No / Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) are produced in the skin under the influence of UV radiation. These compounds are highly reactive and can induce DNA lesions in epidermal cells. Melanin is considered to protect human skin against DNA damage by absorbing UV radiation. We have investigated whether melanin can, in addition, offer protection against the effects of H2O2 in human melanocytes and HaCaT keratinocytes. In the present study, it was shown that 40 and 100 μM H2O2 increased the number of DNA strand breaks as measured using the comet assay, in melanocytes of Caucasian origin. In melanocytes of the same origin in which melanin levels were increased by culturing in presence of 10 mM NH4Cl and elevated l-tyrosine, H2O2-induced DNA damage was reduced compared to that in control melanocytes. Similarly, HaCaT cells that were loaded with melanin were better protected against H2O2-induced DNA strand breaks than control HaCaT cells. These protective effects of melanin were mimicked by the intracellular Ca2+-chelator BAPTA. Thus, BAPTA reduced the level of H2O2-induced DNA strand breaks in melanocytes. Like BAPTA, melanin is known to be a potent chelator of Ca2+ and this was confirmed in the present study. It was shown that melanin levels in melanocytic cells correlated directly with intracellular Ca2+ binding capacity and, in addition, correlated inversely with H2O2-induced increases in intracellular Ca2+. Our results show that melanin may have an important role in regulating intracellular Ca2+ homeostasis and it is suggested that melanin protects against H2O2-induced DNA strand breaks in both melanocytes and keratinocytes and through its ability to bind Ca2+.

No / Numerous factors may influence the incidence of diabetes in the population. The production of reactive oxygen species (ROS) is elevated in diabetes patients. Based on the reported involvement of reactive species and nitrate/nitrite in diabetes, this present study has examined in the alkaline Comet assay, the effect of different levels of NaNO2 in the presence of the oxygen radical generating agent, hydrogen peroxide (H2O2). Peripheral lymphocytes from diabetic and non-diabetic Caucasians and Asians of both sexes were studied in vitro. Endogenous factors (e.g., sex, age, body mass index-BMI) and exogenous factors (lifestyle factors e.g., smoking and drinking habits, diet) were taken into account. A preliminary study in two individuals showed that DNA damage remained constant over a wide dose range of NaNO2 (1-75 mM), but when H2O2 was added at a constant concentration of 50 ¿M per dose of NaNO2, there was an increase in DNA damage corresponding with the varying levels of NaNO2 investigated. This was also seen with the 44 individuals (non-diabetic, n = 24; type 1 diabetic, n = 11; type 2 diabetic, n = 9) investigated. NaNO2 was capable of inducing a significant level of DNA damage in lymphocytes (p<0.001), but only with the addition of H2O2. When levels of DNA damage were analysed in terms of the different variables there were few significant differences in damage between diabetic and non-diabetic subjects, or other sub-population groups, and no statistically significant differences in susceptibility were observed between subject covariates using regression techniques.

