg of GNS was suspended in 1 mL of water. Before the analysis, the solution was homogenized for 3 min in an ultrasonic bath. The samples were injected into the chamber with sterile syringes. Many individual particles are tracked during their Brownian motion by the software, which uses the Stokes–Einstein Equation (2) to provide sample information:An AF4 system  coupled online to a 21-angle MALS detector  and UV-Vis diode array detector  was used. The MALS detectors were calibrated using bovine serum albumin monomer and detectors at different angles were normalized with respect to a 90° detector measuring a sodium poly(styrenesulfonate) (PSS) standard. The AF4 channel was trapezoidal-shaped, 350 μm thick (defined by a spacer), 29.8 cm long (inlet to outlet) and had a maximum width of 2 cm. Particle recoveries over AF4 were tested with several commonly used membranes. The analytical parameters and characteristics of our AF4 system are presented in 6 was used as a pattern to determine the instrumental broadening). FWHM for GNS was higher than for MG  and graphene nanosheets (GNS) samples were examined by XRD. r MG see . The cryinstrumental is referred to LaB6 and equal to 0.130.The instrumental broadening effect on FWHM was subtracted out using Warren’s method on the assumption of a Gaussian peak :β2 = β2s002) due to the exfoliation of the MG [Liquid-phase exfoliation by ultrasound-assisted synthesis for obtaining graphene nanosheets (GNS) produced smaller crystallite sizes. Moreover, the thickness of the crystallites along c axis decreased because the full width at half-maximum (FWHM) of the peak (002) was higher than that of the starting micrographite (MG) ,43. Thusf the MG . In thisThe surface morphology of the original graphite and the synthesized graphene was examined by TEM images. Nanometric particles of graphite flakes are shown in 2g in the Brillouin zone. The intensity of the D band indicates the degree of disorder that the material possesses, which is related to several factors such as functionalization in the graphene macromolecular sp2 ring or, in our case, the ultrasonic exfoliation in ODCB. In many studies, the ratio of ID/IG intensities is used to verify that the material has undergone a structural change during the synthesis process [D/IG ratio indicates a smaller sheet size because the ratio of edge defects is greater for smaller layers [D/IG = 0.10 while this ratio increased to 0.38 for the exfoliated GNS. These values confirmed the exfoliation of the graphite in ODCB using the ultrasound probe, which caused a certain disorder in the material. Raman spectroscopy was performed to confirm the exfoliation of the micrographite by ultrasound irradiation. The typical bands of graphene materials were observed in the spectra . The G p process . In addir layers . The ref−1 and so, applying the equation proposed by Wang et al. [−1. It has been shown that in the case of multilayers graphene, the 2D peak shifts toward higher Raman shift and becomes broader [−1, similar to MG, although there was a clear difference in peak intensity between them. It is common to calculate the ratio of peak intensity I2D/IG. An approximate value of 2 identifies a single layer of graphene [The calculation of the number of graphene layers is very relevant in this type of study. Many investigations relate the position of the G peak with the number of graphene layers. The G peak of the GNS was at a Raman shift of 1582 cmg et al. , it can g et al. . Normall broader . In the graphene . The oriN-methyl-2-pyrrolidone [In order to study the composition of MG and GNS, XPS spectra of these samples were measured. rolidone .h), which is defined as the radius of an equivalent hard sphere diffusing at the same rate as the particle under observation, and so it is indicative of the apparent size adopted by the GNS in the aqueous dispersion. GNS exhibited a Gaussian peak located at 450 ± 14 nm. The measurement carried out for the MG material revealed a particle size outside the quantification limits of this technique (>1 μm).The size distribution and intensity correlation function normalized between one and zero of the GNS using dynamic light scattering (DLS) are shown in 2. A value of PDI < 0.1 indicates that the sample is monodisperse. Instead, if PDI is between 0.1 < PDI < 0.2, the sample would have a narrow particle size distribution. In the case of GNS, PDI was 0.36, value between 0.2 < PDI <0.5, which indicates that the sample has a wide particle size distribution according to the results reported by J. Lohrke et al. [DLS also provides the polydispersity index (PDI), which indicates the width of the particle size distribution, being calculated as (peak width/peak height)e et al. .9 ± 6.48 × 107 particles/g. However, most particles had sizes between ca. 30–200 nm, although the concentration of particles around 300 nm was also significant. The number of larger particles (>350 nm) was much lower. A comparison between DLS and NTA reveals that DLS could overestimate the particle sizes of the sample. Both techniques provide a hydrodynamic radius (Rh) value but larger particles scatter stronger and are preferably detected by DLS than the smaller particles since the scattering intensity effect depends on size rather than on the number of particles with similar diameter. DLS is a fast, simple and non-destructive technique, but it presents this inherent feature when analysing samples that present some polydispersity [In order to further define the size of the graphene nanosheets, nanoparticle tracking analysis (NTA) was used . This tespersity . In thesspersity .Firstly, the influence of the membrane composition on retention properties and recovery from the AF4 channel was studied. Polyvinylidene fluoride (PVDF), polyacrylonitrile (PAN) and regenerated cellulose (RC) were used. 0 are the peak areas without void peak of the detector signal , obtained with and without cross-flow, respectively. The MALS detector allows the direct measurement of the radius of gyration in the 1–1000 nm particle size range [The recovery from AF4 runs was determined as follows:ze range .The fractograms (90° light scattering detector) showed a low recovery using PAN and PVDF (less than 30%) due to the retention of graphene nanosheets in these membranes. It was easily visualized because they became black. This had to be due to the interaction of the graphene sheets with these polymeric membranes. However, the fractogram exhibited a broad peak centred at around 33 min using a RC with a recovery of 30%, thus suggesting a weaker interaction with this membrane. To increase the recovery, pure water was essayed as carrier. g), which is defined as the mass weighted average distance from the core of a particle to each mass element in the particle. Rg is more dependent on the structure of the particle than the value of Rh. Rg increases with increasing the elution volume. The size distribution derived from the MALS detector showed the presence of different populations of particles . The mosf). Df gives a detailed information of the shape of the materials, thus allowing to understand the distribution of particles in aqueous media. A sphere has a Df of 3, whereas Df is 2 for a planar structure and 1 for a rigid rod [MALS detector coupled to AF4 can provide relevant information about the mechanism of aggregation and nanoparticle structure. This information is included in the fractal dimension structural parameter  and Rh is the Z-average hydrodynamic radius provided by DLS (450 nm). The theoretical value of p for a hard sphere is 0.778 and for a stiff rod of approximately 2 [Also, additional information on the particle shape can be obtained by calculating the shape factor, p = R by AF4 3 nm and Rmately 2 ,62. The In summary, AF4 and NTA give much richer information on particle size than DLS when dealing with a polydisperse material as graphene nanosheets. AF4 can be considered a promising technique for the separation and characterization of a variety of graphene structures, including not only graphene nanosheets, as described in this work, but also graphene oxide, graphene quantum dots and other carbon nanostructures. Unlike DLS and NTA, AF4 is a separation technique and can be coupled to a great variety of detectors, thus gathering rich information from the sample. It separates particles in the range from 1 nm to 1–2 μm, although other field flow fractionation techniques could expand this range up to particle sizes higher than 100 μm. Interestingly, the existence of semipreparative channels would allow the separation and collection of milligram quantities of these graphene structures. In addition, NTA can provide the concentration of GNS nanoparticles. Nevertheless, stability concerns of aqueous dispersions of large graphene particles, a more limited range of particle size determination and the current limited availability in many laboratories are among the disadvantages of NTA and AF4 relative to DLS.The ultrasound-assisted exfoliation of micrographite (MG) to graphene nanosheets (GNS) was confirmed by different techniques, such as XRD, TEM (sheets size between 200–500 nm) and Raman spectroscopy. The particle size distribution of GNS was firstly determined by DLS (ca. 450 nm), which provided the hydrodynamic radius and polydispersity of GNS. Subsequently, two different techniques, i.e., NTA and AF4, were applied here for the first time to graphene. NTA provided an average size of ca. 150 nm and higher resolution than DLS as well as approximate concentrations. In addition, it proved that DLS gave an average particle size whose intensity was biased towards the larger graphene particles. AF4 was able to separate various populations of GNS with different radius of gyration (centered at approx. 360 nm) and in addition it provided information concerning the structure and shape of the particles. Clearly, the application of NTA and AF4 besides DLS allows gathering much rich information on graphene particles. The above-mentioned advantages for NTA and AF4 reveal their usefulness for the determination of the actual polydispersity in graphene preparations, evaluation of their synthetic procedures and size determination and fractionation in aqueous media for studies related to biological applications, sensing and toxicity.


