Dissertations / Theses on the topic 'Strain modulation'

Optical fibre sensors with fibre Bragg grating (FBG) are used widely because of their advantages such as electrical immunity and high sensitivity. The motivation for this thesis is to use the FBG sensors to measure strain gradient and to monitor crack growth, going through the procedures of fabrication and application of fibre FBG sensors for monitoring structural behaviour. The history and advances in FBG sensors are first studied through a literature review, and it highlights several major fabrication methods for the FBG. The FBG sensors used in this study were fabricated using an improved phase mask method. The strains in tensile and bending specimens were successfully measured using both the fabricated and commercial FBG sensors. ABAQUS software was used for simulation of different strain gradient. Spectrum distortion of reflected light was identified by calculating differences in intensity. Furthermore, the coupled mode theory and T-matrix methods were applied to develop an effective model to analyse grating patterns for FBG sensors under strains. Simulation analysis based on MATLAB was performed for the FBG sensors under different strain circumstances. Some strain conditions which were not convenient for the actual test were also analysed using MATLAB and provided a useful reference for studying the FBG sensors under complex strains. Finally, a self-fabricated FBG array was used to monitor mode I interlaminar crack growth in a double cantilever beam (DCB) specimen of glass fibre-reinforced polymer (GFRP) composite. The array with four sets of FBG sensors was attached to the side of cantilever beam of the DCB specimen, the result was analysed, indicating that the array sensor was sensitive to crack growth. This result proved that both the fabrication and the testing method were successful, and attaching FBG sensors on the material surface can be a convenient method for structural health monitoring.

Ce travail est centré sur l'étude des non-linéarités de deuxiéme ordre dans le silicium vers une modulation optique à faible puissance et haute vitesse. Étant un cristal centro-symétrique, le silicium ne possède pas une susceptibilité non linéaire de deuxiéme ordre (X2), ce qui inhibe l'effet Pockels, un effet électro-optique linéaire couramment utilisé dans la modulation de la lumière dans les communications optiques. Une solution possible pour vaincre cette limitation est par application de contraint et déformation de la maille cristalline, ce qui rompt localement la centro-symétrie du cristal et génère X2.Dans cette thèse, nous abordons le problème de la génération de X2 dans le silicium par l'utilisation de la contrainte, couvrant toutes les étapes de la recherche: nous partons de bases théoriques développées par nous, on simule l'ensemble des effets de contraints, optiques et électriques, on décrit la fabrication des dispositifs et finalement on présent la caractérisation expérimentale de ces dispositifs.Dans ce travail de recherche, nous avons pu détecter des effets très particuliers qui sont attribués au effet Pockels, comme par example une dépendance claire de l'orientation du cristal sur l'efficacité de la modulation et aussi la modulation à haute fréquences, plus élevées que celles attendues par autres contributions. Ces résultats sont très prometteurs et se composent d'une nouvelle étape vers la mise en œuvre, dans un avenir proche, de la modulation à grande vitesse et à faible puissance dans les dispositifs de silicium<br>This work is devoted to the study of second order nonlinearities in silicon towards low power, high speed modulation. Being a centro-symmetric crystal, silicon does not possess a second order nonlinear susceptibility (X2), which inhibits Pockels effect, a linear electro-optic effect commonly used in the modulation of light in high speed communications. A possible solution to overcome this limitation is by straining/deforming the crystal lattice, which locally breaks the centro-symmetry of the crystal and generates X2.In this thesis, we approach the problem of generating X2 in silicon through the use of strain, covering all the research stages: we depart from newly developed theoretical grounds, simulate together the strain, optical and electrical effects together, describe the fabrication of the devices and present the experimental characterization.In our research work, we were able to detect very particular effects which are attributed to Pockels effect, such as a clear dependence of the crystal orientation on the modulation efficiency and high speed modulation, at frequencies higher than those expected from other contributions. This results are very promising and consist on a step further towards the possible implementation of high speed, low power modulation in silicon devices in the near future

Fusionless scoliosis surgery is an emerging treatment for idiopathic scoliosis as it offers theoretical advantages over current forms of treatment. Currently the treatment options for idiopathic scoliosis are observation, bracing and fusion. While brace treatment is non-invasive, and preserves the growth, motion, and function of the spine, it does not correct deformity and is only modestly successful in preventing curve progression. In adolescents who fail brace treatment, surgical treatment with an instrumented spinal fusion usually results in better deformity correction but is associated with substantially greater risk. Furthermore in younger patients requiring surgical treatment, fusion procedures are known to adversely effect the future growth of the chest and spine. Fusionless treatments have been developed to allow effective surgical treatment of patients with idiopathic scoliosis who are too young for fusion procedures. Anterior vertebral stapling is one such fusionless treatment which aims to modulate the growth of vertebra to allow correction of scoliosis whilst maintaining normal spinal motion The Mater Misericordiae Hospital in Brisbane has begun to use anterior vertebral stapling to treat patients with idiopathic scoliosis who are too young for fusion procedures. Currently the only staple approved for clinical use is manufactured by Medtronic Sofamor Danek (Memphis, TN). This thesis explains the biomechanical and anatomical changes that occur following anterior vertebral staple insertion using in vitro experiments performed on an immature bovine model. Currently there is a paucity of published information about anterior vertebral stapling so it is hoped that this project will provide information that will aid in our understanding of the clinical effects of staple insertion. The aims of this experimental study were threefold. The first phase was designed to determine the changes in the bending stiffness of the spine following staple insertion. The second phase was designed to measure the forces experienced by the staple during spinal movements. The third and final phase of testing was designed to describe the structural changes that occur to a vertebra as a consequence of staple insertion. The first phase of testing utilised a displacement controlled testing robot to compare the change in stiffness of a single spinal motion segment following staple insertion for the three basic spinal motions of flexion-extension, lateral bending, and axial rotation. For the second phase of testing strain gauges were attached to staples and used to measure staple forces during spinal movement. In the third and final phase the staples were removed and a testing specimen underwent micro-computed tomography (CT) scanning to describe the anatomical changes that occur following staple insertion. The displacement controlled testing showed that there was a significant decrease in bending stiffness in flexion, extension, lateral bending away from the staple, and axial rotation away from the staple following staple insertion. The strain gauge measurements showed that the greatest staple forces occurred in flexion and the least in extension. In addition, a reduction in the baseline staple compressive force was seen with successive loading cycles. Micro-CT scanning demonstrated that significant damage to the vertebral body and endplate occurred as a consequence of staple insertion. The clinical implications of this study are significant. Based on the findings of this project it is likely that the clinical effect of the anterior vertebral staple evaluated in this project is a consequence of growth plate damage (also called hemiepiphysiodesis) causing a partial growth arrest of the vertebra rather than simply compression of the growth plate. The surgical creation of a unilateral growth arrest is a well established treatment used in the management of congenital scoliosis but has not previously been considered for use in idiopathic scoliosis.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Materials Science and Engineering, 2020<br>Cataloged from student-submitted PDF of thesis.<br>Includes bibliographical references (pages 151-159).<br>Electronic and photonic integrated circuits serve as a promising platform for telecommunications and sensing applications. Electroabsorption modulators allow fast modulation, small device footprint, and low power consumption. Epitaxially grown GeSi films on SOI substrates are a suitable materials platform for integrated modulator applications. A modulator's operation wavelength adjustment and its system integration for broadband modulation are two major challenges of fabricating on-chip modulator arrays for telecommunication. Unlike Si MZI modulators, GeSi electroabsorption modulators are not broadband due to its limited working region near absorption edge for the Franz-Keldysh effect. Optimization of a modulator material for a target wavelength can be achieved by tuning material composition or applying strain to the material.<br>In order to realize an integrated system with a broadband modulation, multiple electroabsorption modulators need to be fabricated individually and assembled onto a chip in a conventional approach. Each fabrication step adds cost to design and processing. Integrating more modulators for multiple operating wavelengths allows a broader optical band coverage and higher optoelectronic data processing capacity, which is desirable with lower cost, simpler layout, and easier electronic and photonic circuits integration. In this thesis work, a one-for-all strained GeSi modulator array design is proposed and demonstrated to cover a broad telecommunication band with multiple modulators designed and fabricated simultaneously in the same process flow. A stressor layer applies a homogeneous strain to a waveguide modulator. By changing a modulator width, strain in the modulator changes, tuning the material bandgap, therefore, adjusting the modulator operation wavelength.<br>Modulators made of the same material can operate at various wavelengths with the same stressor layer with a simplified layout and device process flow. The matrix of investigation consists of two compositions (Ge and Ge₀.₉₉Si₀.₀₁) and three types of strain (compressive, tensile, and no strains). Individual GeSi EAMs with waveguide width less than 2 [mu]m have demonstrated an improved extinction ratio/insertion loss value from 1 to 1.7, which is the highest value among Si Mach-Zehnder, and GeSi electroabsorption modulators. Strained Ge₀.₉₉Si₀.₀₁ modulator arrays have demonstrated a broad optical bandwidth of ~100nm in C- and L-bands in telecommunication. An ultralow insertion loss of 2dB and high modulation speed above 100 GHz is achievable with minor improvements in electrode design. An increase in Si composition to 4% allows a strained Ge₀.₉₆Si₀.₀₄ modulator array to cover the optical wavelength from 1300nm to 1450nm.<br>Strained GeSi modulator and detector arrays can be fabricated in the same process flow with the same stressor layers to achieve an integration of transmitters and receivers on a single chip with a simplified design layout and fabrication procedure. That presents a promising platform for integrated photonic transceivers with an ultrawide optical coverage in the entire telecommunication bands.<br>by Danhao Ma.<br>Ph. D.<br>Ph.D. Massachusetts Institute of Technology, Department of Materials Science and Engineering