No / Telomerase-targeted strategies have aroused recent interest in anti-cancer chemotherapy, because DNA-binding drugs can interact with high-order tetraplex rather than double-stranded (duplex) DNA targets in tumour cells. However, the protracted cell-drug exposure times necessary for clinical application require that telomerase inhibitory efficacy must be accompanied by both low inherent cytotoxicity and the absence of mutagenicity/genotoxicity. For the first time, the genotoxicity of a number of structurally diverse DNA-interactive telomerase inhibitors is examined in the Ames test using six Salmonella typhimurium bacterial strains (TA1535, TA1537, TA1538, TA98, TA100, and TA102). DNA damage induced by each agent was also assessed using the Comet assay with human lymphocytes. The two assay procedures revealed markedly different genotoxicity profiles that are likely to reflect differences in metabolism and/or DNA repair between bacterial and mammalian cells. The mutational spectrum for a biologically active fluorenone derivative, shown to be mutagenic in the TA100 strain, was characterised using a novel and rapid assay method based upon PCR amplification of a fragment of the hisG46 allele, followed by RFLP analysis. Preliminary analysis indicates that the majority (84%) of mutations induced by this compound are C→A transversions at position 2 of the missense proline codon of the hisG46 allele. However, despite its genotoxic bacterial profile, this fluorenone agent gave a negative response in the Comet assay, and demonstrates how unwanted systemic effects (e.g., cytotoxicity and genotoxicity) can be prevented or ameliorated through suitable molecular fine-tuning of a candidate drug in targeted human tumour cells. / CAEB, Balearic Islands and Yorkshire Cancer Research

Yes / Genotoxic compounds have induced DNA damage in male germ cells and have been associated with adverse clinical outcomes including enhanced risks for maternal, paternal and offspring health. DNA strand breaks represent a great threat to the genomic integrity of germ cells. Such integrity is essential to maintain spermatogenesis and prevent reproduction failure. The Comet assay results revealed that the incubation of isolated germ cells with n-ethyl-n-nitrosourea (ENU), 6-mercaptopurine (6-MP) and methyl methanesulphonate (MMS) led to increase in length of Olive tail moment and % tail DNA when compared with the untreated control cells and these effects were concentration-dependent. All compounds were significantly genotoxic in cultured germ cells. Exposure of isolated germ cells to ENU produced the highest concentration-related increase in both DNA damage and gene expression changes in spermatogonia. Spermatocytes were most sensitive to 6-MP, with DNA damage and gene expression changes while spermatids were particularly susceptible to MMS. Real-time PCR results showed that the mRNA level expression of p53 increased and bcl-2 decreased significantly with the increasing ENU, 6-MP and MMS concentrations in spermatogonia, spermatocytes and spermatids respectively for 24 hr. Both are gene targets for DNA damage response and apoptosis. These observations may help explain the cell alterations caused by ENU, 6-MP and MMS in spermatogonia, spermatocytes and spermatids. Taken together, ENU, 6-MP and MMS induced DNA damage and decreased apoptosis associated gene expression in the germ cells in vitro. / Libyan Government

Yes / Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) may be protective against tumours, including breast cancer. We have studied the effects of ibuprofen and aspirin on DNA damage in lymphocytes obtained from breast cancer patients and healthy female controls. Both nanoparticle (NPs) and bulk formulations were used in the comet and micronucleus (MN) assays. Non-toxic doses (250 ng/ml ibuprofen; 500 ng/ml aspirin) were tested. Aspirin, both bulk and nano formulations, significantly reduced DNA damage measured with the comet and micronucleus assays; the nano formulation was more effective. Ibuprofen was not effective in the comet assay but showed a significant reduction in MN frequency, with the nano formulation being more effective. NPs may have better penetration through the nuclear membrane relative to the bulk formulation. NSAIDs such as aspirin and ibuprofen may have a promising role in cancer prevention and treatment. / LIBYAN GOVERNMENT

Yes / Our previous case-control study observed isolated lymphocytes from 208 individuals and determined the differences in the sensitivity to genomic damage of lymphocytes derived from cancer patients, pre/suspect cancer patients and healthy volunteers using the Comet assay (Anderson et al, 2014). We adapted the LGS technique using a slightly different method and examined 700 more blood samples from 598 patients with cancer or suspected cancer and 102 healthy individuals. To help increase the sensitivity of the test and detect cancer at the level of each individual, we joined with the IMSTAR team who analysed our cells with their fully automated Pathfinder™ cell reader-analyser system. With this reading and analysis system 4,000 to 10,000 cells were able to be read per slide. The new test which is called TumorScan is a highly sensitive test to detect any cancer at an early stage through the response of the white blood cells to UV treatment. These patient blood samples have also been collected at the stage before confirming diagnosis and treatment. There were four of these individuals with cancer who had received anti-cancer treatment. The results from these patients showed a reverse pattern compared to non-treated cancer patients and followed the pattern seen in healthy individuals. The results are consistent with the early results as reported in the above 2014 paper. Given the results from these samples were in a particularly challenging subgroup, whose cancer status was difficult to distinguish, the data suggest that the technique using the TumorScan system could exceed the area under the ROC curve >93% obtained in the earlier study on a group basis, whereas this present study was to detect cancer at an early stage in each individual. / Department of Research and Knowledge Transfer at the University of Bradford, Bradford, UK