Graphene, the first true two-dimensional material, still reveals the most remarkable transport properties among the growing class of two-dimensional materials. Although many studies have investigated fundamental scattering processes, the surprisingly large variation in the experimentally determined resistances is still an open issue. Here, we quantitatively investigate local transport properties of graphene prepared by polymer assisted sublimation growth using scanning tunneling potentiometry. These samples exhibit a spatially homogeneous current density, which allows to analyze variations in the local electrochemical potential with high precision. We utilize this possibility by examining the local sheet resistance finding a significant variation of up to 270% at low temperatures. We identify a correlation of the sheet resistance with the stacking sequence of the 6H silicon carbide substrate and with the distance between the graphene and the substrate. Our results experimentally quantify the impact of the graphene-substrate interaction on the local transport properties of graphene. Measurement of charge transport in epitaxial graphene is challenging. Here, the authors quantitatively investigate local transport properties of graphene prepared by polymer assisted sublimation growth using scanning tunneling potentiometry and report local sheet resistances with a variation of up to 270% at low temperatures. The high quality and its 2D nature make epitaxial graphene the perfect system to study fundamental transport properties on the nanometer scale. Consequently, in a series of experiments—based on scanning tunneling potentiometry (STP)2 or four-point-probe microscopy3—several groups have focused on local properties like the sheet resistance and the impact of scattering centers like single substrate steps5 or the transition from monolayer to bilayer graphene on transport7. From these results, it is qualitatively well understood that the transport properties of epitaxial graphene are not homogeneous on the nanometer scale. Substrate steps or monolayer-bilayer junctions act as local scattering centers. In addition, for epitaxial graphene on SiC(0001) it is well known that interaction with the substrate drastically affects graphene’s transport properties. In order to reduce this inherent proximity effect, i.e., to improve the transport properties of the graphene sheet, different strategies were pursued such as the refinement of the growth process10, the use of suitable dielectric substrates like boron nitride11, the decoupling of the substrate by intercalation12, or the preparation of suspended graphene13. Moreover, the proximity effect can be deliberately exploited to specifically tune the properties of a graphene sheet18. For example, the almost negligible spin-orbit coupling can be significantly increased by bringing the graphene layer into contact with transition metal dichalcogenides15 and proximity superconductivity can be observed in graphene in the vicinity of superconducting materials19.Charge transport in epitaxial graphene has been subject of theoretical and experimental investigation since its first electronic characterization25. The strong variation in the experimental values of sheet or defect resistances determined by local probe measurements is likely due to the lack of information about the actual local current density. Replacing the probe by a single-electron transistor allows simultaneous measurement of local voltage drop and current distribution in 2D materials26 with a lateral resolution in the range of 350 nm26. In comparison, STP has an angstrom resolution27 and measures the local electrochemical potential with high accuracy, but local variations in the current density are experimentally not accessible and are indistinguishable from spatial variations of the sheet resistance. For conventionally grown graphene on SiC(0001), typically monolayers as well as bilayers are present. Monolayer-bilayer transitions represent strong scattering centers and cause a significant variation of the local current density. Having no better approach, so far local transport properties have been determined using an averaged (sometimes even macroscopic) current density for the whole sheet.In the context of charge transport in epitaxial graphene, a locally varying potential landscape and a spatially inhomogeneous current density are induced by local defects like substrate steps and local variations of the coupling between the graphene layer and the substrate. Analyzing the published results for resistances assigned to specific defects in epitaxial graphene, one finds a large spread28 on SiC substrates with ultra-low step heights. This allows for local transport investigations of monolayer graphene on terraces with different SiC terminations free from bilayer and step edge effects.In this study, we show that the high quality of epitaxial monolayer graphene samples grown by polymer assisted sublimation growth (PASG) opens a promising way to quantify also delicate local transport properties with high precision. Applying the PASG method, it is possible to grow large-scale monolayer graphene sheets without bilayer formationThe aim of this work is to test for local variations in the sheet resistance of epitaxial graphene and to unravel possible intrinsic proximity effects induced by the presence of the substrate.28, drastically reduce lateral current density variations29. In our STP setup, the current flow was deliberately driven parallel to the miscut of the SiC sample, resulting in an overall voltage drop perpendicular to the substrate steps  is visible. It is induced by a lattice mismatch of the graphene sheet and the substrate and originates from actual height corrugation as well as from electronic contrast38. However, this 6 × 6-quasi corrugation is structurally not perfect  at 8K provide insight into the local electronic structure. dI/dV spectra it can be seen that the electronic properties on the two terraces are not identical and even on a given terrace we find local deviations  exhibits six different  terminations , the buffer layer is partially covalently bonded and thus strongly coupled to the SiC substrate60 and electron–electron scattering61. In addition, potential scattering, screening, and their interplay have to be considered in the discussion. While all these processes depend on the charge carrier density, the electron–electron scattering has been found to be most dominant at high temperatures and low doping62. ARPES measurements reveal a high charge carrier concentration of Within the proposed model, we now discuss the temperature-dependence of the sheet resistance, i.e., an increasing conductivity with decreasing temperature. In the semi-classical Boltzmann transport, an increase in the conductivity with decreasing temperature is attributed to freezing out of electron–phononSince the Fermi wavelength of the electrons roughly corresponds to the wavelength of the potential modulations, we have additionally considered phase-coherent transport phenomena. We predominantly observed classical Lorentz magnetoresistance in macroscopic magnetotransport measurements  spectra acquired on S2 and S3 that show slight differences in the spectra at e.g., −300 mV.Having identified the distance between the graphene and the substrate as an important parameter that controls the sheet resistance in general, the question arises whether this parameter also explains the different sheet resistances of the graphene sheet on terraces S2 compared with terraces S3. Figure In summary, the spatial homogeneity of PASG graphene allows for a quantitative analysis of electronic transport on a local scale. We have shown a direct correlation of the structural as well as the electronic transport properties with the substrate. In particular, PASG graphene shows a locally inhomogeneous sheet resistance, which is governed by both the substrate termination of the SiC and the distance between the graphene layer and the substrate. A locally varying distance to the substrate is accompanied by a variation of the impact of the interface states such that a larger distance leads to a reduced resistance. By analyzing the temperature-dependence of the sheet resistance we have disentangled different scattering mechanisms and have thereby revealed a large inhomogeneity in the sheet resistance at low temperatures associated with the imperfections of the 6 × 6-quasi corrugation and localized defects.66. In this context, the question arises as to the limitations of the reported effect, i.e., a maximum variation in the sheet resistance of 270% at low temperatures. Such a strong local inhomogeneity of the electronic transport is an important quality in the field of epitaxial graphene. It e.g., implies that nanometer-sized devices could exhibit a local variation in the mobility of up to 270%. We are convinced that the findings of this study can be generalized and should be considered for other 2D materials grown on and in proximity with a substrate.Besides the investigation of fundamental processes in the interaction between substrate and graphene, the reported anisotropy could be exploited in further transport experiments. For example, it is interesting to simply rotate the sample by 90° such that the current is applied parallel to the steps instead of perpendicular. Generally, terraces S2 with 28. The idea of this method is to support the growth process with an external carbon source. A polymer is deposited on the substrate using liquid phase deposition before high-temperature sublimation growth is initialized28. The samples were initially annealed in vacuum (p = 900 mbar) at 1200 °C and 1400 °C for 10 and 2 min, respectively. Afterward, the samples were heated directly up to 1750 °C and annealed (6 min) while argon flux was kept at 0 sccm10. Samples prepared with this method are almost defect- and bilayer-free and exhibit shallow step heights, as verified in Raman mapping and AFM topographies28.Graphene samples investigated in this study were grown on the (0001) Si-terminated face of semi-insulating 6H-SiC wafers with small nominal miscut angle of 0.06° toward −10 mbar at 300K, 77K, and 8K) using electrochemically etched tungsten tips. STS spectra were acquired using standard lock-in technique and a modulation amplitude of 10 mV. The concept of the STP setup is depicted in Supplementary Fig. Vcross is applied across the sample via two gold contacts. The voltage IT vanishes and is additionally recorded as a function of position. The resulting potential map (Supplementary Fig. j as follows4The experiments were performed in a custom-built low-temperature STM and in a custom-built room temperature STM under UHV conditions (base pressure < 10® using the AC/DC module. As input parameters, we enter the macroscopic ohmic resistance and the global geometry of the sample. Additional topographic information like substrate steps, bilayer regions, and corresponding monolayer-bilayer transitions are included according to the structural information from constant current topographies. Step resistivities used in this study are set to 6 Ωμm, 12 Ωμm, 18 Ωμm for single, double, and triple substrate steps, respectively.The local current density Supplementary Information


