Sterol-binding proteins in late endosomes : Regulation of endosome motility and lipid metabolism

Despite its bad reputation in the mass media, cholesterol is an indispensable constituent of cellular membranes and vertebrate life. It is, however, also potentially lethal as it may accumulate in the arterial intima causing atherosclerosis or elsewhere in the body due to inherited conditions. Studying cholesterol in cells, and research on how the cell biology of cholesterol affects on system level is essential for a better understanding of the disease states associated with cholesterol and for the development of new therapies for these conditions. On its way to the cell, exogenous cholesterol traverses through endosomes, transport vesicles involved in internalizing material to cells, and needs to be transported out of this compartment. This endosomal pool of cholesterol is important for understanding both the common disorders of metabolism and the more rare hereditary disorders of cholesterol metabolism. The study of cholesterol in cells has been hampered by the lack of bright fluorescent sterol analogs that would resemble cholesterol enough to be used in cellular studies. In the first study of my thesis, we present a new sterol analog, Boron-Dipyrromethene (BODIPY)-cholesterol for visualizing sterols in living cells and organism. This fluorescent cholesterol derivative is shown to behave similarly to cholesterol both by atomic scale computer simulations and biochemical experiments. We characterize its localization inside different types of living cells and show that it can be used to study sterol trafficking in living organisms. Two sterol binding proteins associated with the endosomal membrane; the Niemann-Pick type C disease protein 1 (NPC1) and the Oxysterol Binding Protein Related Protein 1 (ORP1) are the subjects of the rest of this study. Sensing cholesterol on endosomes, transporting lipids away from this compartment and the effects these lipids play on cellular metabolism are considered. In the second study we characterize how the NPC1 protein affects lipid metabolism. We show that this cholesterol binding protein affects synthesis of triglycerides and that genetic polymorphisms or a genetic defect in the NPC1 gene affect triglyceride on the whole body level. These effects take place via regulation of carbon fluxes to different lipid classes in cells. In the third part we characterize the effects of another endosomal sterol binding protein, ORP1L on the function and motility of endosomes. Specifically we elucidate how a mutation in the ability of ORP1L to bind sterols affects its behavior in cells, and how a change in ORP1L levels in cells affects the localization, degradative capacity and motility of endosomes. In addition we show that ORP1L manipulations affect cholesterol balance also in macrophages, a cell type important for the development of atherosclerosis.

Anisotropy of the Stone-Wales defect and warping of graphene nanoribbons: A first-principles analysis

Stone-Wales (SW) defects, analogous to dislocations in crystals, play an important role in mechanical behavior of sp(2)-bonded carbon based materials. Here, we show using first-principles calculations that a marked anisotropy in the interaction among the SW defects has interesting consequences when such defects are present near the edges of a graphene nanoribbon: depending on their orientation with respect to edge, they result in compressive or tensile stress, and the former is responsible to depression or warping of the graphene nanoribbon. Such warping results in delocalization of electrons in the defect states.

Language Influence in Services: Perceived Importance of Native Language Use in Service Encounters

A defining characteristic of most service encounters is that they are strongly influenced by interactions in which both the consumer and the service personnel are playing integral roles. Such is the importance of this interaction that it has even been argued that for the consumer, these encounters are in fact the service. Given this, it is not surprising that interactions involving communication and customer participation in the service encounters have received considerable attention within the field of services marketing. Much of the research on interactions and communication in services, however, appear to have assumed that the consumer and the service personnel by definition are perfectly able to interact and communicate effortlessly with each other. Such communication would require a common language, and in order to be able to take this for granted the market would need to be fairly homogenous. The homogenous country, however, and with it the homogenous market, would appear to be gone. It is estimated that more than half the consumers in the world are already speaking more than one language. For a company entering a new market, language can be a major barrier that firms may underestimate, and understanding language influence across different markets is important for international companies. The service literature has taken a common language between companies and consumers for granted but this is not matched by the realities on the ground in many markets. Owing to the communicational and interaction-oriented nature of services, the lack of a common language between the consumer and the service provider is a situation that could cause problems. A gap exists in the service theory, consisting of a lack of knowledge concerning how language influences consumers in service encounters. By addressing this gap, the thesis contributes to an increased understanding of service theory and provides a better practical understanding for service companies of the importance of native language use for consumers. The thesis consists of four essays. Essay one is conceptual and addresses how sociolinguistic research can be beneficial for understanding consumer language preferences. Essay two empirically shows how the influence of language varies depending on the nature of the service, essay three shows that there is a significant difference in language preferences between female and male consumers while essay four empirically compares consumer language preferences in Canada and Finland, finding strong similarities but also indications of difference in the motives for preferring native language use. The introduction of the thesis outlines the existence of a research gap within the service literature, a gap consisting of the lack of research into how native language use may influence consumers in service encounters. In addition, it is described why this gap is of importance to services and why its importance is growing. Building on this situation, the purpose of the thesis is to establish the existence of language influence in service encounters and to extend the knowledge of how language influences consumers on multilingual markets.

