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Hard diffraction in proton collisions, where the initial state proton emerges from the interaction rather undisturbed despite a hard interaction scale, has been studied for a few decades. First observed in proton-proton collisions, the phenomenon is seen as well in deep inelastic electron-proton scattering (DIS) as a leading final state proton and a rapidity gap-region without final state particles. Although a rather successful description in terms of the exchange of a hadronic color singlet pomeron with a parameterized gluon content exists, it is still an open question whether a theoretically more well-founded description can be obtained based on quantum chromodynamics. The soft color interaction model (SCI) attempts this through additional gluon exchanges at momentum scales below the conventional scale of perturbative QCD and the hadronization scale. Such gluons can lead to an effective color singlet exchange and therefore to diffraction. This thesis explores the phenomenology of the SCI model in diffractive W and photon+jet production. For diffractive deep inelastic scattering, a dynamic color screening model is developed based on a summed amplitude for soft gluon exchanges. The studies of the model within Monte Carlo event simulation show that the additional dynamics improve the description of electron-positron scattering data from HERA. Dijet events in proton-proton collisions with an upper limit on the energy flow between the jets is sensitive to large angle gluon emissions. This thesis applies a resummation method which takes into account also secondary emissions to describe this observable and shows that a good description of data from ATLAS can be achieved. Supersymmetric extensions to the Standard Model provide a possible explanation for dark matter in the universe. The next-to-minimal supersymmetric extension (NMSSM) can contain a dark matter candidate in form of the lightest neutralino with a substantial singlino component. This thesis studies the prospects for indirect detection of dark matter for such viable NMSSM model points via the observation of neutrinos from neutralino annihilation in the sun with IceCube and the future extension PINGU. It is shown that with a few years of data taking large parts of the parameter space can be excluded or a discovery be made.

The Fermi Large Area Telescope has observed a gamma-ray excess toward the center of the Galaxy at ~ GeV energies. The spectrum and intensity of the excess are consistent with the annihilation of dark matter with a mass of ~100 GeV and a velocity-averaged cross section of ~ 1e-26 cubic centimeter per second. In the meantime, a population of unresolved millisecond pulsars (MSPs) in the Galactic center remains a possible source of the excess. Furthermore, recent analyses have shown that the excess prefers the spatial morphology of the stellar bulge distribution in the Galactic center, supporting a MSP origin. The new discovery makes it imperative to further study the signals from MSPs. This dissertation studies the gamma-ray emission from Galactic millisecond pulsars to provide new insights into the origin of the Galactic center excess. Using the GALPROP code, we simulate the propagation of e± injected by the putative MSPs in the Galactic bulge and calculate the inverse Compton (IC) emission caused by the e± losing energy in the interstellar radiation field. We find recognizable features in the spatial maps of the IC. Above TeV energies, the IC morphology tends to follow the distribution of the injected e±. Then, we study the Cherenkov Telescope Array (CTA) sensitivity to the IC signal from MSPs. We find that the CTA has the potential to robustly discover the IC signature when the MSP e± injection efficiencies are in the range ≈ 2.9-74.1%. The CTA can also discriminate between an MSP and a dark matter origin for the radiating e± based on their different spatial maps. Next, we analyze the Fermi data from directions of Galactic globular clusters. The globular clusters are thought to be shining in gamma rays because of the MSP population they host. By analyzing their gamma-ray spectra, we reveal evidence for an IC component in the high-energy tail of Fermi data. Based on the IC component in the globular cluster spectra, the e± injection efficiency of millisecond pulsars is estimated to be slightly smaller than 10%. Finally, we study the spatial morphology of the 511 keV signal toward the Galactic center using data from INTEGRAL/SPI. We confirm that the 511 keV signal also traces the old stellar population in the Galactic bulge, which is similar to the Fermi GeV excess. Using a 3D smoothing kernel, we find that the signal is smeared out over a characteristic length scale of 150 ± 50 pc. We show that positron propagation prior to annihilation can explain the overall phenomenology of the 511 keV signal. / Doctor of Philosophy / Dark matter means matter that does not interact with light; therefore, they are invisible to traditional observations. We know that dark matter exists based on plenty of gravitational evidence: the motions of stars in galaxies, the large-scale structure of the Universe, the temperature fluctuations in the cosmic microwave background. However, we still know very little about the particle nature of dark matter. Detecting dark matter is one of the most extensive missions of modern physics. In indirect detection, the dark matter particles are expected to annihilate or decay in the cosmos, producing messenger particles that include gamma rays, cosmic rays, and neutrinos. Astronomical observations could detect those signals and confirm the nature of dark matter. However, understanding the astrophysical sources is essential for indirect detection of dark matter as they may emit similar signals. For a recent example, the Fermi Large Area Telescope launched by NASA is the most sensitive gamma-ray telescope in the energy range of ~ 100 MeV to ~ 100 GeV. It has detected an excess of gamma-ray signals toward the Galactic center consistent with what we expect from dark matter annihilation. However, millisecond pulsars, a type of fast rotating neutron stars, may also generate similar gamma-ray signals. Therefore, the origin of the signal remains unsettled. In this dissertation, we study different prospective of the gamma-ray emission from the millisecond pulsars in the Milky Way. We first study the inverse Compton signal from the millisecond pulsars in the Galactic bulge, caused by the relativistic e± injected by the millisecond pulsars. We find that the signal traces the original distribution of the e± above TeV energies. Next generation ground-based gamma-ray observatories like the Cherenkov Telescope Array (CTA) could be used to detect the signal. We study the CTA sensitivity to such an inverse Compton signal. We find that CTA can detect the inverse Compton signal from millisecond pulsars and discriminate it from a dark matter signal. We also study the gamma-ray emission from globular clusters in the Milky Way. They are dense collections of old stars orbiting our Galaxy, and they are known for hosting many millisecond pulsars. We reveal evidence for inverse Compton emission from the gamma-ray data of globular clusters. Our discovery helps us better understand the high-energy property of millisecond pulsars. Last, we study the morphology of the Galactic 511 keV signal caused by positron annihilation. Compact objects including millisecond pulsars are potential sources of the positrons. We find that the old stellar distribution with a smearing scale of ~ 150 pc best describes the 511 keV signal. Positron propagation from their sources prior to annihilation could explain the measured smearing scale.

Doctor of Philosophy / Department of Chemistry / Stefan Bossmann / Estrogen-derived DNA adducts in human could be the initiating step of breast and prostate cancer, as the scientific literature suggests. Previous studies demonstrated that 4-hydroxy-estrone (estradiol)-1-N3Adenine and 4-hydroxy-estrone (estradiol)-1-N7Guanine were the most abundant adducts found in urine of human subjects. Sensitive detection of these adducts in urine samples could lead to better breast and prostate cancer risk assessment. The standard adducts were synthesized and characterized by NMR and mass spectrometry. Since these adducts are not fluorescent at room temperature an aminomethyl (-CH2NH2) linker was introduced at the C-17 position for derivatization with fluorescence label. This linker allowed to attach highly fluorescent water soluble quantum dots (QDs) for indirect adduct detection. A direct gram-scale synthesis of highly fluorescent, photostable water soluble QDs was executed by developing a new class of 4,4’-bipyridinium salt based twin ligands with 85% and 15% of carboxylic acid and maleimide termini, respectively. These ligands not only stabilized the QDs in water but also provided versatile linkers for two labeling strategies. The twin ligands were afforded by a facile synthesis through SN2 nucleophilic substitution reaction. Labeling of adducts was achieved via a covalent coupling between the (-CH2NH2) linker and the carboxyl (-COOH) terminal ligand on the QDs. However, ELISA experiments utilizing an IgM antibody didn’t reveal any measurable signal from adduct-QD complexes suggesting that one QD is bound to a large number of adducts through –COOH terminal ligands present on QD surface. To explore the binding capabilities of QDs in more detail, a maleimide terminal ligand (a twin partner on the QDs) was synthesized to explore the thiol (-SH) functionality of thiopyrene. Preliminary ELISA showed that these QDs gave detectable fluorescent signal originating from the [pyrene-S-QD] ̶ 8E11 monoclonal antibody (mAb) complex when QD was selectively excited at 470 nm. This clearly indicates that it is necessary to develop a strategy for a distinct 1:1 labeling procedure between QD and the adduct of interest. In addition, IgG (instead of IgM) antibodies should be developed for biosensor application. The latter could afford binding of mAb in upright position, leading to an increase in surface density of mAb and better detection limit.