O,O′-acac)(γ-acac)(dimethyl sulfide (DMS))] on various immortalized cell lines, in primary cultures, and in murine xenograft models in vivo. Recently, we also showed that [Pt(γ-acac)(DMS)] is able to kill Caki-1 renal cells both in vivo and in vitro. In the present paper, apoptotic and autophagic effects of [Pt(γ-acac)(DMS)] and cisplatin were studied and compared using Caki-1 cancerous renal cells. The effects of cisplatin include activation of caspases, proteolysis of enzyme poly ADP ribose polymerase (PARP), control of apoptosis modulators B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and BH3-interacting domain death agonist (Bid), and cell cycle arrest in G2/M phase. Conversely, [Pt(γ-acac)(DMS)] did not induce caspase activation, nor chromatin condensation or DNA fragmentation. The effects of [Pt(γ-acac)(DMS)] include microtubule-associated proteins 1A/1B light chain 3B (LC3)-I to LC3-II conversion, Beclin-1 and Atg-3, -4, and -5 increase, Bcl-2 decrease, and monodansylcadaverine accumulation in autophagic vacuoles. [Pt(γ-acac)(DMS)] also modulated various kinases involved in intracellular transduction regulating cell fate. [Pt(γ-acac)(DMS)] inhibited the phosphorylation of mammalian target of rapmycin (mTOR), p70S6K, and AKT, and increased the phosphorylation of c-Jun N-terminal kinase (JNK1/2), a kinase activity pattern consistent with autophagy induction. In conclusion, while in past reports the high cytotoxicity of [Pt(γ-acac)(DMS)] was always attributed to its ability to trigger an apoptotic process, in this paper we show that Caki-1 cells die as a result of the induction of a strong autophagic process.We have demonstrated the cytotoxic effects of [Pt( Renal cell carcinoma (RCC) is among the top 10 most common cancers in the world; about 20%–30% of patients with RCC have metastasis to the first diagnosis, and over 95% of patients have multiple metastases . HoweverThe development of drugs targeting mammalian target of rapamycin (mTOR)  has led to significant improvement in RCC prognosis. Although these new agents improve progression-free survival, none have shown a statistically significant improvement in overall survival. In effect, none are curative, and the duration of response is often limited . In addiO,O′-acac)(γ-acac)(dimethyl sulfide (DMS))] has been synthesized, a Pt(II) complex containing two acetyl groups (acac) and a sulfide ligand in the Pt coordination sphere  also has high and rapid citotoxicity on renal Caki-1 cells both in vitro and in vivo  also displayed potent antiangiogenic activity though the inhibition of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1) expression in tumor tissues  kills cells through a potent induction of apoptosis. Resistance to apoptosis may be due to various factors. During nephrogenesis, the transcription factor paired box protein 2 (PAX2) is differentially expressed depending upon the kidney development phase, and it is barely quantifiable in mature kidney. In Caki-1 cells, PAX2 is overexpressed and contributes to cisplatin resistance  most often activates the mitochondrial apoptotic pathway, another recent in vitro investigation of neuroblastoma cells has revealed that [Pt(γ-acac)(DMS)] leads to both apoptosis and activation of autophagy  treatment in Caki-1 cells.Thus, the aim of the present paper is to investigate apoptotic and/or autophagic pathways caused by cisplatin and [Pt(γ-acac)(DMS)] at various concentrations and for different incubation periods. Caki-1 cells  were maintained in McCoy’s medium supplemented with 10% fetal bovine serum, penicillin/streptomycin, and 1% O,O′-acac)(γ-acac)(DMS)] and cisplatin, we used both 3--2,5-diphenol tetrazolium bromide (MTT)  or cisplatin were fixed with 4% paraformaldehyde and incubated with 1 mg mL−1 DAPI in phosphate buffeed saline (PBS) for 15–20 min. Cells were mounted on glass slides and analyzed using fluorescence microscopy. For statistical analysis of each experiment, 5–10 fields (magnification 20×) were analyzed using the image analysis software ImageJ so as to detect only the nuclei with chromatin condensation. The mean ± SD was calculated and displayed as a bar graph. For the DNA fragmentation assay, genomic DNA from Caki-1 cells was prepared using the Wizard Genomic DNA Purification Kit  according to the manufacturer’s protocol. DNA was dissolved in Tris-ethylenediaminetetraacetic acid (EDTA) buffer, and 40 µg of DNA was separated on a 1.2% agarose gel containing 0.1 mg mL−1 ethidium bromide, visualized under ultraviolet light, and photographed.For the 4,6-diammine-2-phenylindol (DAPI) staining, cells treated with  on mitochondrial enzymes. Indeed, comparable results were obtained when cell number was directly determined by cell counting. Consequently, we used MTT assay in the reported combined experiments.The cytotoxicity data shown here were obtained by MTT metabolic assay and confirmed by SRB assay to rule out potential effects of [Pt(γ-acac)(DMS)] is approximately 5-fold greater than that observed for cisplatin (γ-acac)(DMS)], half maximal inhibitory concentration (IC50) 6.92 ± 0.084 µM; for cisplatin, IC50 37.35 ± 0.5 µM). Here, a time course cytotoxicity curve was performed using 10 µM [Pt(γ-acac)(DMS)] and 50 µM cisplatin; it was found that [Pt(γ-acac)(DMS)] is more powerful than cisplatin (γ-acac)(DMS)], while it was necessary to incubate for about 48 h to get the same effect using 50 μM cisplatin (γ-acac)(DMS)] treatment, was also measured by quantifying the percentage of cells that exhibited annexin V-FITC and/or PI fluorescence. It can be seen that cell death induced by [Pt(γ-acac)(DMS)] was significantly higher than cell death due to cisplatin (γ-acac)(DMS)] (5 and 10 µM) did not induce variation in cell cycle profiling (γ-acac)(DMS)], while 50 µM cisplatin induced caspase activation after 6 h (γ-acac)(DMS)] did not induce chromatin condensation or DNA fragmentation (γ-acac)(DMS)]-treated cells was observed (10 µM). Thus, these results suggest that in Caki-1 cells, [Pt(γ-acac)(DMS)] cytotoxicity may not be due to apoptosis. No caspase-9 and -3 proteolytic activation was observed in cells treated with 10 µM [Pt(γ-acac)(DMS)]-treated Caki-1 cells. As shown by immunoblotting detection of AIF in Caki-1 extracts, following treatment with AIF siRNA, AIF protein levels were significantly decreased (p = 0.01) or [Pt(γ-acac)(DMS)] (p = 0.06) treatment in Caki-1 cells (γ-acac)(DMS)]-induced apoptosis prompted us to study another mechanism of cell death, autophagy. Monodansylcadaverine may be used as a specific marker for autophagic vacuoles, since it accumulates in acidic compartments enriched in lipids, and staining intensity increases in cells induced to undergo autophagy. Caki-1 cells were then treated with 10 µM [Pt(γ-acac)(DMS)] at different incubation times  and subsequently stained with MDC and DAPI . A time-dependent increase of fluorescence signals was evident in autophagic vacuoles of [Pt(γ-acac)(DMS)]-treated cells (γ-acac)(DMS)] (DMS)] D. O,O′-acac)(γ-acac)(DMS)] induced LC3-I (19 kDa) to LC3-II (17 kDa) conversion in a time-dependent manner; no effects were seen when using 50 µM cisplatin (γ-acac)(DMS)], we observed that Beclin-1 and Atg-3, -4, and -5 increased, Bcl-2 decreased, and JNK1/2 was activated by phosphorylation (γ-acac)(DMS)]-induced Beclin-1 increase (γ-acac)(DMS)]. O,O′-acac)(γ-acac)(DMS)] inhibited the phosphorylation of mTOR already after 1 h treatment, thus promoting the inhibition of p70S6K phosphorylation. Consistently with previous data showing a functional relationship between mTOR and PI3K/AKT  inhibited, in a time-dependent manner, the phosphorylation of AKT (γ-acac)(DMS)] to those exerted by temsirolimus, a soluble ester of rapamycin and a natural product and inhibitor of mammalian target of rapamycin (mTOR)  or temsirolimus. We show that temsirolimus had a significant cytotoxicity starting at 10 µM; such cytotoxicity was lower than that exerted by equal concentrations of [Pt(γ-acac)(DMS)] /AKT-mTOR-p70S6K pathway in Caki-1 cells treated with  D.O,O′-acac)(γ-acac)(DMS)], synthesized for the first time several years ago  is also able to consistently decrease the tumor mass of mouse xenograft model of breast,  is a Pt(II) complex, having two acetylacetonate (acac) ligands and dimethylsulfide (DMS) coordinated to the metal, with the biological activities already cited above. Differently from cisplatin, for which the activity appears to be both genomic and non-genomic, [Pt(γ-acac)(DMS)] shows a small reactivity with nucleobases and a characteristic reactivity with sulfur ligands  capable of acting intracellularly with different modalities from those caused by cisplatin. In the present study we used the renal cancer cells, Caki-1, that are considered to be a cisplatin-resistant cell line; in these cells [Pt(γ-acac)(DMS)] is able to induce a strong cytotoxic effects both in vitro and in vivo  always triggered apoptosis in all the cells tested, it seemed appropriate to determine the cellular effects induced by [Pt(γ-acac)(DMS)] and compared with those obtained with cisplatin. On the other hand, a recent report showed that [Pt(γ-acac)(DMS)] was able to induce autophagy pathway in neuroblastoma cells [[Pt(γ-acac)(DMS)] inducing cytotoxicity