990 resultados para Interactions humain-machine


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The investigations presented in this thesis use various in vivo techniques to understand how trans-acting factors control gene expression. The first part addresses the transcriptional regulation of muscle creatine kinase (MCK). MCK expression is activated during the course of development and is found only in differentiated muscle. Several in vivo footprints are observed at the enhancer of this gene, but all of these interactions are limited to cell types that express MCK. This is interesting because two of the footprints appear to represent muscle specific use of general transcription factors, while the other two correspond to sites that can bind the myogenic regulator, MyoD1, in vitro. MyoD1 and these general factors are present in myoblasts, but can bind to the enhancer only in myocytes. This suggests that either the factors themselves are post-translationally modified (phosphorylation or protein:protein interactions), or the accessibility of the enhancer to the factors is limited (changes in chromatin structure). The in vivo footprinting study of MCK was performed with a new ligation mediated, single-sided PCR (polymerase chain reaction) technique that I have developed.

The second half of the thesis concerns the regulation of mouse metallothionein (MT). Metallothioneins are a family of highly conserved housekeeping genes whose expression can be induced by heavy metals, steroids, and other stresses. By adapting a primer extension method of genomic sequencing to in vivo footprinting, I've observed both metal inducible and noninducible interactions at the promoter of MT-I. From these results I've been able to limit the possible mechanisms by which metal responsive trans-acting factors induce transcription. These interpretations correlate with a second line of experiments involving the stable titration of positive acting factors necessary for induction of MT. I've amplified the promoter of MT to 10^2-10^3 copies per cell by fusing the 5' and 3' ends of the MT gene to the coding region of DHFR and selecting cells for methotrexate resistance. In these cells, there is a metal-specific titration effect, and although it acts at the level of transcription, it appears to be independent of direct DNA binding factors.

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An exciting frontier in quantum information science is the integration of otherwise "simple'' quantum elements into complex quantum networks. The laboratory realization of even small quantum networks enables the exploration of physical systems that have not heretofore existed in the natural world. Within this context, there is active research to achieve nanoscale quantum optical circuits, for which atoms are trapped near nano-scopic dielectric structures and "wired'' together by photons propagating through the circuit elements. Single atoms and atomic ensembles endow quantum functionality for otherwise linear optical circuits and thereby enable the capability of building quantum networks component by component. Toward these goals, we have experimentally investigated three different systems, from conventional to rather exotic systems : free-space atomic ensembles, optical nano fibers, and photonics crystal waveguides. First, we demonstrate measurement-induced quadripartite entanglement among four quantum memories. Next, following the landmark realization of a nanofiber trap, we demonstrate the implementation of a state-insensitive, compensated nanofiber trap. Finally, we reach more exotic systems based on photonics crystal devices. Beyond conventional topologies of resonators and waveguides, new opportunities emerge from the powerful capabilities of dispersion and modal engineering in photonic crystal waveguides. We have implemented an integrated optical circuit with a photonics crystal waveguide capable of both trapping and interfacing atoms with guided photons, and have observed the collective effect, superradiance, mediated by the guided photons. These advances provide an important capability for engineered light-matter interactions, enabling explorations of novel quantum transport and quantum many-body phenomena.

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In the first part of the thesis we explore three fundamental questions that arise naturally when we conceive a machine learning scenario where the training and test distributions can differ. Contrary to conventional wisdom, we show that in fact mismatched training and test distribution can yield better out-of-sample performance. This optimal performance can be obtained by training with the dual distribution. This optimal training distribution depends on the test distribution set by the problem, but not on the target function that we want to learn. We show how to obtain this distribution in both discrete and continuous input spaces, as well as how to approximate it in a practical scenario. Benefits of using this distribution are exemplified in both synthetic and real data sets.

In order to apply the dual distribution in the supervised learning scenario where the training data set is fixed, it is necessary to use weights to make the sample appear as if it came from the dual distribution. We explore the negative effect that weighting a sample can have. The theoretical decomposition of the use of weights regarding its effect on the out-of-sample error is easy to understand but not actionable in practice, as the quantities involved cannot be computed. Hence, we propose the Targeted Weighting algorithm that determines if, for a given set of weights, the out-of-sample performance will improve or not in a practical setting. This is necessary as the setting assumes there are no labeled points distributed according to the test distribution, only unlabeled samples.

