Films were analysed using images captured by a Canon 7D camera utilising 18 mm, 50 mm and 100 mm focal length lenses compared to images scanned with a conventional Epson V700 scanner. The magnitude of the LRA was observed to be dependent on the focal length of the lens used to image the film. A substantial reduction in LRA was seen with the use of the 50 mm and 100 mm lenses, by factors of 3–5 for the 50 mm lens and 4–30 for the 100 mm lens compared to conventional desktop scanner techniques. This is expected to be from the longer focal length camera lens system being able to collect more light from distant areas compared to the scanner-based system. This provides an opportunity to design film dosimetry systems that minimise this artefact.Radiochromic film is a good dosimeter choice for patient QA for complex treatment techniques because of its near tissue equivalency, high spatial resolution and established method of use. Commercial scanners are typically used for film dosimetry, with Epson scanners being the most common. Radiochromic film dosimetry is not straightforward having some well-defined problems which must be considered, one of the main ones being the Lateral Response Artefact (LRA) effect. Previous studies showed that the contributing factors to LRA are from the structure of the active ingredients of the film and the components and construction of the flatbed scanner. This study investigated the effect of the scanner lens on the LRA effect, as part of a wider investigation of scanner design effects and uncertainties. Gafchromic EBT3 films were irradiated with 40 × 40 cm Complex radiotherapy treatment techniques  need patient-specific QA to check dose delivery and target volume localisation in three dimensions. Radiochromic film is a good dosimeter of choice for this purpose because of its properties of near tissue equivalency, very high spatial resolution and established method of use –5. Like The purpose of this work is to investigate a novel technique using cameras and different lenses for radiochromic film imaging and analysis to evaluate the effect of focal length of the scanner lens on the LRA effect in radiochromic film dosimetry and to consider whether LRA effects, and correction factors, could be reduced by using a different lens system. This is part of wider investigations considering each component of the scanning system, aiming to explore the potential for a more optimised design for film dosimetry.The film preparation, handling and irradiation methods were similar to those described in previous work , but essMode: ProfessionalDocument type: Film (with film area guide); this setting allows transmission scanningFilm type: Positive filmImage type: 48-bit colourResolution: 508 dpiNo colour correction was appliedDifferent studies have used different time, ranging from hours to days, for leaving the film in the box before scanning. Roozen  stated tISO: 100Shutter speed; 1/500Aperture: f4.5The room light was onNo colour correction was applied when converting the RAW image to.tiff imageThe following settings were used for the Canon 7D cameraThe lens system of an Epson V700 scanner has two lenses; one has a larger diameter than the other. The smaller one is for high resolution scanning. The larger lens is used for the scanning mode and so is the one used in this work. The lens assembly (both the lenses) was taken out and the focal length measured, by putting it against a vertical steel ruler on the floor on a piece of paper and moving it vertically to get a sharp image of a ceiling light. The distance from the image to the bottom lens is the effective focal length of the lens system. The focal lengths of both the lenses were found to be the same. The focal lengths of the Canon camera lenses were also verified in the same manner.Previous studies have used a variety of methods to quantify the LRA effect, all of which are based on the difference in pixel values between the centre and a lateral position –12. In tThe scanning area, which is smaller than the scanner bed of the Epson V700 scanner is the same as an A4 document size. The short side of EBT3 film is also the same as A4 document size. The edges of the film strip therefore match the edge of the scanning area in the measured profile direction. The film pieces were placed at the central position on the scanner bed to ensure the whole film piece is in the scanning area. Each film piece was scanned 20 times. The scanned images were saved as *.tiff (tagged image file format) which were read and separated into three colour channels in ImageJ V1.49 software.0 to make it stable on the table as the vertical side of it is curved. This change of orientation of the scanner bed (glass) does not have any effect as the orientation of the film with respect to the linear light source remains the same. The film pieces were taped on the scanner bed. A Canon 7D camera was used to take photos with three different lenses of 18 mm, 50 mm and 100 mm focal length. Figure A LED light source, with a similar range of wavelengths as the Epson scanner light source, was wrapped with a diffuser and positioned on a wall. A V700 scanner bed was placed in front of the LED light source to keep the path-length effect  the sameIn ImageJ an average profile was generated across each film for each combination using a rectangular ROI cropped 1 mm in from the film edge. The average profiles for each colour channel, 20 in total, were analysed in MS Excel where they were normalised to the mean of the central 100 data points Fig. .Fig. 3SeMean and standard deviation of these 20 images for each combination were calculated. The LRA effects were calculated from the profiles as the difference between the maximum (centre) and minimum (edges) values as a percentage, where the values used were the average over 25 data points at the centre and each end respectively. The propagation of uncertainty, which is the standard deviation of normalised pixel values of 20 images, was calculated as root mean square of uncertainty values of maximum and minimum mean percentage value.The Epson V700 has two lenses. The smaller one is for high resolution scanning and the bigger lens is used for the scanning mode used in this work (film with film area guide). The effective focal length of each of the lenses of the Epson V700 scanner was measured to be 38 mm. Figure Table The images acquired with different lens systems highlight a systematic variation in the LRA effect with the focal length of the image capturing system. Results show that with a smaller focal length lens system, higher LRA effects are observed. The LRA effect is also observed to increase with dose , 10, 16,It is acknowledged that the two systems being evaluated have some differences. Firstly, the light sources used in the scanner and for the camera studies are different. The Epson V700 camera uses a white cold cathode fluorescent light (CCFL) source, whilst a white LED light source was used in the camera work. Larraga-Guiteraze  comparedAlso, a flatbed scanner and a DSLR camera work quite differently. As above, in the scanner, light travels from the light source to the scanner’s CCD imager through five mirrors and a lens system . In a DSIn addition, the two systems also utilize different detectors; these being a CCD (Epson scanner) or a CMOS (Camera) detector in the respective systems. The RGB components and quantum efficiency of both systems may vary with respect to wavelength in the Red Green and Blue bandwidths. Although this paper does not analyse or quantify these potential variations, the effects of lens focal length shows similar trends in each bandpass component and as such does not diminish the validity of the trends observed in this work.Figure The decreased LRA effect using larger focal length imaging systems to analyze films provides an opportunity to create a film scanner system which has the potential to minimize the lateral response artifact. The increase in focal length necessary to capture more light from the edges of the film requires an increased distance between the film and the detection camera. Thus these results highlight the fact that the LRA can be reduced by design choices of specific characteristics of the equipment and imaging system. However, the practicalities of using longer focal length imaging systems are not simple and imply larger systems. Nevertheless, this provides an avenue for further work to explore optimization of new imaging system designs which may be able to remove or at least minimize the LRA effect for Gafchromic EBT3 film. This could potentially reduce or negate the need for scan processing or corrections to scanned raw data for radiochromic film analysis. Specific impacts on dosimetry would depend on various factors, including clinical situation, dose delivered, field sizes/areas irradiated, position off-axis of fields, film type used, etc. and so any novel scanner designs would need careful cost–benefit evaluation on the balance between dosimetric uncertainty gain versus practical system size and use.One significant contributing factor to the LRA effect from a flatbed scanner is the lens system. This work shows that utilizing longer focal length lenses can significantly reduce this. For example, if using a 100 mm lens instead of the conventional Epson V700 desktop scanner lens and geometry, the measured LRA was reduced by factors of between 4 and 30, depending on MU (dose) delivered and colour channel analyzed, for doses delivered to Gafchromic EBT3 film of between 1 and 11 Gy. Specifically, the LRA effect was reduced from a range of 4.5 to 11.6% with the scanner to values below 1.2% with the 100 mm lens. As such, an imaging system based on a larger focal length lens could potentially improve the film dosimetry system by reducing the LRA effect and the need for making corrections for it, although this would increase system size.