Orientador: Prof. Dr. Jeverson Teodoro Arantes Junior<br>Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Nanociências e Materiais Avançados, Santo André, 2018.<br>Investigamos, sistematicamente, as propriedades estruturais e eletrônicas do óxido de zinco nanoporoso sob tração e compressão biaxial utilizando cálculos de primeiros princípios baseados na Teoria do Funcional da Densidade. O sistema apresenta uma alta concentração de nanoporos lineares orientados nas direções cristalográcas [0001] e [01-10], bem como um lme no nanoporoso. Para compressões maiores do que 4% com relação ao parâmetro de rede, foi observada uma distorção estrutural nas regiões menos densas do material poroso, mostrando uma tendência à mudança de fase localizada. O coe- ciente de Poisson calculado dos nanoporos orientados na direção [0001] foi negativo. Isto signica que quando o material poroso foi tracionado, expandiu-se transversalmente. Já quando comprimido, o material contraiuse na direção transversal. Os materiais que possuem esta característica são conhecidos como materiais auxéticos. Nossos resultados mostram que o valor do gap de energia foi modulado pelas deformações biaxiais com uma tendência oposta ao bulk. A densidade dos estados eletrônicos conrmou nossas observações. A tendência estrutural inversa da superfície dos nanoporos é o principal mecanismo para o comportamento inverso do gap sob compressão e tração. Dentro do nosso conhecimento, este é o primeiro reporte de um comportamento inverso do gap de energia de estruturas de ZnO sob compressão e tração biaxial. Nossos resultados sugerem que a nanoporosidade, conjuntamente com tra- ção e compressão biaxial, podem ser empregadas como um método dentro da engenharia de gap para customizar materiais funcionais que requerem controle da atividade eletrônica.<br>This work investigated, systematically, the structural and electronic properties of nanoporous zinc oxide, under biaxial strain, through rst-principles methods, based on total energy ab initio calculations using Density Functional Theory. The system was in a massive nanopore concentration regime. We studied linear pores in [0001] and [01-10] direction and a porous thin lm. Using a biaxial tension above 4% of the ZnO bulk lattice parameter, we observed a distortion resulting in a local phase change region in the material's structure. The calculated Poisson's coecient was negative for the [0001] pore. When stretched, they become thicker in the perpendicular direction to the applied force. These materials are known as auxetic. Our results show that the energy band gap value is tuned by the strain with an uncommon opposite trend related to the bulk. The density of electronic states conrmed the energy gap modulation. The structural inverse trend of nanopores surface is the principal mechanism for gap inverse behavior under compressive and tensile strain. From the best of our knowledge, this is the rst report about opposite Egap trend in strained nanopores. Our results suggest that nanoporosity and biaxial strain could be employed as a method within the band gap engineering for tailored functional matexi rials that require control of the electronic activity.

Nicotinic acetylcholine receptor (nAChR) stimulation has been found to enhance sensorimotor gating and the trial-specific store of mutable information known as working memory. Working memory function is dependent upon effective stimulus filtering, which leads to the question as to whether nAChR agonists augment working memory function directly, or whether this effect is mediated indirectly through a strengthening of sensorimotor gating. In the present studies, the C57BL/6J and 129X1/SvJ strains of inbred mice were tested at 2 and 8 months of age in the pre-pulse inhibition paradigm (PPI) and the working memory version of the Morris Water Maze task (MWM). The prototypic and non-selective nAChR agonist, nicotine (0.5-2.0 mg/kg), and the α4β2 nAChR subtype specific agonist, RJR-2403 (0.06-0.54 mg/kg), were employed for cholinergic stimulation. Nicotine administration, but not RJR-2403, tended to enhance PPI in 2 month, but not 8 month-old animals. Both nicotine and RJR-2403 were ineffective in modulating working memory function. Hence, with these strains, at these ages, in these paradigms, and at these particular drug dosages, sensorimotor gating and working memory do not appear to be correlated processes nor does nAChR stimulation appear to modulate either process within these experimental parameters. This research demonstrates the importance of fully characterizing the dosage spectrum of drugs in animals commonly used in behavioural testing and, thus, further research into this area is warranted.<br>L'activation des récepteurs nicotiniques pour l'acétylcholine (nAChR) accroît la filtration des stimuli sensori-moteurs ainsi que la mémoire de travail. Le fait que la mémoire de travail soit dépendante de la filtration des stimuli soulève la question à savoir si les agonistes des nAChR joue un rôle direct ou indirect via le renforcement de la filtration des stimuli. Nous avons utilisé deux espèces de souris (C57BL/6J et 129X1/SvJ) consanguines âgées de 2 et 8 mois dans les tests de pré pulse inhibition (PPI) ainsi que dans une version du Morris water maze (MWM) pour la mémoire de travail. La nicotine (agoniste non sélectif), ainsi que le RJR-2403 (agoniste spécifique) furent utilisés pour la stimulation cholinergique. Les résultats révèlent que la nicotine et non le RJR-2403 a produit une tendance à l'augmentation des performances dans le PPI chez les souris âgées de 2 mois, exclusivement. De plus, la nicotine et le RJR-2403 furent inefficace dans la modulation des fonctions de la mémoire de travail. En résumé, il semble que la filtration de stimuli sensori-moteurs ainsi que la mémoire de travail ne seraient pas des processus en corrélation et que l'activation des nAChR ne module pas ces processus, du moins, avec les espèces de souris, l'âge, les tests comportementaux ainsi que les drogues utilisés. Davantage de recherche est nécessaire pour clarifier ces incertitudes. fr

With each heartbeat, major arteries experience circumferential expansion due to internal pressure changes. This pulsatile force is called cyclic strain and has been implicated in playing a pivotal role in the genetic regulation of vascular physiology and pathology. This dissertation investigates the hypothesis that in human umbilical vein endothelial cells (HUVEC), pathological levels of cyclic strain activate the c-Myc promoter, leading to c-Myc transcription and downstream gene induction. To determine expression and time-dependency of c-Myc in HUVEC, mRNA and protein expression of c-Myc under physiological (6-10% cyclic strain) and pathological conditions (20% cyclic strain) were studied. Both c-Myc mRNA and protein expression increased more than three-fold in HUVEC (P4-P5) cyclically-strained at 20%. This expression occurred in a time-dependent manner, peaking in the 1.5-2 hour range and falling to basal levels by 3 hours. Subsequently, the mechanism of c-Myc transcription was investigated by using specific inhibitors to modulate c-Myc transcriptional activation. These compounds, obtained from the University of Arizona Cancer Center, attenuated cyclic-strain-induced c-Myc transcription by about 50%. Having established this reduction in expression, it was investigated how these effects modulate downstream genes that are regulated by c-Myc. The results indicate that direct targeting of the c-Myc promoter may decrease stretch-induced gene expression of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA) and heat shock protein 60 (HSP60). These findings may help in the development of a novel therapeutic opportunity in vascular diseases.

Gut microbiota play a critical role in maintaining human intestinal homeostasis and host health. Bacterial extracellular vesicles are key players in bacteria-host communication as they allow delivery of effector molecules into the host cells. The aim of this thesis was to evaluate the immunomodulatory activity of extracellular vesicles (OMVs) released by two microbiota strains, the probiotic strains Escherichia coli Nissle 1917 (EcN) and the commensal ECOR12. Results obtained using in vitro and ex vivo models of intestinal barrier demonstrated that EcN and ECOR12 OMVs were able to be internalized in the Caco-2 cell line and also immunomodulate through the intestinal epithelium. In addition, OMVs released by Gram-negative bacteria can carry many ligands of PPRs, which are key components of innate immunity, and we have demonstrated that part of the immune responses triggered after EcN and ECOR12 OMVs stimulations were mediated by the activation of NOD1-signalling pathways at early endosomal level by bacterial peptidoglycan contained within OMVs. On the other hand, using an in vivo model of colitis in mice induced by dextran sodium sulphate (DSS), we confirmed the anti- inflammatory properties and the beneficial effect on the intestinal barrier exerted by EcN OMVs (5 µg/day), that were able to counteract most of the inflammatory damages caused by the DSS intake. Finally, we also tested the effect of secreted factors released by EcN on Salmonella enterica serovar Typhymurium infection, two pathogenic bacteria with high impact on health society. Results showed that E. coli supernatants from both EcN and other commensal E. coli strains, but not OMVs reduce Salmonella invasion. Enzymatic treatment confirmed that the active secreted factor is not a protein, DNA or RNA molecules. We also observed that EcN supernatant slightly reduces secretion of invasion Salmonella proteins, and these results suggests that probably EcN secreted factors might diminish Salmonella invasion by interfering with the T3SS secretion system. In conclusion, data presented in this thesis work show that OMVs released by microbiota E. coli strains have a key role in modulating host immune responses and they have a key role to maintain the intestinal homeostasis.

In this study different bioactive agents were used to investigate their single and combined effects on biomechanical properties of osteoporotic bone. Estrogen, the most common hormon replacement therapy (HRT) agent, was used in single and combined with raloxifen, a well known osteoporosis drug. Despite their high clinical uses, they have not been tried before, in combination. They act as agonist of each other in bone and antagonist of each other in uterus and mammary glands. Hence it was expected to prevent HRT side effects by using combinations while enhancing the healing on osteoporotic bone. So, the study was designed to see the interaction effects of these two agents on bone and uterus, to observe the mechanical behaviour upto fracture, and to investigate the bone mechanical properties by strain gauges and bending theory with ovariectomized rat model. Second approach to osteoporosis treatment, VitK2 was chosen to be used alone or in combination with raloxifen in same model. Although recent studies mentioned the effects of VitK2 on bone, its rebuilding or repair effect was not completely established. So, VitK2-bone relation was aimed to be clarified with the project.VitK2 raloxifen combination was also a new study, that has not been carried out so far. As a result of mechanical tests, it was found that E+R combination is the most effective treatment. All treatment&amp<br>#8217<br>s were resulted in numerically (though not statistically significant) higher values on femur mechanical properties, and significantly better on tibia compared to the untreated controls. VitK2 performs well in energy absorption upto fracture, but worse in others (PL, YL etc.) compared to other treatments indicating that it plays a specific role in modifying bone structure thus, rendering bone stronger under high stress. However, similar to estrogen case, its combination with raloxifen performs better than its individual administration. With combinations it was aimed to reduce the adverse effects of estrogen on uterus and mammary glands by using raloxifen. This idea appears to be achieved with better histological results of uterus in combinations than estrogen groups. Additionally it was observed that direct strain data obtained by strain gauge experiments can be more informative than theoretical model in calculating modulus of elasticity, and shown that shear contribution can be neglected if depth/span ratio and set up dimensions properly chosen. Biochemical analysis of the blood showed an increment in bone formation (ALP activity) compared to both controls. ALP activity was the highest in R group, which was lower in combinations. Thus existence of a different mechanism in osteoporotic bone repair in combinations was suggested.