Photophysics of conjugated polymers: interplay between Forster energy migration and defect concentration in shaping a photochemical funnel in PPV

Recent single molecule experiments have suggested the existence of a photochemical funnel in the photophysics of conjugated polymers, like poly[2-methoxy-5-(2'-ethylhexyl)oxy-1,4-phenylenevinylene] (MEH-PPV). The funnel is believed to be a consequence of the presence of conformational or chemical defects along the polymer chain and efficient non-radiative energy transfer among different chromophore segments. Here we address the effect of the excitation energy dynamics on the photophysics of PPV. The PPV chain is modeled as a polymer with the length distribution of chromophores given either by a Gaussian or by a Poisson distribution. We observe that the Poisson distribution of the segment lengths explains the photophysics of PPV better than the Gaussian distribution. A recently proposed version of an extended particle-in-a-box' model is used to calculate the exciton energies and the transition dipole moments of the chromophores, and a master equation to describe the excitation energy transfer among different chromophores. The rate of energy transfer is assumed to be given here, as a first approximation, by the well-known Forster expression. The observed excitation population dynamics confirms the photochemical funneling of excitation energy from shorter to longer chromophores of the polymer chain. The time scale of spectral shift and energy transfer for our model polymer, with realistic values of optical parameters, is in the range of 200-300 ps. We find that the excitation energy may not always migrate towards the longest chromophore segments in the polymer chain as the efficiency of energy transfer between chromophores depends on the separation distance between the two and their relative orientation.

A core-level photoemission spectroscopic study of the electron-doped superconductor, Nd2-xCexCuO4-δ

A photoemission study of superconducting Nd1.85Ce0.15CuO4-δ shows that Ce in the cuprate is essentially in the 4+ state. While the electron donated by Ce does not appear to affect the Cu 3d band, we still find evidence for the presence of considerable Cu1+ - related configurations due to covalency effects. A role for oxygen holes and Cu1+ species is indicated just as in other cuprate superconductors.

An SIMD machine for low-level vision

This paper presents an SIMD machine which has been tuned to execute low-level vision algorithms employing the relaxation labeling paradigm. Novel features of the design include: 1. (1) a communication scheme capable of window accessing under a single instruction. 2. (2) flexible I/O instructions to load overlapped data segments; and 3. (3) data-conditional instructions which can be nested to an arbitrary degree. A time analysis of the stereo correspondence problem, as implemented on a simulated version of the machine using the probabilistic relaxation technique, shows a speed up of almost N2 for an N × N array of PEs.

Yhden uhka, toisen toive? : Somalien ja venäläisten asumistoiveet etnisen segregaatiokehityksen valossa

Ethnic minorities residential patterns and integration are widely discussed issues in many European countries. They have also become topical in Finland due to an increase in foreign migration, especially in recent decades. This dissertation contributes to debates associated with attempts to explain ethnic minorities residential patterns by examining the role of cultural factors and ethnic preferences of the residential choices of Somali and Russian immigrants in Finland. The research is based on in-depth interviews with Somali (n=24) and Russian (n=26) immigrants living in the Helsinki metropolitan area. Housing officials and social workers (n=18) working in cities of Helsinki and Vantaa were also interviewed. The results of this study show that propinquity to one s own ethnic group is important to Somalis living in Finland. This is important for maintaining their traditional, communal life styles, but also as a safe haven against the racism which they experience on a regular basis. They have a preference for mixed neighbourhoods that contain both native Finnish residents and some ethnic minorities. For Russians the spatial propinquity to their country people is less significant at the neighbourhood level. However, this is not to indicate the insignificance of intra-ethnic networks or one s cultural background. Rather, the differences in ethnic preferences between Somalis and Russians predominantly reflect their varying levels of exposure to racial harassment and diverse meanings that they give to social relations with their neighbours. According to this study, the time spent in a host-country and interactions with other ethnic groups affect ethnic preferences. The importance of one s own ethnic community also varies in accordance with life situations. Therefore, ethnic minorities residential preferences and choices should not be viewed as static or something deriving from cultural background alone. Residential preferences and aspirations are constantly being reshaped vis-à-vis to immigrants experiences. Past and present experiences and the way that immigrants observe the host society and its functions are important for the interpretation of residential preferences and patterns.