The governments’ mitigation measures to fight the COVID-19 pandemic are unprecedented in our post-war history. For overcoming this crisis, citizens were expected to act in compliance with these measures in order to control the spread of the virus and keep public health systems functional. This call for protecting the public health at the same time confronted citizens with several and severe limitations of their democratic freedoms and rights: confinement, restriction on freedoms of movement, religion, specific provisions for public protest and finally also limitations to the right of education by school closures. This paper analyzes how citizens perceive the threat the COVID-19 pandemic and especially the mitigation measures posed for democracy. We assume that pandemic waves and pandemic fatigue have an impact on the perception of threat. To see the overall societal picture, we exploit a large-scale archive of online discourse on Twitter out of which we extract democracy-related discourse with the same temporal and geospatial coverage for our investigation. From that data source, we apply computational methods to extract time series data reflecting aggregated opinions and their evolution over time concerned with the correlation of attitudes towards democracy. We them move deeper using a longitudinal panel survey we conducted in November/December 2020, March/April 2021, and July/August 2021. to have a view of the relationship between citizens’ socio-economic status and basic political attitudes. Our multi-method analysis bases on the German case and covers the period from December 2020 to August 2021. The governments’ mitigation measures to fight the COVID-19 pandemic during the years 2020 and 2021 have been unprecedented in the post-war history. Public life came to a standstill, the likes of which had never been seen on this global scale since World War II and possibly even before. The measures, which very quickly diffused as best practices, included curfews and school and workplace closures, cancellation of public events, restrictions on public gatherings including religious celebrations, sports activities, closures of public institutions, stores and businesses, restrictions on movement, and international travel. All these measures implied the limitation or even suspension of political rights and civil liberties including freedom of assembly, the exercise of religious rights, freedom of movement, and not least the right on education  is the increased concern about democracy and that concerns are getting more emotional throughout the course of the pandemic. Thus, as the pandemic took its course, the public discourse on Twitter became more polarized.Our study makes an important contribution to the research debate on the implications of the Covid-19 responses and how the citizens’ perceived the tension between the measures to protect health and the possible damages to democracy. The relevance of examining this trade-off lies in the fact that other crisis may also imply limitations to citizen rights. For political science research as well as for policy makers it remains of upmost importance to understand how far citizens are willing to accept democratic limitations without losing their belief in democracy.Τimes of crisis are also times of executive power. A broad part of the early literature on COVID-19 pandemic therefore concentrated on the executive branch, in what way and with what measures governments responded to the outbreak and the course of the pandemic and how efficient these measures were. Part of the attention to the executive branch was directed at the question of what consequences declared states of emergency, as well as crisis management measures, would have on the health of democracy. The Varieties of Democracy research group generated two indices—the Pandemic Backsliding and Pandemic Violations of Democractic Standards Index— which might distort the results as such a extreme situation as a curfew is might rather increase trust while loosening measure then might decrease it again. This assumption is corroborated by the Cosmo Project (COVID-19 Snapshot Monitoring), a highly relevant source on public trust in Germany which monitored whether and how trust in institutions changes over the pandemic, but was especially interested in the two health institutions that were giving evidence based information—the Robert-Koch-Institute (RKI) and the Bundeszentrale für gesundheitliche Aufklärung (BZgA)  a match between seed terms and the vocabulary used in Twitter discourse and (b) high relevance of seed terms for the respective issue of concern. For the time between 20.02.20 and 20.02.21, we select all German language tweets from TweetsKBArch (see the detailed procedure in the Appendix A).The complete Twitter archive underlying TweetsKB, denoted as Similar to the methodology applied for creating TweetsKB, we calculate the sentiment scores for all of the retrieved tweets using SentiStrength  for all tweets per day.Following the approach described above and in more detail in Appendix A, we extract Twitter discourse based on different seed lists. Details of the obtained datasets are shown in Table corona, covid, sars-cov‑2, sarscov2, sars_cov_2. Overall, we observe that tweet frequency drops through the second constraint of requiring COVID-19 terms, i.e. the total amount of tweets about solidarity discourse with explicit references to COVID-19 terms decreases over time. With respect to tweet frequency trends, we will ignore the SLX + COV seed lists on the basis that the overall explicit mention of COVID19-terms on Twitter has been decreasing steadily throughout the pandemic. However, that is not to be taken as indicator of decreasing relevance of COVID-19 but is an artefact of the discourse data, where increasingly obvious contextual information, i.e. some relation with the pandemic context, is not mentioned explicitly.In Table As shown in Fig. n = 152 (153). The trend detection was done computing each interval’s correlation with a continuously increasing time series representing the same resolution and length, i.e. . As correlation coefficient we used the Kendall’s tau implementation from scipy 1.7.3.With respect to sentiments expressed in Twitter discourse, for more precise results, we refer to SL1 + COV and show the evolution over time in Fig. Summarizing our findings with respect to the research questions, we indeed observe an increased concern about democracy during the pandemic, where concern—measured through tweet frequency and polarization of tweet sentiments—increases over time, indicating that concerns related to democracy are increasing and getting more emotional throughout the course of the pandemic. This is an indication in support of our first hypothesis that satisfaction with democracy drops over time as the pandemic continues while perceived threat to democracy increases.Online discourse enables to observe how attitudes interact with each other in real-life discourse environments. Twitter is not the only source of online discourse but is widely used for sharing opinions on societal and political matters and part of the news cycle where news from online media are picked up in Twitter discourse and vice versa. Thus, data from social media discourse has been widely used to mine opinions and attitudes on a variety of topics, for instance, political views  this information has to be taken with a grain of salt. In the next step, looking at different demographic groups (age and gender) we find significant differences among them regarding satisfaction with democracy. Figure The same exercise is now applied to the perceived damage to democracy variable Fig. . BreakinTurning to the question if there is a difference in the distribution of satisfaction with democracy between genders, we see in Fig. Our hypotheses were based on the differences among educational groups, supporters of political parties and those who are not trusting of the government as opposed to those who were not trusting. Turning our attention to the division of the results on the basis of educational achievement to find indication to support or reject our second hypothesis, Fig. Our third hypothesis distinguished between various levels of trust. Figure Looking now at the political variables, Fig. Moving on to the question to what extent there is a difference in the distribution of the belief that the pandemic will bring damage to the function of democracy among party groups, we see Fig.  a similaOur first research question asking for the perception of German citizens regarding the threat for democracy can be answered in the following way: Indeed, Germans saw the threat for a damage to democracy and this perception increased in the course of the pandemic. The analysis showed that it is the less educated people and the age group between 40 and 60 which most perceive this damage. This result corresponds to the results on satisfaction how democracy worked during the pandemic. Interestingly, however, the voting preference is relevant insofar as respondents near to the AfD are the group which most are worried about a damage to democracy and this remains constant during the period of investigation. This result resonantes with the rare evidence of other countries, namely that citizens disadvantaged by income, education or race (in the USA) are less willing to sacrifice rights than their more advantaged peers  where concern emerged or intensified, but more liberties on a personal level . This suggests that citizens were quite able to endure restrictions on their basic democratic rights, but less able to endure constraints on their rights in everyday life.The evidence of change over time is equally reflected in the Twitter data. Firstly, the Twitter discourse shows an increasing concern for democracy-related issues over time, expressed through increasing frequency of tweets within the considered pandemic time period. And secondly, the sentiments of the discourse also evolve over time: the positive sentiment getting more positive and the negative sentiments more negative. This can be interpreted as an additional sign of increased concern for democracy-related issues and is mirrored by trends observed through the other seed lists. But more than that it points to an increasingly polarized discourse regarding the concern for damage to democracy.This paper offers a descriptive account of the perceptions on democratic performance during pandemic years of 2020 and 2021 which were most relevant in terms of harsh restrictions. We used a dual methodological approach to achieve a birds-eye shot on attitudes on the micro level looking at the public discourse as it unfolded on Twitter before zooming to the individual level presentation of specific connections between socio-economic positioning, political attitudes, and perceptions of democratic performance. The findings relate to the period from the beginning of the pandemic until the summer 2021 and thus cover a broader time span than other studies.As an important factor for the perception of democratic damage we detect time-relatedness , but also the intensity of the pandemic (increasing COVID-19 cases and deaths) as relevant factor for the fluctuation of satisfaction with democracy. In May 2021, respondents were less satisfied with the way democracy functioned in Germany in comparison to December 2020, but the trend did not hold. In August 2021 satisfaction with democracy went slightly up again. We also found that some elements of the socio-economic position matter. Those in the age categories 40–49 and 50–59, as well as those with vocational education (as opposed to academic education) show lower levels of satisfaction with democracy. Political trust has the expected positive relationship with democratic evaluation, while support for AfD, Die Linke, and FDP is connected to higher levels of democratic dissatisfaction and fear of democratic damage, and this relationship increased over time.These findings, when put together, give an interesting picture of the German citizenry during the pandemic. An important takeaway is the fact that as the pandemic took its course on the one hand the public discourse on Twitter became more polarized. The positive sentiments over democracy became more positive and the negative ones more negative, which implies that as the time went by statements on democracy became more emotional. This finding can be supported also with the survey findings that show that, as the time went by, the democratic dimension of the pandemic became increasingly politicized and thus polarized.The combined analysis from survey and twitter data show the way for future work. Twitter data offer an overview of the public debate that both reflects the mood of society, but can also shape perceptions of individuals. Results from survey analyses can corroborate the results of twitter analysis and offer a more into-depth analysis of global phenomena.Our analysis contributes to the emerging topic of trade-offs in crises, especially those trade-offs that concern difficult choices regarding democratic rights and democratic standards. In view of the most recent crisis of climate and energy, again such trade-offs are looming. Therefore, more research on the citizens’ attitudes regarding their willingness to accept hardships and constraints is needed. Future studies should spread more light especially on the mechanisms of polarization and politicization of this topic.


