Sarcoidosis is a multisystemic disease of connective tissue with granuloma formation of unknown etiology and unclear prevalence. Internet search data has been shown to correlate with disease incidences and the population’s interest as well as seasonal variations. Accordingly, aim of this study was to leverage internet search data on sarcoidosis-related keywords to identify unmet needs, geographical and seasonal factors influencing sarcoidosis and estimating its prevalence. In this retrospective longitudinal study, Google Ads Keyword Planner was used to determine the internet search volume of terms related to sarcoidosis across Germany as a whole and in 17 major German cities between July 2015 and June 2019. Identified keywords were qualitatively categorized, converted into number of searches per 100,000 inhabitants and analyzed including regional and seasonal differences. With 3,068,200 queries and 425 different sarcoidosis-related search terms in the studied time period, the search volume was very high for a rare disease. Most searches (67.9%) related to general disease information with “sarcoidosis”, "Löfgren's syndrome", "sarcoidosis lung", "Morbus Boeck" and "neurosarcoidosis" as the top five keywords. Searches per 100,000 inhabitants were comparable in all 17 cities but higher than in Germany as a whole. Overall, the search volume increased from 2015 to 2019 and peaked annually in European springtime with annual lows in European autumn and winter months. The overall high search volume suggests an unmet need for sarcoidosis-related information and a diagnostic gap. Seasonal fluctuations indicate environmental as well as climatic factors that may influence sarcoidosis. Histologically, non-necrotic granulomas with giant multinucleated cells dominate1. With an average lung involvement of about 90%, sarcoidosis most frequently causes pulmonary manifestations and often affects the mediastinal and hilar lymph nodes4. The prognosis depends on the type of sarcoidosis, the response to therapy, and the general condition of the individual5. Prevalence and incidence are not known for certain partly due to the disease’s nonspecific symptoms and its subsequent long diagnostic process7. In Europe, the annual sarcoidosis incidence is estimated at 5–60 cases per 100,000 inhabitants with a lifetime prevalence of 44 cases per 100,000 inhabitants9. Overall, it is estimated that there are about 30,000 cases in Germany with its total population of 83 million. The etiology of sarcoidosis is still unclear5. Currently, it is assumed that in a genetically predisposed person an immune dysfunction can be triggered by an as yet unidentified environmental factor4. This immune disorder, in turn, triggers a cascade which ends in a systemic granulomatous inflammation5. Infectious agents are repeatedly discussed as being possible environmental triggers, although a case–control study based on Swedish population registers found no significant correlation between infectious diseases and the development of sarcoidosis10. However, other studies concluded that exposure to aerosol infectious as well as seasonal and geographical variations in disease incidence could provide indications of the etiological significance of infectious agents14. Studies have also shown that the number of sarcoidosis cases varies within a country depending on the region. Although no clear urban or rural differentiation can be identified16.Sarcoidosis, also known as Boeck’s disease, is a multisystemic disease of connective tissue with granuloma formation and is described as the chameleon among the multisystemic diseases because of its varying manifestations, initial clinical signs, and course from patient to patient18. Approximately 95% of Germans use Google as a search engine in everyday life, which is why data tracking offers a variety of possibilities19. As demonstrated in previous studies, the analysis of Google search data is an unconventional approach to investigating people's needs and interest in various diseases21. Furthermore, websearch data has been shown to significantly correlate with the incidence of infectious diseases22. Hence, the aim of this study was to analyse nationwide and regional internet search data on sarcoidosis in Germany to identify unmet needs and geographical factors influencing the disease.There are no clear epidemiological data on prevalence and incidence of sarcoidosis in Germany. One approach to better understand the incidence and prevalence of diseases is to analyse the search volume of related search terms in online search engines such as Google, as the Internet is used as a common source of health information23. The term search volume applies to the number of searches for a topic or search term. To assess its volume within a specific field, words are initially entered into the Keyword Planner; thereupon, the program provides keywords that are most relevant to the topic. Only data from German IP addresses using Google in the German language were considered. Due to the described seasonal differences in sarcoidosis incidence, we defined the summer/spring months as March to August and the autumn/winter months as September to February13.In this retrospective longitudinal analysis, Google Ads Keyword Planner was used to assess the search volume of terms related to the German word for sarcoidosis (‘Sarkoidose’) across Germany as a whole and in 17 large German cities  between July 2015 and June 2019. Cities were chosen not only for their size but also for their geographic distribution across the country. In order to provide a better overview, the selected cities were allocated according to their geographical location as north, east, south and west and then graphically displayed together accordingly. The Keyword Planner is normally used in advertising to optimize marketing campaigns, but since the tool provides the monthly search volume of a specific topic, it can also be used for scientific purposes24.All identified keywords were qualitatively assessed and classified by the authors. Keywords that were not relevant to sarcoidosis were excluded from analysis . The cities with the lowest relative search volume were Berlin , Bremen , and Hamburg . In contrast, the highest number of searches per 100,000 inhabitants was observed in Freiburg , followed by Muenster  and Kiel , which reflect how this multisystemic disease often manifests itself first in the lungs and the skin25. The high interest in neurosarcoidosis seen with "neurosarcoidosis" being among the top five search terms is notable considering since it is a rare organ manifestation that only occurs in 5–10% of all cases in conventional studies26. This might underline people's fear of this sarcoidosis subtype or just an exaggerated interest due to the rarity of neurosarcoidosis. For example, “eye melanoma” is a rare disease shown to have similarly high interest in the population21. Another explanation is an increased interest stemming from individuals who show neurological symptoms but have not been diagnosed with neurosarcoidosis informing themselves online on this rare organ manifestation.The three most frequently searched terms, “sarcoidosis”, “Löfgren’s syndrome”, and “sarcoidosis lung”, are representative of their respective diagnoses, since sarcoidosis summarizes all sarcoidosis subtypes, Löfgren’s syndrome is found in up to 50% of all cases, and the lung is the most frequently affected organ13. One possible explanation for the observed increase in search volume in this study is the preceding wave of influenza. Granulomas of (symptomless) pulmonary sarcoidosis are often discovered by chance in chest X-rays, which are performed to identify influenza complications27. Another possible explanation is the strain on the immune system by high pollen counts in the spring that prompt inflammation of the respiratory epithelium through oxidase and neutrophil activity. This could augment the risk for developing sarcoidosis and exacerbate chronic sarcoidosis symptoms29. This assumption is supported by the fact that every year the volume of search terms was higher in April and May than in the other months. The deterioration of chronic lung diseases caused by pollen has already been observed in other studies on asthma31. Climate differences could also play a role, which would explain the decline in searches during the winter months. However as mentioned above, in other studies no statistically significant differences could be found, which makes the results of this websearch analysis even more interesting13. Furthermore, April 2019 was particularly striking with search results rising to 138 searches/100,000 inhabitants. That year the Foundation for Sarcoidosis Research (FSR) declared April “Sarcoidosis Month” and through campaigns sought to increase awareness about the disease, which would possibly explain this substantial peak in search volume.The study results indicate an increase in search volume for sarcoidosis during springtime. One study does indicate differences in terms of decreasing numbers in autumn compared to higher numbers in spring, which however, where not statistical significance33. However, it can be assumed that there are differences in access to specialists between urban and rural regions because of disparities in infrastructure and the allocation of health insurance fund seats according to the density of the patient population34. Previous studies have shown that people living in rural areas are less likely to visit specialists35. Accordingly, people living closer to specialists might consult a specialist instead of