A Simple Five-Level Inverter Topology for Induction Motor Drive Using Conventional Two-Level Inverters and Flying Capacitor Technique

This paper proposes a new five-level inverter topology for open-end winding induction motor (IM) drive. The popular existing circuit configurations for five-level inverter include the NPC inverter and flying capacitor topologies. Compared to the NPC inverter, the proposed topology eliminates eighteen clamping diodes having different voltage ratings in the present circuit. Moreover it requires only one capacitor bank per phase, whereas flying capacitor schemes for five level topologies require six capacitor banks per phase. The proposed topology is realized by feeding the phase winding of an open-end induction motor with two-level inverters in series with flying capacitors. The flying capacitor voltages are balanced using the switching state redundancy for full modulation range. The proposed inverter scheme is capable of producing two-level to five-level pulse width modulated voltage across the phase winding depending on the modulation range. Additionally, in case of any switch failure in the flying capacitor connection, the proposed inverter topology can be operated as a three-level inverter for full modulation range. The proposed scheme is experimentally verified on a four pole, 5hp induction motor drive.

Electronic structure of high-Tc superconductors from core-level spectroscopies

Using the configuration-interaction approach, we show that various core-level spectroscopic observations on the high-Tc superconducting oxides can be consistently described in terms of mixing between d9 and d10 configurations, with a negligible amount of the d8 (Cu3+) state. From our analysis of the existing experimental data, we provide evidence of a wide and continuous valence transition in these systems as a function of temperature. The changes in the hybridization strengths deduced here are indicative of structural modifications of the square-planar CuO4 clusters with decreasing temperature.

Vitamin A and thyroxine carrier proteins in chicken plasma Steady-state control of the plasma level of free retinol-binding protein and free thyroxine

1. 1. The binding parameters of prealbumin-2 with retinol-binding protein and thyroxine (T4) revealed the existence of distinct and multiple sites for both retinol-binding protein and T4. 2. 2. From the analysis of binding parameters of retinol-binding protein with prealbumin-2 it is clear that under steady-state conditions about 99% of the holo-retinol-binding protein remains bound to prealbumin-2. 3. 3. Equilibrium dialysis studies on binding properties of thyroid hormones with prealbumin-2 revealed that it has a single high affinity site and three low affinity sites. 4. 4. The occurrence of three carrier proteins for thyroid hormones, thyroxine-binding globulin, prealbumin-2 and albumin has been demonstrated. However, the chicken thyroxine-binding globulin differs from human thyroxine-binding globulin by being relatively less acidic and occuring at a two-fold lower concentration. But the thyroid hormone binding parameters are comparable. 5. 5. Highly sensitive methods were developed for determination of T4 binding capacities of the various proteins and plasma level of total T4 by fractionation of carrier proteins and further quantitatively employing in electrophoresis and equilibrium dialysis. 6. 6. The thyroxine-binding proteins were found to be two types, one (viz., thyroxine-binding globulin) of great affinity but of low binding capacity, which mainly acts as reservoir of T4, and another (viz.,prealbumin-2) of low affinity but of high binding capacity, which can participate predominantly in the control of the free T4 pool.

Shell-model calculation of defect energies in alkali halides employing crystal-independent interionic potential parameters

Shell model calculation of defect energies in alkali halides have been carried out using the ion-dependent, crystal-independent potential parameters of Sangster and Atwood (1978). Results indicate that appreciable differences exist between barrier heights for migration of cations and anions. While barrier heights for cations are generally lower than for anions in alkali halides of NaCl structure, the opposite is true in alkali halides of CsCl structure.

System effects in double‐channel gated‐integrator‐based deep‐level transient spectroscopy

The effects of the two sampling gate positions, and their widths and the integrator response times on the position, height, and shape of the peaks obtained in a double‐channel gated‐integrator‐based deep‐level transient spectroscopy (DLTS) system are evaluated. The best compromise between the sensitivity and the resolution of the DLTS system is shown to be obtained when the ratio of the two sampling gate positions is about 20. An integrator response time of about 100 ms is shown to be suitable for practical values of emission time constants and heating rates generally used.