In large molecular systems such as DNA, supramolecular complexes and dendrimers, functional groups located at different parts of the molecular structure can act as charge donors or acceptors, and photoinduced intramolecular charge transfer can occur. An analogous scenario can be found in colloidal semiconductor nanocrystals, most evident in type-II heterostructures, where the relative band-alignment of the constituent materials are in a stagger configuration. Such a configuration, provides an energetically favourable situation for an photo-generated electron to be transferred from one material to the other, confining the electron and the hole in different domains of the nanostructure. A less obvious scenario in nanocrystals is when the core is thought of as the donor group, and the surface as the acceptor group. In such a scenario, the localization of electron or hole at surface defect sites, a process that occurs in every nanocrystal, can be thought of as an ``intramolecular" charge transfer. The studies presented in this dissertation are an attempt to further understand charge transfer processes in semiconductor nanostructures, in particular, those occurring within the same nanocrystals. This is carried out by a combination of spectroscopic techniques and modelling. First, time-resolved fluorescence measurements are used to investigated surface trapping/de-trapping dynamics in CdSe and CdSe/CdS/ZnS core/shell/shell quantum dots. A kinetic model, in which trapping/de-trapping is described with Marcus' classical electron transfer theory, is used to analyzed our results, yielding excellent agreement between model and experiment. Second, the influence of temperature and solvent environment in the optical spectra of CdSe/CdTe nanorods are examined. Solvatochromic shifts in these heterostructures are found to be larger than those observed in core-only quantum dots. Finally, ultrafast dynamics and biexciton states in CdSe/CdTe quantum dots are probed using two-dimensional optical spectroscopy. The fine structure of the lowest exciton and biexciton states are calculated for a model system with type-II band-alignment and simulations of 2D spectra are performed.

Animal and clinical studies have shown an acceleration of bone healing by the application of pulsed low-intensity ultrasound (PLIUS). Several studies have reported that pulsed low-intensity ultrasound increase the synthesis of proteoglycan and type II collagen of cultured animal chondrocytes. The objectives of this study were to exam the bioeffect of pulsed low-intensity ultrasound on in vitro cultured human chondrocytes. Human chondrocytes were isolated from the amputated polydactyly digit of six different 1 to 10 years patients and cultured in agarose suspension for 3 days before treatment. PLIUS with intensities of 3.6, 18, 48, 72 and 98 mW/cm2was respectively applied to human chondrocytes for a single 10-min per day treatment. A control group was treated without PLIUS. The results demonstrated that PLIUS-treated human chondrocytes increased the proteoglycan synthesis compared with the control in a time-dependent manner. It is shown that the effect of 48 mW/cm2 is the most potent among a variety of PLIUS intensities tested determined by ELISA method. PLIUS at 48 mW/cm2 also increased type II collagen synthesis by up to 48.5+8.0% of the control determined by western blotting analysis. However, PLIUS has no significant influence on the cell proliferation of human chondrocytes compared with the control. It revealed that the PLIUS can enhance extracellular matrix synthesis. The response to PLIUS of chondrocytes harvested from 1 year old donor was significantly better than that of chondrocytes of 10 years old patient. These observations may lead to a better understanding of the bioeffect of PLIUS on in vitro cultured human chondrovytes.

Superconductivity in high magnetic fields has attracted considerable atten- tion in recent years. The topic is important both for our fundamental un- derstanding of superfluids and for numerous practical applications. In this thesis, we consider several effects originating from the interplay between the Landau level structure of the normal state quasiparticle spectrum, and the tendency of the quasiparticles to form Cooper pairs below the critical tem- perature. A formalism designed to describe extreme type-II superconductors close to the upper critical field H_c2 is developed. The theory which utilizes the selection rules coming from the symmetry properties of the vortex lattice, simplifies the algebra describing a superconductor in the mixed state signifi- cantly. We are, on the mean field level, able to include the quantizing effects of the magnetic field on the electron motion exactly. A main achievement is the exact calculation of the expansion coefficients giving the grand canonical potential of a superconductor in terms of a power series in the size of the or- der parameter. The result is an expression for the grand canonical potential in terms of a polynomial in a finite set of variables close to H_c2. Using this formalism, a theory for the experimentally observed damped de Haas-van Alphen (dHvA) oscillations in the mixed state of a 2-dimensional (2D) superconductor is presented. The theory is compared with numerical results and the agreement is found to be good. A simple physical interpreta- tion of the damping is provided. The dependence of the damping on a finite Zeeman term, temperature, and the magnetic field is considered. A compar- ison of the theory with experimental data for the quasi-2D superconductor K-(ET)₂Cu(NCS)₂ yields good agreement. The attenuation of a longitudinal sound wave in the mixed state is then calculated. In analogy with the dHvA effect, we predict that there should be damped oscillations in the sound attenuation in the mixed state as the exter- nal magnetic field is varied. Furthermore, the dependence of the oscillations on the sound frequency and temperature is shown to yield information on the low lying quasiparticle spectrum. Especially, the presense of gapless excita- tions due to the magnetic field makes the attenuation qualitatively different as compared to the attenuation in the Meissner state. Some formal convergence properties of the Gor'kov theory for type-II su- perconductors close to H_c2 are derived. We show that the theory is essentially a high temperature expansion; the convergence radius of the Gor'kov series is proportional to k_BT when there is a Landau level at the chemical potential.