using Google for health-related information. In the case of sarcoidosis, this could mean that people living in rural areas are less likely to be diagnosed36. In smaller cities people might get the diagnosis, but as the medical care to specialists is less in comparison to big cities, they have less opportunity to ask questions about the disease. This deficit in information supply might be compensated by search queries. Another explanation could be that smaller cities like Freiburg, Muenster, Kiel, and Rostock, have a higher proportion of medical students and healthcare professionals within the respective inhabitants than large cities do and that the higher search volume of sarcoidosis related keywords in these cities can be attributed to medical students performing online research on the disease. Overall, the search queries in each city were higher than the national average. This was particularly noticeable in Kiel, Freiburg, and Erfurt. This phenomenon could also be explained by the lack of diagnosis in rural areas. The high search volume in Freiburg may be explained by the presence of the National Action Alliance for People with Rare Diseases, which has established appropriate structures for patient care in the University Hospitals of Freiburg and Tübingen37. Furthermore, it was shown that older people use the Internet less common, which might be one reason for the lower number of search queries in the whole of Germany compared to the cities examined38. Assuming that a higher search volume correlates with a higher prevalence of sarcoidosis like shown in studies on melanoma36, the study results contradict those from a previous study that found a higher prevalence among people living in rural areas12. The results of the Google analysis could accordingly indicate a much higher prevalence of sarcoidosis than previously assumed.The result showed that the search volume per 100,000 inhabitants was sustainable higher in smaller cities such as Freiburg and Muenster than in larger cities like Berlin and Hamburg. The lower number of search queries in bigger cities might be explained by the better access to medical care with specialists in larger cities than in smaller cities. There are some studies on the over- and undersupply of specialists in rural areas, such as neurologists and psychiatrists, but none specifically related to sarcoidosisUltimately, the discrepancy in search volume between individual cities and Germany as a whole can suggest an actual variation in sarcoidosis prevalence, but it also reflects different demographic distributions and better availability of resources, closer networking such as self-help groups and medical care in urban areas.39. Another study reported that online tools play an important role in gathering information regarding rare diseases40. Based on these findings, it can be assumed that there is a relation between search behavior and the occurrence of sarcoidosis. Another limitation is that Google through its autocomplete function provides search suggestions that could as well distort search behavior. Moreover, data provided by Google Ads Keyword Planner are based on monthly estimations instead of exact numbers and thus might slightly differ from the actual search volume. Therefore, the search behavior in cities might be rather overestimated, while it might be underestimated for Germany as a whole36.There are some study limitations. Google analyses are limited to people who have access to the Internet and use Google as a search engine. Although 95 percent of Germans use Google as a search engine, only including data collected from Google excludes information from a portion of the population. In general, young people use the Internet more than older people. On user demographics, the study is not able to show correlations with people’s age, gender, or nationality. Accordingly, the study might underestimate the disease burden through exclusion of elderly members of the population as well as foreign, non-German speaking residents. Another limitation of the present study is that the searches do not necessarily have to originate from affected individuals, but also from physicians, medical students, or relatives who are interested in the topic as well. It must be taken into consideration that most of the cities included in the study have large medical schools, which can lead to a disproportionately high number of searches through online student activity and medical research. Accordingly, this could be another explanation for the higher number of searches per 100,000 inhabitants in Freiburg for example. Furthermore, there is no information whether a few individuals searched very often or whether many people searched once or twice. So far, there is no study that assessed the correlation between online searches and the prevalence of sarcoidosis. However, considering other studies, a correlation between the number of Google searches and the number of registered cases such as skin cancer or multiple sclerosis was foundThe study demonstrated that there is an unmet need for information within affected individuals and the population for sarcoidosis-related keywords, as the search volume for this rare disease is relatively high in relation to the estimated prevalence in Germany. Another perspective of course could be that the prevalence is higher than previously assumed based on conventional studies, given the high number of searches in the cities in comparison to the overall search volume across the whole of Germany. Furthermore, low web search numbers in rural areas indicate a diagnostic gap and the clearly increased web search frequency in spring suggests environmental and climatic trigger factors, worthy of further investigation.


Zhang et al.  recently reported that SARS-CoV-2 RNA can be retrotranscribed and integrated into the DNA of human cells by the L1 retrotransposon machinery. This phenomenon could cause persistence of viral sequences in patients and may explain the prolonged PCR-positivity of SARS-CoV-2 infected patients, even long after the phase of active virus replication has ended. This commentary does critically review the available data on this topic and discusses them in the context of findings made for other exogenous viruses and ancestral endogenous retroviral elements. The COVID pandemic that started at the end of 2019 led to a remarkable mobilization of scientific efforts as evidenced by > 175.000 publications to date. Among these, the work by Zhang et al. triggered an animated debate in the scientific community [These original reports opened a heated debate on the correctness of the findings and their relevance for recovered COVID patients and subsequent work was initiated to test alternative explanations. It was proposed early on that the observed chimeric RNAs could be artifacts generated during cDNA library preparation. Two findings hint at this possibility. First, the directionality of the observed chimeric transcripts, in which a large fraction of SARS-CoV-2 RNA derives from the (–) strand, in contrast to the predominance of ( +) strand RNAs in SARS-CoV-2 natural infection. Second, the absence of the 3’ end and polyA tail of the viral genome, which are commonly present in integrated sequences processed by L1 elements.The origin of the chimeric human-SARS-CoV-2 reads in RNA-seq libraries was subsequently investigated in a dedicated study , which sTo put these recent reports in a broader context, some consideration should be given to the molecular biology of L1 elements and their interplay with viruses. L1 elements represent the most abundant subfamily of non-LTR retrotransposons, accounting for ∼17% of the human genome. L1 elements are autonomous for self-mobilization by encoding two proteins (ORF1 and ORF2) that together mediate reverse transcription of their own RNA and subsequent integration of the resulting dsDNA in the cellular genome . This prThere are few reports on L1-mediated mobilization of viral transcripts. In hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV), recurrent integration of HBV subgenomic RNAs was reported to yield a chimeric long non-coding RNA between the HBV mRNA for the X antigen (HBx) and L1 RNA in > 23% of patient samples . Of noteThe most remarkable case of L1-virus interplay does however not involve “modern” human viruses, but rather a group of human endogenous retroviruses (HERVs) that were acquired by the primate genome some 20–43 million years ago through infection of the germ line by now-extinct retroviruses . The haltrans-mobilization has been infrequent even for exogenous retroviruses that use integration as a key feature of their replication cycle. Accordingly, despite the evidence that the primate DNA genome has been invaded repeatedly by exogenous retroviral infections during evolution, only a single HERV group was copied-and-pasted by the L1 machinery, and the molecular signatures that facilitate viral RNA retrotransposition by the L1 apparatus are still poorly defined. It is known that SINE non-autonomous retrotransposons exploit the L1 machinery for retrotransposition, which is based on 3′ end sequence similarity between LINEs and SINEs [Overall, it seems unlikely that the L1 machinery is responsible for “genuine” SARS-CoV-2 genomic integration in infected cells. In fact, this process of nd SINEs . Given tFurther studies are necessary to assess the actual impact of active retrotransposons in the mobilization of viral and host transcripts and to characterize the molecular mechanisms underlying their integration in the host genome and their subsequent expression.