O objetivo deste estudo é descrever o dano de DNA através das variáveis Tail Moment e Tail Intensity e investigar a associação entre o dano do DNA, padrão alimentar e concentrações plasmáticas de vitaminas em crianças e adolescentes em Ribeirão Preto (São Paulo, Brasil). Estudantes de 9 a 13 anos foram selecionados de três escolas de Ribeirão Preto (São Paulo, Brasil), totalizando uma amostra de 120 indivíduos. A coleta de dados incluiu antropometria, composição corporal, avaliação da ingestão utilizando um questionário de frequência alimentar (QFA) e o Índice de Qualidade da Dieta Revisado (IQD-R) e coleta de sangue para a dosagem de vitaminas e determinação do dano do DNA pelo método de eletroforese em gel de célula única - comet assay. Os indivíduos foram divididos em dois grupos opostos de dano do DNA usando duas técnicas distintas: análise de k-cluster e classificação por escala de dano. Padrões de ingestão de nutrientes também foram gerados, utilizando robust sparse k-means cluster, e associados com o dano de DNA. Para análise utilizaram-se os testes T de Student, Mann-Whitney e ANCOVA. Na primeira análise, o cluster 1 (n = 73), com menor dano de DNA, apresentou maior consumo de vegetais verdes escuros e alaranjados (p = 0,047), vegetais totais (p = 0,041) e carnes, ovos e leguminosas (p = 0,022), através do IQD-R, e um escore de IQD total maior (p = 0,030), indicando melhor qualidade de dieta em comparação ao cluster 2 (n = 47), de maior dano de DNA. O cluster 2 apresentou maior consumo de laticínios, em comparação ao cluster 1 (p = 0,008). Em relação a vitaminas plasmáticas, o cluster 1 apresentou maior concentração de riboflavina (p = 0,004). No segundo método de divisão, o grupo 1 (n = 108), com menor dano de DNA, apresentou maior concentração de retinol (p = 0,010), beta-caroteno (p = 0,017) e riboflavina (p = 0,046), após teste de ANCOVA ajustado para o índice de massa corporal (IMC) em comparação ao grupo 2 (n = 12). Na divisão por padrão alimentar, o cluster 2 (n = 58), com menor consumo de aminoácidos e micronutrientes, apresentou maior consumo de energia (p = 0,001) e uma tendência de maior dano do DNA (p = 0,063) em relação ao cluster 1 (n = 27), com maior ingestão de nutrientes. Estes achados corroboram a literatura, afirmando o papel protetor de vitaminas e antioxidantes contra o dano do DNA. / The aim of this study is to describe the DNA damage using values of Tail Moment and Tail Intensity and investigate the association between DNA damage, dietary pattern and vitamin status in children and adolescents in Ribeirão Preto (São Paulo, Brazil). 9 to 13 year old students were selected from three schools in the city of Ribeirão Preto (São Paulo, Brazil), totalizing a sample of 120 subjects. Data collection included anthropometry, body composition, assessment of food intake using a food frequency questionnaire (FFQ), quality of diet through Revised Health Eating Index (HEI-R), and blood sampling for vitamins dosage and determination of DNA damage with single cell gel electrophoresis - comet assay. The subjects were divided into two opposing groups according to DNA damage using two different methods: k-cluster analysis and classification by scale of damage. Nutrients intake patterns were also generated through robust sparse k-means cluster and associated with DNA damage. The statistical analysis were performed using Student\'s T test, Mann-Whitney test and ANCOVA. In the first analysis, cluster 1 (n = 73), with less DNA damage presented higher intake of dark green and orange vegetables (p = 0,047), total vegetables (p = 0,041), meat, eggs and legumes (p = 0,022), assessed through HEI, as well as a higher total HEI-R level (p = 0,030), indicating higher quality of diet compared to cluster 2 (n = 47), with increased DNA damage. Cluster 2 presented a higher intake of milk and dairy products, compared to cluster 1 (p = 0,008). In relation to vitamins plasma levels, cluster 1 presented higher levels of riboflavin (p = 0,004). In the second method of division, group 1 (n = 108), with less DNA damage, presented higher levels of retinol (p = 0,010), beta-carotene (p = 0,017) and riboflavin (p = 0,046), after ANCOVA teste adjusted for body mass index (BMI) compared to group 2 (n = 12). In the division by dietary pattern, cluster 2 (n = 58) with a lower consumption of amino acids and micronutrients had higher energy intake (p = 0,001) and a tendency of higher DNA damage (p = 0,063) compared to cluster 1(n = 27), with higher intake of nutrients. These findings corroborate the literature, asserting protective role of vitamins and antioxidants against DNA damage.