faster and greater than that induced by cisplatin. The different and important observation in renal cells was that the high mortality rate associated with [Pt(γ-acac)(DMS)] was not due to apoptotic processes  was not degraded, nor were DNA degradation or formation of condensed chromatin observed). Instead, the Caki-1 cells incubated with [Pt(γ-acac)(DMS)] underwent a remarkable autophagic process that is not seen with the use of cisplatin. This conclusion is based on evidence that several autophagic markers are activated in the presence of [Pt(γ-acac)(DMS)]. Autophagy does not always produce the same cellular effect, especially when it is triggered by antitumor drugs. Indeed, sodium selenite, . This data suggests that autophagy triggered in Caki-1 cells is a process fostering cell death. The MAPK JNK1/2 is known to be involved in the regulation of autophagy of cancer cells in response to pharmacological stress -treated cells and that its inhibition blocked the [Pt(γ-acac)(DMS)]-induced Beclin-1 increase. Beclin-1, a key component of the autophagosome nucleation complex, can interact with Bcl-2 to form Beclin-1/Bcl-2 complex, which functions as an inhibitor of autophagy  in inducing Caki-1 cell death. Several studies demonstrated that autophagy was often triggered by the inhibition of the PI3K/AKT/mTOR/p70S6K pathway concomitantly with the activation of the JNK pathway . Cisplatin cytotoxicity was scarce, probably because Caki-1 cells are intrinsically able to resist and inhibit apoptosis  was strong compared to that observed in other cancer cell lines, due to autophagy through a mechanism mediated by JNK and PI3K/AKT/mTOR/p70S6K pathways. [Pt(γ-acac)(DMS)] may therefore represent an alternative approach to reducing renal cancer mass. However, to assess the general applicability of these findings on renal cell cancer patients, further experiments performed on more renal cancer cell lines are required.In conclusion, we have shown a drastic difference in Caki-1 cell response to cisplatin and [Pt(poptosis ,48. The


GNSS) offers a solution adapted to outdoor testing, but the relationship between the point where the antenna is attached and the real centre of mass (CoM) position is still unknown. This article proposes to compare different points of the body used to quantify the performance of alpine skiers. 3D models of seven elite skiers performing giant slalom (GS) were built using multiple camera system and dedicated motion tracking software. CoM as well as pelvis, head and feet trajectories were deduced from the data. The potential and kinetic energies corresponding to these points were calculated, as well as the evolution of the turn radius during the turn cycle. Differences between values given by the CoM and the other morphological points were analyzed. The pelvis offered the best estimation of the CoM: No differences were found for the biomechanical parameters, except for the kinetic energy, where 2% of the turn cycle had significant different values. The head was less accurate compared to the pelvis, showing significant differences with CoM between 7 and 20% of the turn cycle depending on the parameter. Finally, the feet offered the worst results, with significant differences between 16 and 41% of the turn cycle. Energies and turn radius calculated by using pelvis in place of CoM offered similar patterns, allowing the analysis of mechanical and dissipation energy in GS. This may potentially enable easier testing methods to be proposed and tested.Alpine ski analysis has always been very challenging, mainly due to the environmental conditions, large field and rapid and dynamic skiers’ movements. Global navigation satellite system ( Mechanics of different sports have widely been studied, showing the necessity to calculate the CoM with a good accuracy to perform precise analysis  participated in the study. All participants were healthy males without any joint motion problems  were positioned around the GS run, about 35 m from the center of the zone of acquisition . Each camera was mounted on a special tripod head, especially built to always keep the sensor center of the camera at the same 3D coordinate, even when the camera was rotated to track the skier. Reference markers mounted on poles were positioned around the run to act as calibration and reference points for the panning and tilting reconstruction. The capture volume was around 60 ∗ 20 ∗ 2 m . The cameras’ 3D coordinates were calculated as the median of two points on either side of the tilting axis of the camera. Each camera was connected with Gigabit Ethernet to a dedicated laptop which directly recorded the frames in the RAM memory of the computer, using a software developed for this specific purpose . Cameras were also connected to battery packs and dedicated synchronization boxes . The selected runs were processed with SIMI motion software , using the panning and tilting modules. The camera’s internal  and external  parameters needed for the analysis were determined using the DLT 11 calibration method  were also defined: The Pelvis position was defined as the middle point between the 2 trochanters’ markers, the Feet position as the middle point between the 2 ankle-bone markers and the Head position as the center of the helmet.Participants had to wear a white racing suit previously equipped with 14 black markers, a black helmet, and black gloves. t Figure . The CoMThe accuracy of the reconstruction method was measured in two different ways. First, the positions of three gates as given by the total station were compared with the positions calculated by the software. Second, the error in the length of each body segment was determined.Epot (J/kg), Ekin (J/kg), and Trad (1/m), were calculated for the CoM and the three morphological points . For analysis purposes, each trial was normalized to fit a 100% temporal turn cycle, where 0 and 100% were the time points when the projection of the CoM was between the two skis. A cubic B-splines interpolation method was used to achieve the normalization , the acceleration due to gravity (g) and the delta height (ΔHi(t)) of the analyzed point in a global reference system:As the different morphological points are positioned at different heights of the body, the ΔEkini evolution during the turn was calculated using the speed (Vi) of the analyzed points  and M, using the following equation:The Ekin (Ekinm) was also calculated over the whole turn cycle, to show the overall error when using a morphological point instead of the CoM.The mean Tradi were calculated directly with SIMI motion, using the Frenet-Serret formula ((Tentryi) was defined as the instant where the Tradi dropped below the natural radius of the skis  and the turn exit (Texiti) as the instant where the turn radius went over 25 m again.The  formula . The turSPM) was used on paired Student T-Tests . Paired Student T-tests were also used to assess statistical differences between the CoM and the morphological points for the Ekinm, Tentry, and Texit, given as mean ±SD. For all statistical analyses, significance was accepted at p < .05.Statistical parametric mapping .Using the Pelvis was used instead of the CoM to calculate ΔEpot, no significantly different values were obtained. Figure Epot between the CoM and the Pelvis with the corresponding SPM curve on Figure tt threshold at ±6.16).When the Feet to estimate the ΔEpot, 41% of the measures during the turn cycle had significantly different values (tt threshold at ±6.33) compared to the values obtained using the CoM, as seen in Figures Concerning the use of the Ekin calculation, it can be seen that the Head induced significantly different values for 20% of the measures during the turn cycle compared to the results obtained using the CoM. Figure tt threshold at ±5.99). Compared to the CoM, the Head induced a significant underestimation of −2.57 ± 1.22 J/kg (p < 0.001) when calculating Ekinm.From the CoM, The Pelvis induced significantly different values for only 2% of the Ekin measurement during the turn cycle . No significant difference were found between the CoM and the Pelvis for Ekinm .Compared to the  Figures  . The Feet induced a significant overestimation of Ekinm [5.77 ± 4.00 J/kg (p < 0.001)] compared to the result obtained with the CoM.For the Head instead of the CoM for the calculation of Trad indicated significant differences for 7% of the turn cycle. Evolution of Trad is described in Figure tt threshold at ±6.67).The results obtained using the Trad using the Pelvis instead of the CoM induced no significant differences during the whole turn cycle (tt threshold at ±6.79). The corresponding curves are plotted on Figures The calculation of Feet instead of the CoM to estimate Trad revealed that 16% of the measures had significantly different values during the turn cycle. Figures Trad curve and SPM results for the comparison of the CoM and the Feet during the turn cycle (tt threshold at ±6.76).Using the Tentry and Texit between the CoM and the morphological points can be found in Table Comparison of Pelvis and the CoM. Indeed, when looking at the different parameters analyzed, the Pelvis offered the best estimation for the ΔEpot, Ekin and Trad calculation. No significant differences were found for the ΔEpot and Trad during the whole turn whilst only 2% of the turn cycle significantly differed in the case of the Ekin. The difference was encountered only at the beginning of the turn.The most important finding of this study was the high level of agreement between the Feet and the Head as extreme points of the skier, while the Pelvis is more centered and near the CoM. Nevertheless, the Head allowed slightly better estimations than the Feet for the analyzed parameters showing more similar patterns of the CoM. The angulation of the hips during the second half of the turn can probably explain this result, as the Head is more centered vertically on the CoM while the Feet follow an external trajectory. The best morphological point to estimate ΔEpot and Ekin is therefore the Pelvis, followed by the Head and finally by the Feet that offer poor reliability.As a global observation, it is quite intuitive to see the Epot is directly correlated to vertical displacement, the curves of ΔEpot obtained in this study can be compared to the work proposed by CoM compared to the ground. As expected, the CoM was higher during transitions between turns and lower at gate crossings. This corresponds well to the interpretation of ΔEpot curves calculated using the CoM and the Feet in the present study.As Ekin values depend on the square power of the speed, the shape of the curves obtained in this study can also be compared to those obtained by As the (Emech), which involved addition of the Ekin and the Epot. They also calculated the corresponding dissipated energy (Edissip) as the change in mechanical energy per change of vertical distance  d’éthique de la recherche sur l’être humain.” The protocol was approved by the “Commission cantonale (VD) d’éthique de la recherche sur l’être humain.” All subjects gave written informed consent in accordance with the Declaration of Helsinki.