Lateral open‐wedge distal femoral osteotomy (DFO) has been used to treat valgus deformity of the knee, with good clinical outcomes. However, there is a lack of biomechanical studies regarding the angle of correction. The objective of this study was to apply computer‐aided design (CAD) for osteotomy planning in a three‐dimensional (3D) anatomical model and to assess the biomechanical differences among the varying correction angles on joint loading by finite element analysis (FEA).To model different angles of lateral open‐wedge DFO correction, the CAD software package Mimics 21.0 was used to accurately simulate the operated knee. The femur was cut to 0°, 2°, 4°, 6°, 8°, and 10° of varus . The original knee model and the corrected models were processed by FE software. Then, the FE models were subjected to an axial force to obtain the von Mises stress (VMS) and shear stress distributions within the femoral cartilages and menisci.Under a compressive load of 740 N, the highest VMS in lateral and medial compartments of the intact knee model was 3.418 and 3.303 MPa. The maximum value of both the VMS and the shear stress in the lateral compartment decreased as the varus angle increased, but the corresponding values in the medial compartment increased. When the hip‐knee‐ankle (HKA) angle was 180°, the VMS in the lateral and medial compartments was balanced . Meanwhile, when the HKA angle was 178° , the shear stress in the lateral and medial compartments was balanced. In addition, the magnitude of change in the stress was significantly higher in the medial compartment (90.9%) than in the lateral compartment (19.3%).The optimal correction angle of the valgus knee is close to neutral alignment or slightly varus (0° ‐ 2°). Overcorrection is not recommended, as it can result in a steep increase of the stress within the medial compartment and may accelerate the process of medial compartment OA. This study combined computer‐aided design (CAD) with finite element analysis (FEA) to investigate the effect of simulated lateral open‐wedge distal femoral osteotomy (DFO) with varying correction angles on stress distributions within the cartilages and meniscus. This individualized non‐invasive analysis of stress distribution provided a promising novel approach for clinical evaluation of the mechanical loading of cartilage and meniscus. Based on CT images with different thresholds, the bone was segmented. The masks of the femur, tibia, fibula and patella were segmented by using the region‐growing function, and the corresponding 3D bone models were generated Fig. .The femoral mechanical axis was defined as the line from the center of the femoral head through the center of the knee, and the mechanical axis of the tibia was defined as the line from the center of the ankle through the center of the knee Fig. .14 TheUnder the guidance of experienced orthopedic surgeons and based on preoperative measurements, a lateral open‐wedge DFO was performed. The osteotomy plane is generally located 5–6 cm above the femoral articular surface  Fig. . The ostTo simplify the model and facilitate FEA calculations, we made the assumptions that the period of bone healing after DFO has been completed and that screws and plates have been removed Fig. . The 3D The meshed models were then exported as INP files and imported into an Abaqus 6.14  to calculate the stress distributions. In our work, the femur, fibula, and tibia were defined as isotropic linearly elastic materials. The cartilage and menisci were also defined as linear elastic and isotropic materials. The mechanical properties of the bone, menisci, and cartilage surrounding the bone are presented in Table The distal ends of the fibula and tibia were fixed in all degrees of freedom, while the femur was free in all degrees of freedom. The contacts were modeled between the femoral cartilage and meniscus, and between the femoral cartilage and tibia cartilage for both the medial and lateral sides, resulting in four contact pairs.The peak VMS distribution in the menisci and femoral cartilage was recorded and considered to indicate the risk of cartilage damage and meniscal tears. Shear stress generated by compression harms cartilage matrix production and decreases biosynthetic activity of cartilage, resulting in cartilage damage.t‐test or non‐parametric test, calculated with SPSS 25.0 software . Statistical significance was designated as P < 0.05.Statistical analysis comparing the intact model and osteotomy models was performed using a paired Student's Because of the scarce number of reported studies about valgus knee models, we could only compare the VMS of the neutrally aligned knee model with those intact knee models reported in the literature. In our study, under a compressive load of 740 N, the highest VMS in lateral and medial compartments of the intact knee model was 3.418 and 3.303 MPa, respectively.P < 0.05).The maximum stress in the lateral and medial compartments was located in the anterior half of the lateral meniscus and medial meniscus, respectively Fig. . The peathe maximum value at −14° varus (2.776 MPa) and the minimum value at 2° varus (2.521 MPa). In addition, when the HKA angle was 178° (2° varus), a substantially balanced shear stress distribution between the lateral and medial compartments was attained.The peak shear stress in the medial and lateral compartments was also concentrated on the menisci Fig. . When thThis study combined CAD with FEA to investigate the effect of lateral open‐wedge DFO with different correction angles on stress distributions within the femoral cartilage and menisci. We found that the maximum and mean values of VMS in the lateral compartment showed an increasing trend as the varus angle increased, while that in the medial compartment showed an increasing trend. Furthermore, the stress change magnitude was significantly higher in the medial compartment than in the lateral compartment.The main novelty of this study was simulating DFO with CAD software to establish 3D correction models, which are more precise than the conventional approach of correction on the frontal plane.et al.et al.,The goal of DFO is to restore the balance of loading between two compartments of the knee.The highlight of the present study is that the FE models are based on a real clinical case rather than remodeling a normal case in the literature.In this study, we applied FEA to quantify alterations in the biomechanics of the knee. The peak VMS was applied to quantitatively assess the severity of wear of the menisci and cartilage. Additionally, according to the literature, peak shear stress is considered to play a major role in accelerating cartilage degeneration.Another key finding of the study indicated a greater magnitude of change in stress in the medial compartment  than in the lateral compartment  as the varus angle increased, which may be related to an increase in the knee adduction moment. This result also suggested that overcorrection would increase the possibility of medial OA.Some limitations of this work must be recognized. This study was carried out by only considering a uniaxial load. Therefore, we did not consider the dynamic mechanical behavior of the models. Moreover, simplifications were made regarding the knee model and details of DFO and the impacts of surrounding soft tissues were ignored. Therefore, the menisci and cartilage may be subjected to additional stress if the actions of the surrounding muscles and ligaments are considered in the knee model.By comparing stress distributions within knee models with different degrees of correction, this study demonstrates that the optimal correction angle of the valgus knee is close to neutral alignment or slightly varus (0° ~ 2°). Overcorrection is not recommended, as it can result in a steep increase of the stress within the medial compartment and may accelerate the process of medial compartment OA. Furthermore, more patients need to be studied to determine if similar stress distributions exist in order to draw more precise biomechanical conclusions. Additional clinical imaging studies or cadaveric biomechanical investigations are warranted to verify these findings. Although the generality of our findings is limited, we provide a method that is expected to be a valuable tool in the preoperative planning of DFO surgery for valgus knee deformity.Yanfei Wu, Jianxiong Ma, and Xinlong Ma contributed in the conception and design of study. Yanfei Wu and Xingwen Zhao contributed in data acquisition. Ying Wang, Bin Lu, Haohao Bai, and Xin Jin contributed to the execution of the experiments. Yanfei Wu and Xingwen Zhao analyzed and interpreted the data and drafted the manuscript. All the authors approved the final version of the manuscript to be published. All authors listed meet the authorship criteria according to the latest guidelines of the International Committee of Medical Journal Editors. All authors are in agreement with the manuscript.This work was supported in part by the National Natural Science Foundation of China , and in part by Tianjin Science and Technology Program (grant Nos. 18PTLCSY00070 and 16ZXZNGX00130).There were no conflicts of interest in this study.