Finally, we propose a new class of matching algorithms that can be used to match the training set to a desired distribution, such as the dual distribution (or the test distribution). These algorithms can be applied to very large datasets, and we show how they lead to improved performance in a large real dataset such as the Netflix dataset. Their computational complexity is the main reason for their advantage over previous algorithms proposed in the covariate shift literature.

In the second part of the thesis we apply Machine Learning to the problem of behavior recognition. We develop a specific behavior classifier to study fly aggression, and we develop a system that allows analyzing behavior in videos of animals, with minimal supervision. The system, which we call CUBA (Caltech Unsupervised Behavior Analysis), allows detecting movemes, actions, and stories from time series describing the position of animals in videos. The method summarizes the data, as well as it provides biologists with a mathematical tool to test new hypotheses. Other benefits of CUBA include finding classifiers for specific behaviors without the need for annotation, as well as providing means to discriminate groups of animals, for example, according to their genetic line.

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This thesis puts forth a theory-directed approach coupled with spectroscopy aimed at the discovery and understanding of light-matter interactions in semiconductors and metals.

The first part of the thesis presents the discovery and development of Zn-IV nitride materials.The commercial prominence in the optoelectronics industry of tunable semiconductor alloy materials based on nitride semiconductor devices, specifically InGaN, motivates the search for earth-abundant alternatives for use in efficient, high-quality optoelectronic devices. II-IV-N2 compounds, which are closely related to the wurtzite-structured III-N semiconductors, have similar electronic and optical properties to InGaN namely direct band gaps, high quantum efficiencies and large optical absorption coefficients. The choice of different group II and group IV elements provides chemical diversity that can be exploited to tune the structural and electronic properties through the series of alloys. The first theoretical and experimental investigation of the ZnSnxGe1−xN2 series as a replacement for III-nitrides is discussed here.

The second half of the thesis shows ab−initio calculations for surface plasmons and plasmonic hot carrier dynamics. Surface plasmons, electromagnetic modes confined to the surface of a conductor-dielectric interface, have sparked renewed interest because of their quantum nature and their broad range of applications. The decay of surface plasmons is usually a detriment in the field of plasmonics, but the possibility to capture the energy normally lost to heat would open new opportunities in photon sensors, energy conversion devices and switching. A theoretical understanding of plasmon-driven hot carrier generation and relaxation dynamics in the ultrafast regime is presented here. Additionally calculations for plasmon-mediated upconversion as well as an energy-dependent transport model for these non-equilibrium carriers are shown.

Finally, this thesis gives an outlook on the potential of non-equilibrium phenomena in metals and semiconductors for future light-based technologies.

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An automatic experimental apparatus for perturbed angular correlation measurements, capable of incorporating Ge(Li) detectors as well as scintillation counters, has been constructed.

The gamma-gamma perturbed angular correlation technique has been used to measure magnetic dipole moments of several nuclear excited states in the osmium transition region. In addition, the hyperfine magnetic fields, experienced by nuclei of 'impurity' atoms embedded in ferromagnetic host lattices, have been determined for several '4d' and '5d' impurity atoms.

The following magnetic dipole moments were obtained in the osmium transition region μ2+(190Os) = 0.54 ± 0.06 nm μ4+(190Os) = 0.88 ± 0.48 nm μ2+(192Os) = 0.56 ± 0.08 nm μ2+(192Pt) = 0.56 ± 0.06 nm μ2+’(192Pt) = 0.62 ± 0.14 nm.

These results are discussed in terms of three collective nuclear models; the cranking model, the rotation-vibration model and the pairing-plus-quadrupole model. The measurements are found to be in satisfactory agreement with collective descriptions of low lying nuclear states in this region.