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Phased energy storage technologies are highly advantageous and feasible for storing and utilizing clean renewable energy resources, for instance, solar energy and waste heat, and it is an effective method to improve energy efficiency and save energy. However, phase change energy storage has some problems, for example, low thermal conductivity and phase change leakage, which lead to limited application. In this paper, anisotropic graphene aerogels were prepared by ice crystal template method with high thermal conductivity of graphene, and silver was attached to the pore wall graphene sheets and the graphene sheet boundaries of the aerogels. The results show that anisotropic graphene aerogels were successfully prepared, and SEM and EDS indicate that up to 9.14 at % silver was successfully attached to the graphene sheets and boundaries. The anisotropic thermal conductivity of the PArGO phase change composites after adsorption of the paraffin is significant, with a maximum axial thermal conductivity of PArGO of 1.20 W/(mK) and radial thermal conductivity of 0.54 W/(mK), compared to the pure paraffin (0.26 W/(mK)) increased by 362% and 108%, respectively. The enthalpy of the composite has been reduced to 149.6 J/g due to the silver particles attached, but the thermal properties have been greatly improved. In experiments simulating real temperature changes, PArGO achieves phase transitions very fast, with a 74% improvement on thermal efficiency of storage and discharge over the pure paraffin. With the growing demand of energy consumption, the problem of shortages of common fossil fuels and the accompanying environmental pollution has become more serious. The need to find renewable and clean energy sources is becoming urgent. Thermal energy storage technology is one of the ideal solutions that offers clear economic advantages in terms of reducing energy wastage and costs. Moreover, it is also a clean and reusable technology. Phased energy storage technologies are highly advantageous and feasible for storing and utilizing clean renewable energy sources, such as solar energy and waste heat, and it is one of effective methods to improve energy efficiency and save energy. Phase change material (PCM) is a key factor in phase change energy storage technology.There are many types of PCMs, including organic PCMs such as paraffin ,2,3 and The emergence of graphene provides a good idea to solve both problems. Graphene has an ultra-high thermal conductivity, which is up to 5300 W/(mK) . Thus, i. Although anisotropic graphene aerogels can better decrease the thermal resistance and enhance the thermal conductivity, the thermal conductivity in the normal direction of the pore wall is still low, and the thermal resistance of the graphene sheet boundaries in contact with the PCM is still high.Many researchers have prepared graphene aerogels by oxidation-reduction method to adsorb PCMs and study their improvement effects on the thermal properties of composite phase change materials. It is found that graphene aerogel alone does not improve the thermal conductivity of phase change composites well, mainly because the random contact conduction of the graphene sheets increases the contact thermal resistance of the graphene sheets in the thermal conductivity pathway, while a large number of the graphene sheet boundaries also increase the boundary thermal resistance of the thermal conductivity pathway. Therefore, many researchers have proposed anisotropic graphene aerogels, in which the pore walls are relatively thick and the graphene sheets are regularly arranged so that the previously haphazard graphene sheets are tightly assembled into a single unit, thus reducing the contact thermal resistance and the boundary thermal resistance. Peng et al. used the ice crystal template approach to prepare anisotropic graphene aerogels, and the thermal conductivity was as high as 8.87 W/(mK) after adsorbing paraffin . AlthougSilver nanoparticles are of great importance owing to its high thermal conductivity of 429 W/(mK) at room temperature. They are expected to have good thermal properties preferably suitable for heat transfer applications ,20 and pThe ice crystal template method, using cold source directed freezing of graphene wet gels, was used to prepare anisotropic graphene aerogels. Silver is attached to the graphene sheets and the boundaries, thereby greatly reducing the normal thermal conductivity of the pore wall and the contact thermal resistance between the graphene sheet boundaries and the PCM.2SO4 solution on an ice bath below 5 °C after cooled to room temperature. During dilution, the temperature of the solution should not exceed 5 °C. Subsequently, H2O2  was added, the solution turned bright yellow, stirred reaction for 1 h before centrifugation. Following the solid was centrifugal washed with 10 vol % HCl for several times, then washed with 2 vol % HCl. Finally, the precipitate was washed with distilled water several times and freeze-dried to obtain graphene oxide (GO).A modified Hummers′ method  was usedObtained GO (0.4 g) and 50 mL of water were added into the glass bottle in the reaction kettle, and then the solid–liquid mixture was placed in an ultrasonic bath with a cold-water circulating system. After 1 h, added concentrated ammonia (500 µL) and stirred evenly, and then the reaction kettle was placed into the oven for 3 h at 90 °C. Next, the reactor was taken out and put in deionized water for two days, during which the water was changed every eight hours, followed by 3 h of directional freezing at −45 °C, and then freeze-dried for two days. Finally, the reduced graphene oxide aerogel (rGO) was obtained after being microwaved under vacuum. The obtained rGO samples were immersed into the heated and melted paraffin  and absorbed by vacuum for 30 min, and then taken out and cooled naturally to obtain paraffin/rGO composite material, denoted as PrGO.3 ethanol (20%) solution slowly until a large amount of precipitation occurred. After a small amount of acetaldehyde was added in the solution and stirred well, the obtained rGO samples were immersed into this solution at 40 °C for a period of time to obtain a graphene wet gel with silver attached. Then the wet gel was freeze-dried to obtain a graphene aerogel with silver attached (Ag-rGO). The prepared aerogel was immersed in the heated and melted paraffin  and absorbed by vacuum for 30 min, and then taken out and cooled naturally to obtain paraffin/Ag-rGO composite material, denoted PArGO.2% ammonia solution was added dropwise into 20 mL of 2 wt % AgNOScanning electron microscopy (SEM) images were acquired on an EVO18 microscope . Aerogel samples were pasted on a conductive adhesive without spraying Au and directly observed, but the composite PCM was surface sprayed with gold  before observation.X-ray energy dispersion (EDS) analysis was performed using chemical microanalysis INCA 350  for the elemental analysis after surface treatment of the samples (ethanol rinsed and vacuum dried).2 protection, 50 mL/min, and a temperature rise rate of 10 °C/min.A differential scanning calorimetry (DSC) instrument was used to analyze the thermal properties of the PCM-adsorbed composite material samples using Q2000 , with the following detection conditions: NThe thermal conductivity of PCM composite material samples was measured using the transient hot wire method on a thermal conductivity meter TC3100 .Anisotropic graphene aerogels were prepared by directional freezing. Further characterization by EDS verified the silver attachment on the graphene aerogel pore walls. From After the prepared aerogel adsorbed paraffin, a composite phase change material was obtained, and its appearance and morphology were investigated as well as thermal properties. The thermal properties of the composite PCM were also tested. In The thermal conductivity of the composite has a significant anisotropy, with a significant difference between radial and axial thermal conductivity. As shown in The phase change behavior of the PCM was investigated in an environment simulating actual temperature changes. As in In this research, anisotropic graphene aerogels were prepared by directional freezing, and then silver particles were attached on the sheet layers and boundaries of graphene by silver mirror reaction to improve the thermal conductivity of the phase change material. The samples were subjected to apparent morphology and thermal properties studies. The results show that anisotropic graphene aerogels were successfully prepared, and SEM and EDS results indicate that up to 9.14 at % silver was successfully attached to the graphene sheets and boundaries. The anisotropic thermal conductivity enhancement of the PArGO phase change composites after silver attached is significant, with a maximum axial thermal conductivity of PArGO of 1.20 W/(mK) and radial thermal conductivity of 0.54 W/(mK), compared to the pure paraffin (0.26 W/(mK)), which increased by 362% and 108% respectively. The enthalpy of the composite has been reduced to 149.6 J/g due to the silver particles attached, but the thermal performance has been greatly improved. In the experiments simulating real temperature changes, PArGO achieves phase transitions very fast, with a 74% improvement on thermal efficiency of storage and discharge over the pure paraffin.