Straintronics is a new concept to enhance electronic device performances by strain for next-generation information sensors and energy-saving technologies. The lattice deformation in graphene can modulate the thermal conductivity because phonons are the main heat carriers. However, the device fabrication process affects graphene’s heat transport properties due to its high stretchability. This study experimentally investigates the change in the thermal conductivity when biaxial tensile strain is applied to graphene. To eliminate non-strain factors, two mechanisms are considered: pressure-induced and electrostatic attraction–induced strain. Raman spectroscopy and atomic force microscopy precisely estimate the strain. The thermal conductivity of graphene decreases by approximately 70% with a strain of only 0.1%. Such thermal conductivity controllability paves the way for applying graphene as high-efficiency thermal switches and diodes in future thermal management devices. For effective thermal management and energy recycling of devices, understanding the thermal transport properties of materials is crucial. A heat spreader requires a high thermal conductivity material to dissipate the heat generated from electronic devices efficiently. On the other hand, thermoelectric conversion has attracted much attention as a renewable energy. This technology requires materials with higher electrical but lower thermal conductivities. Consequently, many theoretical and experimental studies have investigated the reduction in thermal conductivity to improve the thermoelectric conversion efficiency.1. As a representative 2D material, graphene has potential for mechanical4 and electrical8 devices. Graphene displays much higher thermal transport properties than existing materials12. Due to its 2D nature, its thermal conductivity can easily be modified by introducing carbon isotopes15, structural defects19, and domain boundaries21. These modifications can control the thermal conductivity in applications such as thermal management devices.Two-dimensional (2D) materials composed of one-atom-thick layers exhibit outstanding characteristics, which differ from those of three-dimensional materials, and are expected to realize future electronic devices22, the change in its thermal conductivity due to the continuous introduction of strain has yet to be elucidated. In this study, we investigate the thermal conductivity changes due to strain in identical graphene drums. To eliminate other factors that may alter the thermal conductivity, strain was introduced by two different mechanisms: pressure difference–induced strain (DEVICE 1) and electrostatic attraction–induced strain (DEVICE 2). The thermal conductivity was measured using Raman spectroscopy, which is very sensitive to the number of layers25, temperature27, and strain29. AFM-based analyses were used to precisely estimate the strain into graphene.Since phonons are the main heat carriers in graphene, strain-induced lattice deformation easily modulates phonon propagation, leading to changes in the thermal conductivity. Due to its high stretchability, the device fabrication process affects graphene’s heat transport properties. To utilize graphene in electronic and thermal management devices, elucidating its thermal transport properties against strain is essential. Although the thermal conductivity of graphene with strain was recently reported6 and C4F8 gases . The holes with the depth of approximately 170 μm do not pass through the substrate  in a Si/SiO2 substrate on which the Cr/Au (20 nm/80 nm) electrodes were deposited in advance. The graphene film, which was mechanically exfoliated from kish graphite, was transferred to produce a suspended drum-shaped graphene membrane as described previously. Strain was applied by the electrostatic force generated with the electrical voltage VG between graphene and the Si substrate  was used to observe the surface morphology of the graphene bulge at various pressures Fig. . The samses Fig. b. It sho34. The thermal conductivity κ is calculated bya is the radius of the graphene drum (7.5 μm), r0 is the radius of the laser beam, t is the graphene thickness, Qabs is the laser power absorbed by graphene, and ΔT is the temperature rise induced by laser irradiation. In our setup, α is 0.9819. The graphene thickness estimated by AFM is 6.1 nm, which corresponds to 18 layers. Assuming that the temperature of the drum edge is at room temperature, the temperature rise ΔT at the center of the drum is estimated by35We measured the thermal conductivity of graphene using Raman thermometryentclass1pt{minimaχ and out. The samples were set in a vacuum chamber , where the pressure in the chamber was changed with a variable leak bulb. After reaching the appropriate pressure, Raman spectra were collected with the vacuum pump turned off to avoid the vibration problem. Raman spectra were obtained with a 100 × objective using a 532-nm laser as an excitation source. The Raman line scanning mode across a steep edge of a gold electrode on Si/SiO2 substrate estimated the diameter is 0.65 μm36. Figure out decreases due to the induced strain, except at 100 kPa, where the graphene drum is initially bent inward  to calculate ned Fig. b. Changiout was changed. Then an analytical model37 estimated the stress and strain induced at the center of the membrane when the circular graphene drum bulged. In this model, in-plane stress (σ) and in-plane strain To estimate the strain induced by the pressure difference, AFM measured the mechanical deformation of the graphene membrane as PP is the pressure applied to graphene a is the radius of the graphene membrane (7.5 μm). t is the graphene membrane thickness (6.1 nm). h is the height of the bulge measured by AFM, and h0 is the height of the membrane at a strain of 0. This model can be applied when the membrane is initially slack. From the above equations, stress Δout is 87 kPa, the in-plane stress and strain induced into graphene can be calculated at a given pressure by Eqs. ..\documen29. Since the Raman peak positions are temperature-dependent27, the effect of laser heating on the Raman spectra cannot be ignored. Therefore, we extrapolated the G peak position without the laser heating effect from the y-intercept in Fig. Then we extracted the change in the Raman peaks due to strain from Fig. out, the strain induced into graphene can be estimated more precisely. Figure G0 is 1581.6 cm-1. This coincides with the experimentally obtained G band position without the strain effect. Hence, the strain can be estimated from the Raman spectra Finally, by combining the strain estimated from AFM Figure G between graphene and the Si substrate. Figure G. The displacement of the graphene drum increases with increasing VG. The trend is consistent with the finite element calculation (COMSOL) with a graphene thickness of 3.4 nm and Young’s modulus of 0.78 TPa  using the device shown in Fig. G. As mentioned above, the y-intercepts were obtained as the values of G and 2D band peak positions without the laser heating effect. Consistent with a previous report44, the G and 2D peak positions change positively with respect to the applied voltage VG  of the strain vector (slope: 2.1) with G was estimated relative to that when VG = 0 V  and − 0.0296 cm-1/K (DEVICE 2) in our experiment compared to the reported value (− 0.011 cm-1/K)45. The strain induced in graphene may vary depending on the temperature when measuring the temperature coefficient47, implying that the temperature coefficients became unexpectedly high. As expressed in Eq. . Thus, the thermal conductivity reduction by the strain introduction is typical for graphene samples irrespective of the number of layers.Since the deflection mechanisms differ between DEVICE 1 (pressure difference) and DEVICE 2 (electrostatic attraction), the change in the thermal conductivity primarily originates from the biaxial strain induced into the graphene network. It is noteworthy that the stain-induced thermal conductivity change is observed not only for multilayer graphene used in this study but also for exfoliated monolayer graphene48. Because long-wavelength phonons mainly contribute to the thermal energy transport, the phonon group velocity for heat conduction is nearly equal to the speed of sound in a material. The speed of sound in a material is proportional to the square root of the stiffness due to the nonlinear character of lattice elasticity. Consequently, the phonon group velocity decreases significantly as the tensile strain increases. Thermal conductivity κ is expressed as C is the specific heat, v is the phonon group velocity, and λ is the mean free path (MFP) of a phonon. In other words, the thermal conductivity decreases as the phonon group velocity decreases. In addition, biaxial tensile strain also reduces the stiffness in the out-of-plane direction48, drastically changing the thermal conductivity in multilayer graphene compared to that in single-layer graphene.The tensile strain decreases the stiffness tensor and increases in lattice anharmonicityλph, λdef, λGB, and λel are the phonon MFP due to intrinsic phonon–phonon, phonon–defect, phonon–grain boundary, and phonon–electron scatterings, respectively. Here, the effect of phonon–phonon scattering must be considered because both DEVICE 1 and DEVICE 2 show identical thermal conductivity changes, implying that other factors may have a relatively small effect.Next, the change in the phonon MFP due to strain must be considered. According to Matthiessen’s rule, the phonon MFP is described by 49. The downshift of phonon frequencies causes more activated phonon modes, enhancing Umklapp scattering. All the aforementioned effects significantly reduce λph. Consequently, the decreased phonon MFP drastically reduces the thermal conductivity of the graphene drums.The strain responsible for thermal conductivity reduction in this study may be nonuniformly distributed over the graphene membrane. Nonuniform strain typically breaks the crystal symmetry of graphene by enhancing phonon–phonon scattering. On the other hand, strain also splits the two degenerate optical dispersion branches (LO and TO) at the G points to create a phonon bandgapHerein we investigated the change in the thermal conductivity of single crystalline multilayer graphene by biaxial strain. Two mechanisms were used to introduce strain: pressure difference–induced strain and electrostatic attraction–induced strain. By precisely estimating the strain using AFM and Raman spectroscopy, we found that both mechanisms drastically reduce the thermal conductivity by 60–70% with a strain of approximately 0.1%. This reduction does not originate from convective heat transfer or phonon–electron scattering, but it may be due to the decreased phonon group velocity and MFP caused by strain. Consequently, strain-controlled heat conduction may realize thermal management devices such as high-efficiency thermal switches and diodes.Supplementary Figures.