B cells play crucial roles in the development of the two human autoimmune diseases, type 1 diabetes (T1D) and systemic lupus erythematosus (SLE). In the past decade, numerous studies showed positive responses of B cell depletion therapies in these two diseases. However, the beneficial effects are temporary and accompanied with adverse events. In this dissertation, we aimed to identify novel targets for a better modulation of disease development using mouse models. These diseases have circulating autoantibodies that are mostly mutated with an IgG isotype, indicating B cells that are producing them have been through the process of affinity maturation. Activation-induced cytidine deaminase (AID) is a core enzyme that regulates somatic hypermutation (SHM) and class switch recombination (CSR), the two key mechanisms in affinity maturation. We showed that genetic ablation of AID significantly inhibited the development of TID in NOD mice. Homologous recombination (HR) pathway is important for the repair of AID-induced DNA double strand breaks during CSR. 4,4'-Diisothiocyano-2,2'-stilbenedisulfonic acid, also known as DIDS, is a small molecule that inhibits HR pathway and subsequently leads to apoptosis of class switching cells. DIDS treatment remarkably retarded the progression of TID, even when started at a relatively late stage, indicating the potential of this treatment for disease reversal. In both approaches, we observed a notable expansion of CD73+ B cells, which exerted an immunosuppressive role and could be responsible for T1D resistance. Next we examined the effect of targeting affinity maturation through these two approaches in lupus-prone mice. The genetic abrogation of AID in BXSB mice significantly ameliorated lupus nephritis and prolonged their lifespan. AID-deficient mice also exhibited improvement on disease hallmarks with increased marginal zone B cells and more normal splenic architecture. DIDS treatment notably reduced class switching when B cells were stimulated in vitro. However, the administration of DIDS did not strikingly alter the course of SLE in either BXSB mice or MRL/lpr mice. These findings demonstrated that affinity maturation could be a potential target for T1D and SLE, while further explorations into targeting other components in the repair pathway are warranted for SLE. Lastly, we assessed the effect of maternal AID modulation on the SLE development in the offspring using BXSB mouse model. Interestingly, the absence of maternal AID resulted in offspring that developed significantly more severe lupus nephritis compared to control. The offspring born to AID-deficient dams also exhibited elevated levels of pathogenic autoantibodies and exacerbated disease features. Therefore, the modulation of maternal AID could influence the SLE development in the offspring, and future investigations are needed to determine the underlying mechanisms responsible for the disease acceleration.<br>Doctor of Philosophy<br>The failure of the immune system to differentiate self from non-self leads to the development of autoimmune diseases. Type 1 diabetes (T1D) and systemic lupus erythematosus (SLE) are complex autoimmune diseases affecting millions of people in the world. Despite intensive research regarding these two diseases, no known cure is available indicating an imperative need for the development of novel therapies. With the importance of B cells in the pathogenesis of these two diseases, intensive research focused on whole B cell depletion therapies. However, these therapies exhibited high risks of infections as a result of depleting all the B cells. In this dissertation, we sought to selectively target specific B lymphocyte subsets that are crucial contributing factors in the development of T1D and SLE. While the effect of therapeutic treatment varied among different mouse models, the genetic manipulation of specific B cells successfully retarded the progression of both T1D and SLE and extended the lifespan of the mice. Further studies shed light on the possible mechanisms that are responsible for the disease inhibition. These data proved that targeting specific B cell compartment could be a potential disease management in T1D and SLE patients. In addition, using the established mouse model, we demonstrated the modulation of maternal factors significantly impact the SLE development in the offspring. Future experiments to identify the underlying mechanisms could provide more targets for the therapeutic development.

The use of Lactic Acid Bacteria (LAB), such as Lactococcus lactis (LL), as DNA delivery vehicles represents an interesting strategy as they are regarded as safe. Wild type (wt) LL or recombinant invasive LL, were able to trigger DNA expression by epithelial cells both in vitro and in vivo. However, important information about how LL can transfer DNA plasmids is still missing. Therefore, we decided to construct a new recombinant invasive LL strain expressing mutated Internalin A (mInlA) from the pathogen Listeria monocytogenes to understand the manner by which the DNA is transferred to mammalian cells. mInlA expression was detected by FACS analysis and LL-mInlA strain showed to be more invasive than the wt strain after co-incubation assays with non-confluent or polarized intestinal epithelial cells (IECs). Confocal microscopy confirmed the invasive status of LL-mInlA which demonstrated to deliver more efficiently the eukaryotic expression vector coding the allergen β-lactoglobulin, pValac:BLG, in vitro to IECs and to dendritic cells (DCs). LL-mInlA was also capable to transfer pValac:BLG to DCs across a monolayer of differentiated IECs. In vivo, invasive lactococci tended to increase the number of mice expressing BLG. Moreover, noninvasive or invasive LL-mInlA stimulated the secretion of the pro-inflammatory cytokine IL-12 in DCs and, in vivo, after oral or intranasal immunization trials, non-invasive LL polarized the immune response more in the type 1 direction while invasive LL generated a Th2-type response in immunized animals. All these data gives new insights on the mechanism of lactococci uptake for delivery of therapeutics.

Orientador: Katia Sivieri<br>Orientador no exterior: Lene Jespersen<br>Banca: Suzana Marta Isay Saad<br>Banca: Adriane Elisabete Antunes de Moraes<br>Banca: Carla Raquel Fontana Mendonça<br>Banca: Marcia Pinto Alves Mayer<br>Resumo: Diversos subprodutos de frutas tropicais, os quais são frequentemente descartados pelas indústrias alimentícias, apresentam elevado conteúdo de fibras e de compostos bioativos. Estes compostos, assim como determinadas cepas probióticas e algumas pectinas presentes nos subprodutos, têm o potencial de modular a microbiota intestinal humana, promovendo diversos benefícios à saúde, tais como a atenuação de parâmetros relacionados à obesidade. O objetivo deste trabalho foi avaliar os efeitos da pectina do limão, de subprodutos secos de frutas tropicais (acerola e camu-camu) e de diferentes cepas probióticas (Bifidobacterium longum BB-46, Lactobacillus acidophilus LA-5 and L. paracasei L-431) na microbiota intestinal de indivíduos eutróficos e obesos utilizando o Simulador do Ecossistema Microbiano Humano (SEMH®). Seis artigos foram desenvolvidos a fim de se responder os objetivos propostos. O primeiro artigo trata-se de uma mini-revisão e, os cinco restantes, artigos originais. No primeiro artigo, sumarizou-se os principais achados sobre a composição da microbiota intestinal de obesos e, revisou-se as novas estratégias de modulação da microbiota intestinal em favor do tratamento da obesidade. Foi possível mostrar que a composição da microbiota intestinal é essencial para o entendimento de mecanismos envolvidos na etiologia da obesidade e que, várias estratégias, tais como, o consumo de prebióticos e probióticos, bem como a prática de atividade física moderada e regular, podem modu... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: Several by-products of tropical fruits, which are often discarded by the food industry, have high fibre content and bioactive compounds. These compounds, as well as certain probiotic strains and some pectins present in the by-products, have the potential to modulate the human gut microbiota, promoting several health benefits, including the attenuation of obesity parameters. The aim of this work was to evaluate the effects of lemon pectin, dried by-products of tropical fruits (acerola and camu-camu), as well as of different probiotic strains (Bifidobacterium longum BB-46, Lactobacillus acidophilus LA-5 and L. paracasei L-431) on the gut microbiota from healthy-weight and obese individuals using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). Six articles were developed in order to meet the proposed aims. The first article is a mini-review and the other five are original articles. In the first article, we summarized the principal findings on obesity-related microbiota composition and reviewed new strategies for gut microbiota modulation in favour of obesity treatment. We showed that the composition of the microbiota is essential for understanding the mechanisms involved in the aetiology of obesity and, that several strategies, such as consumption of probiotics and prebiotics, as well as moderate and regular physical activity, can modulate the gut microbiota in favour of obesity treatment. In the second article, the chemical composition, the total phenolic co... (Complete abstract click electronic access below)<br>Resumé: Flere biprodukter fra tropiske frugter, som ofte kasseres af fødevareindustrien, har højt fiberindhold og bioaktive forbindelser. Disse forbindelser, såvel som visse probiotiske stammer og nogle pektiner, der er til stede i biprodukterne, har potentialet til at modulere den humane tarmmikrobiota, der fremmer flere sundhedsmæssige fordele, herunder dæmpning af fedmeparametre. Formålet med dette arbejde var at evaluere virkningerne af citronpektin, tørrede biprodukter fra tropiske frugter (acerola og camu-camu), samt forskellige probiotiske stammer (Bifidobacterium longum BB-46, Lactobacillus acidophilus LA-5 og L. paracasei L-431) på tarmmikrobioten fra raske og overvægtige individer, under anvendelsen af den humane intestinale mikrobielle økosystem simulator (SHIME®). Seks artikler blev udviklet for at opfylde de foreslåede mål. Den første artikel er en mini-anmeldelse, og de andre fem er originale artikler. I den første artikel opsummerede vi de vigtigste fund om fedme-relateret mikrobiota sammensætning og gennemgik nye strategier for tarmmikrobiota modulering til fordel for fedmebehandling. Vi viste, at mikrobiotas sammensætning er afgørende for forståelsen af mekanismerne i fedmens etiologi, og at flere strategier, såsom forbrug af probiotika og præbiotika, samt moderat og regelmæssig fysisk aktivitet kan modulere tarmmikrobiotaten til fordel for fedme behandling. I det anden artikel blev den kemiske sammensætning, de samlede phenolforbindelser og in vitro antioxidantkapac<br>Doutor