The identification of the relic particles which presumably constitute cold dark matter is a key challenge for astroparticle physics. Indirect methods for their detection using high energy astro- physical probes such as cosmic rays have been much discussed. In particular, recent ‘excesses’ in cosmic ray electron and positron fluxes, as well as in microwave sky maps, have been claimed to be due to the annihilation or decay of dark matter. In this thesis, we argue however that these signals are plagued by irreducible astrophysical backgrounds and show how plausible con- ventional physics can mimic the alleged dark matter signals. In chapter 1, we review evidence of, and possible particle candidates for, cold dark matter, as well as our current understanding of galactic cosmic rays and the state-of-the-art in indirect detection. All other chapters contain original work, mainly based on the author’s journal publications. In particular, in chapter 2, we consider the possibility that the rise in the positron fraction observed by the PAMELA satellite is due to the production through (hadronic) cosmic ray spallation and subsequent acceleration of positrons, in the same sources as the primary cosmic rays. We present a new (unpublished) analytical estimate of the range of possible fluctuations in the high energy electron flux due to the discreteness of plausible cosmic ray sources such as supernova remnants. Fitting our result for the total electron-positron flux measured by the Fermi satellite allows us to fix the only free parameter of the model and make an independent prediction for the positron fraction. Our explanation relies on a large number of supernova remnants nearby which are accelerating hadronic cosmic rays. Turning the argument around, we find encouraging prospects for the observation of neutrinos from such sources in km^3-scale detectors such as IceCube. Chapter 3 presents a test of this model by considering similar effects expected for nuclear secondary-to-primary ratios such as B/C. A rise predicted above O(100)GeV/n would be an unique confirmation of our explanation for a rising positron fraction and rule out the dark matter explanation. In chapter 4, we review the assumptions made in the extraction of the `WMAP haze' which has also been claimed to be due to electrons and positrons from dark matter annihilation in the Galactic centre region. We argue that the energy-dependence of their diffusion means that the extraction of the haze through fitting to templates of low frequency diffuse galactic radio emission is unreliable. The systematic effects introduced by this can, under specific circumstances, reproduce the residual, suggesting that the ‘haze’ may be just an artefact of the template subtraction. We present a summary and thoughts about further work in the epilogue.

In this thesis we studied dark matter models with strong self-interactions, typically known as self-interacting dark matter (SIDM). This kind of models constitute a promising solution to the tension between small scale structure observations and predictions assuming the standard case of collisionless cold dark matter (CDM) while keeping the success of the standard cosmological model, LambdaCDM, at large scales. The presence of strong self-interactions can increase the dark matter capture and annihilation in astrophysical objects like our sun, enhancing the potential of indirect detection signals. We used the high energy neutrinos produced by such annihilations to probe SIDM models. We established strong constraints on SIDM with velocity independent cross section by comparing the expected neutrino signal with the results of the IceCube-79 dark matter search. Also, we determined the sensitivity for the IceCube-DeepCore and PINGU detectors for SIDM with a velocity dependent self-interacting cross section (vdSIDM). Most of its relevant parameter space can be tested with the three years of data already collected by IceCube-DeepCore, complementing results from direct detection experiments and other indirect detection studies. / Nesta tese investigamos modelos de matéria escura com auto-interações fortes, conhecidos tipicamente como matéria escura auto-interagente (SIDM). Este tipo de modelos constituem uma solução promissora à tensão entre as observações de estrutura a pequena escala e as previsões assumindo o caso padrão de matéria escura fria não colisional (CDM), enquanto se mantêm o sucesso do modelo cosmológico padrão, LambdaCDM, a grandes escalas. A presença de auto-interações fortes podem aumentar a captura e a aniquilação da matéria escura em objetos astrofísicos como o nosso sol, aumentando o potencial de sinais de detecção indireta. Usamos o sinal de neutrinos de alta energia produzidos por essas aniquilações para explorar modelos de SIDM. Estabelecemos fortes vínculos em modelos de SIDM com seção de auto-interação independente da velocidade comparando o sinal de neutrinos esperado com os resultados de busca de matéria escura do IceCube-79. Também, determinamos a sensibilidade dos detectores IceCube-DeepCore e PINGU para modelos de SIDM com uma seção de auto-interação dependente da velocidade (vdSIDM). A maior parte do espaço de parâmetros de interesse pode ser testado com os três anos de dados já coletados pelo IceCube-DeepCore, complementando os resultados de experimentos de detecção direta e outras an análises de detecção indireta.

A existência de matéria escura é sustentada pela observação de efeitos gravitacionais sobre a matéria comum. A partir desses efeitos, com medidas de curvas de rotação e lentes gravitacionais, é possível calcular a densidade de matéria escura necessária para causa-los. Para descrever o comportamento observado, foram criados alguns modelos teóricos, porém a natureza das partículas que constituem matéria escura continua desconhecida. Determinar propriedades como massa e seção de choque da possível partícula de matéria escura é fundamental para o entendimento da natureza de seus efeitos sobre matéria bariônica. No âmbito experimental, os Telescópios Cherenkov medem a radiação gama proveniente do cosmo com energia entre GeV &#8212TeV de forma que uma possível interação (como exemplo a aniquilação de partículas de matéria escura) poderia ter seu resultado final de raios gama detectado em um dos experimentos de observação indireta. Neste trabalho de mestrado analisamos os conceitos de matéria escura a partir de um modelo específico de partículas WIMPs, o neutralino. Estudamos galáxias anãs esferoidais como possíveis fontes do sinal de raios gama proveniente da aniquilação de neutralinos. Para o entendimento dos cálculos, reproduzimos os resultados de dois experimentos importantes para a área, pertencentes aos telescópios VERITAS e MAGIC, validando as implementações realizadas. Estudamos também galáxias anãs esferoidais observadas pelo experimento FERMI-LAT para as quais limites superiores de fluxo foram determinados. Fizemos uso dessas medidas e extrapolamos os espectros de energias para o intervalo a ser observado pelo CTA. Utilizando curvas de sensitividade realistas para uma possível configuração do CTA, determinamos a potencialidade de detectação de matéria escura pelo CTA de 18 fontes estudados pelo FERMI-LAT. A partir dos resultados obtidos com a simulação do Observatório, podemos concluir quais fontes proporcionam melhores avanços para as pesquisas envolvendo matéria escura com o modelo escolhido. / The existence of dark matter is sustained by the observation of its gravitational efects on ordinary matter. By studying these efects, with rotation curves and gravitational lensing measurements, it is possible to calculate the dark matter density necessary to cause them. Theoretical models were created to describe the observed behavior, however the nature of the constituent particles is still unknown. Determining the particles\' properties such as mass and cross section is fundamental for the understanding of the nature of its efects on baryonic matter. On the experimental scope, Cherenkov Telescopes measure the gamma radiation coming from the cosmo with an energy between GeV &#8212TeV making it possible for an interaction to have its final product detected in one of these experiments. In this dissertation, we present an analysis of dark matter concepts considering a specific model of WIMPs particles, represented by the neutralino. We studied dwarf spheroidal galaxies as possible gamma-ray flux sources originated from the neutralino annihilation. We reproduced the results on annihilation cross section of two important experiments for this particular field (VERITAS and MAGIC), validating the codes implemented. This was perfomed with the objective of understanding the calculus involved. We studied dwarf spheroidal galaxies observed by the FERMI-LAT experiment for which upper limits flux were determined. We used these measurements and extrapolated the energy spectrum to the one to be observed by CTA. With realistic sensitivity curves for a possible CTA configuration, we determined the potencial for a dark matter detection for 18 sources studied by FERMI-LAT. With the results obtained with the Observatory simulation, we were able to conclude which of these sources represent improvements for dark matter researches with the specific model described.