Increasingly, firefighting aerosols are being used to extinguish fires. It is assumed that the extinguishing mechanism involves breaking the chain of physicochemical reactions occurring during combustion by binding free radicals at ignition. The radicals are most likely formed from the transformation of water molecules, with the active surfaces of aerosol micro- or even nanoparticles. The aerosol extinguishing method is very effective even though it does not reduce oxygen levels in the air. In contrast to typical extinguishing powders, the aerosol leaves a trace amount of pollutants and, above all, does not adversely affect the environment by depleting the ozone layer and increasing greenhouse effects. Depending on how the firefighting generators are released, the aerosol can act locally or volumetrically, but depending on environmental conditions, its effectiveness can be variable. The article presents the influence of environmental humidity on the atomization of aerosol nanosize, which confirms the radical combustion mechanism. This paper presents the effect of environmental humidity on the atomization of aerosol superfine (nano) particles. The main focus was on the grain distribution and its effect on the surface activity of the FP-40C type firefighting aerosol. Changes in the characteristic parameters of the particle size distribution of RRSB (Rosin-Rammler-Sperling-Bennet) are presented. The mechanism of action of extinguishing spray is not yet well understood. It is assumed to be associated with the inhibition of the combustion reaction. In further explaining this mechanism, it is important to know the form of fuel, oxygen and the environment in which, during a fire, the chain reactions can occur. For simplicity, we can assume that coal and hydrogen are considered as fuels in the environment. Fuel can exist in different states of matter, however, and in the case of a flame combustion reaction, only the gaseous state carrying the mentioned hydrogen and carbon atoms, is present. A similar combustion mechanism may occur in the case of liquid fuel combustion, although in this case the liquid vaporizes first. In other words, it should be assumed that flame combustion occurs only in a gaseous environment. A schematic of the flame combustion of solid and liquid fuels is shown in 3O*, H2O2*, etc., which support combustion reactions. Through radical recombination, the eventual fire is sustained until the potential for radical formation is exhausted 0.632d—average population diameter by RRSB in which 63.2% of the grains are smaller (1 − 1/e = 0.632)a—constant of homogeneityThe cumulative curve of the RRSB function (after integration) is described by the following equation:fA)] with respect to d in logarithmic coordinates, since the linear form can be derived in Equation (3), while the ratio 0.632d/d is the variance form of the nanoparticle size distribution. The convolution of the grain-frequency distribution function of the RRSB in the investigated size range, i.e., from 15–685 nm, can also represent the atomization activity of fA aerosol (neglecting the aspects of mass and shape of aerosol nanoparticles) in a large simplification  . HoweverFixed aerosol extinguishing systems are a generation of very effective systems used to extinguish all groups of fires, except for fire group D , although even here there is no conclusive evidence. Although the fire suppression mechanisms are not well understood, many successful implementations have been made using them.Superfine powder particles act as fire suppressors through heterogeneous free radical inhibition. The heterogeneous  quenching mechanism results in a ‘‘thermal death’’ effect of free radical flame burning (FFR) on the powder surface. The powder remains in the solid phase, does not evaporate and acts as a “cold medium” in which recombination reactions take place to break the chain combustion process. Each single particle of extinguishing powder, in the process of adsorption, contributes to the destruction of radicals, so it is important to have the maximum possible fineness, which can be obtained at the right humidity (70%).Therefore, intensive research is still being conducted. First of all, it has been shown that firefighting aerosols are highly dispersed when atomized in an environment of about 70% humidity. This fact opens new cognitive possibilities towards the elucidation of their mechanism of action. Probably, water molecules and their radicals immediately adhere to the surface of atomized nanosized grains forming an envelope. Such a mechanism, on the one hand, hinders the aggregation of aerosol superfine particles caused by a large surface development, and on the other hand, effectively traps radicals. However, the aqueous envelope can evaporate at high temperatures and the aerosol becomes invisible. This probably occurred in the 70% humidity environment  where thA lower ambient humidity immediately changes the dispersion of aerosols toward larger sizes. This is caused by their rapid aggregation as in In dry (30% humidity) and very humid (90% humidity) environments, the number of aerosol particles decreases over time due to both aggregation and clumping.The size of the mode fraction, median and mean value of the aerosol increases over time from 20 to 50 nm depending on the environmental humidity.The most preferable conditions for extinguishing aerosol atomization occur in an environment with a humidity of about 70%, which may be connected with more effective capture of water radicals of chain reactions occurring in flame fires.


Graphene plasmon resonators with the ability to support plasmonic resonances in the infrared region make them a promising platform for plasmon-enhanced spectroscopy techniques. Here we propose a resonant graphene plasmonic system for infrared spectroscopy sensing that consists of continuous graphene and graphene ribbons separated by a nanometric gap. Such a bilayer graphene resonator can support acoustic graphene plasmons (AGPs) that provide ultraconfined electromagnetic fields and strong field enhancement inside the nano-gap. This allows us to selectively enhance the infrared absorption of protein molecules and precisely resolve the molecular structural information by sweeping graphene Fermi energy. Compared to the conventional graphene plasmonic sensors, the proposed bilayer AGP sensor provides better sensitivity and improvement of molecular vibrational fingerprints of nanoscale analyte samples. Our work provides a novel avenue for enhanced infrared spectroscopy sensing with ultrasmall volumes of molecules. With the ability to probe the vibrational characteristics of inorganic, organic, and polymer compounds samples, infrared spectroscopy possesses the advantages of rapid testing, convenient operation, good repeatability, high sensitivity, and less sample consumption ,2. The bTo address this problem, various types of strategies have been proposed to enhance the absorption signal of molecules. Among these strategies, plasmonic enhancement is one of the most effective approaches to improve light–molecule interaction in the mid-infrared range ,9,10. CoIn this work, we proposed a resonant graphene plasmonic system to far-field excite AGP mode between a bilayer graphene gap for ultra-sensitive molecular infrared spectroscopy sensing. Here the AGPs are excited in the graphene/nano-gap/graphene plasmon cavity instead of the graphene/nano-gap/metal plasmon cavity. The excitation efficiency of AGPs is improved by placing a reflection mirror below the graphene gratings to form an F–P resonant cavity in the vertical direction. In this bilayer graphene plasmonic biosensor, the tightly confined AGP mode inside the bilayer graphene gap provides strong coupling between ultra-compressed mode-volume plasmon cavity mode and molecular vibrational fingerprints mode, resulting in the significant enhancement of the molecular infrared spectroscopy. For illustration, the protein molecules are selected as the sensing analytes in order to evaluate and analyze the biosensing performance of this bilayer AGPs sensor platform. By adjusting the Fermi energy of graphene via external gate voltage, the AGPs’ resonant wavelength can be actively tuned over the infrared region, which enables us to sensitively detect the absorption band of ultra-thin target molecules.p = 82 nm, a width of graphene grating w = 42 nm, and a thickness of nanogap g = 3 nm as shown in e is the elementary charge, ℏ is the reduced Planck constant, c is the speed of light in vacuum, and x-direction and that in the y-direction is infinitely. The refraction index of silicon spacer layer is The ultra-compressed mode-volumes graphene plasmon cavity are formed by graphene/ nano-gap/graphene van der Waals heterostructure with a period of  formula ,33(1)σ(We first investigate the excitation of graphene acoustic plasmons in the proposed bilayer plasmonic system. Under the illumination of transverse magnetic (TM) waves, graphene plasmons can be excited with the assistance of the patterned graphene nanoribbons. According to the F–P resonant model, the resonance condition of such graphene plasmonic modes can be given as following equation:m represents the order of the resonance, Re means taking the real part of the complex quantity, and Here, r system .In order to improve the conversion efficiency of graphene acoustic plasmon, the dielectric spacer layer and gold mirror are further introduced to form an F–P resonance cavity ,34 to eng = 3 nm thickness protein coating over a lossless silicon dioxide substrate is plotted by red line in this picture, and the maximum value of absorption peak are 0.11% and 0.078%, indicating the positions (dash line) of the amide I band  feature