Understanding pellet ablation physics is crucial to realizing efficient fueling into a high temperature plasma for the steady state operation of ITER and future fusion reactors. Here we report the first observation of the formation of fluctuation structures in the pellet plasmoid during the pellet ablation process by a fast camera in a medium-sized fusion device, Heliotron J. The fluctuation has a normalized fluctuation level of ~ 15% and propagates around the moving pellet across the magnetic field. By comparing the fluctuation structures with the shape of magnetic field lines calculated with the field line tracing code, we successfully reconstruct the spatio-temporal structure of the fluctuations during the pellet ablation process. The fluctuations are located at the locations displaced toroidally from the pellet and propagate in the cross-field direction around the pellet axis along the field line, indicating a three-dimensional behavior and structure of fluctuations. The fluctuation would be driven by a strong inhomogeneity formed around the pellet and invoke the relaxation of the gradient through a cross-field transport induced by the fluctuations, which could affect the pellet ablation and pellet fueling processes. Such fluctuations can be ubiquitously present at the inhomogeneity formed around a pellet in the pellet ablation process in fusion devices. The cryogenic pellet injection method is a promising tool to solve this issue, which injects a small hydrogen ice pellet into a high temperature plasma with fast speed and realizes an efficient fueling to the core plasma region compared to the conventional gas puff4. The pellet injection method is also applied for density profile control, suppression of instabilities, and diagnostic purposes4. The method has been technically developed well7, and a neutral gas and plasma shielding (NGPS) model has been developed including the description of the ionized pellet ablatant12. However, the experimental validation of the physics related to the pellet injection process has not yet been fully achieved due to the lack of ablation measurement, for example, regarding drift of plasmoid, plasmoid expansion, ablation process, particle deposition, plasma responses to pellet injection4. These processes are complicated, mediating interactions among different states of solid, gas, and plasma.Efficient fueling to a high temperature plasma is a critical issue for the steady state operation of fusion reactors since only a small portion of neutral gas injected with a conventional gas puff fueling can penetrate across the separatrix and reach into the plasma core in high temperature plasmas15, the spatial and temporal resolution of the measurement is not enough to understand the pellet ablation dynamics progressing with the fast time scale within a small spatial extent. The recent development of fast camera technology with higher time resolution has been expected to open a new horizon for understanding the dynamics of plasma18 including pellet physics. At present, a fast camera is an optimum tool to visualize the pellet dynamics and ablation process with high spatial and temporal resolutions25, although quantitative measurements of physical quantities are difficult.One of the difficulties in understanding the pellet ablation physics is that the measurement of the ablation is still challenging even nowadays because the plasmoid surrounding the ablation cloud has the strong inhomogeneity of plasma parameters within a small spatial extent and a three-dimensional shape elongated to the magnetic field lines, accompanied by fast dynamics (1–100 μs). Although the spectroscopic technique is a powerful tool to measure the pellet plasmoid parametersIn this study, we report the first observation of the fluctuation structures formed in the vicinity of a pellet ablation cloud on the fast camera measurement. The observed fluctuation propagates in the perpendicular direction to the magnetic field, which implies that this phenomenon with a three-dimensional feature could play an important role in the fueling process with the pellet ablation. The new finding gives us a novel insight into understanding the physics of the pellet ablation and fueling processes.27. The magnetic field is generated with a single helical coil, two types of toroidal coils, and three sets of vertical field coils. The device is equipped with three heating methods of electron cyclotron heating (ECH), ion cyclotron resonance heating, and neutral beam injection(NBI) heating. The typical plasma parameters are the line averaged electron density of 1 × 1018–1020/m3, the electron temperature of Te < 3 keV, and the ion temperature of Ti < 400 eV.Heliotron J is a medium-sized helical device with the magnetic field strength B = 1.2 T on axis and the major/averaged minor radii of R/a = 1.2/0.15 m29. The pellet injection leads the plasma to the high density regime with higher stored energy in Heliotron J29.A cryogenic pellet is injected into the Heliotron J plasma with the typical velocity of 260 ± 30 m/s with a pellet diameter of ~ 0.7 mm31. Due to the influence of the strong magnetic field on the camera operation, the camera body is placed at a distance from the Heliotron J and the optical signal is transmitted by an imaging fiber.Figure The field of view of the camera system can be reconstructed in a three-dimensional model, as shown in Fig. 19/m3. The target plasma was produced and sustained by 70 GHz ECH with the auxiliary heating of NBI. The injection power of ECH is ~ 250 kW, and the NBI power is ~ 150 kW.In this experiment, a pellet was injected into the Heliotron J plasma with the line averaged electron density of 0.6 × 1028. In this experiment, fluctuation structure was observed inside the plasmoid in the vicinity of the ablation cloud, as can be seen in supplementary video Sequential images of the pellet injection process taken by the fast camera are shown in Fig. rCoG = ∫rI(r)dS/∫I(r)dS, where I(r) is the light emission distribution from the pellet, rCoG is the coordinate of the CoG of the emission profile on each image, and ∫dS represents a surface integral on each image. The fluctuation part is expressed as ∂I(r-rCoG) = I(r-rCoG)−< I(r-rCoG) > in the pellet coordinate, where the bracket term corresponds to the slowly varying part obtained with a moving averaging of the 50 μs time window. The raw, time-averaging and extracted fluctuation parts of pellet images are shown in Fig. 3a–c and supplementary video To separate the pellet motion and the fluctuation dynamics around the pellet, the fluctuation part was extracted from an image on the pellet coordinates. The pellet coordinate is defined here as a relative coordinate to the center of gravity(CoG) of the light emission profile from the moving pellet, as follows. The CoG of the emission profile was evaluated as 34. A similar visualization of ambient turbulence in the background plasma would be possible during a pellet ablation process due to the neutral gas surrounding a pellet. However, the normalized density fluctuation level observed in this experiment is ~ 0.15 under a general assumption of ∂I/I ~ ∂ne/ne. This fluctuation level is much higher than the turbulence fluctuation level in the core region of Heliotron J, which demonstrates the fluctuation is not identical to background turbulence. Note that turbulence fluctuation level is generally less than 1% in the core region in both tokamaks and stellarators35, and this situation is the same in Heliotron J36. It is therefore reasonable to conclude that the observed fluctuation is induced by the pellet itself.The observed fluctuation appears to originate from the pellet, not from the visualization of ambient turbulence structure accentuated by neutral gas originating from the pellet ablation. As is well known, turbulence is visualized with a fast camera by puffing a small amount of gas and highlighting the turbulence structure, which is called gas puff imagingFrom the extracted images in Fig. 37. Since magnetic field lines with different tilt angles are stacked in the depth direction of the camera's line of sight, as exhibited in Fig. By comparing the shape of the fluctuations with the magnetic field lines, the position of each fluctuation can be identified, and thereby the spatio-temporal structure of each fluctuation can be reconstructed. The magnetic surface at the toroidal section of the pellet injection port and typical magnetic field lines are shown in Fig. 21/m3, estimated from the Stark broadening of Hα measured with the visible spectrometer in a typical pellet experiment on Heliotron J. At the density, optical thickness could need to be considered. It should be noted that, however, the spectrometer is not a spatially resolved measurement, and the estimated value corresponds to the density at the brightest Hα region, which is the ablation cloud (or pellet plasmoid) closest to the pellet core, as shown in Fig. In this analysis, one can consider plasma to be transparent, and opacity is not an issue, based on the following consideration. The electron density of the pellet plasmoid close to the ablation cloud is about 10ε defined as ε = ∫(xCOG(y)−xline)2dy, as shown on the left side of Fig. xCOG(y) = ∫∂I· xdx/∫∂Idx is the CoG of the emission profile in the x direction at an arbitrary y position, ∂I is the emission profile of the fluctuation part on the x–y plane of each image, and xline represents the coordinate of a magnetic field line expressed as xline = lR,Z(y), projected on the x–y plane of each image. The ε values are evaluated for all the magnetic field lines which intersect with the fluctuation on each image, and then at the minimum ε value, εmin, one can find the magnetic field line on which the fluctuation likely localizes.A schematic of the analysis procedure for localizing fluctuation is shown in Fig. ε, we introduce a scoring parameter expressed as s = εmin/ε. The fluctuation with the filament structure has the most likelihood to be located on the field line where s has the maximum value of 1. Since each magnetic field line on the camera’s view intersects at each point on the R–Z plane as shown on the right side of Fig. s and ε parameters can be plotted on the R–Z coordinates at the toroidal section of the pellet injection port. Here the full width at half maximum for the s value on the R–Z plane is regarded as an error, in other words, spatial extent in the range of 0.5 < s < 1 corresponds to the uncertainty of fluctuation localization.For simplicity of interpretation, by normalizing and inverting s distribution for a single fluctuation structure is plotted on the R–Z plane in Fig. s value is plotted as color, and the plots with s < 0.5 are shown as grey. In this case, the fluctuation should localize on the magnetic field line passing through the coordinate of  =  at the toroidal section of the pellet injection port. As shown in the figure, good localization of the fluctuation is possible at ~ 6 mm in the Z