The following hyperfine magnetic fields of 'impurities' in ferromagnetic hosts were determined; Hint(Cd Ni) = - (64.0 ± 0.8)kG Hint(Hg Fe) = - (440 ± 105)kG Hint(Hg Co) = - (370 ± 78)kG Hint(Hg Ni) = - (86 ± 22)kG Hint(Tl Fe) = - (185 ± 70)kG Hint(Tl Co) = - (90 ± 35)kG Hint(Ra Fe) = - (105 ± 20)kG Hint(Ra Co) = - (80 ± 16)kG Hint(Ra Ni) = - (30 ± 10)kG, where in Hint(AB); A is the impurity atom embedded in the host lattice B. No quantitative theory is available for comparison. However, these results are found to obey the general systematics displayed by these fields. Several mechanisms which may be responsible for the appearance of these fields are mentioned.

Finally, a theoretical expression for time-differential perturbed angular correlation measurement, which duplicates experimental conditions is developed and its importance in data analysis is discussed.

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Two new phenomena have been observed in Mössbauer spectra: a temperature-dependent shift of the center of gravity of the spectrum, and an asymmetric broadening of the spectrum peaks. Both phenomena were observed in thulium salts. In the temperature range 1˚K ≤ T ≤ 5˚K the observed shift has an approximate inverse temperature dependence. We explain this on the basis of a Van Vleck type of interaction between the magnetic moment of two nearly degenerate electronic levels and the magnetic moment of the nucleus. From the size of the shift we are able to deduce an “effective magnetic field” H = (6.0 ± 0.1) x 106 Gauss, which is proportional to ‹r-3M‹G|J|E› where ‹r-3M is an effective magnetic radial integral for the 4f electrons and |G› and |E› are the lowest 4f electronic states in Tm Cl3·6H2O. From the temperature dependence of the shift we have derived a preliminary value of 1 cm-1 for the splitting of these two states. The observed asymmetric line broadening is independent of temperature in the range 1˚K ≤ T ≤ 5˚K, but is dependent on the concentration of thulium ions in the crystal. We explain this broadening on the basis of spin-spin interactions between thulium ions. From size and concentration dependence of the broadening we are able to deduce a spin-spin relaxation time for Tm Cl3·6H2O of the order of 10-11 sec.

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The cytolytic interaction of Polyoma virus with mouse embryo cells has been studied by radiobiological methods known to distinguish temperate from virulent bacteriophage. No evidence for "temperate" properties of Polyoma was found. During the course of these studies, it was observed that the curve of inactivation of Polyoma virus by ultraviolet light had two components - a more sensitive one at low doses, and a less sensitive one at higher doses. Virus which survives a low dose has an eclipse period similar to that of unirradiated virus, while virus surviving higher doses shows a significantly longer eclipse period. If Puromycin is present during the early part of the eclipse period, the survival curve becomes a single exponential with the sensitivity of the less sensitive component. These results suggest a repair mechanism in mouse cells which operates more effectively if virus development is delayed.

A comparison of the rates of inactivation of the cytolytic and transforming abilities of Polyoma by ultraviolet light, X-rays, nitrous acid treatment, or the decay of incorporated P32, showed that the transforming ability has a target size roughly 60% of that of the plaque-forming ability. It is thus concluded that only a fraction of the viral genes are necessary for causing transformation.

The appearance of virus-specific RNA in productively infected mouse kidney cells has been followed by means of hybridization between pulse-labelled RNA from the infected cells and the purified virus DNA. The results show a sharp increase in the amount of virus-specific RNA around the time of virus DNA synthesis. The presence of a small amount of virus-specific RNA in virus-free transformed cells has also been shown. This result offers strong evidence for the persistence of at least part of the viral genome in transformed cells.