of protein vibrational modes after plasmonic enhancement with varying graphene Fermi energy is further extracted and plotted as a function of wavelength in  sensors .To illustrate the advantage of tunable bilayer AGP biosensor, we finally compare the enhancement performance of the proposed bilayer AGP system to that of single-layer GP biosensor by removing top continuous graphene sheet, as shown in The extinction spectra of the GP sensor and AGP biosensor with varying widths of graphene ribbons are shown in  of 4 nm b. While  of 2 nm e. It is Our proposed structure can be fabricated with a similar process as previous literature ,30,34. TIn conclusion, we have suggested a method of probing vibrational fingerprints of extremely ultra-small volume molecules with a bilayer graphene acoustic plasmons biosensor, which is formed by continuous ultra-compressed mode-volume graphene-insulator-graphene plasmon cavity. Compared to graphene-gap-metal AGP structures, the proposed design is expected to solve the difficulty of metal unevenness or surface roughness which significantly attenuates far-field signals and requires a complex fabrication process to realize ultraflat metal surfaces. Furthermore, we have found that strong absorption and tight electromagnetic field confinement are realized in mid-infrared frequency for such a biosensor. The acoustic plasmons modes are squeezed into the nano-metric gap by far-field excitation with high efficiency at normal incidence. By placing protein molecules inside bilayer graphene nano-gap, the molecular fingerprints can be frequency-selectively enhanced by extreme plasmon overlap. The extinction spectra and the absorption band of thin protein molecules can be precisely resolved by sweeping the graphene Fermi energy and extracting plasmon-enhanced excitation peak signals. The maximum enhancement factor can be up to 510 for the amide I band and 560 for the amide II band of enhanced molecular absorption IR spectroscopy. We further demonstrate that the sensitivity of the AGP biosensor is much higher than that of the conventional GP biosensors due to highly confined plasmon mode overlap (<3 nm) and ultra-strong interaction of light and biomolecules. Our proposal provides a new platform to study nanoscale light-matter interactions and ultrasensitive infrared spectroscopy for single-molecule optics, extreme biosensing ,41, and


UV–Vis spectroscopy, transmission electron microscopy (TEM), zeta potential , and X-ray photoelectron spectroscopy (XPS) were used to characterize the AuNPs and nanocomposites. The addition of reduced graphene oxide (rGO) resulted in greater dispersion of AuNPs on the rGO surface compared with carbon-based nanomaterials used as a support. Differences in morphology due to the nature of the carbon support were observed and are discussed here. AuNPs/rGO seem to be the most promising candidates for the development of LSPR biosensors among the three composites we studied . Simulations based on the Mie scattering theory have been used to outline the effect of the phytochemicals on LSPR, showing that when the presence of the residuals is limited to the formation of a thin capping layer, the quality of the plasmonic resonance is not affected. A further discussion of the application framework is presented.Aiming to develop a nanoparticle-based optical biosensor using gold nanoparticles (AuNPs) synthesized using green methods and supported by carbon-based nanomaterials, we studied the role of carbon derivatives in promoting AuNPs localized surface plasmon resonance (LSPR), as well as their morphology, dispersion, and stability. Carbon derivatives are expected to work as immobilization platforms for AuNPs, improving their analytical performance. Gold nanoparticles (AuNPs) were prepared using an eco-friendly approach in a single step by reduction of HAuCl Plasmonic biosensors are widely explored as promising sensing tools due to their low cost, simplicity, and short response time. These devices can be useful in a variety of situations, such as medical emergencies in more isolated populations or/and with poor access to health services . For theGold nanoparticles (AuNPs) have been widely used in the development of optical biosensors . Their uWhen AuNPs are used as optical transducers, the region of confinement in which the evanescent wave is propagated is smaller than the wavelength of the incident light. In this case, the phenomenon is called localized surface plasmon resonance (LSPR), where the collective oscillation of the electrons originates a dipolar or multipolar moment in the nanoparticle. LSPR is excited at a specific light wavelength, which is determined by the morphology, size, and composition of the nanoparticle . Any modWhen the analyte of interest is recognized by the BRE, the surface refractive index of the AuNPs changes, promoting a shift in the LSPR wavelength .The interest in AuNPs for the development of biomedical diagnostic devices is related to their sensitivity and the possibility of controlling and optimizing the limit of detection (LOD) .2sp hybridization [Moreover, these interesting properties may act synergistically with graphene when this carbon nanomaterial is added to form a nanocomposite . For exadization , can be The oxidation of graphene, yielding graphene oxide (GO), allows the addition of oxygen functional groups to its surface, reducing electrical conductivity and malleability, and increasing solubility in polar solvents, as well as reducing the aggregation of carbon-based nanomaterials in aqueous solutions.Graphene oxide shows a greater functionalization capacity due to the presence of a larger number of oxygen groups, but for the same reason there is also restriction of the mobility of electrons on its surface. Reduction of the number of oxygen groups, yielding reduced graphene oxide, allows the restructuring of electrical and thermal conductivity towards pristine graphene, maintaining functionalization capacity and the distance between graphene sheets . The mai4) [In this work, the influence of a variety of carbon-based materials on gold nanoparticles’ (AuNPs) localized surface plasmon resonance (LSPR) has been studied and, considering environmental concerns, an ecofriendly approach in the synthesis of gold nanoparticles was chosen, using tea extract as a reducing/capping agent. As a matter of fact, the phytochemicals present in tea, such as polyphenols and tannins, have the interesting capacity of reducing metallic salts, such as chloroauric acid (HAuCl4) ,11,12.Although the use of composite materials based on metal nanoparticles and graphene allotropes to explore plasmonic properties in sensing applications has already been reported in the literature ,14, a grSensors based on the local surface plasmon resonance of metal nanoparticles are characterized by simple structures and good sensitivities. Despite the good sensing properties of LSPR structures, full commercialization has been prevented by the production costs associated with the bio-functionalization and the high-precision systems necessary to extract the optoelectronic output. There is a great interest in new strategies for bringing the excellent detection properties of LSPR sensors into play in low-cost devices made with low-cost materials . The comThe main advantages of these nanomaterials are their biocompatibility, high chemical stability, and high surface areas. The reduced dimensions and weight, high resistance, simplicity of use, and low cost makes graphene and its derivatives excellent candidates for the development of biosensors.An optical sensor has, by definition, the ability to convert an external stimulus into an optical output signal.The π–π binding capacity of graphene with biomolecules allows the use of this carbon-derived nanomaterial as a substrate, and the SPR technique can be used to detect the interaction with the analyte of interest, in which the angle of an incident polarized light is adjusted as a result of the change in the refractive index caused by the interaction between them. rGO has advantages over graphene, since its oxygen functional groups improve the interaction of this nanomaterial with biomolecules .Optical sensors, such as those based on fluorescence, surface-enhanced Raman scattering (SERS), optical fiber biological sensors, among other kinds of optical sensors, are being developed due to the amazing properties of graphene and its derivatives. Various sensing applications, such as single-cell detection, cancer diagnosis, and protein and DNA sensing, have been reported in recent years .Due to its unique optical and electrical properties, graphene and its derivatives are widely used in photonic and optoelectronic devices as they have displayed several ideal properties, including broadband light absorption, the ability to quench fluorescence, excellent biocompatibility, and strong polarization-dependent effects, making them very popular platforms for optical sensors. Graphene and its derivatives-based optical sensors have numerous advantages, such as high sensitivity, low-cost, fast response time, and small dimensions. The use of metallic nanoparticles, namely, gold nanoparticles, may improve the response of biosensors, amplifying the signals obtained and increasing the sensitivity of these devices .Several applications of graphene and its derivatives-based optical sensors are summarized in the following It is undeniable that there are still many challenges in this area. The need to synthesize high-quality graphene, to achieve a low-cost, environmentally friendly method for synthesizing graphene and its derivatives are issues still to be addressed. With this study, the use of a simple green method to produce light-responsive