Scanning electron microscopy and Raman tests showed that decorating with multilayer graphene and amorphous boron promoted the dispersion of Al3Mg2 alloy. The results showed that decorating with 1% boron and 2% multilayer graphene improved the combustion heat of Al3Mg2 alloy to 32.8 and 30.5 MJ/kg, respectively. The coexistence of two phases improved the combustion efficiency of the matrix Al3Mg2 alloy.To improve the engine-driven performance of propellants, high-energy alloys such as Al and Mg are usually adopted as annexing agents. However, there is still room for improvement in the potential full utilization of alloy energy. In this study, we investigated how to improve combustion efficiency by decorating Al Different researchers have studied how to remove aluminum-based oxide on the surface. One study showed that a CuF2 solution can simultaneously remove the Al2O3 layer on Al particles and form the Cu–Al nanocomposite [−1, which is approximately 1.8 times that of raw Al. Energetic materials have been widely used in propellants. With increased demand for high-energy-density materials, more metals, such as Al, Mg, and Ti, have been investigated ,2. Al-baomposite . The max3)3 and Cu(IO3)2 have been adopted to modify the Al powder [3)x for the combustion of solid composite propellants. To enhance the combustion performance of aluminum, ultra-fine iron and amorphous boron additives have been added to Al-based propellants [In addition to the high purity Al powder, Al-based alloys such as Al–Mg binary alloys have been investigated as additive materials for propellants. To improve the combustion performance of Al–Mg-based micron particles, zirconium particles are modulated to the matrix . The resl powder . The respellants . When Al2 have also been employed to fully use the Al-based materials in propellants [The aluminothermic reactions of Al/CuO and Al/MnOpellants ,10,11,12pellants . The compellants . Based oIn addition to Al-based materials, boron-based materials have also been widely investigated by researchers. Boron is usually used in amorphous states . The com3Mg2 alloys. The results show that the Al3Mg2 particles can be encapsulated by multilayer graphene, which promotes the combustion of the alloys and enhances combustion heat. Boron particles can also be mounted on the surface to decorate the Al3Mg2 particles and enhance the combustion heat of the Al3Mg2 alloy.In this paper, we report the structure and combustion heat of multilayer graphene and boron particles modulated with AlThe Al and Mg powders and amorphous boron were obtained from the Aladdin Chemical Reagent Co., Ltd. . The diameters of the Al and Mg were distributed in the range of 3~5 µm. The particles of amorphous boron were about 100 nm in diameter. The multilayer graphene was obtained through improved Hummers’ methods in our laboratory . It was 3Mg2 alloy was prepared by induction melting in a water-cooled copper crucible  in an argon atmosphere. The ingot was re-melted three times to ensure the homogeneity of the alloy. Then the alloy was mechanically milled in an argon atmosphere by a high energy grinding machine  and sieved to obtain a grey powder with particle diameter less than 50 nm. The amorphous boron-decorated and multilayer graphene-decorated Al3Mg2 alloys were also obtained by high-energy ball milling methods in an argon atmosphere with a weight ratio of ball to materials of 10:1. The ground materials were heat to 600 °C at a rate of 5 °C/min in a cylinder oven  and kept 1 h in an argon atmosphere. Then the heated materials were cooled down to ambient temperature naturally.The Al−1 in an argon atmosphere. Nitrogen adsorption-desorption isotherm measurements were performed using a Micromeritics ASAP 2020 analyzer  to investigate the specific surface area. Before analysis, the multilayer graphene was pretreated by degassing at 200 °C for 8 h to remove any adsorbed species. X-ray powder diffraction (XRD) tests were conducted using a Bruke D8 focus instrument  with graphite-filtered Cu-Kα radiation. The scanning speed was 5 degrees per minute, with a step of 0.02 degrees from 10 to 80 degrees. SEM tests were conducted using a Hitachi (S-4800) scanning electron microscope (SEM)  equipped with an energy-dispersive spectroscopy analyzer with charges of 15 kV and 10 pA. The combustion heat was examined with oxygen bomb equipment with an oxygen pressure of 10 MPa. The combustion heat tests were conducted 5 times and the average value of the tests was provided to eliminate the differences caused by the test system.Thermogravimetric (TG) analysis and synchronously differential scanning calorimeter (DSC) tests were carried out using a TA SDT 2960 thermoanalyzer  with a heating rate of 5 °C min2 adsorption-desorption curve is clearly a type III curve [2g−1. The pore size distribution of the multilayer graphene was also obtained and is displayed in 3Mg2 particles to be loaded into the interlayer space of the multilayer graphene.II curve . The tes3Mg2 alloy was first examined via the metallography method. The results are shown in The structure of the Al3Mg2 alloy with different magnifications. The grain boundary of the alloy can be clearly observed. There were no obvious impurities in the alloy. To further investigate the structure of the alloy, an X-ray diffraction (XRD) test was also conducted on the alloy, the results of which are shown in 3Mg2 alloy was easily indexed as 29-0048, which clarified that the alloy had a cubic structure and a space group of Fd-3m(227). A similar structure was observed by other researchers [3Mg2 alloy, respectively. There were no impurities on the crystal particle, which is consistent with the results from the XRD tests. The EDS in  of Fd-3m7. A simi2O and certain gases. However, the weight of the sample slightly increased with the increase in temperature. This can be attributed to the oxidation of boron by trace oxygen in the argon carrier gas.Thermogravimetric (TG) analysis and differential scanning calorimeter (DSC) tests were conducted on amorphous boron. The results are shown in Correspondingly, the DSC curve increased slightly at first due to the evaporation of materials on the surface of the boron. The curve then decreased with an increase in temperature, which can be attributed to the exothermal reaction caused by the oxidation of trace oxygen in the argon carrier gas.3Mg2 alloy and multilayer graphene, Raman tests were conducted on the multilayer graphene and the composite of the multilayer graphene-decorated Al3Mg2 alloy. The results are shown in To investigate the mutual interaction between the Al1g zone-edge phonon mode induced by the disorder of finite crystal-sized effects and the high-frequency E2g first-order mode, respectively. 3Mg2 alloy decorated with multilayer graphene and clearly shows that compared to the spectra in 3Mg2 alloy and the graphene. The structure of the multilayer graphene was destroyed during the high-energy ball milling and heat treatment process. The intensity ratio of the D band and G band (ID/IG) in the two samples was also obtained. The ID/IG of the multilayer graphene was much lower than that of the Al3Mg2 alloy decorated with multilayer graphene. The strong D peak suggests that there are more nanocrystalline structures and defects such as distortion, vacancies, and strain on graphitic lattices—which are prevalent features in carbon—in the ball-milled graphene [−1 are also displayed in 3Mg2 alloy [3Mg2 alloy.graphene . The Ramg2 alloy , which c3Mg2 alloys are supplied in The scanning electron microscopy (SEM) test results from the boron-decorated and multilayer graphene-decorated Al3Mg2 alloy had an aggregated structure, caused by the high-energy ball milling. All of the Al3Mg2 alloy particles were ground and the amorphous boron particles were eventually distributed onto the Al3Mg2 alloy surface. After grinding for a long period of time, all of the boron particles were implanted into the Al3Mg2 alloy particles. All the elements were evenly distributed. The elemental mapping test results in 3Mg2 alloy are supplied in 3Mg2 alloy particles were uniformly loaded onto the surface of the multilayer graphene. This can be attributed to the large specific surface area of the multilayer graphene. The amorphous boron particles were evenly distributed onto the layer space of the multilayer graphene after grinding for a certain amount of time. The SEM test results also showed that some particles cohered together, which could be connected by the multilayer graphene. The close contact in the interface between the multilayer graphene and the Al3Mg2 alloy could promote the combustion characteristics [The SEM test results from multilayer graphene-decorated Aleristics .3Mg2 alloy, B-doped Al3Mg2 alloy, and multilayer graphene-decorated Al3Mg2 alloy were tested with the oxygen bomb method. The results showed that the combustion heats of the materials were 27.4 ± 0.20, 32.8 ± 0.18, and 30.5 ± 0.15 MJ/kg, respectively, which means that decoration with both boron and multilayer graphene promoted the combustion of the Al3Mg2 alloy. Studies on the combustion of the B–Fe system also found that the combustion reactions were altered when boron was doped with iron, which was attributed to the catalytic performance of iron for boron oxidation [3Mg2 alloy was catalyzed by the doped boron and the multilayer graphene. It has also been reported that a multiwall carbon nanotube accompanied by Al powder was adopted to improve the combustion performance of hydroxyl ammonium nitrate [3Mg2 alloy. As for the boron-decorated Al3Mg2 alloy, the combustion of the boron was improved by the high-energy ball milling and the subsequent heat treatment [3Mg2 alloys were eventually improved with a modified combustion zone width by the decoration of boron and multilayer graphene.The combustion heats of the Al nitrate . The homreatment ,30. Shabreatment . It can 3Mg2 alloys decorated with multilayer graphene and boron particles. The results showed that high-energy ball milling can evenly set boron particles into the Al3Mg2 alloy. The distance between the layers in multilayer graphene can also provide enough space for Al3Mg2 alloy particles. The even dispersion and appropriate distance between the two phases promoted the combustion of the materials, which eventually resulted in the combustion heat increasing by more than 10 percent.This paper mainly reported on the structure and combustion heat of Al