O objetivo deste estudo é descrever o dano de DNA através das variáveis Tail Moment e Tail Intensity e investigar a associação entre o dano do DNA, padrão alimentar e concentrações plasmáticas de vitaminas em crianças e adolescentes em Ribeirão Preto (São Paulo, Brasil). Estudantes de 9 a 13 anos foram selecionados de três escolas de Ribeirão Preto (São Paulo, Brasil), totalizando uma amostra de 120 indivíduos. A coleta de dados incluiu antropometria, composição corporal, avaliação da ingestão utilizando um questionário de frequência alimentar (QFA) e o Índice de Qualidade da Dieta Revisado (IQD-R) e coleta de sangue para a dosagem de vitaminas e determinação do dano do DNA pelo método de eletroforese em gel de célula única - comet assay. Os indivíduos foram divididos em dois grupos opostos de dano do DNA usando duas técnicas distintas: análise de k-cluster e classificação por escala de dano. Padrões de ingestão de nutrientes também foram gerados, utilizando robust sparse k-means cluster, e associados com o dano de DNA. Para análise utilizaram-se os testes T de Student, Mann-Whitney e ANCOVA. Na primeira análise, o cluster 1 (n = 73), com menor dano de DNA, apresentou maior consumo de vegetais verdes escuros e alaranjados (p = 0,047), vegetais totais (p = 0,041) e carnes, ovos e leguminosas (p = 0,022), através do IQD-R, e um escore de IQD total maior (p = 0,030), indicando melhor qualidade de dieta em comparação ao cluster 2 (n = 47), de maior dano de DNA. O cluster 2 apresentou maior consumo de laticínios, em comparação ao cluster 1 (p = 0,008). Em relação a vitaminas plasmáticas, o cluster 1 apresentou maior concentração de riboflavina (p = 0,004). No segundo método de divisão, o grupo 1 (n = 108), com menor dano de DNA, apresentou maior concentração de retinol (p = 0,010), beta-caroteno (p = 0,017) e riboflavina (p = 0,046), após teste de ANCOVA ajustado para o índice de massa corporal (IMC) em comparação ao grupo 2 (n = 12). Na divisão por padrão alimentar, o cluster 2 (n = 58), com menor consumo de aminoácidos e micronutrientes, apresentou maior consumo de energia (p = 0,001) e uma tendência de maior dano do DNA (p = 0,063) em relação ao cluster 1 (n = 27), com maior ingestão de nutrientes. Estes achados corroboram a literatura, afirmando o papel protetor de vitaminas e antioxidantes contra o dano do DNA. / The aim of this study is to describe the DNA damage using values of Tail Moment and Tail Intensity and investigate the association between DNA damage, dietary pattern and vitamin status in children and adolescents in Ribeirão Preto (São Paulo, Brazil). 9 to 13 year old students were selected from three schools in the city of Ribeirão Preto (São Paulo, Brazil), totalizing a sample of 120 subjects. Data collection included anthropometry, body composition, assessment of food intake using a food frequency questionnaire (FFQ), quality of diet through Revised Health Eating Index (HEI-R), and blood sampling for vitamins dosage and determination of DNA damage with single cell gel electrophoresis - comet assay. The subjects were divided into two opposing groups according to DNA damage using two different methods: k-cluster analysis and classification by scale of damage. Nutrients intake patterns were also generated through robust sparse k-means cluster and associated with DNA damage. The statistical analysis were performed using Student\'s T test, Mann-Whitney test and ANCOVA. In the first analysis, cluster 1 (n = 73), with less DNA damage presented higher intake of dark green and orange vegetables (p = 0,047), total vegetables (p = 0,041), meat, eggs and legumes (p = 0,022), assessed through HEI, as well as a higher total HEI-R level (p = 0,030), indicating higher quality of diet compared to cluster 2 (n = 47), with increased DNA damage. Cluster 2 presented a higher intake of milk and dairy products, compared to cluster 1 (p = 0,008). In relation to vitamins plasma levels, cluster 1 presented higher levels of riboflavin (p = 0,004). In the second method of division, group 1 (n = 108), with less DNA damage, presented higher levels of retinol (p = 0,010), beta-carotene (p = 0,017) and riboflavin (p = 0,046), after ANCOVA teste adjusted for body mass index (BMI) compared to group 2 (n = 12). In the division by dietary pattern, cluster 2 (n = 58) with a lower consumption of amino acids and micronutrients had higher energy intake (p = 0,001) and a tendency of higher DNA damage (p = 0,063) compared to cluster 1(n = 27), with higher intake of nutrients. These findings corroborate the literature, asserting protective role of vitamins and antioxidants against DNA damage.

The Comet Interceptor is a joint mission by European Space Agency (ESA) and Japan Aerospace Exploration Agency (JAXA) which seeks to perform a flyby over a Long Period Comet using a multi-element spacecraft. The Comet Interceptor comprises three spacecrafts- A, B1 and B2. All three spacecrafts will observe and map the comet at three different points on the coma of the comet, thereby making this mission the first ever multipoint mission dedicated to study a Long Period Comet. Out of the eleven instruments aboard the Comet Interceptor, the work done for this thesis aims to help the team designing the instrument-Optical Periscope Imager forComets (OPIC). The team designing OPIC uses the imaging simulation software Space Imaging Simulator for Proximity Operations (SISPO) to render images of theoretically modelled dust and gas densities of the coma of a comet to obtain prerequisite knowledge of the images which is to be taken by OPIC during its flyby. Using the theoretical model of the coma, a 3D model was created as part of the thesis which shall be later implemented in SISPO. The structure of the coma was made with the help of a sparse volumetric data manipulation tool OpenVDB, which was coded and run in Python. The generated data was imported in Blender to visualise the volumetric data with the help of Blender’s rendering engine-Cycles. To visualise the 3D model with utmost physical realism as the software Blender allows, a study on the scattering properties of the dust and gas model was done. Also, a motion blur was implemented in Blender to simulate the high relative velocity between the instrument and comet. Multiple approaches of varying complexities and time consumption were considered for importing and visualising the volumetric data. The final render images were brightness-matched with reference to images from previous cometary missions. Finally, a qualitative analysis was done by visually comparing the render images to the images from previous missions. With the help of this qualitative analysis, several features and characteristics were identified which were analogous to the real life images, thus establishing the correctness of the renders produced.

COMET ist ein zukunftsweisendes Experiment der neuen Generation. Es wird nach dem kohärenten neutrinolosen Übergang eines Myons zu einem Elektron im Coulombfeld eines Aluminiumatomkerns suchen. Dieser Prozess eröffnet herausragende Möglichkeiten zur Erforschung und Entdeckung neuer Physik, da die kohärente Myonen-zu-Elektronen Umwandlung die geladene Leptonenzahlerhaltung verletzt und im Standardmodell der Teilchenphysik bis weit unterhalb messbarer Beiträge unterdrückt ist. Das Experiment befindet sich derzeit in der Aufbauphase. In Phase-I wird angestrebt, das bestehende Limit auf das Verzweigungsverhältnis von 7x10^-13 um zwei Größenordnungen zu verbessern, wobei eine zusätzliche Verbesserung um mindestens zwei weitere Größenordnungen für Phase-II erwartet wird. Zur Realisierung dieser beeindruckenden Verbesserung benötigt das COMET-Experiment einen äußerst intensiven, niederenergetischen Myonenstrahl. Über die geplante Laufzeit des Experiments von 146 Tagen erreichen etwa 1,6x10^17 Myonen den Detektorbereich. Allerdings kann nur ein Bruchteil dieser Myonen genutzt werden, da diese zuerst gestoppt und an einen Atomkern gebunden werden müssen, bevor eine kohärente Umwandlung in Elektronen möglich ist. Diese Arbeit widmet sich der detaillierten Untersuchung der Komponente, die für diese Aufgabe verantwortlich ist: dem sogenannten Myonen-Stop Target. Mithilfe modernster Simulationstechnik werden die Parameter des Myonen-Stop Targets analysiert und optimiert, um die Anzahl der gestoppten Myonen zu maximieren, während gleichzeitig eine hohe Akzeptanz für die Signal-Elektronen gewährleistet wird. Darüber hinaus wird das Vorhaben untersucht, die Anzahl der gestoppten Myonen durch die Messung von charakteristischen myonischen Röntgenstrahlen mittels eines hochreinen Germaniumdetektors zu bestimmen. Es wird gezeigt, dass die 'Single Event Sensitivity' des Experiments um einen Faktor zwei auf bis zu 1,5x10^-15 verbessert werden kann, wenn ein Myonen-Stop Target verwendet wird, das aus 66 Aluminiumscheiben mit einer Dicke von 0,1mm besteht. Es wird eine spezielle Aufhängestruktur zur Befestigung dieser Scheiben entworfen und mithilfe eines entwickelten Prototyps umfangreich getestet. Installations- und Stabilitätstests zeigen eine Positionsgenauigkeit von +-1mm in x- und +-5mm in y- und z-Richtung. Innerhalb dieser Genauigkeit wird keine negative Auswirkung auf die Anzahl der gestoppten Myonen erwartet. Die Aufhängestruktur wurde auf Stabilität optimiert, wobei der Verlust an Signalakzeptanz durch Interferenz mit Signalelektronen auf 3,4% begrenzt werden konnte. Die Umsetzbarkeit des myonischen Röntgendetektors wird demonstriert. Die Platzierung des Detektors in einem Abstand von 6m und einem Winkel von 8,5° relativ zum Myonen-Stop Target, zusammen mit einer eigens entwickelten Detektorabschirmung, die ein 2m langes Kollimatorrohr mit einem Durchmesser von 50mm enthält, ist ausreichend, um die Untergrundrate im Germaniumdetektor auf ein arbeitsfähiges Niveau zu senken.:Kurzfassung Abstract List of Tables List of Figures 1. Introduction to Muons 1.1. Muons in the Standard Model 1.1.1. The Free Muon Decay and Flavour Conservation 1.1.2. Muonic Atoms 1.2. Muons in Beyond Standard Model Physics 1.2.1. Motivation behind (Charged) Lepton Flavour Violation 2. The COMET Experiment 2.1. A Staged Approach: COMET Phase-I and Phase-II 2.2. The μ−e Conversion Signal 2.2.1. Detecting Conversion Electrons: A Cylindrical Detector System 2.2.2. The Single Event Sensitivity 2.3. Understanding and Suppressing Background 2.3.1. Primary Beam: Proton Target, Energy, and Timing Structure 2.3.2. Particle Transport: Particle Selection with Bent Solenoids 2.3.3. Muon-Stopping Target: Shape and Material 3. The COMET Simulation: ICEDUST 3.1. Simulating the Primary Beam 3.2. Direct Simulation of Conversion Electrons and X-rays 3.3. Details of the Geometry and Magnetic Field 3.4. Handling of Physics in ICEDUST 3.5. General Optimization Strategy 4. The Muon-Stopping Target 4.1. Introduction: Status Quo and Motivation 