Thesis (Ph.D.)--University of Melbourne, Dept. of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, 2010. / Typescript. Includes bibliographical references (p. 101-111)

Glycogen storage disease type II (GSDII) is an autosomal recessive lysosomal storage disorder caused by acid alpha-1,4-glucosidase (GAA) deficiency. This study aimed to provide an in-depth description of a late-onset GSDII (LO-GSDII) cohort (n=36) and assess potential genotype-phenotype correlation. We performed a clinical record-based study, some patients (n= 19) were also followed prospectively. Phenotypes were highly variable. We focused our clinical assessment onrespiratory failure, as it is the most frequent cause of death in LO-GSDII. In addition to standard spirometric measures, in a subgroup of patients (n = 10) we utilized a new tool, optoelectronic plethysmography (OEP), to investigate the pathophysiology of respiratory muscle impairment.The GAA gene was sequenced in every patient, and pathogenic mutations were identified inall of them. Almost all (35/36) patients carried the same mutation on one allele, IVS1-32-13T>G, which was in compound heterozygosity with a variety of other GAA mutations. To investigate genotype-phenotype correlation, we divided the patient cohort in two groups, according to the severity of the mutation on the second allele. The respiratory function study focused on diaphragmatic weakness. According to the change in forced vital capacity in supine position (ΔFVC), we defined patients with ΔFVC>25% ashaving diaphragmatic weakness (DW) and those with ΔFVC<25% as without diaphragmatic weakness (noDW). We measured pulmonary function and chest wall volumes using OEP inboth groups. We found a good correlation between the supine abdominal contribution to tidal volume (%VAB) and ΔFVC. Patients showed reduced chest wall and abdominal inspiratory capacity and low abdominal expiratory reserve volume. In terms of genotype-phenotype correlation, we counted more subjects in the group with severe second mutations (n=21) who had severe motor disability and respiratory dysfunction. However, this finding remains preliminary because differences were not significant, likely because of small sample size. Finally, in two smaller substudies, we investigated the occurrence of urinary and fecal incontinence in LO-GSDII, and reported a possibly non-fortuitous association of LO-GSDII and hydromyelia in two individuals. Overall, this work 1) provided new insight into genotype-phenotype correlation in GSDII, suggesting that it is of complex nature; 2) refined the analysis of respiratory muscle impairment and showed the utility of OEP for respiratory assessment in this neuromuscular disorder, and possibly in others as well; 3) indicated some so far little studied phenotypic features of LO-GSD-II that deserve further investigation. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Type II diabetes mellitus (TIIDM) causes multiple complications under chronic hyperglycemia. Long term persistent exposure to elevated glucose conditions is considered one of the major factors for diabetic complications. Pathologically, mechanical and biochemical stimuli will induce a signaling cascade in cardiac fibroblasts, which causes myocardial fibrosis and leading to ventricular stiffness. Non-enzymatically, high levels of glucose can react with long-lived proteins, such as collagen to form advanced glycation end-products (AGEs). AGEs have been shown to be associated with many of the diabetic cardiovascular complications due to their interaction with the receptor for AGE (RAGE). AGE/RAGE activation stimulates the secretion of growth factors, promotes increased collagen production that leads to tissue fibrosis, and increased RAGE expression. The purpose of this study is to identify the role for Rap1a in regulating fibrosis under TIIDM conditions, as well as to offer insight into the AGE-RAGE signaling cascade definition for cardiovascular extracellular matrix remodeling under TIIDM condition. To test our hypothesis, both loss-ofunction and gain-ofunction based experiments were performed to manipulate Rap1a protein expression in AGE-RAGE mediated fibrosis. Also, we down-regulated the activity of downstream molecules in the AGE-RAGE signaling cascade, such as protein kinase C-ζ (PKC-ζ) and ERK1/2 by specific inhibitor treatments, to test their positions in AGE-RAGE mediated fibrosis pathway. To perform our experiment in vivo, we used high fat diet to feed Rap1a heterozygous mice in order to build a Rap1a heterozygous diabetic animal model. Our results showed that Rap1a protein plays a key role in AGE-RAGE signaling pathway under TIIDM, and changes in Rap1a activity altered the signaling pathway. Also, we found that PKC-ζ is the upstream player relatively to ERK1/2, and Rap1a is the upstream player for both PKC-ζ and ERK1/2. By understanding the role Rap1a played in AGE-RAGE signaling cascade, a new molecular mechanism is found possibly to reduce the cardiac fibrosis in TIIDM patients.

No / Burkholderia cepacia is known to invade and survive within respiratory epithelial cells. Previous studies have employed transformed cell lines and it is not known whether the bacterium is capable of manifesting the same phenomena in primary cell culture. Two strains of B. cepacia of environmental (NCTC 10661) and clinical origin (C1359) were examined for their ability to invade and survive (over a 24 h period) within type II pneumocytes in primary culture using a gentamicin¿ceftazidime antibiotic protection assay. Both strains of B. cepacia were capable of invasion of type II pneumocytes in primary culture. Strain C1359 was capable of multiplying intracellularly as indicated by a seven-fold increase in the numbers of bacteria from 4¿24 h, whereas strain 10661, although unable to replicate intracellularly, was found to survive in the pneumocytes for at least 24 h. Future studies on the invasiveness of B. cepacia can employ A549 cells as a valid surrogate for primary cell culture assays which are time-consuming, labour-intensive and expensive to perform.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 142-167).

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