direction corresponding to the vertical direction of a camera image, whereas there exists considerable uncertainty in the R direction, of ~ 25 mm, in the depth direction of the camera’s sightline.A typical result of scoring parameter R direction could be attributed to the specific magnetic field configuration of Heliotron J and the line-integral effect in the camera's depth direction. Although a larger variation in the tilt angle of magnetic field lines in the camera-depth direction is favorable for identifying the fluctuation position in the R-direction, the tilting of the magnetic field lines does not vary much in the depth direction due to the small magnetic shear in the Heliotron J configuration. Moreover, due to the line-integral effect arising from the transparency of the plasma, the filament axis (filament CoG) on the camera image would become thicker and less sharp, which is also unfavorable for localizing fluctuation. These two factors would contribute to the increase in error in the R direction, although it is difficult to evaluate these effects independently.The large error in the s for a single fluctuation structure is plotted in Fig. R–Z plane with the flux surfaces at the pellet injection port  itself. The dynamics of fluctuations evoked by the pellet exhibit a three-dimensional feature.In the same way, we reconstructed the spatio-temporal behavior of fluctuation structures surrounding the pellet ablation cloud, as shown as schematic in Fig. 39.The driving and propagation mechanisms of the observed fluctuation are critical issues for understanding pellet physics. One can immediately notice that one-dimensional models cannot describe such a three-dimensional structure and motion of the fluctuation. One interpretation is that a strong density gradient inside the pellet plasmoid across the magnetic field can be a source of the fluctuation, i.e., drift instability observed universally in plasmas. The fluctuation propagation direction is in the ion diamagnetic direction, and this is the opposite direction of drift instabilities driven by electron density gradient, however, an electric field could account for the determination of fluctuation propagation, rather than the drift velocity, as observed in various plasma experimentsm = 1 Rayleigh–Taylor instability40, as observed in the ablation process in the pellet experiments42. Although only the m = 1 mode has attracted attention so far as a mechanism of striation40, if the instability with a higher m mode number is destabilized, the instability should resemble the fluctuations observed in this experiment. In addition, an MHD simulation study suggests that magnetic field perturbation can be induced by plasmoid43. More systematic experiments in the wider parameter range are required to identify the driving mechanism to compare the experimental results and theories mentioned above for the basic properties of fluctuation, such as frequency, wavenumber, and propagation speed.Other possible interpretations for the driving mechanism include the followings. The observed fluctuation might also be related to the “striation” caused by the E × B drift of ~ 1000–3000 m/s should be induced by the perpendicular electric field of ~ 10–30 V/cm at the magnetic strength B = 1 T. An electric field in the perpendicular direction to a field line can be present even in the plasmoid44, although some modeling studies neglect the electric field inside a plasmoid along a field line since the potential structure is homogenized along a field line quickly due to the high conductivity inside the plasmoid45. A schematic of this simple interpretation described above is summarized in Fig. 40, however, energetic ions produced with the 24 kV NBI could affect the electric field distribution inside the plasmoid, which might make the simple picture of the reference more complex. Controlling the power of NBI may vary the velocity and could change the direction of fluctuation rotation, which is beyond the scope of present work but will be an interesting subject for future work.If one assumes the electric field dominantly determines the destabilized fluctuation propagation, the velocity of Regardless of instability type, a destabilized fluctuation generally causes a relaxation of the gradient of plasma parameters. The fluctuation appearing in the ablation process is predicted to induce transport that causes a relaxation of the gradient in the cross-field direction, thereby affecting fueling by a pellet. Such fluctuations could universally exist during the pellet ablation process inside the pellet plasmoid, contributing to the pellet ablation and fueling process. The observation, however, is expected to be difficult without a fast camera with higher spatial and temporal resolutions, because such fluctuations would appear as a small-scale instability driven by strong inhomogeneity within a small spatial extent inside the pellet plasmoid.46. The spatio-temporal structures of fluctuation should link with the particle deposition in the pellet fueling process, and systematic experiments in different heating schemes and different magnetic field configurations, for example, with a reversed field are necessary.In this experiment, the fluctuations were observed only in the pellet traveling direction on the front side of the pellet within the camera's field of view. If our simple hypothesis described in Fig. Finally, it should be mentioned that, in this experiment, the plasma density was lower than in the standard pellet experiment, resulting in moderate ablation of the pellet. This situation coincidentally facilitated the observation of fluctuations inside the plasmoid. Even in the standard conditions for pellet experiment with higher density, similar fluctuations can be observed in Heliotron J, however, it is difficult to clearly visualize the spatial structure of fluctuations using the present fast camera because the emission profile from the pellet is smaller than in this experiment, and the emission fluctuates more strongly and faster, probably due to the stronger gradient in the more intense pellet ablation. Further study with a fast camera having higher temporal and spatial resolutions is necessary for a more general understanding of the fluctuation inside the pellet plasmoid.The formation and propagation of fluctuation structures in the vicinity of the pellet ablation cloud have been visualized and discussed through the analyses of the fast camera images in Heliotron J. The normalized fluctuation level is 15% and is significantly higher than the turbulence level in background turbulence, which indicates that the pellet invoked the fluctuation. The spatiotemporal structure of the fluctuations in the pellet plasmoid was reconstructed by comparing fluctuation structures with the magnetic field line calculated with the field line tracing code KMAG. The fluctuations are present at the location displaced from the pellet in the toroidal direction and propagate in the cross-field direction, which implies that the fluctuation-induced cross-transport would affect the pellet ablation/fueling process. The three-dimensional dynamics of fluctuations observed in this experiment cannot be described by a one-dimensional model. The fluctuations driven by a strong inhomogeneity of plasma parameters around a pellet could exist ubiquitously during the pellet ablation, which would bring a modification of the present understanding of pellet ablation physics. Further experimental studies dedicated to observing a pellet ablation with a higher spatial and temporal resolution are required to understand the behavior of fluctuation under different experimental conditions, such as different heating schemes and magnetic configurations with a wider plasma parameter range.Supplementary Video 1.Supplementary Video 2.Supplementary Video 3.


In this study, the photothermal effect and up-conversion florescence imaging effect of gold nanobipyramids in liver cancer cells are investigated theoretically and experimentally to explore the photothermal ablation tumor therapy with higher photothermal conversion efficiency, shorter laser action time, smaller action range and lower laser power. The small-size gold nanobipyramids with good biocompatibility and infrared absorption peak located in the first biological window are synthesized. Femtosecond laser is focused on the nanobipyramids clusters in cells and the cells die after being irradiated for 20 s at a power as low as 3 mW. In contrast, the control cells die after irradiation with 30 mW laser for 3 min. The theoretical simulation results show that: under femtosecond laser irradiation, the local thermal effect of gold nanoclusters is produced in the range of hundreds of square nanometers and the temperature rises by 516 °C in 106 picoseconds. This therapy reduces the treatment time to seconds level, and the treatment range to square micrometer level, the power to milliwatt level. In this treatment, cells die by apoptosis rather than necrosis, which reduces inflammation. This result opens up a new way to develop photothermal ablation therapy with less side effects and more minimally invasive. Photothermal effect caused by plasma resonance is a hot topic in the application of gold nanoparticles in cancer imaging and treatment11. Previous studies have included the use of photothermal effects to promote drug release from nanoparticles14 or the combination of photothermal effects with chemotherapy17, or use the photothermal effect to create a "fever" like environment21, so as to increase the temperature of the whole tissue by about tens of degrees, so as to achieve the effect of slowly reducing the tumor volume. For these purposes, the previous treatment using photothermal effect is characterized by the irradiation time of a few minutes to more than ten minutes, the illumination power is basically about hundreds of milliwatts, and the illumination range generally covers a large number of cells, on the level of square centimeter.Cancer has been one of the deadliest diseases for humans in recent decades. Human beings continue to make new attempts in diagnosis and treatment technology to fight cancer. In recent years, gold nanomaterials have become one of the main materials for combined treatment of cancer due to their characteristics of unique surface plasmon resonance23. In addition, it is always expected to achieve the goal of local in situ inactivation of the tumor to avoid damage to normal tissues such as blood vessels near the tumor. Therefore, the development of photothermal therapy with less trauma, less postoperative inflammation and less residual scar has become a research hotspot in recent years. To achieve the above purposes, photothermal therapy is required to achieve significant results in a short time and a small range.For some photothermal tumor treatment methods, such as laser tumor ablation technology, the goal of this technology is to rapidly increase the temperature of the tumor