The solar minimum of 2009 has been identified as an exceptional event with regard to cosmic ray (CR)modulation, since conditions in the heliosphere have reached unprecedented quiet levels. This unique minimum has been observed by the Earth–orbiting satellite, PAMELA, launched in June, 2006, from which vast sets of accurate proton and electron preliminary observations have been made available. These simultaneous measurements from PAMELA provide the ideal opportunity to conduct an in–depth study of CR modulation, in particular charge–sign dependent modulation. In utilizing this opportunity, a three–dimensional, steady–state modulation model was used to reproduce a selection of consecutive PAMELA proton and electron spectra from 2006 to 2009. Thiswas done by assuming full drifts and simplified diffusion coefficients, where the rigidity dependence and absolute value of themean free paths for protons and electrons were sequentially adjusted below 3 GV and 300 MV, respectively. Care has been taken in calculating yearly–averaged current–sheet tilt angle and magnetic field values that correspond to the PAMELA spectra. Following this study where the numerical model was used to investigate the individual effects resulting from changes in the tilt angle, diffusion coefficients, and global drifts, it was found that all these modulation processes played significant roles in contributing to the total increase in CR intensities from 2006 to 2009, as was observed by PAMELA. Furthermore, the effect that drifts has on oppositely charged particles was also evident from the difference between the peak–shaped time profiles of protons and the flatter time profiles of electrons, as is expected for an A < 0 polarity cycle. Since protons, which drift into the heliosphere along the heliospheric current–sheet, haven’t yet reached maximum intensity levels by 2008, their intensities increased notably more than electrons toward the end of 2009. The time and energy dependence of the electron to proton ratios were also studied in order to further illustrate and quantify the effect of drifts during this remarkable solar minimum period.<br>Thesis (M.Sc. (Physics))--North-West University, Potchefstroom Campus, 2012.

Thesis (M. S.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2008.<br>Committee Chair: John D. Cressler; Committee Member: John Papapolymerou; Committee Member: Shyh-Chiang Shen.

Early innate response of intestinal epithelial cells is the first line defense against enteric pathogens. Toxoplasma gondii infections acquired naturally via the peroral route, encounter intestinal epithelial cells early post-infection. Although the population structure of T. gondii is known to be highly clonal, clinical strains of T. gondii have been classified into three genotypes based on their virulence. In this study we investigated whether human intestinal epithelial cell immune response to T. gondii is virulence dependent. We demonstrated distinct virulence of the three T. gondii genotype strains evaluated in human intestinal epithelial cells by their capacity to replicate and induce host cell cytotoxicity. The early host innate mechanisms such as activation of signaling pathways and induction of innate effectors were likewise differentially elicited by the three T. gondii strains. Low levels of TLR dependent NF-kB activation and a failure to rapidly up-regulate innate cytokine and chemokine genes was observed after virulent Type I strain infection. In contrast, early innate response to the less virulent Type II strain was rapid, efficient and led to high levels of IL-8 and IL-6 secretion, whereas response to Type III parasites was intermediate. Early expression of b-defensin 2 gene was suppressed specifically by virulent Type I strain and its activation prior to infection in intestinal epithelial cells led to decreased parasite viability. These findings provide evidence for T. gondii strain virulence dependent down-modulation of early human intestinal epithelial cell innate responses and highlight the importance of these cells in host defense against this infection.<br>Doctorat en Sciences biomédicales et pharmaceutiques<br>info:eu-repo/semantics/nonPublished

The Voyager 1 spacecraft is now about 25 AU beyond the heliospheric termination shock and soon it should encounter the outer boundary of the heliosphere, the heliopause. This is set to be at 120 AU in the modulation model used for this study. This implies that Voyager 1, and soon afterwards also Voyager 2, should be able to measure the heliopause spectrum, to be interpreted as the lowest possible local interstellar spectrum, for low energy galactic electrons (1 MeV to 120 MeV). This could give an answer to a long outstanding question about the spectral shape (energy dependence) of the galactic electron spectrum at these low energies. These in situ electron observations from Voyager 1, until the year 2010 when it was already beyond 112 AU, are used for a comparative study with a comprehensive three dimensional numerical model for the solar modulation of galactic electrons from the inner to the outer heliosphere. A locally developed steady state modulation model which numerically solves the relevant heliospheric transport equation is used to compute and study modulated electron spectra from Earth up to the heliopause. The issue of the spectral shape of the local interstellar spectrum at these low energies is specifically addressed, taking into account modulation in the inner heliosheath, up to the heliopause, including the effects of the transition of the solar wind speed from supersonic to subsonic in the heliosheath. Modulated electron spectra from the inner to the outer heliosphere are computed, together with radial and latitudinal profiles, focusing on 12 MeV electrons. This is compared to Voyager 1 observations for the energy range 6–14 MeV. A heliopause electron spectrum is computed and presented as a new plausible local interstellar spectrum from 30 GeV down to 10 MeV. The comparisons between model predictions and observations from Voyager 1 and at Earth (e.g. from the PAMELA mission and from balloon flights) and in the inner heliosphere (e.g. from the Ulysses mission) are made. This enables one to make conclusions about diffusion theory applicable to electrons in the heliosphere, in particular the rigidity dependence of diffusion perpendicular and parallel to the local background solar magnetic field. A general result is that the rigidity dependence of both parallel and perpendicular diffusion coefficients needs to be constant below P < 0.4 GV and only be allowed to increase above this rigidity to assure compatibility between the modeling and observations at Earth and especially in the outer heliosphere. A modification in the radial dependence of the diffusion coefficients in the inner heliosheath is required to compute realistic modulation in this region. With this study, estimates of the intensity of low energy galactic electrons at Earth can be made. A new local interstellar spectrum is computed for these low energies to improve understanding of the modulation galactic electrons as compared to previous results described in the literature.<br>Thesis (M.Sc. (Physics))--North-West University, Potchefstroom Campus, 2012.

The transport of cosmic rays in the heliosphere is studied by making use of a newly developed modulation model. This model employes stochastic differential equations to numerically solve the relevant transport equation, making use of this approach’s numerical advantages as well as the opportunity to extract additional information regarding cosmic ray transport and the processes responsible for it. The propagation times and energy losses of galactic electrons and protons are calculated for different drift cycles. It is confirmed that protons and electrons lose the same amount of rigidity when they experience the same transport processes. These particles spend more time in the heliosphere, and also lose more energy, in the drift cycle where they drift towards Earth mainly along the heliospheric current sheet. The propagation times of galactic protons from the heliopause to Earth are calculated for increasing heliospheric tilt angles and it is found that current sheet drift becomes less effective with increasing solar activity. Comparing calculated propagation times of Jovian electrons with observations, the transport parameters are constrained to find that 50% of 6 MeV electrons measured at Earth are of Jovian origin. Charge-sign dependent modulation is modelled by simulating the proton to anti-proton ratio at Earth and comparing the results to recent PAMELA observations. A hybrid cosmic ray modulation model is constructed by coupling the numerical modulation model to the heliospheric environment as simulated by a magneto-hydrodynamic model. Using this model, it is shown that cosmic ray modulation persists beyond the heliopause. The level of modulation in this region is found to exhibit solar cycle related changes and, more importantly, is independent of the magnitude of the individual diffusion coefficients, but is rather determined by the ratio of parallel to perpendicular diffusion.<br>PhD (Space Physics), North-West University, Potchefstroom Campus, 2013

碩士<br>國立陽明大學<br>生命科學系暨基因體科學研究所<br>105<br>[PSI+] is the prion form of Sup35, a subunit of the yeast translation termination complex. When multiple [PSI+] strains co-infect a dividing host, only one prevails in the end. The host genetic background is involved in winner selection. In the 5V-H19 background, the VK strain dominated over the VL strain. The order of dominance was reversed in the 74-D-694 background: VK and VL temporarily co-existed, and VL eventually took over. Heat shock proteins could also influence the outcome of strain competition. Over-expressing the Hsp70 proteins Ssa1 or Ssa2 caused VL dominance in both 5V-H19 and 74-D-694. Conversely, deleting the SSA1 gene from 74-D-694 caused VK dominance. Expanding the Glycine/Methionine-rich domain of Sis1, an Hsp40 protein, also changed the dominance relationship in both 5V-H19 and 74-D-694, causing VL to flourish. However, swapping the polymorphic alleles of SSA1 and SIS1 between 5V-H19 and 74-D-694, including cognate promoters, did not change the original background-specific dominance order. Our results demonstrated that differential interaction of heat shock proteins with distinct strain conformations. The fact that swapping alleles of heat shock proteins between 5V-H19 and 74-D-694 were not sufficient to alter background-specific dominance relationships further implied the existence of other unidentified polymorphic cellular factors, which differentially interact with [PSI+] strains to modulate their cellular competition.