The politically charged nature of many of these communities suggests their activity is migrated to other Twitter hashtags . Future analysis of Twitter activity might focus on tracking communities across topics and time.Social Media platforms in Cyberspace provide communication channels for individuals, businesses, as well as state and non-state actors  to conduct messaging campaigns. What are the spheres of influence that arose around the keyword  On July 22, 2016, a mass shooting occurred in a shopping mall in Munich, Germany. The attacker was quickly identified by local police as an 18 year old German-Iranian dual national resident of Munich  The general analysis of the cumulative network of retweets for this incident. (3) The evolution of the influence flow-based communities in temporal network of timeslices by day. In section 2 we discuss related work. Section 3 covers the problem definition and the details of the collected dataset. In sections 4 and 5, we discuss the methodology and results, respectively. The paper concludes with several future directions.The main contributions of the paper are: (1) The collection of the hashtaged In the current era of social networking, information sharing has been easier by posting microblogs  Every unique Twitter account that occurred in our data is represented by a node,u to node v if user u retweets the tweet that was initially posted by user v,(2) A directed edge is placed from node u retweeted user v's tweets, and(3) Edge weights represent the number of times user G0 did not contain any temporal information.(*) Edges in G0 has 147, 116 nodes, 191, 002 edges. To this graph we apply a standard community detection algorithm called Louvain  add an edge between communities if they have a shared user. Let Ut be the set of users comprising community U on day (t), and Vt+1 be the set of users comprising community V on day (t + 1). We then compute the similarity between two communities as,We further propose a metric to compare leader-centric communities across time, computed in two steps: (1) run Louvain community detection on sub-graphs Similarity metric assigns the value while considering the sizes of the communities, as community sizes may vary a lot due to their sphere of influence. Next, we present the analysis results using the discussed metrics.#Munich, we notice that about 80% of the Tweets were individuals retweeting other users. This dynamically captures the influence of a very small portion of the overall accounts, because these tweets include content that a large number of other users identify with as they get retweeted.In exploring the data set of all the Tweets with The distribution of retweets vs. day is shown in G* from G0 by selecting the 20 largest communities in G0. G* contains less than 1% of the communities, but it still accounts for over 70% of the nodes and 75% of the edges in G0. G* using the ForceAtlas visualization from Gephi : socially conservative communities, politically neutral communities/news sources, socially liberal communitiesVertically (top to bottom): English language communities, French language communities, Spanish language communities.Note that the FC Bayern Munich community might be outside the scope of the study of the July 22nd attack, rather tweets on football using the same hashtag(#Munich). Since the data captured it anyway, we have shown it in the analysis.The partitioning of communities along language and political views reinforces the findings of the Pew study  attach themselves to a particular hashtag  and form topic communities. This creates the following cases for followers and leaders.A user exists in the fundamental community but not in the topic communityA user exists in both the fundamental community and the topic communityA user exists in a topic-specific community but not in the underlying fundamental community.u agrees with the sentiment of leader v's Tweet on the topic of the #Munich and retweets v's message. Users u and v are in the same topic community, but not necessarily in the same fundamental communities if in general their views do not coincide.For example, user k, if any node is ended up having degree k or less, will also be removed in the same iteration. The method is stopped once each node has been assigned a k-shell value. k-core of a network contains all the nodes having k-shell value equal to or higher than k. To understand the influential hierarchy of the network, we first apply the core-periphery analysis of the network using K-shell decomposition method Seidman, . The k-sIn this section, we study the evolution of the communities found in the cumulative graph for the first 4 days succeeding the attack. This subset is deemed adequate by examining the frequency of retweets in each day for the whole period. As seen in In this multilayer network, the nodes represent each of the top 20 communities, and a single layer is created for each day. The nodes are sized by the number of users in that community and colored by the communities they belong to in the cumulative graph. The label of each node corresponds to the leader in that community as defined by Equation (1). We then add an edge from a node in one layer to a node in another layer if there are any shared users between the two communities. This captures the continuity of community membership. The weight of the edge is then computed using Equation (2) as described in the methodology.The resulting network provides significant insight into the evolution of communities over time. We further observe that a significant amount of users retweet from the same community. Although this observation is prevalent in the data, it is most evident in the community labeled as French conservative social commentary. We observe that a high amount of users that retweeted from @tprincedelamour on July 23, 2016, did so again on the next day.Following communities from left to right we see how they can merge from several nodes to one or split from one over each day, as is the case with the English conservative social commentary (USA based) community. Lastly, the @jazayerli community is seen to grow from the 24 to 25 of July with no connecting edge. The lack of an edge between these two nodes is because the community consists of just one Twitter message generated by @jazayerli that is retweeted several times over the 2 days.#Munich retweets on July 25.The cumulative and temporal graphs of the Twitter data complement each other by providing overlapping insight into the communities described. #Munich July 2016 attack corresponding to a month-long period after the July 22 shootings in Munich. We study the community structure in the cumulative dataset as well as daily partitions and classify each community based on the nature of its leaders and their tweets. This study provides insight on how information spreads on Twitter in case of an event, and we observe how the important leaders disappear from the network of #Munich retweets after a week of the attack. The leaders in the first week tended to be news organizations or social leaders with strong or extreme views. Communities expressing strong opinions were the most active; however, as mentioned, the collected data is unable to account for passive users . One can further study the impact of the event on other users who are not directly involved in tweeting and retweeting, however, have been affected by the event. The analysis can also be extended to different social media platforms for better understanding.In this work, we collect and analyze the Twitter data of This research opens up several questions to be studied for a better understanding of the evolution of the network in case of terrorist attacks. One can identify the leaders and follow them across multiple hashtags to determine topic communities of leaders for each hashtag. By comparing a leader's topic networks and identifying users that retweet the leader across multiple different topics, we can understand the development of the fundamental and topic-based communities represented by that leader. These communities can be further classified based on different parameters, such as is the community passive where the leader has many followers, but few retweets; or is it active where the majority of users following a leader actively retweet the leader across many different topics.All these approaches will be fruitful in a deeper understanding of how communities generate influence in social media networks. Given the increasing use of online social media, the implications for how corporations, organizations, and nation states conduct influence campaigns will continue to grow as part of future information operations.The datasets generated for this study are available on request to the corresponding author.IB, DC, EK, and TN collected the dataset, discussed the research methodology, implemented the project, and contributed to the writing of the manuscript. RG and AS contributed to the research methodology and its implementation, analysis of the results, and writing of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In this prospective study, radiation dermatitis severity of 142 Caucasian early breast cancer patients undergoing whole-breast irradiation was evaluated by physicians, the patients themselves and objective technical measurements. The primary aim and a substantial novelty of this study was to identify patient- and treatment-related risk factors for radiation dermatitis by using objective spectrophotometry: 24 patient or radiotherapy related parameters were evaluated as potential risk factors. Objective and significant risk factors for radiation dermatitis were the breast volume and the applied irradiation technique; a boost radiotherapy administration also showed a trend towards a slightly more severe radiation dermatitis. These results can help to identify those patients at increased risk of developing a severe radiation dermatitis, as susceptible patients may require special monitoring and timely treatment.Background: Radiation-induced dermatitis (RID) is frequent in breast cancer patients undergoing radiotherapy (RT). Spectrophotometry (SP) is an objective and reliable tool for assessing RID severity. Despite intensive research efforts during the past decades, no sustainable prophylactic and treatment strategies have been found. Estimation of new and reevaluation of established risk factors leading to severe RID is therefore of major importance. Methods: 142 early breast cancer patients underwent whole-breast irradiation following breast-conserving surgery. RID was evaluated by physician-assessed Common Terminology Criteria of Adverse Events (CTCAE v4.03). Spectrophotometers provided additional semi quantification of RID using the L*a*b color-space. A total of 24 patient- and treatment-related parameters as well as subjective patient-assessed symptoms were analyzed. Results: Values for a*max strongly correlated with the assessment of RID severity by physicians. Breast volume, initial darker skin, boost administration, and treatment technique were identified as risk factors for severe RID. RID severity positively correlated with the patients’ perception of pain, burning, and reduction of everyday activities. Conclusions: Physician-assessed RID gradings correlate with objective SP skin measurements. Treatment technique and high breast volumes were identified as objective and significant predictors of RID. Our data provide a solid benchmark for future studies on RID with objective SP. Radiation-induced dermatitis (RID) is one of the most common side effects during and following radiation therapy (RT) . RID canIn early breast cancer, breast-conserving therapy is standard of care as it facilitates improved cosmetic results . To prevDespite the frequency of radiation dermatitis in WBI patients, there is still no comprehensive and, importantly, objective severity classification. Two of the most widely used severity gradings are the Common Terminology Criteria of Adverse Events (CTCAE) and RTOG/EORTC systems which are based on the visible skin color and integrity defined by erythema and desquamation . These gSuch a technical approach to assess RID is spectrophotometry (SP) with which the skin color can be evaluated objectively and reliably by three distinct numerical parameters, the L*, a*, and b* value: together, these parameters define the so-called L*a*b color space in which every color in every lightness can be precisely depicted. In clinical routines and also in clinical trials it is, of course, desirable that the technical effort as well as the time spent on such measurements is reasonable . SpectroIn this prospective study, RID severity of 142 early breast cancer patients undergoing WBI was evaluated by CTCAE gradings and SP. The primary aim and a substantial novelty of this study were to identify patient- and treatment-related risk factors for RID by using objective SP skin measurements. We also investigated the correlation of the subjective CTCAE score with the objective SP measurements; these subjective and objective data were additionally correlated with patient-reported symptoms using the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) providing new insights into the relationship between subjectively experienced RID symptoms and objective, semi-quantitative skin measurements.142 women were prospectively enrolled from October 2017 to July 2019 and participated in this study. Patient data were gathered in our comprehensive academic cancer center, participating clinics, and radiation oncology community practices. The study design was previously