target24. Compared with gold nanostars, GNB has better biocompatibility. Due to the anisotropy of GNBs, its longitudinal absorption peak can be adjusted in the near-infrared region of the first biological window to reduce the absorption and scattering of excitation light by biological tissues25. Most GNBS previously reported for biological applications are usually larger than 100 nm in size if their absorption peak is located in the first biological window27. However, the smaller the size of GNB, the easier it is for the particles to be taken up by cells28. In conclusion, the combination of small size GNB and laser is expected to achieve minimally invasive treatment with fewer traumas, shorter action time and fewer side effects compared with traditional photothermal therapy, and improve the light energy utilization efficiency of cancer ablation. Therefore, it is necessary to explore the mechanism and experimental phenomenon of the photothermal effect of GNB under ultrafast laser irradiation. However, the related reports are lacking.Compared with previous photothermal therapy, gold nanobipyramid (GNB) have great potential in improving the light energy utilization efficiency of cancer ablation. First: the specific heat capacity of gold is very small, and the heating rate is very fast. Secondly, Compared with gold spheres and gold nanorods (GNRs), gold nanobipyramids have stronger surface plasmon resonance effect2 level). To sum up, this new photothermal therapy combined with GNB and fs laser shortens the treatment time, compresses the treatment range, reduces the damage and side effects caused by photothermal effect, and improves the efficiency of photothermal therapy. It opens up a new way for the application of nanoparticles in tumor therapy.In this paper, the photothermal effect of GNBs was studied theoretically and experimentally, and a new photothermal therapy with low laser power, short treatment time and small treatment range was developed. In this work, two small size GNBs were synthesized. They are easily taken up by cells and the surface plasmon resonance absorption peak remains in the first biological window. Under the excitation of infrared laser, upconversion fluorescence imaging of cells co-cultured with GNBs can be observed. And the plasmon resonance effect of gold nanoparticles clusters in cells can rapidly heat organelles and induce cell death. Human hepatoma (HepG2) cells co-cultured with GNBS died after being irradiated with 3 mW femtosecond (fs) laser or 8.4 mW continuous laser for 20 s. The photothermal treatment efficiency of GNB was proved higher than that of GNR. The laser power used in GNB group was much lower than that used to induce cell death in the control group. The Apoptosis time of the cancer cells can be controlled by adjusting light intensity. In this low-power laser photothermal treatment, the cells were induced apoptosis rather than necrosis, which can reduce the inflammatory response caused by cell necrosis. At the same time, the simulation results show that the combination of GNBs and fs laser can achieve rapid (nanosecond level) heating or cooling in a small range -2,5-diphenyltetrazolium bromide assay was used to measure the cell viability. The results are shown in Fig. 31 showed that particles with a size between 50 and 200 nm were mainly absorbed by clathrin-mediated endocytosis. The content of Au in the cells was measured using ICP-MS and TEM to study the uptake ability of cells to GNBs and GNRs. Table Seyed et al.When the infrared fs laser was used to excite cells co-cultured with gold nanoparticles, upconversion fluorescence images of cells could be obtained due to light scattering and upconversion luminescence properties of gold nanoparticles. By observing the upconversion fluorescence image, the location of the gold nanoparticle clusters could be determined so that the gold nanoparticle clusters could be further excited by an infrared laser for photothermal treatment. First, gold nanoparticles with a concentration of 60 μg/mL were incubated with HepG2 cells for 24 h. Then, the cells were scanned at low power with a fs pulsed laser with the same wavelength as the longitudinal absorption peak of GNBs and GNRs. Therefore, the upconversion fluorescence images could be obtained. Figure The fluorescence intensity values of the selected cells in Fig. 32.In this work, the position of the gold nanorod cluster in the cell could be obtained by fast scanning the cell with a low power 800-nm laser and observing the up-conversion fluorescence emission image of the cell. After determining the location of the GNP cluster, a high-power femtosecond laser could be used to simply excite the GNP clusters. Due to the high peak power and short pulse time of fs pulse, the gold nano particle clusters in the cell can be irradiated in a very short time, so that the clusters can obtain high local energy and rapid heating. The schematic diagram of the experimental device is shown in Fig. Figure In addition to the photothermal experiment with fs laser, the photothermal effect under continuous light excitation has also been studied. Due to the strong plasma resonance effect of GNBs, continuous laser irradiation on GNBs clusters can also produce high temperature. Under this high temperature condition, cancer cells can also be effectively induced to die. Moreover, compared with a fs laser, the price of a continuous wave laser is much cheaper. Therefore, it is of great significance to study the response of cells co-cultured with gold nanoparticles under continuous light irradiation. Figure In addition to studying the photothermal effect of laser on cells co-cultured with gold nanoparticles, the form of cell death induced by photothermal effect was also studied due to its significance for clinical application. The main form of cell death were apoptosis, necrosis, and programmed death. The dye Hoechst33342 and propidium iodide (PI) were used to determine whether the cell death form was apoptosis or necrosis in this work. After the cells co-cultured with nanoparticles were irradiated with pulse lasers of different powers, they were stained with Hoechst33342 dye solution for 15 min in the dark. Then the staining of the cells was observed under ultraviolet light irradiation to determine the dead form of cells which were irradiated by the laser. The experimental results of fs laser treatment groups are shown in Fig. After obtaining a series of experimental results, in order to further analyze the experimental results and explore the mechanism of heat generation of gold nanoparticles under laser irradiation, COMSOL software was used for numerical simulation. Mathematical models were established to study the field enhancement and temperature distribution around gold nanoparticles excited by near-infrared laser.34:When the gold nanoparticles were excited by continuous Gaussian light, the photothermal process could be described using the following equations0 is the vacuum permittivity; ω is the angular frequency of input light; k0 is the wave vector of the input light; σ is electrical conductivity; μr is the relative permeability, which, in this case, was 1 both for media (assuming water) around the nanoparticle and gold. εr is the relative permittivity. For media in this work, it is set to 1.77. For gold, εr is obtained from Johnson and Christy35. Equation (r) is the imaginary part of relative permittivity. The imaginary part of the relative permittivity of media (water) is so small that it can be ignored, as reported in two previous studies25. Therefore, the imaginary part was set to zero in this simulation. Equation -(3) to study the response of gold nanoparticle clusters to the continuous laser. In these simulations, we ignore the influence of the phase transition of the medium in order to simplify the model. Figure In addition to the temperature response of nanoclusters irradiated by a continuous laser, the thermodynamics of gold nanoclusters irradiated by a fs laser was also studied based on Eqs. –7). In . In 7). 2. Under continuous laser irradiation, the range of temperature raised above 50 °C near GNB clusters reaches the μm2 level, which is about 100 times higher than that under fs laser. This kind of local efficient heating is more conducive to the application of photothermal effect in photothermal therapy. The influence of nanoparticle density on photothermal temperature are also be simulated  was used to functionalize the prepared GNRs. See Supplementary Material for a description of specific experimental procedures.GNRs were prepared by referring to the seedless synthesis method reported by El-Sayed et al.41, and then polyethylene glycol  at an accelerating high voltage of 200 kV. An ultraviolet–visible spectrophotometer  was used to measure the absorption spectra of GNRs and GNBs.42. For the detailed measurement method, please refer to Supplementary Material.The HepG2 cells used for the cell culture experiments which were procured from the Cell Laboratory of the Cell Resource Center of the Chinese Academy of Sciences. Before the experiment, a certain concentration of HepG2 cells was seeded in a 96-well plate and placed in an incubator  for 12 h. The experimental method for testing the activity of HepG2 cells was similar to that described in a previous study43 The number of gold nanoparticles in a single cell could be obtained by dividing the test results of ICP-MS by the cell density in the sample and then by the mass of a single gold nanoparticle.Inductively coupled plasma mass spectrometry (ICP-MS)  was used to measure the uptake of GNRs and GNBs by a single HepG2 cellTEM  was used to observe the distribution of GNRs and GNBs in HepG2 cells. Please refer to Supplementary Material for the description of specific experimental methods.www.comsol.com) was employed to simulate the distribution of electric field and thermal response of gold nanoparticles excited by Gaussian light. In COMSOL simulations, the water around the gold nanoparticles was set to a spherical shape with a radius of 1700 nm. The water was divided into three layers; the outermost layer was set as an infinite element layer with a thickness of 500 nm to simulate thermal conduction in an infinite space, and the second outer layer was a perfectly matched layer with a thickness of 500 nm to simulate light propagation in an infinite space. Non-uniform grids with the smallest grid of 1 nm were employed.The finite element method software developed by COMSOL Multiphysics  with a repetition frequency of 76 MHz was reflected to an inverted microscope  La, California CA, USA), and a 60× objective lens was used to focus and observe the target cells. The radius of the laser spot was about 1 μm. In the photothermal treatment experiment, the cells were incubated in a medium containing GNRs and GNBs for 24 h. Then, the medium containing GNRs and GNBs was removed, and a new medium without GNRs and GNBs was added to a Petri dish.Supplementary Information.


