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The electromagnetic form factors are the most fundamental observables that encode information about the internal structure of the nucleon. The electric ($G_{E}$) and the magnetic ($G_{M}$) form factors contain information about the spatial distribution of the charge and magnetization inside the nucleon. A significant discrepancy exists between the Rosenbluth and the polarization transfer measurements of the electromagnetic form factors of the proton. One possible explanation for the discrepancy is the contributions of two-photon exchange (TPE) effects. Theoretical calculations estimating the magnitude of the TPE effect are highly model dependent, and limited experimental evidence for such effects exists. Experimentally, the TPE effect can be measured by comparing the ratio of positron-proton elastic scattering cross section to that of the electron-proton $\large(R = \frac{\sigma (e^{+}p)}{\sigma (e^{-}p)}\large)$. The ratio $R$ was measured over a wide range of kinematics, utilizing a 5.6 GeV primary electron beam produced by the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab. This dissertation explored dependence of $R$ on kinematic variables such as squared four-momentum transfer ($Q^{2}$) and the virtual photon polarization parameter ($\varepsilon$). A mixed electron-positron beam was produced from the primary electron beam in experimental Hall B. The mixed beam was scattered from a liquid hydrogen (LH$_{2}$) target. Both the scattered lepton and the recoil proton were detected by the CEBAF Large Acceptance Spectrometer (CLAS). The elastic events were then identified by using elastic scattering kinematics. This work extracted the $Q^{2}$ dependence of $R$ at high $\varepsilon$ ($\varepsilon > $ 0.8) and the $\varepsilon$ dependence of $R$ at $\langle Q^{2} \rangle \approx 0.85$ GeV$^{2}$. In these kinematics, our data confirm the validity of the hadronic calculations of the TPE effect by Blunden, Melnitchouk, and Tjon. This hadronic TPE effect, with additional corrections contributed by higher excitations of the intermediate state nucleon, largely reconciles the Rosenbluth and the polarization transfer measurements of the electromagnetic form factors.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22376号 / 医博第4617号 / 新制||医||1043(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 道行, 教授 林 康紀, 教授 江藤 浩之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Two-photon laser scanning microscopy is a modern method of in vivo neurophysiological research, capable of imaging up to hundreds of neurons at once. However, this method produces a large amount of data, difficult to process and analyze manually. This thesis presents Two-Photon Processor, a new toolkit for complex processing of data from two-photon microscope. During the work on this thesis, we designed the SeNeCA segmentation algorithm for detection of neurons in full-frame recording from a two-photon microscope. SeNeCA combines high speed and high quality of segmentation and, according to our evaluation, it currently is the best algorithm for segmentation of neurons in in vivo data. Two- Photon Processor is already routinely used in the Institute of Experimental Medicine of the ASCR, Department of Auditory Neuroscience, and it was published in the Journal of Neurophysiology.

Highly correlated quantum chemical methods have been appliedto study the photophysical properties of substituted benzenes.With the inclusion of spin-orbit coupling, the phosphorescencesof these molecules have been calculated usingMulti-CongurationalSelf- Consistent Field (MCSCF) quadraticresponse theory. The Herzberg-Teller approximation has beenadopted to evaluate the vibronic contributions tophosphorescence. The performance of hybrid density functional theory (DFT) atthe B3LYP level is examined in comparison to the MP2, CCSD andCCSD(T) methods for the geometry and permanent dipole moment ofp-aminobenzoic acid. The time-dependent DFT/B3LYP method isapplied to calculate the two-photon absorption of a series ofZinc-porphyrin derivatives in combination with a two-statemodel. The transitions between excited singlet and tripletstates of Zinc and Platinum based organometallic compounds havebeen computed using DFT quadratic response theory. The resultsare used to simulate the non-linear propagation of laser pulsesthrough these materials utilizing a dynamical wave propagationmethod.

This thesis presents a novel method of modulating silicon photonic circuits using 3D printed microfluidic devices. The fluids that pass through the microfluidic device interact directly with the silicon waveguides. This method changes the refractive index of the waveguide cladding, thus changing the effective index of the system. Through using this technique we demonstrate the shift in resonant wavelength by a full free spectral range (FSR) by increasing the concentration of the salt water in the microfluidic device from 0% to 10%. On a 60 μm microring resonator, this equals a resonant wavelength shift of 1.514 nm when the index of the cladding changes by 0.017 refractive index units (RIU), or at a rate of 89.05 nm/RIU. These results are confirmed by simulations that use both analytical and numerical methods. This thesis also outlines the development of a process that uses two-photon absorption(TPA) in silicon to produce a photoelectrochemical (PEC) etching effect. TPA induces free carriers in silicon that then interact with the Hydroflouric Acid (HF) solution that the wafer is submerged in. This interaction removes silicon away from the wafer, which is the etching observed in our experiments. Non-line-of-sight PEC etching is demonstrated. The optical assemblies used in these experiments are presented, as are several of the results of the etching experiments.