博士<br>國立交通大學<br>材料科學與工程學系所<br>105<br>In this thesis, we study how the polarization in complex oxides are affected by the strain. It is discussed in two parts: in the first part, the reversal of the ferroelectric polarization of multiferroic BiFeO3 (BFO) is constrained to enhance the ferroelectric retention, and in the second part flexoelectricity is created through a compositional gradient. Firstly, Non-volatile electronic devices based on magnetoelectric multiferroics have triggered new possibilities of outperforming conventional devices for applications in information storage, the emerging field of spintronics, and sensors. However, ferroelectric reliability issues, such as imprint, retention, and fatigue, must be solved before the realization of practical devices. In this study, everlasting ferroelectric retention in the heteroepitaxial constrained multiferroic mesocrystal is reported, suggesting a new approach to overcome the failure of ferroelectric retention. Studied by scanning probe microscopy and transmission electron microscopy, and supported via phase-field simulations, the key to the success of ferroelectric retention is to prevent the crystal from ferroelastic deformation during the relaxation of the spontaneous polarization in a ferroelectric nanocrystal. On the other hand, complex oxides present versatile properties, such as ferroelectricity, superconducting, and colossal magnetoresistance (CMR), and have been widely studied. To improve or manipulate the properties, complex oxides are designed and well grown into different structures, from the thin film of a single material to hetero-structures combining at least two materials. With the advance of growth techniques, the accuracy of growth is controlled on the scale of a unit cell via the assistance of reflection high-energy electron diffraction (RHEED). Utilizing the ability to control the growth at the atomic scale, a non-uniformity with compositional gradient along the out-of-plane (OOP) direction is created. The model system is constituted by SrTiO3 (STO) and LaAlO3 (LAO). Under this circumstance of an OOP compositional gradient, a strain gradient ensues. Polarity discontinuities between STO and LAO are also expected compared to the bi-layer system. Through the coupling among the charge, orbital, and lattice, a spontaneous polarization is created. Since the spontaneous polarization is induced and manipulated by the strain gradient, the behavior is named “flexoelectricity”.

博士<br>國立中山大學<br>光電工程研究所<br>96<br>In this work, we have reported the design, MBE-growth and fabrication of strain-balanced n-type modulation-doped (MD) InGaAlAs/InGaAs multiple quantum wells laser/SOAs on InP. The quantum well contains a lattice-matched InGaAs core, a compressive-strained InGaAs padding, and a tensile-strained InGaAlAs spacer. Two kinds of samples having similar structure but different fundamental transition wavelength of 1.55 μm and 1.48 μm are separately prepared for investigating their characteristics in optical amplification under forward bias and electro-absorption under reversed bias. Also, the technique of growing high-quality InGaAlAs with solid-source molecular beam epitaxy has been established and the resulting InGaAlAs bulk and QWs samples are extensively characterized by double-crystal X-ray diffraction, transmission electron microscopy, electroluminescence, and photoluminescence measurements. For λ = 1.55 μm samples, ridge-waveguide lasers of Fabry-Perot (FP) type and tilted-end-facet (TEF) type were fabricated by a new developed multi-step wet-etching process. When injection current density > 20A/cm^2, electroluminescence spectra show higher optical gain for the quantum well e1-hh2 transition at λ = 1460 nm than the e1-hh1 transition at λ = 1550 nm. The FP laser shows a lasing peak of λ = 1514 nm at threshold. Additional lasing wavelength at λ =1528 nm and 1545 nm were observed sequentially as the injection current increased. However, for the TEF laser, only the emission at λ = 1511 nm was observed. These TE-polarized lasing wavelengths are consistent with the δ-like absorption peaks in photocurrent spectra. The lasing performance is possible attributed to optical transitions within quantum dots/wires which are formed by the strain-field profile and alloy segregation/migration. For λ = 1.48 μm samples, the differential absorption spectroscopy, which measures the change of transmission (ΔT/T) in the presence of electric field, is used to study the electro-absorption modulation behavior of MD-SOA’s. A sample with n-type modulation-doping amounting to a sheet density of 3.5 × 10^11 cm^-2 per QW and combining with a hole-stopping barrier represents the largest chirp parameter (Δn/Δk) under reversed bias, which offers an excellent platform to realize electro-refractive devices with larger refractive index changes (Δn) but lower differential absorption (Δα) near λ = 1.55 μm, which is also our interested region of operation. In addition, we have succeeded in reducing the length of conventional constant-width multimode interference (MMI) coupler of K = 0.15 and 0.28 more than 32% by a novel stepped-width design concept. By extending the stepped-with idea, we show that it is possible to obtain 2x2 waveguide couplers with new power splitting ratios of 7%, 64%, 80% and 93% for cross coupling by cascading two short MMI sections. We further realize freely chosen power splitting ratio by interconnecting a pair of unequal-width waveguides as the phase-tuning section into the middle of two short MMI sections. These compact and low loss MMI-based devices use only rectangular geometry without any bent, curved, and tapered waveguides. They offer valuable new possibilities for designing waveguide-based photonic integrated circuits.

碩士<br>國立臺灣科技大學<br>電子工程系<br>91<br>Contactless electroreflectance (CER)、Piezoreflectance (PzR) and Photoluminescence (PL) measurements of the InGaAsP/InP strained-Layer Multiple Quantum Well and the InGaAsP/ InGaAsP strain-compensated Multiple Quantum Well as a function of temperature in the rang of 15-300 K have been carried out. A careful analysis of the PzR and CER spectra has led to the identification of various excitonic transitions energy (EmnH(L)) between the mth conduction band state and the nth heavy(light)-hole band state. The parmeters that describe the temperature dependence of EmnH(L)(T) are evaluated and compared with that of the bulk material. A detailed study of the temperature variation of excitonic transition energy indicates that the main influence of temperature on quantized transition is through the temperature dependence of the band gap of the constituent material in the well. The temperature dependence of the broadening of Γ11H(T) and Γ11L(T) are evaluated and compared with that of the bulk material.

博士<br>國立清華大學<br>電子工程研究所<br>91<br>1.3 and 1.55 μm semiconductor laser are most popular for the application in subscriber networks and optical interconnection systems. 1.3 μm-based semiconductor lasers have lower dispersion but higher attenuation compared to that of 1.55 μm-based semiconductor lasers. Besides, one of the most troublesome components in present laser modules is a thermoelectric cooler, which both makes the modules expensive and complicated but also may degrade its long-term reliability. In order to overcome these problems, 1.3 μm high power and without thermoelectric cooler AlGaInAs with high conduction band offset than conventional GaInAsP are used as light source in optical interconnection systems. The higher conduction band offset can alleviate the Auger recombination that will affect the performance of long wavelength laser diode so that increase the light output power. In this thesis, we first investigate the 1.3 μm AlGaInAs/AlGaInAs strain compensated multiple-quantum well. The compress strain wells which have several merits in optical and reduction of threshold current and compensated by tensile barriers to increase the well number. The threshold current density and differential quantum efficiency for the as-cleaved BA LDs with a 900 μm cavity length are 400 A/cm2 and 22%, respectively. We also calculate the internal quantum efficiency, internal optical loss, and threshold gain as 54.1%, 6.5cm-1, and 45 cm-1. The characteristic temperature of 75 K between 20 and 80 ℃, and the longitudinal mode oscillation has a red-shift rate of 0.5 nm/℃ under 25 ℃ and 60 mA. Graded index separate confinement heterostructure (GRINSCH) has superior optical confinement and smooth electric field intensity distribution than that of step (or abrupt) structure. Besides, to tailor the electric field intensity distribution in the abrupt junction between InGaAs and InP, we introduce a thin graded composition (GC) GaInAsP layer between InGaAs and InP. With the GC GaInAsP layer, the 3μm-ridge-stripe LDs without facet coating under the CW operation exhibit a lower threshold current of 14 mA, a lower resistance of 7.8 Ω, a higher differential quantum efficiency of 47.46%, a higher characteristic temperature of 79 K in the range from 20 to 80 ℃and 42 K in 80 to 100 ℃, and a red-shift rate of 0.43 nm/℃, which are better than those of the LDs without the GC GaInAsP layer. The differential gain for LDs with GC GaInAsP layer is about 8.45x10-16 cm2 for 300-μm cavity length and decreases to 4.68x10-16 cm2 for 900 μm. The relaxation oscillation frequency is about 9.2 GHz under the 80 mA driving current at 20℃. With neglecting the effect of damping factor and couple loss, the calculated 3-dB frequency width can reach to 14.26 GHz under the 80 mA driving current at 20℃. More recently, modulation doping in the barriers will serve several merits such as lower transparency carrier density and higher optical gain. The BA LDs with this optimum concentration of 5 x 1018 cm-3 in the doped barriers exhibit the threshold current density, internal quantum efficiency, internal optical loss, threshold gain (for the cavity length of 300 μm), and transparency current density of 215 A/cm2, 61.7%, 7.5 cm-1, 47.5 cm-1, and 71 A/cm2, respectively, which are much better than those of the LDs with undoped and other doping concentrations in the barriers. In addition, the ridge-stripe LDs without facet coating have a lower threshold current of 12.5 mA, an enhanced differential quantum efficiency of 52.3%, a characteristic temperature of 85 K in the temperature range from 20 to 80 ℃, and a red-shift rate of 0.38 nm/℃ under the CW operation. The relaxation oscillation frequency with driving current of 80 mA under 20 ℃ is about 9.9 GHz. Without consideration to damping factor and couple loss, the calculated 3-dB bandwidth is about 15.34 GHz. InAsP/InP/InGaP MQW has higher conduction band offset than that of GaInAsP MQW. In this thesis, InAsP/InP/InGaP with n-type doping laser diode is also investigated. The optimum doping concentration is 1x1018 cm-3 in the Si-doped barrier and InP intermediate layer. The threshold current density can be reduced to 0.8 kA/cm2 for 900-μm-cavity length for these optimum thickness and doping concentration. In addition, the LDs exhibit an enhanced differential quantum efficiency of 25% and an internal quantum efficiency of 31%. The internal optical loss can be also lowered to 19.01 cm-1. The threshold gain will be reduced to 43.07 cm-1 compared to 44.1 cm-1 for the LDs with undoped active region.

碩士<br>明新科技大學<br>精密機電工程研究所<br>102<br>This research is mainly to develop a measurement and control system for bolt torque. It uses pulse width modulation (PWM) technique to drive a DC motor and measures bolt torque magnitude with strain gauge. The tension of the bolt is then measured and controlled by quickly positioning process with the driving motor. Microchip PIC16F877 is used as the microprocessor of the system for measuring bolt torque. The uni-axial strain gauge is used in the system for sensing the bolt torque which can be displayed on an LCD display. It shows the tension condition for the bolt during the process. In order to enhance the processing speed of the bolt, the PWM technique is used to control the forward and reverse speeds of the motor for driving torque. It is achieved in this research to adjust the bolt torque to a preset value by applying the system with measuring deformation of strain gauge for the bolt torque and then control it with a motor.