A existência de matéria escura é sustentada pela observação de efeitos gravitacionais sobre a matéria comum. A partir desses efeitos, com medidas de curvas de rotação e lentes gravitacionais, é possível calcular a densidade de matéria escura necessária para causa-los. Para descrever o comportamento observado, foram criados alguns modelos teóricos, porém a natureza das partículas que constituem matéria escura continua desconhecida. Determinar propriedades como massa e seção de choque da possível partícula de matéria escura é fundamental para o entendimento da natureza de seus efeitos sobre matéria bariônica. No âmbito experimental, os Telescópios Cherenkov medem a radiação gama proveniente do cosmo com energia entre GeV &#8212TeV de forma que uma possível interação (como exemplo a aniquilação de partículas de matéria escura) poderia ter seu resultado final de raios gama detectado em um dos experimentos de observação indireta. Neste trabalho de mestrado analisamos os conceitos de matéria escura a partir de um modelo específico de partículas WIMPs, o neutralino. Estudamos galáxias anãs esferoidais como possíveis fontes do sinal de raios gama proveniente da aniquilação de neutralinos. Para o entendimento dos cálculos, reproduzimos os resultados de dois experimentos importantes para a área, pertencentes aos telescópios VERITAS e MAGIC, validando as implementações realizadas. Estudamos também galáxias anãs esferoidais observadas pelo experimento FERMI-LAT para as quais limites superiores de fluxo foram determinados. Fizemos uso dessas medidas e extrapolamos os espectros de energias para o intervalo a ser observado pelo CTA. Utilizando curvas de sensitividade realistas para uma possível configuração do CTA, determinamos a potencialidade de detectação de matéria escura pelo CTA de 18 fontes estudados pelo FERMI-LAT. A partir dos resultados obtidos com a simulação do Observatório, podemos concluir quais fontes proporcionam melhores avanços para as pesquisas envolvendo matéria escura com o modelo escolhido. / The existence of dark matter is sustained by the observation of its gravitational efects on ordinary matter. By studying these efects, with rotation curves and gravitational lensing measurements, it is possible to calculate the dark matter density necessary to cause them. Theoretical models were created to describe the observed behavior, however the nature of the constituent particles is still unknown. Determining the particles\' properties such as mass and cross section is fundamental for the understanding of the nature of its efects on baryonic matter. On the experimental scope, Cherenkov Telescopes measure the gamma radiation coming from the cosmo with an energy between GeV &#8212TeV making it possible for an interaction to have its final product detected in one of these experiments. In this dissertation, we present an analysis of dark matter concepts considering a specific model of WIMPs particles, represented by the neutralino. We studied dwarf spheroidal galaxies as possible gamma-ray flux sources originated from the neutralino annihilation. We reproduced the results on annihilation cross section of two important experiments for this particular field (VERITAS and MAGIC), validating the codes implemented. This was perfomed with the objective of understanding the calculus involved. We studied dwarf spheroidal galaxies observed by the FERMI-LAT experiment for which upper limits flux were determined. We used these measurements and extrapolated the energy spectrum to the one to be observed by CTA. With realistic sensitivity curves for a possible CTA configuration, we determined the potencial for a dark matter detection for 18 sources studied by FERMI-LAT. With the results obtained with the Observatory simulation, we were able to conclude which of these sources represent improvements for dark matter researches with the specific model described.

Este trabalho apresenta o desenvolvimento de metodologias cromatográficas para a análise de Bisfosfonatos em medicamentos acabados, matérias-prima e em fluidos biológicos utilizando Cromatografia Iônica com detecção Indireta no UV e detecção por Condutividade com Supressão de Eluente. No capítulo 1, descreve-se a pesquisa bibliográfica das propriedades farmacológicas dos BP´s, suas principais rotas sintéticas e sobre os métodos analíticos apresentados na literatura científica. No capítulo 2, foi descrito o desenvolvimento de um método para a determinação dos BP´s etidronato, clodronato, pamidronato e alendronato em matéria-prima e para medicamentos de alendronato, utilizando Cromatografia Iônica e detecção indireta no Ultravioleta. A metodologia foi validada e aplicada na análise de medicamentos contendo alendronato em comprimidos de referência e em comprimidos genéricos. No capítulo 3, descreve-se estudos visando a determinação de etidronado em plasma humano, utilizando Cromatografia Iônica Multidimensional com detecção indireta no Ultravioleta. No capítulo 4, foi desenvolvida outra metodologia para a determinação do BP´s etidronato, clodronato, pamidronato e alendronato em matéria-prima e em medicamentos contendo alendronato, utilizando