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I. ELECTROPHORESIS OF THE NUCLEIC ACIDS

A zone electrophoresis apparatus using ultraviolet optics has been constructed to study nucleic acids at concentrations less than 0.004%. Native DNA has a mobility about 15% higher than denatured DNA over a range of conditions. Otherwise, the electrophoretic mobility is independent of molecular weight, base composition or source. DNA mobilities change in the expected way with pH but the fractional change in mobility is less than the calculated change in charge. A small decrease in mobility accompanies an increase in ionic strength. RNA’s from various sources have mobilities slightly lower than denatured DNA except for s-RNA which travels slightly faster. The important considerations governing the mobility of nucleic acids appear to be the nature of the hydrodynamic segment, and the binding of counterions. The differences between electrophoresis and sedimentation stem from the fact that all random coil polyelectrolytes are fundamentally free draining in electrophoresis.

II. THE CYTOCHROME C/DNA COMPLEX

The basic protein, cytochrome c, has been complexed to DNA. Up to a cytochrome:DNA mass ratio of 2, a single type of complex is formed. Dissociation of this complex occurs between 0.05F and 0.1F NaCl. The complexing of cytochrome to DNA causes a slight increase in the melting temperature of the DNA, and a reduction of the electrophoretic mobility proportional to the decrease in net charge. Above a cytochrome:DNA mass ratio of 2.5, a different type of complex is formed. The results suggest that complexes such as are formed in the Kleinschmidt technique of electron microscopy would not exist in bulk solution and are exclusively film phenomena.

III. STUDIES OF THE ELECTROPHORESIS AND MELTING BEHAVIOUR OF NUCLEOHISTONES

Electrophoresis studies on reconstituted nucleohistones indicate that the electrophoretic mobility for these complexes is a function of the net charge of the complex. The mobility is therefore dependent on the charge density of the histone complexing the DNA, as well as on the histone/DNA ratio. It is found that the different histones affect the transition from native to denatured DNA in different ways. It appears that histone I is exchanging quite rapidly between DNA molecules in 0.01 F salt, while histone II is irreversibly bound. Histone III-IV enhances the capacity of non-strand separated denatured DNA to reanneal. Studies on native nucleoproteins indicate that there are no gene-sized uncomplexed DNA regions in any preparations studied.

IV. THE DISSOCIATION OF HISTONE FROM CALF THYMUS CROMATIN

Calf thymus nucleoprotein was treated with varying concentrations of NaCl. The identity of the histones associated and dissociated from the DNA at each salt concentration was determined by gel electrophoresis. It was found that there is no appreciable histone dissociation below 0.4 F NaCl. The lysine rich histones dissociate between 0.4 and 0.5 F NaCl. Their dissociation is accompanies by a marked increase in the solubility of the chromatin. The moderately lysine rich histones dissociate mainly between 0.8 and 1.1 F NaCl. There are two arginine rich histone components: the first dissociates between 0.8 F and 1.1 F NaCl, but the second class is the very last to be dissociated from the DNA (dissociation beginning at 1.0 F NaCl). By 2.0 F NaCl, essentially all the histones are dissociated.

The properties of the extracted nucleoprotein were studied. The electrophoretic mobility increases and the melting temperature decreases as more histones are dissociated from the DNA. A comparison with the dissociation of histones from DNA in NaClO4 shows that to dissociate the same class of histones, the concentration of NaCl required is twice that of NaClO4.

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Interactions between fluid flows and elastic bodies are ubiquitous in nature. One such phenomena that is encountered on a daily basis is the flapping and fluttering of leaves in the wind. The fluid-structure interaction that governs the physics of a leaf in the wind is poorly understood at best and has potential applications in biomechanics, vehicle design, and energy conversion. We build upon previous work on the flapping dynamics of inverted flags, which are cantilevered elastic sheets with free leading edge and fixed trailing edge that display unique large amplitude oscillatory behaviors. We model a leaf in the laboratory using modified inverted flags, experimentally probing the governing parameters behind leaf fluttering as well as shedding light on the physics behind the inverted flag phenomena. The behavior of these "inverted leaves" studied here display sensitive dependence on two biomechanically relevant parameters, stem-to-leaf rigidity and stem-to-leaf length. In addition, leaves on a tree are not often found alone. We seek to understand the complex interactions of multiple fluttering and flapping leaves by way of examining the interactions between pairs of inverted flags. Coupling through their flow fields, pairs of inverted flags exhibit striking emergent phenomena. We report these observed dynamical behaviors and the conditions upon which they arise.