Torsion of the gravid uterus is very rare in obstetric practice. We report a case of torsion in the uterus didelphys at term which is rare and a lifetime experience for an obstetrician.The patient, a 25-year-old gravida 2 para 1 was admitted to the labor ward at 37 weeks and six days of gestation with abdominal pain. Her previous delivery was a caesarean section performed four years back. She was taken to the operating room for an emergency caesarean section for fetal distress and the lie was transverse. On entering the peritoneal cavity, we found an engorged infundibulopelvic ligament with the fallopian tube and ovary covering the lower segment of the uterus. The baby was successfully delivered by breech extraction. Due to uterine torsion of more than 180 degrees, the posterior surface of the uterus was placed anteriorly, and the incision was made on the posterior surface of the uterus. There was a hemi uterus on the left side of the pelvic cavity with the fallopian tube and ovary attached to it; a diagnosis of uterus didelphys was made. The diagnosis of uterine torsion is intraoperative and prompt and timely decision by surgeons is crucial. We had favorable maternal and fetal outcomes in this rare and interesting case. The diagnosis, though rare, should be kept in mind in all cases of abdominal pain during pregnancy, especially in those with malpresentation. Torsion of the uterus is a rare condition which is infrequently encountered in clinical practice. Encountering a patient with an unusual and rare combination of torsion in the uterus didelphys at term makes it a lifetime experience for an obstetrician . There aA 25-year-old, gravida 2 para 1 was admitted to the labour ward with abdominal pain at 37 weeks and six days of gestation. Her last childbirth was by caesarean section four years back. Her antenatal period was uneventful with regular check-ups as per schedule. She had transverse lie and was planned for elective repeat caesarean section at 39 weeks.On examination, there were mild uterine contractions and the lie was transverse. Ultrasound was done which showed a single live fetus with an estimated fetal weight of 3.2 kg. The placenta was anterior and low-lying, ending 1 cm above the internal os. A mass of 12 x 7.6 cm was found in the pelvis which was suspected to be a cervical myoma. Cardiotocography indicated fetal distress and she was prepared for an emergency caesarean section. The abdomen was opened by Pfannenstiel incision. On entering the peritoneal cavity, we were surprised to see the engorged infundibulopelvic ligament with the fallopian tube and ovary stretched across the operative field  Activity Respiration (APGAR) score of 9 with a birth weight of 3.17 kilograms. After the separation of the placenta, it was observed that due to uterine torsion, the incision was made on the posterior surface of the uterus. Manual untwisting of the uterus was done in the direction opposite to that of the torsion. The uterus had torsion by more than 180 degrees on its own longitudinal axis, at the level of the junction of the cervix, the corpus and the right adnexa was covering the operative site. The posterior surface of the uterus was placed anteriorly due to torsion Figures -3. Another intact uterus was found on the left side of the pelvic cavity (about 12 weeks in size) with a tube and ovary attached to it. The final diagnosis was uterus didelphys with torsion of the gravid uterus. The uterine incision was repaired in two layers and anti-adhesive barrier gel was placed posteriorly. After ensuring hemostasis, the abdomen was closed. The post-operative period was uneventful. Both mother and baby were discharged on the third postoperative day.Uterine torsion is defined as the twisting of the uterus by more than 45 degrees around its long axis at the junction between the cervix and the corpus . TorsionVery few cases of torsion in uterus didelphys have been published as of date. Only two cases of torsion of uterus didelphys (one at term pregnancy and the other in labour) were published in 1954 .In our case, malpresentation (transverse lie) and Mullerian anomaly (uterus didelphys) predisposed to torsion of the uterus. The diagnosis of uterus didelphys was missed during the previous Caesarean section which was operated on for fetal distress in emergency hours. During the current pregnancy, the other uterus was thought to be a myoma in ultrasound and was a surprise during surgery. Moreover, the torsion of more than 180 degrees placed the anterior surface of the uterus posteriorly and vice versa. The baby was delivered through a transverse incision on the posterior surface of the uterus.From the literature review, it has been observed that a pre-operative diagnosis of uterine torsion is not possible. It is also difficult to correct uterine torsion before the delivery of the fetus. Maternal and perinatal morbidity and mortality depend on the degree of rotation of the uterus and the period of gestation.In this case, prompt intraoperative planning and decision by the surgeon enabled a favourable outcome for both the mother and the baby. In cases of uterine torsion, a prompt and timely decision by the surgeon is crucial. The uterine incision should be planned to avoid injury to vital structures. The diagnosis, though rare, should be kept in mind in all cases of abdominal pain during pregnancy, especially in those with malpresentation. A pelvic mass in pregnancy can rarely be a uterus too in case of Mullerian anomaly.


The present study used physics to synthesize silver nanoparticles using aqueous extract of fresh garlic as reducing and as a stabilizing agent silver nitrate solution. This method has proven to be environmentally friendly and safe for the synthesis of stable silver nanoparticles. The acquisition of silver nanoparticles was confirmed by optical detection, that is, by changing the color of the liquid to transparent orange and then blackish brown. Then, the characterization was confirmed using other assays. In this study, it was found that the absorption peak of silver nanoparticles was at a wavelength of 420 nm and the particle size ranged between [50–350] nm. The surface roughness of silver oxide/silver nanoparticles was 9.32 nm with an average square roughness of 21.19 nm, and the energy dispersive spectra showed that the absorption peak was in the region of 3 keV, indicating that the nanoparticles contained crystalline silver. In this study, the stability of the silver nanoparticles was good, as ZP reached (− 19.5). The results confirm that the conductivity increases with the increase in frequency due to the high energy of the photons, which causes the electrons to vibrate in the energy levels and thus increase the energy in the mitochondria and increase the movement of sperm in the Diabetic mice treated with doses of silver nanoparticles. The toxic effect of silver nanoparticles has been evaluated in other studies, in addition to evaluating antioxidants, antifungals, treating cancer cells, regulating cholesterol levels, the effect of these nanoparticles on sex cells in pregnant female mice, heart tension, and many other tests. In this study, the activities and efficacy of silver nanoparticles on sperms were determined in male mice with diabetes caused by STZ, and the treatment period was long (35 days) so that the evaluation period was a complete life cycle of male sex cells and within a long period of time and at an average nano size. This has not been studied in other previous studies. The results indicate that the biosynthesis of silver nanoparticles using garlic plant led to positive results on sperm treatments by contributing to an increase in the number of sperm with reactivation and a decrease in abnormalities in addition to a decrease in mortality due to diabetes. This is evidence that the synthesis of silver nanoparticles using garlic plant size (50–350 nm) can treat impotence and be used in the future in the treatment of many diseases without side effects. When compared with its larger counterpart (Bulk), nanoparticles have distinctive physical, chemical and biological characteristics due to their small size and large surface area, which led to improved interaction or stability during the physical and chemical process, increased mechanical strength and other factors4. Nanoparticles are distinguished by their different shapes and sizes5, in addition to their different diameters. Nanoparticles may be spherical or cylindrical in shape and can be tubular, spiral, flat or irregular in shape and size and range from 1 to 100 nanometers7. Nanotechnology is rapidly developing, and many intensive studies have been conducted to synthesize nanoparticles with distinctive characteristics in terms of cost, speed of completion and the distinctive characteristics of the resulting nanoparticles8. NPs have been used in a variety of applications including cooking utensils, renewable energies, agricultural pest control and have been used extensively in the medical field, treating a wide range of diseases, as well as transporting medicines and improving the quality of materials9. Silver nanoparticles are among the most important and most common nanoparticles due to the unique properties they possess, such as good conductivity and stability. They are also used in the manufacture of therapeutic alloys, in the treatment of burns and infections resulting from wounds, as anti-cancer cells, and against viruses, bacteria and free radicals10, and can be used in the manufacture of tools in contact with food, as a result, it can cause direct contact between silver nanoparticles and workers in this field, and this in turn can cause semi-chronic toxic effects and may interact with the health of the organism, as it was found that AgNPs have the ability to precipitate in The kidneys, testicles, lungs, heart and other organs of the body result in the generation of reactive oxygen species in living cells and can cause immunological or neurotoxicity11, on the other hand, many studies have shown that exposure to silver nanoparticles can treat many diseases resulting from External and chronic causes, such as diabetes, pressure, or immune diseases14. There are few studies that show the effect of silver nanoparticles on sex cells, as many have shown Among the studies, there is a relationship between the amount of the dose once and the approved period in which the infected body is exposed to a quantity of therapeutic nanoparticles again and between the health of the sperm15. There are various methods for the synthesis of nanoparticles, including chemical methods, in which highly dangerous compounds are used and toxic for the purpose of minimization and stabilization, causing environmental damage in addition to being expensive and time consuming with high energies. Biological and physical methods are among the ideal methods used for the synthesis of nanoparticles because they are simple, harmless, environmentally friendly, and effective at the same time17. Research and studies have increased to use the biophysical method to manufacture nanoparticles, as it is considered the best to use effective plant-derived compounds such as polyphenols, flavonoids, anthocyanins, ellagic acid and other plant materials that can improve the properties of silver nanoparticles and reduce toxicity resulting from the use of nanoparticles. Metals and salts used in the manufacture of commercial silver nanoparticles18.Nanotechnology is described in this study. It is a technique that has attracted a lot of interest in recent years. Nanoparticles represent all types of particles that fall within a diameter of 1–100 nm, and