material is our aim and contribution.Addressing the above challenges, we hope to show the potential of green methods as well as the importance of graphene and its derivatives in the development of optical sensing technologies, which will ultimately increase the quality of future life.4·3H2O) to a tea extract (5% w/w), a change of color from yellow to red was observed, which is consistent with the formation of AuNPs. The AuNPs’ characteristic LSPR was observed only after one week (t1w), the absence of LSPR at the initial time (t0) possibly being associated with the period of reduction required to originate AuNPs or due to the fact that in the case of hybrid nanostructures, carbon materials may be responsible for radiation absorption, inhibiting the detection of AuNPs, as described by Biris et al. [After the addition of chloroauric acid  and second week (t2w) after synthesis no significant differences in LSPR response was observed, confirming that polyphenols guarantee a certain stability to the synthesized AuNPs. As proven previously by the authors of [The stability of the synthesized nanoparticles was evaluated. We found that between the first  (LSPR = 541 nm) and reduced graphene oxide (rGO) (LSPR = 542 nm). The composite containing graphene oxide (AuNPs/GO) did not show any LSPR shift after the addition of carbon-based nanomaterials. For the AuNPs/G hybrid nanostructure, band amplitude decreased by ~10% when compared to the sample without any of the carbon-based nanomaterial, while for AuNPs to AuNPs/rGO, it increased by ~0.29, which corresponds to 46% of the naked/unsupported AuNPs’ absorbance. This result may be ascribed to a dispersion of the AuNPs [he AuNPs  in the phe AuNPs .LSPR properties depend not only on the AuNPs’ shape, size, and dispersion but also on the surrounding dielectric constant. TEM characterization showed the formation of spherical AuNPs . Althoug0, we assumed that the nucleation of metallic salts occurred near the rGO functional oxygen groups [The probable formation of π–π bonds between AuNPs and the functional oxygen groups of rGO  may be rn groups  which man groups .π–π interactions between AuNPs and functional oxygen groups of rGO; (ii) π–π interactions between benzene rings of the polyphenols and the surface of rGO; and (iii) electrostatic interactions between the OH on the surface of rGO and the polyphenols capping the AuNPs. After mixing, the shape of the AuNPs appeared to be the same when observed by TEM (The reason for using a pre-prepared solution of AuNPs stabilized with polyphenols then mixed with rGO is to help anchor the polyphenol-protected AuNPs to the rGO surface. This process could be assisted by: (i) d by TEM , but thed by TEM , the intIn the case where GO is added to the AuNPs, no significant deviation in the LSPR occurs relative to the value observed prior to the addition of this carbon-based material (λ = 556 nm). TEM images  show a gAfter the addition of both GO and rGO, sharper resonance bands as well as an increase in the resonance intensity or amplitude were observed . In factThe partial reduction of oxygen groups in GO driven by tea polyphenols  may contWe also measured the electrostatic potential at the electrical double layer surrounding a nanoparticle in solution, commonly referred to as the zeta potential. Nanoparticles with a zeta potential between −10 and +10 mV are considered approximately neutral, while nanoparticles with zeta potentials of greater than +30 mV or less than −30 mV are considered strongly cationic and strongly anionic, respectively . Since mpω) of the free electron gas depends linearly on the density of the electrons (Ne). Such a consideration leads, in the Drude model, to a linear dependence of the metal dielectric function on the value of Ne. Within the dipole approximation, i.e., when the nanoparticle size is much smaller than the light wavelength, and under the Fröhlich condition, it can be shown that the LSPR frequency (LSPRω) can be directly related to pω by the following equation:mε is the dielectric constant of the surrounding medium [According to the classical physical theory for the electromagnetics of metals, the plasma frequency  and 2 weeks (t2w) after synthesis. 1w vs. t0). These data show that the synthesis of the nanoparticles did not cease after 20 min of vigorous stirring of chloroauric acid with the tea extract. This shift could mean that the diameters of the AuNPs increased between t0 and t1w. As mentioned above, the increased band amplitude after a week suggests that there was an increase in the concentration of nanoparticles, indicating that the formation of AuNPs was still happening [The stability of the synthetized nanoparticles was also evaluated by the sample’s characterization, 1 week (tappening .2w) showed that LSPR did not shift in comparison to that observed after 1 week (t1w)  . The pol1w and t2w, we can observe a slight increase in the absorbance value without a change in the behavior of the plasmonic response. Tea contains a multitude of different chemicals. Some of these, e.g., tannins, are fairly dark to begin with, but, if they are allowed to react with the oxygen [1w and t2w is more obvious in the 5%_AuNPs/GO in comparison with the 5%_AuNPs/rGO sample, since GO has more oxygen groups on its surface.Between te oxygen  in the ae oxygen , creatin4 with the phytochemicals present in tea extract as a reducing agent, we have considered the gold nanosphere capped by a thin uniform layer of tea polyphenols, immersed in pure water. This approach agrees with the morphology observed in The variation in the transmission spectra caused by the plasmonic resonance of the nanoparticles can be calculated by recourse to the Mie Theory , and theThe effect of increasing the thickness of the cover layer results in the LSPR shifting towards the red region. Simultaneously, the intensity of the LSPR shows a marked reduction as the capping thickness increases.We can conclude from this simulation analysis that the residual polyphenols which remain after AuNP fabrication have a negligible effect on the quality of the plasmonic response. An excessive accumulation of the residual polyphenols on the AuNP surface would reduce the LSPR intensity, but the simulation shows that for the range of the capping thickness observed in the TEM images, such a level of EGCD accumulation is not reached. The red shift foreseen by the simulation has no impact on the operation mechanism of a sensor device built with these materials. At the same time, the presence of the capping layer can be expected to physically separate the nanoparticles, preventing their aggregation. Thus, AuNPs synthesized by this green method combine the advantage of a simplified fabrication method that avoids aggregation with a reliable plasmonic resonance that can be successfully exploited in a sensing device.The wavelength and intensity of LSPR are strongly dependent on the refractive index of the surrounding medium. An alteration of this parameter provokes a shift of the LSPR peak which can be used as the output value of a sensing system. To evaluate the sensing efficiency of the AuNPs, the spectral shift (Δλ) of the resonance wavelength, as a function of the variation in the refractive index (Δn) of the surrounding medium, can be translated into a sensitivity parameter (S):4·3H2O) was purchased from Sigma-Aldrich ; the black tea leaves (Thea sinensis) for the tea extract preparation used as a reducing agent for chloroauric acid was purchased from Pingo Doce ; graphene [Chloroauric acid  with a 6 mL total volume. This mixture was stirred for 20 min at 400 rpm at room temperature. After that, 1 mg of graphene or derivative was added to every 2 mL of the samples previously obtained (Sequence 1 (SQ1): 1 mL of chloroauric acid (0.1 M) was added to each tea extract obtained a.Sequence 2 (SQ2): The same weight of graphene or derivatives was added before the addition of chloroauric acid b. The re0, t1w and t2w, to determine the stability of the AuNPs and the nanocomposites over time, t0 being the starting moment, immediately after stirring the samples, t1w one week after, and t2w two weeks after. All samples were preserved in cold conditions and protected from light. TEM images were obtained between t0 and t1w, as was the zeta potential of the samples.Both nanoparticles and nanocomposites were characterized by UV–Vis spectroscopy  and transmission electron microscopy  with a ThermoNoran EDS light and zeta potential . The characterization by UV–Vis was undertaken at 3 distinct moments, t2 C-C and C-H peak set at 284.4 eV [Modified and unmodified graphene were analyzed by X-ray photoelectron spectroscopy with a XSAM800 spectrometer from KRATOS. Non-monochromatic radiation from a Mg Kα source was used (hν = 1253.6 eV). Powdered samples were fixed on the XPS holder with a double face tape and analyzed at UHV, at TOA = 45°. The BE was corrected considering the charge shift observed for the sp284.4 eV . Other o284.4 eV .Thea sinensis) showed reducing capacity of chloroauric acid, allowing the synthesis of spherical gold nanoparticles. The production of AuNPs through this green synthetic approach proved to be sustainable, not only due to its low cost but also because of the reducing capacity of the tea and its coating agent function, conferring stability to the synthesized AuNPs. We found that 2 weeks after stirring of the reagents, polyphenols prevailed as coating agents, sustaining the stability of the AuNPs. Simulation results based on the Mie theory for the LSPR effects support the conclusion that, even with a thin capping layer of residuals, no significant reduction of plasmonic resonance should be expected.The black tea extract (The addition of carbon-based