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The Mössbauer technique has been used to study the nuclear hyperfine interactions and lifetimes in W182 (2+ state) and W183 (3/2- and 5/2- states) with the following results: g(5/2-)/g(2+) = 1.40 ± 0.04; g(3/2- = -0.07 ± 0.07; Q(5/2-)/Q(2+) = 0.94 ± 0.04; T1/2(3/2-) = 0.184 ± 0.005 nsec; T1/2(5/2-) >̰ 0.7 nsec. These quantities are discussed in terms of a rotation-particle interaction in W183 due to Coriolis coupling. From the measured quantities and additional information on γ-ray transition intensities magnetic single-particle matrix elements are derived. It is inferred from these that the two effective g-factors, resulting from the Nilsson-model calculation of the single-particle matrix elements for the spin operators ŝz and ŝ+, are not equal, consistent with a proposal of Bochnacki and Ogaza.

The internal magnetic fields at the tungsten nucleus were determined for substitutional solid solutions of tungsten in iron, cobalt, and nickel. With g(2+) = 0.24 the results are: |Heff(W-Fe)| = 715 ± 10 kG; |Heff(W-Co)| = 360 ± 10 kG; |Heff(W-Ni)| = 90 ± 25 kG. The electric field gradients at the tungsten nucleus were determined for WS2 and WO3. With Q(2+) = -1.81b the results are: for WS2, eq = -(1.86 ± 0.05) 1018 V/cm2; for WO3, eq = (1.54 ± 0.04) 1018 V/cm2 and ƞ = 0.63 ± 0.02.

The 5/2- state of Pt195 has also been studied with the Mössbauer technique, and the g-factor of this state has been determined to be -0.41 ± 0.03. The following magnetic fields at the Pt nucleus were found: in an Fe lattice, 1.19 ± 0.04 MG; in a Co lattice, 0.86 ± 0.03 MG; and in a Ni lattice, 0.36 ± 0.04 MG. Isomeric shifts have been detected in a number of compounds and alloys and have been interpreted to imply that the mean square radius of the Pt195 nucleus in the first-excited state is smaller than in the ground state.

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The nature of the intra- and intermolecular base-stacking interactions involving several dinucleoside monophosphates in aqueous solution have been investigated by proton magnetic resonance spectrosocopy, and this method has been applied to a study of the interaction of polyuridylic acid with purine and adenosine monomers.

The pmr spectra of adenylyl (3' → 5') cytidine (ApC) and cytidylyl (3' → 5') adenosine (CpA) have been studied as a function of concentration and temperature. The results of these studies indicate that the intramolecular base-stacking interactions between the adenine and cytosine bases of these dinucleoside monophosphates are rather strong, and that the stacking tendencies are comparable for the two sequence isomers. The chemical shifts of the cytosine H5 and adenine H2 protons, and their variations with temperature, were shown to be consistent with stacked conformations in which both bases of the dinucleoside monophosphates are preferentially oriented in the anti conformation as in similar dApdC, and dCpdA (dA = deoxyadenosine; dC = deoxycytidine) segments in double helical DNA. The intramolecular stacking interaction was found to have a pronounced effect on the conformations of the ribose moieties, and these conformational changes are discussed. The concentration studies indicate extensive self-association of these dinucleoside monophosphates, and analysis of the concentration data facilitated determination of the dimerization constant for the association process as well as the nature of the intermolecular complexes.

The dependence of the ribose conformation upon the extent of intramolecular base-stacking was used to demonstrate that the base-base interaction in cytidylyl (3' → 5') cytidine (CpC) is rather strong, while there appears to be little interaction between the two uracil bases of uridylyl (3' → 5') uridine (UpU).

Studies of the binding of purine to several ribose and deoxyribose dinucleoside monophosphates show that the mode of interaction is base-stacking, and evidence for the formation of a purine-dinucleoside monophosphate intercalated complex is presented. The purine proton resonances are markedly broadened in this complex, and estimates of the purine linewidths in the complex and the equilibrium constant for purine intercalation are obtained.