are made of carbon, metal, metal oxides, or organic compounds19. An aqueous extract of garlic was used21, and testing the toxicity of silver nanoparticles on the sperm of healthy mature mice, and evaluating the role of therapeutic silver nanoparticles in stimulating sperm movement and reducing deformities in sperms as a result of STZ-induced diabetes, and possibly death in some of them and a decrease in the number of sex cells. Treatment with manufactured silver nanoparticles was tested with a long treatment period of up to 35 consecutive days and at a rate of one dose per day, that is, according to the entire life cycle of the sperm, which was not observed in another research. The results indicate that there is no significant toxicity resulting from the silver nanoparticles, and this is considered a success in using a quick and inexpensive method of synthesis, it can be used in the treatment of many diseases and negative effects resulting from diabetes.Our current study focuses on the synthesis of silver nanocomposites derived from biological sources to reduce harmful ions and toxicity resulting from substances that are a source of stabilization and reduction22. Ethanol was taken from DUKSAN Company The deionized water was used during the preparation of the aqueous extract and all the tools used were washed using distilled water and left to dry using a hot oven before use.Silver nitrate, Streptozotocin obtained from Sigma Corporation, USA industry was used. Fresh garlic was purchased from the traditional medicine store in Baghdad. The garlic plant sample was classified by an expert at the University of Baghdad, College of Science, Department of Biology (AlliumL type/Alliaceae family)23.Fresh garlic was used after washing several times with deionized water (DIW) to remove dust particles, then the plant was left in the air to dry to remove residual moisture. Dry garlic was ground using an ordinary grinder. 15 g of finely ground garlic powder was dispersed in 500 ml DIW, which is of very high purity, using a magnetic stirrer for 30 min at 100 °C. Then, the solution was filtered through filter paper and centrifuged at 4000 rpm for 30 min to remove any impurities and obtain a clear solution. The extract is kept in the refrigerator for later use in the preparation of silver nanoparticles25 with some modification. 2 g of silver nitrate was dissolved in 25 ml of distilled water by a 600 RPM magnetic stirrer for 30 min. After that, we add 25 ml of garlic extract gradually with continuous magnetic stirring for an hour at 80 °C. Then a precipitate will form and the color of the solution will turn black. The solution was then left overnight and the precipitate was separated by centrifuge and washed with water and ethanol more than once. The precipitate is dried in an oven at 85 °C for 4 h.The preparation was carried out according to24.It is a technique used to study the arrangement of atoms inside crystals, where X-ray diffraction of silver nanoparticles was measured using XRD analysis. The examination was carried out by placing the sample in a centrifuge at 10,000 rpm for 15 min. The precipitate was collected and the resulting silver pellets dried at 50 °C in an oven. The size of silver nanoparticles is calculated using the Scherer equation, which is shown below, 26.The structure of silver nanoparticles and the size and shape of the nanoparticles were studied using scanning electron microscope (EDS-Mapping-Line-EBSD) made in Germany. The examination was carried out after placing the sample in a centrifuge at a rotation speed of 10,000 rpm for 15 min, after which the sample was washed with distilled water and dried at a temperature of 50 degrees Celsius. The sample was placed on a platinum mesh coated with palladium and the sample was analyzed by the radiation passing through the sample and the image was at a dispersion spectrum of (250 INCA Energy)27.Atomic force microscopy was used to examine the surface morphology of silver nanoparticles produced by garlic extract. The examination was carried out after the examined sample was dispersed and placed on a small glass slide under the microscope and at room temperature28.It is a very powerful technique in materials science that can be described by a beam of high-energy electrons passing through very thin samples. The properties of silver nanoparticles in terms of particle shape and size were studied using TEM technology. An amount of the dried precipitate of nano silver was dissolved in ethanol alcohol, the suspension was placed in the ultrasonic bath for 15 min, then a drop is taken from the suspension and placed on a carbon-coated copper grid. We note that after the sample dries and forms a partially transparent layer, the sample is examined and the resulting image is formed from the shadow of the electron beam falling on the sample3 solution with garlic extract. Distilled water was used as a blank reference for background yellowing from other sources29.The UV–visible spectrum of stable silver nanoparticles and aqueous extract of fresh garlic plant was recorded using a UV–Vis spectrometer (Shimadzu-Japanese uv-2450) at 1 nm resolution to ensure the reduction of silver Ag + ions to AgO using garlic extracts as a reducing agent. Samples were scanned in the 300–800 nm range, with a scanning speed of 475 nm/min, at 1 cm optical path and at room temperature. UV–vis absorption spectra were recorded 24 h after incubating the AgNO30. The analysis time was 60 s, and the average zeta potential was determined. Dispersion was determined as such without dilution.The surface electric charge of Ag NPs was determined by measuring the most stable particles when electrostatic repulsion occurs between the particles. Zeta potential was determined using HAS 300. Zeta sizer based on photon correlation spectroscopy31.The hydrodynamic diameter of silver nanoparticles in solution was determined by dynamic light scattering (DLS) and multiple scattering laser diffraction method. Malvern Zeta sizer from Origin/Germany was usedThirty healthy male albino mice weighing about 30 ± 5 g used in the experiment were purchased from Biotechnology Research Center/Al-Nahrain University. All animals were kept in standard conditions of 22 ± 3 °C with a constant 12 h dark and 12 h light exposure cycle, and in a controlled environment at an equilibrium humidity of 50 ± 5%. The animals were left for a week to acclimatize to the experimental conditions while being provided with the standard healthy diet of food and water. The experiment was conducted in the animal house of Al-Nahrain University.32.Diabetes was induced in all male experimental albino mice, except for the healthy control, by giving them a single dose of fresh streptozotocin after being dissolved in saline in an amount 33. Sperm motility, normal and damaged morphology, and sperm count were examined, and the number was found to be at least 150 sperms from each mouse. Sperm activity and motility analysis was performed by Makler Chamber and using a light microscope . Where motility was expressed as fast (Grade A) and slow (Grade B) sperm, non-progressive (Grade C) and non-motile (Grade D) sperm. On the other hand, the shapes of sperms were identified by adjusting the optical microscope to magnification × 4034.The mice were divided into sex groups that were forced to observe the mice. The first group is the negative control group shown, watching these mice. The second group, control diabetic mice, took doses of streptozotocin, the third group was diabetic and treated with metformin (600 mg/kg body weight/day) for 28 days, the fourth group was diabetic and treated with Silver and the fifth was diabetic and treated silver nanoparticles (2 mg/kg body weight/day)The authors declare that: (1) All methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by ethics committee in Biotechnology research center, at University of Al-Nahrain, Baghdad 35,095 Iraq: Application number 60, Reference number 21-3, date 20 May 2022. (2) All methods are reported in accordance with ARRIVE guidelines for the reporting of animal experiments. ”).35. Figure 36:X-ray diffraction is an important technique for determining crystal structure. It is used to determine the atomic arrangement, lattice parameters, crystal sizeThe field emission scanning electron microscope (FESESM) provides the ability to study the topography of the surfaces of nanomaterials and determine the possibility of their application in different fields. The morphological images of Ag/AgO NPs created using the biosynthetic process are shown in Fig. AgNPs existence and crystalline structure were study by using EDS analysis. It is widely known that surface Plasmon resonance causes Ag spherical nanoparticles to have a characteristic optical absorption peak about 37.The presence of a high content of oxygen may be attributed to the presence of silver oxides in the prepared sample, these results are consistent with the results of XRD analysis. The present results are consistent with the results of the work38. Figure TEM is one of the advanced analytical measurement tools used for imaging and distinguishing the size and shape of nanoparticles39. The results showed that the surface roughness of AgO/AgNPs was The roughness and surface morphology of AgO/AgNPs are indicated in the AFM images, and Fig. 40. The present results are consistent with the results of the work42. Figure 43.Figure 26.The attenuation of light intensity as it passes through a substance is described by the absorption coefficient 45.Figure 46:Figure 46:The Urbach region (U region) Fig.  represenThe Urbach energy was calculated by the inverse of slope to the curve. In Fig. The determination of the optical bandgap 47.After plotting It has been reported that, the refractive index 48. The difference is that our compound is formed by AgO nanoparticles in addition to Ag nanoparticles.As can be seen Fig. 49:The optical conductivity 51. Figure The optical conductivity of a material determines the relationship between the amplitude of the induced electric field and the density of the induced current in the material for any given frequency. This linear response function is a generalization of electrical conductivity, which is often considered in terms of static electric fields with slow or time-independent differences. It has to do with how conductive a material is, or how much electricity can flow through it. The conductivity of a particular material depends on the frequency of the electric field The results confirm that the conductivity increases with increasing frequency due to the high energy of the photons, causing the electrons to vibrate in the energy levels.52. The negative value in this test confirms the occurrence of repulsion between the silver nanoparticles and proves that they are very stable.Figure Figure The results presented in Table 54.The results showed that the effect of silver nanoparticles on the treatments was positive and significantly increased in motility and living with a significant decrease in deformities and thus mortality in the treated groups. Silver nanoparticles prepared using the environmentally friendly garlic plant protect sperm by increasing the oxidative activity in the immune system, thus preventing reactive oxygen species from lipid peroxidation stimulation responsible for subsequent sperm damage. Our result clearly indicates the important role of silver nanoparticles in various medical applicationsIn this study, silver nanoparticles were successfully generated using a simple, efficient and inexpensive protocol from fresh garlic plant as reducing agent, and silver nanoparticles with a diameter of