4.2. Methodology 4.2.1. Interpreting Plots: The Centered Coordinate System 4.2.2. Investigating the Number of Muons Stopped 4.2.3. Investigating the Signal Acceptance 4.2.4. Investigating Detector Background Rates 4.2.5. Treatment of Uncertanties 4.3. Performance Overview: Default Configuration 4.3.1. Additional Information: Single Layer Occupancy 4.4. Starting Point: The Tube-like Disk Structure 4.4.1. Matching the Target Shape to the Beam Profile 4.4.2. Using Multiple Separate Target-Disks Forming a Tube 4.5. Changing the Target-Disk Radius 4.5.1. The Effect on Total Number of Muons Stopped 4.5.2. The Effect on Signal Acceptance 4.5.3. The Effect on Detector Background 4.5.4. Summary and Performance Overview 4.6. Material Budget: Target-Disk Thickness 4.6.1. Summary and Performance Overview 4.7. Material Budget: Total Number of Target-Disks 4.7.1. The Effect on Total Number of Muons Stopped 4.7.2. The Effect on Signal Acceptance 4.7.3. The Effect on Detector Background 4.7.4. Summary and Performance Overview 4.8. Disk Positioning Along the Beam Axis 4.9. Signal Background from Muon Decay In Orbit 4.9.1. Updated Results for the Default Configuration 4.9.2. Results for New Configurations 4.9.3. DIO Background from Other Isotopes 4.9.4. DIO Background from the Surrounding Helium Gas 4.10. Single Event Sensitivity for New Configurations 4.10.1. Calculating the SES 4.10.2. Summary and Interim Results 4.11. Production of Target-Disks 5. The Muon-Stopping Target Suspension 5.1. Technical Layout of the Suspension Structure 5.1.1. The Outer Ring Structure 5.1.2. The Three Long Bars 5.1.3. The Support Ring 5.2. Holding the Target-Disks in Place: The Spokes 5.3. The Installation Procedure 5.4. ICEDUST Study of Key Parameters 5.4.1. Positional Accuracy 5.4.2. Size of the Three Long Bars 5.5. Final Results and Summary 6. The Muon-Stopping Monitor 6.1. Methodology: The Two Main Parameters 6.1.1. Assessing the Germanium Detector Background 6.1.2. Calculating the Germanium Detector Signal Acceptance 6.2. Results: Positioning and Collimator 6.3. Discussion and Outlook 6.3.1. Moving Toward a Realistic Shielding 6.3.2. HPGe Data Acquisition: Read-out and Dead Time 6.3.3. Estimation of Accuracy 6.3.4. COMETs Timing Structure and Supplementary Measurements 7. Conclusion List of Acronyms References A. Collimator Performances / COMET is a next-generation experiment. It will search for the coherent neutrinoless transition of a muon to an electron in the Coulomb field of an atomic aluminium nucleus. This process provides a golden channel for probing and discovering new physics since coherent muon-to-electron conversion violates charged lepton flavor conservation and is suppressed below measurable contributions in the Standard Model of particle physics. During Phase-I, the experiment currently under construction seeks to improve the existing branching ratio limit of 7x10^-13 by two orders of magnitude, with an additional improvement by at least two orders of magnitude anticipated for Phase-II. To realize such remarkable improvements, the COMET experiment requires an incredibly intense, low-energy muon beam. Over a planned runtime of 146 days, approximately 1.6x10^17 muons will reach the detector area. However, only a fraction of these muons are usable, as they must first be stopped and bound to a nucleus to undergo conversion. Within this thesis, the component responsible for this task is under detailed scrutiny: the muon-stopping target. A simulation-based study evaluates and optimizes the muon-stopping target's parameters to maximize the number of stopped muons while maintaining a high acceptance for signal conversion electrons. In addition, the scheme to monitor the number of stopped muons by measuring muonic X-rays with a high-purity germanium detector is investigated. A twofold improvement in single event sensitivity to 1.5x10^-15 is shown to be achievable by employing 66 target-disks with a thickness of 0.1mm. A dedicated suspension structure to hold these target-disks is designed, prototyped, and