A study of the interaction of unsubstitued purine with polyuridylic acid at 29°C by pmr indicated that purine binds to the uracil bases of the polymer by base-stacking. The severe broadening of the purine proton resonances observed provides strong evidence for the intercalation of purine between adjacent uracil bases of poly U. This interaction does not result in a more rigid or ordered structure for the polymer.

Investigation of the interaction between adenosine and polyuridylic acid revealed two modes of interaction between the monomer and the polymer, depending on the temperature. At temperatures above 26°C or so, monomeric adenosine binds to poly U by noncooperative A-U base stacking. Below this temperature, a rigid triple-stranded 1A:2U complex is formed, presumably via cooperative hydrogen-bonding as has previously been reported.

These results clearly illustrate the importance of base-stacking in non-specific interactions between bases, nucleosides and nucleotides, and also reveal the important role of the base-stacking interactions in cooperatively for med structures involving specific base-pairing where both types of interaction are possible.

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Due to their high specific strength and low density, magnesium and magnesium-based alloys have gained great technological importance in recent years. However, their underlying hexagonal crystal structure furnishes Mg and its alloys with a complex mechanical behavior because of their comparably smaller number of energetically favorable slip systems. Besides the commonly studied slip mechanism, another way to accomplish general deformation is through the additional mechanism of deformation-induced twinning. The main aim of this thesis research is to develop an efficient continuum model to understand and ultimately predict the material response resulting from the interaction between these two mechanisms.

The constitutive model we present is based on variational constitutive updates of plastic slips and twin volume fractions and accounts for the related lattice reorientation mechanisms. The model is applied to single- and polycrystalline pure magnesium. We outline the finite-deformation plasticity model combining basal, pyramidal, and prismatic dislocation activity as well as a convexification based approach for deformation twinning. A comparison with experimental data from single-crystal tension-compression experiments validates the model and serves for parameter identification. The extension to polycrystals via both Taylor-type modeling and finite element simulations shows a characteristic stress-strain response that agrees well with experimental observations for polycrystalline magnesium. The presented continuum model does not aim to represent the full details of individual twin-dislocation interactions, yet it is sufficiently efficient to allow for finite element simulations while qualitatively capturing the underlying microstructural deformation mechanisms.

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This thesis explores the dynamics of scale interactions in a turbulent boundary layer through a forcing-response type experimental study. An emphasis is placed on the analysis of triadic wavenumber interactions since the governing Navier-Stokes equations for the flow necessitate a direct coupling between triadically consist scales. Two sets of experiments were performed in which deterministic disturbances were introduced into the flow using a spatially-impulsive dynamic wall perturbation. Hotwire anemometry was employed to measure the downstream turbulent velocity and study the flow response to the external forcing. In the first set of experiments, which were based on a recent investigation of dynamic forcing effects in a turbulent boundary layer, a 2D (spanwise constant) spatio-temporal normal mode was excited in the flow; the streamwise length and time scales of the synthetic mode roughly correspond to the very-large-scale-motions (VLSM) found naturally in canonical flows. Correlation studies between the large- and small-scale velocity signals reveal an alteration of the natural phase relations between scales by the synthetic mode. In particular, a strong phase-locking or organizing effect is seen on directly coupled small-scales through triadic interactions. Having characterized the bulk influence of a single energetic mode on the flow dynamics, a second set of experiments aimed at isolating specific triadic interactions was performed. Two distinct 2D large-scale normal modes were excited in the flow, and the response at the corresponding sum and difference wavenumbers was isolated from the turbulent signals. Results from this experiment serve as an unique demonstration of direct non-linear interactions in a fully turbulent wall-bounded flow, and allow for examination of phase relationships involving specific interacting scales. A direct connection is also made to the Navier-Stokes resolvent operator framework developed in recent literature. Results and analysis from the present work offer insights into the dynamical structure of wall turbulence, and have interesting implications for design of practical turbulence manipulation or control strategies.

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Optical Coherence Tomography(OCT) is a popular, rapidly growing imaging technique with an increasing number of bio-medical applications due to its noninvasive nature. However, there are three major challenges in understanding and improving an OCT system: (1) Obtaining an OCT image is not easy. It either takes a real medical experiment or requires days of computer simulation. Without much data, it is difficult to study the physical processes underlying OCT imaging of different objects simply because there aren't many imaged objects. (2) Interpretation of an OCT image is also hard. This challenge is more profound than it appears. For instance, it would require a trained expert to tell from an OCT image of human skin whether there is a lesion or not. This is expensive in its own right, but even the expert cannot be sure about the exact size of the lesion or the width of the various skin layers. The take-away message is that analyzing an OCT image even from a high level would usually require a trained expert, and pixel-level interpretation is simply unrealistic. The reason is simple: we have OCT images but not their underlying ground-truth structure, so there is nothing to learn from. (3) The imaging depth of OCT is very limited (millimeter or sub-millimeter on human tissues). While OCT utilizes infrared light for illumination to stay noninvasive, the downside of this is that photons at such long wavelengths can only penetrate a limited depth into the tissue before getting back-scattered. To image a particular region of a tissue, photons first need to reach that region. As a result, OCT signals from deeper regions of the tissue are both weak (since few photons reached there) and distorted (due to multiple scatterings of the contributing photons). This fact alone makes OCT images very hard to interpret.

This thesis addresses the above challenges by successfully developing an advanced Monte Carlo simulation platform which is 10000 times faster than the state-of-the-art simulator in the literature, bringing down the simulation time from 360 hours to a single minute. This powerful simulation tool not only enables us to efficiently generate as many OCT images of objects with arbitrary structure and shape as we want on a common desktop computer, but it also provides us the underlying ground-truth of the simulated images at the same time because we dictate them at the beginning of the simulation. This is one of the key contributions of this thesis. What allows us to build such a powerful simulation tool includes a thorough understanding of the signal formation process, clever implementation of the importance sampling/photon splitting procedure, efficient use of a voxel-based mesh system in determining photon-mesh interception, and a parallel computation of different A-scans that consist a full OCT image, among other programming and mathematical tricks, which will be explained in detail later in the thesis.

Next we aim at the inverse problem: given an OCT image, predict/reconstruct its ground-truth structure on a pixel level. By solving this problem we would be able to interpret an OCT image completely and precisely without the help from a trained expert. It turns out that we can do much better. For simple structures we are able to reconstruct the ground-truth of an OCT image more than 98% correctly, and for more complicated structures (e.g., a multi-layered brain structure) we are looking at 93%. We achieved this through extensive uses of Machine Learning. The success of the Monte Carlo simulation already puts us in a great position by providing us with a great deal of data (effectively unlimited), in the form of (image, truth) pairs. Through a transformation of the high-dimensional response variable, we convert the learning task into a multi-output multi-class classification problem and a multi-output regression problem. We then build a hierarchy architecture of machine learning models (committee of experts) and train different parts of the architecture with specifically designed data sets. In prediction, an unseen OCT image first goes through a classification model to determine its structure (e.g., the number and the types of layers present in the image); then the image is handed to a regression model that is trained specifically for that particular structure to predict the length of the different layers and by doing so reconstruct the ground-truth of the image. We also demonstrate that ideas from Deep Learning can be useful to further improve the performance.

It is worth pointing out that solving the inverse problem automatically improves the imaging depth, since previously the lower half of an OCT image (i.e., greater depth) can be hardly seen but now becomes fully resolved. Interestingly, although OCT signals consisting the lower half of the image are weak, messy, and uninterpretable to human eyes, they still carry enough information which when fed into a well-trained machine learning model spits out precisely the true structure of the object being imaged. This is just another case where Artificial Intelligence (AI) outperforms human. To the best knowledge of the author, this thesis is not only a success but also the first attempt to reconstruct an OCT image at a pixel level. To even give a try on this kind of task, it would require fully annotated OCT images and a lot of them (hundreds or even thousands). This is clearly impossible without a powerful simulation tool like the one developed in this thesis.