nanomaterials before stirring of the tea extract with chloroauric acid proved not to be efficient with respect to the stability of synthesized AuNPs, and, in some cases, LSPR did not take place at any of the moments of characterization. The reverse order of material addition, i.e., the addition of carbon-based nanomaterials after the stirring of the tea extract with metallic salt, proved to be more efficient, both in terms of the synthesis and stability of the AuNPs.Of the three materials studied, rGO proved to be the most efficient carbon-based nanomaterial used as a support for AuNPs to be applied in biosensors. The stability revealed by the zeta potential, the greater dispersion of AuNPs, and the conductivity of this nanomaterial reported by several authors support this statement. Khalil et al.  corrobor0 and t1w so that we can determine when this reaction ceases. In addition, trying other brands of black tea could supply additional valuable information, since different conditions, both soil and climatic, may be associated with different antioxidant properties.The topic of this paper has not been widely explored in the literature and it will be necessary to carry out more exhaustive research in order to reach conclusions about certain questions raised in our study. Nevertheless, we believe that this work can be a good starting point for this investigation. Regarding future work, it would be interesting to monitor the synthesis of AuNPs between t


Four N-doped graphene materials with a nitrogen content ranging from 8.34 to 13.1 wt.% are prepared by the ball milling method. This method represents an eco-friendly mechanochemical process that can be easily adapted for industrial-scale productivity and allows both the exfoliation of graphite and the synthesis of large quantities of functionalized graphene. These materials are characterized by transmission and scanning electron microscopy, thermogravimetry measurements, X-ray powder diffraction, X-ray photoelectron and Raman spectroscopy, and then, are tested towards the oxygen reduction reaction by cyclic voltammetry and rotating disk electrode methods. Their responses towards ORR are analysed in correlation with their properties and use for the best ORR catalyst identification. However, even though the mechanochemical procedure and the characterization techniques are clean and green methods , they are time consuming and, generally, a low number of materials can be prepared, characterized and tested. In order to eliminate some of these limitations, the use of regression learner and reverse engineering methods are proposed for facilitating the optimization of the synthesis conditions and the materials’ design. Thus, the machine learning algorithms are applied to data containing the synthesis parameters, the results obtained from different characterization techniques and the materials response towards ORR to quickly provide predictions that allow the best synthesis conditions or the best electrocatalysts’ identification. Nitrogen-doped graphene , obtained by the substitution of carbon atoms from the graphene layers with nitrogen, possesses interesting structure and electronic, magnetic and optical properties ,2,3. DueIn recent years, research aimed at the development of efficient and inexpensive oxygen reduction reaction (ORR) catalysts has involved the use of the N-doped graphene materials, coupled or not with some transitional metals, such as iron or cobalt ,11,12,13− reaction pathway is preferred to the 2e− one yielding to water molecules, and it9 is considered a plausible pathway for ORR on doped graphene in both acid and alkaline media [The oxygen reduction reaction (ORR) is a kinetically slow process, requiring a transfer up to four electrons and four protons, and at least three intermediates are involved during the catalytic procedure . The 4e−ne media . Howeverne media . Moreovene media .In our research, we have performed a ball milling treatment in order to prepare nitrogen-doped graphene from graphite and melamine as nitrogen source. In addition to the advantage of obtaining large quantities of functionalized graphene-based materials, this protocol allows the development of materials by a green approach (a clean and safe chemistry), without the employment of polluting solvents. Four types of N-doped graphene with N wt.% between 8.34 and 13.1 have been obtained and their ORR performance has been evaluated using cyclic voltammetry and rotating disk electrode protocols. To determine the correlation of the ORR catalytic performance with the materials’ structure, we analysed the hybrid materials by different methods, including transmission and scanning electron microscopy , thermogravimetric measurements (TGA), elemental analysis, X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction (XRD) and Raman spectroscopy. Moreover, to facilitate the materials’ design and to establish the best synthesis conditions, the machine learning algorithms have been trained on variables containing as input the data that combine both the experimental conditions and different characterization parameters, and as output the number of electrons transferred during the ORR process. The predicted results were then used to identify the optimization of material properties and the best synthesis conditions by applying the reverse engineering process.These images indicate the nitrogen doping of the graphene and the presence of oxygen species on the graphene surface. Moreover, the graphene obtained by ball milling procedure appears to have a fluffy structure, very different from that synthetised by CVD or chemical methods ,19,20 orA first idea about the functionalities found on the graphenes’ surface is given by the thermogravimetric analysis of nanocomposites under the argon atmosphere . The phy2, can be also seen in this region [For the hybrid materials, the TG and DTG curves, obtained under the argon atmosphere, show nearly no weight loss for graphite —region I of the TGA—and from the O-functional groups that are formed during the grinding process, considering that the materials are obtained in air and not under argon or nitrogen atmosphere. According to the data from Further analysis of the N-doped graphene surfaces has been performed by X-ray photoelectron spectroscopy (XPS) and the results are presented in Three major nitrogen types—pyridinic-N 398.4 eV, pyrrolic-N 399.5 eV, and pyridine-N-oxide ~404.9 eV—have been identified from the XPS measurements . The pre2/Csp3 ratio and the content of oxygen functionalities from the graphene surface .The quality of the four materials has been investigated by considering the XPS percentages obtained for the C1s, in terms of the Csp surface . The res2 hybridized carbons [The X-ray diffraction (XRD) patterns of the four N-doped graphene are presented in  carbons . The maiAccording to these results, the number of graphene sheets depends on the quantity of melamine and the reaction time; when a large quantity of melamine is involved, a reaction time of 24 h is not enough to lead to low graphene layers (larger quantities of billing agent/reactant need more energy to accomplish the graphite exfoliation). When the reaction time is 48 h, the differences between the general parameters of the two composites are small . The cor−1. Thus, the 1355 cm−1 peak, which is characteristic of polycrystalline graphite, can be attributed to a particle size effect and its intensity is inversely proportional to the crystallite size [−1) and D + G (about 2950 cm−1) [−1 to 1596 cm−1) as the N concentrations increase, and the 2D′ peaks show a down-shifting (from 3241 to 3215 cm−1) associated with the N content rising. The 2D peaks are located between 2707 and 2704 cm−1; however, the slight redshift of the 2D bands could not be directly associated with the increasing of the N amounts in the composite  . In Figuomposite .D/IG ratio and the nitrogen content of the four hybrid materials. However, the ratio between ID’ and IG (ID′/IG)—calculated for the four N-doped graphene materials—increases from 0.41 to 0.56, showing a better correlation with the N materials’ content than that of the ID/IG. Nevertheless, when attention is paid to the differences between all ID’/IG values, we observe that these differences are not entirely connected with the concentrations’ differences , their investigation requires that this wavelength be used. The obtained results are presented in The electrocatalytic activity for ORR of the four N-doped graphene samples, prepared by the green procedure , was tested in alkaline solutions of 1M NaOH. 2- or O2-saturated 1M NaOH solutions at a scan rate of 50 mV/s using the N-doped graphene/glassy carbon (GC) modified electrodes; for comparison, the 10 wt.% Pt/C modified GC has been prepared and tested towards ORR in alkaline medium  measurements have been performed in Ne medium .According to these results, neither the use of large amounts of melamine nor the increase in the reaction time is justified for ball milling preparation of efficient catalysts for oxygen reduction in alkaline media.As can be seen in −1 vs. ω−1/2) at different potentials and show clear linearity. From the Koutecky–Levich (K–L) equation, presented below, the number of electrons (n) transferred in the ORR process is evaluated and presented in j—measured current density; lj—diffusion-limiting current density; kj—kinetic-limiting current; ω—electrode rotation rate (rpm); F—Faradaic constant ; O2C—O2 concentration in 1M NaOH solution (0.843 × 10−6 mol/cm3); O2D—O2 diffusion in 1M NaOH solution (1.43 × 10−5 cm2/s); n—number of electrons transferred in the ORR process; ν—kinematic viscosity of the electrolyte (1.13 × 10−2 cm2/s) [A comparative study was also conducted using the rotating disc electrode (RDE) at different rotating rates from 400 to 2500 rpm on the appropriate N-doped graphene/glassy carbon (GC) . These e2 cm2/s) ,31,32.Based on the K–L equation, there is a variation of the numbers of electrons transferred with the potentials, indicating a complex mechanism. The best results are observed for N-Gr-3-24 and N-Gr-10-24, of about 3.96 and 4.1 at −0.45 V, which are close to the theoretical value of Pt/C (4 electrons). These hybrid materials appear to be more efficient for ORR compared to N-Gr-3-48 and N-Gr-10-48 (numbers of electrons transferred: 3.41 and 3.08 at −0.45 V).2 for 10 wt.