Dissertação de mestrado em Genética Molecular<br>The yeast Saccharomyces cerevisiae has emerged as one of most important model organisms to clarify the environmental and genetic factors associated with aging. The nutrientsignaling pathways involved in the regulation of yeast chronological lifespan (CLS) is affected by the composition of the culture medium and therefore, culturing cells in different media leads to differences in CLS. Manipulation of components of the culture medium, such as reducing glucose concentration, is known to extend CLS. However, other componentes of the culture medium such as amino acids and the products of fermentation have also been implicated in the regulation of CLS. In auxotrophic S. cerevisiae strains CLS is highly affected by the concentration of the auxotrophy-complementing amino acids. Ammonium (NH4 +), a commonly used nitrogen source, is another extrinsic factor affecting CLS regulation in S. cerevisiae. Cells starved for auxotrophic-complementing amino acids and aged in water are particularly sensitive to ammonium-induced cell death and this process is mediated through the regulation of the evolutionary conserved pathways TOR, PKA and SCH9. This effect of ammonium on aging yeast depends on the specific amino acid they are deprived off with starvation for leucine enhancing ammonium-induced CLS shortening (Santos et al., 2013). This work aimed to further elucidate the role of ammonium as a nutrient capable of regulating CLS of S. cerevisiae in culture medium and unveil its interplay with other extrinsic factors, such as pH or glucose, and with the evolutionary conserved pathways. Moreover, the role of glutamine as another rich nitrogen source in aging media was also addressed. The results showed that cells grown with low concentrations of auxotrophy-complementing amino acids and in the presence of ammonium lost viability very fast displaying a very short CLS which was accompanied by an inhibition of a proper cell cycle arrest in G0/G1 phase. Furthermore, the CLS shortening effect induced by amino acid restriction was completely reverted by removing ammonium from the aging medium. It was also observed that buffering media not only to pH 6.0 but also to pH 3.4 largely extended CLS in media with high concentrations of auxotrophycomplementing amino acids (HAA) and with or without NH4 + and in media with low concentrations of auxotrophy-complementing amino acids (LAA) without NH4 +. Buffering LAA media in the presence of NH4 + to either pH 3.4 or pH 6.0 had no measurable effect on CLS. Reducing glucose concentration in media (from 2% to 0.5%) showed that the beneficial effect of calorie restriction (CR) is only observed in LAA medium and in the presence of NH4 +. In fact, the absence of ammonium seems to be so effective in extending CLS that no effect could be observed by imposing CR conditions. In conclusion, this data suggest that ammonium, independently of glucose concentration and pH in the medium during aging is a major responsible for the CLS shortening under amino acid restriction conditions. The deletion of tor1Δ, ras2Δ and sch9Δ showed that Tor1p, Ras2p and Sch9p seem to mediate cell death in LAA media whereas in HAA media Ras2p and Sch9 mediated survival and Tor1p had no effect. Since ammonium-induced cell death is involved in different human disorders that are accompanied by hyperammonemia, these results may also provide new insights into the understanding of the cell molecular bases triggering cell death in such pathologies. Furthermore, the study of the interaction of amino acids and ammonium in the survival of S. cerevisiae offers new approaches for the improvement of wine fermentations.<br>A levedura Saccharomyces cerevisiae tem-se destacado como um dos organismo modelo mais importantes para clarificar os factores genéticos e ambientais associados ao envelhecimento. As vias de sinalização de nutrientes envolvidas na regulação da longevidade cronológica são afectadas pela composição do meio de cultura e portanto, a cultura de células em diferentes meios leva a diferenças na longevidade cronológica. Como descrito na literatura, a manipulação dos componentes do meio de cultura pode extender a longevidade cronológica, como acontece com a redução da concentração de glucose. Contudo, também outros componentes do meio de cultura, tal como, os aminoácidos e os produtos da fermentação de leveduras tem sido associados á regulação da longevidade cronológica. Em estirpes auxotróficas de S. cerevisiae a longevidade cronológica é principalmente afetada pela concentração de aminoácidos essenciais (correspondentes ás marcas auxotróficas). O amónio (NH4 +), uma fonte de azoto comum, é outro factor extrínseco que afecta a regulação da longevidade cronológica de S. cerevisiae em meio de cultura. Células cultivadas até á fase estacionária com restrição de aminoácidos essenciais e posteriormente transferidas para água são sensíveis á adição de amónio, ocorrendo um decréscimo significativo na longevidade cronológica. Este processo de morte celular induzida por amónio é mediado pelas vias de regulação TOR, PKA and SCH9 e depende do aminoácido para o qual há restrição, uma vez que se verficou que a diminuição da longevidade é mais acentuada quando há uma restrição especifica de leucina (Santos et al., 2013). O objectivo do presente trabalho consiste no aprofundamento do estudo do papel do amónio como um nutriente capaz de regular a longevidade cronológica de S. cerevisiae em meio de cultura, nomeadamente na elucidação da interação com outros factores extrínsecos como glucose e pH, e com as vias de sinalização. Além disso, foi também abordado o papel da glutamina como outra fonte de nitrogénio capaz de regular a longevidade. Os resultados mostraram que as células cultivadas em meio com restrição de aminoácidos na presença de amónio perdem rapidamente a viabilidade exibindo uma diminuição da longevidade cronológica a qual é acompanhada por uma inibição da entrada na fase G0/G1 do ciclo celular. Mais ainda, o efeito da diminuição da longevidade cronológica induzida pela restrição de aminoácidos pode ser completamente revertido pela remoção do amónio do meio de cultura. Foi também observado que o tamponamento do meio, tanto a pH 3.4 como pH 6.0, estende a longevidade cronológica em meio com alta concentração de aminoácidos com ou sem a adição de amónio e em meio com baixa concentração de aminoácidos sem adição de amónio. Pelo contrário em meio com baixa concentração de aminoácidos na presença de amónio o pH parece não tem qualquer influência na longevidade cronológica. A redução da concentração de glucose no meio de cultura (de 2% para 0.5%) mostrou que o efeito benéfico da restrição calórica só é observado em meio com baixa concentração de aminoácidos e na presença de amónio. De facto, a ausência de amónio parece ser tão eficaz na extensão da longevidade cronológica que nenhum efeito adicional é observado pela imposição das condições de restrição calórica. Em conclusão, estes resultados sugerem que o amónio, independentemente da concentração de glucose e do pH do meio é o principal responsável pela diminuição da longevidade cronológica sob condições de restrição de aminoácidos. A utilização dos mutantes tor1Δ, ras2Δ e sch9Δ mostrou que Tor1p, Ras2p e Sch9p intervêm na morte celular em meio com baixa concentração de aminoácidos enquanto que em meio com alta concentração de aminoácidos Ras2p e Sch9p contribuem para a sobrevivência celular e Tor1p não tem qualquer efeito. Sabendo que a morte celular induzida por amónio está envolvida em patologias humanas que são acompanhadas de hiperamonémia, estes resultados podem fornecer novas pistas para a compreensão desta patologia. Além disso, o estudo da interação de aminoácidos e amónio na sobrevivência de S. cerevisiae oferece novas abordagens que podem ser relevantes para melhorar as fermentações alcoólicas, em particular as vínicas.

博士<br>國立中興大學<br>食品暨應用生物科技學系所<br>101<br>Lactic acid bacteria are important human commensal microbiota that are considered to be probiotics as they have been shown to reduce pathogenic infections and chronic inflammation. In this study, six strains of lactobacilli were compared for their probiotic potential. These 6 strains showed varying capacities for adhesion, pathogen inhibition and cytokine induction IL(interleukin)-8 and IL-10) in different human epithelial cells, such as primary cultures of buccal cavity cells, and established cell lines derived from epithelia of the pharynx, stomach, intestine, and cervix. After exposure to lactobacilli, secretion of cytokines (IL-10, IL-12p70, interferon-γ, tumor necrosis factor-α, IL-5 and transforming growth factor-β) was induced at varying levels in different cultures of human immune cells, including dendritic cells, monocyte-depleted peripheral blood mononuclear cells, CD14+ cells, CD4+CD25- T cells, and regulatory T-cells (CD4+CD25+ T cells). Growth inhibition of pathogenic strains was detectable in the presence of lactobacilli in vitro. Using animal models, regulation of gastric acid, carrageenan-induced edema in the hind paw was studied to indicate inflammatory condition and histopathologic changes accompanying anti-H. pylori activity. Moreover, Lactobacillus acidophilus TYCA15 was found the strongest inhibition of H. pylori but no function of immunomodulation; Lactobacillus johnsonii MH-68 was found stronger inhibition of H. pylori than others and a little function of immunomodulation; Lactobacillus gasseri AI-88 was found to skew TH1/TH17 pathway and the highest inhibition of growth and adhesion of pathogen except H. pylori; Lactobacillus rhamnosus CT-53 was found to skew TH2/TH1 pathway and stronger antagonism of pathogen than others except H. pylori; Lactobacillus acidophilus F-1 was found to balance TH1/TH2 or TH17/Treg pathway, and the higher inhibition of growth and adhesion of pathogen than others except H. pylori and the strongest antagonism of pathogen except H. pylori, too. Lactobacillus salivarius sp. salicinius AP-32 was found to have the highest probiotic potential to modulate the inflammation which was induced by pathogen and the ability of inhibition activity of pathogen was better than others. This study highlights the complex host-pathogen-microbiota interactions and indicates that a combination of strains may have to be used to provide all the desirable probiotic benefits if the immunomodulation pathway was in the same way.

<p>The unique physical properties of graphene and its potential uses in nanoscale devices make it a compelling subject of study^1. Graphene, a two dimensional crystal which consists of a single layer of carbon atoms bonded together in a hexagonal lattice, has a conical band structure at low energies. Therefore, the charge carriers of graphene obey the Dirac equation for relativistic particles and can be thought of as massless Dirac fermions ^1,2,3 However, recent scanning tunneling microscopy (STM) studies of graphene on silicon dioxide substrates have found corrugations in the graphene samples, and more importantly have observed deviations in the tunneling spectra from the expected Dirac-like behavior ^(4,5,6). Several possible explanations exists for this observed deviation from Diraclike behavior, including phonon-mediated inelastic tunneling ^4,7, charge impurities ⁶, and changes to the band structure to due the underlying substrate ⁸.</p> <p>We present scanning tunneling spectroscopy and microscopy data of graphene on a silicon dioxide substrate at a temperature of 77 K. The topographical studies reveal surface corrugations in graphene due to rippling and partial conformation to the underlying silicon dioxide substrate. In the tunneling spectra, a deviation from the expected Dirac-like behavior is observed. A lack of correlation between the Dirac voltage and conductance maps at a low bias voltage indicates charge impurities are not the primary cause for deviations from Dirac-like behavior. A strain map is computed from the topography and green's functions are fitted to estimate the contribution of phonon coupling to the tunneling conductance. We find that regions of higher strain correspond to higher phonon frequencies, indicating that phonon-mediated inelastic tunneling is a major contributor to the deviation from Dirac-like behavior found in tunneling spectra.</p>

博士<br>國立臺灣科技大學<br>工程技術研究所<br>83<br>We have studied InxGa1-xAs/GaAs strained-layer quantum well heterostructures by modulation spectroscopy. Various techniques include photoreflectance (PR), contactless electroreflectance (CER), and piezoreflectance (PzR) are carried out on several samples in the temperature range of 20 to 300 K. We measured the PR and PzR spectra of a strained-layer (001) In0.21Ga0.79As/ GaAs single quantum well (SQW) as a function of temperature in the range of 20 to 300 K. A careful analysis of the PR and PzR has led to the identification of various excitonic transitions. The result indicates that the main influence of temperature on intersubband transition energy is through the temperature of the band gap of the consitituent material in the well. We the conduction-band offset ratio Qc of the InGaAs/GaAs SQWs by modulation spectroscopy at room temperature and 20 K. The samples have In composition x=0.05 (sample A), 0.11 (sample B), 0.14 (sample C), and 0.21 (sample D), respectively. It has been shown that Qc depends linearly with the In composition x 0.05 and 0.21. We performed the PR, CER, and PzR measurements on an InGaAs/GaAs strained-layer asymmetric triangular quantum well (ATQW) heterostructure fabricated by molecular beam epitaxy using digital alloy compositional grading method.

Oncolytic viral therapies have shown great promise pre-clinically and in human clinical trials for the treatment of various cancers. Oncolytic viruses selectively infect and replicate in cancer cells, destroying tumor tissue via cell lysis, while leaving noncancerous tissues unharmed. Vaccinia virus (VACV) is arguably one of the safest viruses, which has been intensively studied in molecular biology and pathogenesis as a vaccine for the eradication of smallpox in more than 200 million people. It has fast and efficient replication, and cytoplasmic replication of the virus lessens the chance of recombination or integration of viral DNA into the genome of host cells. Anti-tumor therapeutic efficacy of VACV has been demonstrated for human cancers in xenograft models with a variety of tumor types. In addition recombinant oncolytic VACVs carrying imaging genes represent an advance in treatment strategy that combines tumor-specific therapeutics as well as diagnostics. As for other targeted therapies, a number of challenges remain for the clinical translation of oncolytic virotherapy. These challenges include the potential safety risk of replication of oncolytic virus in non-tumor tissue, the relatively poor virus spread throughout solid tumor tissue and the disadvantageous ratio between anti-viral and anti-tumoral immunity. However, manipulation of components of the tumor microenvironment may help oncolytic virus infection in killing the tumor tissue and thereby increasing the anti-tumor efficacy. Furthermore, dogs with natural cancer are considered as one of the best animal models to develop new drugs for cancer therapy. Traditionally, rodent cancer models have been used for development of cancer therapeutics. However, they do not adequately represent several features that define cancer in humans, including biology of initiation of tumor, the complexity of cancer recurrence and metastasis and outcomes to novel therapies. However, the tumor microenvironment, histopathology, molecular and genomics data from dog tumors has significant similarities with corresponding human tumors. These advantages of pet dog cancers provide a unique opportunity to integrate canine cancer patients in the studies designed for the development of new cancer drugs targeted against both human and canine cancers. This dissertation centers on the use of VACV strains in canine cancer xenografts with the aim of understanding the effects of modulation of tumor microenvironment on VACV-mediated tumor therapy. In the first studies, wild-type VACV strain LIVP6.1.1 was tested for its oncolytic efficiency in canine soft tissue sarcoma (STSA-1) and canine prostate carcinoma (DT08/40) cells in culture and xenografts models. LIVP6.1.1 infected, replicated within, and killed both STSA-1 and DT08/40 cells in cell culture. The replication of virus was more efficient in STSA-1 cells compared to DT08/40 cells. In xenograft mouse models, LIVP6.1.1 was safe and effective in regressing both STSA-1 and DT08/40 xenografts. However, tumor regression was faster in STSA-1 xenografts compared to DT08/40 xenografts presumably due to more efficient replication of virus in STSA-1 cells. Biodistribution profiles revealed persistence of virus in tumors 5 and 7 weeks post virus injection in STSA-1 and DT08/40 xenografts, respectively, with the virus mainly cleared from all other major organs. Immunofluorescence staining detected successful colonization of VACV in the tumor. Consequently, LIVP6.1.1 colonization in the tumor showed infiltration of innate immune cells mainly granulocytes and macrophages in STSA-1 tumor xenografts. These findings suggest that virotherapy-mediated anti-tumor mechanism in xenografts could be a combination of direct viral oncolysis of tumor cells and virus-dependent infiltration of tumor-associated host immune cells. In further studies, the effects of modulation of tumor angiogenesis of VACV therapy were analyzed in canine cancer xenografts. GLV-1h109 VACV strain (derived from prototype virus GLV-1h68) encoding the anti-VEGF single chain antibody GLAF-1 was characterized for its oncolytic efficacy in STSA-1 and DT08/40 cancer cells in culture and tumor xenografts. Concomitantly, the effects of locally expressed GLAF- 1 in tumors on virus replication, host immune infiltration, tumor vascularization and tumor growth were also evaluated. GLV-1h109 was shown to be similar to the parental virus GLV-1h68 in expression of the two marker genes that both virus strains have in common (Ruc-GFP and gusA) in cell cultures. Additionally, the anti-VEGF single-chain antibody GLAF-1 was expressed by GLV-1h109 in both cell cultures and tumor xenografts. The insertion of GLAF-1 did not significantly affect the replication and cytotoxicity of GLV-1h109 in the STSA-1 and DT08/40 cell lines, although at early time points (24-48 hpi), the replication of GLV-1h109 was higher in STSA-1 cells compared to DT08/40 cells. In addition, STSA-1 cells were more susceptible to lysis with GLV-1h109 than DT08/40 cells. GLV-1h109 achieved a significant inhibition of tumor growth in both STSA-1 and DT08/40 canine xenografts models. Consequently, the significant regression of tumor growth was initiated earlier in STSA-1 tumor xenografts compared to regression in DT08/40 xenografts. The reason for the higher efficacy of GLV-1h109 in STSA-1 xenografts than DT08/40 xenografts was attributed to more efficient replication of virus in STSA-1 cells. In addition, tumor-specific virus infection led to a continued presence of GLAF-1 in peripheral blood, which could be useful as a pharmacokinetic marker to monitor virus colonization and persistence in GLV-1h109- injected xenograft mice. GLAF-1 is a single-chain antibody targeting human and murine VEGF. It was demonstrated that GLAF-1 was functional and recognized both canine and human VEGF with equal efficiency. Histological analysis of tumor sections 7 days after GLV-1h109 injection confirmed that colonization of VACV and intratumoral expression of GLAF-1 translated into a significant decrease in blood vessel number compared to GLV-1h68 or PBS-treated control tumors. Subsequently, reduction in blood vessel density significantly improved the spread and replication of VACV as observed by FACS analysis and standard plaque assay, respectively. Inhibition of tumor angiogenesis and increased replication of virus further improved the infiltration of innate immune cells mainly granulocytes and macrophages in STSA-1 tumor xenografts. Both the results, i.e. improved virus spread and increased infiltration of innate immune cells in tumor, were explained by a phenomenon called “vascular normalization”, where anti-VEGF therapy normalizes the heterogeneous tumor vasculature thereby improving delivery and spread of VACV. In summary, the effects of inhibition of tumor angiogenesis on virus spread and replication were demonstrated using a vaccinia virus caring an anti- angiogenic payload targeting vascular endothelial growth factor (VEGF) in canine cancer xenografts. In the final studies, the effects of VACV therapy on modulation of the immune system were analyzed in canine cancer patients enrolled in a phase I clinical trial. V-VET1 (clinical grade LIVP6.1.1 VACV) injection significantly increased the percentages of CD3+CD8+ T lymphocytes at 21 days after initiation of treatment. CD3+CD8+ T lymphocytes are mainly cytotoxic T lymphocytes that have potential to lyse cancer cells. Subsequently, the frequency of immune suppressor cells, mainly MDSCs and Treg was also analyzed in peripheral blood of canine cancer patients. Increase in the MDSC population and decreased CD8/Treg ratio is known to have inhibitory effects on the functions of cytotoxic T cells. We demonstrated that injection of V-VET1 in canine cancer patients significantly reduced the percentages of MDSCs at 21 days post initiation of treatment. Additionally, CD8/Treg ratio was increased 21 days after initiation of V-VET1 treatment. We also showed that changes in the frequency of immune cells neither depends on dose of virus nor depends on tumor type according to the data observed from this clinical trial with eleven analyzed patients. This preclinical and clinical data have important clinical implications of how VACV therapy can be used for the treatment of canine cancers. Moreover, dogs with natural cancers can be used as an ideal animal model to improve the oncolytic virotherapy for human cancers. Furthermore, modulation of tumor microenvironment mainly tumor angiogenesis and tumor immunity has significant impact on the success of oncolytic virotherapy<br>Therapien für verschiedenste Krebsarten mittels onkolytischer Viren zeigten sowohl in präklinischen- als auch in humanen klinischen Studien ein erfolgversprechendes Potenzial. Onkolytische Viren infizieren selektiv Krebszellen und replizieren ausschließlich in diesen. In der Folge zerstören sie Tumorgewebe durch Zelllyse, während gesundes Gewebe unbeeinträchtigt bleibt. Das Vaccinia-Virus besitzt ein äußerst geringes Risikopotential, und wurde intensiv auf molekularbiologischer Ebene und in Bezug auf seine Pathogenese untersucht. All das qualifizierte es als Vakzin zur Ausrottung der Pocken und seit Markteinführung mehr als 200 Millionen Menschen injiziert. Das Vaccinia-Virus zeigt eine schnelle und effiziente Replikation, welche im Zytoplasma der Zelle stattfindet. Dies verringert die Möglichkeit der Rekombination oder Integration der viralen DNA in das Wirtsgenom. Die therapeutische Wirksamkeit onkolytischer Vaccinia-Viren (VACVs) wurde in humanen Xenograft-Mausmodellen mit unterschiedlichen Tumorarten gezeigt. Rekombinante onkolytische VACVs, welche mit fluoreszierenden Genen ausgestattet sind, kombinieren die Vorteile tumorspezifischer Therapeutika und dienen gleichzeitig als Diagnostika. Wie auch andere spezifische Therapien, steht auch die onkolytische Virustherapie vor einer Reihe von Herausforderungen. Dazu gehören die Replikation onkolytischer Viren in nicht-kanzerogenem Gewebe, relativ schlechte Virusverbreitung durch solides Tumorgewebe und ein unvorteilhaftes Verhältnis zwischen antiviraler und antitumoraler Immunität. Die gezielte Manipulation einzelner Komponenten des Tumormikromilieus kann jedoch zu einer verbesserten Virusinfektion und Lyse des Tumorgewebes führen und somit die Effizienz der antitumoralen Therapie verstärken.

碩士<br>國立清華大學<br>電機工程學系<br>85<br>A new alternative-strain compensated InP/InGaAs/InP/InAsP/InP polarization independent anti-symmetric coupled-quantum-well (CQW) structure with both blue and red quantum-confined Stark shift for the first heavy-hole-to-electron (or the first light- hole-to-electron) excitonic transition is studied theoretically in this thesis. In the anti-symmetric coupled-quantum-well (CQW), an anti-symmetric-like pair of potential profile between the shallow-deep conduction band profile and the deep-shallow valence band profile is formed. The subband eigenenergies and the associated envelope wave functions in the CQW structures with or without applied electric field are calculated by the transfer matrix method. The effects of the strain on the pseudomorphic layers has been taken into account. The influence of various anti-symmetric CQW structure parameters such as the total well width, the individual well width, the central barrier thickness and the composition of the strained layer on transition energy, QCSE, the envelope wavefunction overlap, and on/off ratio are studied systematically. In addition, the tradeoff between the polarization-independent requirement and the strength of the blue Stark Effect has been discussed. Results indicated that: First, the use of the tensile-strained well is to help to meet the polarization-insensitive condition while that of the remaining compressive-strained well and middle barrier is to help tuning the transition energy to the desired wavelength and simultaneously achieving larger blue shift and wavefunction overlap. Second, in either blue- or red- shift applications, the alternative-strain compensated anti-symmetric polarization-independent CQW structure could gather around superior properties to design the polarization independent electroabsorption modulator because the novel structure could give large enhancement of both blue and red Stark Effect. The design of the novel polarization-independent electroabsorption modulator operated at 1.3mm utilizing either blue or red Stark Effects in the alternative-strain compensated polarization-independent anti-symmetric couple quantum well (CQW) is proposed and studied theoretically in this thesis. The InP/In0.379Ga0.621As(40A)/InP(6A)/InAs0.4P0.6(40A)/InP alternative-strain compensated polarization-independent anti- symmetric CQW is adopted. A value of as high as 5.7 can be achieved by either blue or red Stark Effects shift of the anti- symmetric CQW in the electric field range of 0 to 125kV/cm for blue-shift and 0 to -250kV/cm for red-shift applications. Also, we use In0.409Ga0.591As(52A)/InP operated at 1.3 mm to design the modulator for comparison. Our result shows that in virtue of our novel strain compensated polarization independent anti- symmetric CQW structure, the performance of our novel device, such as switching energy, drive voltage, and the net strain in the device, could be dramatically improved in comparison with the conventional InGaAs/InP SQW modulator.

Semiconductor nanowire field-effect transistors (NWFET) have been recognized as a possible alternative to silicon-based CMOS technology as traditional scaling limits are neared. The core-shell nanowire structure, in particular, also allows for the enhancement of carrier mobility through radial band engineering. In this thesis, we have evaluated the possibility of electron confinement in strained Si-Si1-xGex core-shell nanowire heterostructures. Cylindrical strain distribution was calculated analytically for structures of various dimensions and shell compositions. The strain-induced conduction band edge shift of each region was found using k•p theory coupled with a coordinate system shift to account for strain. A positive conduction band offset of up to 200 meV was found for a Si-Si0.2Ge0.8 structure. We have also designed and characterized a modulation doping scheme for p-type, Ge-SiGe core-shell NWFETs. Finite element simulations of hole density versus radial position were done for different combinations of dopant position and concentration. Three modulation doped nanowire samples, each with a different boron doping density in the shell, were grown using a combined vapor-liquid-solid and chemical vapor deposition process. Low temperature current-voltage measurements of bottom- and top-gate samples indicate that hole mobility is limited by the proximity of charged impurities.<br>text

碩士<br>國立成功大學<br>物理學系<br>89<br>In this thesis, the techniques of modulation spectroscopy of Photoreflectance and phase suppression were employed to examine the built-in electric fields, energy band diagrams and possible interband transitions in a series of InGaAs/GaAs heterostructures. All the samples studied consist of a d-doping and a single quantum well (SQW). From the sample structures and the band gaps and lattice symmetries of the related materials, a preliminary band diagram of each sample was schematically drawn and the possible built-in electric fields in the sample were located. Photoreflectance spectra (PR) of each sample were measured at room temperature. From the features in the PR spectra and the band diagram, the origin and magnitude of each build-in electric field and the interband transition energies were determined. Results obtained allow the band diagram of each sample to be defined more realistically. In addition, the energies of interband transitions were calculated theoretically, using method of intersection (method of point mass). By comparing the transition energies obtained experimentally and theoretically, the specific confined levels (subbands) in the SQW involved in each interband transition can be defined. 第二章 光調制光譜學的理論 2-1 低電場調制 2-2 高電場調制 Franz-Keldysh 振盪 第三章 實驗裝置與樣品的介紹 3-1 實驗裝置 3-2 樣品的介紹 第四章 Si d-doped 下的InGaAs/GaAs 單一量子井結構之研究 4-1光調制光譜 4-2 FKO-B與表面電場的探討 4-3 FKO-A震盪及其對應之電場 4-4 量子井能階的分析與計算 4-4-1應變的影響 4-4-2壓電的產生 4-4-3能階躍遷的理論計算與實驗數據的擬合 4-4-4費米能階對譜線的影響 第五章 總結 參考文獻

碩士<br>國立臺灣大學<br>電機工程學研究所<br>87<br>This thesis is concentrated on what effect quantum wells consisting of thin coupling layer have on semiconductor laser, electroabsorption modulator and semiconductor laser integrated with EA-modulator. We use propagation matrix method to simulate and design device structure. In the simulation results we investigate the effect of thickness of thin coupling layer and strain on QCSE. For symmetric quantum well consisting of thin coupling layer, when thickness of thin coupling layer is getting larger, QCSE is becoming larger, and when we add more strain in quantum well, QCSE is becoming smaller. Then we choose the design range of 26A for thin coupling layer from the point of view of heavy hole wavefunction localization. For asymmetric quantum well consisting of thin coupling layer, we explain the special phenomenon of first blue shift then red shift, and design the best structure 30A/15A/55A from the point of view of built-in E-field. In experiment we estimate characteristics of semiconductor laser and EA-modulator by using photocurrent measurement of PIN diode and static measurement of broad area laser. For characteristics of EA-modulator, the estimated operation voltage of symmetric quantum well consisting of thin coupling layer is 1.2V,which is better than 1.7V for conventional square quantum well. And the photocurrent measurement result of asymmetric quantum well consisting of thin coupling layer is not obvious, so we explain it indirectly by photoreflectance. For characteristics of semiconductor laser, the thickness of thin coupling layer will have influence on infinite cavity length current density and internal quantum efficiency which is 346A/cm2 and 0.66 for square well, 541A/cm2 and 0.57 for symmetric quantum well consisting of 10 A thin coupling layer and 741A/cm2 and 0.51 for asymmetric quantum well consisting of 15 A thin coupling layer. We guess the reason is that thin coupling layer will affect pumping efficiency of semiconductor laser. For characteristics of laser integrated with EA-modulator, the wavelength detuning of laser spectrum peak and exciton absorptiopn peak is largest which is 32nm for asymmetric type quantum well. The largest detuning is good for integration of laser and modulator. And the wavelength detuning of laser spectrum peak and exciton absorptiopn peak is smallest which is 16nm for symmetric type quantum well,even smaller than detuning of square well which is 26 nm. The reason is that the symmetric structure has largest red shift among 3 types of quantum wells when there is no external applied voltage.