The locus coeruleus (LC) projects ubiquitously to the cortex, and noradrenaline (NA) exerts powerful neuromodulatory control on cortical excitation and inhibition. Previous work has shown that NA plays an important role in motor processes, and further posits that dysregulation in NA function could be one of the culprits of motor-related deficits in many neurodevelopmental disorders, including Autism Spectrum Disorder. In order to characterize the change in NA levels during motor learning in awake and behaving mice, I employed a newly developed optical NA sensor, combined with in vivo two-photon imaging, to visualize spatiotemporal activation patterns of NA in the motor cortex. This experimental approach allows us to track and chronically image the same region of the motor cortex over multiple days, thus permitting the characterization of NA activity throughout the entirety of the motor learning process. I found that NA levels increase significantly during the initial phase of learning, which coincides with the structural and functional plastic changes that have been previously reported in the motor cortex during early stages of motor learning. The NA activity returns to baseline levels as the mice develop their movement strategy; however, the regions of NA release become more spatially clustered during the learning process. The results reported in this thesis provide a novel glimpse into the dynamics of NA activity in the motor cortex during motor learning, and it will provide new direction for the development of therapeutic strategies and diagnostic criteria for motor-related dysfunction in neurodevelopmental diseases.

Le premier traitement standard pour les tumeurs cérébrales est la résection chirurgicale. Dans cette procédure un enjeu important demeure, l'identification des berges tumorales pour assurer une résection totale et éviter le risque de récidive pour le patient. A ce jour aucune technique d'imagerie peropératoire est capable de résoudre l'infiltration tumorale du tissu sain. La norme pour le diagnostic des berges tumorales est l'analyse histologique des biopsies. Une méthode ex vivo qui requiert un à plusieurs jours pour fournir ler apport pathologique final, un lapse de temps qui peut s'avérer fatal pour le patient. La microscopie optique a récemment été développer vers une utilisation clinique peropératoire pour répondre à cet enjeu. Dans travail, la technique de microscopie à deux-photons a été préférée pouressayer de répondre à cette problématique. Cette méthode donne accès à deux contrastes d'imagerie, la génération de seconde harmonique et l’émission de fluorescence, qui peuvent être combinés à des mesures quantitatives, tel que la spectroscopie et le temps de vie de fluorescence. Combiner ces quatre modalités de détection donnera une information complète sur la structure et le métabolisme de la région observée. Pour soutenir le développement technique vers une sonde endomicroscopique visant une utilisation peropératoire, les données en résultants doivent être fiables, et se montrer d'un intérêt pour le chirurgien. Par conséquent, une base de données sur le signal d'autofluorescence des tissus a été construite et présentée dans ce manuscrit, avec des algorithmes capables de discriminer de façon fiable les régions tumorales des régions saines. Des algorithmes qui ont montré le potentiel d'être automatisé dans une configuration clinique, afin de fournir une réponse en temps-réel au chirurgien. / The first standard approach for brain tumor treatment is the surgical resection. In this protocol an important challenge remains, the identification of tumor margins to ensure a complete resection and avoid risk of tumor recurrence. Nowadays no intra-operative means of contrast are able to resolve infiltrated regions from healthy tissue. The standard for tumor margin diagnosis is the histological analysis of biopsies. An ex vivo method that requires one to several days to issue a final pathological reports, a time lapse that could be fatal to the patient. Optical microscopy have recently been developed towards an intra-operative clinical use to answer this challenge. In this work, the technique of two-photon microscopy based on the autofluorescence of tissue have been favored. This technique gives access to two imaging contrasts, the second-harmonic generation and emission of fluorescence, and can be combined to quantitative measurements, such as spectroscopy and fluorescence lifetime. The combination of these four modalities of detection will give a complete structural and metabolic information on the observed region. To support the technical development towards an endomicroscopic probe, the resulted data have to be reliable and proved to be of interest for the surgeon. Consequently, an extensive database of the autofluorescence response of brain tumor tissue have been constructed and presented in this manuscript, with algorithms able to discriminate with reliability tumoral from healthy regions. Algorithms that have shown potential to be automatized in a clinical setting, in order to give a real-time answer to the surgeons.

This dissertation is author version of following the journal article. Rei Mizuno, Yuji Kamioka, Kenji Kabashima, Masamichi Imajo, Kenta Sumiyama, Eiji Nakasho, Takeshi Ito, Yoko Hamazaki, Yoshihisa Okuchi, Yoshiharu Sakai, Etsuko Kiyokawa, and Michiyuki Matsuda. "In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines" J Exp Med 2014 211:1123-1136. Published May 19, 2014, doi:10.1084/jem.20132112 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18542号 / 医博第3935号 / 新制||医||1006(附属図書館) / 31442 / 京都大学大学院医学研究科医学専攻 / (主査)教授 岩井 一宏, 教授 千葉 勉, 教授 長澤 丘司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20245号 / 医博第4204号 / 新制||医||1020(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 道行, 教授 羽賀 博典, 教授 鈴木 茂彦 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM