Experimental approach for studying structural changes in axonal membrane upon nerve excitation

The Hodgkin and Huxley (HH) model of action potential has become a central paradigm of neuroscience. Despite its ability to predict action potentials with remarkable accuracy, it fails to explain several biophysical findings related to the initiation and propagation of the nerve impulse. The isentropic heat release and optical phenomena demonstrated by various experiments suggest that action potential is accompanied by a transient phase change in the axonal membrane. In this study a method was developed for preparing a giant axon from the crayfish abdominal cord for studying the molecular mechanisms of action potential simultaneously by electrophysiological and optical methods. Also an alternative setup using a single-cell culture of an Aplysia sensory neuron is presented. In addition to the description of the method, the preliminary results on the effect of phloretin, a dipole potential lowering compound, on the excitability of a crayfish giant axon are presented.

Teatterinjohtamisen dramaturgiaa : Keskeiset tehtävät, arjen ongelmat ja rakenteelliset muutostarpeet

DRAMATURGY OF THEATRE MANAGEMENT Essential tasks, everyday problems and the need for structural changes Theatre justifies its existence only through high quality performances. Maintaining the artistic level and organizing performances are the primary tasks of a manager, even though in everyday life this often seems to be overshadowed by all the other tasks of a manager s work. How does a theatre manager design strategies and make everyday decisions if aims are to have artistically meaningful performances, financial success and a socially healthy ensemble, when not only artistic work or leadership of an organization are to be taken into consideration, but also a manpower-based art institution with long traditions? What does theatre management consist of and what kind of dramaturgical movement happens in it? Based on interviews carried out in five different city theatres in Finland in the years 2004-2008, incident stories were written within a continuous comparison theory frame. Social constructionism within a dramaturgic framework enabled versatile dialog on a manager s work and problem areas. The result is an interpretative study, where instead of common regularities, many details are collected that can be taken into consideration when similar situations occur. Based on the interviews and historical data, four factors that influence a manager s work were chosen: ownership, media, work community and programme. Within theatre management, the central problems were 1) the inconsistent use of theatre resources and problems in corporate governance caused by the administrative models; 2) the theatre s image, based on the image of its manager, as presented by the media and its influence on the wellbeing of the staff; 3) unsolved problems between the staff left behind by the previous managers and problems related to casting; 4) knowledge of the audience. These points influence how the manager plans the artistic programme and divides the resources. The theatre manager s job description has remained quite the same since the early days of Kaarlo Bergbom. In the future, special attention should be placed on why managers face fairly similar problems decade after decade. Reducing these problems partly depends on whether structural improvements are made to a theatre s close network of owners, financers and labour unions. During this study clear evidence was seen that structural changes are necessary in the production of performances and in the creation of a more versatile programme. In this process, different kinds of co-operation, experiments, development projects, continuing education and international relations have special importance, especially if the aim is to make it possible for all citizens of Finland to enjoy a vibrant and revitalized theatre.

Makt, konst, elit - konstfältets positioner, relationer och resurser i 1940- och 1950-talens Helsingfors

The dissertation examines the power mechanisms and institutional power hierarchies of the 1940s-1950s era arts elite in Helsinki and their influence on issues of taste in the visual arts. For the purposes of this study, the elite is understood to consist mainly of the board members of the principal elected bodies in the field of the arts. The theoretical framework employed is based on Pierre Bourdieu s field theory and the network perspective. The author has examined what the key, pervasive valuations were that governed the exercising of power by the arts elite in issues of taste, involving determination of who was an acknowledged artist and what was good art. The dissertation demonstrates that this exercising of power was governed by certain collective practices which maintained the illusion that the exercising of power was democratic and based on artistic quality. These practices were the corporate system, using artistic arguments in issues of taste, and using networks in the exercising of power. The struggle in the field of the arts was about who ultimately was entitled to define the value of contemporary art; the issue did not arise regarding historical art. Artists managed to gain a leading position as gatekeepers in issues regarding contemporary art. The author discusses a number of conflicts in the field of the arts that highlight the institutional hierarchies and the capital held by the various players. The structural changes that occurred in administration in the field of cultural production in the 1950s led to the separation of bureaucratic competence on the one hand and aesthetic competence on the other. There was a hierarchy in the field of the arts between institutions, between instruments of legitimisation, and between the symbolic and social capital of players in the field. The hierarchy in the arts ultimately depended on how well the elite could influence tastes through the instruments at their disposal. The various instruments of legitimisation grants, purchases, etc. were ranked differently in the evaluation of acknowledged artists and good art. The dissertation discusses what values, in the form of types of symbolic capital, the arts elite embraced and what role these played in the elite s exercising of power, with particular focus on gender, language, region and economic capital. The aesthetic capital of an artist was of only minor importance in the exercising of power by the arts elite. The dissertation further discusses the points of contact between the arts elite and players in other fields, such as the economic, media and consumer fields. When the arts elite, through the Academy of Fine Arts, became an active player in the art market, this led to a hierarchy where the division between acknowledged and not-acknowledged galleries became sharper.

Metsänomistajakunnan rakenteen ennustaminen

The general change in the population structure and its impacts on the forest ownership structure were investigated in the thesis. The research assumed that the structural change in society has an effect on the outlook of the non-industrial private forest ownership. The changes in the structure of society were mainly restricted to population, education and occupation structures. The migration of the rural population into cities was also taken into consideration. The structural changes both in society and the non-industrial private forest ownership were examined as phenomena and their development directions were investigated since the middle of the 1970s. It could be established that the changes in the structures were mainly of the same kind in society as in forest owner structure. The clearest similarities between the changes in population and forest owner structure could be found in an increased mean age, a decrease in the 18 to 39 age bracket, those without a degree and in the farmers' shares. Furthermore it could be stated that migration into cities had taken place among both the forest owners and the general population. The main part of the research was concentrated on estimating regression models that explain the non-industrial private forest ownership change by the structural change in the population. A panel data was gathered from population statistics and previous forest ownership research information. The panel contained the years 1990 and 1999. With the assistance of the panel data it was possible to estimate regression and fixed effects' models that explained the structural changes in the non-industrial private forest ownership by evolution in the whole population. In the use of the estimated models authorities' forecasts considering the population were exploited. Only a few of the estimated models were statistically significant. This could be explained due to lack of a larger panel data. In addition the structural change of the non-industrial forest ownership was forecasted by trends.

Determinants of farmer retirement and farm succession in Finland

In the past decade, the Finnish agricultural sector has undergone rapid structural changes. The number of farms has decreased and the average farm size has increased when the number of farms transferred to new entrants has decreased. Part of the structural change in agriculture is manifested in early retirement programmes. In studying farmers exit behaviour in different countries, institutional differences, incentive programmes and constraints are found to matter. In Finland, farmers early retirement programmes were first introduced in 1974 and, during the last ten years, they have been carried out within the European Union framework for these programmes. The early retirement benefits are farmer specific and de-pend on the level of pension insurance the farmer has paid over his active farming years. In order to predict the future development of the agricultural sector, farmers have been frequently asked about their future plans and their plans for succession. However, the plans the farmers made for succession have been found to be time inconsistent. This study estimates the value of farmers stated succession plans in predicting revealed succession decisions. A stated succession plan exists when a farmer answers in a survey questionnaire that the farm is going to be transferred to a new entrant within a five-year period. The succession is revealed when the farm is transferred to a suc-cessor. Stated and revealed behaviour was estimated as a recursive Binomial Probit Model, which accounts for the censoring of the decision variables and controls for a potential correlation between the two equations. The results suggest that the succession plans, as stated by elderly farmers in the questionnaires, do not provide information that is significant and valuable in predicting true, com-pleted successions. Therefore, farmer exit should be analysed based on observed behaviour rather than on stated plans and intentions. As farm retirement plays a crucial role in determining the characteristics of structural change in agriculture, it is important to establish the factors which determine an exit from farming among eld-erly farmers and how off-farm income and income losses affect their exit choices. In this study, the observed choice of pension scheme by elderly farmers was analysed by a bivariate probit model. Despite some variations in significance and the effects of each factor, the ages of the farmer and spouse, the age and number of potential successors, farm size, income loss when retiring and the location of the farm together with the production line were found to be the most important determi-nants of early retirement and the transfer or closure of farms. Recently, the labour status of the spouse has been found to contribute significantly to individual retirement decisions. In this study, the effect of spousal retirement and economic incentives related to the timing of a farming couple s early retirement decision were analysed with a duration model. The results suggest that an expected pension in particular advances farm transfers. It was found that on farms operated by a couple, both early retirement and farm succession took place more often than on farms operated by a single person. However, the existence of a spouse delayed the timing of early retirement. Farming couples were found to co-ordinate their early retirement decisions when they both exit through agricultural retirement programmes, but such a co-ordination did not exist when one of the spouses retired under other pension schemes. Besides changes in the agricultural structure, the share and amount of off-farm income of a farm family s total income has also increased. In the study, the effect of off-farm income on farmers retirement decisions, in addition to other financial factors, was analysed. The unknown parameters were first estimated by a switching-type multivariate probit model and then by the simulated maxi-mum likelihood (SML) method, controlling for farmer specific fixed effects and serial correlation of the errors. The results suggest that elderly farmers off-farm income is a significant determinant in a farmer s choice to exit and close down the farm. However, off-farm income only has a short term effect on structural changes in agriculture since it does not significantly contribute to the timing of farm successions.

Entsymaattisen hydrolyysin vaikutuksista mikrokiteisen selluloosan rakenteeseen

Cellulose can be used as a renewable raw material for energy production. The utilization requires degradation of cellulose into glucose, which can be done with the aid of enzymatic hydrolysis. In this thesis, various x-ray methods were used to characterize sub-micrometer changes in microcrystalline cellulose during enzymatic hydrolysis to clarify the process and factors slowering it. The methods included wide-angle x-ray scattering (WAXS), small-angle x-ray scattering (SAXS) and x-ray microtomography. In addition, the samples were studied with transmission electron microscopy (TEM). The studied samples were hydrolyzed by enzymes of the Trichoderma reesei species for 6, 24, and 75 hours, which corresponded to 31 %, 58 %, and 68 % degrees of hydrolysis, respectively. Freeze-dried hydrolysis residues were measured with WAXS, SAXS and microtomography, whereas some of them were re-wetted for the wet SAXS and TEM measurements. The microtomography measurements showed a clear decrease in particle size in scale of tens of micrometers. In all the TEM pictures similar cylindrical and partly ramified structures were observed, independent of the hydrolysis time. The SAXS results were ambiguous and partly imprecise, but showed a change in the structure of wet samples in scale of 10-30 nm. According to the WAXS results, the degrees of crystallinity and the crystal sizes remained the same. The gained results support the assuption, that the cellulosic particles are hydrolyzed mostly on their surface, since the enzymes are unable to penetrate into the nanopores of wet cellulose. The hydrolysis therefore proceeds quickly in easily accessible particles and leaves the unaccesible particles almost untouched. The structural changes observed in the SAXS measurements might correspond to slight loosening of the microfibril aggregates, which was seen only in the wet samples because of their different pore structure.

Enzyme molecular choreography : studies on soluble inorganic pyrophosphatases

Inorganic pyrophosphatases (PPases, EC 3.6.1.1) hydrolyse pyrophosphate in a reaction that provides the thermodynamic 'push' for many reactions in the cell, including DNA and protein synthesis. Soluble PPases can be classified into two families that differ completely in both sequence and structure. While Family I PPases are found in all kingdoms, family II PPases occur only in certain prokaryotes. The enzyme from baker's yeast (Saccharomyces cerevisiae) is very well characterised both kinetically and structurally, but the exact mechanism has remained elusive. The enzyme uses divalent cations as cofactors; in vivo the metal is magnesium. Two metals are permanently bound to the enzyme, while two come with the substrate. The reaction cycle involves the activation of the nucleophilic oxygen and allows different pathways for product release. In this thesis I have solved the crystal structures of wild type yeast PPase and seven active site variants in the presence of the native cofactor magnesium. These structures explain the effects of the mutations and have allowed me to describe each intermediate along the catalytic pathway with a structure. Although establishing the ʻchoreographyʼ of the heavy atoms is an important step in understanding the mechanism, hydrogen atoms are crucial for the mechanism. The most unambiguous method to determine the positions of these hydrogen atoms is neutron crystallography. In order to determine the neutron structure of yeast PPase I perdeuterated the enzyme and grew large crystals of it. Since the crystals were not stable at ambient temperature, a cooling device was developed to allow neutron data collection. In order to investigate the structural changes during the reaction in real time by time-resolved crystallography a photolysable substrate precursor is needed. I synthesised a candidate molecule and characterised its photolysis kinetics, but unfortunately it is hydrolysed by both yeast and Thermotoga maritima PPases. The mechanism of Family II PPases is subtly different from Family I. The native metal cofactor is manganese instead of magnesium, but the metal activation is more complex because the metal ions that arrive with the substrate are magnesium different from those permanently bound to the enzyme. I determined the crystal structures of wild type Bacillus subtilis PPase with the inhibitor imidodiphosphate and an inactive H98Q variant with the substrate pyrophosphate. These structures revealed a new trimetal site that activates the nucleophile. I also determined that the metal ion sites were partially occupied by manganese and iron using anomalous X- ray scattering.

Essays on Finnish Economic Growth and Productivity, 1860-2005

This study examines Finnish economic growth. The key driver of economic growth was productivity. And the major engine of productivity growth was technology, especially the general purpose technologies (GPTs) electricity and ICT. A new GPT builds on previous knowledge, yet often in an uncertain, punctuated, fashion. Economic history, as well as the Finnish data analyzed in this study, teaches that growth is not a smooth process but is subject to episodes of sharp acceleration and deceleration which are associated with the arrival, diffusion and exhaustion of new general purpose technologies. These are technologies that affect the whole economy by transforming both household life and the ways in which firms conduct business. The findings of previous research, that Finnish economic growth exhibited late industrialisation and significant structural changes were corroborated by this study. Yet, it was not solely a story of manufacturing and structural change was more the effect of than the cause for economic growth. We offered an empirical resolution to the Artto-Pohjola paradox as we showed that a high rate of return on capital was combined with low capital productivity growth. This result is important in understanding Finnish economic growth 1975-90. The main contribution of this thesis was the growth accounting results on the impact of ICT on growth and productivity, as well as the comparison of electricity and ICT. It was shown that ICT s contribution to GDP growth was almost twice as large as electricity s contribution over comparable periods of time. Finland has thus been far more successful as an ICT producer than a producer of electricity. Unfortunately in the use of ICT the results were still more modest than for electricity. During the end of the period considered in this thesis, Finland switched from resource-based to ICT-based growth. However, given the large dependency on the ICT-producing sector, the ongoing outsourcing of ICT production to low wage countries provides a threat to productivity performance in the future. For a developed country only change is constant and history teaches us that it is likely that Finland is obliged to reorganize its economy once again in the digital era.

Herpes Simplex Virus Infection, Pathological Pain and Recurrent Lymphocytic Meningitis

Background: Aims of the study were: (i) to characterise the clinical picture, immunological features and changes in brain morphology and function in patients with widespread unilateral pain and HSV-infections, and (ii) to analyse the prevalence, clinical symptoms and immunological predisposing factors of HSV-2 induced recurrent lymphocytic meningitis (RLM) in Southern Finland. Patients and methods: Patients for the studies were recruited from the Pain Clinic, and from the Department of Neurology, at Helsinki University Central Hospital. Plasma concentrations of IgM, IgA, IgG, and IgG1-4, and serum concentrations of C3, C4 were measured. Serological anti-HSV-1 and -2 antibody status was tested. C4 genotyping, HLA-A, HLA-B and HLA-DRB1 typing, MBL2 genotyping, and IgG1 and IgG3 allotyping (Gm) were performed. Clinical neurological examination, quantitative sensory testing, skin biopsy, and functional magnetic resonance imaging were also performed. Results: HSV probably has a role in the generation of a pathological pain state. Low serum IgG1 and IgG3 levels, made the patients vulnerable for recurring HSV infections. Both functional and structural changes were observed in the brain pain-processing areas in the patients: they had less pain-related activity in the insular cortices bilaterally, in the anterior cingular cortex (ACC), and in the thalamus, and the gray matter density was lower in the ACC, in the frontal and prefrontal cortices. In the meningitis studies it was shown that RLM is more common and less benign than previously reported, and that neuropathic pain is frequently present both during and after meningitis episodes. HLA-DRB1*01, HLA-B*27, and low IgG1 levels are predisposing factors for RLM. Conclusions: Patients are vulnerable to recurrent HSV infections because of subtle immunological abnormalities. HSV causes diverse clinical manifestations. First, the herpes simplex virus, or the inflammatory process triggered by it, may cause pathological widespread pain probably by activating glial cells in the CNS. In these patients, signs of alterations in the brain pain-processing areas can be demonstrated by functional brain imaging methods. Secondly, HSV-2 induced RLM is a rare complication of HSV-2 virus. The predisposing factors include low IgG1 subclass levels, HLA-DRB1*01 and HLA –B*27 genotypes. Neuropathic pain is frequently associated with RLM.

Opioid dependence: Brain structure and function : a magnetic resonance imaging, neuropsychological, and electromagnetic study

Background: Opiod dependence is a chronic severe brain disorder associated with enormous health and social problems. The relapse back to opioid abuse is very high especially in early abstinence, but neuropsychological and neurophysiological deficits during opioid abuse or soon after cessation of opioids are scarcely investigated. Also the structural brain changes and their correlations with the length of opioid abuse or abuse onset age are not known. In this study the cognitive functions, neural basis of cognitive dysfunction, and brain structural changes was studied in opioid-dependent patients and in age and sex matched healthy controls. Materials and methods: All subjects participating in the study, 23 opioid dependents of whom, 15 were also benzodiazepine and five cannabis co-dependent and 18 healthy age and sex matched controls went through Structured Clinical Interviews (SCID) to obtain DSM-IV axis I and II diagnosis and to exclude psychiatric illness not related to opioid dependence or personality disorders. Simultaneous magnetoencephalography (MEG) and electroencephalography (EEG) measurements were done on 21 opioid-dependent individuals on the day of hospitalization for withdrawal therapy. The neural basis of auditory processing was studied and pre-attentive attention and sensory memory were investigated. During the withdrawal 15 opioid-dependent patients participated in neuropsychological tests, measuring fluid intelligence, attention and working memory, verbal and visual memory, and executive functions. Fifteen healthy subjects served as controls for the MEG-EEG measurements and neuropsychological assessment. The brain magnetic resonance imaging (MRI) was obtained from 17 patients after approximately two weeks abstinence, and from 17 controls. The areas of different brain structures and the absolute and relative volumes of cerebrum, cerebral white and gray matter, and cerebrospinal fluid (CSF) spaces were measured and the Sylvian fissure ratio (SFR) and bifrontal ratio were calculated. Also correlation between the cerebral measures and neuropsychological performance was done. Results: MEG-EEG measurements showed that compared to controls the opioid-dependent patients had delayed mismatch negativity (MMN) response to novel sounds in the EEG and P3am on the contralateral hemisphere to the stimulated ear in MEG. The equivalent current dipole (ECD) of N1m response was stronger in patients with benzodiazepine co-dependence than those without benzodiazepine co-dependence or controls. In early abstinence the opioid dependents performed poorer than the controls in tests measuring attention and working memory, executive function and fluid intelligence. Test results of the Culture Fair Intelligence Test (CFIT), testing fluid intelligence, and Paced Auditory Serial Addition Test (PASAT), measuring attention and working memory correlated positively with the days of abstinence. MRI measurements showed that the relative volume of CSF was significantly larger in opioid dependents, which could also be seen in visual analysis. Also Sylvian fissures, expressed by SFR were wider in patients, which correlated negatively with the age of opioid abuse onset. In controls the relative gray matter volume had a positive correlation with composite cognitive performance, but this correlation was not found in opioid dependents in early abstinence. Conclusions: Opioid dependents had wide Sylvian fissures and CSF spaces indicating frontotemporal atrophy. Dilatation of Sylvian fissures correlated with the abuse onset age. During early withdrawal cognitive performance of opioid dependents was impaired. While intoxicated the pre-attentive attention to novel stimulus was delayed and benzodiazepine co-dependence impaired sound detection. All these changes point to disturbances on frontotemporal areas.

The Pathobiology of the Saccular Cerebral Artery Aneurysm Rupture and Repair : A Clinicopathological and Experimental Approach

Backround and Purpose The often fatal (in 50-35%) subarachnoid hemorrhage (SAH) caused by saccular cerebral artery aneurysm (SCAA) rupture affects mainly the working aged population. The incidence of SAH is 10-11 / 100 000 in Western countries and twice as high in Finland and Japan. The estimated prevalence of SCAAs is around 2%. Many of those never rupture. Currently there are, however, no diagnostic methods to identify rupture-prone SCAAs from quiescent, (dormant) ones. Finding diagnostic markers for rupture-prone SCAAs is of primary importance since a SCAA rupture has such a sinister outcome, and all current treatment modalities are associated with morbidity and mortality. Also the therapies that prevent SCAA rupture need to be developed to as minimally invasive as possible. Although the clinical risk factors for SCAA rupture have been extensively studied and documented in large patient series, the cellular and molecular mechanisms how these risk factors lead to SCAA wall rupture remain incompletely known. Elucidation of the molecular and cellular pathobiology of the SCAA wall is needed in order to develop i) novel diagnostic tools that could identify rupture-prone SCAAs or patients at risk of SAH, and to ii) develop novel biological therapies that prevent SCAA wall rupture. Materials and Methods In this study, histological samples from unruptured and ruptured SCAAs and plasma samples from SCAA carriers were compared in order to identify structural changes, cell populations, growth factor receptors, or other molecular markers that would associate with SCAA wall rupture. In addition, experimental saccular aneurysm models and experimental models of mechanical vascular injury were used to study the cellular mechanisms of scar formation in the arterial wall, and the adaptation of the arterial wall to increased mechanical stress. Results and Interpretation Inflammation and degeneration of the SCAA wall, namely loss of mural cells and degradation of the wall matrix, were found to associate with rupture. Unruptured SCAA walls had structural resemblance with pads of myointimal hyperplasia or so called neointima that characterizes early atherosclerotic lesions, and is the repair and adaptation mechanism of the arterial wall after injury or increased mechanical stress. As in pads of myointimal hyperplasia elsewhere in the vasculature, oxidated LDL was found in the SCAA walls. Immunity against OxLDL was demonstrated in SAH patients with detection of circulating anti-oxidized LDL antibodies, which were significantly associated with the risk of rupture in patients with solitary SCAAs. Growth factor receptors associated with arterial wall remodeling and angiogenesis were more expressed in ruptured SCAA walls. In experimental saccular aneurysm models, capillary growth, arterial wall remodeling and neointima formation were found. The neointimal cells were shown to originate from the experimental aneurysm wall with minor contribution from the adjacent artery, and a negligible contribution of bone marrow-derived neointimal cells. Since loss of mural cells characterizes ruptured human SCAAs and likely impairs the adaptation and repair mechanism of ruptured or rupture-prone SCAAs, we investigated also the hypothesis that bone marrow-derived or circulating neointimal precursor cells could be used to enhance neointima formation and compensate the impaired repair capacity in ruptured SCAA walls. However, significant contribution of bone marrow cells or circulating mononuclear cells to neointima formation was not found.

Morphogenesis of Mammalian Endoplasmic Reticulum and Golgi Apparatus throughout the Cell Cycle

The endoplasmic reticulum (ER) and the Golgi apparatus are organelles that produce, modify and transport proteins and lipids and regulate Ca2+ environment within cells. Structurally they are composed of sheets and tubules. Sheets may take various forms: intact, fenestrated, single or stacked. The ER, including the nuclear envelope, is a single continuous network, while the Golgi shows only some level of connectivity. It is often unclear, how different morphologies correspond to particular functions. Previous studies indicate that the structures of the ER and Golgi are dynamic and regulated by fusion and fission events, cytoskeleton, rate of protein synthesis and secretion, and specific structural proteins. For example, many structural proteins shaping tubular ER have been identified, but sheet formation is much more unclear. In this study, we used light and electron microscopy to study morphological changes of the ER and Golgi in mammalian cells. The proportion, type, location and dynamics of ER sheets and tubules were found to vary in a cell type or cell cycle stage dependent manner. During interphase, ER and Golgi structures were demonstrated to be regulated by p37, a cofactor of the fusion factor p97, and microtubules, which also affected the localization of the organelles. Like previously shown for the Golgi, the ER displayed a tendency for fenestration and tubulation during mitosis. However, this shape change did not result in ER fragmentation as happens to Golgi, but a continuous network was retained. The activity of p97/p37 was found to be important for the reassembly of both organelles after mitosis. In EM images, ER sheet membranes appear rough, since they contain attached ribosomes, whereas tubular membranes appear smooth. Our studies revealed that structural changes of the ER towards fenestrated and tubular direction correlate with loss of ER-bound ribosomes and vice versa. High and low curvature ER membranes have a low and high density of ribosomes, respectively. To conclude, both ER and Golgi architecture depend on fusion activity of p97/p37. ER morphogenesis, particularly of the sheet shape, is intimately linked to the density of membrane bound ribosomes.