Cromatografia Iônica e detecção por Condutividade com supressão de eluente. A metodologia foi validada e aplicada na análise de medicamentos contendo alendronato em comprimidos similares e em comprimidos manipulados. No capítulo 5, uma metodologia utilizando Cromatografia Iônica e detecção por Condutividade com supressão de eluente foi desenvolvida e validada para determinar clodronato em urina humana. / This work presents the development of chromatografic methodologies for analysis of Bisphosphonates in drugs, raw material and biological fluids using Ion Chromatography with indirect UV detection and conductivity detection with eluent suppression. In chapter 1, an extensive bibliographical research was accomplished in relationship to the pharmacological properties of bisphosphonates, their more important synthetic routes and about the analytical methods presented in the scientific literature. In chapter 2, the development of a method was described for the determination of BP´s etidronate, clodronate, pamidronate and alendronate in raw material and for alendronate tablets, using Ionic Chromatography with indirect UV detection. The methodology was applied to the analysis of medicines containing alendronate in both forms, generic and reference. In chapter 3, studies conducted to determinate etidronate in human plasma, using Multidimensional ionic chromatography with indirect UV detection are decribed. In chapter 4, a methodology developed for the determination of etidronate, clodronate, pamidronate and alendronate in raw material and for alendronate tablets using ionic chromatography and detection for conductivity with eluente suppression is described. The methodology was applied in the analysis of medicines with alendronate generic and reference. In chapter 5, a methodology using ion chromatography and detection for conductivity with eluente suppression was developed and validated to determine clodronate in human urine.

Este trabalho apresenta o desenvolvimento de metodologias cromatográficas para a análise de Bisfosfonatos em medicamentos acabados, matérias-prima e em fluidos biológicos utilizando Cromatografia Iônica com detecção Indireta no UV e detecção por Condutividade com Supressão de Eluente. No capítulo 1, descreve-se a pesquisa bibliográfica das propriedades farmacológicas dos BP´s, suas principais rotas sintéticas e sobre os métodos analíticos apresentados na literatura científica. No capítulo 2, foi descrito o desenvolvimento de um método para a determinação dos BP´s etidronato, clodronato, pamidronato e alendronato em matéria-prima e para medicamentos de alendronato, utilizando Cromatografia Iônica e detecção indireta no Ultravioleta. A metodologia foi validada e aplicada na análise de medicamentos contendo alendronato em comprimidos de referência e em comprimidos genéricos. No capítulo 3, descreve-se estudos visando a determinação de etidronado em plasma humano, utilizando Cromatografia Iônica Multidimensional com detecção indireta no Ultravioleta. No capítulo 4, foi desenvolvida outra metodologia para a determinação do BP´s etidronato, clodronato, pamidronato e alendronato em matéria-prima e em medicamentos contendo alendronato, utilizando Cromatografia Iônica e detecção por Condutividade com supressão de eluente. A metodologia foi validada e aplicada na análise de medicamentos contendo alendronato em comprimidos similares e em comprimidos manipulados. No capítulo 5, uma metodologia utilizando Cromatografia Iônica e detecção por Condutividade com supressão de eluente foi desenvolvida e validada para determinar clodronato em urina humana. / This work presents the development of chromatografic methodologies for analysis of Bisphosphonates in drugs, raw material and biological fluids using Ion Chromatography with indirect UV detection and conductivity detection with eluent suppression. In chapter 1, an extensive bibliographical research was accomplished in relationship to the pharmacological properties of bisphosphonates, their more important synthetic routes and about the analytical methods presented in the scientific literature. In chapter 2, the development of a method was described for the determination of BP´s etidronate, clodronate, pamidronate and alendronate in raw material and for alendronate tablets, using Ionic Chromatography with indirect UV detection. The methodology was applied to the analysis of medicines containing alendronate in both forms, generic and reference. In chapter 3, studies conducted to determinate etidronate in human plasma, using Multidimensional ionic chromatography with indirect UV detection are decribed. In chapter 4, a methodology developed for the determination of etidronate, clodronate, pamidronate and alendronate in raw material and for alendronate tablets using ionic chromatography and detection for conductivity with eluente suppression is described. The methodology was applied in the analysis of medicines with alendronate generic and reference. In chapter 5, a methodology using ion chromatography and detection for conductivity with eluente suppression was developed and validated to determine clodronate in human urine.