tested. Installation and stability tests demonstrate a positional accuracy of +-1mm in x and +-5mm in y and z directions. Within this accuracy, no negative impact on the number of muons stopped is foreseen. The suspension structure is optimized for stability while limiting the decrease in signal acceptance from interference with signal electrons to 3.4%. The feasibility of the muonic X-ray detector is demonstrated. Placing the detector 6m away at an 8.5° angle relative to the muon-stopping target, along with dedicated shielding and a 2m long, 50mm diameter tube collimator, is sufficient to achieve workable background rates for the high-purity germanium detector.:Kurzfassung Abstract List of Tables List of Figures 1. Introduction to Muons 1.1. Muons in the Standard Model 1.1.1. The Free Muon Decay and Flavour Conservation 1.1.2. Muonic Atoms 1.2. Muons in Beyond Standard Model Physics 1.2.1. Motivation behind (Charged) Lepton Flavour Violation 2. The COMET Experiment 2.1. A Staged Approach: COMET Phase-I and Phase-II 2.2. The μ−e Conversion Signal 2.2.1. Detecting Conversion Electrons: A Cylindrical Detector System 2.2.2. The Single Event Sensitivity 2.3. Understanding and Suppressing Background 2.3.1. Primary Beam: Proton Target, Energy, and Timing Structure 2.3.2. Particle Transport: Particle Selection with Bent Solenoids 2.3.3. Muon-Stopping Target: Shape and Material 3. The COMET Simulation: ICEDUST 3.1. Simulating the Primary Beam 3.2. Direct Simulation of Conversion Electrons and X-rays 3.3. Details of the Geometry and Magnetic Field 3.4. Handling of Physics in ICEDUST 3.5. General Optimization Strategy 4. The Muon-Stopping Target 4.1. Introduction: Status Quo and Motivation 4.2. Methodology 4.2.1. Interpreting Plots: The Centered Coordinate System 4.2.2. Investigating the Number of Muons Stopped 4.2.3. Investigating the Signal Acceptance 4.2.4. Investigating Detector Background Rates 4.2.5. Treatment of Uncertanties 4.3. Performance Overview: Default Configuration 4.3.1. Additional Information: Single Layer Occupancy 4.4. Starting Point: The Tube-like Disk Structure 4.4.1. Matching the Target Shape to the Beam Profile 4.4.2. Using Multiple Separate Target-Disks Forming a Tube 4.5. Changing the Target-Disk Radius 4.5.1. The Effect on Total Number of Muons Stopped 4.5.2. The Effect on Signal Acceptance 4.5.3. The Effect on Detector Background 4.5.4. Summary and Performance Overview 4.6. Material Budget: Target-Disk Thickness 4.6.1. Summary and Performance Overview 4.7. Material Budget: Total Number of Target-Disks 4.7.1. The Effect on Total Number of Muons Stopped 4.7.2. The Effect on Signal Acceptance 4.7.3. The Effect on Detector Background 4.7.4. Summary and Performance Overview 4.8. Disk Positioning Along the Beam Axis 4.9. Signal Background from Muon Decay In Orbit 4.9.1. Updated Results for the Default Configuration 4.9.2. Results for New Configurations 4.9.3. DIO Background from Other Isotopes 4.9.4. DIO Background from the Surrounding Helium Gas 4.10. Single Event Sensitivity for New Configurations 4.10.1. Calculating the SES 4.10.2. Summary and Interim Results 4.11. Production of Target-Disks 5. The Muon-Stopping Target Suspension 5.1. Technical Layout of the Suspension Structure 5.1.1. The Outer Ring Structure 5.1.2. The Three Long Bars 5.1.3. The Support Ring 5.2. Holding the Target-Disks in Place: The Spokes 5.3. The Installation Procedure 5.4. ICEDUST Study of Key Parameters 5.4.1. Positional Accuracy 5.4.2. Size of the Three Long Bars 5.5. Final Results and Summary 6. The Muon-Stopping Monitor 6.1. Methodology: The Two Main Parameters 6.1.1. Assessing the Germanium Detector Background 6.1.2. Calculating the Germanium Detector Signal Acceptance 6.2. Results: Positioning and Collimator 6.3. Discussion and Outlook 6.3.1. Moving Toward a Realistic Shielding 6.3.2. HPGe Data Acquisition: Read-out and Dead Time 6.3.3. Estimation of Accuracy 6.3.4. COMETs Timing Structure and Supplementary Measurements 7. Conclusion List of Acronyms References A. Collimator Performances