Essays on Platforms: Business Strategies, Regulation and Policy in Telecommunications, Media and Technology Industries

The growth of the information economy has been stellar in the last decade. General-purpose technologies such as the computer and the Internet have promoted productivity growth in a large number of industries. The effect on telecommunications, media and technology industries has been particularly strong. These industries include mobile telecommunications, printing and publishing, broadcasting, software, hardware and Internet services. There have been large structural changes, which have led to new questions on business strategies, regulation and policy. This thesis focuses on four such questions and answers them by extending the theoretical literature on platforms. The questions (with short answers) are: (i) Do we need to regulate how Internet service providers discriminate between content providers? (Yes.) (ii) What are the welfare effects of allowing consumers to pay to remove advertisements from advertisement-supported products?(Ambiguous, but those watching ads are worse off.) (iii) Why are some markets characterized by open platforms, extendable by third parties, and some by closed platforms, which are not extendable? (It is a trade-off between intensified competition for consumers and benefits from third parties) (iv) Do private platform providers allow third parties to access their platform when it is socially desirable? (No.)

Empirical Studies on Labor Market Matching (summary section only)

This thesis analyzes how matching takes place at the Finnish labor market from three different angles. The Finnish labor market has undergone severe structural changes following the economic crisis in the early 1990s. The labor market has had problems adjusting from these changes and hence a high and persistent unemployment has followed. In this thesis I analyze if matching problems, and in particular if changes in matching, can explain some of this persistence. The thesis consists of three essays. In the first essay Finnish Evidence of Changes in the Labor Market Matching Process the matching process at the Finnish labor market is analyzed. The key finding is that the matching process has changed thoroughly between the booming 1980s and the post-crisis period. The importance of the number of unemployed, and in particular long-term unemployed, for the matching process has vanished. More unemployed do not increase matching as theory predicts but rather the opposite. In the second essay, The Aggregate Matching Function and Directed Search -Finnish Evidence, stock-flow matching as a potential micro foundation of the aggregate matching function is studied. In the essay I show that newly unemployed match mainly with the stock of vacancies while longer term unemployed match with the inflow of vacancies. When aggregating I still find evidence of the traditional aggregate matching function. This could explain the huge support the aggregate matching function has received despite its odd randomness assumption. The third essay, How do Registered Job Seekers really match? -Finnish occupational level Evidence, studies matching for nine occupational groups and finds that very different matching problems exist for different occupations. In this essay also misspecification stemming from non-corresponding variables is dealt with through the introduction of a completely new set of variables. The new outflow measure used is vacancies filled with registered job seekers and it is matched by the supply side measure registered job seekers.

Modelling and Forecasting Property Rents and Returns (summary section only)

Recently, focus of real estate investment has expanded from the building-specific level to the aggregate portfolio level. The portfolio perspective requires investment analysis for real estate which is comparable with that of other asset classes, such as stocks and bonds. Thus, despite its distinctive features, such as heterogeneity, high unit value, illiquidity and the use of valuations to measure performance, real estate should not be considered in isolation. This means that techniques which are widely used for other assets classes can also be applied to real estate. An important part of investment strategies which support decisions on multi-asset portfolios is identifying the fundamentals of movements in property rents and returns, and predicting them on the basis of these fundamentals. The main objective of this thesis is to find the key drivers and the best methods for modelling and forecasting property rents and returns in markets which have experienced structural changes. The Finnish property market, which is a small European market with structural changes and limited property data, is used as a case study. The findings in the thesis show that is it possible to use modern econometric tools for modelling and forecasting property markets. The thesis consists of an introduction part and four essays. Essays 1 and 3 model Helsinki office rents and returns, and assess the suitability of alternative techniques for forecasting these series. Simple time series techniques are able to account for structural changes in the way markets operate, and thus provide the best forecasting tool. Theory-based econometric models, in particular error correction models, which are constrained by long-run information, are better for explaining past movements in rents and returns than for predicting their future movements. Essay 2 proceeds by examining the key drivers of rent movements for several property types in a number of Finnish property markets. The essay shows that commercial rents in local markets can be modelled using national macroeconomic variables and a panel approach. Finally, Essay 4 investigates whether forecasting models can be improved by accounting for asymmetric responses of office returns to the business cycle. The essay finds that the forecast performance of time series models can be improved by introducing asymmetries, and the improvement is sufficient to justify the extra computational time and effort associated with the application of these techniques.