approved by the local ethics committee (186/2016). Written informed consent was obtained by all participants. All analyzed patients completed WBI as intended. Patient characteristics are summarized in Inclusion criteria: WBI dose-fractionation regimen of 50 Gy in 25 fx (CF) or 40.05 Gy in 15 fx (HF), breast-preserving surgery, >18 years, nonsmoker. Exclusion criteria: neoadjuvant/adjuvant/concomitant chemotherapy, previous irradiation of the ipsilateral breast, nodal irradiation indicated, mastectomy, breast implants, any prior surgical procedures in the irradiation area, use of corticosteroids, active dermatitis or chronic dermatological disorders, tattoos within the treated integument, and patient refusal.2 = 0.4437; p < 0.0001). SP revealed a proportional decrease in skin lightness   D and an  values) E. Howeve values) F. A detap = 0.005 and R2 = 0.06. For spectrophotometrically obtained a*maximum values, the linear regression yielded a p = 0.051 and R2 = 0.05. Taking the strong positive correlation between CTCAE gradings and a*maximum values into account, the comparably low R2 values for the linear regressions with breast volumes were indicative of a skewed distribution pattern: consequently, subgroups were established allowing to draw more clinically relevant conclusions  with p = 0.82 and R2 = 0.0004; HI(D2-D98)/D50 with p = 0.71 and R2 = 0.001; L* (baseline) with p = 0.28 and R2 = 0.018; a* (baseline) with p = 0.29 and R2 = 0.017; b* (baseline) with p = 0.37 and R2 = 0.012; b* (maximum) with p = 0.52 and R2 = 0.004; rel. D2% with p = 0.5635 and R2 = 0.002; rel. D50% with p = 0.5532 and R2 = 0.002; rel. D98% with p = 0.5595 and R2 = 0.002. Detailed results on all investigated parameters in relation to the CTCAE scoring, maximum L* value and maximum a* values are provided in The following patient-related factors did not correlate linearly with the severity of physician-assessed RID: patient age with A sequential boost RT led to a tendentially more severe RID A with anp < 0.0001 and inversely correlated with symptoms measured by RISRAS : pain (p = 0.0115); burning (p = 0.025) and reduction in activities of daily living (p = 0.0011). Maximum L* values did not correlate with the subjective perception of “Itching” (p = 0.8369). This finding is similar to RID assessments via maximum a* values and CTCAE. Similar to the maximum a* values and CTCAE v4.03 ratings, itching did not correlate with the maximum L* values (p = 0.8369).To quantify the impact of RID severity on distinct subjective symptoms, patients enrolled in this study filled the RISRAS questionnaire. We performed statistical analyses based on CTCAE as well as maximum values for the green-red-axis within the L*a*b color-space . With both assessment approaches, we found that an increasing RID severity proportionally increases the perception of pain and burning sensation A,B,E,F. An important and frequent adverse reaction of adjuvant WBI is RID, often considerably impairing the patients’ quality of life during the course of WBI and up to weeks thereafter ,2. GenerFor decades, radiation oncologists used to rely on visually assessed and thus subjective criteria such as the CTCAE for the assessment of RID. Owing to the simple and quick application, these subjective gradings are widely accepted. However, such visual assessments were shown to be prone to considerable biases due to substantial intra- and inter-evaluator differences ,11,16,17While initially developed for the dye and textile industry, SP was consequently utilized in the objective and reliable assessment of skin color differences. Feasibility studies showed that SP can determine even slight skin luminance and color differences which may not be perceived by a human observer or photographs ,16,17,18Along with objectivity, a continuous scale enumerating even slight changes in the skin color also allows us to draw precise conclusions on both the development of RID and the efficacy of specific treatments ,11,22,23So far, our series yields the largest WBI patient cohort investigated by SP for dermatitis evaluation. As expected , physiciSuch an objective assessment of RID also serves an exact estimation of possible RID risk factors, as susceptible patients may require special monitoring and timely treatment . Back beOur series complies with this recommendation and is, to the best of our knowledge, the first to evaluate potential risk factors associated with RID in WBI based on objective SP. We found the breast volume to be a positive predictor of a more severe RID during WBI and confirmed this correlation by objective SP. Subgroup analyses revealed a significantly increased risk of a more severe RID in breasts exceeding 800 mL , whilst SP already indicated significant erythema differences in breasts with more than 400 mL. A sequential tumor bed boost also induced a more severe RID, as measured by CTCAE and SP alike, while the aspired significance level was slightly exceeded. Large breast volumes and a boost administration have already been suggested as such predictors ,26, but Unexpectedly, a significant difference in RID severity was observed for different WBI treatment approaches: patients benefited from VMAT as compared with SW-IMRT. Conventional tangents or forward-planned 3D-conformal RT techniques were explicitly not used in our study since it was shown that modern techniques offer better dose conformity and homogeneity, and deliver lower doses to the ipsilateral lung and breast . Up to nAnother finding was that the pre-treatment skin color was not predictive of final RID severity in this Caucasian cohort. However, following stratification for pre-treatment skin lightness, objective SP indicated that those patients with darker skin developed significantly more intense erythema. Our objective measurements stand in contrast to previous, non-objective studies describing a relationship between light skin and RID susceptibility ,26.Additionally, we evaluated the impact of objective and subjective dermatitis severity on patient-experienced symptoms caused by RID. We determined whether higher objective skin color differences or physician-assessed severity gradings would affect the patients’ symptoms or vice versa. This may sound trivial at first glance and was thus not investigated yet, but it is highly relevant since substantial differences between patients’ and clinicians’ toxicity evaluations have been reported ,31. PainIdeally, future objective studies in the field of RID research should also reflect patients’ genetic, epigenetic, and molecular profiles, since several promising relationships of tissue sensitivity towards radiotherapy have been described. Even though this kind of research is still in its infancy, we expect it to provide further clinically relevant insights into risk factors for radiotherapy-induced side effects ,33,34.After 3D planning, patients were randomly assigned to either 50 Gy in 25 fractions (fx) or 40.05 Gy in 15 fx using 6 MV photons or a combination with 10 MV photons. Treatments were performed as sliding-window intensity-modulated radiotherapy (IMRT) via photon beams or via volumetric  arc therapy (VMAT). The selection of the irradiation technique was based on the individual patient anatomy, with due consideration of the target volume coverage, dose homogeneity, and sparing of organs at risk. A sequential tumor bed boost of 16 Gy with 2 Gy/fx was performed in those patients up to the age of 50 years, with close or positive resection margins or with high-grade tumors. WBI was performed in a supine position on a Varian True-Beam STx  linear accelerator. Treatment of left-sided breasts was administered using deep-inspiration breath-hold. For skin-care purposes, patients were instructed to use 5% urea lotion  two times daily during the WBI treatment period.Radiation-induced dermatitis (RID) assessments were reported corresponding to the CTCAE v4.03 at treatment completion and in the first follow-up visit after two weeks. To prevent a potential grading variability between different observers, only the treating radiation oncologist visually assessed the skin toxicity in his/her patients. Additionally, patients completed a questionnaire on their most severe experience of itching, burning, pain, pigmentation changes, incapacity for work, and limitations in everyday activities related to their acute skin reactions. Therefore, we designed a modified version of the Radiation-Induced Skin Reaction Assessment Scale (RISRAS); patients scored the symptom severity as follows: 0 = not at all, 1 = a little, 2 = quite a bit, 3 = very much.One day after the last WBI fraction and again after two weeks, ten erythema readings were obtained within the treatment area (two in each breast quadrant and one at the center intersection points of the upper and lower quadrants including the inframammary folds). The CR-10 Plus reflectance spectrophotometer  was used, which was applied to the skin region of interest avoiding any pressure. The measurement is initiated by illuminating the skin and detecting the reflecting light. Postprocessing using multiple photocells and a build-in microcomputer concludes the procedure and provides a distinct value within the L*a*b color space. The output data is based on the CIE  system of tristimulus values using the L*a*b* coordinate system. The brightness of the skin is described by the L* parameter ranging from 0 (dark) to 100 (light). a* values enumerate the skin color from green (negative) to red (positive), whereas the b* value provides precise information regarding the blue (negative) to yellow (positive) color axis.2 and the statistical slope deviance from zero was described by the according p-value. For comparison between two groups of non-intraindividual distinct numeric parameters, unpaired t-tests (univariate) were performed resulting in P values. This approach was chosen, omitting the Welch or Mann–Whitney approach, as the identified data presumably yielded comparable standard deviations and normal distributions. For intraindividual distinct numeric parameters, paired t-tests (univariate) were conducted when applicable. If a statistical analysis was preceded by the grouping of data according to discrete or non-discrete parameters, subsequent t-tests must be considered bivariate. For breast volumes, a skew value-to-effect pattern (with the effect being RID severity) was identified using FlowJo 10 (Beck and Dickenson) leading to arbitrary categorization for breast volumes into (1) <400 mL (2) 400–800 mL (3) >800 mL. A depiction of the skew value-to-effect distribution pattern is provided in p < 0.05, ** for p < 0.01, *** for p < 0.001 and **** for p < 0.0001.For bivariate correlations, simple linear regressions were calculated for pairs of distinct parameters. The goodness of fit of the linear regression line was determined by RThe portrayed series yields the largest objective data analysis of SP-assessed RID during WBI. SP measurement values were correlated with physician-assessed CTCAE and, for the first time, with a total of 24 RT parameters, patient characteristics, and patient-reported symptoms. We were thus able to scrutinize prior works conducted in this field of research.Objective and significant risk factors for RID were the breast volume and the use of SW-IMRT instead of VMAT; a sequential boost administration also showed a trend towards a slightly more severe RID. Due to the fact that these results are based on both physician-evaluated and objective RID measurements, they may contribute to the inconsistent or even contradictory debate on possible risk factors for RID.Although CTCAE gradings strongly correlated with objective SP measurements, future RID research should endeavor to meet the requirement for a more objective approach in the RID evaluation process to augment visual examinations and overcome intra- and inter-evaluator bias in RID assessments. Our set up reference values may, therefore, serve as a solid benchmark and facilitate further work on this important research topic.