% Pt/C and 7.84 mA/cm2 for N-Gr-3-24, suggesting a better response towards ORR of the N-doped graphene material.It is clear that the changes occurring in the materials during the additional 24 h of the synthesis process are determinant for their ORR behaviours . For theThe long-term stability of the four nitrogen doped materials and Pt/C was investigated using cycling voltammetry . The cat2 and CO saturated 1M NaOH electrolyte, respectively   and a high current density (4.7 mA/cm2) .To summarize, the hybrid materials’ response for the ORR seems to be strongly influenced by the quality of graphene structure .Looking to the electrochemical response towards ORR of the investigated materials and analysing these results by comparison with the results obtained from different characterization techniques, some questions need to be addressed: have we tested the best materials for ORR or is it possible to find an N-doped material, prepared by ball milling procedure, with improved electrochemical properties for our study?2 (0.67) values were found for the Stepwise Linear Regression model. 2 value obtained for the model.K. Min et al.  have alrinvpred) has been applied to the predicted values, and to the most significant variables, when the number of electrons transferred during ORR is four.The predicted values of the numbers of electrons have been further employed in the reverse engineering process to establish the best synthesis conditions or the best material characteristics that should be obtained if we wish to improve the materials’ performances towards ORR. Thus, the inverse prediction function , the FWHM of the XRD peak, and the ID′/IG, I2D/IG and G peak positions from Raman measurements. The results are presented in Firstly, we applied the reverse engineering process for the synthesis parameters; our data make it possible to obtain perspective for the reaction time, but not for the melamine amounts. We continued with the most significant variables, the material characteristics that could provide information regarding the materials’ properties: the nitrogen doping percentage, the pyridinic and pyrrolic N content, the quality of graphene  and 2,4,6-triamino-1,3,5-triazine , further denoted as melamine, in a planetary ball milling machine .During the grinding process, a high amount of energy was released and activated the reactants, thus making the doping process possible. Therefore, the nitrogen atoms from the melamine could be introduced in the graphite network, yielding to the nitrogen functionalized material. Thus, the synthesis was conducted at a temperature much lower than the temperature commonly used for chemical synthesis.Our process was performed at room temperature. The weighted graphite and melamine were transferred to a stainless-steel grinding jar with grinding balls  made of stainless steel. Two ratios between graphite and melamine were chosen: 1:3 and 1:10; in addition, two reaction times of 24 and 48 h were investigated.Briefly, 1 g of graphite and the appropriate amounts of melamine were loaded in the milling bowl, sealed by fixing in the planetary ball-milling machine and grounded at 400 rpm for 24 h or 48 h, respectively. The obtained materials are denoted as N-Gr-3-24, N-Gr-3-48, N-Gr-10-24, N-Gr-10-48, in agreement with the ratios and reaction times employed in the synthesis procedure. Afterward, the materials were washed thoroughly with hot water to remove the un-reacted melamine.Transmission and scanning electron microscopy (TEM and SEM) were realized on a Hitachi HD 2700  equipped with energy dispersive X-ray analysis (EDX).−1.Thermogravimetry measurements were carried out in argon using TA Instruments SDT Q 600 equipment  in the temperature range from 25 to 800 °C, with a heating rate of 10 °C minA Flash 2000 CHNS/O analyzer  analyzer was used to perform elemental analysis of the N doped material.For X-ray Photoelectron Spectroscopy (XPS), a SPECS XPS  equipped with an Al/Mg dual-anode X-ray source, PHOIBOS hemispherical energy analyzer, 150 2D CCD, and a multichanneltron detector, were employed. The spectra were recorded for nitrogen, carbon, and oxygen elements by performing multiple scans with high resolution. Data analysis and curve-fitting were performed by employing a Gaussian–Lorentzian product function and a nonlinear Shirley background subtraction. The high-resolution spectra were deconvoluted into the components corresponding to different types of bonds.θ< 85° with a step size of 0.01°/s.The X-ray powder diffraction (XRD) analyses were recorded by using a Bruker D8 advanced diffractometer  with Cu Kα1 radiation, operating voltage 40 kV, and current 40 mA. The diffraction patterns were measured in the range 15° < 2−1 were employed to record the spectra in the range of 73–4200 cm−1. Each spectrum was collected with an exposure of 100 s and a minimum of three scans; the data were analyzed using OriginPro 2017 software.The Raman spectra were obtained using a JASCO NRS-3300 Raman Spectrometer  with a CCD detector and excitation at 514.5 nm from an argon-ion laser. An Olympus objective UMPLFL 100X, 600 L/mm grating, 0.1 × 6mm slit, and the wavenumber centered at 2300 cm2) as the working electrode, Ag/AgCl , and platinum plate electrodes as the reference and auxiliary electrodes; all the measurements were realized in N2- or O2-saturated 1M NaOH solutions. For the RDE measurements, the spectra were recorded in O2-saturated 1M NaOH solution at various electrode rotating rates (400 to 2500 rpm) and a potential scan rate of 10 mV/s. The procedure for CO stripping experiments employed the following steps: (i) N2 was bubbled on the electrolyte (1 M NaOH) at a constant potential of −0.9 V vs. Ag/AgCl for 30 min, (ii) the gas was switched to CO and purged at the same potential for 30 min, (iii) the gas was switched back to N2 for 30 min, keeping the potential at −0.9 V vs. Ag/AgCl to remove the excess of CO gas from the electrolyte. The CO stripping voltammograms were recorded by cycling the potential between −1.0 and 0.2 V vs. Ag/AgCl with 20 mV/s scan rate.Electrochemical investigations, cyclic voltammetry (CV), rotating disk electrode voltammetry (RDE) and CO stripping voltammetry were performed on Autolab Potentiostat/Galvanostat 302N , controlled by the Nova 1.11 software. The three-electrode system employed a graphene-based electrode  were suspended in 1 mL dimethylformamide and sonicated for 3 min using a finger sonicator . Afterwards, 20 µl from these suspensions were drop-casted on the clean GC electrode and dried at room temperature.The glassy carbon electrode (GC) having a diameter of 3 mm was used for modified electrode preparation. Before any treatment, the glassy carbon electrode was mechanically polished with chromium (III) oxide powder. An electrochemical treatment was also applied in 0.5 M Hinvpred) was applied to the predicted results, and the most significant variables, when the number of electrons transferred during ORR was 4.Machine learning studies were performed using the Regression learner app implemented in MATLAB R2017b . The best predicted model was exported in the Matlab workspace and the predicted results were then used in the reverse engineering process; thus, the inverse prediction function (We have prepared, by a green and easily scalable method, four types of N-doped graphene materials with a nitrogen content ranging from 8.34 to 13.1 wt.%. These materials have been tested towards ORR by cyclic voltammetry and rotating disk electrode protocols and their electrochemical responses have been compared with the results obtained from the surfaces and chemical investigation techniques.D′/IG and I2D/IG ratios exhibit a good correlation with the nitrogen content and the crystallite size/number of graphene sheets, while the ID/ID′ values are similar with the current density responses obtained for the investigated materials.Thus, morphological, thermal, elemental analyses and XPS investigations have been used to obtain data about the materials’ properties. Moreover, as a rapid screening for the performance of N-doped graphene in the ORR process, we showed that the correlation between the XRD and Raman spectroscopy methods can be effective. These methods give valuable information about the graphene crystallite size and number of graphene sheets, while some parameters attained from Raman data can be correlated with the nitrogen contents and crystallite size/number of graphene layers. Thus, the G peaks shift to higher frequencies when the N concentrations increase in the materials, the IBy combining the synthesis parameters, the data obtained from different characterization techniques and the materials response towards ORR, we tested the possibility of using the machine learning algorithms for the optimization of synthesis conditions and prediction of the best structure parameters. The regression learner and reverse engineering methods have been employed to obtain these predictions. Our results highlight the advantage of using machine learning for the optimization of synthesis conditions and the design of materials.